Mayer et al. (2008)

USA

RCT

PEDro=6

N=31

Population: TBI=21, Stroke=8, Hypoxic encephalopathy=2; Motor Point Group: Mean Age=37.9yr; Mean Time Post Injury=256.7 d. Distributed Group: Mean Age=34.7yr; Mean Time Post Injury=481.9yr.

Intervention: Patients with severe elbow flexor hypertonia received one of two interventions: the motor point injection technique (1 site biceps and 1 site brachioradialis), or the distributed quadrants technique (4 sites rectangularly configured – 2 biceps and 2 brachioradialis). Following two baseline measures, each elbow was randomized to receive injections of Botox. In total 90 units were given to patients in each group. However, the sites and injection techniques varied between the groups. Mean follow up was 23.5±4.4d.

Outcome Measure: The Ashworth Scale, Modified Tardieu Scale.

1.       The median decrease in Ashworth Scores after intervention was 1 point in both groups (p=0.53) and the Tardieu catch angle post intervention did not differ significantly between groups (p=0.31).

2.       Both groups showed significant improvement from baseline on all outcomes measured (all p<0.01); however, there were no between-group differences at 3wk.

3.       For both groups, a clinicophysiologic effect was observed at 3wk post-intervention.

Verplancke et al. (2005)

UK

RCT

PEDro=4

N=35

Population: TBI=20, Neurosurgery=11, Anoxia=4; Gender: Male=25, Female=10. Group 1 (n=11): Median Age=40yr; Mean Time Post Injury=9.3d, Mean Glasgow Coma Scale (GCS) score 4.3. Group 2 (n=12): Median Age=33.5yr; Mean Time Post Injury=13.25 days; Mean GCS score=4.7. Group 3 (n=12): Median Age=41.5yr; Mean Time Post Injury=10.6d; Mean GCS score=5.2.

Intervention:  Participants entered one of three groups: group 1 received a physical intervention (controls), group 2 received casting plus injections of saline (4 ml), and group 3 received casting with botulinum toxin (100 units per leg) into the gastrocnemius and soleus muscles. Patients were re-cast if a 10° change in dorsiflexion occurred.

Outcome Measure: Calf contracture, Modified Ashworth Scale (MAS), Passive Range of Motion.

1.       Eighty-eight percent of patients developed spasticity within 14 days of injury.

2.       Mean change in angle of passive ankle dorsiflexion was 4.59° in controls, 11.69° in group 2 and 13.59° in group 3.

3.       There were significant improvements in MAS scores in treated groups (group 2, p<0.03; group 3, p=0.04) but not controls (p>0.05).

Intiso et al. (2014)

Italy

Pre-Post

N=22

Population: ABI=16, Cerebral Palsy=6; Mean Age=38.1yr; Gender: Male=12, Female=10; Brain Injury: Mean Time Post Injury=3.8yr.

Intervention: Patients with severe spasticity of the upper and lower limbs received injections of onabotulinum toxin A (BoNT-A; up to 840 IU).

Outcome Measure: Modified Ashworth Scale (MAS), Glasgow Outcome Scale (GOS), Frenchay Arm Test (FAT), Barthel Index (BI), Visual Analog Scale, Visual Analogue Scale–Pain (VAS).

1.       Seventeen patients had spastic hemiparesis and 5 had paraparesis.

2.       A significant reduction in spasticity was seen at 4 and 16wk post intervention, shown by a decrease in mean MAS scores in the elbow, wrist, finger and hand (all p<0.05) and ankle (p<0.03).

3.       No significant improvements were seen on the GOS, BI, or FAT at 4 or 16 wk.

4.       A significant reduction in pain was seen from baseline (7.6±1.1) to 4 (3.5±0.7) and 16 wk (3.6±0.5) post intervention (p<0.001).

Clemenzi et al. (2012)

Italy

Pre-Post

N=21

Population: TBI=11, ABI=10; Mean Age=42.2yr; Gender: Male=16, Female=5; Median Time Post Injury=5yr; Severity: Severe.

Intervention: Patients received repeated injections of Botulinum Toxin Type A (maximum dose 600 U diluted in 50 ml^-1) followed by rehabilitation program that consisted of hand and/or foot adhesive taping maintained for 7d and checked daily.

Outcome Measure: Barthel Index (BI), Modified Ashworth Score (MAS),  Visual Analogue Scale- pain (VAS).

1.       Spasticity was in the lower limb in 33.3% of patients, upper limb in 9.5%, and both in 57.1%.

2.       MAS lowered at the follow up, and improvement in spasticity was seen at the second and last injection (T3) time points compared to baseline (p<0.0001).

3.       BI significantly improved at follow up (T3) in relation to initial scores (p=0.0001).

4.       VAS score improved at the end of the second injection, a reduction in score was noted after each injection.

5.       Greater improvement on BI was correlated to a shorter period between ABI onset and first injection (p<0.0001), the same effect was not discovered for MAS or VAS.

Fock et al. (2004)

Australia

Pre-Post

N=7

Population: TBI; Mean Age=29.9 yr; Gender: Male=5, Female=2; Mean Time Post Injury=14 mo.

Intervention: Subjects received botulinum toxin A (total of 300 U) into the lower extremities. Muscles targeted for injections included the gastrocnemius and soleus. The tibialis posterior was also injected in some subjects.

Outcome Measure: Modified Ashworth Scale (MAS) scores, walking speed, cadence, stride length, peak ankle dorsiflexion angle during walking over a 10 m level track, and ankle range of motion.

1.       12 wk post-injection, there were significant improvements in walking speed, stride length, cadence, dorsiflexion on contact with the ground and passive dorsiflexion in supine position (all p<0.03).

2.       None of these measures showed significant changes at 2 wk post-injection.

3.       There were no significant changes in dorsiflexion at mid-stance, active dorsiflexion in supine position, and MAS scores at 2 or 12 wk post-injection.

4.       At 12wk, chronic patients had a mean improvement in ankle dorsiflexion range of 19% (3.3°); those who had their injury sooner had a mean range improvement of 41% (7.4°).

Yablon et al. (1996)

USA

Case Series

N=21

Population: TBI; Mean Age=28.2yr; Gender: Male=12, Female=9; Mean Time Post Injury: Acute Group=142.7d, Chronic Group=89.5mo.

Intervention: Subjects received Botulinum Toxin A injections (20-40 units per muscle) into the upper extremity. Targeted muscles included: the flexor carpi radialis, flexor carpi ulnaris, flexor digitorum profundus, and flexor digitorum superficialis. Some patients also received injections into the biceps and brachialis due to coexisting spasticity in the elbow flexors. After injection, patients received therapeutic modalities as needed. Patients were grouped based on time between injury and injection: acute (<12mo; n=9) or chronic (≥12mo; n=12).

Outcome Measure: Modified Ashworth Scale (MAS), passive ROM at the wrist.

1.       The acute group showed significant improvements in ROM (wrist extension improved by a mean of 42.9±24.7°, p=0.001) and spasticity severity (mean MAS improvement 1.5±0.5 points, p=0.01).

2.        All patients in the acute group showed an improvement in spasticity and no patient worsened or remained unchanged.

3.       The chronic group showed significant improvements in ROM (wrist extension improved by a mean of 36.2±21.7°, p<0.001) and spasticity severity (mean MAS improvement 1.47±0.9 points, p=0.002).