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Interventions Based on Active Movement (Including FES-assisted Movement)

Physical therapy approaches are often advocated as the first treatment choices for reducing spasticity and are deemed as the foundation upon which other therapies are built (Merritt 1981; Kirshblum 1999; Rosche 2002). Despite these contentions, there is a relative paucity of literature addressing the efficacy of either the passive techniques noted in the previous section or approaches involving active movement in individuals with SCI. In practice, active movement approaches may be conducted using a variety of exercise forms that may also provide benefits beyond spasticity reduction (e.g., strength, endurance, gait re-training). The studies meeting the criteria for the present review involve exercises performed in a therapeutic pool (i.e., hydrotherapy) (e.g., Kesiktas et al. 2004), those associated with FES-assisted cycling (e.g., Krause et al. 2008), locomotor training programs, whether assisted by FES (e.g., Granat et al. 1993; Kapadia et al. 2014; Mirbagheri et al. 2002), or a FES-powered orthosis (e.g., Mirbagheri et al. 2015; Thoumie et al. 1995).

Table 2 Studies of Active Movement-based Approaches for Reducing Spasticity

Author Year

Country
Research Design Score
Total Sample Size

MethodsOutcome
Robot-Assisted Exercise
Fang et al. 2015

Taiwan

RCT Crossover

PEDro=5

N=10

Population: SCI: Mean age: 30.1 yr; Gender: males=8, females=2; Level of injury: C2-C6=2, T3-T7=6, L2-L11=2; Mean time since injury: 5.7 yr.

Intervention: Individuals wore robot-assisted passive exercise devices on their ankle joints. Individuals were randomly assigned in a crossover design to one of three interventions: high speed cyclic passive exercise (50 cycles/min), low speed cyclic passive exercise (20 cycles/min), or electrical stimulation-induced contractions (ES) for 8 min, 1 x/wk for 3 wk. There were allocated to the other interventions 2 wk later. Outcomes were assessed before each intervention and at 10, 20 min after each intervention.

Outcome Measures: H reflex, M waves, Total resistance during cyclic stretching, Isometric torque.

1.     The amplitude of the H reflex was significantly reduced at 10- and 20-min post high-speed cyclic passive exercises (p<0.05), and 20 min post low-speed cyclic passive exercises (p<0.05).

2.      There were no significant changes in M waves after any of the interventions (p>0.05).

3.      For individuals whom received ES, and then the high speed cyclic passive exercise, the total resistance during cyclic stretching increased significantly (p<0.05).

4.      Isometric torque decreased significantly after 8 min of ES and the reduction persisted up to 20 min (p<0.05).

Mirbagheri et al. 2015

USA

RCT

PEDro=6

N=46

Population: Intervention group: Mean age: 46.4 yr; Gender: males=16, females=7; Mean time since injury: 10.1 yr. Control group: Mean age: 47.9 yr; Gender: males=15, females=8; Mean time since injury: 8.9 yr. All subjects: Level of injury: C2-T9; Level of severity: AIS C or D.

Intervention: Subjects were randomly allocated to either the intervention group or the control group. All participants in the intervention group received 1-hr sessions of robotic-assisted step training (RAST), 3x/wk for 4 wk. Each session included up to 45 min of training. To measure the neuromuscular properties of the ankle joint of all 46 subjects, ankle perturbations were applied to one of the subject’s ankles to elicit the stretch reflex. Ankle position and torque were recorded. Evaluations were performed at baseline (prior to training) and after 1, 2, and 4 wk of RAST. The measured joint torque due to perturbations was then separated into intrinsic (musculotendinous) and reflex contributions using a parallel-cascade system identification technique. This analysis was performed for each ankle position yielding stiffness versus joint angle curves for each subject (intrinsic=K, reflex=G). Growth mixture modelling (GMM) was used to stratify groups based on similar intrinsic/reflex recovery patterns of neuromuscular parameters for both RAST and control groups. Random coefficient regression (RCR) was then used within each class to model the recovery pattern as an exponential function of time, and to determine whether the change in the parameter value was significant. The linearly transformed RCR function was: lnC(t)=lnC0 + βt.

Outcome Measures: Stiffness parameters [A=offset or intercept, AB=slope, Gmax/Kmax=maximum value of G/K over the passive range of motion (PROM)], correlation between mean baseline values and rates of change (Co* β), and the exponential trend parameter, β.

1.   Using GGM, three classes were identified for each of the reflex parameters and two classes were identified for the intrinsic parameters. Classes were numbered by increasing baseline value.

2.   The reflex stiffness parameters showed significant decreases, evident because β was significantly lower than zero for all classes (p<0.05).

3.   Rates of change for reflex stiffness became more negative with increasing class number. There was a strong correlation between the mean baseline values and rates of change (r2=0.94, p=0.0001).

4.   The intrinsic stiffness parameters showed significant decreases, evident because β was significantly lower than zero for all classes (p<0.05).

5.   Rates of change for reflex stiffness became more negative with increasing class number. There was a strong correlation between the mean baseline values and rates of change (r2=0.84, p=0.01).

6.   Three classes were identified by GMM and RCR for the control group. β was not significantly different from zero for any of these classes (p>0.05 for all).

Effect Sizes: Forest plot of standardized mean differences (SMD±95%C.I.) as calculated from pre- and post-intervention data.

Mirbagheri et al. 2013a

USA

Prospective Controlled Trial

N=46

Population: Intervention group (n=23): Mean age: 46.4 yr; Gender: males=16, females=7; Injury etiology: SCI=23. Control group (n=23): Mean age: 47.9 yr; Gender: males=15, females=8; Injury etiology: SCI=23.

Intervention: Each of the subjects in the intervention group participated in 1-hr LOKOMAT training sessions 3x/wk for 4 wk, with each session containing up to 45 min of training. Neuromuscular properties were evaluated (for both intervention and control groups) at four time points-prior to the start of training, and 1, 2, and 4 wk after the start of training. For the neuromuscular assessments, a custom joint-stretching device was used to measure position and torque of the ankle joint. A Parallel-Cascade System Identification Technique was used to separate total ankle torque into the sum of the intrinsic (muscular) pathway and the reflex pathway. From which, intrinsic (K) and reflex (G) stiffness were calculated and plotted against ankle angle. Subjects were stratified using growth mixture modelling (GMM) based on similar intrinsic and reflex recovery patterns/the slopes of the exponential fit (Mk and MG).

Outcome Measures: Mk and MG.

1.   Three classes were identified for the reflex slope, and two classes were identified for the intrinsic slope of the intervention group. Classes were numbered by increasing baseline value.

2.   Statistically significant values of reduction in reflex stiffness slope (p<0.05):

a.   Class one:

5.2 N-m.s/rad2

b.   Class two:

16.3 N-m.s/rad2

c.    Class three:

32.1 N-m.s/rad2

3.   Statistically significant values of reduction in intrinsic slope (p<0.05):

a.   Class one:

46.5 N-m.s/rad2

b.   Class two:

38.7 N-m.s/rad2

4.   Control subjects presented no significant change in either reflex slope or intrinsic slope over time (p=NS for all groups).

Exoskeleton Walking Device
Juszczak et al. 2018

USA

Pre-Post

N=45

 

Population: SCI (n=45): Mean age=35±12.65yr; Gender: males=37, females=8; Level of injury: T1-T8=27, T9-L2=18; Mean time since injury=3.9±5.13yr; AIS scale: A=30, B=5, C=10.

Intervention: Participants received 3-4 gait training sessions/wk over 8 wk while using the Indego Powered Exoskeleton. At the outset, sessions consisted of learning how to sit and stand, as well has how to ambulate indoors on smooth surfaces while using the exoskeleton. As participants became more proficient, training shifted towards managing doors, ramps, sidewalk curbs, and various indoor and outdoor surfaces. Outcome measures were assessed before and after each training session.

Outcome Measures: Modified Ashowrth Scale (MAS); self-reported spasticity.

1.     Self-reported spasticity indicated significant decreases in spasticity at the end of the study compared to the beginning (p<0.001).

2.     However, the majority of participants (n=28, 62.2%) did not experience in mAS score when comparing pre to post trial. 26.7% (n=12) showed decreases in spasticity according to the mAS; 11.1% (n=5) showed increases in spasticity.

 

Aach et al. 2014

Germany

Pre-Post

N=8

Population: Mean age: 48.0 yr; Gender: males=6, females=2; Level of severity: AIS A=4, AIS B=1, AIS C/D=3.

Intervention: All individuals underwent body weight supported treadmill training 5x/wk for 90 days using the hybrid assistive limb (HAL) exoskeleton (mean number of sessions=51.75).

Outcome Measures: Walking index for SCI II (WISCI II), Treadmill-associated walking distance, speed, and time, 10-m walk test (10MWT), Timed-up and go test (TUG test), 6-min walk test (6MWT).

1.       The mean improvement of the WISCI II was not statistically significant (p>0.05). At baseline the mean WISCI II was 10±4.34 which increased to 11.13±6.68 after training.

2.       Mean walking speed increased from 0.91±0.41 m/s at baseline, to 1.59±0.5 m/sec post- intervention.

3.       The mean walking time increased from 12.37±4.55 min at baseline, to 31.97±9.45 min post- intervention.

4.       The mean walking distance increased from 195.9±166.7 m at baseline, to 954.13±380.4 m post- intervention.

5.       The 10MWT speed significantly increased from 0.28±0.28 m/sec at baseline to 0.5±0.34m/s post- intervention (p<0.05).

6.       The TUG test significantly decreased from 55.34±32.20 sec at baseline to 38.18±25.98 sec post- intervention (p<0.05).

7.       The 6MWT distance significantly increased from 70.1±130m at baseline to 163.3±160.6m post- intervention (p<0.05).

Kressler et al. 2014

USA

Case Series

N=3

Population: Mean age: 30.3 yr; Gender: males=2, females=1; Injury etiology: complete SCI=3; Level of injury: T9/10=1, T7=1, T1/2=1; Level of severity: AIS A=3.

Intervention: Individuals performed over-ground bionic ambulation (OBA) training using a bionic device (Esko).

Outcome Measures: 10-m walk test (10MWT), 2-minute walk test (2MWT), Spinal Cord Assessment Tool for Spastic Reflexes, Spinal reflex excitability, Recordings of electromyographic activity, Electroencephalography (EEG), Graded exercise test, Heart rate monitor, International SCI Basic Pain Dataset, Multidimensional Pain Inventory (SCI version) Subscale for pain severity, Neuropathic Pain Symptom Inventory.

1.     All participants increased the number of steps taken and distance walked per session in the device.

2.     Functional walking capacity increased two-to three-fold for subjects one, two and four over the training period.

3.     No changes in clinical measures of spasticity beyond what is attributable to typical variability observed.

4.     With training, participants were able to achieve walking speeds and distances in the OBA device similar to those observed in persons with motor-incomplete SCI (10-m walk speed, 0.11-0.33 m/s; 2-min walk distance, 11-33 m).

5.     The energy expenditure required for OBA was similar to walking in persons without disability (i.e., 25%-41% of peak oxygen consumption).

6.     The unchanged energy cost resulted in improved walking economy for all participants.

7.     Subjects with lower soleus reflex excitability walked longer during training, but there was no change in the level or amount of muscle activity with training.

8.     No change in cortical activity patterns.

9.     All participants reported an average reduction in pain severity over the study period ranging between-1.3 and 1.7 on a 0-to-6 numeric rating scale.

Del-Ama et al. 2014Switzerland

Case Series

N=3

Population: Not Reported.

Intervention: To determine the effects of electrical-muscle stimulation (EMS)-induced hybrid gait training (interventions with a hybrid bilateral exoskeleton for 4 days).

Outcome measures: 6-minute walk test (6MWT), 10-minute walk test (10MWT), Manual muscle test (MMT) for the lower limbs, Ashworth Scale (AS).

1.     All subjects responded favorably to the hybrid walking intervention as indicated by statistically significant improvements in walking tests after 1-2 wk of the intervention.

2.     Participants demonstrated statistically significant improvements after the intervention on muscle controlling hip and knee joints as shown by improved MMT scores.

3.     There were improvements in knee flexor and extensor muscle groups (intervention wk I-II).

4.     Participants demonstrated an improvement in spasticity as marked by differences in Ashworth and Penn scales: average relative increments in AS was -0.2±0.4 and Penn Spasm Frequency Scale was -0.4±0.5 after the intervention.

5.     Statistics are not provided to support statistical significance statements. Data was presented graphically.

Functional Electrical Stimulation
 

Kapadia et al. 2014

Canada

RCT

PEDro=5

N=34

Population: Mean age: 55.3 yr; Gender: males=26, females=8; Injury etiology: motor vehicle accident=9, fall=15, gunshot wounds=1, sports=5, other=4; Level of injury: paraplegia=8, tetraplegia=26; Level of severity: AIS C-D=8, AIS C-D=26; Mean time since injury: 9.5 yr.

Intervention: Individuals were randomly assigned to the intervention or control groups. In the intervention group individuals received functional electrical stimulation (FES) on their quadriceps, hamstrings, dorsiflexors, and plantarflexors while performing ambulation exercises on a body weight supported treadmill. The control group received conventional resistance and aerobic training. Both groups received 45 min sessions, 3x/wk for 16 wk. Outcomes were assessed at baseline, 16 wk, 6 mo, and 12 mo.

Outcome Measures: 6-minute walk test (6MWT), 10-meter walk test (10MWT), Timed up and go test (TUG), Spinal cord independence measure (SCIM), Modified Ashworth Scale (MAS), Pendulum test.

1.      Both groups significantly improved over time on the 6MWT (p=0.002), and there were no significant differences between groups (p=0.096).

2.      The 10MWT had no significant time effects (p=0.084) or between groups differences (p=0.195).

3.      Both groups had significant improvements in the TUG over time (p=0.016), and there were no significant differences between groups (p=0.528).

4.      Over time the intervention group had significantly greater improvements on the SCIM compared to the control group (p<0.01).

5.      MAS scores significantly worsened for both groups in the right quadriceps over time (p=

0.015), and there were no significant differences between groups (p=0.942).

6.      The pendulum test had no significant time effects (p<0.05) or between groups differences (p<0.05).

Effect Sizes: Forest plot of standardized mean differences (SMD±95%C.I.) as calculated from pre- and post-intervention data.

Ralston et al. 2013

Australia

RCT Crossover

PEDro=7

N=14

Population: Median age: 25.0 yr; Gender: males=11, females=3; Injury etiology: suprathoracic SCI=14; Level of severity: AIS A=13, AIS B=1.

Intervention: Individuals were randomized to receive either the experimental or control intervention first. Each intervention persisted for 2 wk with a 1 wk washout period in between interventions. The experimental intervention consisted of cycling with functional electrical stimulation (FES) for 30-45 min/day, 4 days/wk. FES was directed to the quadriceps, hamstrings and gluteals of each leg. During the control intervention, individuals received no FES cycling. All individuals also received usual care consisting of standard inpatient physiotherapy and occupational therapy including treatment for poor strength, restricted joint mobility, limited fitness, reduced dexterity, pain and functional skills training.

Outcome Measures: Urine output, lower limb swelling, Ashworth Scale (AS) spasticity and individuals’ perception of treatment effect (Patient reported impact of spasticity measure-PRISM and Global impression of change scale-GICS).

1.     Urine output was increased by 82mL with FES cycling compared to the control.

2.     With FES cycling:

·       Lower limb swelling was lower (-0.1 cm between group difference)

·       Spasticity was lower (-1.9 points between groups difference on AS)

·       PRISM was lower (-5 points between groups difference)

3.     12 individuals reported improvements with FES cycling on the GICS with a median improvement of 3 points.

4.     Two individuals reported adverse events: an increase in spasticity and the precipitation of a bowel accident.

Effect Sizes: Forest plot of standardized mean differences (SMD±95%C.I.) as calculated from pre- and post-intervention data.

 

 

 

 

 

 

Rayegani et al. 2011

Iran

RCT

PEDro=3

NInitial=74,

NFinal=64

Population: Mean age: 43.0 yr; Gender: males=60, females=4; Level of injury: cervical=11, upper thoracic=22, lower thoracic=29, lumbar=2; Level of severity: AIS A=63, AIS B=1.

Intervention: Individuals were randomly allocated to either the passive cycling group (n=37) or the controlled physical therapy group (n=37). The passive cycling intervention consisted of individuals sitting in their wheelchair while a motor passively moved their legs for up to 20 min/set, 3 sets/day for 2 mo (weekly regiment unspecified). The physical therapy included stretching, range of motion (ROM) and strengthening exercises (no further details provided).

Outcome Measures: Level of SCI, Kondal scale (for muscle strength), Modified Ashworth Scale (MAS), Goniometer measurements (for passive range of motion in the hip, knee and ankle) and electrodiagnostic parameters (H-reflex, H (max)/M (max), and F-wave parameters).

1.     MAS scores significantly decreased in the passive cycling group post intervention (p=0.003).

2.     Range of motion of the hip, ankle dorsiflexion and plantar flexion increased significantly post intervention in the passive cycling group (hip: p=0.005; ankle dorsi: mean difference=10°, p=0.000; ankle plantar: mean difference=9.4643, p=0.000) no significant change was observed in the knee flexion ROM in the passive cycling group (p=0.111).

3.     The F/M ratio (p<0.027) and the H max/M max (p=0.000) decreased significantly in the passive cycling group post intervention.

4.     H-reflex amplitude was not significantly different post intervention in either group.

5.     No significant differences were observed in the physical therapy group in regard to MAS scores and ROM of the hip, knee flexion, ankle dorsiflexion or plantar flexion.

Effect Sizes: Forest plot of standardized mean differences (SMD±95%C.I.) as calculated from pre- to post-intervention and pre-intervention to retention.

Krause et al. 2008

Germany

RCT Crossover

PEDro=5

N=5

Population: Mean age: 46.0 yr; Gender: males=3, females=2; Level of injury: thoracic=5; Level of severity: AIS A=5.

Intervention: In a crossover design, individuals with SCI were randomly assigned to FES induced leg cycling movement group versus passive-movement with cycle ergometer. interventions were delivered over a single session of 60-100 min.

Outcome Measures: Pendulum test (Relaxation index, peak velocity), Ashworth Scale (AS) conducted within 30 min prior or following intervention.

1.     A reduction in spasticity was seen after each intervention although the effect was significantly greater for FES-assisted versus passive movement.

2.     The relaxation index and peak velocity were significantly greater in the active session with FES than (68%, 50%, p=0.01); passive movement session increase was not significantly different (12%, 1%).

3.     In the active FES session significant increase in relaxation index and peak velocity was seen in both the left and right leg, while in the passive session such an increase was only present in the left leg relaxation index.

4.     Reduction in the MAS was seen after both active FES (p<0.001) and the passive movement session (p<0.05).

Effect Sizes: Forest plot of standardized mean differences (SMD±95%C.I.) as calculated from pre- and post-intervention data.

Reichenfelser et al. 2012

Austria

Prospective Controlled Trial

N=36

Population: Intervention group (n=23): Mean age: 40.0 yr; Gender: males=20, females=3; Level of injury: paraplegia=16, tetraplegia=7; Level of severity: AIS B-D; Mean time since injury: 9 mo. Control group (n=13): Mean age: 35.0 yr; Gender: males=9, females=4.

Intervention: Intervention group subjects performed training sessions 3x/wk over an average timespan of 2 mo. A training session consisted of pre-training (MAS assessment, transfer to the functional electrical stimulation (FES) cycling system, and electrode attachment), training, and post-training phases (electrode detachment, transfer, and MAS assessment). The intervention group was stratified based on each patient’s averaged MAS scores over all training sessions (Group A: MAS>1, n=8, Group B: MAS<1, n=15). Control group (Group C) participants performed the training session twice.

Outcome Measures: Active power output (30 and 60 rpm), Spasticity (instantaneous decrease in passive resistance to the pedalling motion due to FES cycling training/average decrease in Modified Ashworth Scale (MAS) scores).

1.       Monthly increase in power output averaged over all subjects was 4.4 W at 30 rpm and 18.2 W at 60 rpm.

2.       Group A showed the highest decrease in passive resistance overall.

3.       Groups B and C showed very similar results of decreased passive resistance. However, the difference between these two groups increases at higher rpm. Passive resistance decreases more in Group C across the various rpm.

 

Sadowsky et al. 2013

USA

Cohort

N=45

Population: Mean age: 36.0 yr; Gender: males=38, females=7; Level of injury: C1-T1=28, T2-L5=17; Level of severity: AIS A=31, AIS B=9, AIS C=5; Mean time since injury: 85.8 mo.

Intervention: Individuals underwent lower extremity Functional Electrical Stimulation (FES) during cycling (using ERGYS2 FES cycle ergometers) to determine long term effects on physical integrity and functional recovery. Individuals non-randomly grouped into intervention (n=25) and control (n=20) and did not differ significantly by important characteristics at baseline.

Outcome Measures: International Standards for Neurological Classification of Spinal Cord Injury, American Spinal Injury Association Impairment scale (AIS), Composite Motor–Sensory Score (CMSS), Spasticity and strength were measured quantitatively, total thigh, muscle, intra-and intermuscular fat volumes, Medical Outcomes Study 36-Item Short Form Survey, Functional Independence Measure (FIM), Multi-field questionnaire that captures neurogenic bowel habits.

1.     Spasticity as indicated by the ratio of maximal resistance torque to the maximal voluntary-plus-stimulated torque in the same muscle was ~40–50% greater in the control group than the FES group for all comparisons at the knee joint (p<0.05) but not significantly different at the ankle (p=0.60).

2.     Motor function improvement was observed in 20 of 25 (80%) FES subjects but in only 9 of 20 (45%) controls (p=0.02).

3.     CMSS improved in 20 of 25 (80%) FES subjects compared with eight of 20 (40%) controls (p=0.006).

4.     There was no significant difference in AIS grades following FES during cycling.

5.     The FES and control groups showed no significant difference (p=0.24) in total thigh volume.

6.     Total thigh fat measured by MRI was 44% less in the FES group than in the controls (462 versus 828 cc; p=0.003).

7.     Strength values were significantly greater in the trained muscles of the FES group (quadriceps, p=0.006; hamstrings, p=0.011) than in the controls, but not in the untrained ankle (triceps surae muscles, p=0.234).

8.     Quality of life and daily function measures were significantly higher in FES group.

9.     Mean bowel function scores were significantly higher in the FES group than in the controls (36.7 FES versus 33.6 control; p=0.04).

Kuhn et al. 2014

Germany

Pre-Post

N=30

 

Population: Mean age: 44.0 yr; Gender: males=30, females=0; Level of injury: C4-C7=13, T4-T12=11, L1-L5=6; Level of severity: AIS A=10, AIS B=3, AIS C=15, AIS D=2; Median time since injury: 2 mo.

Intervention: Individuals participated in functional electrical stimulated (FES) cycling programs. FES was targeted to the hamstrings, quadriceps and gluteal muscles. Sessions were 20 min, 2x/wk for 4 wk. Outcomes were assessed at before and after each session.

Outcome Measures: Circumferential measurement, Muscular ultrasound, Manual muscle test, Modified Ashworth Scale (MAS), Walking index for spinal cord injury II (WISCI II), Timed up and go (TUG) test, 6-minute walk test (6MWT).

 

 

1.     No significant changes in circumferential measurement (p>0.05).

2.     AIS A and AIS B individuals had significant improvements on muscular ultrasound measurements after their first session (p=0.016). Additionally, all participants had significant improvements on their muscular ultrasound measurements after their last session (AIS A + B, p=0.019; AIS C+D, p=0.006).

3.     Manual muscle strength was significantly increased in the hamstrings (p<0.001), quadriceps (p<0.001), and gluteal muscles (p<0.001) from the first to last session.

4.     MAS scores had significant improvements (p=0.002); where improvements were significant in hip abduction (p=0.016), knee flexion (p=0.003), knee extension (p=0.001), and dorsal extension (p=0.001).

5.     Of the seven participants whom demonstrated walking ability, there were significant improvements in WISCI II (p=0.04) and 6MWT (p=0.03) scores from the first to last session.

6.     TUG scores did not improve (p=0.5).

Manella et al. 2013

USA

Pre-Post

N=12

 

Population: Tibialis Anterior (TA) activation group (n=6): Mean age: 44.2 yr; Gender: males=6, females=0; Median level of injury: C7; Level of severity: AIS D=6; Mean time since injury: 10.8 yr. Soleus (SOL) H-reflex suppression group (n=6): Mean age: 45.2 yr; Gender: males=4, females=2; Median level of injury: C5; Level of severity: AIS D=6; Mean time since injury: 10.8 yr.

Intervention: Individuals were randomly assigned to either the TA or SOL groups.

In the TA group, operant conditioning training via electromyography feedback was performed to induce voluntary TA activation to enhance supraspinal drive. While in the SOL group, training was performed to modulate reflex pathways at the spinal cord level. Training was performed in both groups 3x/wk for 5wk. Individuals were assessed the wk before and after completion of training.

Outcome Measures: Maximal voluntary contraction % (MVC%), H-reflex during dorsiflexion % (HDF%), Ankle clonus drop test (Mean clonus duration, Plantar flexion threshold angle (PF RTA)), Timed toe tapping tests, Voluntary dorsiflexion (DF) active range of motion (ROM), ASIA lower extremity motor scores), Foot clearance, Walking speed, Walking distance, SOL H-reflexes % (Presynapic inhibition, reciprocal inhibition, and low-frequency post-activation depression), SOL/TA co-activation ratio.

1.     The TA group had significant improvements in: MVC% amplitude (p=0.01), foot clearance (p=0.05) and walking distance (p=0.02).

2.     The SOL group had significant decreases for HDF% (p=0.09), and SOL/TA co-activation (p=0.02) over time.

3.     None of the other outcome measures had significant changes (p>0.05).

Mazzoleni et al. 2013

Italy

Pre-Post

N=5

Population: Mean age: 43.0 yr; Gender: males=4, females=1; Injury etiology: suprathoracic SCI=5; Level of severity: AIS A=1, B=2, C=2.

Intervention: All individuals received cyclo-ergometer training in conjunction with functional electrical stimulation (FES) 3 days/wk for 20 wk. Training consisted of pedaling on the cycle for 15-30 min/day with the pedaling time increasing as individuals progressed through the intervention period. FES was delivered to the quadriceps, femoral biceps and gluteus during cyclo-ergometer training. The motor either assisted movements if muscles weren’t trained enough or provided a resistance when muscles are able to achieve the minimum power. Individuals also received a rehabilitation program during the intervention period consisting of exercises to increase movement of the head, trunk and arm.

Outcome Measures: ASIA lower extremity motor control, Spinal cord independence measure (SCIM), Modified Ashworth Scale (MAS), 4-point spasms scale, Muscle area measurements at 5, 10 and 15 cm above the knee and kinetic measurements during cycling (mean speed, maximum speed, resistance, mean power, maximum power and distance).

1.     Thigh circumference at 10 cm and 15 cm above the kneecap increased significantly from baseline to post intervention (p<0.05).

2.     The distance travelled during cycling increased significantly from baseline to post intervention (p<0.05).

3.     No significant changes were observed in mean speed, max speed, resistance, mean power, max power, MAS and the spasms scale from baseline to post intervention.

Mirbagheri et al. 2002

Canada

Pre-Post
NInitial=9,

NFinal=5

Population: Age range: 25-49 yr; Gender: males=5, females=4; Level of injury: C5-L1; Level of severity: AIS C-D=5; Time since injury range: 3.1-12.3 yr.

Intervention: FES-assisted walking for as much time as possible during daily living (~1-3 hr/day) for 16-18 mo following 4 wk of training.

Outcome Measures: Reflex and intrinsic stiffness (mathematical modelled responses of torque resistance to movement), Modified Ashwoth Scale (MAS) collected prior to and following the 16-18 mo trial.

1.     Spasticity was reduced in those that did FES-assisted walking as indicated by reductions in decreased reflex (p<0.001) and intrinsic (p<0.001) stiffness.

2.     Spasticity increased for the non-FES subject as indicated by increased reflex stiffness and no change in intrinsic stiffness.

3.     The MAS either showed no change following the training period or was not collected (this was not clearly presented by the authors).

Thoumie et al. 1995

France

Pre-Post

N=21

Population: Age range: 20-53 yr; Gender: males=20, females=1; Level of injury: C8-T12; Time since injury range: 4-72 mo.

Intervention: Fitting of a Reciprocating Gait Orthosis II (RGO) hybrid (FES-assisted) system and subsequent locomotor training program of 2, 1 hr sessions/wk for 3-14 mo.

Outcome Measures: Spasticity (subjective self-report scale) collected prior to and following the 3-14 mo trial.

1.     No group analysis reported for spasticity measure–No marked changes reported, decrease in spasticity for 7 subjects at 0.5-5 hr and increase in spasticity for 4 subjects at 0.5-1 hr. No long-term effects were observed.
Granat et al. 1993

Scotland

Pre-Post

N=6

Population: Age range: 20-40 yr; Gender: males=3; females=3; Injury etiology: SCI=6; Level of injury: C4 to L1; Level of severity: Frankel grade C=3, D=3; Time since injury range: 2-18 yr.

Intervention: FES-assisted locomotor training for at least half an hr each day for a minimum of 5 days/wk for a minimum of 3 mo.

Outcome Measures: Spasticity (Ashworth Scale (AS) and Pendulum Test), Manual muscle tests using Oxford Scale, Maximum voluntary contraction, Upright motor control, Gait Performance (Energy Cost), postural stability (Centre of Pressure), Modified Barthel Index. Spasticity tests were conducted at least 24 hr after FES use.

1.     Significant reductions in spasticity as indicated by increased relaxation index of pendulum test (p<0.05).

2.     No changes were evident with Ashworth scale.

3.     Gait and muscle strength changes are elaborated in Chapter entitled “Lower Limb Rehabilitation”.

Effects of Standing
Sadeghi et al. 2016

Canada

Prospective Controlled Trial

N=10

Population: Mean age: 40.4 yr; Gender: males=9, females=1; Injury etiology: SCI=10.

Intervention: Individuals underwent two different standing training interventions (dynamic and static). These interventions were given for 20 min and separated by 1 wk. Outcomes were assessed immediately before standing training, 5 min after, and 1 hr afterwards.

Outcome Measures: Modified

Ashworth Scale (MAS), Visual Analog Scale (VAS), Electromyography (EMG).

1.     Non-significant decrease in spasticity in both dynamic and static standing trials for individuals with SCI as measured by MAS, VAS or EMG.

2.     There was no statistical difference in spasticity between dynamic and static standing training in individuals with SCI as measured by MAS, VAS or EMG.

Body Weight Support Treadmill Training versus Tilt Table Standing
Manella & Field-Fote 2013

USA

RCT

PEDro=5

N=18

Population: Mean age: 35.1 yr; Gender: males=16, females=2; Injury etiology: motor incomplete SCI=18; Level of severity: AIS C=9, AIS D=9.

Intervention: Individuals were randomized to receive 1/4 body-weight supported locomotor training interventions: treadmill based training with manual assistance (TM-n=4), treadmill based training with stimulation of the common peroneal nerve (TS-n=6), lokomat robotic assistance (LR-n=3) or over ground training with stimulation of the common peroneal nerve (OG-n=5). Individuals underwent locomotor training for 1 hr/day, 5 day/wk for 12 wk. Body-weight was supported through the use of a harness in all interventions. Peroneal stimulation was delivered to assist with stepping (flexor reflex response in TS, ankle dorsiflexion in OG). Manual assistance was provided for TM and LR. Results were reported as clonus versus no-clonus (not by different intervention groups) based on number of beats recorded during the drop test.

Outcome Measures: Drop test (thigh manually raised up a point 10 cm above the knee, the leg is then released and contacts a 10 cm raised platform, eliciting a passive plantar flexion stretch to cause clonus), spinal cord assessment of spastic reflexes (SCATS: measures ankle clonus-plantar flexors are stretched by ankle dorsiflexion and clonus duration recorded-and extensor spasm duration-leg is flexed at the hip and knee then rapidly extended), electromyographic (EMG) recordings during drop test (recordings of the soleus, medial gastrocnemius and tibialis anterior), soleus H-reflex (after stimulating the posterior tibial nerve) and over ground walking speed (patients walked 6m at self-selected pace, speed during central 2m recorded).

1.     Extensor spasm duration significantly decreased in the clonus group (mean difference=-13.20 sec, p=0.05).

2.     Overground walking speed increased significantly in the clonus group (mean difference=0.06 m/sec, p<0.01).

3.     The clonus duration observed from the drop test (mean difference=-3.99 sec, p=0.06) and the plantar flexion reflex threshold angle (mean difference=-5.82°, p=0.09) decreased non-significantly.

4.     The no clonus group showed no significant changes in any outcome measure.

Effect Sizes: Forest plot of standardized mean differences (SMD±95%C.I.) as calculated from pre- and post-intervention data.

Adams et al. 2011

Canada

RCT Crossover

PEDro=5

N=7

Population: Gender: males=6, females=1; Inury etiology: SCI=7; Chronicity: chronic.

Intervention: Twelve sessions of body-weight supported treadmill training (BWSTT) and tilt-table standing (TTS).

Outcome Measures: Modified Ashworth Scale (MAS), Soleus H/M ratio, Four self-report questionnaires, Spinal Cord Assessment Tool for Spinal reflexes, Spinal Cord Injury Spasticity Evaluation Tool (SCI-SET), Penn Spasm Frequency Scale (PSFS), Quality of life (Quality of Life Index Spinal Cord Injury Version–III), Functional mobility (FIM Motor Subscale).

1.     Extensor spasms exhibited a decrease in extensor spasms following TTS but not after BWSTT (ES=0.68).

2.     There was a greater reduction in passive resistance to movement (Ashworth; ES=0.69) and flexor spasms (ES=0.57) after BWSTT compared to TTS.

3.     Following BWSTT, there was a greater reduction in the H/M ratio compared to TTS (ES=0.50).

4.     Findings suggested that extensor spasms were reduced after TTS (ES=0.95) with a greater reduction after TTS than BWSTT (ES=0.79). However, flexor spasms were observed to be reduced to a greater extent after BS TT as compared to TTS (ES=0.79).

5.     There were no observed changes in the H/M ratio following either BWSTT or TTS.

6.     There were no group changes in SCI-SET scores or PSFS scores.

7.     BWSTT was associated with an improved quality of life and positive changes in FIM motor Subscale scores (ES=0.50 and ES=1.24).

*No comments were made on statistical significance of findings.

Dynamic Standing
 

 

Boutilier et al. 2012

Canada

Pre-Post

NInitial=9,

NFinal=8

Population: Mean age: 44.1 yr; Gender: males=7, females=1; Injury etiology: SCI=9; Chronicity: chronic.

Intervention: Participants underwent a 4 wk dynamic standing program using a Segway (3x/wk, 30 min sessions).

Outcome measures: Modified Ashworth Scale (MAS), Spinal Cord Injury Spasticity Evaluation Tool (SCI-SET), Pain Outcomes Questionnaire (POQ-VA), Fatigue Severity Scale (FSS).

1.     Individual muscle MAS scores decreased after the intervention in at least 2/3 muscle groups for every subject.

2.     There was a statistically significant reduction in MAS sum immediately from pre-to post training (p<0.001) though there was no significant improvement over time.

3.     Spasticity evaluations using the SCI-SET showed an improvement in SCI-SET scores from -0.91±0.30 at initial visit, to -0.63±0.24 for midway and at the final visit from

-0.57±0.24, although these differences were not statistically significant.

4.     There was a statistically significant reduction in pain over time (p<0.05) for the three visits (initial 42.75±8.49, midway 40.88±10.10 and final 32.88±7.17).

5.     There was no significant difference between initial and final visits for fatique, though mean fatigue scores did improve (mean=4.2±0.42 to 3.7±0.54).

Upper Limb
Cortes et al. 2013

Spain

Pre-Post

N=10

Population: Mean age: 44.8 yr; Gender: males=8, females=2; Injury etiology: SCI=10; Level of injury: tetraplegia=10; Chronicity: chronic.

Intervention: Subjects received a 6 wk wrist-robot training intervention from the InMotion 3.0 Wrist robot, for 1 hr/day, 3 days/wk, for a total of 18 training sessions per participant.

Outcome measures: Upper extremity motor score (UEMS), Modified Ashworth Scale (MAS), Visual Analog Scale (VAS).

1.     There was a statistically significant improvement in kinematic variables for aim and smoothness after the training program (aim: pre 1.17±0.11 radians, post: 1.03±0.08 radians, p=0.03)

2.     6 wk of robotic training was not associated with a statistically significant change in motor strength of the trained arm (p=0.4) or in the untrained left arm (p=0.41).

3.     There were no significant changes in upper limb spasticity in the right trained arm (p=0.43) and left untrained arm following training (p=0.34).

4.     There were no changes observed in pain levels following training (p=0.99).

5.     There were no changes in any neurophysiological parameters after the 6 wk training (MEP amplitude, p=0.28; latency, p=0.28).

Hydrotherapy
Kesiktas et al. 2004

Turkey

Pre-Post

N=20

Population: Hydrotherapy group (n=10): Mean age: 32.1 yr; Gender: males=8, females=2; Level of injury: C5-6=3, T8-9=7; Level of severity AIS: A/B-C/D=3/3/4; Mean time since injury: 7.7 yr. Control group (n=10): Mean age: 33.1 yr; Gender: males=7, females=3; Level of injury: C5-6=3, T8-9=7; Level of severity: AIS: A/B-C/D=3/3/4; Mean time since injury: 8.6 yr.

Intervention: 20 min of underwater exercises at 71°F, 3x/wk for 10 wk in addition to conventional rehabilitation (passive range of motion (ROM) exercises, oral baclofen, psychotherapy) versus conventional rehabilitation alone.

Outcome Measures: Ashworth Scale (AS), Penn Spasm Frequency Severity (PSFS), Functional Indepednece Measure (FIM) scores and oral baclofen intake were recorded weekly and evaluated at the beginning and end of the intervention period.

1.     Both groups showed a significant decrease in AS (hydrotherapy p=0.01 and control p=0.02) with hydrotherapy having a larger reduction in spasticity but this difference was not significant.

2.     Spasticity was significantly reduced with hydrotherapy (p<0.001) and with Control (p<0.05) as indicated by Penn Spasm Severity. Post- intervention hydrotherapy scores were reduced versus Controls (p<0.02).

3.     Oral baclofen intake was significantly reduced for the hydrotherapy group but not for the control group (p<0.002).

4.     Both groups demonstrated significant increases in FIM scores (hydrotherapy p=0.0001 and control p=0.01), with a larger increase for the hydrotherapy group (p<0.001).

Resistance Training
Bye et al. 2017

Australia

RCT

PEDro=8

N=30

 

Population: SCI (n=30): Mean age=46yr (IQR=25-65); Gender: males=24, females=6; Level of injury: C1-4=10, C5-8=14, T1-S5=6; Median time since injury=2mo (IQR=1.4-3.1); AIS scale: A=8, B=1, C=11, D=10.

Intervention: One of the following was selected as the target muscle group for each participant; Elbow flexors, elbow extensors, knee flexors, knee extensors. The target muscle on one side of each participants’ body was randomly allocated to the experimental condition; the target muscle group on the other side of the body was allocated to the control condition. The experimental condition underwent a progressive resistance training program consisting of concentric and isometric target muscle contractions in addition to the usual standard of care. The control condition received the usual standard of care including gait and functional training for activities of daily living. The experimental limb was trained 3X/wk for 12 wk. Outcome measures were assessed at baseline and post-intervention.

Outcome Measures: Maximal voluntary isometric strength (MIVS); spasticity; muscle fatigue; participant perception of strength; participant perception of function.

1.     The between-group difference for MIVS had a 95% confidence interval which spanned the clinically meaningful intervention effect, indicating an uncertainty as to whether the intervention effect was clinically meaningful.

2.     The between group difference in spasticity indicated no change due to intervention effect.

3.     The between-group difference for fatigue had a 95% confidence interval which spanned the clinically meaningful intervention effect, indicating an uncertainty as to whether the experimental condition had a clinically meaningful change.

4.     Between-group differences indicate a clinically meaningful increase in participants’ perception of functional and strength improvement.

Combination Therapy
Martinez et al. 2018

USA

RCT Crossover

PEDro=5

NInitial=21

NFinal=12

 

Population: SCI (n=12): Mean age=40.33±7.84yr; Gender: males=9, females=3; Level of injury: C=3, T=9; Mean time since injury=7.92±7.01; AIS scale: A=1, B=1, C=7, D=3.

Intervention: In this randomized control trial crossover, participants received two 48-session interventions separated by a 6-wk washout period. 30min/session, 3-5x/wk. Interventions included treadmill exercise (TM) and multimodal exercise (MM). For TM, participants walked on a robotic-assisted treadmill at initial speeds of 1-1.5km/h. Speeds were graduated increased as tolerated to a maximum of 3.2 km/h. Additionally, the amount of assistance to reach a predefined gait pattern was gradually reduced as tolerated. MM consisted of simultaneous balance and upper extremity exercises. Outcome measures were assessed at baseline, post intervention, and 6-wk follow up.

Outcome Measures: modified Ashowrth Scale (mAS); Spinal Cord Injury Spasticity Evaluation Tool (SCI-SET).

1.     There was minimal SCI-SET change on both the individual and group level.

2.     Four participants showed a decrease in mAS and 5 showed no change in mAS after TM.

3.     Two participants showed an increase in mAS and 3 showed no change after MM.

Estes et al. 2017

USA

RCT Crossover

PEDro=4

NInitial=18

NFinal=10

Population: SCI (n=10): Mean age=46.2±12.8yr; Gender: males=8, females=2; Level of injury: C=6, T=4; Mean time since injury=5.5±3.7yr; AIS scale: B=3, C=2, D=5.

Intervention: This RCT crossover study consisted of four different physical therapeutic/electroceutic interventions and a sham control. Interventions were separated by at least 48 hr. Interventions included, 1) stretching targeting hip, knee, and ankle flexors and extensors, 2) cyclic passive movement (CPM) using a treadmill-mounted robotic gait orthosis for the lower limbs, 3) transcutaneous spinal cord stimulation (tcSCS) consisting of biphasic stimulation using anodes placed on the back in the region of T11-T12 and the umbilicus, 4) transcranial direct current stimulation (tDCS) by placing an anode 1 cm anterior to the vertex, and a cathode over the inion, and 5) a sham control condition using electrodes. For the stretching, each stretch position was held for 60 seconds and muscle were stretched three times each. tcSCS, CPM, and the sham were administered for 30 min each. tDSC was administered for 20 minutes. Outcome measured were assessed at baseline, immediately after the intervention, and 45-min post-intervention.     

Outcome Measures: First swing excursion (FSE) angle from the pendulum test.

1.     Between-group comparisons against the sham group showed significantly greater increases in FSE for stretching, CPM and tcSCS immediately after the intervention (p<0.05). However, there was no significant between-group difference in FSE change when comparing tDCS and sham (p>0.05).

2.     Only CPM and tcSCS had significantly greater increases in FSE when compared to sham at 45 min post-intervention (p<0.05).

3.     There were no significant between-group differences in FSE change when comparing the intervention groups to each other at both follow-up assessments (p>0.05).

4.     The sham condition showed a significant within-group decrease in FSE immediately after intervention and 45 min post-intervention (p<0.05).

5.     There were no significant within-group changes in FSE for CPM, tcSCS, and tDCS at both follow-up assessments (p>0.05).

6.     There was a significant within-group increase in FSE for stretching immediately following the intervention (p<0.05).

Gant et al. 2018

USA

Pre-Post

N=8

 

Population: SCI (n=8): Mean age=31.38±11.64yr; Gender: males=6, females=2; Level of injury: T=8; Time since injury=all >1yr; AIS scale: A=4, B=4.

Intervention: All participants underwent three 4-wk multimodal training sessions separated by 1 wk each; 1) body-weight-supported treadmill training (BWSTT) was administered using a treadmill-based robotic orthosis 2x/wk. Treadmill speed was increased by 2.5%/wk with the most tolerable percentage of body-weight support provided. 2) Upper extremity circuit resistance training (CRT) was administered 3x/wk on non-consecutive days. 30-45 min/session. Participants performed 10 repetitions of each weightlifting maneuver followed by 2 min of arm cranking on a stationary machine. 3) Functional electrical stimulation (FES) cycling was performed on a cycle ergometer 3x/wk on non-consecutive days. 15 min/session. Stimulation consisted of computer-sequenced electrical stimulation with a frequency of 35 Hz, current amplitude of 100-140 milliamperes, and a pulse width of 350 microseconds. Resistance (torque) was applied and increased at each successive session. Outcome measures were assessed at baseline before the initiation of the intervention, during the 1-wk period in between each intervention, and at the completion of the study.

Outcome Measures: Spinal Cord Assessment Tool for Spastic reflexes (SCATS); modified Ashworth Scale (mAS); first swing excursion of pendulum test (FSE); EMG activity of soleus (SL), tibilais anterior (TA), rectus femoris (RF), and biceps femoris (BF).

1.     Participants with high SL and TA F/M ratios at baseline showed significant declines in SL and TA F-wave to M-wave ratio (F/M) at the end of the study (rho=-.69, p=.047; rho=.952, p<0.001, respectively).

2.     Participants with high SL F/M ratios at baseline also showed significant declines in the SCAT extensor score at the end of the study (rho=-.70, p=.047).

3.     No other outcome measures differed significant when comparing baseline to the end of the study.

Mazzoleni et al. 2017

Italy

Pre-Post

N=7

 

Population: SCI (n=7): Mean age=45.28±3.09yr; Gender: males=5, females=2; Level of injury: T=7; Mean time since injury=NR; AIS scale: A=7.

Intervention: Participants underwent a two-phase robot-assisted rehabilitation training program. The first phase consisted of functional electrical stimulation (FES) cycling. The quadriceps and femoral biceps of both legs were stimulated using a square biphasic alternated wave with a frequency of 50 Hz. Duration and cycle duty were set to 500 microseconds and 50%, respectively. Simulation amplitude range was 35-75 mA and 25-50 mA for the quadriceps and femoral biceps, respectively. The second phase consisted of overground robotic exoskeleton training consisting of assisted step initiation and active self-initiated modality interactions. Outcome measures were assessed at baseline, and after each phase.    

Outcome Measures: modified Ashworth Scale (mAS); Numerical Rating Scale on spasticity (NRS).

1.     mAS was significantly lower after completing phase 1 and 2 compared to baseline (p<0.05 for both).

2.     There was no significant change in NRS after completing FES cycling (p>0.05). However, after completing exoskeleton training, there was a significant decrease in NRS compared to baseline (p<0.05).

Discussion

Robot Assisted Exercise (involving voluntary or electrically assisted movement)

In Fang et al.’s (2015) crossover RCT (n=10) noted in the passive movement section previously, one of the conditions involved electrical stimulation-induced contractions for eight min, once/week over three weeks in addition to high speed cyclic passive exercise (50 cycles/min) or low speed cyclic passive exercise (20 cycles/min). Although the focus of that study was on the effects of robot passive-assisted exercise, a key finding related to ES-assisted muscle contractions was that H reflex amplitudes were reduced after passive exercise at both speeds but not after repeated ES-elicited contractions. This suggests reflex excitability is more affected by passive movement (i.e., stretching) than active muscle contraction. Also, electrical stimulation-induced contractions only had an effect in reducing total resistance during slow (p<0.05) but not fast cyclic stretching, whereas there was actually an ES-mediated increased resistance (p<0.05). Isometric torque decreased significantly after 8 minutes of electrical stimulation-induced contractions and the reduction persisted up to 20 minutes (p<0.05), thereby indicating fatigue.

Mirbagheri et al. (2002) previously reported on the use of a custom-made device producing sinusoidal ankle movements as well as mathematical modelling to assess variations in intrinsic (musculotendinous) and reflex contributions to spasticity calculated from measured ankle joint torque due to perturbations. This was employed as part of an RCT (n=46) reprted across two separate publications (Mirbagheri et al. 2015; 2013) examining the effects of robotic-assisted step training using Lokomat vs no treatment on ankle spasticity. The treatment group (n=23) received 1-hour sessions of robotic-assisted step training, three x/week for up to 45 minutes, for four weeks with measures completed prior to training and after 1, 2, and 4 weeks of robotic-assisted step training. The key finding was that reflex stiffness and intrinsic stiffness parameters of spasticity all showed significant decreases (p<0.05) whereas the control group did not show any change (p>0.05) for any of the parameters calaculated. Subjects were stratified into groups based on similar reflex or intrinsic parameter recovery patterns for both robotic-assisted step training and control groups. Three classes were identified based on greater baseline values for each of the reflex parameters and two classes were identified for the intrinsic parameters. Essentially, greater reductions in spasticity were seen in those with higher baseline levels of either reflex (r2=0.94, p<0.0001) or intrinsic (r2=0.84, p=0.01), although these changes were only apparent in the treatment group as there were no significant changes with the “no treatment” control condition.

In summary, there is some evidence that robot-assisted exercise (whether including voluntary or ES- assistance) appears to decrease all components of spasticity in the spinal cord injured individual: isometric torque, reflex and intrinsic stiffness. However, there is certainly more research required to identify more specific information associated with both the treatment and resulting spasticity parameters.

Exoskeleton Walking Device

Kressler et al. (2014) completed a case series study (n=3) of over-ground bionic ambulation training using an exoskeleton (Ekso). The study showed that there were no changes in Spinal Cord Assessment Tool for Spastic Reflex (SCATS), Spinal reflex excitability, recordings of electromyographic activity (EMG), or electroencephalography measures.

Del-Ama et al. (2014) conducted a case series study (n=3) to determine the effects of electrical-muscle stimulation -induced hybrid gait training (interventions with a hybrid bilateral exoskeleton for 4 days). Study subjects demonstrated improvements in spasticity as marked by differences in the AS (-0.2±0.4) and Penn Spasm Frequency Scale (PSFS) (-0.4±0.5) after the intervention.

With a larger cohort of individuals (N=45), Juszczak et al (2018) reported significantly reduced self-reported spasticity (p<0.001) after 8 weeks of graduated training over 3-4 sessions with the Indego Powered Exoskeleton. The importance of this finding is somewhat muted when it is noted that the self-reported spasticity assessment (i.e. 0-10 numerical rating) has not been psychometrically studied for SCI spasticity. Conversely, the MAS has been validated for use in assessment SCI spasticity and in this trial, the majority of participants (62.2%; n=28) did not register a change in spasticity with MAS. Of the remaining participants, reduced or increased spasticity, as measured by MAS, was detected in 26.7% (n=12) and 11.1% (n=5) after Indego training.

Functional Electrical Stimulation

Kapadia et al. (2014) completed an RCT (n=34) to assess FES walking and mobility, with spasticity (i.e., MAS, pendulum test) as primary outcomes. The intervention group (n=17) received FES on their quadriceps, hamstrings, dorsiflexors, and plantarflexors while performing ambulation exercises on a body weight supported treadmill. The control group (n=17) received conventional resistance and aerobic training. Both groups received 45-minute sessions, threex/week for 16 weeks with assessments at baseline, 16 weeks, 6 months, and 12 months post intervention. In general, there were no significant differences over time or between groups for the majority of the MAS and pendulum test. However, MAS scores significantly worsened over time (i.e., more spasticity) for both groups in the right quadriceps (p=0.015).

As part of a larger RCT, Manella et al. (2013) conducted an analysis (n=18) of high vs low clonus participants (i.e., high=at least four beats of clonus during drop test) in order to study the effect of various forms of locomotor training on ankle clonus and quadriceps muscle spasm. Study subjects were randomized to receive one of four body-weight supported locomotor training interventions, although sub-analyses were not conducted for each of these related to the spasticty measures. Participants underwent locomotor training for 1 hour per day, 5 days per week for 12 weeks. Only high clonus subjects showed significantly decreased extensor spasm duration (mean difference=-13.20 s, p=0.05), significantly increased overground walking speed (mean difference=0.06m/s, p<0.01) and non-significant decreases in clonus duration observed from the drop test (mean difference=-3.99s, p=0.06) and plantar flexion reflex threshold angle (mean difference=-5.82°, p=0.09). The low clonus group did not show any significant changes in any of theoutcome measures. The key finding was that walking speed improvements (no matter the modality of locomotor training) were strongly correlated with reductions in spasticity (i.e., reduced clonus and spasms).

Ralston et al. (2013) completed a crossover RCT (n=14) to study the effect of FES-assisted cycling. Study subjects were randomized to receive 2 weeks of either FES cycling for 30-45 minutes per day, 4 days per week combined with usual care vs only usual care, with a 1-week washout between the two conditions. FES was applied to the quadriceps, hamstrings and gluteals of each leg. Usual care consisted of standard inpatient physical and occupational therapies including treatment for poor strength, restricted joint mobility, limited fitness, reduced dexterity, pain and functional skills training. Urine output, as the primary measure, as well as lower limb swelling, spasticity (Ashworth) and individuals’ perception of treatment effect (patient reported impact of spasticity measure- and Global impression of change scale-GICS) were measured. No measures achieved statistical significance, perhaps related to the relative brevity of the intervention. However, all means were improved in favour of an effect of FES-cycling. Urine output increased by 82 mL with FES cycling compared to the control group. Lower limb swelling (-0.1 cm), Ashworth scores (-1.9 points on a 32-point scale obtained by summing four muscle groups bilaterally), and individual reported impact of spasticity measure reports (-5 points) were all reduced with FES. All 12 study subjects reported improvements with FES cycling on the GICS with a median improvement of three points. During the study, two individuals reported adverse events: an increase in spasticity and one reported a bowel accident.

Kuhn et al. (2014) completed a pre-post FES cycling study (n=30) involving training sessions of 20 minutes, two times per week for 4 weeks. MAS scores had significant improvements (p=0.002) in hip abduction (p=0.016), knee flexion (p=0.003), knee extension (p=0.001), and dorsal extension (p=0.001). In contrast, no significant changes were seen on the MAS and four-point spasms scale in a small pre-post trial (n=5) of FES cycling conducted by Mazzoleni et al. (2013). This study involved training for 15-30 minutes per day, 3 days per week for 20 weeks with the pedaling time increasing as individuals progressed over time.

Sadowsky et al. (2013) reported an increase in muscle strength but not spasticity levels associated with a retrospective, controlled cohort trial (n=45) of lower extremity FES cycling. Participants were non-randomly grouped into intervention (n=25) and control (n=20) groups.

Reichenfelser et al. (2012) completed a prospective controlled trial (n=36) to study the effects of FES cycling over a period of 2 months. The treatment group was divided into Group A (n=13; non-spastic group, MAS score<1) and Group B (n=13; spastic group, MAS score>=1). The study subjects performed training sessions three times per week over an average timespan of 2 months. The control group (n=13; Group C, able=bodied individuals) performed the training session twice. Active power output (30 and 60 rpm), and spasticity (decrease within the cycling session as measured by passive resistance over the cycle) were assessed as part of a customized, commercial tri-cycle ergometer system. Group A treatment subjects showed the highest decrease in passive resistance overall (i.e., within a session and greater as time progressed) with Groups B treatment subjects and Group C control subjects showing lesser and comparable decreased passive resistance. However, the difference between these two groups increased at higher rpm and passive resistance decreased more in Group C control subjects across the various rpm. In addition, there was a monthly mean increase in power output of 4.4 W at 30 rpm and 18.2 W at 60 rpm.

Krause et al. (2008) used a randomized, crossover study design in which five individuals with complete AIS A SCI underwent 1) FES cycling and 2) passive movement by a motor-assisted cycling ergometer. For both of the interventions, the legs were moved for the same period of time at the same velocity and frequency. The study demonstrated that FES (i.e., active muscle contractions) was significantly more effective than passive movements at reducing spastic muscle tone in individuals with complete SCI, although even passive movement resulted in spasticity reductions. This was indicated by a greater reduction in the MAS for FES versus passive movement (p<0.001 versus p<0.05, respectively), also with the Pendulum Test (p=0.01). Further research may be useful in determining precise stimulation patterns to use for FES-cycling as Mela et al. (2001) have noted that specific stimulation frequency parameters may influence spastic reactions variably which suggests careful selection of stimulation parameters so as to optimize the delivery of FES as a clinical tool to reduce spasticity.

Mirbagheri et al. (2002) calculated reflex and intrinsic stiffness of the ankle, as described earlier, as a means of assessing spasticity prior to and following a FES-assisted walking training program. This program involved four individuals with longstanding AIS C or D SCI who underwent locomotor training for a minimum of 16 months. Both reflex and intrinsic stiffness were reduced following FES-assisted walking. Conversely, an individual with SCI, who was not using FES-assisted walking demonstrated no reduction in spasticity. Although the MAS was noted as an outcome measure in the methods, the authors failed to report the final results associated with this clinical measure.

In a similar trial of FES-assisted walking in people with longstanding SCI (Frankel C or D), Granat et al. (1993) also found reductions in spasticity as assessed by a pendulum drop test but did not show any change pre-and post-training when considering AS scores. Granat et al. (1993) performed the final spasticity assessment 24 hours after the final FES-assisted walking session; thereby ensuring the final outcomes would not be unduly influenced by the short-term effects of muscle stimulation.

Thoumie et al. (1995) examined the effects of a FES-assisted Reciprocating Gait Orthosis II on spasticity following a long-term program (i.e., three-13 months) of gait training. No group results (n=21) were reported for spasticity although it appeared that no systematic effects were obtained on a customized self-report version of the AS. Some subjects (n=7) reported decreases in spasticity in the short-term, while others reported increased spasticity (n=4).

Effects of Standing

Sadeghi et al. (2016) completed a prospective controlled trial (n=10) where study subjects underwent two different standing training interventions (dynamic and static). These interventions were given for 20 minutes and separated by 1 week. Outcome measures including the MAS, VAS, andEMG were completed immediately before standing training, at 5 minutes after, and at 1 hour after training. The study showed non-significant decreases in spasticity for both dynamic and static standing trials for individuals with SCI as measured by MAS, VAS and EMG.

Body Weight Supported Treadmill Training (BWSTT) verses Tilt Table Standing (TTS)

Adams et al. (2011) completed a small crossover RCT (n=7) to determine the effects of 12 sessions of body-weight supported treadmill training and tilt-table standing on clinically assessed and self-reported spasticity, MAS, soleus H/M ratio, SCATS, SCI-SET, and the PSFS. The study showed that extensor spasms decreased following tilt-table standing but not after body-weight supported treadmill training (electrical stimulation=0.68) and there was a greater reduction in passive resistance to movement (Ashworth; ES=0.69) and flexor spasms (electrical stimulation=0.57) after body-weight supported treadmill training compared to tilt-table standing . Following body-weight supported treadmill training, there was a greater reduction in the H/M ratio compared to tilt-table standing (electrical stimulation=0.50). Extensor spasms were reduced after tilt-table standing (electrical stimulation=0.95) with a greater reduction after tilt-table standing than body-weight supported treadmill training (electrical stimulation=0.79); however, flexor spasms were observed to be reduced to a greater extent after body-weight supported treadmill training as compared to tilt-table standing (electrical stimulation=0.79). There were no observed changes in the H/M ratio, SCI-SET or PSFS scores following either body-weight supported treadmill training or tilt-table standing.

Dynamic Standing

Boutilier et al. (2012) completed a pre-post study (n=8) on dynamic standing using the Segway device. Study subjects underwent a 4-week dynamic standing program using a Segway, three times a week, for 30-minute sessions. Outcomes were measured by the MAS and the SCI-SET. The study showed that in individual muscle MAS scores there was a decrease after the intervention in at least two out of three muscle groups for every subject. There was a statistically significant reduction in MAS immediately from pre-to post training (p<0.001) though there was no significant improvement over time. In spasticity evaluations using the SCI-SET, an improvement from -0.91±0.30 initial, to -0.63±0.24 midway, to -0.57±0.24 final scores were observed. These improved SCI-SET scores were not statistically significant. However, there was a statistically significant reduction in pain over time (p<0.05) for the three visits (initial 42.75±8.49, midway 40.88±10.10, final 32.88±7.17). There was no significant difference between initial and final visits for fatique, though mean fatigue scores did improve (mean=4.2±0.42 to 3.7±0.54).

Upper Limb

Cortes et al. (2013) completed a pre-post study (n=10) of wrist spasticity using a robot training intervention with a primary focus on enhancing motor performance and neurorecovery. Study subjects received a 6-week wrist-robot training intervention from the InMotion 3.0 Wrist robot, for 1 hour/day, 3 day/week, for a total of 18 training sessions. After 6 weeks of robotic training there was no significant changes in upper limb spasticity as assessed by the MAS in the right trained arm (p=0.43) or left untrained arm following training (p=0.34).

Hydrotherapy

Kesiktas et al. (2004) employed an experimental non-RCT design to test the effectiveness of a water-based exercise (i.e., hydrotherapy) program in reducing spasticity in a group of individuals (n=10) with complete and incomplete paraplegia and tetraplegia. Subjects were matched within a treatment group (i.e., hydrotherapy + conventional rehabilitation) versus a control group (conventional rehabilitation only) on the basis of age, gender, time post-injury, injury level and severity, spasticity (Ashworth) and function (Functional Independence Measure FIM). This study produced consistent results across all spasticity-related measures with spasticity reductions evident following the 10-week hydrotherapy treatment program for both AS scores and the Penn Spasm Severity scores. The control group also showed significant spasticity reductions relative to baseline with these measures but not to the same degree. In addition to these measures, dosages of oral baclofen were significantly reduced for those receiving hydrotherapy versus conventional rehabilitation only (i.e., >50%) and the hydrotherapy treated group made much greater FIM gains than did the control group. These latter results may reflect the deleterious effect that high baclofen doses can have on motor and cognitive function and the benefits of reduced spasticity on motor function. Kesiktas et al. (2004) did not indicate how soon after the final intervention the measures were taken so there is no indication of how long the beneficial effect might have been maintained.

Resistance Training

Although unblinded study participants perceived that strength training of partially paralyzed muscles improved their strength and function, the clinically measured effect on spasticity (and strength) was inconclusive with respect to clinically meaningful changes as measured by the Ashworth (and maximal voluntary isometric strength). Importantly though, strength training did not have a deleterious effect on spasticity (or strength).

Combination Therapy

Combination therapies are intended to leverage simultaneous targeting of more than a single type of neural circuitry during rehabilitation training. Martinez et al (2018; level 2 evidence), in a small level 2 crossover trial, were not able to show significant differences between multimodal training and robotic treadmill training for spasticity as assessed with the SCI-SET (and lower extremity strength and reflexes and ambulation and pain). The control intervention consisted of 48 sessions of robotic treadmill training at increasing speeds and decreasing body-weight support to reach a predefined gait pattern and was compared to the control intervention augmented with simultaneous balance and skilled upper extremity exercises (i.e. multimodal intervention). Participants were assigned to start with treadmill only or multimodal training and after a washout period of 6 weeks, continued with the comparison intervention. Two of 9 participants actually showed an increase in spasticity after multimodal training while 4 of 9 showed a decrease after the control intervention. Three and 5 showed no change, respectively. These less than clear results may have been the result of only 43% (9/21) or participants completing both arms of the trial.

Physical and electroceutic neuromodulatory methods are sought as an alternative to pharmacological control of spasticity due to the avoidance of deleterious side effects accompanying drug treatments. Estes et al 2017 (level 2 RCT) systematically tested 4 non-pharmacological approaches against a sham-control to achieve spasticity reduction in the lower extremeties as quantified by the pendulum test. Stretching (hip/knee/ankle flexors/extensors), cyclic passive movement ( through a treadmill-mounted robotic gait orthosis), transcutaneous spinal cord stimulation ( using biphasis stimulation at T11/12 and umbilicus), and transcranial direct current stimulation (with anode 1cm anterior to the vertex and cathode over inion) while the sham-control consisted of a brief ramp-up/-down of knee/ankle stimulation with the leg extended and participant in the reclined position. Each participant was randomized to receive a different order of the 4 interventions and sham (all single sessions only), after 48 hours washout between sessions. Continuous passive motion and transcutaneous spinal cord stimulation were shown to be viable non-pharmacological treatments for induction of prolonged periods (45 minutes) of spasticity reduction. For immediate and only short-term spasticity reduction, stretching was the most effective compared to sham. The sham-control condition confirmed that spasticity is problematic with increased immobility. Further investigations of dosing and timing would be necessary to maximize efficacy for these alternative anti-spasticity treatments.

Controlling for confounding variations in overall body condition is a factor to be considered when assessing efficacy of novel interventions such as pharmacological and cellular therapies. To understand the effects of various rehabilitation therapies without the addition of novel interventions, Gant et al (2018; level 4 evidence)) utilized a 12-week training program for participants with chronic thoracic level motor-complete participants, to deliver body-weight-supported treatmill training for locomotion, circuit resistance training for upper body conditioning, FES for activation of sublesional muscles and wheelchair skills training for overall mobility. Without the addition of any novel intervention, upper extremity strength improved for all 8 participants and some also experienced improved function that was likely a result of the improved strength. However, no improvements led to a change in neurological function and changes to pain and spasticity were highly variable between participants. Obviously, a larger study is required to validate these findings in a generalizable way but the current small trial is an indication of the importance of balancing, standardizing and documenting rehabilitation therapies whether additional novel interventions are included when attributing functional recovery to the intervention under study. In this study, spasticity (assessed with SCATS) was not consistently influenced by this 12-week multi-modal training program.

Mazzoleri et al (2017; level 4 evidence) investigated the effect of integrated gait training (20 sessions of functional electrical stimulation cycling followed by 20 sessions of overground robotic exoskeleton training) on spasticity (and patient-robot interaction). Spasticity was assessed with the MAS, numerical rating scale and PSFS. Spasticity was significantly reduced after the first phase of FES based training (MAS; p<0.05) with a further decrease after the second phase of robotic exoskeleton training (MAS and NRS; p<0.05 for both). The effects on spasticity also likely contributed to improved gait parameters after overground robot-assisted gait training (significant increase of standing time and number of steps). Although the anti-spasticity effect reported here conflicts with results of other combination therapy studies (Martinez et al 2019, Estes et al 2017, Gant et al 2018), the particular combination and intensity of integrated gait training may be key to the differing results.

Robot-Assisted

There is level 1b evidence from two RCTs (Fang et al. 2015; Mirbagheri et al. 2015) robot-assisted exercise appears to decrease all components of spasticity (isometric torque, reflex and intrinsic stiffness).

Functional Electrical Stimulation

There is level 4 evidence that single bouts of FES-assisted cycling ergometry, with a single level 2 study also showing that similar passive cycling movements are effective in reducing spasticity over the short-term although FES is more effective than passive movement.

There is level 1 evidence from 1 study, with conflicting evidence across two level 4 evidence studies, that show FES cycling decreases spasticity over the long-term.

There is level 4 evidence from three studies that a program of FES-assisted walking acts to reduce ankle spasticity in the short-term (i.e., £ 24 hours), however, a level 2 study showed no reduction across several lower limb muscles when considering an overall sustained effect.

There is no evidence to describe the optimal length and time course of FES-assisted walking for reducing spasticity.

Effects of Standing

There is level 2 evidence (from one prospective controlled trial; Sadeghi et al. 2016) that dynamic and static standing training does not reduce spasticity.

Body Weight Support Treadmill Training versus Tilt Table Standing

There is level 2 evidence (from one RCT; Manella & Field-Fote 2013) that electrical stimulation treadmill training and LOKOMAT robotic-assisted training decreases ankle clonus.

There is level 4 evidence (from one pre-post study; Adams et al. 2011) that use of tilt-table standing decreases extensor spasms and body-weight support treadmill training results in a reduction in passive resistance to movement and flexor spasms.

Dynamic Standing

There was level 4 evidence (from one pre-post study; Boutilier et al. 2012) that showed use of a Segway device for dynamic standing results in a reduction of spasticity.

Exoskeleton

There is conflicting level 4 evidence (from two case series; Kressler et al. 2014; Del-Ama et al. 2014) that use of an exoskeleton walking device results in a reduction in spasticity.

Upper Limb

There is level 4 evidence (from one pre-post study; Cortes et al. 2013) that use of robotic training of the wrist does not improve upper limb spasticity.

Hydrotherapy

There is level 4 evidence (from one pre-post study; Kesiktas et al. 2004) that hydrotherapy is not more effective in producing a short-term reduction in spasticity than conventional rehabilitation alone.

Resistance Training

Resistance training is not deleterious but does not decrease spasticity as evidenced by one level 1b RCT (Bye et al 2017).

Combination Therapy

There is level 2 evidence (from 2 RCTs; Martinez et al 2018, Estes et al 2017, further supported by 1 small level 4 pre-post study by Gant et al 2018)) that combination therapies do not consistently reduce spasticity. This is slightly challenged by level 4 evidence (small pre-post, Mazzoleri et al 2017) that FES cycling followed by robotic exoskeleton training may reduce spasticity.

Active exercise interventions such as hydrotherapy, FES-assisted cycling and walking and robot-assisted exercise (including specific exercises combined) may produce short-term reductions in spasticity.