Mortality and Life Expectancy

Survival rates for individuals with SCI have made steady improvements over the past five decades.  Prior to World War II, however, life expectancy for individuals with SCI was quite poor (Geisler et al. 1983).  Leading causes of death were those resulting from renal failure and infection (Lammertse 2001).  Since the introduction of antibiotics, improved emergency transportation, advances in long-term health interventions, and the availability of preventative care at specialized treatment centers, mortality rates have been steadily decreasing, and the causes of death have begun to mirror those of the general population (Whiteneck et al. 1992; DeVivo et al. 1999).  However, the life expectancy is still diminished compared to the general population (Geisler et al. 1983; Whiteneck et al. 1992; Hartkopp et al. 1997; McColl et al. 1997; Frankel et al. 1998; DeVivo et al. 1999; Yeo et al. 2000; Krause et al. 2004).

In 2002, the leading causes of death in high- and middle-income countries for the general population included coronary heart disease, stroke and other cerebrovascular diseases, cancer, and lower respiratory infections (WHO 2007).  Similarly, two leading causes of death in the SCI population are respiratory complications and heart disease (Hartkopp et al.1997; Frankel et al.1998; DeVivo et al. 1999; Soden et al. 2000; Zeilig et al. 2000; Garshick et al. 2005; NSCISC 2006).  The latest report from the National Spinal Cord Injury Database (NSCIDB), which has yielded information on the aging SCI population in the United States, indicates the main causes of death are pneumonia, pulmonary emboli, and septicemia (NSCISC 2008).  The cases of septicemia were typically associated with decubitus ulcers, urinary tract or respiratory infections (NSCIS 2006).  The high rates of cardiovascular disease in the SCI population may be partly due to physiological and functional changes following injury (Bauman et al. 1992a; Dearwater et al. 1986; Gupta 2006; Yekutiel et al. 1989; Bauman et al. 1992b).  Interestingly, cancer is a growing cause of death in persons with SCI (DeVivo et al. 1999; Zeilig et al. 2000; Imai et al. 2004; NSCISC 2006). It is unclear if there is an increased risk for all types of cancer, but there is some evidence that individuals with SCI may be at an increased risk for the development of bladder cancer (El-Masri and Fellows 1981; Stonehill et al.1996; West et al. 1999). In general, it appears that as individuals with SCI age, the causes of death become more closely associated with the typical age-related causes of death rather than those associated with the SCI itself (Capoor and Stein 2005).  However, some causes may be occurring prematurely (e.g., cardiovascular disease; Yekutiel et al. 1995), and there are some notable differences in mortality patterns between the SCI and the general populations.

A report from the NSCIDB on data between 1993 and 1998 indicated that external causes (i.e., unintentional injuries, homicide, suicide, etc.) were the third leading causes of death. In particular, suicide was the second leading cause of death in persons younger than 30 years of age, and in persons with paraplegia (DeVivo et al. 1999). These findings were consistent with other studies examining suicide as a cause of death after SCI (e.g., Charlifue and Gerhart 1991; DeVivo and Stover 1995; Hartkopp et al. 1997). The prevalence of these types of death highlight the need to focus energies on improving both treatment procedures and preventative measures since causes of death such as coronary heart disease might be prevented or minimized by promoting healthy lifestyle habits. Similarly, clinical interventions geared at improving coping skills after SCI may help to minimize the risk of suicide (Hartkopp et al. 1997; Imai et al. 2004; Krause et al. 2004).  Overall, important prognostic factors influencing length of survival include age and impairment, which includes neurological level, degree of injury completeness, and ventilator dependency (Kraus et al. 1979; Kiwerski et al. 1981; Le and Price 1982; Sneddon and Bedbrook 1982; Geisler et al. 1983; Whiteneck et al. 1992; Daverat et al. 1989; DeVivo et al. 1992; Alander et al. 1994; DeVivo and Ivie, 1995; DeVivo et al. 1999; Alander et al. 1997; McColl et al. 1997; Coll 1998; Frankel et al. 1998;Yeo et al. 1998; DeVivo et al. 1999; Strauss et al. 2000; Strauss et al. 2006).

In this section, the evidence reviewed (see Table 1) is consistent with the general findings on mortality and life expectancy in the SCI literature.

Table 1:  Mortality and Life-Expectancy

Discussion

In summary, causes of death in persons with SCI appear to be similar to those of the able-bodied population, but mortality may be occurring earlier due to higher rates of disease possibly attributed to metabolic changes. Samsa et al. (1993) found that the life expectancy of male veterans with traumatic SCI who survived at least 3 months (N = 5545) was significantly lower (p < .01) than those of a non-disabled veteran control group (N = 6967).  The mean life expectancy of the SCI group was 39 years after injury, 85% that of similarly aged American males. Hence, life expectancy in persons with SCI is lower than the general population. These findings are consistent with studies not meeting the chapter inclusion criteria examining life-expectancy post- SCI (i.e. Whiteneck et al. 1992; Hartkopp et al. 1997; McColl et al. 1997; Yeo et al. 2000; Imai et al. 2004).

Although Samsa et al. (1993) found that neurologic impairment was not a significant predictor for mortality, they noted a moderate effect (p < .06) for persons with cervical injuries that were complete.   A few studies have shown a lack of association between impairment and mortality (e.g., Liang et al. 2001; Imai et al. 2004; Garshick et al. 2005), whereas several studies have highlighted the importance of impairment as a prognostic factor (Whiteneck et al. 1992; McColl et al. 1997; Coll et al. 1998; DeVivo et al. 1998; Soden et al. 2000; Yeo et al. 2000; Strauss et al. 2006).  Consistent with previous findings of studies not meeting the chapter inclusion criteria (i.e., Whiteneck et al. 1992; Frankel et al. 1998), Samsa and colleagues (1993) found age of onset to be a significant predictor of long-term survival.

With regards to causes of mortality, Samsa et al. (1993) found that diseases of the genitourinary system (i.e., renal failure, septicemia) disproportionately accounted for death in their SCI sample and the patterns of death began to approach that of the general population by 20 years post-injury.  For instance, the rates of circulatory disease and neoplasms steadily increased across time points.  Interestingly, the causes of death due to injury and poisoning, and external conditions were the highest at 3-months to 5 years post-SCI, and steadily decreased across time points.  Although not discussed, their findings on these causes of death may have included suicides.  Regardless, the findings of lower levels of evidence highlighting the high rates of suicide as a cause of death (i.e., Imai et al. 2004) reinforces the need to provide psycho-social services to help minimize the occurrence of suicide in persons with SCI.  An acknowledged limitation of the study by Samsa et al. (1993) is the reliance on secondary data sources for case identification, control selection, and mortality assessment.  The study was also only on male veterans that did not include women or persons who did not survive acute SCI (i.e., less than 3 months post-SCI).

Conclusion

• There is Level 5 evidence from an observational study (Samsa et al. 1993) that life expectancy for males with SCI is lower than the general male population.
• There is Level 5 evidence from an observational study (Samsa et al. 1993) that persons who were injured at a younger age (SCI onset approximately < 30 years) will have a longer life expectancy than persons injured at an older age (SCI onset approximately > 30 years).
• There is Level 5 evidence from an observational study (Samsa et al. 1993) that causes of death post-SCI are beginning to approximate those of the general population.

• Life-expectancy for males with SCI is likely lower than the general male population.
• Persons injured at a younger age will likely have a longer life expectancy than persons injured at an older age.
• Causes of death post-SCI may be beginning to approximate those of the general population.

Physiological Aging

Even at the biological level, aging is a highly complex phenomenon that can be examined at the genetic, cellular, organ-system, and even the psycho-social level(Aldwin and Gilmer 2004).  To address physiological aging after SCI, the identified studies were separated into different body systems, which include the cardiovascular and endocrine systems (see Table 2), immune system (see Table 3), musculoskeletal system (see Table 4), respiratory system (see Table 5), nervous system (see Table 6), skin and subcutaneous tissues (see Table 7), and the genitourinary and gastrointestinal systems (see Table 8).

• SCI may represent a model for premature aging. There is strong evidence that the endocrine and musculoskeletal systems are prematurely aging, while there is limited evidence for the respiratory, skin and subcutaneous tissues, genitourinary, and gastrointestinal systems. There is weak and limited evidence that the immune and nervous system are prematurely aging.

Quality of Life and Community Reintegration

It is not surprising that the majority of articles that met the inclusion criteria for this chapter were on quality of life (QoL).  As more persons survive into their second, third, and even later decades, living with a disability becomes a life-long process for persons with SCI (Hallin et al. 2000).  As a result, the goal of rehabilitation is to maximize functionality and independence to allow for successful community reintegration and high QoL.  QoL describes the well-being and life satisfaction of an individual, and is a multi-factorial construct, which includes but is not limited to, interpersonal relationships and social support, physical and mental health, environmental comfort, and a host of psycho-social factors (Kaplan and Erickson 2000).  Community reintegration is an important constructs shown to be predictive of life satisfaction in persons with SCI (e.g., Pierce et al. 1999; Richards et al. 1999; Putzke et al. 2002b; Tonack et al. 2008). The term community reintegration is used to refer to returning to the mainstream of family and community life, engaging in normal roles and responsibilities, actively contributing to one’s social groups and of society as a whole (Dijkers 1998).  Thus successful reintegration means resuming occupations or activities deemed important to the individual (i.e., self-care, employment, leisure, etc.; Yasui and Berven 2008).  The environment (e.g., social, institutional, cultural or physical), can either create barriers or facilitate access to the community at large. Without exception successful reintegration can lead to improved QoL (Anderson 2004).

In the general population, older adults may face limitations with activities of daily living (e.g., Hoyer et al. 1999), and experience functional declines in the physical domain (e.g., Branch and Jette 1983), which can negatively impact community reintegration and QoL. Similarly, both physical and mental health factors influence quality of life in persons with SCI. For instance, issues with poor physical health, secondary health conditions (e.g., pressure ulcers, pain, etc.), depression and stress, and have all been shown to negatively impact on QoL.

With regards to aging, however, there are some mixed findings in relation to community reintegration and QoL, even within the same studies. For instance, there are some reports that life satisfaction and community reintegration (at least in some domains) improve with years post-SCI (e.g., Zarb et al. 1990; Tonack et al. 2008), whereas older age is associated with poorer community reintegration and quality of life (e.g., Krause and Crewe 1990; Eisenberg and Saltz 1991; Whiteneck et al. 1992; Tonack et al. 2008). As well, some reports provide evidence that QoL improves with increasing age (e.g., Pentland et al. 1995; Westgren and Levi, 1998; Dijkers 1999; McColl 1999). However, discrepancies with aging and quality of life tend to be more evident in cross-sectional analyses whereas longitudinal studies “mostly show relatively high and stable levels of QoL over long periods of time” (Kemp and Ettelson 2001, p. 119).  As well, these differences may arise due to the use of different instruments, which may not all assess the same underlying QoL construct.

In this section (see Table 9), eleven longitudinal studies and one observational study on community reintegration and QoL after SCI are reviewed.  

Table 9: Quality of Life and Community Reintegration

Discussion

Aging is a complex process that not only encompasses biology.  Environmental factors also change over time, which may be particularly critical to persons with SCI, because they not only face physical limitations associated with their SCI, but also social and economic changes that result from injury (Krause and Coker 2006).  As seen in Bushnik and Charlifue (2005), changes were related to changes in economics and technology, and not related to SCI or aging per se.  For example, letter writing, which probably included emails, increased in the sample over time because home computing had likely become more common.  Although not significant, the high percentage of persons who switched to a portable ventilator or pneumobelt from a fixed ventilator may have improved community reintegration for these individuals.  As well, the findings that economic self-sufficiency steadily improves with time (e.g., Charlifue and Gerhart 2004a; Krause and Broderick 2005; Krause and Coker 2006) supports Bushnik’s (2002) speculation that increased economic standing may improve community reintegration.  In the case of Bushnik’s (2002) sample, improved financial status enabled access adaptive equipment (e.g., modified van).  Conversely, level of community reintegration for Charlifue and Gerhart’s (2004a) sample did not significantly change over time, but this may have been due to sample differences between the studies (i.e., high level tetraplegia versus homogeneous impairment groups), and that the time between data collection intervals in the other studies reviewed were further apart. As well, the individuals in Gerhart and Charlifue’s (2004a) study were at least 20 years post-injury when they entered the study.  At 20 years post-injury, it is likely that routines and strategies for community participation have been well-established, and are not likely to dramatically change over 3 year periods.  However, an understanding of environmental factors is important for assessing quality of life since there is evidence that an individual’s adjustment over time is influenced by corresponding environmental changes (Krause and Sternberg 1997).

With regards to change in activity patterns, Bushnik and Charlifue (2005) attributed the changes to the natural progression of time utilization from external social activities associated with youth (e.g., card games with friends) to other activities not captured by the study (e.g., spending time with family).  Further, the reported declines in activity by the SCI cohorts as they aged (Bushnik’s (2002), Charlifue and Gerhart’s (2004a), and Krause and Broderick’s (2005) might be similar to declines in activity patterns in the general population (Christensen et al. 1996; Bukov et al. 2002).

One of the main strengths of the studies by Krause (1997), Krause and Broderick (2005), and Krause and Coker (2006) is they assessed whether there were any differences between their current sample and those who were lost to follow-up. Based on these analyses, clear survivor effects emerged in both studies as the characteristics of respondents (persons who participated in both data collection periods) at Time 1 were younger, younger at age of SCI-onset, were less years post-injury, had higher levels of education, more likely to have cervical injuries, greater sitting tolerance, and had more social outings than non-respondents (persons who only participated in the first data collection period). These findings highlight that some care should be taken when interpreting the findings from these studies as it may only reflect ‘survivors’.

Although having a SCI inevitably does place some form of activity limitation from the onset of injury, aging “may magnify issues of dependency as needs, ability, and limitation change over time” (Charlifue and Lammertse 2001, p. 415).  As with the general population (Roy 1986; Gaston-Johansson et al. 1996; Poluri et al. 2005), issues of fatigue and pain can limit the independence of a person with SCI.  Fatigue can be defined as an overwhelming sense of tiredness, lack of energy and often a feeling of total exhaustion (Herlofson & Larsen, 2002).  Fatigue after SCI is a prevalent issue (Gerhart et al. 1999; McColl et al. 2003; McColl et al. 2004; Fawkes-Kirby et al. 2008).  The findings on the associations between age and fatigue after SCI have been somewhat conflicting.  For example, one study found that males with SCI reported an increased fatigue with increasing age (Pentland et al., 1995), whereas some have found greater reports of fatigue in younger persons with SCI with short durations of injury (McColl et al. 2003). 

Both pain and fatigue have been both found to negatively impact on several domains of function and QoL (Rintala et al. 1998; Ingles et al. 1999; Herlofson and Larsen 2002).  As well, there is some evidence of a relationship between fatigue and pain after SCI (Fawkes-Kirby et al. 2008; Hammell et al. 2008).  When examined together, the study by Charlifue and colleagues (1999) and by Putzke and colleagues (2002a) highlight chronological age as a factor that mediates the expression and/or onset of change. In the study by Charlifue et al. (1999), the youngest and oldest group reported no significant changes between Time 1 and Time 2.  Similarly, the youngest and oldest group reported the least amount of pain interference between Year 1 and Year 2. 

The finding by Charlifue and colleagues (1999) that increasing age is associated with increased fatigue and additional physical assistance is congruent with other studies examining the effects of long-term SCI (e.g., Gerhart et al. 1993; Thompson, 1999; Liem et al. 2004).   A limitation noted by Charlifue et al. (1999) was that their sample was a relatively ‘young’ age (M = 37.1 years), and none having lived with their SCI for more than 20 years (M = 9.3), and may not have been impacted by the aging process to significantly impact overall health and functional status.  However, the consistent findings for increased fatigue between Time 1 and Time 2 do highlight that there is a consistent physical decline occurring.  Charlifue and colleagues (1999) recognized the systematic changes in their sample (i.e., improved health but declining functionality) but attributed them to external factors such as less contact with the healthcare system, funding changes, which lead to fewer participants reporting particular outcomes.  As well, they noted the need for increased physical assistance over time in their sample may have reflected attitude changes in rehabilitation practice where maintaining functionality is preferred over complete physical independence.  Although the strength of the study is its provision of several perspectives to aging with a SCI, an alternative analysis strategy might have helped to provide a more cohesive model of how the factors assessed related to one another.  For instance, the increases in physical assistance between Time 1 and Time 2 were often accompanied with improvements in health but also with increases in fatigue.  Reporting on associations (or lack of) between these variables may have provided additional support for their conclusions. 

The studies reviewed provide some interesting findings regarding living long-term with SCI, but do highlight some of the challenges associated with assessing quality of life in relation to aging.  The findings appear to provide some conflicting evidence where in some cases life satisfaction remained stable over time (i.e., Charlifue et al. 2004; Charlifue and Gerhart 2004b), decreased with time (i.e., Krause 1997; Charlifue et al. 1998), or improved with time (Kemp and Krause 1999).  The discrepancies in these studies are partly due to theoretical and methodological differences.  For instance, the study by Charlifue et al. (1998) was the only study that explicitly provided a theoretical model for assessing life satisfaction.  Specifically, Charlifue and colleagues (1998) framed aging with SCI within a global thesis of function, which took into account physical, psychological, and environmental factors.  Several studies with lower levels of evidence predicting life satisfaction have used other models that incorporate a variety of domains thought to impact on QoL (i.e., Pierce et al. 1999; Richards et al. 1999; Tonack et al. 2008).  Unfortunately, Charlifue et al. (1998) did not provide a clear rationale for including specific predictor variables in their models.  A larger theoretical concern is the issue of response shift (also known as recalibration, reprioritization, and reconceptualization; Schwartz and Spangers 2000), which refers to a dynamic process where an individual undergoes simultaneous changes in their internal standards, values, and conceptulizations of QoL in response to health and physical functioning changes (Tate et al. 2002).  Ambiguous or paradoxical findings can occur because of differences among people or changes within people regarding internal standards, values, or conceptualization of health-related QoL (Schwartz et al. 2007).  As a result, the psychometric properties (e.g., validity and reliability) of measurement tools can be affected (Schwartz et al. 2007).  Hence, issues of response shift should be considered when assessing QoL in persons with SCI, and several recommendations are put forth by Schwartz and colleagues (2007) on how to address them.

In terms of research design, comparing persons with SCI to control groups will also likely provide a different picture on QoL in different domains.  A strength of Kemp and Krause’s (1999) was the use of an able-bodied, and a disabled (i.e., polio) comparison group when examining issues of QoL after SCI as it provides some context to the extent of some problems for persons post-SCI (i.e., levels of depression).  However, the characteristics of the control groups were significantly different to the group with SCI on some key factors. For instance, the able-bodied and polio groups were significantly older (p < 0.01) and had higher levels of education than the group with SCI (p < 0.05). As well, the polio group was comprised mostly of females, had a mean pediatric age of onset, was 50.9 years post-polio, and 90% were Caucasian, whereas the SCI group was comprised of mostly males from culturally diverse backgrounds, and who had an adult age of onset, and were only 14.5 years post-injury. This limitation was addressed in the study, but highlights that the findings should be interpreted with caution since many socio-demographic and historical factors may have influenced levels of depression and life satisfaction. Nonetheless, the finding that persons with SCI have lower QoL compared to the able-bodied population is consistent with other studies that did not meet the chapter’s inclusion criteria (Kemp and Ettelson 2001).

Conclusion

• There is Level 4 evidence from four longitudinal studies (Bushnik 2002; Bushnik and Charlifue 2005; Krause and Broderick 2005; Krause and Coker 2006) that changes in environmental factors over time (i.e., economics; technology) may influence QoL in persons with SCI rather than the aging process per se.
• There is Level 4 evidence from two longitudinal studies (Charlifue and Gerhart 2004a; Bushnik and Charlifue 2005) that community reintegration declines with age after SCI. However, these changes in community reintegration may be similar as compared to the aging general population.
• There is Level 4 evidence from three longitudinal studies (Bushnik 2002; Charlifue and Gerhart 2004a; Bushnik and Charlifue 2005) that perceived QoL does not change as one ages with SCI.
• There is Level 4 evidence from a longitudinal study (Krause 1997) that selected domains of life satisfaction (i.e., social life and sex life) decrease as one ages with an SCI. It may be that these changes in satisfaction of certain domains are comparable to changes in the general population.
• There is Level 4 evidence from a longitudinal study (Kemp and Krause 1999) that age of SCI-onset may be an influential factor on life satisfaction.
• There is Level 4 evidence from two longitudinal studies (Charlifue et al. 2004a; Charlifue and Gerhart 2004b) that previous perceptions of life satisfaction are predictive of later perceptions of life satisfaction.
• There is Level 5 evidence from an observational study (Kemp and Krause 1999) that life satisfaction is lower for persons with SCI compared to the general population.
• There is Level 5 evidence from a longitudinal study (Putzke et al. 2002a) that previous reports of pain interference after SCI, irrespective of age, are predictive of later pain interference.
• There is Level 5 evidence from a longitudinal study (Charlifue et al. 1999) that fatigue and the need for physical assistance increases over time with SCI.
  

• Selected domains of life satisfaction (i.e., social life and sex life) may decline as one ages with a SCI. It may be that these changes in satisfaction of certain domains are comparable to changes in the general population.
• Changes in environmental factors over time (i.e., economics; technology) may influence QOL in persons with SCI rather than the aging process per se.
• Community participation may decline with age after SCI. However, these changes in community participation may be similar to the aging general population.
• Fatigue and the need for physical assistance may increase over time with SCI.
• Perceived QOL may not change as one ages with SCI.
• Age of SCI-onset may be an influential factor on life satisfaction.
• Previous perceptions of life satisfaction may be predictive of later perceptions of life satisfaction.
  

Summary

The majority of studies for all the systems provide some important findings regarding the role of chronological age (including age of SCI onset) and YPI, but there is still lack of clarity on how all of these factors affect (individually and in combination) the individual living with SCI over time, and further work is needed to determine if SCI is indeed a model for premature aging.  It appears that the field of aging with SCI has yet to make significant advances since many of the issues and questions raised over 15 years ago (Whiteneck et al. 1993) are still relevant today.

In general, longitudinal designs are the preferred method for investigating aging, but a number of longitudinal aging-related studies of SCI are limited in scope and quality due to several methodological issues (Krause 2007).  One limitation with longitudinal research designs are problems with retaining sufficient sample size over many years to observe long term changes with aging.  Problems with attrition lead to another type of cohort effect, namely survivor effects.  Survivor effects describe those individuals who may have outlived other members in their cohort due to some unusual advantage (e.g., environmental, physiological, etc.; Adkins 2001).  Persons who remain in longitudinal studies often represent those who are healthier, wealthier, and better educated whereas persons with poorer functioning drop-out or have died.  Another limitation of longitudinal designs is the possibility that data collected at an earlier time point may become obsolete due to advances or changes in measurement.  Longitudinal research is also considerably more resource intensive than cross-sectional studies in terms of cost and time.

Despite the challenges associated with longitudinal research, gaining an understanding of what changes a person with SCI may undergo over time is important to identify potential problems that can be anticipated and perhaps prevented in some cases.  This in turn may contribute to continued levels of maximum independence and overall well-being.  The field of aging with SCI has made some tremendous strides forward, but the dearth of knowledge in some areas highlights research opportunities that will help to resolve current challenges and more importantly provide information to fill many existing gaps.

• There is Level 5 evidence from an observational study (Samsa et al. 1993) that life expectancy for males with SCI is lower than the general male population.
• There is Level 5 evidence from an observational study (Samsa et al. 1993) that persons who were injured at a younger age (SCI onset approximately < 30 years) will have a longer life expectancy than persons injured at an older age (SCI onset approximately > 30 years).
• There is Level 5 evidence from an observational study (Samsa et al. 1993) that causes of death post-SCI are beginning to approximate those of the general population.
• There is Level 5 evidence from a cross-sectional study (Bauman and Spungen 2001) that plasma homocysteine levels are higher in persons with SCI compared to the AB population, with the greatest discrepancy in older adults with SCI (> 50 years).
• There is Level 5 evidence from seven cross-sectional studies (Zlotolow et al. 1992; Huang et al. 1993; Bauman and Spungen 1994; Bauman et al. 1996; Huang et al. 1998; Bauman et al. 1999; Demirel et al. 2001; Liang et al. 2007; Wang et al. 2007) that abnormal lipid profiles after SCI may contribute to the development of cardiovascular disease.
• There is Level 4 evidence (Apstein and George 1998) that total cholesterol (TC), total glycerides (TG), and low-density lipoproteins (LDL) increased while LDL/high-density lipoproteins (HDL) ratios decreased for males with tetraplegia and paraplegia from the acute phase until 1 YPI. All lipid profiles were significantly depressed compared to controls.
• There is Level 4 evidence (Apstein and George 1998) that persons with tetraplegia had low HDL and elevated LDL/HDL ratios, which placed them at increased risk for coronary artery disease.
• There is Level 5 evidence (Wang et al. 2007) that C-reactive protein levels are higher in males with SCI compared to AB controls, which could also account for the decreases in TC, LDL, HDL. C-reactive protein levels may also partly explain why persons with SCI are at increased risk for accelerated atherogenesis.
• There is Level 5 evidence (Orakzai et al. 2007) that persons with SCI have greater atherosclerotic burden compared to an AB reference population.
• There is Level 5 evidence from two studies that men with complete paraplegia have an abnormal (absent) heart rate response (Petrofsky and Laymon 2002)
• There is Level 5 evidence that men with complete tetraplegia demonstrate increased blood pressure (Yamamoto et al. 1999).
• There is Level 5 evidence (Tsitouras et al. 1995; Wang et al. 1992; Cheville et al. 1995; Shetty et al. 1999) that there is SCI related lower secretion of testosterone and human growth hormone levels in persons with SCI compared to AB controls.
• There is Level 5 evidence from two studies (Tsitouras et al. 1995; Bauman et al. 1994) that serum IGF-I levels are impaired in persons with SCI compared to the AB population, and may be a sign of premature aging.
• There is Level 5 evidence from three studies (Bauman and Spungen 1994; Jones et al. 2004; Liang et al. 2007) that glucose intolerance is lower after SCI, which may lead to an increased risk for premature diabetes mellitus.
• There is Level 5 evidence (LaVela et al. 2006) that diabetes mellitus occurs prematurely in male veterans with SCI compared to AB veteran controls.
• Six studies (Nuhlicek et al. 1988; Bauman et al. 1996; Bauman et al. 1999; Spungen et al. 2000; Jones et al. 2003; Jones et al. 2004) provide Level 5 evidence that persons with SCI are likely to have higher levels of fat mass, and that age-related declines of lean tissue in males with SCI may occur at a significantly faster rate than the AB population.
• There is Level 5 evidence from one monozygotic twin study (Bauman et al. 2004) that basal and resting energy expenditures are lower in males with SCI compared to their AB twin.
• There is Level 5 evidence (Campagnolo et al. 1994; Campagnolo et al. 1996; Furlan et al. 2006) that the immune function of persons with acute and chronic SCI is compromised compared to the AB population, but there is no influence due to aging.
• There is Level 4 evidence from 8 longitudinal studies (Biering-Sorenson et al. 1990; Garland et al. 1992; Wilmet et al. 1995; de Bruin et al. 2000; Frey-Rindova et al. 2000; Garland et al. 2004; de Bruin et al. 2005; Frotzler et al. 2008) and Level 5 evidence from 12 studies (Chow et al. 1996; Szollar et al. 1997a; Szollar et al. 1997b; Szollar et al. 1998; Bauman et al. 1999; Dauty et al. 2000; Kiratli et al. 2000; Garland et al. 2001b; Vlychou et al. 2003; Eser et al. 2004; Giangregorio et al. 2005; Slade et al. 2005) that there is a rapid loss of bone in the hip and lower extremities following SCI, and that this loss is significantly lower than the AB population.
• There is Level 2 evidence (Frotzler et al. 2008) and Level 5 evidence (Eser et al. 2004) that tibial and femoral bone geometry and density properties reach a new steady-state within 3-8 YPI, with the time frame depending on bone parameter and skeletal site.
• There is Level 5 evidence from three studies (Szollar et al. 1997a; Szollar et al. 1998; Garland et al. 2001b) that older males and females with SCI may not experience as rapid of a decline in bone mass compared to AB controls.
• There is Level 5 evidence from two studies (Bauman et al. 1999; Garland et al. 2001b) that YPI may be more associated with bone loss after SCI than chronological age.
• There is Level 5 evidence (Slade et al. 2005) that there are differences in bone geometric indices and in structural properties in the lower extremities of women with SCI compared to the AB women.
• There is Level 5 evidence from five studies (Finsen et al. 1992; Vaziri et al. 1994; Bauman et al. 1995; Szollar et al. 1998; Dauty et al. 2000) suggesting that there are impaired biochemical and bone markers in persons with SCI compared to AB controls that persons with SCI are at greater risk for fracture due to the premature development of osteoporosis.
• There is Level 2 evidence from a longitudinal study with AB controls (Catz et al. 1992), Level 4 evidence from a longitudinal study (Biering-Sorenson et al. 1990), and Level 5 evidence from five studies (Chow et al. 1996; Szollar et al. 1997a; Szollar et al. 1997b; Szollar et al. 1998; Garland et al. 2001b) that premature aging does not occur in the lumbar spine after SCI. The possibility that the lumbar spine becomes the primary weight bearing region, along with immobilization, may serve to protect age-related bone loss changes to this region.
• There is Level 5 evidence (Amsters and Nitz 2006) that persons with SCI, regardless of age or YPI, had increased thoracic kyphosis compared to AB controls.
• There is Level 5 evidence from two studies (Pentland and Twomey 1994; Petrofsky and Laymon 2002) that decreased hand grip strength does not occur in men with complete paraplegia and that continual wheelchair use may retard this aging process.
• There is Level 5 evidence (Pentland and Twomey 1994) that upper limb pain in males with complete paraplegia who use manual wheelchairs may be attributed to longer YPI and not to chronological age.
• There is Level 2 evidence from two longitudinal studies (Siddall et al. 2003; Jensen et al. 2005) showing that the incidence of shoulder pain increases over time in persons with SCI.
• There is Level 2 evidence from a longitudinal study (Lal 1998) and Level 5 evidence (Kivimäki et al. 2008) that highlights chronological age having an important influence on developing shoulder pain.
• There is Level 4 evidence from two longitudinal studies (Bach and Wang 1994; Berlowitz et al. 2005) and Level 5 evidence from two observational studies (Cahan et al. 1993; Biering-Sorenson and Biering-Sorenson 2001) that SDB as characterized by sleep apnea, oxygen desaturation, and snoring is more prevalent in SCI populations.
• There is Level 4 evidence from two longitudinal studies (Bach and Wang 1994; Berlowitz et al. 2005) support that SDB may either increase or persist with the aging process.
• There is Level 2 evidence from a longitudinal study with AB controls (Loveridge et al. 1992) that seated breathing patterns are compromised immediately post injury but recover over time. As well, persons with tetraplegia do not take deep breaths as often as AB individuals.
• There is Level 4 evidence from a longitudinal study that adults over the age of 50 who are aging with ventilator dependency are at greater risk of death and are less likely to be weaned from their ventilators than younger adults aging with a ventilator (Wicks and Menter 1986).
• There is Level 4 evidence (Putzke et al. 2002a; Siddall et al. 2003; Rintala et al. 2004; Jensen et al. 2005) that the early onset of SCI-related pain is likely to be maintained over time, with some evidence indicating that the degree of interference experienced might be impacted by age of onset (Jensen et al. 2005).
• There is Level 2 evidence indicating that males with SCI have higher levels of a collagen metabolite, glu-gal Hyl, than AB controls (Rodriguez and Claus-Walker 1984).
• There is Level 4 evidence (Rodriguez and Garber 1994) that increased excretions of glu-gal Hyl is significantly associated with development of pressure ulcers in males with SCI.
• There is Level 2 evidence (Vaziri et al. 1995) suggesting that plasma fibronectin, as an indicator of wound healing, may rise in SCI male patients with fast healing ulcers but not in SCI patients with poor healing ulcers.
• There is Level 4 evidence (Viera et al. 1986; DeWire et al. 1992; MacDiarmid et al. 1995; Sekar et al. 1997) that there are no differences in renal functioning up to 4 YPI using various bladder management techniques with some decline occurring beyond that time.
• There is Level 4 evidence (Lamid et al. 1988) that repeated episodes of vesicoureteral reflux can cause kidney damage as early as four YPI in some persons with SCI.
• There is Level 4 evidence (Sekar et al. 1997) that renal plasma flow declines until 10 YPI after SCI, at which time, a slight reversal occurs.
• There is Level 5 evidence (Kuhlemeier et al. 1984) that suggests age of SCI onset may be an important factor related to renal function, with persons with SCI who are under 20 and older than 50 having comparable renal function to AB controls, whereas persons between those ages have impaired functioning compared to the general population.
• There is Level 5 evidence from six studies (Konety et al. 2000; Pramjudi et al. 2002; Pannek et al. 2003; Scott Sr et al. 2003; Alexandrino et al. 2004; Shim et al. 2008) that males with SCI do not appear to be at higher risk for the development of prostate cancer compared to the general population.
• There is Level 5 evidence (Scott Sr et al. 2003) that persons with SCI and prostate cancer have higher levels of prostate serum antigen at diagnosis and cancer that was more advanced and metastatic than AB controls with prostate cancer.
• There is Level 5 evidence (Lynch et al. 2000) demonstrating a deterioration in bowel continence with increasing age in an AB population but no change with age in persons with SCI.
• There is Level 4 evidence (Faaborg et al. 2008) suggesting persons with SCI do incur an increase in constipation-related symptoms and decrease in fecal incontincence over time.
• There is Level 5 evidence from three studies (Menardo et al. 1987; Krogh et al. 2000; Emmanuel et al. 2009) that level of injury, and not necessarily age or YPI, plays a primary role in the extent of bowel dysfunction.
• There is Level 4 evidence from four longitudinal studies (Bushnik 2002; Bushnik and Charlifue 2005; Krause and Broderick 2005; Krause and Coker 2006) that changes in environmental factors over time (i.e., economics; technology) may influence QoL in persons with SCI rather than the aging process per se.
• There is Level 4 evidence from two longitudinal studies (Charlifue and Gerhart 2004a; Bushnik and Charlifue 2005) that community reintegration declines with age after SCI. However, these changes in community reintegration may be similar as compared to the aging general population.
• There is Level 4 evidence from three longitudinal studies (Bushnik 2002; Charlifue and Gerhart 2004a; Bushnik and Charlifue 2005) that perceived QoL does not change as one ages with SCI.
• There is Level 4 evidence from a longitudinal study (Krause 1997) that selected domains of life satisfaction (i.e., social life and sex life) decrease as one ages with an SCI. It may be that these changes in satisfaction of certain domains are comparable to changes in the general population.
• There is Level 4 evidence from a longitudinal study (Kemp and Krause 1999) that age of SCI-onset may be an influential factor on life satisfaction.
• There is Level 4 evidence from two longitudinal studies (Charlifue et al. 2004a; Charlifue and Gerhart 2004b) that previous perceptions of life satisfaction are predictive of later perceptions of life satisfaction.
• There is Level 5 evidence from an observational study (Kemp and Krause 1999) that life satisfaction is lower for persons with SCI compared to the general population.
• There is Level 5 evidence from a longitudinal study (Putzke et al. 2002a) that previous reports of pain interference after SCI, irrespective of age, are predictive of later pain interference.
• There is Level 5 evidence from a longitudinal study (Charlifue et al. 1999) that fatigue and the need for physical assistance increases over time with SCI.

Key Points

• Life-expectancy for males with SCI is likely lower than the general male population.
• Persons injured at a younger age will likely have a longer life expectancy than persons injured at an older age.
• Causes of death post-SCI may be beginning to approximate those of the general population.
• SCI may represent a model for premature aging. There is strong evidence that the endocrine and musculoskeletal systems are prematurely aging, while there is limited evidence for the respiratory, skin and subcutaneous tissues, genitourinary, and gastrointestinal systems. There is weak and limited evidence that the immune and nervous system are prematurely aging.
• Greater levels of arthersclerotic burden, higher levels of C-reactive protein levels and abnormal lipid profiles compared to the able-bodied population increases the risk for the development of cardiovascular disease in persons with SCI.
• Men with complete SCI have abnormal heart rate and blood pressure responses compared to able-bodied controls, which are indicative of altered autonomic control, but not from advancing aging per se.
• Impaired secretion of both testosterone and human growth hormone may be due to SCI, and not from advancing age per se.
• Serum IGF-I levels may be impaired compared to the able-bodied population, which may be a sign of premature aging.
• Glucose intolerance may be impaired in persons with SCI, which may lead to an increased risk for premature diabetes mellitus.
• Persons with SCI are at higher risk for the development of cardiovascular disease and diabetes mellitus than the able-bodied population.
• Persons with SCI may have higher levels of fat mass than the able-bodied population.
• Age-related declines of lean tissue in males with SCI may occur at a significantly faster rate than the able-bodied population.
• Age of onset may not influence hematologic abnormalities at the acute phase post-SCI (within first week post-injury).
• Immune function after SCI at both the acute and chronic phase is compromised compared to able-bodied controls, but age may not play an important role.
• Premature aging may occur in the femoral and hip regions in persons with SCI. It may be that declines in bone mass occur rapidly following injury, and reach a new steady-state within 3-8 years post-injury, depending on the bone parameter and skeletal site.
• Older males and females ( < 60 years) with SCI may not experience rapid declines in bone mass in certain regions when compared to able-bodied controls.
• Duration of injury may be more associated with bone loss after SCI than chronological age.
• Women with complete SCI may be at a greater risk for fracture at the knee compared to males with SCI and the able-bodied population.
• Premature aging may not occur in the lumbar spine after SCI.
• Upper limb pain in males with complete paraplegia may be attributed to longer durations of injury and not to the aging process.
• The incidence of shoulder pain increases over time, and that age of onset may contribute to the development of pain. Adults with SCI (< 10 years post-injury) who were 30 years and older were more likely to report shoulder pain over time than those who were less than 30 years of age.
• Premature aging may not occur in hand grip strength in men with complete paraplegia. Rather, continual wheelchair use may retard the aging process in relation to handgrip strength.
• Regardless of age or years post-injury, persons with SCI may have increased thoracic kyphosis than the able-bodied population.
• Persons with SCI may have reduced lung capacity compared to able-bodied controls, but this reduction is due to SCI and not aging.
• Sleep disordered breathing may increase or persist with the aging process in persons with SCI.
• Seated breathing patterns after tetraplegia are compromised early post-injury but recover over time.
• Adults who are older (50 years +) and ventilator dependent have a higher mortality rate and lower weaning rate than adults who are younger and who are ventilator dependent.
• Younger persons (> 30 years) may have less pain interference at one and at two years post-injury than older persons (< 60 years).
• Previous reports of pain interference after SCI, irrespective of age, may be predictive of later pain interference.
• Males with SCI have higher levels of collagen metabolite, glu-gal Hyl, than the able-bodied population, which may be a sign of premature aging of the skin. Further work is needed to conclusively demonstrate this.
• Behavioural factors play a stronger role in the development of pressure ulcers in persons with SCI than either age or YPI.
• Various bladder management techniques (indwelling catheterization versus intermittent catheterization) may not impact renal functioning in persons with SCI over time.
• Repeated episodes of vesicoureteral reflux can cause kidney damage as early as four years post-injury.
• After SCI, renal plasma flow declines until 10 years post-injury, at which time, a slight reversal occurs.
• Age of onset may play a role in minimizing renal decline, with adults who are under 20 and older than 50 having comparable renal functioning to the able-bodied population, while those between those ages have impaired functioning.
• Males with SCI do not appear to be at higher risk for prostate cancer compared to the able-bodied male population. However, males with SCI should be regularly screened since prostate cancer is more advanced and metastatic than the general population when detected.
• Bowel continence increased with age in the able-bodied population but does not change in persons with SCI.
• Persons with SCI may experience an increase in constipation-related symptoms and decrease in fecal incontinence over time.
• Level of injury, and not age or years post-injury, plays a primary role in the extent of bowel dysfunction.
• Selected domains of life satisfaction (i.e., social life and sex life) may decline as one ages with a SCI. It may be that these changes in satisfaction of certain domains are comparable to changes in the general population.
• Changes in environmental factors over time (i.e., economics; technology) may influence QOL in persons with SCI rather than the aging process per se.
• Community participation may decline with age after SCI. However, these changes in community participation may be similar to the aging general population.
• Fatigue and the need for physical assistance may increase over time with SCI.
• Perceived QOL may not change as one ages with SCI.
• Age of SCI-onset may be an influential factor on life satisfaction.
• Previous perceptions of life satisfaction may be predictive of later perceptions of life satisfaction.

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Pathophysiology of AD

AD is most commonly triggered by urinary bladder or colon irritation.  However, many other causes were reported in the literature (Teasell et al. 2000; Mathias & Frankel 2002).  AD is caused by massive sympathetic discharge triggered by either noxious or non-noxious stimuli below the level of the SCI (Krassioukov & Claydon, 2005).  Numerous reports of AD have been described in the literature: episodes are usually short-lived either due to treatment or being self-limiting.  However, there are reports of AD triggered by a specific stimulus, which then continued to be present for a period of days to weeks (Elliott & Krassioukov 2006). 

Numerous mechanisms have been proposed for the development of AD.  It is known from animal studies that autonomic instability following SCI results from plastic changes occurring within the spinal and peripheral autonomic circuits in both the acute and chronic stages following injury (Mathias & Frankel 1988; Teasell et al. 2000; Mathias & Frankel 2002; Krassioukov 2005).  The destruction of the descending vasomotor pathways results in the loss of inhibitory and excitatory supraspinal input to the sympathetic preganglionic neurons; this is currently considered the major contributor to unstable blood pressure control following SCI (Furlan et al. 2003).  Furthermore, there is numerous animal and human data suggesting that plastic changes within the spinal cord (specifically spinal sympathetic neurons and primary afferents) underlies the abnormal cardiovascular control and AD following SCI.  Altered sensitivity of peripheral alphaadrenergic receptors (receptors in the sympathetic nervous system) is one mechanism that may contribute to AD (Osborn et al. 1990; Arnold et al. 1995; Krassioukov & Weaver 1995, 1996; Karlsson 1999; Krassioukov et al. 1999; Krassioukov et al. 2002). 

Table 1: Signs and Symptoms

• severe headache
• feeling of anxiety
• profuse sweating above the level of injury
• flushing and piloerection (body hair “stands on end”) above the injury
• dry and pale skin due to vasoconstriction below the level of injury
• blurred vision
• nasal congestion
• cardiac arrhythmias, atrial fibrillation

Management

Presently there is a well established protocol of management of AD developed by the Consortium for Spinal Cord Medicine (Consortium for Spinal Cord Medicine 1997).  In patients with spinal cord injury, appropriate bladder and bowel routines, in addition to pressure sore prevention are the most effective measures for prevention of autonomic dysreflexia. However, for each individual, the identification and elimination of specific triggers for autonomic dysreflexia should also be employed to manage and prevent episodes of autonomic dysreflexia (Teasell et al. 2000; Mathias & Frankel 2002; Blackmer 2003).

When AD develops, the initial management of an episode involves placing the patient in an upright position to take advantage of an orthostatic reduction in blood pressure, and the loosening of any tight clothing (Consortium for Spinal Cord Medicine 1997). Throughout the episode, the blood pressure should be checked at 5 min intervals.  It is then necessary to search for and eliminate the precipitating stimulus most commonly (in 85% of cases) related to either bladder distention or bowel impaction (Teasell et al. 2000; Mathias & Frankel 2002).  The use of antihypertensive drugs should be considered as a last resort, but may be necessary if the blood pressure remains at 150 mmHg or greater following the steps outlined above (Consortium for Spinal Cord Medicine 1997).   The goal of such an intervention is to alleviate symptoms and avoidthe complications associated with uncontrolled hypertension (Yarkony et al. 1986; Pine et al. 1991; Eltorai et al. 1992; Valles et al. 2005).

• The identification of the possible trigger and decrease of afferent stimulation to the spinal cord is the most effective prevention strategy in clinical practice.

Prevention Strategies

The most effective approach to AD is the prevention of occurrence of this disabling and life threatening condition (Braddom & Rocco 1991).  This includes careful evaluation of individuals with SCI and early recognition of possible triggers that could result in AD.  Improved clinician awareness of AD and greater attention on the need to eliminate noxious stimuli in individuals with SCI is a priority.  Clinicians, family members, and care givers should be aware that increased afferent stimulation (e.g., via surgery, invasive investigational procedures, labour) to persons with SCI will increase the risk for development of AD.  A variety of procedures can be used to prevent occurrence of episodes of AD.

Management of Acute AD

Despite appropriate preventative strategies, AD remains common among individuals with SCI.  As previously noted, especially in individuals with cervical or high thoracic injuries, episodes of AD with a significant increase in arterial blood pressure could be asymptomatic (Linsenmeyer et al. 1996; Ekland et al. 2007; McGillivray et al. 2006).The Guidelines of the Consortium for Spinal Cord Medicine for management of AD recommends employing non-pharmacological measures initially; if they fail, and systolic blood pressure continues to be at or above 150 mmHg in adults, 120 mmHg in children under 5 years old, 130 mmHg in children 6-12 years old, and 140 mmHg in adolescents, pharmacological agents should be initiated (Consortium for Spinal Cord Medicine 2006).

Summary

• There is level 4 evidence (from 4 pre-post studies) (Dykstra et al. 1988; Schurch et al. 2000; Chen et al. 2008; Kuo et al. 2008) that Botulinum toxin injections into the detrusor seem to be a safe and valuable therapeutic option in SCI patients who perform clean intermittent self-catheterization and have incontinence resistant to anticholinergic medications.
• There is level 4 evidence (from 1 pre-post study) (Igawa et el. 2003) that intravesical capsaicin is effective for reducing episodes of AD in SCI.
• There is level 1 evidence (from 2 RCTs) (Kim et al. 2003; Giannantoni et al. 2002) that intravesical resiniferatoxin is effective for reducing episodes of AD in patients with SCI.
• There is level 1 evidence (from 1 RCT) (Giannantoni et al. 2002) that intravesical resiniferatoxin is more effective than intravesical capsaicin.
• There is level 5 evidence that anticholinergics (from 1 observational study) (Giannantoni et al. 1998) are not associated with reduced incidence of AD episodes.
• There is level 4 evidence (from one pre-post study and one case series study) (Hohenfellner et al. 2001; Kutzenberger 2007) that sacral deafferentation may be effective in preventing AD.
• There is level 4 evidence (based on three pre-post/case series studies) (Barton et al. 1986; Sidi et al. 1990; Perkash 2007) that urinary bladder surgical augmentations may result in a decrease of intravesical and urethral pressure and diminish or resolve episodes of AD.
• There is level 4 evidence (based on 1 case series) (Seoane-Rodriguez et al. 2007) that an intraurethral stent may be an effective means for the long-term management of detrusor-sphincter dysynergia for SCI patients, including those who have previously underwent sphincterotomy.
• There is level 1 evidence (from 1 RCT) (Cosman & Vu 2005) that lidocaine anal block significantly limits the AD response in susceptible patients undergoing anorectal procedures.
• There is level 1 evidence (from 1 RCT) (Cosman et al. 2002) that topical lidocaine does not limit or prevent AD in susceptible patients during anorectal procedures.
• There is level 1 evidence (from 1 RCT) (Furusawa et al. 2008) that topical lidocaine may help to prevent AD during gentle bowel stimulation.
• There is level 4 evidence that women with SCI may give birth vaginally. With vaginal delivery or when cesarean delivery or instrumental delivery is indicated, adequate anesthesia (spinal or epidural if possible) is needed.
• There is level 4 and 5 evidence (from 2 case series and 2 observational studies) (Cross et al. 1992; Hughes et al. 1991; Cross et al. 1991; Showronski and Hartman 2008) that epidural anesthesia is preferred and effective for most patients with AD during labor and delivery.
• There is level 5 evidence (from 2 observational studies) (Lambert et al. 1982; Eltorai et al. 1997) that indicate that patients at risk for autonomic dysreflexia are protected from developing intraoperative hypertension by either general or spinal anesthesia.
• Anesthesiologists and surgeons dealing with SCI patients must know how to recognize the AD syndrome, how to prevent its occurrence and how to manage it aggressively.
• There is level 1 evidence (from one RCT) (Matthews et al. 1997) supporting no effect of topical anesthetic for the prevention of AD during FES.
• There is level 2 evidence (from 2 prospective controlled trials) (Steinberger et al. 1990; Lindan et al. 1985) that Nifedipine may be useful to prevent dangerous blood pressure reactions, e.g. during cystoscopy and other diagnostic or therapeutic procedures in SCI injured patients with AD.
• There is level 5 evidence (from clinical consensus) (Joint National Committee on Detection, Evaluation and Treatment of High Blood Pressure 1997), that serious adverse effects from Nifedipine may occur and these have been reported in other populations.
• There is level 5 evidence (clinical consensus) (Consortium for Spinal Cord Medicine 2001; Braddom & Rocco 1991), but no clinical studies which support the use of nitrates in the acute management of AD in SCI.
• There is level 4 evidence (from one pre-post study) (Esmail et al. 2002) for the use of captopril in the acute management of AD in SCI.
• There is level 4 evidence (from 3 pre-post studies) (Vaidyanathan et al. 1998; Swierzewski et al. 1994; Chancellor et al. 1994) that regular use of Terazosin may have positive effects on incontinence and AD.
• There is level 1 evidence (from one RCT) (Krum et al. 1992), that Prazosin is superior to placebo in the prophylactic management of AD.
• There is level 4 evidence (from one pre-post study and one case series study) for use of Phenoxybenzamine in the management of AD, however, the results are conflicting with no effects in one study (Lindan et al. 1985) and positive effects in another (McGuire et al. 1976).
• There is level 2 evidence from a very small prospective controlled study (Frankel & Mathias 1980) which used subjects as their own controls which showed that the level of BP recorded during electrical ejaculation was substantially reduced with Prostaglandin E2.
• There is level 2 evidence (from 1 RCT) (Sheel et al. 1995) that sildenafil citrate had no effect on changes in BP during episodes of AD initiated by vibrostimulation in men with SCI.

Key Points

• The identification of the possible trigger and decrease of afferent stimulation to the spinal cord is the most effective prevention strategy in clinical practice.
• Botulinum toxin injections into the detrusor seem to be a safe and valuable therapeutic option in SCI patients who perform clean intermittent self-catheterization and have incontinence resistant to anticholinergic medications.
• Capsaicin and its analogue, resiniferatoxin, are effective in the management of AD in patients with SCI.
• Anticholinergics do not appear to be sufficient for the management of AD in SCI.
• Sacral deafferentation may educe AD during urodynamic investigations.
• Urinary bladder surgical augmentations may diminish or resolve episodes of AD.
• An intraurethral stent may be an effective alternative to sphincterotomy in reducing episodes of AD.
• Lidocaine anal block can limit the AD response in susceptible patients undergoing anorectal procedures.
• Topical lidocaine may prevent AD during digital bowel stimulation but does not prevent AD during anorectal procedures.
• Adequate anesthesia (spinal or epidural if possible) is needed with vaginal delivery, cesarean delivery or instrumental delivery is required.
• Epidural anesthesia is preferred and effective for most women with AD during labor and delivery.
• Anesthesia should be used during surgical procedures in individuals with SCI despite apparent lack of sensation.
• Topical anesthetic is not effective for the prevention of AD during FES
• Nifedipine may be useful to prevent or control AD in SCI individuals, however, serious adverse effects from may occur as those reported in other populations.
• Nitrates are commonly used in the control of AD in SCI, but no studies have been done to show their effectiveness or safety in SCI.
• Preliminary evidence suggests that captopril is effective for the management of AD in SCI.
• There is limited evidence for the use of Terazosin as an agent for control of AD in SCI individuals.
• Prazosin can reduce severity and duration of AD episodes in SCI.
• It is not known whether Phenoxybenzamine is effective for the management of AD in SCI.
• Prostaglandin E2 is effective for reducing BP responses during eletroejaculation.
• Sildenafil has no effect on AD responses in men with SCI during ejaculation.
  

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Types of Bladder Dysfunction in SCI

There are two main types of bladder dysfunction in SCI:1) neurogenic detrusor overactivity, usually associated with associated sphincter dysynergia (Detrusor external spincter dyssynergia: DESD) and 2) detrusor areflexia. Occasionally detrusor overactivity is seen without associated sphincter dysynergia in the SCI population which can result in difficulty with continence. Methods to improve continence in those with or without DESD are often similar and as such, are addressed in the sections on enhancing bladder volumes in DESD.

DESD Therapy in SCI

Due to the small capacity bladder seen with neurogenic detrusor overactivity, and the potential for high bladder pressures leading to reflux, hydronephrosis, and kidney damage, and due to the potential for the contractions and small volumes to cause incontinence, the goals of therapy are to: 1) enhance bladder volume while lowering bladder filling pressures, and 2) to empty the bladder regularly in a low pressure voiding manner, usually with intermittent catheterization in people with an intact external sphincter, or external drainage in people that have had a procedure to physically or chemically obliterate the external sphincter. Methods to enhance bladder volumes will be discussed first. Note that this pertains to people usually on concomitant intermittent catheterization for drainage. Occasionally the volume enhancing treatments below will be used in combination with an indwelling catheter to avoid leakage around the catheter.

Detrusor Areflexia

Detrusor areflexia is seen most commonly in cauda equina lesions where the sacral reflex is disrupted. It can occasionally occur at other levels of spinal lesions. The clinical manifestation of this results in an inability for the bladder to empty completely or at all, leading to overdistension and stasis. Additionally, there is frequently incontinence due to lack of external sphincter tone, most often due to increased abdominal pressure on the bladder (i.e. stress incontinence). This can be especially problematic in persons with paraplegia that may require high valsalva forces for activities such as transferring from wheelchairs.

Unfortunately, there is a great paucity of research examining the impact and treatment of detrusor areflexia. Although the goals remain the same as with overactive bladder in SCI, (i.e., avoiding incontinence, stasis, UTI’s, and upper urinary tract damage, etc.), these goals may be achieved differently. In general, the goal is either: 1) stopping leakage and improving storage with medications and intermittent catheterization, or 2) improving emptying, either voluntarily in the incomplete injury, and/or into condom drainage in the person with more severe neurogenic bladder impairments. However, further discussion on detrusor areflexia will not occur in this chapter given the extremely sparse evidence base. It should be noted that in some studies described in the sections pertaining to DESD therapy there may have been mixed samples in which a few subjects with detrusor areflexia might have participated in addition to those with detrusor overactivity. In one instance, subjects with detrusor areflexia comprised all study participants providing level 4 evidence from a single case series (n=10) for the surgical anastomosis of the T11 ventral nerve root to the S2-S3 ventral nerve roots in improving bladder function (e.g., Lin et al. 2008 in Table 13.16 for Other Miscellaneous Treatments).

Urinary Tract Infections

Summary

• Level 1 evidence from a single RCT supports the use of propiverine to treat detrusor hyperreflexia by significantly improving bladder capacity.
• Level 1 evidence from a single RCT supports the use of tolterodine vs placebo to significantly increase intermittent catheterization volumes and decrease incontinence in neurogenic detrusor overactivity.
• There is level 2 evidence from a single open label prospective controlled trial that  tolterodine and oxybutynin are equally efficacious in SCI patients with neurogenic detrusor overactivity except that tolterodine results in less dry mouth.
• Level 4 evidence from a single pre-post trial supports the potential benefits of controlled-release oxybutynin. 
• Level 1 evidence from a single RCT supports the use of trospium chloride to increase bladder capacity and compliance, and decrease bladder pressure with very few side effects in SCI individuals with neurogenic bladder.
• Level 1 evidence based on two RCTs supports the use of Botox A injections into the detrusor muscle to provide targeted treatment for detrusor hyperreflexia and urge incontinence resistant to high-dose oral anticholinergic treatments with intermittent self-catheterization in SCI. 
• Level 1 evidence supports the use of vanillanoid compounds such as capsaicin or resiniferatoxin to increase maximum bladder capacity and decrease urinary frequency and leakages in neurogenic detrusor overactivity of spinal origin.
• Level 4 evidence exists to suggest that intravesical capsaicin instillation in bladders of SCI individuals does not increase the rate of common bladder cancers after 5 years of use. 
• Level 1 evidence supports the use of N/OFG, a nociceptin orphan peptide receptor agonist for the treatment of neurogenic bladder in SCI.
• There is level 4 evidence from 3 studies that instillations with oxybutinun or propantheline have equivocal benefits for neurogenic bladder in people with SCI. This lack of effect may be compounded by level 4 evidence suggesting systemic absorption may occur with this therapy, resulting in systemic side effects.
• There is level 1 evidence from a single small RCT (n=10) that intrathecal baclofen may be beneficial for bladder function improvement in individuals with SCI when oral pharmacological interventions are insufficient.
• Level 4 evidence is available from a single, small (n=9), case series study for the use of intra-thecal clonidine to improve detrussor hyperreflexia in individuals with SCI when a combination of oral treatment and sterile intermittent catheterization are insufficient.
• There is level 4 evidence from three studies that surgical augmentation of bladder (ileocystoplasty) may result in enhanced bladder capacity under lower filling pressure and improved continence in persons with SCI who previously did not respond well to conservative approaches for overactive bladder.
• Level 1 evidence suggests that moxisylyte decreases maximum urethral closure pressure by 47.6% at 10 minutes after an optimum dose of 0.75mg/kg in individuals with SCI.
• There is level 1 evidence from a single study that suggests that tamsulosin may improve bladder neck relaxation and subsequent urine flow in SCI individuals. 
• There is level 4 evidence (two studies, n=28 & 9) that  supports terazosin as an alternative treatment for bladder neck dysfunction in SCI individuals provided that side effects and drug tolerance are monitored.
• There is level 4 evidence derived from a single, case series study involving 46 subjects (41 completers) that indicates some potential for phenoxybenzamine as an adjunct treatment for neuropathic bladder following SCI, when tapping or crede is insufficient to achieve residual urine volume of <100mL. Further evidence in required.
• Level 4 evidence from 1 small retrospective chart review suggests that 6 months of alpha 1-blocker therapy may improve upper tract stasis secondary to SCI in men by decreasing the duration of involuntary contractions.
• There is level 1 evidence from a single RCT with support from several additional controlled and uncontrolled trials that botulinum toxin injected into the external urinary sphincter may be effective in improving outcomes associated with bladder emptying in persons with neurogenic bladder due to SCI
• There is level 2 evidence from a single trial that transurethral botulinum toxin injections were significantly more effective in reducing maximum urethral pressure than transperineal injections in persons with neurogenic bladder due to SCI.
• There is level 4 evidence that indwelling urethral catheterization is associated with a higher rate of acute urological complications than intermittent catheterization.
• There is level 4 evidence that prolonged indwelling catheterization, whether suprapubic or urethral, may result in a higher long-term rate of urological and renal complications than intermittent catheterization, condom catheterization or triggered spontaneous voiding.
• There is level 4 evidence that intermittent catheterization, whether performed acutely or chronically, has the lowest complication rate.
• Results are conflicting about the complications associated with chronic use of a spontaneous triggered voiding but some authors present level 4 evidence that this method has comparable long-term complication rates to intermittent catheterization.
• There is level 4 evidence that those who use intermittent catheterization at discharge from rehabilitation may have difficulty continuing, especially those with tetraplegia and complete injuries. To a lesser degree females also have more difficulty than males in maintaining compliance with IC procedures.
• There is level 1 evidence based on 1 RCT that pre-lubricated hydrophilic catheters are associated with fewer UTIs and reduced incidence of urethral bleeding and microtrauma as compared to conventional Poly Vinyl Chloride catheters.
• There is level 2 evidence based on 1 RCT that fewer UTIs, but not necessarily urethral bleeding may result with the use of hydrophilic catheters as compared to conventional PVC catheters.
• There is level 4 evidence that urethral complications and epididymoorchitis occurs more frequently in those using IC programs for bladder emptying, but the advantages of improved upper tract outcome over those with indwelling catheters outweigh these disadvantages.
• There is level 4 evidence that using a portable ultrasound device reduces the frequency and cost of intermittent catheterizations.
• There is level 4 evidence that triggering mechanisms such as the Valsalva or Crede maneuvers may assist some individuals with neurogenic bladder in emptying their bladders without catheterization. However, high intra-vesical voiding pressures can occur which could conceivably lead to renal complications.
• There is level 4 evidence that despite a significant incidence of urological and renal complications associated with acute and chronic indwelling suprapubic catheterization, this may still a reasonable choice for bladder management for people with poor hand function, lack of care-giver assistance, severe lower limb spasticity, urethral disease, and persistent incontinence with urethral catheterization.
• There is level 4 evidence that those with indwelling catheters are at higher risk for bladder cancer than those with non-indwelling catheter management programs.  Screening for cancer may require routine biopsy as well as cystoscopy.
• There is level 4 evidence that condom drainage can be associated with urinary tract infection and upper tract deterioration.
• There is level 4 evidence that penile implants may allow easier use of condom catheters, thereby reducing incontinence and improving sexual function.
• There is level 4 evidence that most individuals who receive catheterizable stomas become newly continent and can self-catheterize.  It appears possible that this surgical intervention could protect upper tract function.  Larger studies are needed to better evaluate true incidence of complications, and long-term bladder and renal outcome.
• There is level 4 evidence that most individuals undergoing cutaneous ileal conduit (ileo-ureterostomy) diversion became newly continent and were more satisfied than with their previous bladder management method. Long-term follow-up demonstrated the presence of a high incidence of urological or renal complications.
• There is level 4 evidence from eight studies that ongoing use of sacral anterior root stimulation (accompanied in most cases by posterior sacral rhizotomy) is an effective method of bladder emptying resulting in reduced incontinence for the majority of those implanted. This is associated with increased bladder capacity and reduced post-void residual volume.
• There is level 4 evidence from five studies that sacral anterior root stimulation (accompanied in most cases by posterior sacral rhizotomy) may be associated with reducing UTIs and autonomic dysreflexia.
• There is level 4 evidence from two studies that direct bladder stimulation may result in reduced incontinence, increased bladder capacity and reduced residual volumes but requires further study as to its potential clinical use.
• There is level 4 evidence from various single studies that other forms of neuroanatomically-related stimulation (e.g., electrical stimulation to posterior sacral, dorsal penile or clitoral nerve or surface magnetic sacral stimulation or direct bladder stimulation) may result in increased bladder capacity but require further study as to their potential clinical use. Further development involving this approach may permit sacral anterior root stimulation without the need for posterior root ablation.
• There is level 4 evidence from a single study that epidural dorsal spinal cord stimulation at T1 or T11 originally intended for reducing muscle spasticity may have little effect on bladder function.
• There is level 4 evidence from a single study that a program of functional electrical stimulation exercise involving the quadriceps muscle originally intended for enhancing muscle function and reducing muscle spasticity has only marginal (if any) effects on bladder function.
• There is level 4 evidence from a single case-series study that sphincterotomy is effective in reducing episodes of autonomic dysreflexia associated with inadequate voiding.
• There is level 4 evidence from a single case-series study that sphincterotomy, as a staged intervention, can provide long-term satisfactory bladder function.
• There is level 2 evidence from a single low-quality RCT but supported by level 4 studies that both sphincterotomy and implantation of a sphincteric stent are effective in reducing incontinence, with little need for subsequent catheterization, and both treatments are associated with reduced detrusor pressure and reduced post-void residual volume but not with changes in bladder capacity. The only significant difference in these 2 treatments was the reduced initial hospitalization associated with the stent, given the lesser degree of invasiveness.
• There is level 4 evidence that implantation of a sphincteric stent may result in reduced incidence of UTIs and bladder-related autonomic dysreflexia over the short-term although several studies have demonstrated the potential for various complications and subsequent need for re-insertion or another approach over the long-term.
• There is level 4 evidence from a single long-term follow-up study of those having a previous sphincterotomy that the incidence of various upper and lower tract urological complications may be quite high.
• There is level 4 evidence from a single case-series study that advocates for placement of a temporary stent early after injury as a reversible option that allows patients to choose from the range of permanent stent placement to less invasive bladder management methods such as intermittent catheterization.
• There is level 4 evidence based on a single study that transurethral balloon dilation of the external sphincter may permit removal of indwelling catheters in place of condom drainage, and also be associated with reduced detrusor pressure and post-void residual volume but not with changes in bladder capacity.
• There is level 4 evidence based on a single study that implantation of artificial urinary sphincter may be useful in the treatment of incontinence in SCI but further study is required.
• There is level 2 evidence from a single study that early treatment with electroacupuncture may shorten the time that it takes to develop low pressure voiding /emptying with minimal residual volume, when combined with conventional methods of bladder management. 
• Level 4 evidence from two studies suggests that intranasal DDVAP may reduce nocturnal urine production with fewer night-time emissions and also may reduce the need for more frequent catheterizations in persons with SCI with neurogenic bladder that is otherwise unresponsive to conventional therapy.
• There is level 4 evidence from four studies that nerve crossover surgery (anastomosis of more rostral ventral nerve roots to S2-S3 spinal nerve roots) may result in improved bladder function in chronic SCI. 
• Level 1 evidence based on a single RCTon SCI inpatients suggests that both limited and full microbial investigation result in adequate clinical response to UTI treatment with antibiotics.  Therefore the cost savings attributed to a limited microbial investigation favours this practice in the investigation of UTI although more rigorous investigation of the patient outcomes and attributed costs is needed.
• There is limited level 1 evidence from a single investigation that refrigeration (up to 24 hours) of urine samples prior to sample processing does not alter urinalysis or urine culture results in SCI patients.
• There is limited level 2 evidence from a single investigation that fewer false positive tests showing bacteriuria occur if indwelling or suprapubic catheters are changed prior to collection for urine culture analysis.
  There is conflicting level 4 evidence from two investigations concerning whether dipstick testing for nitrates or leukocyte esterase is recommended to guide treatment decision-making.
• Level 2 evidence based on two RCTs suggests no difference in UTI rates between sterile vs clean approaches to intermittent catheterization during inpatient rehabilitation, although using a sterile method is significantly more costly.
  There is limited level 4 evidence from a single study that there is no difference in UTI rates between intermittent catheterization conducted by the patients themselves or by a specialized team during inpatient rehabilitation.
• There is limited level 4 evidence from a single study that similar rates of UTI may be seen for those using clean intermittent catheterization during inpatient rehabilitation as compared to those using similar technique over a much longer time when living in the community.
• There is limited level 4 evidence from a single study that differences in residual urine volume ranging from 0-153 ml were not associated with differences in UTI during inpatient rehabilitation.
• There is level 1 evidence based on 1 RCT that pre-lubricated nonhydrophilic catheters are associated with fewer UTIs as compared to conventional Poly Vinyl Chloride catheters.
• There is level 2 evidence based on 1 RCT that fewer UTIs, but not necessarily urethral bleeding may result with the use of hydrophilic catheters as compared to conventional PVC catheters.
• There is level 2 evidence based on a single prospective controlled trial and supported by a case control study that intermittent catheterization may lead to a lower rate of UTI as compared to other bladder management techniques such as use of indwelling or suprapubic catheter.
• There is level 3 evidence based on a single case control study that bladder management with a suprapubic as opposed to indwelling catheter may lead to a lower rate of UTI and reduced mortality in a poor, illiterate population where intermittent catheterization may not be viable as an approach to bladder management.
• There is weak level 2 evidence based on a single low quality RCT that suggests that use of the Statlock device to secure indwelling and suprapubic catheters may lead to a lower rate of UTI.
• There is level 2 evidence based on a single prospective controlled trial that suggests that removal of external condom drainage collection systems at night or for 24 hours/day might reduce perineal, urethral or rectal bacterial levels  but have no effect on bacteriuria.
• There is level 4 evidence based on a single case series that no bladder management method is advantageous in preventing pyelonephritis (though indwelling urethral catheterization does have the highest incidence of upper tract deterioration). However, the presence of reflux results in a 2.8 fold higher incidence of pyelonephritis.
• There is level 1 evidence based on a single RCT and supported by two level 4 investigations that bacterial interference in the form of E. coli 83972 bladder inoculation may prevent UTIs.
• There is level 1 evidence from a single RCT that low-dose, long-term ciprofloxacin may prevent symptomatic UTI.
• There is level 1 evidence from a single RCT that TMP-SMX as prophylaxis may reduce symptomatic UTI rates although conflicting findings were obtained from 2 prospective controlled trials. The potential for emergence of drug resistant bacteria and TMP-SMX related adverse events further limit the potential use of TMP-SMX for prophylaxis.
• There is level 4 evidence from a single study that suggests weekly oral cyclic antibiotic use, customized as to individual allergy and antimicrobial susceptibility, may be effective for UTI prevention in SCI patients. 
• There is level 1 evidence based on a single RCT that oral methenamine hippurate, either alone or in combination with cranberry, is not effective for UTI prevention.
• There is level 2 evidence from separate studies that bladder irrigation with trisdine, kanamycin-colistin or a 5% hemiacidrin solution combined with oral methenamine mandelate (2 mg qid) may be effective for UTI prevention.
• There are varying levels of evidence that bladder irrigation with neomycin/polymyxin (level 1), acetic acid (level 1), ascorbic acid (level 2) or phosphate supplementation (level 4) is not effective for UTI prevention.
• There is level 2 evidence based on a single low quality RCT that supports the use of daily body washing with chlorohexidine and application of chlorhexidine cream to the penis after every catheterization versus using standard soap to reduce bacteriuria and perineal colonization.
• There is conflicting level 1 evidence across 4 RCTs (1 +ive, 3 –ive) to support the effectiveness of cranberry in preventing UTI in patients with neurogenic bladder due to SCI.
• There is level 1 evidence from a single RCT that a single educational session conducted by SCI specialist health professionals with accompanying written materials and a single follow-up telephone call can result in reduced urine bacterial colony counts in community-dwelling individuals with prior history of SCI.
• The beneficial effects of education mediated by SCI specialist health professionals on reducing UTI risk in community-dwelling individuals with SCI are supported by a single level 2 study and two level 4 studies incorporating different features such as one-on one or group workshops, demonstrations, practice of techniques and written materials.
• There is no evidence assessing the relative effectiveness of different educational approaches for reducing UTI risk. 
• There is level 1 evidence from a single RCT that supports the use of 14 vs 3 days of Ciprofloxcin for improved clinical and microbiological outcomes in the treatment of UTI in persons with SCI. 
• There is level 1 evidence from a single RCT suggesting that 3 or 7 day Ofloxacin treatment is more effective than trimethoprim-sulfamethoxazole in treating UTI and results in significant bladder bacterial biofilm eradication in persons with SCI patients. 
• Level 4 evidence from a single study suggests that norfloxacin may be a reasonable treatment choice for UTI in SCI but subsequent resistance must be monitored.
• A low success rate of aminoglycosides in the treatment of SCI UTI is supported by level 1 evidence from a single RCT.
• Optimum antimicrobial treatment duration and dosage is uncertain due to the lack of comparative trials in persons with SCI.
• Level 4 evidence is reported for intermittent neomycin/polymyxin bladder irrigation being effective in altering the resistance of the offending bladder organism(s) to allow for appropriate antibiotic treatment.

Key Points

DESD Therapy in SCI: Enhancing Bladder Volumes Pharmacologically

Anticholinergic Therapy for SCI-Related Detrusor Overactivity

Propiverine, oxybutynin, tolterodine and trospium chloride are efficacious anticholinergic agents for the treatment of SCI neurogenic bladder.

• Treatment with 2 of oxybutynin, tolterodine or trospium may be effective for the treatment of SCI neurogenic bladder in those not previously responding to one of these medications.
• Oxybutynin co-treatment with verapamil may enhance the standard formulation of oxybutynin in the treatment of SCI detrusor hyperreflexia.
• Oral Tolterodine, propiverine or transdermal application of oxybutinin likely results in less dry mouth but are similar in efficacy to oral oxybutynin in terms of improving neurogenic detrusor overactivity.

Toxin Therapy for SCI-Related Detrusor Overactivity

• Overall botulinum toxin for neurogenic detrusor overactivity in SCI is effective in reducing incontinence and excessive bladder pressure while improving bladder capacity for those resistant to, or intolerant of, oral anticholinergics.
• Capsaicin seems to have some clinical benefits but the side effects of pain and AD are concerning for clinical use. Resiniferotoxin seems to be tolerated much better and has similar improvements therapeutically. Pharmaceutical formulation difficulties make it non-existent for clinical use at present.

Intravesical Instillations for SCI-Related Detrusor Overactivity

• Intravesical instillations with oxybutinun or propantheline are ineffective for treating neurogenic bladder in people with SCI.

Other Pharmaceutical Treatments for SCI-Related Detrusor Overactivity

• Intrathecal baclofen and clonidine may be beneficial for bladder function improvement but further confirmatory evidence is needed.

DESD Therapy in SCI: Enhancing Bladder Volumes Non-Pharmacologically

Surgical Augmentation of the Bladder to Enhance Volume

• Surgical augmentation of bladder may result in enhanced bladder capacity under lower filling pressure and improved continence in persons with SCI.
• Extraperitoneal vs intraperitoneal augmentation enterocystoplasty may result in better postoperative recovery.

DESD Therapy in SCI: Enhancing Bladder Emptying Pharmacologically

Alpha-adrenergic Blockers for Bladder Emptying

• Tamsulosin is likely to improve urine flow in SCI individuals with bladder neck dysfunction.
• Mosixylyte is likely able to decrease maximum urethral closure pressure at a dose of 0.75mg/kg in individuals with SCI.
• Terazosin may be an alternative treatment for bladder neck dysfunction in individuals with SCI. but side effects and drug tolerance should be monitored.
• Phenoxybenzamine may be useful as an adjunct therapy for reducing residual urine volume in SCI neuropathic bladders maintained by crede or tapping.
• Six months of alpha 1-blocker therapy in male SCI patients may improve upper tract stasis.

Botulinum Toxin for Bladder Emptying

• Botulinum toxin injected into the sphincter is effective in assisting with bladder emptying for persons with neurogenic bladder due to SCI.

DESD Therapy in SCI: Enhancing Bladder Emptying Non-Pharmacologically

Comparing Methods of Conservative Bladder Emptying

• Intermittent catheterization, whether performed acutely or chronically, has the lowest complication rate.
• Indwelling catheterization, whether suprapubic or urethral or whether conducted acutely or chronically, may result in a higher long-term rate of urological and renal complications than other management methods.
• Persons with tetraplegia and complete injuries and to a lesser degree females may have difficulty in maintaining compliance with intermittent catheterization procedures following discharge from rehabilitation.

Intermittent Catheterization

• Although both pre-lubricated and hydrophilic catheters have been associated with reduced incidence of UTIs as compared to conventional Poly Vinyl Chloride catheters, less urethral microtrauma with their use may only be seen with pre-lubricated catheters.
• Urethral complications and epididymoorchitis occurs more frequently in those using IC programs.
• Portable ultrasound device can improve the scheduling of intermittent catheterizations.

Triggering-Type or Expression Voiding Methods of Bladder Management

• Valsalva or Crede maneuver may assist some individuals to void spontaneously but produce high intra-vesical pressure, increasing the risk for long-term complications.

Indwelling Catheterization (Indwelling or Suprapubic)

• With diligent care and ongoing medical follow-up, indwelling suprapubic catheterization may be an effective and satisfactory bladder management choice for some people, though there is insufficient evidence to report lifelong safety of such a regime.
• Indwelling catheter users are at higher risk of bladder cancer, especially in the second decade of use, though risk also increases during the first decade of use.

Condom Catheterization

• Patients using condom drainage should be monitored for complete emptying and for low pressure drainage, to reduce UTI and upper tract deterioration. Sphincterotomy may eventually be required. 
• Penile implants may allow easier use of condom catheters and reduce incontinence.

Continent Catheterizable Stoma and Incontinent Urinary Diversion

• Catheterizable abdominal stomas may increase the likelihood of achieving continence and independence in self-catherization, and may result in a bladder management program that offers more optimal upper tract protection.
• Cutaneous ileal conduit diversion may increase the likelihood of achieving continence but may also be associated with a high incidence of various long-term complications.

Electrical Stimulation for Bladder Emptying (and Enhancing Volumes)

• Sacral anterior root stimulation (accompanied in most cases by posterior sacral rhizotomy) enhances bladder function and is an effective bladder management technique, though the program (surgery and followup) requires significant expertise.
• Direct bladder stimulation may be effective in reducing incontinence and increasing bladder capacity but requires further study.
• Posterior sacral, pudenal, dorsal penile or clitoral nerve stimulation may be effective to increase bladder capacity but requires further study.
• Early sacral neural modulation may improve management of lower urinary tract dysfunction but requires further study.

Sphincterotomy, Artificial Sphincters, Stents and Related Approaches for Bladder Emptying

• Surgical and prosthetic approaches (with a sphincterotomy and stent respectively) to allow bladder emptying through a previously dysfunctional external sphincter both seem equally effective resulting in enhanced drainage although both may result in long-term upper and lower urinary tract complications.
• Artificial urinary sphincter implantation and transurethral balloon dilation of the external sphincter may be associated with improved bladder outcomes but require further study.

DESD Therapy in SCI: Other Miscellaneous Treatments

• Early electroacupuncture therapy as adjunctive therapy may result in decreased time to achieve desired outcomes.
• Intranasal DDVAP may reduce nocturnal urine emissions and decrease the frequency of voids (or catheterizations).
• Anastomosis of the T11, L5 or S1 roots to the S2-S3 spinal nerve roots may result in improved bladder function in chronic SCI.

Urinary Tract Infections: Detecting and Investigating UTIs

• Both limited and full microbial investigation may result in adequate clinical response to UTI treatment with antibiotics.
• Indwelling or suprapubic catheters should be changed just prior to urine collection so as to limit the amount of false positive urine tests.
• Urinalysis and urine culture results of SCI patients are not likely to be affected by sample refrigeration (up to 24 hours).
• It is uncertain if dipstick testing for nitrates or leukocyte esterase is useful in screening for bacteriuria to assist treatment decision-making.

Urinary Tract Infections: Non-Pharmacological Methods of Preventing UTIs

Intermittent Catheterization and Prevention of UTIs

• Sterile and clean approaches to intermittent catheterization seem equally effective in minimizing UTIs in inpatient rehabilitation.
• Similar rates of UTI may be seen with intermittent catheterization as conducted by the patients themselves or by a specialized team during inpatient rehabilitation.
• Similar rates of UTI may be seen with intermittent catheterization, whether conducted in the short-term during inpatient rehabilitation or in the long-term while living in the community.
• UTIs were not associated with differences in residual urine volumes after intermittent catheterization.

Intermittent Catheterization using Specially Coated Catheters for Preventing UTIs

• A reduced incidence of UTIs or reduced antibiotic treatment of symptomatic UTIs have been associated with pre-lubricated or hydrophilic catheters as compared to standard non-hydrophilic catheters.

Other Issues Associated with Bladder Management and UTI Prevention

• Intermittent catheterization is associated with a lower rate of UTI as compared to use of indwelling or suprapubic catheter.
• The Statlock device to secure indwelling and suprapubic catheters may lead to a lower rate of UTI.
• Removal of external condom drainage collection systems at night or for 24 hours/day may reduce perineal, urethral or rectal bacterial levels but have no effect on bacteriuria.
• The presence of vesicoureteral reflux likely has a greater impact on development of significant infections than the choice of bladder management.

Urinary Tract Infections: Pharmacological and Other Biological Methods of UTI Prevention

Bacterial Interference for Prevention of UTIs

• E. coli 83972 bladder inoculation may prevent UTIs.

Antibiotic Prophylaxis of UTIs

• Ciprofloxacin may be indicated for UTI prophylaxis in SCI but further research is needed to support its use.
• Long-term use of TMP-SMX is not recommended for sustained use as a suppressive therapy for UTI prevention.
• A weekly oral cyclic antibiotic, customized to the individual, may be beneficial in preventing UTI in SCI.

Antiseptic and Related Approaches for Preventing UTIs

• Oral methenamine hippurate, either alone or in combination with cranberry, is not effective for UTI prevention.
• The antiseptic agents delivered via bladder irrigation (5% hemiacidrin solution combined with oral methenamine mandelate) may be effective for UTI prevention, whereas others are not (i.e., trisdine, kanamycin-colistin, neomycin/polymyxin, acetic acid, ascorbic acid and phosphate supplementation).
• Daily body washing with chlorohexidine and application of chlorhexidine cream to the penis after every catheterization instead of using standard soap may reduce bacteriuria and perineal colonization.

Cranberry for Preventing UTIs

• It is uncertain if cranberry is effective in preventing UTIs in persons with SCI.

Urinary Tract Infections: Educational Interventions for Maintaining a Healthy Bladder and Preventing UTIs

• A variety of bladder management education programs are effective in reducing UTI risk in community-dwelling persons with SCI, although limited information exists as to the most effective approaches.

Urinary Tract Infections: Pharmacological Treatments of UTIs

Antibiotics in Treatment of UTIs

• Ciprofloxin administered over 14 (vs 3) days may result in improved clinical and microbiological SCI UTI treatment outcome.
• Ofloxacin administered over either a 3 or 7 day treatment regimen may result in significant SCI UTI cure and bladder bacterial biofilm eradication rate, moreso than trimethoprim-sulfamethoxazole.
• Norfloxacin may be a reasonable treatment choice for UTI in SCI but subsequent resistance must be monitored.
• Aminoglycosides have a low success rate in the treatment of SCI UTI.
• Intermittent neomycin/polymyxin bladder irrigation may be effective in altering the resistance of the offending bladder organism(s) to allow for appropriate antibiotic treatment.

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Fracture Risk following SCI

There is overwhelming evidence that supports the importance of addressing bone health issues early after SCI. A higher incidence of low-trauma fractures exist in people who sustain SCI (Table 1); the majority of low-trauma fractures occur following transfers or activities that involve minimal or no trauma (Comarr et al. 1962; Ragnarsson & Sell; 1981; Freehafer 1995;). The distal femur and proximal tibia (knee region) are most at risk, consistent with site-specific decreases in BMD such that fractures of the distal femur were previously referred to as ‘the paraplegic fracture’ (Comarr et al. 1962).

Risk factors for low-trauma fracture after SCI include: gender, age, time post injury, impairment, low BMI and low knee region BMD. Women have a greater risk compared with men (Vestergaard et al. 1998; Lazo et al. 2001; Nelson et al. 2003; Garland et al. 2004). Increasing age and longer time since injury (Frisbie 1997; McKinley et al.1999; Garland et al. 2004; Garland et al. 2005) increases fracture risk which rises significantly at 10 years post injury. Further, people with paraplegia have more fractures (Frisbie 1997) and those with complete injuries have greater bone mass loss compared with those with incomplete injuries (Garland et al. 2004; Garland et al. 2005). BMD fracture thresholds are values below which low-trauma fractures begin to occur; whereas fracture breakpoints are values below which the majority of fractures occur (Garland et al. 2005). Knee region aBMD and vBMD thresholds for fracture and breakpoint have been identified (Mazess 1990; Eser et al. 2005; Garland et al. 2005). In the general population, individuals with a prior history of low-trauma fracture or a maternal history of fracture have an elevated fracture risk; these risk factors should also be considered during a fracture risk assessments among patients with SCI.

Table 1: Fractures and risk factors for fragility fractures after SCI

• Low trauma fractures, especially around the knee, are common in people with SCI.

SLOP Detection and Diagnosis

In order to assess and understand your patient’s bone health, it is important to measure their BMD and document their fracture risk. We advocate diagnosing the presence of SLOP based on the following DXA criteria (Table 2).

Table 2: Definition of Sublesional Osteoporosis (SLOP)

We recommend documenting your patients fracture risk by completing the risk factor profile check-list (Craven et al. 2008, Craven et al. 2009). We propose that the presence of ≥3 risk factors implies a moderate fracture risk, while ≥5 risk factors implies a high fracture risk (Table 3).

Table 3: Risk Factors for Lower Extremity Low-trauma Fracture After SCI

Bone Outcome Measures

There are multiple methods for assessing bone health, commonly used tools include: bone imaging, biochemical markers and histomorphometry.

DXA is considered by the World Health Organisation as the “gold standard” to diagnose osteoporosis and is the most widely used assessment technique for determining treatment effectiveness; although in some countries, peripheral quantitative computed tomography (p-QCT) is available as a research tool (Frotzler et al. 2008) Areal BMD (g/cm²) is quantified non-invasively with imaging technologies such as dual energy X-ray absorptiometry (DXA) and previously with dual energy photon absorptiometry (DPA). DXA measures areal BMD [aBMD= bone mineral content (BMC)(g)/area (cm²)]; whereas p-QCT measures volumetric BMD [vBMD = BMC(g)/volume (cm³)]. There are several established methods for measuring BMD at the knee (Garland et al. 1993; Moreno et al. 2001; Eser et al. 2004; Morse et al. 2009). Regardless of the methodology chosen, assessment of knee region BMD is crucial as it best predicts knee region fracture risk after SCI (Eser et al. 2005; Garland et al. 2005).

Volumetric BMD (g/cm³) is assessed using peripheral quantitative computed tomography (pQCT). Peripheral QCT is a relatively safe and precise technique to differentiate cortical bone from trabecular bone, assess bone geometry and volumetric density. The imaging resolution has continued to improve and a high resolution (HR) pQCT now exists (80 micrometers) to give detailed information on peripheral bone microstructure.

Increases in aBMD or vBMD are presumed to be a suitable surrogate outcome for fracture risk reduction when assessing the effectiveness of SLOP therapy. Whereby, “optimal therapy” would be defined as increases in knee region BMD above the fracture threshold in the absence of low-trauma fracture.

Biochemical markers of bone turnover can be used as an adjunct to DXA in the assessment of bone health among patients with SCI. Serum and urine markers provide useful insight into bone metabolism at specific time points after injury and are an effective tool for monitoring response to therapy. The current therapeutic utility of bone turnover markers is limited by day-to-day, diurnal, inter-individual, and inter-assay variability. For urine markers, results need to be corrected for creatinine (Reiter et al. 2007).

The bone formation markers include bone-specific alkaline phosphatase (BALP), osteocalcin (OC N-terminal propeptide of type I collagen (PINP), and C-terminal propeptide of type I collagen (PICP).

Markers of bone resorption include urinary free and total pyridinoline (Pyr) and deoxypyridinoline (DPD) crosslinks, type 1 collagen C-telopeptide (CTX), and N-telopeptide (NTX). Pyr and DPD are molecules that provide stability to collagen and, along with CTX and NTX, are released when collagen is degraded during bone resorption (Brown et al. 2009).

For a bone marker to be useful in assessing the rate of bone turnover and/or monitoring therapy effectiveness, the difference in the rate of bone turnover before and after SCI, as well as the early period versus the late period after SCI, needs to be discernable.

Alignment of the choice of biomarkers across future bone health studies may allow for cross-study comparison or future meta-analyses.

Histomorphometry are measurements from bone biopsies to provide an in-depth understanding of bone. There are two types of bone histomorphometry, dynamic and static. Dynamic histomorphometry involves using substances such as tetracycline to measure tissue growth. Static histomorphometry involves determining the size and types of cells; measurements include length, area or cell counts. Although bone histomorphometry is considered an important tool, it is not always feasible because it requires surgically obtaining bone specimens from consenting participants.

Clinical Guide

In the following sections, prevention and treatment interventions for maintaining bone health after SCI are discussed. As bone loss is greatest immediately following SCI, in this review pharmacological and non-pharmacological interventions are classified as either prevention (the participants are less than 1 year post SCI) or treatment (study involved participants who are > 1 year after the injury). The intent is to address two distinct clinical questions: 1.What is the best way to prevent acute regional declines in bone mineral density?; and 2. What are the best treatments for low bone mass of the hip and knee region for people with longstanding SCI?

When selecting a treatment to offer patients, clinicians seek the best available evidence to support their practice. Ideally, one would like to see three randomized control trials (Level 1 evidence) from separate centres demonstrating the efficacy of a therapy prior to routine implementation. Having highlighted this issue, the diversity of interventions, study design and outcome measures make interpretation of the SCI bone health literature challenging and subject to controversy.

The following sections attempt to identify the best available literature to address specific clinical questions.

Pharmacological Therapy: Bisphosphonates

Within weeks after SCI, there is a marked increase in bone resorption (breaking bone down) with a decrease in bone formation (adding new bone) and this is responsible for the significant loss in bone mass. Bisphosphonates are a group of medications that are used to prevent declines in bone mass or treat low BMD; they act to slow down excessive bone resorption. They are generally divided into two types, those with or without nitrogen; each type has a different mechanism of action. Etidronate, Clodronate and Tiludronate do not contain nitrogen while Pamidronate, Alendronate, Ibandronate, Risedronate and Zoledronate contain nitrogen. Etidronate (Didrocal), Alendronate (Fosamax) and Risedronate (Actonel) are oral bisphosphonates, which are currently approved for the treatment of postmenopausal osteoporosis in Canada (Brown et al. 2002). Clodronate (Benefos or Ostac) is available intravenously (IV) and orally for the treatment of osteoporosis.  Tiludronate (Skelid) is available in oral form in the United States. Zoledronic acid (Zoledronate) is a newer once yearly bisphosphonate which is administered via IV infusion. Concurrent supplementation with calcium and vitamin D have been important additions to bisphosphonate therapy for other medical conditions (such as post-menopausal osteoporosis) (Brown et al. 2002) and should be considered when prescribing oral bisphosphonates although the concurrent administration of all three compounds has not been prospectively evaluated.

Non-Pharmacologic Therapy: Rehabilitation Modalities

Rehabilitation options after SCI for bone health focus on stimulating muscles and encouraging weight-bearing. This section includes five modalities; functional electrical stimulation (FES), electrical stimulation (ES), standing and walking, treadmill training and ultrasound. FES is an important option to stimulate muscle with the goal of increasing regional BMD, and involves the use of surface or implanted electrodes to stimulate standing, ambulation or bicycling (cycle ergometry). The FES-cycle ergometer uses a series of electrodes placed over the hamstrings, quadriceps and gluteal muscles of the legs to simulate a cycling pattern. Weight-bearing activities are also used for bone health after SCI; these modalities include either passive (tilt-table or standing frame) or active weight-bearing activities with or without assistance from FES. Many FES studies have enrolled participants with both acute and chronic injuries and are therefore difficult to classify as pure prevention or treatment interventions. For the purpose of this review, studies that enrolled participants that ranged from the acute phase to > 1 year were included with the treatment literature as the majority of their participants were in the chronic phase.

General Discussion

The risk for low trauma fractures after SCI has been established and low bone mass is an important factor to be considered. In 2002, the Canadian Medical Association published clinical practice guidelines for prevention and treatment of bone health (Brown et al. 2002). Currently, these guidelines do not specifically address persons with spinal cord injury. While, they do provide a resourcefor osteoporosis diagnosis, prevention and treatment, the lack of SCI-specific, consensus-based guidelines for SLOP, has resulted in diverse SLOP screening, prevention, and treatment practices among SCI clinicians (Morse et al. 2008; Ashe et al. 2009). Hopefully future national guidelines will provide recommendations for people who have SCI and diverse impairments that lead to reduced weight-bearing, muscle activity and physical activity levels. Recently a decision guide has been published for rehabilitation professionals on the identification and management of bone health related issues for people with SCI (Craven et al. 2008, Craven et al. 2009).

In this review we note some support for pharmacological agents, but less support for rehabilitation modalities for the prevention and management of bone health in people with SCI. Our results have some similarities with the recent systematic review by Bryson and Gourlay (2009). Our results for the non-pharmacological treatment of bone health are consistent with the review by Bering-Sorensen and colleagues (2009) highlighting promise with some modalities. However, this review differs by reporting evidence for early (acute) and late (>12 months) intervention with rehabilitation modalities and therefore provides a description of the results based on whether the goal of therapy is prevention or treatment of SLOP. In the past 40 years there have been a number of interventions (both pharmacological and rehabilitation modalities) aimed to maintain or slow down bone mass decline after SCI yet consistent methodological oversights have emerged including: small sample sizes and broad inclusion criteria that do not always account for gender, time since injury or impairment differences between participants.

The pharmacological interventions (either prevention or treatment interventions) discussed here report stronger methodologies— all except one were RCTs with PEDro scores ranging from 6-10 indicating moderate to high quality. In contrast, the studies employing rehabilitation modalities had low numbers of participants and only 3 of the 25 studies were RCTs. These factors contribute to difficulties drawing generalisible conclusions regarding the impact of rehab interventions on bone parameters. Nonetheless, despite the lack of evidence to establish the effectiveness of these rehab modalities on bone parameters, it does not negate these treatments as beneficial to other body systems. For example, FES-cycling may have small effects on bone, but this modality has been shown to have large effects on cardiovascular health (Jacobs & Nash 2004).

There are a few key points to consider when interpreting the results from interventions designed to maintain and/or improve bone parameters after SCI. These include biological differences in bone development and maintenance between men and women, the natural decline in bone mass with aging and the selected primary outcome measure. Age-related changes in bone mass affect both women and men but the pattern of change is different because estrogen plays such a dominant role in bone remodeling.  Consequently in women, the loss of estrogen at menopause initiates a rapid loss of bone that eventually slows but continues throughout life. Men generally do not experience the rapid phase of bone loss with aging rather, only a slower phase of bone loss is observed. Therefore, keeping in mind that bone mass declines over time, a study that reports no significant difference in BMD between two time periods 6 months apart may be interpreted as positive because of the anticipated loss.

Due to the diversity of primary outcomes (BMD bydual photon absorptiometry [DPA], DXA or pQCT, urine or blood markers) it is difficult to pool the results from multiple studies. When measuring parameters such as urine or blood biomarkers, studies of short duration may yield significant results. However, using imaging, cortical bone remodeling can take at least 9 months in order to observe changes within participants over time. Consequently, investigations that did not maintain an intervention for at least 6 months may not show changes, but, the results cannot be interpreted as negative. Importantly, all primary outcomes for bone health after SCI are surrogate measures, that is, there has yet to be a study published in this area that investigates the effect of an intervention (either pharmacological or non-pharmacological) on fracture reduction. Fracture reduction studies are somewhat infeasible due to cost and the large number of participants that would needed and followed longitudinally. Consequently, the clinical significance of the interventions based on fractures for this population remains to be determined. Prospective multicentre intervention studies using common interventions and outcome assessments are urgently needed.

Conclusion

• There is a significant risk for low-trauma fractures after SCI; the risk increases for women, people with motor complete injuries (AIS A and B) and longer duration of injury. Early assessment and ongoing monitoring of bone health are essential elements of SCI care. There is Level 1 evidence for the prevention and treatment of bone loss using medications; however, non-pharmacological evidence for preventing a decline in bone mass and treating low bone mass is poor. Interpretation and pooling of bone health studies is limited by small samples, diverse treatment protocols, heterogeneous samples (in terms of impairment and injury duration) and short treatment durations given the time required to detect improvements in bone parameters and variability associated with different imaging technologies. As noted in two recent publications (Craven et al. 2008, Ashe et al. 2009), a consensus regarding the ideal duration of therapy and choice of outcome measures would advance the field.

• Early assessment and monitoring of bone mass after SCI are essential to identify low bone mass and quantify risk of lower extremity fragility fracture.
• Prevention with oral bisphosphonates (Tiludronate, Clodronate and Etidronate) may slow the early decline in hip and knee region bone mass after SCI. There is limited evidence that treatment with oral bisphosphonates maintains hip and knee region bone mass late after SCI.
• There is a lack of definitive evidence supporting non-pharmacological interventions for either prevention or treatment of bone loss after SCI.

Summary

• There is level 1 evidence (from 3 RCTs) (Minaire et al. 1981, 1987; Chappard et al. 1995) that oral Tiludronate and Clodronate prevent a decrease in BMD of the hip and knee region with no adverse effects on bone mineralization in men with paraplegia.
• There is level 1 (from 1 RCT) (Pearson et al. 1997) that oral Etidronate prevents a decrease in BMD of the hip and knee region in people with incomplete paraplegia or tetraplegia (AIS D impairment) who return to walking within 3 months of the SCI.
• There is level 1 evidence (from 1 RCT) (Gilchrist et al. 2007) that once weekly oral Alendronate maintains BMD at the hip.
• There is level 1 evidence (from 1 RCT) (Shapiro et al. 2007) once yearly IV Infusion Zoledronate does not prevent a decline in hip region BMD at 12 months among patients with motor complete injuries
• There is level 1 evidence (from 1 RCT) (Bauman et al. 2005) that Pamidronate 60mg IV seven times per year and level 2 evidence (from 1 non-randomized prospective controlled trial) (Nance et al. 1999) that Pamidronate 30 mg IV six times per year is not effective for the prevention of BMD loss at the hip and knee region early after SCI in men and women who have motor complete paraplegia or tetraplegia.
• There is level 1 evidence (from 1 RCT) (Zehnder et al. 2004) that Alendronate 10 mg daily and Calcium 500mg orally 3x/day is effective for the maintenance of BMD of the total body, hip and knee region for men with paraplegia.
• There is level 1 evidence (from 1 RCT) (Bauman et al. 2005b) that vitamin D analog is effective for maintaining leg BMD.
• There is level 1 evidence (from one RCT) (Warden et al. 2001) that short-term (6 weeks) ultrasound is not effective for treating bone loss after SCI.
• There is level 2 evidence (from 1 non-randomized prospective controlled trial) (Shields et al. 2006a) that ES reduced the decline in BMD in the leg.
• There is level 2 evidence (from 1 non-randomized prospective controlled trial) (Eser et al. 2003) that FES-cycling did not improve or maintain bone at the tibial midshaft in the acute phase.
• There is level 4 evidence (from 1 pre-post study) (Giangregorio et al. 2005) that walking and level 1 evidence (from 1 RCT) (Ben et al. 2005) that standing in the acute phase did not differ from immobilization for bone loss at the tibia.
• There is level 2 evidence (from 1 prospective controlled trial) (Bélanger et al. 2000) that electrical stimulation either increased or maintained BMD over the stimulated areas
• There is level 4 evidence (from 1 pre-post study) (Melchiorri et al. 2007) that vibration training did not improve or maintain BMC in the arms.
• There is level 4 evidence that FES cycle ergometry of at least 6 months duration may increased regional lower extremity BMD over areas stimulated.
• There is inconclusive evidence for Reciprocating Gait Orthosis, long leg braces, passive standing or self-reported physical activity as a treatment for low bone mass.

Key Points

Bone Health & Fracture

• Low trauma fractures, especially around the knee, are common in people with SCI.
• Bone health management should begin early following SCI as there is a significant decline in lower extremity BMD in the first year and the efficacy of drug interventions appear to be most effective with a shorter time period between injury onset and drug administration
• Measurement and monitoring of hip and knee region BMD after SCI are essential to identify low bone mass and quantify lower extremity fracture risk.

Pharmacologic Therapy for Prevention of SLOP

• Oral Tiludronate and Clodronate prevent a decrease in BMD of the hip and knee region with no adverse effects on bone mineralization in men with paraplegia.
• Oral Etidronate prevents a decrease in BMD of the hip and knee region in people with AIS D paraplegia or tetraplegia.
• Once weekly oral Alendronate maintains BMD at the hip in men and women with AIS A-C paraplegia.
• Once yearly IV infusion Zoledronate does not maintain hip BMD at 12 months in men and women with AIS A or B paraplegia or tetraplegia.
• Pamidronate 30 mg IV or 60 mg IV 4x/year is not effective for the prevention of BMD loss at the hip and knee region early after SCI people with AIS A paraplegia or tetraplegia.
• In summary, there is limited evidence that bisphosphonates prevent hip and knee region BMD decline after SCI, although they are moderately effective for reducing the rate of bone resorption and degree of BMD decline in the hip and knee region.

Pharmacologic Therapy for Treatment of SLOP

• Alendronate 10 mg daily and Calcium 500 mg orally 3x/day is effective for the maintenance of BMD of the total body, hip and knee region for men with paraplegia.
• Vitamin D analog is effective for maintenance of BMD in the leg.
• Short term (6 weeks) therapeutic ultrasound is not effective for preventing bone loss after SCI.

Non-pharmacologic Therapy for Prevention and/or Treatment

• FES-cycling does not improve or maintain bone at the tibial midshaft in the acute phase but may increase/maintain lower extremity BMD the longer time since injury.
• Electrical stimulation can maintain or increase BMD over the stimulated areas.
• There is inconclusive evidence for Reciprocating Gait Orthosis, long leg braces, passive standing or self-reported physical activity as a treatment for low bone mass.
• There is a lack of definitive evidence supporting non-pharmacological interventions for either prevention or treatment of bone loss after a SCI.

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Spinal Cord Injury and its Impact on Bowel and Ano-rectal Function

Bowel function is a major physical and psychological problem for persons with spinal cord injury. Following a spinal cord injury, changes in bowel motility, sphincter control and gross motor dexterity interact to make bowel management a major life-limiting problem. In 2000, Lynch et al. surveyed 1200 persons with SCI and 1200 age and gender-matched controls to describe bowel function. For persons with SCI, their mean Fecal Incontinence Score (FIS) was significantly higher than controls. It was also noted that for persons with complete SCI, their mean FIS was significantly higher than those persons with incomplete SCI. Quality of life was affected by incontinence in 62% of SCI respondents compared with 8% of controls. Fecal urgency and time spent on bowel management were also significantly higher for persons with SCI. A significantly higher percentage (39%) of SCI respondents use laxatives compared to 4% of controls. The decreased ability to discriminate between gas and liquid for complete SCI patients also makes the chance for fecal incontinence more likely.

Depending on the level of injury, there are two distinct patterns in the clinical presentation of bowel dysfunction: injury above the conus medullaris results in upper motor neuron (UMN) bowel syndrome and injury at the conus medullaris and cauda equine results in lower motor neuron (LMN) bowel syndrome (Singal et al. 2006; Steins et al. 1997).

The UMN bowel syndrome, or hyperreflexic bowel, is characterized by increased colonic wall and anal tones. Voluntary (cortical) control of the external anal sphincter is disrupted and the sphincter remains tight, thereby promoting retention of stool. The nerve connections between the spinal cord and the colon, however, remain intact; therefore, there is preserved reflex coordination and stool propulsion. The UMN bowel syndrome is typically associated with constipation and fecal retention at least in part due to external anal sphincter activity (Steins et al. 1997).  Stool evacuation in these individuals occurs by means of reflex activity caused by a stimulus introduced into the rectum, such as an irritant suppository or digital stimulation.

LMN bowel syndrome, or areflexic bowel, is characterized by the loss of centrally-mediated (spinal cord) peristalsis and slow stool propulsion.  A segmental colonic peristalsis occurs only due to the activity of the intrinsic myenteric plexus, resulting in the production of drier and round- shaped stool. LMN bowel syndrome is commonly associated with constipation and a significant risk of incontinence due to the atonic external anal sphincter and lack of control over the levator ani muscle that causes the lumen of the rectum to open.

Completeness of injury also has a significant impact on bowel function in individuals with SCI.  Those with an incomplete injury may retain the sensation of rectal fullness and ability to evacuate bowels so no specific bowel program may be required.

Table 1: Clinical Presentations in Bowel Functions Following SCI (Singal et al. 2006)

Difficulties with bowel emptying are of concern to most persons with SCI. For the tetraplegic patient, loss of control over visceral function may be seen as more important than the ability to walk (Frost et al. 1993). Urinary problems in patients with SCI have been extensively studied, and with the advent of intermittent self-catheterization, electrical stimulation of the bladder and advances in diagnostic techniques, considerable improvements have been made in managing lower urinary tract and renal function. In contrast, the management of bowel disorders, and in particular, the intractable constipation that is so common in these patients, has remained essentially unchanged over the past two decades (MacDonagh et al. 1990).

Various researchers have shown that electrical stimulation of the somatic nervous system can bring about an alteration in visceral function in humans. Riedy et al. (2000) showed that short periods of electrical stimulation with perianal electrodes resulted in an increase in anal pressures. Bowel reflex centres within the sacral spinal cord may be released from descending inhibition after SCI and may be altered with somatic input (Frost et al. 1993). Electrical sacral root stimulation induces defecation in SCI patients and is currently under examination as a new therapy for fecal incontinence. In contrast to electrical stimulation, magnetic stimulation may produce similar results and is noninvasive (Morren et al. 2001). Morren et al. (2001) studied the effects of magnetic sacral root stimulation on anorectal pressure and volume in both fecal incontinence and SCI patients. Sun et al. (1995) investigated the role of spinal reflexes in anorectal function. Their subjects underwent anorectal manometry and electromyography, before and after having a sacral posterior rhizotomy performed by the same neurosurgeon. They found that all subjects lost conscious control of the external anal sphincter as well as  responses to intra-abdominal pressure and rectal distention. While the use of sacral root stimulation, either electrical or magnetic, seems to be producing positive results, further research is required.

Management

Few SCI patients feel normal desire to defecate and most use a variety of methods to initiate defecation, including laxatives, enemas, suppositories or digital stimulation of the rectum and anal canal. SCI results in severely prolonged colonic transit times both in the acute and chronic phase. However, the type of colorectal dysfunction depends on the level of SCI (Krogh et al. 2000; Stiens et al. 1997). Colorectal problems often restrict their participation in social activities and influence their quality of life. Krogh et al. (2000) and Nino-Murcia et al. (1990) measured colonic transit time in individuals using ingested radiopaque markers and abdominal radiographs taken at 24 hour intervals. They found that the mean transit time through the entire colon in SCI patients was significantly longer than normal adults. Future studies on colonic transit times and anorectal dynamics could aid in the approach used to manage bowel dysfunction in SCI patients. Difficulty with evacuation has been attributed to prolongation of the colonic transit time in individuals with SCI.

The Consortium for Spinal Cord Medicine developed guidelines for neurogenic bowel management (Consortium for Spinal Cord Medicine 1998). A comprehensive evaluation of bowel function, impairment, and possible problems is recommended at the onset of SCI and at least once annually.  The evaluation may include a patient history, physical exam, an assessment of the ability of the individual or his caregiver to perform procedures safely and effectively, as well as of the bowel program design, assistive techniques/devices used, and the patient’s diet. More recently, the Multidisciplinary Association of the Spinal Cord Injury Professionals (MASCIP 2009) in affiliation with the Spinal Cord Injury Centres of the United Kingdom and Ireland released guidelines for the management of neurogenic bowel. These guidelines provide standards for care for both those being admitted for rehabilitation and those living in the community.

Management of neurogenic bowel complications is reliant on the clinician to recognize common complications and their clinical presentation (Consortium for Spinal Cord Medicine, 1998, MASCIP 2009). Common complications include constipation, fecal impaction and hemorrhoids. Recommended management protocols for constipation include the establishment of a balanced diet with adequate fluid and fibre intake, increased daily activity, and if possible, reduction or elimination of medication contributing to constipation. If these recommendations fail, prokinetic medication may be used to promote transit through the gastrointestinal tract.  The step-wise management recommended for fecal impaction is first manual evacuation, then if not successful, oral stimulants, and finally oil retention enemas. To minimize the development of hemorrhoids, oral agents (to maintain soft-formed stool), minimize straining during bowel efforts, and minimal physical trauma during anal stimulation are recommended. Once hemorrhoids have developed, topical anti-inflammatory creams or suppositories are suggested as early treatment. Overall, the Consortium for Spinal Cord Medicine recommends further research in all bowel management areas (Consortium for Spinal Cord Medicine, 1998).

Summary

Gastrointestinal (GI) complications are frequent following a SCI and their daily challenges can severely affect the quality of life of an individual.  In addition, GI complications can lead to visits to physicians, re-hospitalizations, and even death.  The evidence suggests that a multi-faceted approach to bowel management is effective and includes consideration of diet, medications, fluid intake, and evacuation schedules.  When severe constipation persists and a bowel program cannot be attained, surgical options such as a colostomy or implanted stimulator may be considered.

• There is level 1 evidence (from one RCT; N=68) (Coggrave et al. 2009) that systematic use of less invasive interventions do not reduce the need for oral laxatives and invasive interventions. There is also level 1 evidence (Coggrave et al. 2009 that use of multifaceted bowel management programs increase the duration of time required for bowel management. This is in contrast with  level 4 evidence (from three pre-post studies; aggregate N=65) (Coggrave et al. 2006; Correa and Rotter 2000; Badiali et al. 1997;) that multifaceted bowel management programs reduce gastrointestinal transit time, incidences of difficult evacuations, and duration of time required for bowel management.
• There is level 4 evidence (from 1 case series; N=11) (Cameron et al. 1996) that indicates high fibre diets may lengthen colonic transit time.
• There is level 4 evidence (from 1 pre-post study; N=6) (Korsten et al. 2007) that digital rectal stimulation increases motility in the left colon.
• There is level 1 evidence (from 1 RCT) (Korsten et al. 2004) that electrical stimulation of the abdominal wall muscles can improve bowel management for individuals with tetraplegia.
• There is level 2 evidence (from 1 prospective controlled trial) (Binnie et al. 1991) that support the use of sacral anterior root stimulation to reduce severe constipation in complete injuries.
• There is level 4 evidence (from 3 pre-post studies) (Tsai et al. 2009, Lin et al. 2001; 2002) that functional magnetic stimulation may reduce colonic transit time in individuals with SCI.
• There is level 4 evidence (from 1 pre-post study with two subjects) (Mentes et al. 2007) that posterior tibial nerve stimulation improves bowel management for those with incomplete SCI.
• There is level 4 evidence (from 1 pre-post study with two subjects) (Johnston et al. 2005) that the Praxis FES system increases the frequency of defecation and decreases time required for bowel care in individuals with SCI.
• There is level 4 evidence (from 1 case series study) (Puet et al. 1997) that supports using pulsed water irrigation (intermittent rapid pulses) to remove stool in individuals with SCI.
• There is level 1 evidence (from 1 RCT) (Christensen et al. 2006) that supports the use of transanal irrigation (Peristeen Anal Irrigation system) over conservative bowel treatment (as outlined by the Paralyzed Veterans of America clinical practical guidelines).
• There is level 4 evidence (from 1 case series study, and one post-test) (Faaborg et al. 2008; Christensen et al. 2000) that supports the use of an Enema Continence Catheter to treat the neurogenic bowel.
• Cisapride: There is level 1 evidence (from 3 RCTs) (De Both et al. 1992; Rajendran et al. 1992; Geders et al. 1995) that cisapride significantly reduces colonic transit time for chronic constipation.
• Prucalopride: There is level 1 evidence (from 1 RCT) (Krogh et al. 2002) that prucalopride increases stool frequency, improves stool consistency and decreases gastrointestinal transit time.
• Metoclopramide: There is level 2 evidence (from 1 prospective controlled trial; N=20) (Segal et al. 1987) that intravenous administration of metoclopramide corrects impairments in gastric emptying.
• Neostigmine: There is level 1 evidence (from 1 RCT) (Korsten et al. 2005) that neostigmine, administered with or without glycopyrrolate, leads to a greater expulsion of stool.
• There is level 1 evidence that neostigmine with glycopyrrolate decreases total bowel evacuation times and improves bowel evacuation.
• Fampridine: There is level 1 evidence (from 1 RCT) (Cardenas et al. 2007) that fampridine can increase the number of days with bowel movements.
• There is level 1 evidence (from 1 RCT) (House and Stiens 1997) to support polyethylene glycol-based suppositories for bowel management. There is a clinically significant decrease in the amount of nursing time for persons requiring assistance and less time performing bowel care for the independent individual.
• There is level 4 evidence (from six studies) (Frisbie et al. 1986; Stone et al. 1990; Kelly et al. 1999; Rosito et al. 2002; Branagan et al. 2003, Munck et al. 2008) that colostomy reduces the number of hours spent on bowel care.
• There is level 4 evidence (from 1 retrospective pre-post study) (Frisbie et al. 1986) that colostomy greatly simplifies bowel care routines.
• There is level 4 evidence (from 1 case study) (Rosito et al. 2002) that colostomy reduces the number of hospitalizations caused by gastrointestinal problems and improves physical health, psychosocial adjustment and self-efficacy areas within quality of life.
• There is level 4 evidence (from 4 retrospective reviews) (Teichman et al. 1998; Christensen et al. 2000; Teichman et al. 2003, Worsoe et al. 2008) that the Malone Antegrade Continence Enema successfully treats the neurogenic bowel.
• There is level 4 evidence (from 1 retrospective review) (Christensen et al. 2000) that the Enema Continence Catheter can be used to treat the neurogenic bowel.  
• There is level 5 evidence (from 1 case report with one subject) (Hoenig et al. 2001) that a standing table alleviates constipation in individuals with SCI.
• There is level 4 evidence (from 1 post-test study) (Uchikawa et al. 2007) that a newly developed washing toilet seat with a CCD camera monitor for visual feedback reduces time spent on bowel care.
• There is level 4 evidence (from 1 pre-post study; N=24) (Ayas et al. 2006) that the abdominal massage is ineffective for treating the neurogenic bowel.

Key Points

• There is limited evidence that supports a multifaceted program for managing a neurogenic bowel.
• There is a need for further research to examine the optimal level of dietary intake in spinal cord injured patients.
• Digital rectal stimulation increases motility in the left colon in individuals with SCI.
• Electrical stimulation of the abdominal wall muscles can improve bowel management for individuals with tetraplegia.
• Functional magnetic stimulation may reduce colonic transit time in individuals with SCI.
• Sacral anterior root stimulation reduces severe constipation in individuals with SCI.
• More research is needed to warrant the use of the Praxis FES system for bowel management in individuals with SCI.
• Posterior tibial nerve stimulation is a relatively new treatment for fecal incontinence and while preliminary results show promise, the sample size is limited and more research is needed to warrant this new modality.
• Pulsed water irrigation may remove stool in individuals with SCI and transanal irrigation alleviates constipation and fecal incontinence. Often, more than one procedure is necessary for individuals that are unable to develop an effective bowel routine.
• Cisapride, prucalopride, metoclopramide, neostigmine, and fampridine may be used for the treatment of chronic constipation in persons with SCI.
• Cisapride and Prucalopride are not currently available in Canada or the United States due to adverse side effects. More research is required on these prokinetic agents prior to their regular use.
• Polyethylene glycol-based suppositories (10 mg. bisacodyl) are effective in maintaining or enhancing a successful bowel management program, especially for persons with an upper motor neuron SCI.
• Colostomy is a safe and effective treatment for severe, chronic gastrointestinal problems and perianal pressure ulcers in persons with SCI, and greatly improves their quality of life.
• The Malone Antegrade Continence Enema is a safe and effective treatment for severe, chronic gastrointestinal problems in persons with SCI when conservative bowel management options are unsuccessful.
• There is limited evidence that the use of a standing table and a washing toilet seat improves bowel function in individuals with SCI. 
• There is limited evidence that a washing toilet seat with visual feedback may assist bowel care.
• The abdominal massage appears to be ineffective for treatment of the neurogenic bowel.

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The Risk for Cardiovascular Disease in Persons with SCI

The majority of CVD events are the result of atherosclerosis (i.e., narrowing and hardening of the arteries) (Grey et al 2003). Persons with SCI appear to be particularly susceptible to the development of atherosclerotic disease (Bravo et al 2004). Researchers have revealed that persons with SCI exhibit a series of risk factors for atherosclerotic disease and thus CVD (as shown in Table 2).

A healthy endothelium (interior lining of blood vessels) is essential for the protection against atherosclerosis (Anderson 2003). Relatively limited data exists regarding the vascular health of individuals with SCI (Zbogar et al 2008, de Groot et al 2005,). However, the majority (if not all) of the risk factors for CVD in persons with SCI will have a significant negative impact upon endothelial function. As such, it would appear that vascular dysfunction is also a central step in the development of CVD in persons with SCI. 

Table 2: Risk Factors for Cardiovascular Disease in Persons with SCI

Exercise Rehabilitation and Cardiovascular Fitness

Exercise rehabilitation has been shown to be an effective means of attenuating or reversing chronic disease in persons with SCI. Similar to the general able-bodied population (Warburton et al 2006a), habitual physical activity (beyond activities of daily living) can lead to numerous health benefits that significantly reduce the risk for multiple chronic conditions (in particular CVD) and premature mortality in persons with SCI. However, supporting evidence is relatively low in comparison to the general population and other clinical conditions (e.g., chronic heart failure (Warburton et al 2006b)).

The cardiovascular research conducted within the field of SCI has examined predominantly the effects of aerobic exercise and/or functional electrical stimulation (FES) training. In the following sections we will review the literature regarding to the effects of varied exercise interventions on the risk for CVD in persons with SCI. Particular attention will be given to the changes in cardiovascular fitness, glucose metabolism, and lipid lipoprotein profiles that occur after training interventions in persons with SCI.

Our search revealed 58 studies examining cardiovascular fitness before and after an exercise intervention. It is important to highlight, that our original search included many studies that examined the acute effects of an exercise intervention. However, for inclusion in this systematic review the article must have included the examination of the changes in cardiovascular fitness that occurred as a result of the training intervention (and not simply the temporal changes in cardiovascular parameters with the exercise modality). Within this context, our current search included investigations related to treadmill training (6 studies; n = 56), arm exercise (26 studies; n = 444), and FES (26 studies; n = 307) training.

Glucose homeostasis

Glucose intolerance and decreased insulin sensitivity are independent risk factors for CVD (Hurley and Hagberg 1998). Abnormal glucose homeostasis is associated with worsened lipid lipoprotein profiles and an increased risk for the development of hypertension and type 2 diabetes ( Warburton et al 2001b, 2001a, Hurley and Hagberg 1998). It is well-established that habitual physical activity is an effective primary preventative strategy against insulin resistance and type 2 diabetes in the general population.(Warburton et al 2006c). Although comparatively less information is available for SCI, it appears that exercise training programs are effective in improving glucose homeostasis (Mahoney et al 2005, Phillips et al 2004, de Groot et al 2003, Chilibeck et al 1999, Hjeltnes et al 1998). Key terms used when assessing glucose homeostasis are provided in Table 9.

Table 9: Glucose homeostasis key terms.

Table 10: Effects of exercise training on glucose metabolism in persons with spinal cord injury.

Discussion

The majority of the data is from experimental non-RCT trials. A search of the literature revealed seven investigations (n = 47). This included one RCT (de Groot et al 2003)and six experimental non-RCT (pre-post) trials(Mahoney et al 2005, Phillips et al 2004, Jeon et al 2002, Mohr et al 2001, Chilibeck et al 1999, Hjeltnes et al 1998). The single RCT involved the randomization to two different forms of exercise, and, as such, an exercise condition served as the control (Table 10). The majority (five) of these trials examined the effectiveness of FES training.

Similar to other studies in the field of SCI research, this area of investigation is limited by the lack of quality RCTs. Moreover, the majority of the research relates to the effects of FES training. Limited work has been conducted using aerobic and/or resistance exercise training. As a whole, however, these studies are consistent and reveal several important findings. For instance, the improvements in glucose homeostasis may be the result of increased lean body mass (and associated changes in insulin sensitivity) and increased expression of GLUT-4, glycogen synthase, and hexokinase in exercised muscle.

Consistent with findings in able-bodied individuals (Warburton et al 2001b, 2001a), the improvement in glucose homeostasis after exercise interventions (e.g., aerobic training or FES) does not appear to be related solely to decreases in body adiposity and/or increases in VO₂max. This is due to the fact that significant improvements in glucose homeostasis can occur with minor changes in body composition and/or aerobic fitness.

It is also important to note that there appears to be a minimal volume of exercise required for improvements in glucose homeostasis. For instance, Mohr et al.(Mohr et al 2001)revealed that a reduction of FES training was not sufficient to maintain the beneficial changes in insulin sensitivity and GLUT-4 protein observed during a three days/week FES training program.     

Conclusion

• There is level 1 evidence from 1 RCT (de Groot et al. 2003) and multiple level 4 studies (Jeon et al. 2002; Mohr et al. 2001; Chillibeck et al. 1999) that both aerobic and FES training (approximately 20–30 min/day, three days/week for eight weeks or more) are effective in improving glucose homeostasis in persons with SCI.
• There is level 4 evidence from multiple pre-post studies that the changes in glucose homeostasis after aerobic or FES training are clinically significant for the prevention and/or treatment of type 2 diabetes.

• Aerobic and FES exercise training may lead to clinically significant improvements in glucose homeostasis in persons with SCI. Preliminary evidence indicates that a minimum of 30 min of moderate intensity training on 3 days per week is required to achieve and/or maintain the benefits from exercise training.

Lipid lipoprotein profiles

Abnormal lipid lipoprotein profiles have been associated with an increased risk for CVD (Warburton et al 2006c, 2006b, Warburton et al 2001b, 2001a, Hurley and Hagberg 1998). Several studies have revealed worsened lipid lipoprotein profiles in persons with SCI (Dallmeijer et al 1997, Maki et al 1995, Krum et al 1992, Bauman et al 1992a, Brenes et al 1986, Dearwater et al 1986). Routine physical activity has been shown to enhance lipid lipoprotein profiles by reducing triglycerides (TG), increasing HDL, and lowering LDL/HDL in the general population.( Warburton et al 2006b, Warburton et al 2001b, 2001a). Although limited, similar findings have been observed in persons with SCI (El-Sayed and Younesian 2005, Stewart et al 2004, de Groot et al 2003, Nash et al 2001, Solomonow et al 1997, Hooker and Wells 1989,)(Table 12). Table 11 describes the common lipid lipoprotein measurements.

Table 11: Lipid Lipoprotein Profiles

Table 12: Effects of exercise training on lipid lipoprotein profiles in persons with spinal cord injury

Discussion

The information regarding the effects of exercise training on lipid lipoprotein profile is derived from one high-quality RCT (level 1),(de Groot et al 2003)one nonrandomized, prospective controlled trial (level 2),(Hooker and Wells 1989)and several level 4 studies (El-Sayed and Younesian 2005, Stewart et al 2004, Nash et al 2001, Solomonow et al 1997,)(N = 110). The majority of the investigations examined a form of aerobic training (either arm ergometry or assisted treadmill walking). Another investigation examined the effects of reciprocating gait orthosis powered with electrical muscle stimulation.

These findings provide level 1 evidence (based on one high-quality RCT and several lower quality studies) for the role of exercise in the reduction of atherogenic lipid lipoprotein profiles and the reduction of the risk for CVD in persons with SCI. It appears that a minimal threshold of training exists for changes in lipoprotein profile. For instance, authors have reported that 70% of maximal HRR (for at least 20 min/day, three days/week for eight weeks) is the threshold necessary to achieve significant improvements in lipid lipoprotein profiles. Future research is warranted, however, to quantify the effects of varying forms of exercise (including aerobic exercise, resistance exercise, and FES) on lipid lipoprotein profiles in persons with SCI.

Conclusion

• There is level 1 evidence from 1 high quality RCT (de Groot et al. 2003) to suggest that aerobic exercise training programs (performed at a moderate to vigorous intensity 20-30 min/day, 3 days per week for 8 weeks) are effective in improving the lipid lipoprotein profiles of persons with SCI.
• Preliminary evidence (level 4; Solomonow et al. 1997) also indicates that the use of a reciprocating gait orthosis with FES training (3 hours/week, for 14 weeks) may improve lipid lipoprotein profiles in SCI.

• Aerobic and FES exercise training may lead to improvements in lipid lipoprotein profile that are clinically relevant for the at risk SCI population. The optimal training program for changes in lipid lipoprotein profile remains to be determined. However, a minimal aerobic exercise intensity of 70% of heart rate reserve on most days of the week appears to be a good general recommendation for improving lipid lipoprotein profile in persons with SCI.

Summary

Mountingevidence to suggests that persons with SCI are at an increased risk for CVD. Increasing data indicates that persons with SCI experience an earlier onset and increased prevalence of CVD. Similar to able-bodied individuals, physical inactivity plays a significant role in the risk for CVD in persons with SCI. In fact, the ordinary activities of daily living do not appear to be sufficient to maintain cardiovascular fitness in persons with SCI. Moreover, extremely low levels of physical activity and fitness may lead to a vicious cycle of further decline. Ultimately these changes will have significant implications for the development of CVD (and associated comorbidities) and the ability to live an independent lifestyle. It appears that SCI presents an additional risk for CVD above that observed in able-bodied individuals owing to marked physical deconditioning and injury-related changes in metabolic function (e.g., insulin resistance) ( Myers et al 2007, Bravo et al 2004).

Physical activity interventions have been shown to be effective at attenuating the progression of CVD and related comorbidities. The forms of exercise interventions are varied, and the experimental data are limited in comparison to other patient populations (i.e., chronic heart failure). However, there is compelling evidence supporting the health benefits of upper extremity aerobic exercise (level 1 and 4) and FES (level 4) training (see Tables 13 and 14). For instance, there is research indicating that upper extremity exercise at a moderate-to-vigorous intensity, three days/week for at least six weeks, improves cardiovascular fitness and exercise tolerance in persons with SCI. The optimal exercise intervention for improving cardiovascular fitness remains to be determined. There is level 1 evidence (de Groot et al 2003)that high-intensity (70%–80% HRR) exercise leads to greater improvements in peak power and VO₂peak than low-intensity (50%–60% HRR) exercise. Further investigation is required to determine the relative roles that cardiac and peripheral muscle function play in the improvement of exercise capacity in persons with SCI. There is level 4 (pre-post) evidence that resistance training at a moderate intensity for at least two days/week also appears to be appropriate for the rehabilitation of persons with SCI (Mahoney et al 2005, Jacobs et al 2001, Nash et al 2001, Cooney and Walker 1986,).

Table 13: Management of the risk for cardiovascular disease in persons with spinal cord injury through aerobic exercise training interventions.

Table 14: Management of the risk for cardiovascular disease in persons with spinal cord injury through functional electrical stimulation training interventions.

There is growing evidence (predominantly level 4) from several pre-post trials that FES training for a minimum of three days/week for two months can improve oxidative metabolism (Crameri et al 2004, Crameri et al 2002, Mohr et al 1997, Andersen et al 1996)exercise tolerance (Thijssen et al 2005, Wheeler et al 2002, Mohr et al 1997, Barstow et al 1996, Hooker et al 1992, Pollack et al 1989)and cardiovascular fitness (Wheeler et al 2002, Hjeltnes et al 1997, Mohr et al 1997, Barstow et al 1996, Thijssen et al 2005, Hooker et al 1992, Pollack et al 1989,). There is limited (level 4) evidence (Ditor et al 2005a, Ditor et al 2005b)that BWSTT can improve indicators of cardiovascular health in individuals with complete and incomplete SCI.

Preliminary (levels 1 and 4) evidence indicates that aerobic and FES exercise training programs (performed 30 min/day, three days per week for eight weeks or more) are effective in improving glucose homeostasis in persons with SCI (de Groot et al 2003, Jeon et al 2002). The magnitude of change in glucose homeostasis appears to be of clinical significance for the prevention and/or treatment of type 2 diabetes in persons with SCI.

There is level 1 evidence from a  high-quality RCT (de Groot et al 2003)and several pre-post studies (El-Sayed and Younesian 2005, Stewart et al 2004, Hooker and Wells 1989)to suggest that aerobic exercise training programs (performed at a moderate-to-vigorous intensity 20–30 min/day, three days/week for eight weeks) are effective in improving the lipid lipoprotein profiles of persons with SCI. The optimal training program for changes in lipid lipoprotein profile remains to be determined. However, a minimal aerobic exercise intensity of 70% of HRR on most days of the week appears to be a good general recommendation for improving lipid lipoprotein profile. Preliminary level 4 data also indicate that FES training (three hr/week for 14 weeks) may improve lipid lipoprotein profiles in SCI (Solomonow et al 1997).

As discussed throughout this article, a growing body of evidence supports the existence of an increased risk for CVD and CVD-related mortality in persons with SCI. Marked physical inactivity appears to play a central role in the increased risk for CVD in persons with SCI. Intuitively, exercise training should lead to significant reductions in the risk for CVD and improved overall quality of life in the SCI population. However, the relationship between increasing physical activity and health status of SCI has not been evaluated adequately to date. Based on preliminary evidence (primarily level 4), it would appear that various exercise modalities (including arm ergometry, resistance training, BWSTT, and FES) may attenuate and/or reverse abnormalities in glucose homeostasis, lipid lipoprotein profiles, and cardiovascular fitness. As such, exercise training appears to be an important therapeutic intervention for reducing the risk for CVD and multiple comorbidities (such as type 2 diabetes, hypertension, obesity) in individuals with SCI. Well-designed RCTs are required in the future to establish firmly the primary mechanisms by which exercise interventions elicit these beneficial changes. Similarly, further research is required to evaluate the effects of lesion level and injury severity on exercise prescription, such that exercise programs can be developed that address the varied needs of persons with SCI. Moreover, long-term follow-up investigations are required to determine whether training-induced changes in risk factors for CVD translate directly into a reduced incidence of CVD and premature mortality in persons with SCI.

• There is level 1 evidence (Millar et al. 2009) that BWSTT improves cardiac autonomic balance in persons with tetraplegia and paraplegia (with similar results for varying degrees of lesion level and severity).
• There is level 4 evidence that BWSTT increase peak oxygen uptake and heart rate, and decreases the dynamic oxygen cost for persons with SCI.
• Level 4 evidence (Ditor et al. 2005b) indicates that BWSTT can improve arterial compliance in individuals with motor-complete SCI.
• There is level 2 evidence (de Carvalho et al. 2006) that neuromuscular electrical stimulation gait training can increase metabolic and cardiorespiratory responses in persons with complete tetraplegia.
• There is level 1 evidence (Davis et al. 1987) that moderate intensity aerobic arm training (performed 20–60 min/day, three days/week for at least 6-8 weeks) is effective in improving the aerobic capacity and exercise tolerance of persons with SCI.
• There is level 1 evidence (de Groot et al. 2003) that vigorous intensity (70%–80% HRR) exercise leads to greater improvements in aerobic capacity than moderate intensity (50-60% HRR) exercise.
• The relative importance of changes in cardiac function and the ability to extract oxygen at the periphery in persons with SCI after aerobic training remains to be determined.
• There is level 2 evidence that hand cycling exercise increases the power output, oxygen consumption, and muscle strength in paraplegic, but not tetraplegic subjects during active rehabilitation. Conversely, there is level 4 evidence that hand cycling increases power output and oxygen consumption in tetraplegic subjects.
• There is level 4 evidence from multiple pre-post studies that FES training performed for a minimum of three days per week for two months may be effective for improving musculoskeletal fitness, the oxidative potential of muscle, exercise tolerance, and cardiovascular fitness.
• There is level 4 evidence from multiple pre-post studies that FES training may be effective in improving exercise cardiac function in persons with SCI.
• There is level 5 evidence that arm-cranking exercise assisted by FES increases peak power output, and may increase oxygen uptake.
• There is level 1 evidence from 1 RCT (de Groot et al. 2003) and multiple level 4 studies (Chillibeck et al. 1999; Mohr et al. 2001; Jeon et al. 2002) that both aerobic and FES training (approximately 20–30 min/day, three days/week for eight weeks or more) are effective in improving glucose homeostasis in persons with SCI.
• There is level 4 evidence from multiple pre-post studies that the changes in glucose homeostasis after aerobic or FES training are clinically significant for the prevention and/or treatment of type 2 diabetes.
• There is level 1 evidence from 1 high quality RCT (de Groot et al. 2003) to suggest that aerobic exercise training programs (performed at a moderate to vigorous intensity 20-30 min/day, 3 days per week for 8 weeks) are effective in improving the lipid lipoprotein profiles of persons with SCI.
• Preliminary evidence (level 4; Solomonow et al. 1997) also indicates that the use of a reciprocating gait orthosis with FES training (3 hours/week, for 14 weeks) may improve lipid lipoprotein profiles in SCI.

Key Points

• There is growing evidence that BWSTT can improve indicators of cardiovascular health in individuals with complete and incomplete tetraplegia and paraplegia.
• Tetraplegics and paraplegics can improve their cardiovascular fitness and physical work capacity through aerobic arm cycling exercise training which are of moderate intensity, performed 20-60 min day, at least three times per week for a minimum of six to eight weeks. Resistance training at a moderate intensity at least two days per week also appears to be appropriate for the rehabilitation of persons with SCI. It remains to be determined the optimal exercise intervention for improving cardiovascular fitness.
• Interventions that involve FES training a minimum of 3 days per week for 2 months may improve muscular endurance, oxidative metabolism, exercise tolerance, and cardiovascular fitness.
• Aerobic and FES exercise training may lead to clinically significant improvements in glucose homeostasis in persons with SCI. Preliminary evidence indicates that a minimum of 30 min of moderate intensity training on 3 days per week is required to achieve and/or maintain the benefits from exercise training.
• Aerobic and FES exercise training may lead to improvements in lipid lipoprotein profile that are clinically relevant for the at risk SCI population. The optimal training program for changes in lipid lipoprotein profile remains to be determined. However, a minimal aerobic exercise intensity of 70% of heart rate reserve on most days of the week appears to be a good general recommendation for improving lipid lipoprotein profile in persons with SCI.

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Prevalence of Depression Post-SCI

Estimates of the prevalence of depression are affected by the nature of the measures used, how depression is defined, aging characteristics of the samples studied and when symptoms are assessed post-injury (Elliott & Frank 1996)  The common research practice of employing self-report measures is both convenient and cost-effective.  However, the resulting prevalence rates may reflect subjective anxiety and overall distress rather than symptoms specific to depression, per se.  In clinical practice, self-report measures may serve to alert the clinician to the need for additional evaluation and can aid in monitoring symptom severity over time.  For reviews of depression and other psychosocial measures frequently used in spinal injury research and practice see Vahle et al. (2000), Richards et al. (2006), SCIRE chapter 25.and Sakakibara et al. (2009).

In their review, Bombardier et al. (2004) found rates of major depression or probable major depression following SCI vary widely across studies and can range from 7% to 31% of persons, with estimates of major depressive disorder typically reported in 15%-23% of individuals. In a recent survey of 568 adult traumatic SCI inpatient rehabilitation clients, approximately 22% met self reported symptoms consistent with major depressive disorder on average less than two months post injury (Krause, Bombardier and Carter, 2008). Bombardier et al. (2004) surveyed 849 SCI outpatients at one-year post injury and found 11.4% met criteria for MDD. Krause et al. (2000) suggest a 42% overall rate of depression with a 21% probable rate of major depression – indicative of a 4-fold increase of depressive disorders among individuals with SCI when compared with samples of non-disabled individuals.  Of note, many studies do not include information regarding use of antidepressants, other medications, or psychotherapeutic interventions in their reports.  Accordingly, observed rates of depressive symptoms may potentially be a reflection of multiple additional factors and the “net effect of all treatments” (Krause et al.  2008).

With up to 25% of men and 47% of women affected (Consortium for Spinal Cord Medicine 1998) a recent case-matched comparison found an absence of gender differences in probable major depression and symptom severity (Kalpakjian and Albright 2006). In an Italian sample averaging 6 years post-SCI, Scivoletto et al. (1997) found 16% reported significant symptoms of depression and 13% anxiety.  Migliorini et al. (2008) employed an Australian sample who averaged 19 years post-SCI, 37% were identified as depressed, 30% suffered anxiety, 25% experienced significant stress and 8.4% reported post-traumatic stress disorder.  Of note, approximately 60% of individuals with one probable diagnosis were likely to suffer at least one other comorbid condition highlighting the potential complexity of mental health issues. 

In a 6-year follow-up study of 233 Albertans with SCI, 28.9% were treated for depression following their traumatic SCIs, with approximately 59% of these individuals beginning treatment during their initial hospitalization (both acute and rehabilitation admissions). An additional 10% of people were treated during the remainder of the first year.  This exceeded depression treatment rates reported in able-bodied controls of approximately 11% (Dryden et al. 2004), with those at highest risk reporting permanent neurological deficit, a preinjury history of depression, or substance abuse (Dryden et al. 2005).  Kennedy and Rogers (2000) reported that anxiety, depression and hopelessness gradually increased beginning at week 30 post injury and continued until discharge from rehabilitation (week 48).  At that point 60% of SCI clients scored above a clinical cut-off for depression (i.e. Beck Depression Inventory).  Krause et al. 2008 suggested that depressive symptoms may not peak during inpatient rehabilitation and it may take additional time for the “low point of emotional adaptation to appear”.

In a cross sectional study, Richardson and Richards (2008) found that rates of clinically significant depressive symptoms (PHQ-9 scores >10) were reported by approximately 21%, 18%, 12% and 12% of SCI survivors surveyed at 1, 5, 15 and 25 years post injury, suggesting rates tended to decrease with time since injury.  Data obtained in earlier studies also suggested that in newly injured persons who met criteria for major and minor depression, many remit within 3 months of onset (Kishi et al. 1994) and that the frequency of reported problems decreases over the first year (Richards 1986).  In a longitudinal analysis, Pollard and Kennedy (2007) found a substantial relationship between reported depressive symptoms at 3 months and approximately a decade post injury, with 38% and 35% of SCI survivors surveyed meeting a criterion for moderate depression at these times.  Hoffman et al. (2008) followed 411 SCI model system participants and found approximately 20% of at 1 year post injury and 18% at year 5 post-injury reported symptoms consistent with major depression.  Further, approximately a third of those reporting scores suggestive of moderate depression at year 1 experienced remission, while approximately 9% were newly depressed at year 5.  The authors summarized that the natural history of depression post SCI was variable over time with some showing improvement while others exhibited emotional decline. 

It has been questioned whether, despite its reported prevalence, efforts to improve the detection and treatment of depression in individuals with SCI has improved (Bombardier et al. 2004). In an editorial comment, Faber (2005) expressed concern that given possible underestimates, about half of all persons hospitalized for traumatic SCI may benefit from treatment for depression.  Similarly, while a substantial percentage of their SCI clinic sample reported symptoms suggestive of major depression, Kemp and Krause (1999) found that none were receiving treatment (psychotherapy or medications).  In a review of American veterans with spinal cord injuries and disabilities, Smith et al. (2007) concluded that many may not be receiving adequate treatment for depression and the authors encouraged more aggressive screening and treatment.   

As health problems can produce pain, fatigue, sleep disturbances, physical sensations and digestive troubles, the overlap of somatic symptoms can pose diagnostic challenges.  Krause, Bombardier and Carter (2008) noted that on average, nearly a third of a large sample of SCI adult inpatient rehabilitation clients cited sleep, energy and appetite changes, while symptoms of persistent depressed mood and anhedonia were reported by approximately 10% and 15% of the sample, respectively.  In a large outpatient sample, 80% of SCI survivors with probable MDD reported symptoms of depressed mood, anhedonia, feelings of failure, disturbed sleep and decreased energy (Bombardier et al. 2004).  In general, despite the potential for an increase in “false positives”, reports of somatic symptoms merit clinician review given their strong association with affective or more general symptoms of depression (Richardson and Richards, 2008; Krause et al. 2008). 

Conclusions

• While not universal, for many persons with spinal cord injury, depression can be a complication that poses a significant impediment to their functioning and adaptation.
• Identifying depression can be difficult, but is most likely to develop during the initial year post-injury. Though many will experience a remission of symptoms over time, for others depressive symptoms may persist for many years, 
• Self-report measures of depression should be viewed as screening tools to alert the clinician to arrange a more thorough evaluation.  In addition to affective symptoms, endorsement of somatic symptoms (e.g. sleep disturbance, poor energy and appetite disturbance) during inpatient or outpatient contact merits clinical review to clarify possible mechanisms underlying their emergence. 

• Depression is a common consequence of SCI.
• Depression post SCI can interfere with function and adaptation.

Interventions for Treatment of Depression following SCI

The American Psychological Association (APA 2005) states that evidence-based practice involves the integration of the best of existing research with clinical expertise and the reality of the patient’s needs and wishes. Practical and ethical concerns may limit the availability of SCI research evidence.

Difficulties inherent in conducting intervention studies are numerous (King & Kennedy 1999).  The SCI population can be heterogeneous.  Most sites do not have access to a large number of patients and obtaining treatment and appropriate control groups requires the participation of multiple sites.  Also, ethical concerns over providing the best possible care to all SCI patients are obvious, so that withholding aspects of treatment in order to establish control conditions is no longer acceptable (e.g. Kahan et al. 2006).   To date, research strategies have frequently used self-report screening measures (e.g. Beck Depression Inventory, Zung Depression Inventory, Patient Health Questionnaire-9, Center for Epidemiological Studies – Depression Scale; Older Adult Health and Mood Questionnaire; Depression, Anxiety and Distress Scale), and while they offer many benefits (e.g. low cost, quick, easy to complete), they require further evaluation to support a diagnosis of depression. 

Typical SCI interventions to encourage post-SCI adjustment are often multi-faceted; thereby posing difficulties in identifying which combination of components can offer optimal care for any particular patient.  Further, psychosocial interventions cannot be independent of other aspects of care (e.g. medical, rehabilitation). Wait-list control conditions do not address personal contact, attention and perceived support available in intervention conditions.  In addition, many pre-morbid psychological and historical influences are very difficult to determine. 

As the nature of SCI studies make it more difficult to limit certain biases, the validity and generalizability of the findings is less clear.  Despite these challenges, researchers have made invaluable clinical contributions using smaller groups, non-randomized control groups, or controls chosen from historical data.  However, in summarizing the limited research currently available, Elliott and Kennedy (2004) suggested “we have many untested assumptions regarding the available treatments for depression among persons with SCI” and have questioned whether the current “glaring lack of intervention data” reflects a lack of interest on the part of consumers, researchers and funding agencies with regard to various interventions for treatment of depression in those with SCI.  Kahan et al. (2006) stressed that treatment of depression in people aging with a disability is “far from being developed”, noting a “massive dearth” of research of any kind for individuals with disabilities.

Final Comments

This chapter has summarized research highlighting several promising approaches to the management of post-SCI depression. Additionally, their is also some evidence for the effectiveness of these approaches for related therapeutic targets such as anxiety and self-esteem. However, many of the studies cited note limitations that may introduce caution regarding the generalizability of conclusions to other samples and settings. These have included:

• Small samples sizes and high rates of attrition (due to illness or other factors)
• Possible selection biases
• Ethical concerns that may preclude randomized designs
• Multifaceted interventions complicate understanding of most relevant component(s)
• Impact of social contact in the intervention group often not accounted for in “standard treatment” or “wait list” controls
• Potential impact of adjunctive psychological interventions is unclear
• Use of antidepressant medications not consistently reported
• Lacking long term follow up
• Variability of outcome measures limit comparisons across studies

When leavened with clinical judgment, this research offers preliminary empirical support to guide the practitioner in employing evidenced-based therapeutic strategies.  Future investigations, particularly those employing more stringent research designs, will continue to expand the options and confidence of clinical efforts to assist those individuals who have sustained spinal cord injuries. The reader is encouraged to also consider the following topic reviews of depression and SCI (Consortium for Spinal Cord Medicine 1998; Elliott & Frank 1996; Elliott & Kennedy 2004) and also, more generally, a recent state of the science review of SCI rehabilitation (Sipski & Richards 2006).

Summary

• While not universal, for many persons with spinal cord injury, depression can be a complication that poses a significant impediment to their functioning and adaptation.
•  Identifying depression can be difficult, but is most likely to develop during the initial year post-injury. Though many will experience a remission of symptoms over time, for some individuals, depressive symptoms may persist for many years.  
• Self-report measures of depression should be viewed as screening tools to alert the clinician to arrange a more thorough evaluation.  In addition to affective symptoms, endorsement of somatic symptoms (e.g. sleep disturbance, poor energy and appetite disturbance) during inpatient or outpatient contact merits clinical review to clarify possible mechanisms underlying their emergence.
• There is level 2 evidence from 6 studies supporting the use of small group CBT based treatment packages to decrease depressive symptoms following SCI.
• Follow up findings (up to 1 year post treatment) showed maintenance of affective improvement in 4 level 2 studies. Conversely, evidence from 2 level 2 studies found that post intervention reduction of depressive symptoms were not sustained at follow up (up to 1 year).
• One level 2 study did not identify significant improvement in depressive symptoms.
• Evidence of the benefits of pharmacotherapy alone and in combination with individual psychotherapy in the treatment of depressive symptoms individuals with SCI is encouraging, although support is largely from investigations in other populations.
• There is level 4 evidence from four non-RCT studies indicating the effectiveness of pharmacotherapy combined with cognitive behavioral psychotherapy for treatment of depression in SCI and other chronic disabling conditions.
• Regular physical exercise may contribute to a reduction of pain, stress, and depression as well as potentially offering a prophylactic effect on sources of recurrent pain and in preventing a decline in quality of life following SCI. 
• There is level 1 evidence from 2 RCTs and level 2 evidence from 1 RCT that exercise based programs reduced subjective pain, stress and resulting depressive symptoms.
• There is level 1 evidence from 1 RCT and level 4 evidence from 1 pre-post study that exercise reduces depressive symptoms.
• Level 2 evidence from 1 cohort study of individuals with unrealistic expectations report more depressive symptoms following an FES exercise program.
• There is level 2 evidence from 1 RCT suggesting a wellness and health promotion program did not significantly decrease intensity of depressive symptoms.
• In 1 non-RCT, access to medical follow-up for individuals with SCI found reports of better health, independence, less depression and fewer secondary complications. 
• There is level 1 evidence that massage therapy can reduce depressive symptoms
• There level 1 evidence for the effectiveness of TMS in reducing depressive symptoms.

Key Points

• Depression is a common consequence of SCI.
• Depression post SCI can interfere with function and adaptation.
• Cognitive behavioural interventions provided in a group setting appear helpful in reducing post-SCI depression and related difficulties.
• The benefits of drug treatment for post-SCI depression are largely extrapolated from studies in non-SCI populations.
• Programs to encourage regular exercise, reduce stress, and improve or maintain health appear to have benefits in reducing reports of depressive symptoms in persons with SCI.

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Incidence and Prevalence of SCI by Continent and Country

The primary search yielded 1,538 article titles of which 69 were selected for a full article review. The secondary search captured 10 additional articles. Of those 79, 51 articles fulfilled the inclusion and exclusion criteria for incidence studies (tables 1-4) and 9 articles were selected as adequate prevalence studies (table 5).

Frequency of SCI by Cause

It is well established that using safe practices at work and at play can prevent many SCIs.  Although significant efforts have recently been made towards the prevention of SCI, further improvements can be made to prevention strategies by identifying and studying the various causes of SCI throughout the world.

In tables 6 through 13, we present a global perspective on the frequency of the leading causes of SCI (motor vehicle crashes (MVC), falls, sports, self harm, violence, work-related incidents, natural disasters, and other).

Discussion

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• Yang NP, Deng CY, Lee YH, Lin CH, Kao CH, Chou P. The incidence and characterisation of hospitalised acute spinal trauma in Taiwan--a population-based study. Injury 2008;39(4):443-450.
• Ye C, Sun T, Li J, Zhang F. Pattern of sports- and recreation-related spinal cord injuries in Beijing. Spinal Cord 2009;47(12):857-60.
• Yeo JD. Prevention of spinal cord injuries in an Australian study (New South Wales). Paraplegia 1993;31(12):759-763.

Pathophysiology of Heterotopic Ossification

The mechanism underlying heterotopic ossification following spinal cord injury is not fully understood but it appears to be initiated by mesenchymal cells into bone precursor cells (Schuetz et al. 2005). Pape et al. (2004) has noted that mesenchymal stem cells can differentiate into osteogenic cells given the right stimuli within the right environment, even soft tissues (Chalmers et al. 1975).  These mesenchymal stem cells can generate cartilage, bone, muscles, tendons, ligaments or fat (Williams et al. 1999) and are thought to play a pivotal role in the development of HO (Pape et al. 2004). HO then forms through a typical process beginning with the formation of a protein mixture created by bone cells (osteoid) that eventually calcifies within a matter of weeks (Pape et al. 2001).   Over the next few months, the calcified osteoid remodels and matures into well-organized trabecular bone (Pape et al. 2001).  Months following the initial trauma patients develop bone formation in muscle and soft tissues adjacent to a joint (paraarticular) with resultant restriction in range of motion, pain and ankylosis (Banovac & Gonzalez 1997, Garland et al. 1980).  The bony lesion has a high metabolic rate, adding new bone at more than three times the rate of normal bone.  Osteoclastic (bone removal cell) density is more than twice that found in healthy bone (Puzas et al. 1987).    It is suspected there may be a neurogenic factor contributing to HO but the mechanism is poorly understood (Hurvitz et al. 1992, Pape et al. 2001, Pape et al. 2004).

Figure 1

Clinical Presentation and Natural History

Schuetz and coworkers (2005) has noted that the symptoms of heterotopic ossification appear 3-12 weeks after spinal cord injury.  SCI patients typically present with joint and muscle pain, parasthesias and tissue swelling in the involved region, accompanied by mild fever (Thomas & Amstutz 1987; Orzel & Rudd 1985; Smith 1998;Shehab et al. 2002).  In the initial stages of HO, clinical signs of inflammation are nonspecific (Neal 2003).

Diagnosis

In the early phase of HO, three phase bone scanning demonstrates increased uptake of osteotropic radionucleotides. Bone scanning has proven to be more sensitive than plain radiography in detecting early HO. Neurogenic HO becomes evident on plain radiography approximately 2 to 6 weeks after diagnosis using the three phase bone scan (Orzel et al. 1985; Freed et al. 1982). However, bone scans have lower specificity than radiography (Freed et al. 1982). CT or MRI scanning may be a useful tool when considering surgery as it allows for better visualization of the heterotopic bone (Amendola et al. 1983). Some studies have looked into diagnosing HO through elevations of biochemical markers such as alkaline phosphatase (Singh et al. 2003; Tibone et al. 1978) and creatine phosphokinase (Singh et al. 2003; Welch et al. 1973; Rossier et al. 1973). The predictive value of alkaline phosphatase has not been validated (Singh et al. 2003; Welch et al. 1973; Rossier et al. 1973), while there is conflicting evidence of an association of HO with increased serum creatine phosphokinase levels (Singh et al. 2003; Welch et al. 1973). Schurch et al. (1997) studied individuals with acute SCI and found increases in the 24 hour prostaglandin E₂ (PGE₂) urinary excretion a valid indicator of early HO formation.

Treatment of Heterotopic Ossification

The published literature on treatment of HO provides evidence for non-steroidal anti-inflammatory drugs, warfarin, bisphosphonates, pulse low-intensity electromagnetic field therapy, radiation and surgical excision.

Summary

• Schuetz and coworkers (2005) note that after a SCI, heterotopic ossification still remains a therapeutic challenge.  Anti-inflammatory medications provided early prevent the development of HO while warfarin was associated with a decreased risk of HO.  Both radiotherapy and etidronate appear to halt the progression of HO once it is diagnosed. Although more research is needed, early work is encouraging demonstrating that HO post SCI is treatable.
• There is strong Level 1 evidence that non-steroidal anti-inflammatory medications can reduce the incidence of heterotopic ossification when administered early after a spinal cord injury.
• There is Level 5 evidence that Warfarin inhibits the development of heterotopic ossification post spinal cord injury.
• There is Level 2 evidence that etidronate can stop the progression of heterotopic ossification once the diagnosis is made; it is most effective if given when  the nuclear bone scan is positive but the radiographs are negative.
• There is Level 4 evidence that Etidronate is not effective once radiographs are positive for HO.
• There is Level 4 evidence that pamidronate effectively halts secondary HO progression after surgical resection of HO.
• There is Level 1 evidence that PLIMF is an effective prophylaxis of HO post SCI
• There is limited Level 4 evidence that radiotherapy reduces the progression of heterotopic ossification.
• There is level 4 evidence that resection of HO about the hip post SCI can dramatically improve restricted hip range of motion.
• There is Level 4 evidence that surgical resection combined with pamidronate treatment effectively halts secondary progression of HO.

Key Points

• Anti-inflammatory medications given early post-SCI reduces development of heterotopic ossification.
• Warfarin may inhibit the development of heterotopic ossification post-SCI.
• Etidronate can halt the progression of heterotopic ossification.
• Paminodrate halts secondary progression of HO post surgical excision.
• Pulse low intensity electromagnetic field therapy is effective in preventing HO post SCI.
• Radiotherapy can reduce the progression of heterotopic ossification.
• Surgical resection of HO can improve hip range of motion.
• Surgical resection and pamidronate treatment halts secondary HO progression.

References

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Housing

Housing is a primary need for all individuals. The necessity of having a safe home compatible with one’s personal needs increases when an individual is vulnerable. One of the first questions asked when a person has sustained and survived an SCI is where he/she will be able to live. Successful community reintegration is intimately linked to housing within the background of the person’s needs, the attributes of relevant environmental factors, and the preferred choice of living environment of the person with the injury. Until recently, SCI authors generally only discussed the issue of the suitability of a home regarding its physical accessibility and adaptations (Heywood, 2004; Forrest and Gombas 1995; McAweeney et al. 1996). Forrest and Gombas (1995) revealed that a lack of accessible housing increases a person’s length of stay on the rehabilitation unit, thus increasing the overall cost of healthcare services after SCI.

The choice of living environment for people with SCI is critical because of their increased need for human and environmental support, requiring them to carefully consider who they will live their life with and where. In some cases, individuals with SCI do not have a choice because of the lack of accessible housing inventory. Having a range of choices of housing likely hastens and enhances the transition from rehabilitation to community while improving the personal match to the living environment. Ten non-intervention housing articles are presented below. Given that stable housing is a basic human need, it is virtually impossible to develop intervention studies in this research area of inquiry.

Table 1: Housing

Discussion

From the onset of SCI, the rehabilitation services and the resources required for independent living remain two of the key elements for successful community reintegration. This is particularly true for people with spinal cord injury who use more services (particularly related to housing) than other consumers with disabilities such as TBI or Stroke (Fuhrer et al 1990). According to Tate and Forchheimer (1998) participation in an independent living program (e.g., peer counseling, group support, etc.) can provide better knowledge of the resources needed and may lead to better personal control and adjustment upon return to the community. However, a follow-up study of an independent living program revealed it had little or no impact on life satisfaction or personal control of participants with SCI (Forchheimer and Tate 2004). Marital status and transportation barriers are the most important predictors related to living arrangement post-SCI (DeJong et al 1984). Boschen (1996) found that the best predictor of residential satisfaction was having the perception of choice of residence, and that satisfaction with residential placement was correlated with life satisfaction.

Boschen (1988, 1990) found that the level of satisfaction with the home is also related to difficulties encountered living in the home, primarily because of environmental barriers. Moreover, the level of satisfaction was higher among persons with SCI living in their own apartment. In previous work, Boschen (1988) revealed that having one’s own apartment was preferred by the individuals with SCI and that their choice is determined by the quality of the environment, particularly in terms of accessibility. The choice of residence is limited by many factors and the limitations are magnified as the severity of disability increases. Therefore individuals with tetraplegia are at a significant disadvantage. The findings indicate that those with tetraplegia move several times after discharge from rehabilitation. The moves are influenced by factors such as information, money, accessibility, insurance, personal assistance, etc. Individuals with SCI who eventually end up living with their parents or in an institution consider such living arrangement as their last option (Bergmark et al 2008). Anzai et al (2006) found that certain social and personal factors (e.g., age, having insurance or private funding) reduce the risk of moving to a nursing home after discharge from rehabilitation. Living in an environment considered to be minimally restrictive which enables active participation in daily decisions according to the principles of independent living is more likely to contribute to improved quality of life (DeJong and Hughes 1982).  Finally, safety at home is important to persons with SCI, particularly related to fire. Many participants indicated they would need assistance with that dimension of home safety (Cesar et al. 2002).

The evidence reveals the importance of the continuity of services between rehabilitation and return to the community (Fuhrer et al 1990). The lack of accessible housing is an important barrier that may have an impact on the community reintegration process as well as on rehabilitation service costs. Community services play an important role, especially in housing and peer support to return to independent living (Fuhrer et al. 1990; Tate and Forchheimer 1998). Finally, the quality of the built environment is one of the key determinants of the ability to find housing that meets the needs of persons with SCI, which also affects their level of satisfaction with respect to where they reside. Freedom of choice related to selecting where they will live constitutes a salient feature of life satisfaction for many. However those individuals who encounter obstacles (related to accessibility, financial support and so on) will likely have little choice when it comes to selection of housing (Boschen 1988; 1990). Despite opportunities to participate in transitional or independent living programs before discharge from rehabilitation, the common finding of this body of work is that the move back into the community following SCI seems to be a real test of both the supportiveness of the environment and the resilience and resourcefulness of the individual in determining the success of the reintegration.

Conclusions

• There is level 5 evidence (Forrest and Gombas 1995) that discharge from hospital was delayed for a significant portion of SCI patients due to lack of accessible housing, which leads to unnecessary increase of cost of care.
• There is level 5 evidence (Fuhrer et al 1990) that ILCs with MRP relationships serve more clients than those without, and that the most frequently serviced individuals are those with SCI who attend for peer counseling, skills training, and discharge planning.
• There is level 5 evidence (DeJong and Hughes 1982) that living with a spouse and/or children, living alone, or living with unrelated persons were more desirable arrangements than living with parents and spouse/children together, living with distant family (i.e. grandparents), or living with parents and siblings.
• There is level 4 evidence (DeJong et al 1984) that marital status, transportation barriers, education level, medical supervision requirements, economic disincentives, services received, and severity of disability are predictors of independent living.
• There is level 5 evidence  (Boschen 1996) that issues of choice and control are important when planning living situations and setting goals with clients because they are directly related to residential and life satisfaction.
• There is level 5 evidence (Boschen 1990) that individuals with SCI have lower perceived life satisfaction, locus of control and satisfaction with certain aspects housing than a normative sample.
• There is level 5 evidence (Boschen 1988) that accommodation options for a person with a disability are limited. The preferred accommodation is a private house or apartment.
• There is level 5 evidence (Anzai et al 2006) that living with someone prior to SCI, having insurance or private funding for equipment, and being younger decreases the risk of being discharged to an extended care facility following SCI rehabilitation.
• There is level 5 evidence (Cesar et al 2002) that individuals with SCI have a need for assistance with fire safety to increase their perception of home safety.
• There is qualitative evidence (Bergmark et al 2008) that suggests individuals with SCI move multiple times after injury. In most cases they start living with their parents and/or in an institution before moving into their own homes.

• In many cases, discharge from hospital is delayed for SCI patients due to lack of accessible housing, which leads to unnecessary increase of cost of care.
• ILCs with MRP relationships serve more clients than those without, and the most frequently serviced individuals are those with SCI who attend for peer counseling, skills training and discharge planning.
• Living with a spouse and/or children, living alone, or living with unrelated persons are more desirable arrangements than living with parents and spouse/children together, living with distant family (i.e. grandparents), or living with parents and siblings.
• Marital status, transportation barriers, education level, medical supervision requirements, economic disincentives, services received, and severity of disability are predictors of independent living.
• Choice and control are important when planning living situations and setting goals with clients with SCI because they are directly related to residential and life satisfaction.
• Individuals with SCI have lower perceived life satisfaction, locus of control, and satisfaction with certain aspects of housing than a normative sample.
• Accommodation options for a person with a disability are limited. The preferred accommodation is a private house or apartment.
• Living with someone prior to SCI, having insurance or private funding for equipment, and being younger decreases the risk of being discharged to an extended care facility following SCI rehabilitation.
• Individuals with SCI have a need for assistance with fire safety to increase their perception of home safety.
• Individuals with SCI move multiple times after injury. In most cases they start living with their parents and/or in an institution before moving into their own homes.

Attendant Care

Advances in medical technology have increased survival rates for traumatic injuries and as a result, more people are living longer with an SCI (Adams and Beatty 1998).  However, functional impairment due to SCI may necessitate the use of attendant care or personal assistance services (PAS).  Attendant care can be broadly defined as home-based support that assists individuals to perform tasks they would otherwise not be able to perform themselves. Attendant care service providers are usually either non-paid family members or paid workers who help with everyday personal or self-care tasks such as bathing, dressing, grooming, and transfers (Berry et al. 1995; Cockerill and Durham 1992; Meyer et al. 2007). They may also assist with instrumental activities of daily living such as cooking, chores, and shopping (Berry et al. 1995; Cockerill and Durham 1992). In this way, personal assistance or attendant care facilitates what was called independent living 20 - 30 years ago and is now commonly referred to as community integration and social participation, and which may also include accommodated employment and/or adapted sports and recreation (Adams and Beatty 1998). In addition, home-based attendant care, which is typically provided only part-time and not on a full-day basis, has long been recognized as more cost-effective when compared to institutional costs (Hoeman and Winters 1990).

It should be noted that independent living does not require that a person be able to carry out their routine tasks alone without help from someone else. While tasks are completed with some assistance, the emphasis of independent living is placed on the individual’s right to decide when, where, and how tasks are performed (Litvak et al. 1987). Indeed, recipients of paid personal care assistance (PCA) have emphasized the importance of being in control of training the assistant. How the assistance is to be provided is discussed with the attendant at the outset of the professional relationship (Meyer et al. 2007). Some individuals prefer untrained attendants so they can train and direct them to suit their own particular needs. Being able to direct attendants to assist with managing personal care post-SCI maximizes the ability to promote good health and enables the person with the SCI to live more independently and productively. Personal care attendants may be skilled or unskilled workers, licensed or unlicensed, registered nurses, nursing assistants, nurse’s aids, home health aids, or paid or unpaid family members (Berry et al. 1995; Pomeranz et al. 2006).  Typically, individuals with tetraplegia in need of 24-hour care will require such care from nurses with specialized training, whereas persons with lower-level injuries may be fairly self-sufficient and require less-skilled assistance with daily tasks.

Attendant care is a common and essential aspect of daily living for many individuals with an SCI (Berry et al. 1995). The United States Federal Bureau of Statistics predicted that the number of personal care attendants would be 827,000 in 2005 (Frost et al. 1999). Attendant care services can be expensive and are therefore an important financial as well as social consideration. In 1992, the average individual yearly cost of attendant care services for all levels of SCI combined was $14,359 USD two years after injury (Johnson et al. 1996). However, costs ranged dramatically and these data are now clearly outdated. But for comparison purposes it is instructive to know that the annual mean cost of PAS for individuals with high tetraplegia (C1-C4) was $92,441 while average costs were $2,184 for persons with paraplegia (T1-S5). Another study found a range of $38-$798 spent per day on attendant care (Mattson-Prince 1997). A third costing study, also from the 1990’s, found that 44% of total costs related to SCI were for attendant care (Harvey et al. 1992).

Regardless of cost, PCA is essential for many SCI consumers and is correlated with a variety of factors. Previous studies have found that gender may influence PCA use; men tend to rely on family members whereas women are more likely to pay for services from an outside agency (Shackleford et al. 1998). A 1992 study revealed that approximately two-thirds of individuals with SCI received an average of 25 hours of paid or unpaid weekly PCA; more than half received 40 hours per week or less. The majority of this care was provided voluntarily (Harvey et al. 1992). Family caregivers tend to be female, a spouse, and over 40 years of age (Foster et al. 2005). It is important to understand the patterns of PCA use, the characteristics of family support providers, and the impact of this role on these lifelong assistants (Boschen et al. 2005a, 2005b). Families often play a central role in providing home services, which is beneficial to the injured person but has significant health, career, social, and other personal consequences for the informal provider (Boschen and Gargaro 2009). One generic rehabilitation study documented that family caregivers may experience poorer health, higher rates of anxiety and depression, and possibly develop more long-term health problems (Holicky 1996). The evidence base from the above studies of these family caregiver consequences is crucial for justifying healthcare and social support direct service allocation to SCI families, and highlights the need for promoting self-care for all PCA providers to improve stability of services.

Despite using a broad definition of attendant care or personal assistance there are very few high-quality academic articles in the literature on this topic. The articles reviewed in Table 2 below focus both on the characteristics of attendant care for the adult SCI population and on the promotion of their independent function and behaviours that will maintain or improve their health. Specifically, articles were included if they addressed the effectiveness of in-home attendant care services, factors influencing the use of and access to attendant care, and/or future interventions to improve outcomes. Qualitative data were included in this review due to the paucity of intervention articles and the utility of the data obtained from these studies which met the chapter inclusion criteria.  Most of the research evidence comes from observational studies, with few randomized controlled trials (RCTs). All intervention studies involving facilitation of the individual to direct their own attendant care have been included in Table 3 in this chapter.

Summary

• There is level 5 evidence (Forrest and Gombas 1995) that discharge from hospital was delayed for a significant portion of SCI patients due to lack of accessible housing, which leads to unnecessary increase of cost of care.
• There is level 5 evidence (Fuhrer et al 1990) that ILCs with MRP relationships serve more clients than those without and that the most frequently serviced individuals are those with SCI who attend for peer counseling, skills training and discharge planning.
• There is level 5 evidence (DeJong and Hughes 1982) that living with a spouse and/or children, living alone, or living with unrelated persons were more desirable arrangements than living with parents and spouse/children together, living with distant family (i.e. grandparents), or living with parents and siblings.
• There is level 4 evidence (DeJong et al 1984) that marital status, transportation barriers, education level, medical supervision requirements, economic disincentives, services received, and severity of disability are predictors of independent living.
• There is level 5 evidence  (Boschen 1996) that issues of choice and control are important when planning living situations and setting goals with clients because they are directly related to residential and life satisfaction.
• There is level 5 evidence (Boschen 1990) that individuals with SCI have lower perceived life satisfaction, locus of control and satisfaction with certain aspects housing.
• There is level 5 evidence (Boschen 1988) that accommodation options for a person with a disability are limited. The preferred accommodation is a private house or apartment.
• There is level 5 evidence (Anzai et al 2006) that living with someone prior to SCI, having insurance or private funding for equipment, and being younger decrease the risk of being discharged to an extended care following SCI rehabilitation.
• There is level 5 evidence (Cesar et al 2002) that individuals with SCI have a need for assistance with fire safety to increase their perception of home safety.
• There is qualitative evidence (Bergmark et al 2008) that suggests individuals with SCI move multiple times after injury. In most cases they start living with their parents and/or in an institution before moving into their own homes.
• There is level 5 evidence (Foster et al 2005; Robinson-Whelan and Rintala 2003) indicating that most informal caregivers are female spouses of SCI consumers who required additional assistance in fulfilling and maintaining provided services.
• There is level 5 evidence (Berry et al 1995) suggesting general satisfaction with informal attendant services from both clients and attendants although there are variations with some aspects of care.
• There is level 5 evidence (Weitzenkamp et al 2002) that the most significant predictors of PCA use are motor function, days spent in rehabilitation, and length of stay in a nursing home.
• There is level 5 evidence (Bushnik et al 2007) indicating that personal attendant turnover is positively correlated with higher injury level and increased need for assistance in exercise and transfers.
• There is qualitative evidence (Cockerill and Durham 1992) that both consumers and attendants agree that the emphasis of care in transitional centres should be placed on facilitating consumer independence which may be accomplished by delineating the role of attendants. 
• There is level 1 evidence (Cohen and Schemm 2007) indicating that client-centred visits by an occupational therapist can increase the number of life roles performed and improve life satisfaction.
• There is level 4 evidence (Barber et al. 1999) that suggests recurrent UTIs can be reduced below threshold levels through a simple cost-effective educational intervention by a clinical nurse.
• There is level 4 evidence (Beck and Scroggins 2001) that suggests that health can be maintained after participation in an educational intervention focused on skill development and support in the “real world.”
• There is level 2 evidence (Schopp et al 2007) that a skills training project can improve knowledge in both consumers and personal assistants up to six months post-training.
• There is insufficient evidence (Frost et al 1999) to determine the efficacy of training persons with disabilities to provide SCI attendant care.
• There is Level 4 evidence (Mattson-Prince, 1997) suggesting that an independent living self-managed model for attendant care results in decreased costs, better health outcomes and life satisfaction, and fewer re-hospitalizations than agency-based care.

Key Points

• In many cases, discharge from hospital is delayed for SCI patients due to lack of accessible housing, which leads to unnecessary increase of cost of care.
• Independent Living Centres (ILCs) that have relationships with hospital Medical Rehabilitation Programs (MRPs) serve more clients than those without, and the most frequently serviced individuals are those with SCI who attend for peer counseling, skills training, and discharge planning.
• Living with a spouse and/or children, living alone, or living with unrelated persons are more desirable arrangements than living with parents and spouse/children together, living with distant family (i.e., grandparents), or living with parents and siblings.
• Marital status, transportation barriers, education level, medical supervision requirements, economic disincentives, services received, and severity of disability are predictors of independent living.
• Choice and control are important when planning living situations and setting goals with clients with SCI because they are directly related to residential and life satisfaction.
• Individuals with SCI have lower perceived life satisfaction, locus of control, and satisfaction with certain aspects of housing than normative samples.
• Accommodation options for a person with a disability are limited. The preferred accommodation is a private house or apartment.
• Living with someone prior to SCI, having insurance or private funding for equipment, and being younger decrease the risk of being discharged to an extended care facility following SCI rehabilitation.
• Individuals with SCI have a need for assistance with fire safety to increase their perception of home safety.
• Individuals with SCI move multiple times after injury. In most cases they start living with their parents and/or in an institution before moving into their own homes.
• Most informal caregivers are female spouses of individuals with SCI who require assistance in fulfilling and maintaining services.
• There is general satisfaction with informal attendant services.
• The most significant predictors of Personal Care Assistance (PCA) use are motor function, days spent in rehabilitation, and length of stay in a nursing home.
• Personal attendant turnover is positively correlated with higher injury level and increased need for assistance in exercise and transfers.
• Goal-directed occupational therapy can achieve gains in role performance and improvements in life satisfaction.
• Re-hospitalization might be reduced after participation in an educational intervention involving a workshop, a collaborative home visit, and access to follow-up.
• Counselling on proper technique and hygiene for at least one session might reduce the risk of urinary tract infections (UTIs) to below-threshold for individuals at risk for UTIs.
• Workshops for attendants and consumers can increase knowledge about SCI.
• Directing, training, and financing one’s personal attendant care may lead to financial savings, better health outcomes, and increased life satisfaction.

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Electrical Stimulation to Enhance Lower Limb Muscle Function

After SCI, it is well established that muscles experience deconditioning, especially those denervated following complete SCI. The most visible effect of deconditioning is muscle atrophy, characterized by a reduction in size of individual muscle fibers (Castro et al. 1999a; Castro et al. 1999b). Deconditioning is also associated with a complex cascade of biochemical events and alterations over time in muscle composition such as changes to muscle fiber type (Stewart et al. 2004; Round et al. 1993). Functionally, these changes manifest as loss of strength and endurance of muscular contractions and have been targets for various interventions. It should be noted that there might be additional benefits to enhancing muscle structure and function in addition to the immediate functional consequences of enhancing strength and endurance. For example, muscular contractions have the added potential of ameliorating loss of bone density following SCI. In addition, Anderson (2004) noted that future treatments developed for chronic SCI may require the reversal of muscle atrophy in order for benefits of the treatment to be detectable. Others have noted the potential health benefits (e.g., reduction in secondary conditions) that may be associated with reducing muscle atrophy and enhancing muscular strength and endurance (Shields and Dudley-Javoroski 2006). Various rehabilitation techniques have focused on reducing or reversing these detrimental changes to the muscles of the lower limb following SCI.

A variety of electrical stimulation techniques have been employed to enhance lower limb muscle structure and function in people with SCI. These typically involve delivering a series of electrical pulse trains to the muscle (or nerve supplying the muscle) over time such that it simulates the “normal” exercise experience. Specific stimulation parameters (i.e., pulse width, train duration, between train interval, method of application) and other exercise-related variables (i.e., frequency, duration, intensity, program length) may each be varied to attain an optimal training stimulus. Given the number and variety of these factors, it is not surprising that there is considerable heterogeneity among the specific electrical stimulation interventions that have been investigated to date. In the present review we focus on two strategies: patterned electrical stimulation (PES) and functional electrical stimulation (FES). Whereas both methods typically employ cyclical patterns of electrical stimulation that simulate natural muscular activity, FES is directed towards the attainment of purposeful movement such as cycling or walking. PES, on the other hand, is focused on producing muscle contractions that may be used to generate muscle force such as in an isometric condition. In some applications, PES techniques have been used as a training stimulus to prepare muscles for a subsequent FES training condition (e.g. Kern et al. 2005; Hjeltnes and Lannem 1990). In situations where increased muscle torque and endurance are primary goals to improve function, for example in the quadriceps in an incomplete SCI, the outcomes of these experimental studies have direct clinical relevance.

Gait Retraining Strategies to Enhance Functional Ambulation

Summary

The studies reviewed here suggest that facilitating the practice of walking during rehabilitation can enhance the recovery of functional ambulation in incomplete SCI. Although specific treatment parameters that depend on the injury location, severity, and chronicity remain to be elucidated, there exists some evidence to help guide the clinical decision-making process. Task-oriented gait retraining with partial body weight support, whether provided by a treadmill and partial BWS or overground with assistive devices, appears to be more beneficial when applied sooner rather than later after the onset of injury in people with motor-incomplete lesions. Where resources permit, therapists may use a body-weight support system combined with a treadmill and manual assistance from additional personnel to implement task-oriented gait training. However, there is increasing evidence that equivalent outcomes can be obtained independent of the specific gait retraining strategy (Dobkin et al. 2006; Field-Fote et al. 2005). Some recent preliminary evidence suggests that gait training strategies may also be potentiated by nutrient supplements (Nash et al. 2007) or resistance training of specific muscles (Gregory et al. 2007).

For individuals with more chronic spinal lesions and who have recovered some walking, FES may provide additional gains in functional ambulation. When resources are available, more complex FES systems, with or without bracing, may be used to provide support of upright mobility in individuals with complete paraplegia. Further evidence is required to determine whether combination therapies offer significant advantages over any given approach alone. Future studies should also examine the role of falls risk and history in ambulatory performance following SCI. Early evidence suggests that the more active a person is, the less likely that they will experience a fall (Brotherton et al. 2007). Finally, although this review has focused on functional ambulation outcomes following various rehabilitation strategies, we must also keep in mind the additional health benefits (e.g. improved cardiovascular or bone health) of performing gait exercises.

• There is level 2 evidence (Baldi et al. 1998) that PES-assisted isometric exercise reduces the degree of lower limb muscle atrophy in individuals with recent (~10 weeks post-injury) motor complete SCI, but not to the same extent as a comparable program of FES-assisted cycling exercise.
• There is level 4 evidence (Sabatier et al. 2006) that PES-assisted exercise may partially reverse the lower limb muscle atrophy found in individuals with long-standing (>1 year post-injury) motor complete SCI.
• There is level 2 evidence (Shields and Dudley-Javoroski 2006) that a program of PES-assisted exercise increases lower limb strength and muscular endurance.
• There is level 2 evidence (Baldi et al. 1998) that FES-assisted cycling exercise prevents and reverses lower limb muscle atrophy in individuals with recent (~10 weeks post-injury) motor complete SCI and to a greater extent than PES.
• There is level 4 evidence (Scremin et al. 1999; Crameri et al. 2002) that FES may partially reverse the lower limb muscle atrophy found in individuals with long-standing (>1 year post-injury) motor complete SCI.
• There is level 4 evidence (Gerrits et al. 2000) that FES-assisted cycle exercise may increase lower limb muscular endurance.
• There is level 3 evidence (Wernig et al. 1995) using historical controls that BWSTT is effective in improving ambulatory function. However, stronger evidence from one level 1 RCT (Dobkin et al. 2006) demonstrates that BWSTT has equivalent effects to conventional rehabilitation consisting of an equivalent amount of overground mobility practice for gait outcomes in acute/sub-acute SCI.
• There is level 1 evidence from 1 RCT (Field-Fote et al. 2005) that different strategies for implementing body weight support gait retraining all yield similar ambulatory outcomes in people with chronic, incomplete SCI. It is recommended that therapists may choose a body weight support gait retraining strategy based on available resources (Field-Fote et al. 2005).
• There is level 4 evidence from pre-test/post-test studies (Winchester et al 2009; Hicks et al. 2005; Wirz et al. 2005; Thomas and Gorassini 2005; Protas et al. 2001; Wernig et al. 1998) that BWSTT is effective for improving ambulatory function in people with chronic, incomplete SCI.
• There exists level 1 evidence (Walker and Harris 1993), limited by a small sample size, that GM-1 ganglioside combined with physical therapy improves walking ability in chronic incomplete SCI patients.
• There is limited level 4 evidence (Norman et al. 1998) that clonidine and cyproheptadine use in conjunction with BWSTT enhances walking ability in non-ambulatory incomplete SCI patients such that overground ambulation with assistive devices can be achieved.
• There is level 4 evidence (Thrasher et al. 2006; Ladouceur and Barbeau 2000a; 2000b; Wieler et al. 1999; Klose et al. 1997; Granat et al. 1993; Stein et al. 1993; Granat et al. 1992) that FES-assisted walking can enhance walking speed and distance in complete and incomplete SCI.
• There is level 4 evidence from 2 independent laboratories (Ladouceur and Barbeau 2000a,b; Wieler et al. 1999) that regular use of FES in gait training or activities of daily living leads to persistent improvement in walking function that is observed even when the stimulator is not in use.
• None of the studies investigating the effectiveness of brace/orthotic devices for upright support and mobility are randomized or blinded, but that is in part due to the ethical dilemma of providing safe and appropriate bracing and the fact that participants will be able to distinguish which device they received. There is weak evidence from post-test studies (Scivoletto et al. 2000; Franceschini et al. 1997) that bracing alone results in significant gains in functional ambulation for people with complete SCI. Two studies reported pre-test/post-test results (Nakazawa et al. 2004; Saitoh et al. 1996) (total n = 8) that the use of long-leg braces could enhance gait speed and endurance in people with complete SCI.
• There is level 4 evidence (Yang et al. 1996) that a combined approach of bracing and FES results in additional benefit to functional ambulation in paraplegic patients with complete SCI. However, in subjects who achieve little benefit from bracing alone, the addition of FES appears to help improve standing or short-distance walking function (Marsolais et al. 2000). In incomplete SCI, however, there is some indication that a combination of bracing and FES provides greater ambulatory function than either approach alone (Kim et al. 2004).
• There is level 4 evidence that whole body vibration improves walking function (Ness & Field-Fote, 2009).
• There is level 4 evidence (Field-Fote 2001) that most forms of locomotor training (i.e., including body weight supported treadmill training with various assists and FES-assisted overland training) increase lower limb muscle strength in chronic SCI as indicated by overall increases in total lower extremity motor scores.
• There is level 3 evidence (Wernig et al. 1995) that body weight supported treadmill training is not significantly different than conventional rehabilitation therapy in enhancing lower limb muscle strength in acute SCI, although these studies are confounded by the natural recovery that may take place in the acute period.
• There is level 4 evidence (Gregory et al. 2007) that a resistance and plyometric training program can enable improvements in overground gait speed in chronic incomplete SCI.

Key Points

• PES programs are beneficial in preventing and restoring lower limb muscle atrophy as well as improving lower limb muscle strength and endurance.
• FES-assisted exercise programs are beneficial in preventing and restoring lower limb muscle atrophy as well as improving lower limb muscle strength and endurance in motor complete SCI.
• For patients less than 12 months post-SCI, body weight supported treadmill training has equivalent effects on gait outcomes to conventional rehabilitation consisting of overground mobility practice.
• Body weight-support gait training strategies can improve gait outcomes in chronic, incomplete SCI, but no body weight-support strategy (overground, treadmill, with FES) is more effective.
• There is limited evidence for the benefits of combining the use of certain pharmacological agents with gait training on ambulation in individuals with SCI.
• FES-assisted walking can enable walking or enhance walking speed in incomplete SCI or complete (T4-T11) SCI. Regular use of FES in gait training or activities of daily living can lead to improvement in walking even when the stimulator is not in use.
• There is limited evidence that bracing alone does not enable significant gains in functional ambulation for people with complete SCI. The advantages of bracing appear largely restricted to the general health and well-being benefits related to practice of standing and the ability to ambulate short-distances in the home or indoor settings. The benefits of bracing-alone on functional ambulation are primarily with people with incomplete spinal lesions.
• There is limited evidence that a combined approach of bracing and FES results in additional benefit to functional ambulation in paraplegic patients with complete SCI.
• Locomotor training programs are beneficial in improving lower limb muscle strength although in acute SCI similar strength increases may be obtained with conventional rehabilitation. The real benefit of locomotor training on muscle strength may be realized when it is combined with conventional therapy. This should be further explored in acute, incomplete SCI where better functional outcomes may be realized with the combination of therapies.

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Nutrition-Related Complications

Nutritional Intervention Programs for Obesity & Wellness

Nutritional Interventions for Dyslipidemia

Vitamin Deficiencies and Supplementation

Although little work has been done examining the vitamin profiles of individuals following SCI it is generally thought that vitamin deficiency is a significant issue. Moussavi et al. (2003) reported that 16 to 37% of community-dwelling SCI subjects had serum levels below the reference range for vitamins A, C and E compared with general population norms.   

A case controlled study by Lynch et al. (2002) assessed complete blood count, white blood cells, iron status, ferritin, red blood cell folate, vitamin B12, magnesium, zinc, albumin and prealbumin in persons with chronic SCI and compared values to those of age and gender-matched non-SCI controls.  Results were not outside the normal ranges for either group; however, the SCI group had significantly different median values than the control group for hemoglobin, white blood cell count, albumin, prealbumin, serum iron and % saturation.

Creatine Supplementation for Muscle Function and Exercise Capacity

Synthesized by the liver, kidney and pancreas, creatine occurs naturally and is found primarily in skeletal muscle. It can be obtained from eating foods rich in creatine such as meat and fish or be consumed in the form of supplement powders.The most predominant form of creatine is phosphocreatine which contributes to the rapid resynthesis of adenosine triphosphate (ATP) during short-term, high-intensity exercise.  Dietary supplementation of creatine has been shown to improve strength, power and recovery from high-intensity exercise in the able-bodied population (Casey et al 1996; Balsom et al 1995; Earnest et al 1995; Greenoff et al 1993; Harris et al 1993). Creatine serves as a short duration reservoir for the energy required for muscle contraction in skeletal muscle. Low levels of intramuscular creatine are seen in some neuromuscular diseases. Creatine supplementation improves muscle strength in some patient populations with neurological disorders (Kendall et al 2005).

Table 8 Creatine Administration Post SCI

Discussion

Kendall et al (2005) reported findings of a study that sought to determine whether creatine supplementation improves muscle strength, endurance and function in weak upper limb muscles in person with tetraplegia.  Eight individuals with tetraplegia and mild wrist extensor weakness were randomized to receive creatine or a placebo in a double-blind crossover design.  During creatine supplementation, participants received oral doses of creatine monohydrate powder (10 grams orally twice per day for 6 days then were maintained on 5 grams daily until they underwent testing).  There was no change in any of the functional tests performed by the participants and none of the participants had a change in self-reported motor Functional Independence Measure (FIM) scores.

Persons with SCI have decreased upper extremity work capacity.  Individuals with cervical-level SCI have limited proficiency in the repeated tasks of daily living that require endurance and strength (Lin et al., 1993; Hopman et al., 1992; Jehl et al., 1991; Van Loan et al., 1987).   A study by Jacobs et al (2002) sought to determine the effects of oral creatine monohydrate supplementation on upper-extremity work capacity in persons with complete cervical-level SCI.  Sixteen men with complete tetraplegia (C5 – 7) were randomly assigned to one of two groups and received either 20 grams per day of creatine monohydrate supplement powder or placebo for the first treatment phase; treatment was reversed in the second phase.  Each treatment phase lasted for 7 days with a 21-day washout period.  Peak power output, time to fatigue, heart rate and metabolic measures including oxygen uptake, minute ventilation, tidal volume and respiratory frequency were assessed.  Significantly greater values of oxygen uptake, tidal volume and carbon dioxide production were observed in the groups receiving the creatine monohydrate supplementation.  The investigators concluded that creatine supplementation enhances exercise capacity in persons with complete tetraplegia and may promote greater exercise training benefits. 

Conclusion

• There is level 1 evidence based on one RCT (Kendall et al., 2005) that creatine supplementation did not result in improvements in wrist extensor strength or muscle function.
• There is level 1 evidence based on one RCT cross-over trial (Jacobs et al., 2002) that creatine supplementation enhances exercise capacity in persons with complete tetraplegia and may promote greater exercise training benefits.

• Creatine supplementation does not result in improvements in muscle strength, endurance or function in weak upper limb muscles.
• Creatine supplementation enhances exercise capacity in persons with complete tetraplegia and may promote greater exercise training benefits.

Cardiovascular and Hormonal Responses to Food Ingestion

Persons with chronic primary autonomic failure and widespread sympathetic denervation and postural hypotension often have postprandial hypotension (Mathias, 1991).  Food consumption often exacerbates symptoms and the degree of postural hypotension in certain groups.  The cardiovascular responses to food ingestion in individuals with tetraplegia have not been investigated.

Table 9 Cardiovascular and Hormonal Responses to Food Ingestion

Discussion

A fall in blood pressure following the ingestion of food has been described in individuals with secondary autonomic failure of various causes; however, the cardiovascular and hormonal responses to food ingestion in individuals with tetraplegia with cervical spinal cord transection have not been studied.  Baliga et al. (1997) investigated the effects of a standard liquid meal (300 mL total liquid volume, 550 kilocalories, 66 grams carbohydrate, 22 grams fat, 18 grams protein) on blood pressure (BP), heart rate (HR) and neurohormonal levels in tetraplegics with physiologically complete cervical cord transection.  Five paraplegics with complete lesions (T12-L3) and essentially intact sympathetic nervous systems who did not experience postural hypotension served as the control group.  The experimental group consisted of 6 tetraplegics (C4 – 7) with chronic and complete cervical spinal cord transection.  All had postural hypotension.  After food ingestion there was no fall in BP in tetraplegics or controls.  HR did not change in either group.  Following food ingestion plasma noradrenaline was unchanged in tetraplegics but rose in controls.  Plasma renin activity (PRA) rose in tetraplegics but not in controls.  The fall in BP and rise in HR on head-up tilt after the meal in tetraplegics was similar to that before the meal.  There was no change in PRA following the pre-prandial tilt in either group; post-prandial tilt raised levels in the tetraplegics but not in the controls.  The authors summarized that there is a difference in the responses to food ingestion between tetraplegics and paraplegic controls and even more pronounced differences from other autonomic disorders with sympathetic dysfunction which may relate to the site and nature of the sympathetic lesion and compensatory mechanisms.   

Conclusion

• There is level 3 evidence from one case control study (Baliga et al., 1997) that consumption of a standard liquid meal does not change blood pressure, heart rate or noradrenalin levels in tetraplegics with postural hypotension. 

• Consumption of a standard liquid meal does not change blood pressure, heart rate or noradrenalin levels in tetraplegics with postural hypotension.

The Effects of Nutrient Intake on Ambulation Performance

Reconditioning exercises pursued by persons with incomplete SCI have shown to reverse the decline in function imposed by the paralysis (Jacobs et al 2001).  Nutrition-related modifications that optimize physical performance for individuals with SCI have not been studied extensively compared to that of individuals without disability.

Table 10 Nutrient Intake on Ambulation Performance

Discussion

Dietary, pharmacologic and nutrient modifications that may optimize physical performance for individuals with SCI have not been extensively studied.  In the able-bodied population an effective nutrient supplementation combination to hasten recovery from intense activity and to improve performance in subsequent bouts of exercise is whey protein and carbohydrate (Ivy, 2001; Ivy 1998).  Nash et al (2007) investigated the effect of protein and carbohydrate intake on ambulation in three persons with incomplete SCI (C5 – T4).  The subjects walked to fatigue on 5 consecutive days; upon fatigue, participants consumed 48 grams of whey plus 1 gram per kilogram of body weight of carbohydrate.  The process was repeated following a weekend of rest.  Following a 2-week wash-out period the process was repeated using 48 grams of soy supplement.  Oxygen consumption, carbon dioxide production, respiratory exchange ratio, distance and time of walk and calculated calorie expenditure were measured.  The authors concluded that the combination of whey protein plus carbohydrate supplement ingestion following fatiguing ambulation improved subsequent ambulation by increasing distance, time to fatigue and caloric expenditure compared to soy supplement consumption.  

Conclusion

• There is level 2 evidence based on one RCT cross-over trial (Nash et al., 2007) that the consumption of a whey protein plus carbohydrate supplement following fatiguing ambulation improves subsequent ambulation by increasing distance, time to fatigue and caloric expenditure in persons with incomplete SCI. 

• The consumption of a whey protein plus carbohydrate supplement following fatiguing ambulation improves subsequent ambulation by increasing distance, time to fatigue and caloric expenditure in persons with incomplete SCI.

Post-Meal Resting Energy Expenditure

Food ingestion increases the metabolic rate to levels above basal (Jequier 1986; Lusk 1930).  This rise in metabolic rate in the able-bodied population is initiated within minutes following meal ingestion, reaches its maximum after approximately one hour and lasts up to 6 hours after food consumption.  The mechanisms whereby nutrients stimulate energy expenditure are not fully understood.  The potential role of the central sympathoadrenal system in the stimulation of nutrient-induced thermogenesis requires investigation.   

Table 11 Post-Meal Resting Energy Expenditure Post SCI

Discussion

The increase in the metabolic rate above basal levels following food ingestion is known as nutrient-induced thermogenesis (Jequier 1986; Lusk 1930).This post-meal rise in metabolic rate is significant to daily heat production and body weight homeostasis and may have a potential role in counteracting the development of obesity.  In many obese individuals and in other conditions of insulin resistance nutrient-induced thermogenesis is reduced below normal levels (Brundin et al 1992; Segal et al 1990; Segal et al 1985; Shetty et al 1981; Pittet et al 1976). The rise in resting energy expenditure following food consumption has been generally considered to be mediated by central activation of the sympathoadrenal system; the purpose of a study by Aksnes et al (1993) was to determine the possible role of central sympathoadrenal stimulation for thermogenesis after ingestion of a normal mixed meal, in liquid form, in seven male subjects with chronic complete lesions of the cervical spinal cord (C4 – C7) (group A).  The thermogenic responses were compared to those in healthy males as well as to the responses in a control group of tetraplegic patients who received equal volumes of water instead of the liquid meal (group B).  The authors concluded that nutrient-induced thermogenesis in tetraplegic individuals with low sympathoadrenal activity is not diminished compared to healthy controls; efferent sympathoadrenal stimulation from the brain is not necessary for nutrient-induced thermogenesis in man. 

Conclusion

• There is level 3 evidence based on one case control study (Asknes et al., 1993) that meal-induced thermogenesis is not decreased in tetraplegic individuals with low sympathoadrenal activity and that efferent sympathoadrenal stimulation from the brain is not necessary for nutrient-induced thermogenesis.

• Meal-induced thermogenesis is not decreased in tetraplegic individuals with low sympathoadrenal activity and efferent sympathoadrenal stimulation from the brain is not necessary for nutrient-induced thermogenesis.

Cardiovascular, Endocrine and Renal Responses to Dietary Sodium Restriction in Persons with Paraplegia and Tetraplegia

The kidneys are richly innervated by the sympathetic nervous system (Gazdar and Dammin, 1970, Muller and Barajas, 1972 in Sutters 1992).  The role of the sympathetic renal nerves in the adaptation to changes in dietary sodium intake in persons with spinal cord injury and impaired sympathetic nervous systems warrant study. 

Table 12 Responses to Dietary Sodium Restriction in Persons Post SCI

Discussion

In a study by Sutters et al (1992) the effects of change from a high to low sodium diet on renal sodium and water excretion and hormonal responses were studied in nine individuals with tetraplegia and dissociated sympathetic control (DS) and in six controls with paraplegia with intact sympathetic systems (IS).  Total and fractional urinary sodium excretion, supine mean arterial pressure, creatinine clearance, plasma renin activity and plasma atrial natriuretic peptide concentration were measured.  The authors reported that the results suggested that direct sympathetic control of the kidney is not required for renal sodium conservation in response to dietary salt restriction; however, is likely involved in the hemodynamic and hormonal responses.    

Conclusion

• There is level 3 evidence based on one case control study (Sutters et al., 1992) that sympathetic control of the kidney is not required for renal sodium conservation in response to dietary salt restriction.    

• Impairment of sympathetic control of the kidney secondary to SCI resulting in tetraplegia does not impact renal sodium conservation in response to dietary salt restriction.

Summary

There is a paucity of intervention studies investigating nutritional status and associated risk for persons with SCI. Many descriptive and observational publications address the risk for obesity, dyslipidemia and cardiovascular disease, impaired glycemic control and diabetes mellitus. Blood lipid profiles and indicators of impaired glucose tolerance and hyperinsulinemia of persons with SCI have been compared with those of able-bodied controls. Despite the high risk for CVD morbidity and mortality in individuals with SCI as evidenced by blood values, metabolic and lifestyle factors, few studies have addressed the benefits of risk reduction interventions aimed at modifiable factors and have been limited to exercise. Other studies have investigated vitamin and mineral status of persons with SCI and compared values to those of able-bodied controls or to general population norms and have found lower levels of a variety of nutrients in the SCI population. Few publications have suggested screening and supplementation strategies to address these trends.

• There is level 2 evidence that glucose uptake is higher in SCI individuals compared to able bodied individuals.
• There is level 4 evidence that SCI individuals with complete tetraplegia have higher rates of altered glucose metabolism than other SCI individuals.
• There is level 2 evidence that diabetic and obese SCI individuals show gallbladder emptying compared to healthy SCI individuals.
• There is level 4 evidence from one pre-post trial (Chen et al., 2006) that an intervention program combining diet and exercise is effective for reducing weight among overweight persons with SCI.
• There is level 1 evidence based on one RCT (Zemper et al., 2003) that improved health related behaviours are adopted following a holistic wellness program for individuals with SCI.
• There is level 4 evidence from one pre-post study (Liusuwah et al., 2007) that an education program combining nutrition, exercise and behaviour modification is effective in increasing whole body lean tissue, maximum power output, work efficiency, resting oxygen uptake and shoulder strength in persons with SCI.  
• There is level 2 evidence from one prospective controlled trial (Szlachic et al., 2001) that standard dietary counseling (daily total fat <30% of kcal, saturated fat <10% of kcal, cholesterol <300 mg, carbohydrate 60% of kcal) can reduce total and LDL cholesterol among individuals with SCI and total cholesterol >5.2mmol/L.
• There is level 4 evidence from one pre-post study (Javierre et al., 2005) that daily supplementation with DHA (1.5 g) and EPA (0.75 g) increases plasma DHA and EPA levels but does not alter total cholesterol, HDL, LDL, VLDL, triglycerides, or glucose.
• There is level 4 evidence from one pre-post study (Javierre et al., 2006) that omega-3 fatty acid supplementation increases upper body strength and endurance in persons with SCI.
• There is level 4 evidence from two pre-post studies (Bauman et al., 2005) that vitamin D3 supplementation raises serum 25(OH)D levels.  However, the dose and duration required to ensure vitamin D3 sufficiency remains unclear.
• There is level 1evidence based on one RCT (Kendall et al., 2005) that creatine supplementation did not result in improvements in wrist extensor strength or muscle function.
• There is level 1 evidence based on one RCT cross-over trial (Jacobs et al., 2002) that creatine supplementation enhances exercise capacity in persons with complete tetraplegia and may promote greater exercise training benefits.
• There is level 3 evidence from one case control study (Baliga et al., 1997) that consumption of a standard liquid meal does not change blood pressure, heart rate or noradrenalin levels in tetraplegics with postural hypotension. 
• There is level 2 evidence based on one RCT cross-over trial (Nash et al., 2007) that the consumption of a whey protein plus carbohydrate supplement following fatiguing ambulation improves subsequent ambulation by increasing distance, time to fatigue and caloric expenditure in persons with incomplete SCI. 
• There is level 3 evidence based on one case control study (Asknes et al., 1993) that meal-induced thermogenesis is not decreased in tetraplegic individuals with low sympathoadrenal activity and that efferent sympathoadrenal stimulation from the brain is not necessary for nutrient-induced thermogenesis.
• There is level 3 evidence based on one case control study (Sutters et al., 1992) that sympathetic control of the kidney is not required for renal sodium conservation in response to dietary salt restriction.    
• More research is needed to evaluate the role of nutrition in the management of post-acute SCI to provide the evidence base required for optimal clinical decisions.

Key Points

• Individuals with complete tetraplegia have higher rates of altered glucose metabolism.
• Impaired gallbladder emptying is seen in diabetic and obese SCI individuals.
• A combined diet and exercise program can help patients reduce weight following SCI without compromising total lean mass and overall health.
• Participation in a holistic wellness program is positively associated with improved eating and weight-related behaviours in persons with SCI.
• A combined nutrition, exercise and behaviour modification program can help persons with SCI increase metabolically active lean tissue, work efficiency, resting oxygen uptake and strength.
• Dietary counseling results in improved lipid profile; consultation with a registered dietitian should be obtained, because individualized diets may enhance compliance.
• Blood concentrations of DHA and EPA increased as the result of n-3 fatty acid supplementation; however, no significant changes in lipid profile were identified. 
• Omega-3 fatty acid supplementation increases upper body strength and endurance in persons with SCI.
• Individuals with SCI should be screened for vitamin D deficiency and, if needed, replacement therapy should be initiated.
• Clinicians should conduct early screening for and treatment of vitamin B12 deficiency.
• Creatine supplementation does not result in improvements in muscle strength, endurance or function in weak upper limb muscles.
• Creatine supplementation enhances exercise capacity in persons with complete tetraplegia and may promote greater exercise training benefits.
• Consumption of a standard liquid meal does not change blood pressure, heart rate or noradrenalin levels in tetraplegics with postural hypotension.
• The consumption of a whey protein plus carbohydrate supplement following fatiguing ambulation improves subsequent ambulation by increasing distance, time to fatigue and caloric expenditure in persons with incomplete SCI.
• Meal-induced thermogenesis is not decreased in tetraplegic individuals with low sympathoadrenal activity and efferent sympathoadrenal stimulation from the brain is not necessary for nutrient-induced thermogenesis.
• Impairment of sympathetic control of the kidney secondary to SCI resulting in tetraplegia does not impact renal sodium conservation in response to dietary salt restriction.
• More research is needed to evaluate the role of nutrition in the management of post-acute SCI to provide the evidence base required for optimal clinical decisions.

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Pharmacological Management of OH in SCI

The majority of our knowledge in managing OH is obtained from patients presenting OH consequent to non-SCI causes (e.g. heart disease, Parkinson’s disease, dyautonomia).  Numerous medications, including Midodrine, fludrocortisone, and ephedrine, have been successful in managing OH in these chronic conditions.  However, as the mechanisms underlying the development of OH are different in individuals with SCI, it is important to assess the effectiveness of these medications specifically in people with SCI.

Table 3: Pharmacological Management of OH in SCI

Discussion

Midodrine (ProAmatine)

Midodrine, a selective alpha1 adrenergic agonist, exerts its actions by activating the alpha-adrenergic receptors of the arteriolar and venous vasculature, thus producing an increase in vascular tone and blood pressure. In the body, Midodrine has a half-life of approximately 25 minutes. Specifically, plasma levels of Midodrine peak at about half an hour, with this amount halved every 25 minutes. However, the primary metabolite reaches peak blood concentrations about 1 to 2 hours after a dose of Midodrine and has a half-life of about 3 to 4 hours. Usual doses are 2.5mg two or three times daily. Doses are increased quickly until a response occurs or a dose of 30 mg/day is attained (Wright et al. 1998). Midodrine does not cross the blood-brain barrier and is not associated with CNS effects.  Benefits of Midodrine in the OH management in individuals with SCI were reported in a level 2 RCT (Nieshoff et al. 2004), two level 4 studies ( Barber et al. 2000; Senard et al. 1991)  and one level 5 study (Mukand et al. 1992). Of note, a recent case report on 2 male subjects demonstrated urinary bladder dysreflexia with the use of midodrine (Vaidyanathan et al. 2007) and suggests Midodrine should be employed cautiously.    

Although the only controlled trial consisted of 4 subjects (Nieshoff et al. 2004), this study used a rigorous double-blind placebo-controlled, randomized, within-subjects cross-over trial.  Not only was systolic blood pressure increased during peak exercise (3/4 subjects), but exercise performance was also enhanced.  Thus, there is level 2 evidence (Nieshoff et al. 2004) that Midodrine enhances exercise performance in some individuals with SCI, similar to other clinical populations with cardiovascular autonomic dysfunction.  Nevertheless, it would be useful to confirm this evidence with a larger trial.

Fludrocortisone (Florinef)

Fludrocortisone is a mineralocorticoid that induces more salt to be released into the bloodstream. As water follows the movement of salt, fludrocortisone increases blood volume. Furthermore, fludrocortisone may enhance the sensitivity of blood vessels to circulating catecholamine (Van Lieshout et al. 2000; Schatz 1984). The starting dose is 0.1 mg daily. Blood pressure rises gradually over several days with maximum effect at 1-2 weeks.  Doses should be adjusted at weekly or biweekly intervals. Adverse effects include hypokalemia (low potassium), which occurs in 50% of individuals, and hypomagnesemia, which occurs in 5%. Both may need to be corrected with supplements. Fludrocortisone should not be used in persons with congestive heart failure due to its effect on sodium retention.  Headache is a common side effect. The benefit of Fludrocortisone has not been sufficiently proven in individuals with SCI.  One level 4 case series (Barber et al. 2000), one level 5 case report (n=1) (Groomes & Huang 1991), and one level 5 observational (Frisbie & Steele 1997) study described the use of Fludrocortisone for management of OH in the SCI population.

In Barber et al.’s (2000) study involving two patients, no effect of fludrocortisone was observed. However, Groomes & Huang (1991) found an improvement in one patient within 10 days of treatment. The other study conducted by Frisbie and Steele (1997) combined fludrocortisone with other pharmacological and physical agents in three patients; unfortunately, since outcomes specific to this group were not described, the specific effects of fludrocortisone could not be discerned. Therefore, at this point, there remains only level 4 evidence (Barber et al. 2000) from one case series of two patients that fludrocortisone is not effective for OH in SCI.  

Dihydroergotamine

Dihydroergotamine, or Ergotamine, is an ergot alkaloid that interacts with alpha adrenergicreceptors and has selective vasoconstrictive effects on peripheral and cranial blood vessels. Plasma levels peak around 2 hours after ingestion.  One case report combined Ergotamine with fludrocortisone to successfully prevent symptomatic OH in one individual with SCI (Groomes & Huang 1991). Hence, there is level 5 (Groomes & Huang 1991) evidence that Ergotamine, taken daily combined with fludrocortisone, successfully prevents OH in one individual with SCI.

Ephedrine

Ephedrine, a non-selective, alpha and beta receptor agonist, acts centrally and peripherally. Its peripheral actions are attributed partly to norepinephrine release and partly to direct effects on receptors. Ephedrine is usually given at a dosage of 12.5-25 mg, administered orally, three times a day.  Side effects may include tachycardia, tremor and supine hypertension. Ephedrine raises blood pressure both by increasing cardiac output and inducing peripheral vasoconstriction. Its plasma half-life ranges from 3 to 6 hours (Kobayashi et al. 2003). Systematic review of the literature elicited level 5 evidence from one retrospective chart review (Frisbie & Steele 1997) and a cross-sectional observation study (Frisbie 2004). Frisbie (2004) reported that daily urinary output of salt and water was inversely related to the prescribed dose of Ephedrine in 4 patients with OH. While results suggest that Ephedrine resulted in an improvement in hyponatremia, renal conservation of water still exceeded that of sodium in 3 of the 4 cases. Frisbie and Steele (1997) report in their retrospective review of 30 patients taking ephedrine that one dose in the morning is usually sufficient to reduce OH symptoms but that some patients failed to recognize the need for a repeated dose later in the day. Hence, there is level 5 evidence (Frisbie & Steele 1997) that Ephedrine may reduce symptoms of OH.

L-threo-3,4-dihydroxyphenylserine (L-DOPS)

L-DOPS is an exogenous, neutral amino acid that is also a precursor of noradrenalin. Only one published study (Muneta et al. 1992)evaluates the effects of L-DOPS on OH. This level 5 study involving one person with nontraumatic SCI, showed that treatment with salt supplementation in combination with L-threo-3,4-dihydroxyphenylserine, markedly improved the syncope and drowsiness associated with hypotension and increased the patient's daily activity. There is level 5 evidence (Muneta et al. 1992) based on one case study that L-DOPS, in conjunction with salt supplementation may be effective for reducing OH.

Nitro-L-arginine methyl ester (L-NAME)

L-NAME decreases the production of the vasodilator nitric oxide by inhibiting the expression of its enzyme, nitric oxide synthase. Increased nitric oxide release has been associated with orthostatic intolerance after cardiovascular deconditioning and is proposed to play a role in OH after SCI (Wecht et al. 2007). Only one study (Wecht et al. 2009) was found that examined the use of L-NAME in the treatment of OH following SCI. The study found that after infusion of 1.0 mg/kg of L-NAME, people with tetraplegia had a higher mean arterial pressure in response to head tilt procedure compared with people who received a placebo and this pressure was not significantly different than non-SCI controls.  It should be noted that the increase in mean arterial pressure in the treatment group was not maintained over the entire head tilt procedure.  In summary, there is level 2 evidence that L-NAME increases the blood pressure of SCI subjects following a head up tilt procedure.

General Discussion

In summary, the studies addressing the pharmacological management of OH following SCI involve a small number of trials with low number of subjects and numerous case reports.  Furthermore, it is often difficult to determine the effects of individual medications when used as combination therapies.  Midodrine hydrochloride should be included in the management protocol of OH . Further research needs to quantify the effects of the many pharmacological interventions which have been shown to be effective in conditions other than spinal cord injury.  

Conclusion

• There is level 2 evidence (from 1 RCT) (Nieshoff et al. 2004) that Midodrine enhances exercise performance in some individuals with SCI, similar to other clinical populations with cardiovascular autonomic dysfunction. 
• There is level 4 evidence (from 1 case series) (Barber et al. 2000) that fludrocortisone is not effective for OH in SCI.
• There is level 5 evidence (from 1 case report) (Groomes & Huang 1991) that Ergotamine, combined daily with fludrocortisone, may successfully prevent symptomatic OH.
• There is level 5 evidence (from 1 observational study) (Frisbie & Steele 1997) that Ephedrine may prevent some symptoms of OH.
• There is level 5 evidence (from 1 case report) (Muneta et al. 1992) that L-DOPS, in conjunction with salt supplementation may be effective for reducing OH.
• There is level 2 evidence (from 1 prospective control trial) (Wecht et al. 2009) that L-NAME may be effective for reducing OH.

• Midodrine hydrochloride should be included in the management protocol of OH in individuals with spinal cord injury.
• There is limited evidence that fludrocortisone is effective for the management of OH in SCI
• There is limited evidence that ergotamine is effective for the management of OH in SCI
• There is little evidence that ephedrine is effective for the management of OH in SCI
• There is limited evidence that L-DOPS is effective for the management of OH in SCI
• There is limited evidence that L-NAME is effective for the management of OH in SCI

Non-pharmacological Management of OH in SCI

Of the non-pharmacological studies, three involved the regulation of fluid and salt intake while 14 investigated physical modalities such as abdominal binders, physical activities, and electrical muscle stimulation.

Summary

• There is level 2 evidence (from 1 RCT) (Nieshoff et al. 2004) that Midodrine enhances exercise performance in some individuals with SCI, similar to other clinical populations with cardiovascular autonomic dysfunction. 
• There is level 4 evidence (from 1 case series) (Barber et al. 2000) that fludrocortisone is not effective for OH in SCI.
• There is level 5 evidence (from 1 case report) (Groomes & Huang 1991) that Ergotamine, combined daily with fludrocortisone, may successfully prevent symptomatic OH.
• There is level 5 evidence (from 1 observational study) (Frisbie & Steele 1997) that Ephedrine may prevent some symptoms of OH.
• There is level 5 evidence (from 1 case report) (Muneta et al. 1992) that L-DOPS, in conjunction with salt supplementation may be effective for reducing OH.
• There is no evidence on the effect of salt or fluid regulation alone for OH management in SCI. Salt and fluid regulation was evaluated in combination with other pharmacological interventions and thus, the effects of salt and fluid regulation cannot be determined. 
• There is conflicting evidence that elastic stockings/abdominal binders have any effect on cardiovascular responses in individuals with SCI. 
• There is level 2 evidence stress (from 1 prospective controlled trial) (Krassioukov & Harkema 2006) that application of a harness in individuals with SCI could alter baseline cardiovascular parameters and the response to orthostatic.
• There is level 2 evidence (from small, lower quality RCTs) (Elokda et al. 2000; Faghri & Yount 2002; Sampson et al. 2000) that FES is an important treatment adjunct to minimize cardiovascular changes during postural orthostatic stress in individuals with SCI.
• There is level 2 evidence (from 1 RCT) (Lopes et al. 1984) that simultaneous upper extremity exercises does not improve orthostatic tolerance during a progressive tilt exercise. 
• There is level 4 evidence (from 1 pre-post study) (Ditor et al. 2005) that 6 months of body-weight support treadmill training does not substantially improve orthostatic tolerance during a tilt test.
• There is level 4 evidence (from 1 pre-post study) (Harkema et al. 2008) that 80 sessions of active stand training improves cardiovascular control such as response to orthostatic stress after cervical SCI.

Key Points

• Midodrine hydrochloride should be included in the management protocol of OH in individuals with spinal cord injury.
• There is limited evidence that fludrocortisone is effective for the management of OH in SCI.
• There is limited evidence that ergotamine is effective for the management of OH in SCI.
• There is little evidence that ephedrine is effective for the management of OH in SCI.
• There is limited evidence that L-DOPS is effective for the management of OH in SCI.
• There is limited evidence that L-NAME is effective for the management of OH in SCI
• The benefits of salt loading have not been sufficiently proven in individuals with SCI.
• There is insufficient evidence that elastic stockings or abdominal binders have any effect on cardiovascular responses in SCI
• The use of FES is an effective adjunct treatment to minimize cardiovascular changes during changes in position.
• Simultaneous arm exercise during a tilt test is not effective for improving orthostatic tolerance.
• There is limited evidence that regular physical activity may improve orthostatic tolerance during a tilt test.
• There is limited evidence that active stand training may improve the response to orthostatic stress in cervical SCI. 

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Incidence, Quality and Significance

Location and Quality of SCI Pain

Widerstrom-Noga et al. (2001) conducted a careful analysis of the relationship between the location of the pain and the patients’ description of the pain.  In this study 217 of 330 patients reporting chronic pain in a previous survey agreed to participate in the study.  Participants had been injured for an average of 8.2 ± 5.1 years and 55.4% were quadriplegic.  Most subjects in this study marked multiple areas on a pain drawing with the back area being most frequently implicated (61.8%).  59.9% complained of a burning pain while 54.9% described an aching pain.  Interestingly burning pain was significantly associated with pain localized to the front of the torso and genitals, buttocks and lower extremities.  In contrast, aching type pain was significantly associated with pain localized to the neck, shoulders and back.

Widerstrom-Noga et al. (2001) noted that the descriptor “burning” is often associated with neuropathic pain (Siddall et al. 1999, Ragnarsson 1997, Fenollosa et al. 1993) whereas “aching” is often associated with musculoskeletal pain (Siddall et al. 1999, Tunks 1986).  However, since there is a significant overlap in the quality of pain types it is difficult to establish a definitive clinical relationship(Eide 1998, Bowsher 1996, Widerstrom-Noga et al. 2001).  The authors then go on to suggest that musculoskeletal-type pain (best characterized by the aching pain in the neck, shoulders and back) is potentially amenable to therapeutic interventions and aggressive attempts should be made to ameliorate this type of pain.  All of this underscores the need for a reproducible classification system of the pain experienced following SCI.  Bennett et al (2007) have noted that the increasing reliance on validated screening tools may help “form the basis of forthcoming clinical diagnostic criteria”.

Conclusion

• The most common types of pain post SCI are: 1) a burning pain (likely neuropathic) usually localized to the front of torso, buttock or legs or 2) an aching pain (likely musculoskeletal) usually localized to the neck, shoulders and back.

• Post-SCI pain is most commonly divided into neuropathic or musculoskeletal pain.

Classification of SCI Pain

Siddall et al. (1997) noted that one of the concerns regarding SCI-related pain was a lack of consensus over a classification system for SCI pain.  This has led to considerable variation in incidence and prevalence rates for pain post SCI depending on the classification system used.  Twenty-eight (28) classification schemes have been published between 1947 and 2000.   A Task Force on Pain Following Spinal Cord Injury of the International Association for the Study of Pain has introduced a taxonomy, which classified SCI pain based on presumed etiology (Burchiel and Hsu 2001, Siddall 2000).

Table 1 Proposed IASP Classification of Pain Related to SCI (Burchiel & Hsu 2001)

Table 2 SCI pain types according to major classification

Table 3 Reliability of SCI pain classification systems

A new International Classification of Spinal Cord Injury Pain (ICSCIP) has been proposed.  This new classification aims to be more comprehensive in the types of pain directly related to or commonly found in individuals with SCI.

Musculoskeletal or Mechanical Pain

Musculoskeletal or mechanical pain occurs at or above the level of the lesion and is due to changes in bone, tendons or joints (Guttmann 1973).  This is referred to as nociceptive pain caused by a variety of noxious stimuli to normally innervated parts of the body (Ragnarsson 1997).  Overuse of remaining functional muscles after spinal cord injury or those recruited for unaccustomed activity may be of primary importance in some patients (Farkash 1986).  Pain may also be secondary to spinal osteoporosis or facet arthropathy (Farkash 1986).  Instability of the vertebral column may also be a problem (Farkash 1986).  Pain is usually dull and aching in character and although more common soon after SCI, it may become chronic.

Sie et al. (1992) studied 239 SCI outpatients for the presence of upper extremity pain.  Of the 136 patients with quadriplegia, 55% reported upper extremity pain, most commonly at the shoulder (46% of all subjects).  In the case of shoulder pain, 45% were orthopedic-related including tendonitis, bursitis, capsulitis and osteoarthritis.  Of the 103 paraplegics, 66 reported upper extremity pain with two-thirds reporting symptoms of carpal tunnel syndrome and 13 reporting musculoskeletal-related shoulder pain. Daylan et al (1999), in a questionnaire returned by 130 SCI patients, found that 58.5% of patients reported upper extremity pain. Of these, 71% had shoulder pain, 53% wrist pain, 43% hand pain, and 35% elbow pain. Pain was most likely to be associated with pressure relief, transfers, and wheelchair mobility. Subbarao et al (1995), in a survey of 800 SCI patients, found that 72.7% of responders reported some degree of chronic pain at the wrist and shoulder, with wheelchair propulsion and transfers being responsible for most of the pain. McCasland et al (2006) noted that in their survey, 70% of SCI had shoulder pain, one-third had a previous injury to their shoulder and 52% reported a bilateral pain. Quadriplegics were more likely to have shoulder pain (80%). Previous shoulder trauma increased the risk of having shoulder pain.

Central or Neurogenic Dysesthetic Pain

"Central" dysesthesia or "deafferentation" pain is the most common type of pain experienced below the level of SCI and is generally characterized as a burning, aching and/or tingling sensation.  In many cases this dysesthetic or deafferentation pain has defied a pathophysiological explanation (Britell, 1991) although most researchers firmly support a central nervous system origin for this pain.  Nashold (1991) goes as far as stating that except for radicular pain, all other pains of paraplegia are central or deafferentation in origin.  This pain is most often perceived in a generalized manner below the level of the lesion, often a diffuse burning type of pain (Britell 1991, Tunks 1986).  Burning pain is reportedly most common with lesions at the lumbar levels, although it may be found with SCI at thoracic and cervical levels (Tunks 1986).  Nashold (1991) reported this pain occurred almost immediately after SCI and persisted.

Beric (1997) refers to this pain as central dysesthetic pain (CDP) and found dissociative sensory loss and absence of spinothalamic-anterolateral functions, with different degrees of dorsal column function preservation present almost exclusively in incomplete SCI patients.  CDP takes weeks or months to appear and is often associated with recovery of some spinal cord function.  Paradoxically CDS is often characterized by complete loss of temperature, pinprick, and pain perception below the level of the lesion.  It rarely occurs in spinal cord Injuries with complete sensory loss or loss of both sensory and motor functions below the level of the lesion.  Davidoff et al. (1987a) concurred and further noted dysesthetic pain was more likely to be found in incomplete paraplegia resulting from penetrating wounds of the spinal cord, and in spinal fractures treated with conservative management.   

A number of factors may contribute to exacerbations of these "central" pain syndromes; these include visceral diseases or disturbances, movement, smoking or alcohol, emotional factors, fatigue, and even weather changes (Botterell 1953, Davis 1947, Davis 1975, Tunks 1986).  Pressure sores, particularly if infected, or an occult injury such as a fracture, may result in an increase in burning, dysesthetic pain.  These stimuli often provoke autonomic dysreflexic-like symptoms and simultaneously also may aggravate this "burning" pain.

Borderzone or Segmental Pain

Individuals with SCI frequently experience a band of pain and hyperalgesia at the border zone between diminished or abnormal and preserved sensation (Tunks 1986, Botterell 1953, Davis 1975, Heliporn 1978, Kaplan 1962, Maury 1978, Melzack 1978, Michaelis 1970).  In the more recent literature, this segmental pain is further described as occurring at or just above the level of sensory loss in the cutaneous transition zone from the area of impaired/lost sensation to areas of normal sensation, involving at least one to three dermatomes (Friedman 1989, Nashold 1991, Ragnarsson 1997) and is often associated with spontaneous painful tingling or burning sensations in the same area.   Ragnarsson (1997) also noted that in an individual with a cervical cord injury, segmental pain may be described as tingling, burning or numbing pain in the shoulders, arms or hands, those with a thoracic cord injury frequently describe a circumferential, feeling of tightness and pain around the chest and abdomen while lumbar lesions tend to be localized to the groins and different parts of the lower extremities.  According to Nashold (1991) paraplegics often complain that touching the skin in the pain region activates the pain causing it to radiate into the lower parts of the body, especially the legs.  Pain can be triggered by stroking and/or touching the skin in adjacent painful dermatomes (Nashold 1991).  Even light touch or the pressure of clothing or bed sheets over this region may provoke marked discomfort (Tunks 1986).  It may be accompanied by sweating or vasodilation at or below the level of hyperalgesia.  Segmental pain is generally symmetrical although a partial spinal cord injury with asymmetrical neurological involvement will produce asymmetries (Nashold 1991). 

This pain has also been described as "neuropathic at level pain" (Siddall et al 1997) Although several theories have been proposed (Tunks 1986, Nashold 1981, Pollock 1951, Matthews 1972, Levitt 1983, Melzack 1978) the neurological mechanism responsible for this area of hyperalgesia after spinal injury is not well understood (Farkesh 1986).  Although radicular pain is most severe in incomplete SCI lesions, it is also seen in transected cauda equina lesions which are by definition radicular types of pain (Heaton 1965, Siddall et al. 1997). It may also be secondary to spinal cord instability by facet or disc material, or to direct damage to the nerve root during the initial injury (Burke 1973, Nashold 1991).  This “radicular” pain is associated with sensory change in the involved painful dermatome (Nashold 1991) and is most common to cervical or lumbosacral nerve roots.  Non-neural structures, such as the dura mater, have also been suggested as a source of radicular pain (Cyriax 1969, Farkash 1986).  In addition, it has been suggested that central borderzone pain may be generated in the damaged spinal cord just proximal to the spinal cord injury (Nashold 1991, Pollock 1951).  Unfortunately, unless there is definitive evidence on imaging of nerve root damage, it is difficult to distinguish between these various mechanisms of pain.

To reflect this uncertainty Siddall et al. (1997) in their proposed classification of SCI pain note that this "neuropathic at level pain" is divided into radicular and central pain.  Radicular pain is due to nerve root pathology while central pain is due to changes within the spinal cord or possibly supraspinal structures.  Pain attributable to nerve root damage is suggested by features of neuropathic pain (i.e. burning, stabbing, shooting, electric-like pain, allodynia) and increased pain with spinal movement. Sjolund (2002) notes that this pain is thought to occur from nerve root entrapment and may occasionally benefit from decompression.

However, pain, which appears radicular in nature, may occur in the absence of nerve root damage.  This leads to the second grouping of borderzone pain, namely central pain or that which is due to pathology within the spinal cord thought to be the result of damage to the gray matter of the dorsal horn of the spinal cord (Ragnassaron 1997, Woolsey 1995).  According to Ragnassaron (1997), such an injury “has been said to result in hyperactivity of the nociceptor cells within the dorsal horn (Nashold and Bullitt 1981, Nashold and Ostdahl 1979)which can be electrically recorded (Nashold and Alexander 1989).”    Sojlund(2002) notes that this second type of at level neuropathic pain is experienced as a girdle pain uni- or bilaterally in 2-4 segments of the transitional region.  This pain is described as stimulus independent, often accompanied by troublesome allodynia or hyperalgesia and thought to arise from segmental deafferentation (Sjolund 2002).

Psychological Factors

Most studies of chronic SCI pain have focused on the medical causes and clinical manifestations of pain while much less is understood about how psychosocial factors impact SCI pain (Summers 1991).  A negative psychosocial environment along with increased age, depression, anxiety and intellect were found to be associated with reports of greater post-SCI pain severity interfering with activities of daily living (Richards et al. 1980).  Greater pain severity was not associated with physiological factors such as injury level, completeness of injury, surgical fusion and/or instrumentation or veteran status.  The authors were unable to distinguish whether the psychological factors were a consequence of, or contributors to, greater pain severity.  Summers et al (1991) studied 54 SCI patients (19 with quadriplegia and 35 with paraplegia) and of these, 42 patients assessed with the Pain questionnaire found that anger and negative cognitions were associated with greater pain severity.  Severity of pain was higher in patients who reported pain in response to a question on general well being , those that were less accepting of their disability and those that perceived that a significant other would express punishing responses to their pain  behaviours.  Pain itself was found to be associated with greater emotional distress than the SCI itself.  The authors concluded that the experience of pain was associated with psychosocial factors.  Hence treatment of post-SCI pain should involve these multidimensional aspects.

Cohen et al. (1988) found that patients with complete SCIs reported significantly less severe pain than did pain clinic patients.  However, they did not differ from patients with incomplete lesions.  Patients with complete SCIs and pain clinic patients showed a significantly more disturbed MMPI (Minnesota Multiphasic Personality Inventory)profile than did patients with incomplete SCIs.  It was hypothesized that those patients with complete lesions view themselves as more functionally limited than patients with incomplete lesions, and the completeness of the SCI may be more important in determining psychosocial adjustment than pain per se.  Rintala (1998) in community-based men with SCI found that chronic pain was associated with more depressive symptoms, more perceived stress and poorer self-assessed health.

Woollaars et al (2007) administered questionnaires to persons with a SCI. Of the potential 575 subjects, 49% provided responses. SCI pain prevalence was 77%. Factors associated with less pain intensity included more internal pain control and coping, less catastrophizing, a higher level of lesion and a non-traumatic SCI cause. More pain was associated with greater pain-related disability. Lower catastrophizing was related to better health. Factors related to greater well-being included less helplessness and catastrophizing, greater SCI acceptance and lower anger levels. Greater levels of depression were associated with higher levels of SCI helplessness, catastrophizing and anger. The authors noted that chronic SCI pain and quality of life were both largely associated with several psychological factors of which pain catastrophizing and SCI helplessness were more important. Surprisingly, pain intensity showed no independent relationships with health, well-being and depression.

Widerström-Noga et al (2007) studied 190 patients with SCI and chronic pain and were able to identify 3 subgroups. The first group was described as ‘dysfunctional’, characterized by higher pain severity, life interference, affective distress scores, and lower levels of life control and activities scores. The second group was described as ‘interpersonally supported’, characterized by moderately high pain severity, and higher life control, support from significant other, distracting responses, solicitous response, and activities scores. The final group was described as ‘adaptive copers’, characterized by lower pain severity, life interference, affective distress , support from significant others, distracting responses, solicitous responses, activities and higher life control scores. Compared with dysfunctional subgroup, the interpersonally supported group reported significantly greater social support.

Non-Pharmacological Management of Post-SCI Pain

Before moving to pharmacological and surgical interventions, it is important to deal with those factors which may intensify or worsen the experience of pain.  As mentioned previously, SCI pain may be worsened by decubitus ulcers, a urinary tract infection or stone, autonomic dysreflexia, increased spasticity, anxiety, depression, psychosocial factors and other contributors to post-SCI pain (Davis 1998, Tunks 1986).  There are a number of non-pharmacological interventions for post-SCI pain which have been studied from massage to hypnosis.

Pharmacological Management of Post-SCI Pain

Pharmacological interventions are the standard treatment for SCI pain.  The limited effectiveness of non-pharmacological treatments has contributed to increasing use of pharmacological interventions to deal with what is often very severe and disabling pain.

Surgical Interventions

Summary

Pain following SCI is quite common. The most common type of pain post SCI is central or neuropathic in nature characterized by a dysesthetic, burning pain below the level of SCI. Borderzone or segmental pain is much less common; occurring along the border between normal and absent sensation. The precise etiology of central/neuropathic or borderzone segmental pain is not known. There is some evidence suggesting an association may exist between the central or neuropathic dysesthetic burning pain and abnormalities of the sympathetic nervous system. Musculoskeletal pain, either secondary to the original trauma or to overuse is both common and well understood. Unfortunately, the management of central or neuropathic pain remains difficult and largely ineffective.

• For many SCI patients pain has a significant impact on quality of life.
• Over 50% of SCI patients develop chronic pain.  Severe pain is more common the lower down the lesion in the spinal cord. Pain post-SCI most often begins within the first 6-12 months post-SCI. 
• The most common types of pain post SCI are: 1) is a burning pain (likely neuropathic) usually localized to the front of torso, buttock or legs; 2) an aching pain (likely musculoskeletal) usually localized to the neck, shoulders and back.
• There is limited level 4 evidence that massage and heat are the best non-pharmacological treatments for pain post SCI.
• There is level 1 evidence that in general acupuncture is no more effective than Trager therapy or sham acupuncture in reducing nociceptive musculoskeletal shoulder pain post SCI.
• There is level 4 evidence that acupuncture and electroacupuncture reduces neuropathic pain of patients with SCI.
• There is level 1 evidence that a regular exercise program significantly reduces post-SCI pain.
• There is level 2 evidence (from one RCT and one PCT) that a shoulder exercise protocol reduces the intensity of shoulder pain post SCI.
• There is level 4 evidence that the MAGIC wheels 2-gear wheelchair results in less shoulder pain.
• There is level 4 evidence that hypnosis reduces pain intensity post SCI.
• There is level 2 evidence that a cognitive behavioural pain management program with pharmacological treatment improves chronic pain post SCI over the short term.
• There is level 2 evidence that cognitive-behavioural therapy alone does not change post-SCI pain intensity.
• There is limited (Level 4) evidence, based on one pre-post study with small numbers, that visual imagery may reduce neuropathic pain post SCI.
• Based on three level 1 studies, there is strong evidence, of the benefits of transcranial electrical stimulation in reducing post-SCI pain.
• There is limited (Level 4) evidence that using a static field magnet helps to reduce reports of sharp, stabbing nociceptive shoulder pain but does not significantly reduce the VAS score of pain in individuals with a SCI.
• There is limited (level 4) evidence that TENS reduced at-the-injury site pain in only a minority of patients with thoracic or cauda equina SCI, but not those with cervical SCI.
• There is level 1 evidence that transcranial magnetic stimulation significantly reduced post-SCI pain significantly over the long-term.
• There is level 1 evidence that Gabapentin and pregabalin improve neuropathic pain post SCI. 
• There is level 4 evidence that the anticonvulsant Gabapentin is more effective when SCI pain is <6 mos than >6 mos.
• There is level 2 evidence that lamotrigine improves neuropathic pain in patients with incomplete SCI.
• Based on one Level 1 study, Levetiracetam is not effective in reducing neuropathic pain post SCI.
• There is Level 1 evidence that valproic acid does not significantly relieve neuropathic pain post SCI.
• There is level 1 evidence that amitriptyline is effective in the treatment of post-SCI pain in depressed individuals.
• There is Level 1 evidence that trazodone does not reduce post-SCI neuropathic  pain.
• There is level 1 evidence (based on one RCT) that Lidocaine delivered through a subarachnoid lumbar catheter provides short-term relief of pain greater than placebo.
• There is level 1 evidence (based on one RCT) that intravenous Ketamine significantly reduces allodynia when compared to placebo.
• There is level 1 evidence (based on one RCT) that mexilitene (a derivative of lidocaine) does not improve SCI dysesthetic pain when compared to placebo.
• There is level 1 evidence (based on one RCT) that Intrathecal Baclofen reduces dysesthetic pain post SCI.  However, the sample size was small and a before and after trial reported contradictory results.
• There is level 4 evidence that Intrathecal Baclofen reduces musculoskeletal pain post-SCI by reducing spasticity.
• There is level 4 evidence that motor point phenol block is effective in reducing short term spastic shoulder pain post SCI.
• There is level 4 evidence that local botulinum toxin injections to treat focal spasticity reduces pain.
• There is level 1 evidence that intravenous morphine significantly reduces mechanical allodynia more than placebo.
• There is level 1 evidence that tramadol is effective in reducing neuropathic pain post SCI.
• There is level 1 evidence that alfentanil reduces overall post SCI pain.
• There is level 1 evidence that alfentanil is more effective at reducing wind up like pain than ketamine.
• There is conflicting evidence for the use of THC in reducing spastic pain in SCI individuals.
• There is level 1 evidence (based on only one RCT) that Intrathecal Clonidine alone did not provide pain relief greater than placebo, although there was a trend.
• There is level 2 evidence (based on only one prospective controlled study) that the combination of Intrathecal Morphine and Clonidine did provide pain relief greater than placebo.
• There is level 4 evidence that topical capsaicin reduces post-SCI radicular pain.
• There is level 4 evidence that spinal cord stimulation improves post-SCI pain.
• There is level evidence to support the use of dorsal longitudinal T-myelotomy procedures, in particular Pourpre’s technique, to reduce spastic pain post SCI.
• There is limited (Level 4) evidence to support the use of the DREZ surgical procedure to reduce pain post SCI. It may be that some populations (segmental pain) are more likely to benefit from this procedure.

Key Points

• Pain post SCI has a significant effect on quality of life.
• Post-SCI pain is common and often severe beginning relatively early post injury.
• Post-SCI pain is most commonly divided into neuropathic or musculoskeletal pain.
• Massage and heat may be helpful for post-SCI pain.
• Acupuncture may reduce post-SCI pain.
• Regular exercise reduces post-SCI pain.
• A shoulder exercise protocol reduces post-SCI shoulder pain intensity.
• MAGIC wheels 2 gear wheelchair reduces shoulder pain.
• Hypnosis may reduce pain intensity post SCI.
• Transcranial magnetic stimulation reduces post-SCI pain.
• Cognitive behavioral therapy combined with pharmacological treatment results in short term improvement in chronic pain.
• Cognitive-behavioral pain management programs alone do not alter post-SCI pain.
• Visual imagery may reduce neuropathic pain post SCI
• Transcranial electrical stimulation is effective in reducing post-SCI neuropathic pain.
• Static field magnet may reduce nociceptive shoulder pain post SCI.
• Transcutaneous electrical nerve stimulation may reduce pain at site of injury in patients with thoracic but not cervical injury.
• Transcranial magnetic stimulation reduces post-SCI pain.
• Gabapentin and pregabalin improve neuropathic pain post SCI.
• Lamotrigine may improve neuropathic pain in patients with incomplete SCI.
• Levetiracetam is not effective in reducing neuropathic pain post SCI.
• Valproic acid does not reduce neuropathic pain post SCI.
• Amitriptyline is effective in reducing pain in depressed SCI individuals.
• Trazodone does not reduce post-SCI pain.
• Lidocaine through a subarachnoid lumbar catheter and intravenous Ketamine improve post SCI pain short term.
• Mexilitene does not improve SCI dysesthetic pain.
• Intrathecal Baclofen improves musculoskeletal pain post SCI and may help dysethetic pain related to spasticity.
• Motor point phenol block reduces spastic shoulder pain.
• Botulinum toxin injections for treatment of focal spasticity improves pain.
• Intravenous morphine reduces mechanical allodynia.
• Tramadol reduces neuropathic pain.
• Alfentanil reduces chronic pain post SCI.
• Alfentanil is more effective in reducing wind up like pain post SCI than ketamine.
• Cannabinoids are a potential new treatment for post-SCI pain in need of further study.
• Intrathecal Clonidine alone does not provide pain relief although it may be helpful in combination with Intrathecal Morphine.
• Topical capsaicin reduces post-SCI radicular pain.
• Spinal cord stimulation may improve post-SCI pain.
• Dorsal longitudinal T-myelotomy procedures reduce pain post SCI.
• DREZ surgical procedure reduces pain post SCI.

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Effects of Physical Activity

SCI impacts many body systems both immediately and in the long-term as noted in numerous reviews (Bauman et al. 1999; Shields 2002; Nash 2005). In particular, Nash (2005) and Jacobs and Nash (2004) point to physical deconditioning across the musculoskeletal system (i.e., bone, muscle and joint) and alterations in both cardiac and peripheral vascular structure and functioning in persons with SCI. These issues, when combined with continued inactivity, result in seemingly inevitable body system decline and are linked to the increased incidence of various secondary complications and other health conditions associated with SCI such as cardiovascular disease, respiratory complications, osteoporosis, pain, spasticity and diabetes. Evidence for routine physical activity has been noted as an important factor in maintaining health and wellness and preventing many of these conditions in the able-bodied population and in those with chronic disease such as arthritis (US Department of Health and Human Services 1996; Warburton et al. 2006; Kruk 2007). However, the evidence linking health and physical activity in persons with SCI or similar conditions is far from established, despite the importance placed on physical activity by clinicians, consumers and researchers alike in optimizing recovery and maintaining health (Rimmer 1999; Anderson 2004; Fernhall et al. 2008).

In reviewing the literature associated with various physical activity and exercise interventions in SCI, it was apparent that the vast majority of studies examine physiological parameters (e.g., VO₂, cardiovascular responses to exercise) that would be characterized as relating to body function and structure within the framework of the International Classification of Functioning, Disability and Health (ICF). We do not report here the numerous studies that address these physiologic outcome measures other than to note the various conclusions made surrounding specific risk factors associated with the development of cardiovascular disease or other health conditions. There is a relative dearth of studies examining the effect of physical activity interventions on functional outcomes, especially those that might be characterized as measures of activity or participation (as per the ICF). This suggests a target for future research in elucidating either the functional consequences or societal participation benefits associated with physical activity interventions for persons with SCI.

It should be noted that while one of the aims of this chapter is to bring the information about physical activity and SCI into one place, most of these topic areas comprise individual chapters with SCIRE. Therefore, when there may be substantial duplication with an existing SCIRE chapter we have selected to simply reference the existing chapters that contain information about physical activity interventions and to also bring forward the conclusions (evidence statements and bottom-line conclusions) from these chapters so the reader will gain a sense of the degree of evidence across these various conditions. The reader is encouraged to examine the referenced chapter for surrounding discussion and more information concerning the various studies and details about the specific interventions comprising the evidence. Of note, many of the therapies associated with upper limb or lower limb management involve therapeutic exercise programming (often associated with physical or occupational therapy) and for these we simply refer the reader to SCIRE Chapter’s: Upper Limb Rehabilitation Following Spinal Cord Injury (Connolly et al. 2010) and Lower Limb Rehabilitation Following Spinal Cord Injury (Lam et al. 2010) respectively. This has meant that the conclusions related to specific rehabilitation interventions (e.g., Body weight supported treadmill training, FES upper and lower limb applications) may not be comprehensive within the present chapter, but should be augmented by those from the noted chapters.

The following section describes the evidence for physical activity as an intervention directed towards persons with SCI in enhancing strength, muscle function, rehabilitation recovery (i.e., functional outcomes) and subjective well-being (including depression and quality of life) as well as in preventing or minimizing common secondary conditions typically encountered following SCI. These include the role of physical activity in maintaining or enhancing cardiovascular health and bone health as well as preventing or mitigating disability associated with respiratory complications, pain, spasticity and periodic leg movements.

Increasing Physical Activity Participation in SCI

It is generally accepted that physical activity is associated with numerous physical and psychological benefits for both the able-bodied and for persons with SCI. The previous section outlined numerous investigations providing evidence that various forms of physical activity and exercise programming are effective for a variety of SCI-related issues. However, more research is needed to determine the effect of specific parameters such as mode, duration, frequency and intensity to more fully delineate the specific characteristics that would guide exercise prescription for individuals with SCI. There are even fewer studies that are directed towards investigating interventions that are designed to increase participation in physical activity and also that provide the background information needed to effectively design these interventions. Even though it seems obvious and is generally assumed that participation in physical activity is severely limited in persons with SCI, the research base on existing levels of physical activity participation and the specific barriers that persons with SCI must overcome to participate is lacking.

It should be noted that determinations of participation levels and investigations of barriers to participation are not amenable to experimental investigation and typically do not involve an intervention, and therefore comprise subject areas which are typically not addressed according to SCIRE methodology. However, descriptions of the observational studies examining participation levels and barriers to participation are included here as an understanding of these factors is critical for rehabilitation care providers and health promoters to successfully develop and apply physical activity-promoting interventions directed toward persons with SCI. Finally, the effectiveness of interventions that promote physical activity participation of persons with SCI is assessed from the existing literature.

Summary

• There is level 2 evidence from a single study with support from several level 4 studies that an appropriately-configured program of functional electrical stimulation of lower limb muscle in persons with SCI produces muscle adaptations such as increasing individual muscle fibre and overall muscle size and may result in the prevention and/or recovery of muscle atrophy.
• There is level 2 evidence from a single study with support from several level 4 studies that an appropriately-configured program of functional electrical stimulation of lower limb muscle in persons with SCI results in an increase in muscle fibre types with more aerobic (endurance) capabilities, (most notably a shift in type IIx to type IIa muscle fibres).
• There is level 1 evidence from a single RCT with support from a single level 4 study that functional electrical stimulation-assisted upper limb cycle ergometry is capable of producing significant increases in upper limb muscle strength in persons with tetraplegia.
• There is level 2 evidence from a single RCT that voluntary upper limb cycle ergometry is capable of producing significant increases in upper limb muscle strength in triceps, biceps and anterior deltoid in persons with SCI.
• There is level 1 evidence from a single RCT that voluntary upper limb resistance exercise is effective in increasing upper limb muscle strength in persons with paraplegia.
• There is conflicting level 1 evidence across two RCTs that electrical stimulation-assisted resistance training of paretic wrist extensors or flexors increases strength and fatigue resistance in persons with tetraplegia.
• There is level 4 evidence from three studies that suggest that body-weight supported treadmill training in persons with SCI produces muscle adaptations of increasing individual muscle fibre size and overall muscle size and may result in the prevention and/or recovery of muscle atrophy.
• There is level 4 evidence from several pre-post studies that circuit resistance training and other forms of resistance training combined with other approaches may increase upper limb muscle strength in triceps, biceps and anterior deltoid in persons with tetraplegia.
• There is level 2 evidence from a low quality RCT that either 16 weeks of physical exercise therapy alone or a combination of 2, 8 week blocks of this therapy, neuromuscular stimulation or EMG biofeedback may enhance self-care and mobility scores.
• There is level 2 evidence from a single prospective, controlled trial that a twice weekly swimming program conducted over 4 months immediately following rehabilitation discharge may enhance motor FIM scores. This finding of exercise-related enhancement of functional outcomes is generally supported by 3 additional level 4 studies that employ different modes of physical activity associated with either increases to overall FIM scores or improved performance of ADLs.
• Prospective, controlled trials are required to better determine the relationship of physical activity programming and functional benefits. There is no evidence for a relationship between specific program parameters (e.g., mode, intensity, frequency, duration) that might be necessary to achieve particular benefits.
• Based on level 1 and 2 evidence from 4 studies (note that these studies draw on a common data set), exercise is an effective intervention for improving two aspects of SWB--quality of life and depressive symptomatology. For the most part, the level 4 and 5 evidence also supports this conclusion.
• Emerging data from these studies suggest that changes in stress and pain may be the mechanisms underlying the effects of exercise on quality of life and depression. Further research is needed to examine other aspects of SWB in relation to physical activity.
• There is level 4 evidence (Ditor et al. 2005a) that body-weight support treadmill training (BWSTT) improves cardiac autonomic balance in persons with incomplete tetraplegia.
• There is level 4 evidence (de Carvalho and Cliquet 2005) that BWSTT can lead to improvements in cardiac autonomic balance in a subset of individuals with motor-complete SCI who respond to ambulation with moderate-to-large increases in heart rate.
• Level 4 evidence (Ditor et al. 2005b) indicates that BWSTT can improve arterial compliance in individuals with motor-complete SCI.
• There is level 2 evidence (de Carvalho et al. 2006) that neuromuscular electrical stimulation gait training can increase metabolic and cardiorespiratory responses in persons with complete tetraplegia.
• There is level 1 evidence (Davis et al. 1987) that moderate intensity aerobic arm training (performed 20–60 min/day, three days/week for at least 6-8 weeks) is effective in improving the aerobic capacity and exercise tolerance of persons with SCI.
• There is level 1 evidence (De Groot et al. 2003) that vigorous intensity (70%–80% heart rate reserve) exercise leads to greater improvements in aerobic capacity than moderate intensity (50-60% heart rate reserve) exercise.
• The relative importance of changes in cardiac function and the ability to extract oxygen at the periphery in persons with SCI after aerobic training remains to be determined.
• There is level 4 evidence from pre-post studies that FES training performed for a minimum of three days per week for two months can be effective for improving musculoskeletal fitness, the oxidative potential of muscle, exercise tolerance, and cardiovascular fitness.
• There is level 4 evidence that FES training is effective in improving exercise cardiac function in persons with SCI.
• Based on the changes observed in VO2max and findings from able-bodied individuals a consensus (level 5; Expert Opinion) was derived stating that aerobic training is effective in improving the ability to extract oxygen at the periphery in persons with SCI.
• There is level 1 (De Groot et al. 2003) and level 4 (Chilibeck et al. 1999; Mohr et al. 2001; Jeon et al. 2002) evidence that both aerobic and FES training (approximately 20–30 min/day, three days/week for eight weeks or more) are effective in improving glucose homeostasis in persons with SCI.
• There is level 4 evidence that the changes in glucose homeostasis after aerobic or FES training are clinically significant for the prevention and/or treatment of type 2 diabetes.
• There is level 1 evidence (De Groot et al. 2003) to suggest that aerobic exercise training programs (performed at a moderate to vigorous intensity 20-30 min/day, 3 days per week for 8 weeks) are effective in improving the lipid lipoprotein profiles of persons with SCI.
• Preliminary evidence (level 4; Solomonow et al. 1997) also indicates that FES training (3 hours/week, for 14 weeks) may improve lipid lipoprotein profiles in SCI.
• There is level 2 evidence (based on 1 prospective controlled trial) (de Carvalho et al. 2006) and level 4 evidence (based on 4 pre-post studies) (Silva et al. 1998; Sutbeyaz et al., 2005; Le Foll-de-Moro et al. 2005; Fukuoka et al. 2006;) to support exercise training as an intervention that might improve resting and exercising respiratory function in people with SCI.
• There is level 4 evidence based on several studies to support inspiratory muscle training as an intervention that might decrease dyspnea and improve inspiratory muscle function in some people with SCI.
• There is level 1 evidence (from one RCT) (Warden et al. 2001) that short-term (6 weeks) ultrasound is not effective for treating bone loss after SCI.
• There is level 2 evidence (from 1 non-randomized prospective controlled trial) (Shields et al. 2006a) that ES reduced the decline in BMD in the leg.
• There is level 2 evidence (from 1 non-randomized prospective controlled trial) (Eser et al. 2003) that FES-cycling did not improve or maintain bone at the tibial midshaft in the acute phase.
• There is level 4 evidence (from 1 pre-post study) (Giangregorio et al. 2005) that walking and level 1 evidence (from 1 RCT) (Ben et al. 2005) that standing in the acute phase did not differ from immobilization for bone loss at the tibia.
• There is level 2 evidence (from 1 prospective controlled trial) (Bélanger et al. 2000) that electrical stimulation either increased or maintained BMD over the stimulated areas.
• There is level 4 evidence (from 1 pre-post study) (Chen et al. 2005) that 6 months of FES cycle ergometry increased regional lower extremity BMD over areas stimulated.
• There is inconclusive evidence for Reciprocating Gait Orthosis, long leg braces, passive standing or self-reported physical activity as a treatment for low bone mass
• There is level 1 evidence from a single RCT (Martin Ginis et al. 2003) that a regular exercise program significantly reduces post-SCI pain.
• There is level 2 evidence (from one RCT and one PCT) that a shoulder exercise protocol reduces the intensity of shoulder pain post-SCI.

  There is level 4 evidence that the MAGIC wheels 2-gear wheelchair results in less shoulder pain.

  There is level 1 evidence from a single study that passive ankle movements may not reduce lower limb muscle spasticity in persons with initial mild spasticity.

• There is level 2 evidence from a single study supported by level 4 evidence from another study that hippotherapy may reduce lower limb muscle spasticity immediately following an individual session.
• There is limited level 1 evidence from a single study that a combination of a 6 week course of neural facilitation techniques (Bobath, Rood and Brunnstrom approaches) and Baclofen may reduce lower limb muscle spasticity with a concomitant increase in ADL independence. More research is needed to determine the relative contributions of these therapies.
• There is level 4 evidence from a single study that rhythmic, passive movements may result in a short-term reduction in spasticity.

  There is level 4 evidence from a single study that externally applied forces or passive muscle stretch as are applied in assisted standing programs may result in short-term reduction in spasticity. This is supported by individual case studies and anecdotal reports from survey-based research.

• There is level 2 evidence from a single study (Kesiktas et al. 2004) that hydrotherapy is effective in producing a short-term reduction in spasticity.
• There is level 2 evidence from a single study that single bouts of FES-assisted cycling ergometry and similar passive cycling movements are effective in reducing spasticity over the short-term with FES more effective than passive movement.
• There is level 4 evidence from three studies (Granat et al. 1993; Thoumie et al. 1995; Mirbagheri et al. 2002) that a program of FES-assisted walking acts to reduce ankle spasticity in the short-term (i.e., <24 hours).
• There is no evidence describing the length and time course of the treatment effect related to spasticity for hydrotherapy or FES-assisted walking.
• There is level 2 evidence from a single study and supported by two additional pre-post trials that a 45 day period of 3/week 30 minute aerobic exercise sessions (arm cycle ergometry) is equally effective as L-dopa in reducing night-time periodic limb movements in persons with complete paraplegia.
• There is tremendous variability in the number of minutes of daily LTPA reported by persons with SCI. There is level 5 evidence from two large-sample studies from separate jurisdictions (i.e., Canada and UK) that approximately 50% of persons with SCI devote some time per week to sports, exercise, and other forms of LTPA.
• There is level 5 evidence from a single study that a person with SCI participates in some form of LPTA for an average of about an hour per day (median ~ 30 minutes) when considering only the approximately 50% of people with SCI who are not inactive.
• There is level 5 evidence from a single study that when physical activity is defined in terms of sports participation, the majority of people with SCI are considered inactive.
• There is level 5 evidence from a single study that indicates that most daily physical activity is accumulated in the form of activities of daily living when physical activity is defined in terms of participation in any activity that requires physical exertion.
• There is tremendous variability in the number of minutes of daily LTPA reported by persons with SCI. There is level 5 evidence from two studies that, although many report no activity whatsoever, there is a minority that devotes several hours per week to sports, exercise, and other forms of LTPA.
• There is level 5 evidence from four studies to suggest that individuals with SCI encounter a variety of factors that impede physical activity participation. Among these factors, the most frequently cited barriers include: (a) intrapersonal barriers such as perceived limitd return on investment, health concerns and a lack of motivation, energy and time, (b) systemic barriers such as a lack of accessible facilities, or unavailability of personal assistants transportation difficulties, and program costs, and (c) expertise barriers such as a lack of knowledge about physical activity prescription and client referral processes.  
• Interventions are needed to help alleviate these obstacles.  Further research must determine the most influential and modifiable barriers that would be optimal targets for intervention.
• There is level 1 evidence from a single RCT and supported by two low quality RCTs and  by an additional level 4 study that the physical activity behaviour of individuals with SCI is amenable to change, and that theory-based interventions may be a means of generating this change.
• There is level 1 evidence from a single study that indicates that coping planning as part of action planning is an effective intervention technique for promoting physical activity participation in the SCI population. 
• There is level 2 evidence from a single study that indicates that facilitating the formation of implementation intentions may be an effective intervention technique for promoting physical activity participation in the SCI population. 
• More research is needed to identify additional, specific behavioural interventions that are effective in the SCI population.  Furthermore, researchers should begin to consider the impact of other types of interventions including informational and environmental interventions. 
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Key Points

Physical Activity: Effects on Muscle Morphology,  Strength and Endurance in Persons with SCI

• Various forms of exercise, most notably functional electrical stimulation of upper and lower limbs, body-weight support treadmill training and circuit resistance training, may be effective in increasing muscle strength and reducing muscle atrophy. The former two are more appropriate for those with greater muscle impairment.

Physical Activity and Functional Improvement Including Activities of Daily Living

• Physical activity programming may be useful in improving functional outcomes such as performance of ADLs but there is very little information describing specific exercise parameters that would be most effective in this respect.

Physical Activity and Subjective Well-Being

• Exercise is an effective strategy for improving at least two aspects of subjective well-being - depression and quality of life.

Physical Activity and Secondary Conditions

• There is limited evidence that BWSTT can improve indicators of cardiovascular health in individuals with complete and incomplete SCI.
• Tetraplegics and paraplegics can improve their cardiovascular fitness and physical work capacity through aerobic exercise training of moderate intensity, performed 20-60 min day, at least three times per week for a minimum of six to eight weeks. Resistance training at a moderate intensity at least two days per week also appears to be appropriate for the rehabilitation of persons with SCI. It remains to be determined the optimal exercise intervention for improving cardiovascular fitness.
• Interventions that involve FES training a minimum of 3 days per week for 2 months can improve muscular endurance, oxidative metabolism, exercise tolerance, and cardiovascular fitness.
• Aerobic and FES exercise training may lead to clinically significant improvements in glucose homeostasis in persons with SCI. Preliminary evidence indicates that a minimum of 30 min of moderate intensity training on 3 days per week is required to achieve and/or maintain the benefits from exercise training.
• Aerobic and FES exercise training may lead to improvements in lipid lipoprotein profile that are clinically relevant for the at risk SCI population. The optimal training program for changes in lipid lipoprotein profile remains to be determined. However, a minimal aerobic exercise intensity of 70% of heart rate reserve on most days of the week appears to be a good general recommendation for improving lipid lipoprotein profile in persons with SCI.

Physical Activity and Respiratory Complications

• For exercise training to improve respiratory function the training intensity must be relatively high (70-80% of maximum heart rate) performed three times per week for six weeks. Ideal training regimes have not been identified.
• There is limited evidence that inspiratory muscle training improves respiratory muscle strength or endurance in people with SCI.

Physical Activity and Bone Health

• Short term (6 weeks) therapeutic ultrasound is not effective for preventing bone loss after SCI.
• FES-cycling does not improve or maintain bone at the tibial midshaft in the acute phase but may increase/maintain lower extremity BMD the longer time since injury.
• Electrical stimulation can maintain or increase BMD over the stimulated areas.
• Six months of FES cycle ergometry may increase lower extremity BMD over areas stimulated.
• There is inconclusive evidence for Reciprocating Gait Orthosis, long leg braces, passive standing or self-reported physical activity as a treatment for low bone mass.

Physical Activity and Pain

• Regular exercise reduces post-SCI pain.
• Shoulder exercise protocol reduces post-SCI shoulder pain intensity.

Physical Activity and Spasticity

• Hippotherapy may result in short-term reductions in spasticity.
• A combination of neural facilitation techniques and Baclofen may reduce spasticity.
• Rhythmic passive movements may produce short-term reductions in spasticity.
• Prolonged standing or other methods of producing muscle stretch may result in reduced spasticity.
• Active exercise interventions such as hydrotherapy and (FES) functional electrical stimulation-assisted walking may produce short-term reductions in spasticity.

Physical Activity and Periodic Leg Movements

• Aerobic exercise is effective in reducing night-time periodic limb movements in persons with complete paraplegia.

Physical Activity Participation Levels in SCI

• There is tremendous variability in the amount of physical activity performed by people living with SCI. A large segment of the population does not engage in any leisure-time physical activity whatsoever.

Barriers to Physical Activity Participation in the SCI Population

• Individuals with SCI encounter numerous impediments to physical activity participation including intrapersonal, systemic, and expertise barriers. Interventions are needed to help people with SCI manage these barriers.

Effectiveness of Interventions to Increase Physical Activity Participation in SCI

• Behavioural interventions promoting physical activity in the SCI population can lead to increased levels of physical activity participation.

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