A variety of benefits related to gross muscle morphology have been demonstrated in numerous investigations employing multi-week progressive exercise programs of FES-assisted cycling in which lower limb muscles (i.e., typically quadriceps, hamstrings and gluteal muscles) are stimulated to produce cycling movements against resistance (Sloan et al. 1994; Hjeltnes et al. 1997; Mohr et al. 1997; Chilibeck et al. 1999; Scremin et al. 1999; Crameri et al. 2004; Heesterbeek et al. 2005; Griffin et al. 2009). Each of these FES-assisted cycling programs consisted of a minimum of three 30 minute sessions per week with program duration ranging from 8 weeks to 1 year with progressive resistance customized to the individual participant. Of note, Heesterbeek et al. (2005) employed a hybrid FES-assisted cycling protocol in which upper limb cycling was also incorporated into the physical activity intervention and Scremin et al. (1999) had a 4 phase intervention in which the final phase consisted of adding upper limb ergometry to FES-assisted lower limb cycling. These were the only investigations that incorporated upper body exercise although outcome measurement was limited to the muscles of the lower limb. All studies, other than that conducted by Crameri et al. (2004), were uncontrolled investigations incorporating either a prospective pre-post or retrospective case series study design. In addition, all of the studies were relatively small with sample sizes of 18 persons or less. Benefits to gross muscle morphology consisted of significant increases in total body lean muscle mass (Griffin et al. 2009), thigh muscle mass (Mohr et al. 1997), cross-sectional area of overall thigh muscle (Sloan et al. 1994; Hjeltnes et al. 1997, Scremin et al. 1999) and overall thigh volume (Heesterbeek et al. 2005) as well as significant reductions in muscle atrophy (Mohr et al. 1997). Significant increases were also seen in overall cross-sectional area or mean muscle fibre cross-sectional area within individual muscles (Chilibeck et al. 1999; Scremin et al. 1999; Crameri et al. 2004).
Other forms of neuromuscular electrical stimulation resistance exercise training have also been shown to produce beneficial muscle adaptations. In a relatively large study, persons with complete denervation due to a conus or caudal lesion (n=20 completing) underwent a two year home-based progressive electrical stimulation program which culminated in 30 minute sessions, 5 days/week involving a combination of twitch and tetanic stimulation patterns focusing on quadriceps but also on gluteal, hamstring and other lower limb muscles (Kern et al. 2010). Quadriceps and hamstring muscle cross-sectional areas were significantly larger with training with these results being more pronounced for the quadriceps. Similarly, significant increases in quadriceps muscle cross-sectional areas were produced in 5 males with ASIA A SCI with a home-based, two day/week program over twelve weeks in which four sets of ten unilateral, dynamic knee extensions were elicited by appropriate stimulation (Mahoney et al. 2005). A later report extended these observations with similar results following 18 weeks (Sabatier et al. 2006).
Other modes of endurance-based resistance exercise also led to similar muscle adaptations. For example, sustained participation in body weight support treadmill training 2 or 3 times/week resulted in significant increases in overall muscle cross-sectional areas in the thigh and lower leg muscles (Giangregorio et al. 2005; Giangregorio et al. 2006; Carvalho et al. 2008) as well as increases in mean individual muscle fibre sizes (Stewart et al. 2004) and partial reversal of muscle atrophy (Giangregorio et al. 2006). Of note, Carvalho et al. (2008; 2009) conducted a controlled trial (n=15) which showed significantly greater increases in MRI-derived quadriceps cross-sectional area with neuromuscular stimulation combined with body-weight supported treadmill gait training as compared to that seen with conventional physiotherapy. This was conducted over a 6 month period after which the gait training was offered to the control group. Gait training sessions consisted of 20 minute sessions at a frequency of twice per week.
To this point, of all studies noted in this section, each of the interventions were applied to individuals with chronic SCI (i.e., > 6 months post-injury) with the exception of Giangregorio et al. (2005) who performed body weight support treadmill training on those more newly injured (i.e., 2-6 months post-injury). In addition, across studies participants had mostly complete or in rare instances near-complete SCI (i.e., AIS A, B or C).
A novel methodology was employed by Crameri et al. (2004) to investigate the effects of load on these types of muscle adaptations. These investigators used a 45 minute/day, three day/week FES-assisted cycling exercise protocol over ten weeks in which only one leg of each study participant was permitted to cycle against minimal load. The contralateral leg was also provided similar stimulation parameters as the “cycling” leg but these were applied against a fixed load so as to provoke rhythmic isometric contractions of the quadriceps and hamstrings against resistance. Exercise progressions were implemented with increases to the work-rest cycle and not to resistance as is often done in trials of FES-assisted cycling ergometry. This controlled investigation demonstrated that the amount of resistance is important in producing a training effect as greater increases in isometric force generation and muscle fibre cross-sectional area were demonstrated for the static, high-resistance training condition.
Additionally, muscle biopsies have been performed before and after training, permitting investigation of the effects of physical activity on fibre type. Following SCI, (especially in those with complete or near complete lesions), there is an established transformation of muscle fibres away from type IIa toward type IIx fibres reflecting a functional shift towards less aerobic, more easily fatigable muscle (Grimby et al. 1976; Round et al. 1993). This shift was reversed over ten weeks (Crameri et al. 2002) and also at 6 months of a 1 year program (Andersen et al. 1996) of three day/week FES-assisted cycling exercise and with six months of three day/week body weight-supported treadmill training (Stewart et al. 2004) as each of these studies reported an increase in type IIa fibres and a corresponding reduction in type IIx (or IIb) fibres following training. More interestingly, similar results were seen in Crameri et al.’s 2004 investigation of the effect of static load vs. dynamic minimal load conditions with shifts of type IIx to type IIa muscle fibres apparent for both conditions along with the additional finding of a significantly greater increase in type I fibres only for the static, high-resistance trained leg. This represents an even more dramatic adaptation toward the aerobic, oxidative capacity of muscle with this type of training. Kern et al. (2010) demonstrated similar findings with their home-based neuromuscular stimulation promotion with increases in muscle fibre size that reverses the atrophic processes noted in denervated muscle.
There is also some evidence that passive cycling using upper-body assistance to drive paralyzed leg muscles involving 2 day/week sessions over 12 weeks may be sufficient to prevent these inactivity-related shifts towards more “fast” type muscle fibers. Willoughby et al. (2000) demonstrated significant increases in mRNA expression for type IIa fibres (and also for type IIx fibres) in the presence of decreasing proteolytic activity typically associated with muscle degradation. This passive exercise was insufficient to produce a significant increase in muscle size as indicated by no change in thigh girth and it is important to note that the leg movement required upper body voluntary exercise.
Strength and Muscular Endurance
In contrast to those investigations assessing outcomes related to muscle morphology, those assessing strength or muscular endurance were much more diverse with respect to the exercise modes employed. Notably, seven investigators incorporated RCT study designs (Needham-Shropshire et al. 1997; Hicks et al. 2003; Hartkopp et al. 2003; Glinsky et al. 2008; Jacobs 2009; Alexeeva et al. 2011; Mulroy et al. 2011) despite the acknowledged difficulty in fully implementing such features as participant blinding with the physical activity interventions typically associated with this design (Ginis and Hicks 2005).
Of these RCTs, six of seven trials resulted in statistically significant increases in strength, although there were different training paradigms used to achieve these results across the trials. Needham-Shropshire et al. (1997) used a paired-randomization approach to assign subjects with chronic cervical SCI (n=27) to one of three groups: 1) those receiving 8 weeks of neuromuscular stimulation-assisted arm ergometry exercise (NMS); 2) those receiving 4 weeks of NMS assisted exercise followed by 4 weeks of voluntary arm crank exercise; and 3) those participating in a control condition – voluntary exercise for 8 weeks without the application of NMS. Muscle strength was assessed by manual muscle testing in the triceps and the largest treatment effect (i.e., more muscles showing an increase of at least one muscle grade) was seen in Group 1 subjects (p<0.0005) although there were also a significant number of muscles that demonstrated an increase in muscle grade in Group 2 (p<0.03) relative to the control condition. In a pre-post study, Cameron et al. (1998) used a prototype of the NMS-assisted arm crank ergometer used by Needham-Shropshire et al. (1997) to elicit significant improvements to triceps muscle strength following a three days/week upper body training program conducted over eight weeks.
These results are consistent with those reported by Hicks et al. (2003) who conducted an RCT (n=34, with 11 of 21 completing in the exercise group) of a twice weekly progressive voluntary arm ergometry cycling and resistance training exercise program with sessions of 90-120 minutes over nine months. These investigators noted significant increases (p<0.05) in muscle strength for 3 different upper body maneuvers involving triceps, biceps and anterior deltoid bilaterally at nine months as compared to baseline, although these increases in muscle strength showed progressive improvement over the nine months.
Similarly, Mulroy et al. (2011) implemented an exercise/movement optimization initiative in which participants received a shoulder home exercise program consisting of a stretching phase, warm-up phase, and a resistive shoulder exercise phase 3 times/week for 12 weeks. There were statistically significant strength gains in all motions tested (elevation in the plane of the scapula, adduction, internal rotation, and external rotation) compared with the control group (p<0.01). Also, all muscle groups, for those in the intervention group, demonstrated increases in maximal torque production as measured by the Micro-FET handheld dynamometer following the intervention (p<0.05).
Alexeeva et al. (2011) compared two body-weight-supported (BWS) training devices; fixed track and treadmill and comprehensive physical therapy for improving walking speed. One of the secondary outcomes measured was muscle strength as determined by the ASIA International Standard Manual Muscle Test. The training program for all participants included 1 hour/day, 3 days/week for 13 weeks. There was a statistically significant increase in muscle strength across all groups (p<0.01), but no differences between groups. There was a mean increase of 6-9% in muscle strength across all three groups.
Jacobs (2009) compared a resistance training paradigm involving 3 sets of 10 repetitions across six stations at 60-70% of a maximal single effort vs endurance training for 30 minutes involving arm cranking at 70%-85% of peak HR in persons with neurologically complete paraplegia (n=18). There were 3 sessions/week over a 12-wk training period with standardized exercise progressions for both the resistance training and endurance training groups and participants were matched between groups by body mass and gender. Muscular strength was significantly increased (p<0.01) with resistance training for each of the 6 isotonic strength testing maneuveurs corresponding to those involved for each of the resistance training stations. There were no strength changes apparent for those in the arm ergometry group (i.e., endurance training). However, muscular endurance, as indicated by performance on the Wingate anaerobic power test, was significantly improved with both forms of training, although these improvements were most pronounced with resistance training.
Harness et al. (2008) implemented an intense exercise (IE) initiative that included 6 categories (active assistance, resistance training, load bearing, cycle ergometry, gait training/supported ambulation, and vibration training). The intervention group participated in the exercise program for an average of 56 ± 6 days and 7.3 ± 0.7 hours per week over a six month time period. The results demonstrated that 15/21 subjects had increased muscle strength in at least one muscle with a mean of 4.1 muscles (3.2 lower extremities) compared with 0/8 subjects in the control group (p<0.0001). Muscle strength was measured as a secondary outcome to motor function.
The RCT conducted by Glinsky et al. (2008) failed to show statistically significant increases in strength or muscular endurance (i.e., fatigue resistance) in wrist extensor or flexor muscles that were at least partially paralyzed in persons with tetraplegia (n=32). There was an overall mean increase of 8% and 11% in strength and muscular endurance respectively with training vs no training groups but this was deemed clinically insignificant. This study involved a resistance training program involving 3 sets of 10 repetitions using a customized device that permitted those with even minimal force generation to participate in a progressive exercise program. These authors noted that unlike other trials (e.g., Hicks et al. 2003), all participants had at least some paresis although it should be noted that there was a slight imbalance between experimental (i.e., training) vs control (i.e., no training) groups with respect to a slightly greater impairment in participants in the training group (i.e., 9 vs 6 persons with ASIA A and 4 vs 0 persons with an initial muscle grade of 2).
A similar training system to that employed by Glinsky et al. (2008) was used by Hartkopp et al. (2003) to examine the effect of electrical stimulation on strength and fatigue resistance in wrist extensor musculature in persons with tetrapegia (n=12 completing trial). This RCT used the non-trained arm as a control and demonstrated significant strength gains with a high resistance protocol, but not a low resistance protocol – each involving 5, 30 min sessions/week over 12 weeks. The high resistance protocol consisted of stimulation against a maximal load, whereas the low resistance protocol used a resistance of 50% of maximal load. Both training protocols were effective in improving resistance to fatigue.
There were also several investigations involving mostly pre-post study designs resulting in improved muscle function with different forms of electrically-stimulated exercise. For example, FES-assisted cycling programs involving the lower limbs and of varying durations and frequencies have demonstrated beneficial effects on muscle function. Griffin et al. (2009) demonstrated improved ASIA motor (and sensory scores) for the lower extremity following FES cycling for 2-3 times per week over 10 weeks in a group of persons with mostly incomplete SCI from C4-T7 (i.e., 13 of 18 with incomplete SCI). In persons with complete chronic SCI, FES-assisted cycling is effective for improving resistance to muscular fatigue as indicated by increases to sustained torque generation with repetitive stimulation in programs employing as little as 3, 30 min sessions/week over 6 weeks (Gerrits et al. 2000). A more extensive long-term program involving 5, 1 hour sessions/week over 1 year also was effective in improving fatigue resistance as well as producing a fivefold increase in maximal electrically stimulated torque (i.e., strength of contraction), although this remained lower than in able-bodied individuals (Duffell et al. 2008). Interestingly, in a later study, Gerrits et al. (2002) demonstrated that fatigue resistance was improved more effectively by low frequency (i.e., 10 Hz) vs high frequency (i.e., 50 Hz) stimulation, although each was equally effective in improving force generation (i.e., tetanic tension development).
In addition, several investigators have employed other approaches to lower limb neuromuscular stimulation such as the long-term home-based stimulation program by Kern et al. (2008) which resulted in a near ten-fold increase in stimulation-elicited muscle force in addition to the benefits to muscle morphology noted above. Sabatier et al. (2006) conducted a smaller pre-post study (n=5 persons with complete SCI) of an eighteen week home-based neuromuscular electrical stimulation resistance training program involving bi-weekly quadriceps training comprised of four sets of 10 dynamic knee extensions against resistance while in a seated position. This resulted in significant increases in strength (i.e., weight lifted), as well as a 60% reduction in muscle fatigue (p = 0.001).
Given the results of these studies, it is clear that there are a variety of approaches involving neuromuscular stimulation to the lower limb that accrue benefits to muscle function. However, information regarding the minimum requirements with respect to frequency, intensity, duration of a training program and how each of these might interact with different patient subgroups remains to be definitively established. Interestingly, Petrofsky et al. (2000) conducted a study to assess the effect of altering various parameters associated with a ten week training program of quadriceps muscle stimulation. These investigators assigned subjects (n=90) to 10 different treatment groups and examined the effect of altering some of the parameters associated with individual treatment sessions. Greater strength changes were seen for 30 minute sessions as compared to 5 or 15 minute sessions and for 3 day/week training as compared to 1 or 5 day/week training programs. In addition, strength gains and total work capacity was optimized by incorporating a pattern of 3 s extension – 3 s flexion – 6 s rest as compared to longer or shorter durations of work-rest cycles. Several investigations of voluntary exercise employing pre-post study designs have demonstrated strength benefits (in addition to other benefits). These studies have been conducted mostly in persons with paraplegia and have included circuit resistance training for 3 days/week (Durán et al. 2001; Jacobs et al. 2001; Nash et al. 2007), a combination of resistance training and plyometric training (Gregory et al. 2007) and 3, 60 minute sessions/week of kayak ergometer training over 10 weeks (Bjerkefors et al. 2006).
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 muscles 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 muscles 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 two RCTs 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 1 evidence from a single RCT that body-weight supported fixed track or treadmill training can increase muscle strength in persons with SCI. There is also level 4 evidence from three studies that suggests 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 2 evidence from a prospective controlled trial and 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 and/or paraplegia.
Circuit resistance training, body-weight support treadmill training and functional electrical stimulation (upper and lower limbs) may be effective in increasing muscle strength and reducing atrophy, with the latter two more appropriate for those with great muscle impairment.