Meythaler et al. (1996)

USA

RCT

PEDro=7

N=11

Population: TBI=10, Anoxia=1; Mean Age=25yr; Gender: Male=9, Female=2.

Intervention: Patients with chronic spastic hypertonia received either a bolus injection of intrathecal baclofen (50µg) or placebo (normal saline). Crossover occurred a minimum of 48hr later. Assessment at 1, 2, 4, and 6hr post injection.

Outcome Measure: Ashworth Scale (AS), Spasm Score, Deep Tendon Reflexes.

1.       For the lower extremity, after baclofen injection, AS scores decreased by a mean of 2 points (p=0.0033), spasm scores decreased by a mean of 2.1 points (p=0.0032), and reflex scores by 2.3 points (p=0.0032) at 4h.

2.       For the upper extremity, after baclofen injection, AS scores decreased by a mean of 1.4points (p=0.0033), spasm scores by a mean of 1.2points (p=0.0070), and reflex scores by 1.0points (p=0.0111) at 4h.

3.       No significant within-group differences were shown for placebo. Between group differences were significant for all measures for both lower and upper extremity (p≤0.0272).

Wang et al. (2016)

Singapore

Case Series

N_Initial=6, N_Final=5

Population: TBI=5, Encephalopathy=1; Mean Age=31.6yr; Gender: Male=3, Female=2; Mean Time Post Injury=39.4mo.

Intervention: A retrospective review of patients that were recruited to undergo surgical implantation of an intrathecal baclofen (ITB) pump. After implantation patients received daily physical therapy. Upon discharge patients continued to receive regular outpatient rehabilitation therapies for 3mo, and ITB pump refills and monitoring by the neurosurgical team for 3-4 mo. Outpatient follow-up was 3-6mo.

Outcome Measure: Modified Ashworth Scale (MAS).

Chow et al. (2015)

Canada

Pre-Post

N=19

Population: TBI=11, Stroke=8; Mean Age=34.2yr; Gender: Male=9, Female=10; Mean Time Post Injury=48.7mo.

Intervention: All patients underwent a 50-µg intrathecal baclofen (ITB) bolus injection via lumbar puncture. Patients were evaluated at baseline, 2hr, 4hr, and 6hr post injection.

Outcome Measure: Gait speed, stride length, cadence, stance duration, ankle range of motion (ROM)-stance & swing, peak medial gastrocnemius (MG) lengthening velocity, average Ashworth Score, Plantar Flexors Ashworth Score, Electromyography-lengthening Velocity (EMG-LV), Coactivation Duration (CoD),  Coactivation Index (CI).

1.       There was no significant difference in gait speed, stride length, cadence, or stance duration across evaluation points.

2.       Ankle ROM in the more-affected leg during stance phase was significantly increased from baseline to 6hr (p=0.009); however, was not significantly different during swing phase.

3.       Peak MG lengthening velocity significantly increased from baseline to 4hr in the less-affected leg (p=0.005) and to 6hr in both legs (p≤0.01).

4.       Average Ashworth Score and plantar flexors Ashworth scores were significantly different across all time posts in the more-affected leg only (p<0.001).

5.       Compared with baseline, both frequency (p=0.02) and average gain (p=0.007) of EMG-LV were significantly lower at 2 hr post but did not reach the significance at 4hr and 6hr post (p≤0.040).

6.       Slope parameters of EMG-LV in the less-affected leg did not change over time (p≥0.129).

7.       CoD significantly decreased over time in the more affected leg during all phases of gait (p≤0.013); and CoI did not significantly change over time in either leg (p>0.107).

Margetis et al. (2014)

Greece

Pre-Post

N=8

Population: TBI=6, Hydrocephalus=1, Cardiac Arrest=1; Mean Age=31.5yr; Gender: Male=8, Female=0; Mean Time Post Injury=37.25mo.

Intervention: Patients who were resistant to oral spasticity treatments received an implanted intrathecal baclofen pump. Mean follow-up period was 38.4mo.

Outcome Measure: Modified Ashworth Scale.

1.       All patients showed improvement in their spasticity scores; mean Modified Ashworth Scale scores were 3.375 pre- and 1.125 post-intervention.

Posteraro et al. (2013)

Italy

Pre-Post

N=12

Population: TBI=8, Hemorrhage=2, Anoxia=2; Mean Age=36yr; Gender: Male=9, Female=3; Time Post Injury Range=31-150d.

Intervention: Patients not experiencing reductions in spasticity following initial interventions with oral baclofen received intrathecal baclofen (ITB). The initial dosage was 50 or 100mcg depending on the severity of the impairment and was increased by 10% every 3d until the maximum dosage of 800 mcg was achieved. Assessments occurred before the implant, and at 3mo and 12mo follow-ups.

Outcome Measure: Modified Ashworth Scale (MAS), Spasm Frequency Scale (SFS), Disability Rating Scale (DRS), Level of Cognitive Functioning (LCF).

1.      Mean ITB dose for participants was 380mcg.

2.       Six patients received ITB within 3mo of injury (early); 6 patients received ITB between 3 and 6mo post injury (late).

3.       At 3mo, both spasticity and spasms significantly decreased compared to the baseline, based on MAS and SFS scores (p<0.001 and p<0.002, respectively).

4.       At 3mo, improvements in DRS and LCF were seen (p<0.001 and p=0.002, respectively).

5.       At 12mo (n=5) all patients demonstrated further improvements in spasticity and spasms, but this was non-significant compared to results at 3 mo.

6.       There were no differences in global outcomes (DRS and LCF) between patients in early ITB initiation group and those in late ITB initiation group.

Hoarau et al. (2012a)

France

Post-Test

N=43

Population: TBI; Mean Age=23.3yr; Gender: Male=33, Female=10; Mean GCS score=4.6.

Intervention: After initial injury, participants who were started on Intrathecal Baclofen Therapy (IBT) to treat dysautonomia and hypertonia and were included for evaluation of long-term outcomes (mean 10±0.6yr post implantation).

Outcome Measure: Coma Recovery Scale-Revised (CRS-R), Modified Ashworth Scale (MAS), Barthel Index (BI).

1.       At follow-up, 9 participants had died, 13 were severely disabled or in an unresponsive wakefulness syndrome and 21 had a good recovery of consciousness.

2.       Mean CRS-R score was 18.9 (Range 1-23), mean BI score was 50.1 (Range 0-100), 34.9% were living at home, and mean MAS for upper limb was 1.6 (Range 0-4).

3.       Most of the participants who had a positive recovery received IBT later than the other participants.

4.       Complications occurred in 62.8% of patients; the most common being operative site infections (20.9%) and overdoses with profound flaccidity, sedation and vomiting (16.3%).

Horn et al. (2010)

USA

Pre-Post

N=28

Population: TBI=12, Hypoxic Encephalopathy=3, Stroke=13; Mean Age=35yr; Gender: Male=12, Female=16; Mean Time Post Injury=45mo.

Intervention: The subjects received a 50µg bolus of baclofen injected into the lumbar intrathecal space.

Outcome Measure: Ashworth Scale, Video-based Motion Analysis Program.

1.       The range of motion (ROM) increased in the ankle on both the more involved side (13±6 versus 15±7, p=0.008) and the less involved side (22±8 versus 24±8, p=0.031) from baseline to post-injection.

2.       ROM improvement occurred most often at 4 and 6hr after injection (p<0.05).

3.       There was a significant correlation between the magnitude of change in ROM at the time of peak response and the magnitude of gait speed change (r=0.1, p<0.001).

4.       Significant reductions in Ashworth scores compared to baseline (2.0±0.5) at 2hr (1.6±0.4), 4 hr (1.4±0.4) and 6 hr (1.3±0.3) post-injection (all p<0.001).

Stokic et al. (2005)

USA

Case Series

N=30

Population: TBI=17, Anoxic=4, Stroke=9; Mean Age=31yr; Gender: Male=17, Female=13; Mean Time Post Injury=3yr.

Intervention: Participants received a single 50µg intrathecal baclofen bolus injection via a lumbar puncture.

Outcome Measure: Ashworth Scale, H-Reflex from Soleus Muscle, F waves from Abductor Hallucis in Supine Position.

1.       Ashworth score on the more involved side significantly decreased between baseline (2.4±0.7) and 4 (1.5±0.6) and 6 hr (1.4±0.6) post-injection (p<0.001).

2.       Maximal individual change in Ashworth scores ranged from 0 to 2.6 points (mean 1.0±0.7).

3.        H/M ratio significantly decreased bilaterally (p<0.001).

4.       F-wave persistence significantly decreased on the more involved side (p<0.05) with no change in F/M ratio.

Francisco et al. (2005)

USA

Case Series

N=14

Population: Anoxic Encephalopathy=6, TBI=5, Stroke=3; Mean Age=35.9yr; Gender: Male=6, Female=8.

Intervention: Patients were surgically fitted with an infusion pump for continuous intrathecal baclofen delivery. This took place a mean of 5.62mo (range 2-12mo) post injury. Follow up occurred at a mean of 13.9mo post pump implantation.

Outcome Measure: Modified Ashworth Scale (MAS), Disability Rating Scale (DRS).

1.       Participants received a mean daily intrathecal baclofen dose of 591.5µg (93-2000.2µg).

2.       From baseline to follow-up, the mean decrease in MAS scores for upper extremities was 1±1.4 (p<0.020) and lower extremities was 2.1±1.4 (p<0.001).

3.       The changes in DRS scores were not significant.

Horn et al. (2005)

USA

Pre-Post

N=28

Population: TBI=12, Stroke=13, Hypoxic Encephalopathy=3; Mean Age=35yr; Gender: Male=12, Female=16; Mean Time Post Injury=45mo.

Intervention: Subjects received a single 50µg intrathecal baclofen bolus injection via lumbar puncture.

Outcome Measure: Walking Performance, Ashworth scores.

1.       Mean change in hip and knee range of motion (ROM) during gait was less than ±2° after injection.

2.       ROM in ankles increased from baseline to post-injection on both the more involved (13° versus 15°, p<0.010) and less involved side (22° versus 24°, p<0.050).

3.       For all joints (n=168), ROM significantly improved in 42%, significantly worsened in 34%, and did not change in 24%.

4.       Significant reductions in Ashworth scores compared to baseline (2.0±0.5) at 2hr (1.6±0.4), 4hr (1.4±0.4) and 6hr (1.3±0.3) post-injection (all p<0.001).

Dario et al. (2002)

Italy

Pre-Post

N=14

Population: TBI=6, Anoxic ABI=8; Mean Age=38.8yr; Gender: Male=10, Female=4; Mean Time Post Injury=36.7mo.

Intervention: Patients received continuous intrathecal baclofen infusions through the implantation of a subcutaneous pump. Mean length of spasticity was 36.7mo post injury.

Outcome Measure: Ashworth Scale (AS), Spasm Frequency Scale (SFS).

1.       Between pre-operative through the last follow up, there was a significant decrease in AS scores in both lower (4.3±0.5 versus 2.7±0.7) and upper (4.1±0.8 versus 2.3±0.9) extremities (both p<0.05).

2.       Significant reduction in SFS scores was found between preoperative and postoperative values (2.5±0.5 versus 0.4±0.6, p<0.001).

3.       Mean daily dose of baclofen was 305µg (range 90-510µg).

Francois (2001)

France

Case Series

N=4

Population: TBI; Mean Age=19.5yr; Gender: Male=1, Female=2, Unknown=1; Mean GCS=3.5.

Intervention: Patients received intrathecal baclofen infusions within 1mo following injury onset.

Outcome Measure: Ashworth scores, Frequency and Intensity of Autonomic Disorders.

1.       Reductions in spasticity, and lower limb Ashworth scores at 6mo post intervention were reported in three of the four cases.

In the last case, a substantial reduction in autonomic disorders and spasticity enabling passive physiotherapy was reported.

Meythaler et al. (1999b)

USA

Pre-Post

N=17

Population: ABI; Mean Age=29yr; Gender: Male=14, Female=3.

Intervention: Patients with spasticity and/ or dystonia were surgically fitted with an infusion pump into the lower abdominal wall for continuous administration of intrathecal baclofen (100µg/day). Patients were assessed at 1yr.

Outcome Measure: Ashworth Rigidity Scale (ARS), Spasm Frequency Scale, Deep Tendon Reflex Score.

1.       One year of intrathecal baclofen treatment (average dose: 302ug/d) resulted in a decrease in ARS (mean 2.2 points), spasm frequency (mean 1.6 points), and reflex scores (mean 2.4 points) for the lower extremity (all p<0.0001)

2.       For the upper extremity, the ARS, spasm frequency, and reflex scores decreased by a mean of 1.4, 1.0, and 1.2 points respectively (all p<0.0001).

3.       No cognitive side effects were observed after 1yr.

Meythaler et al. (1999a)

USA

Pre-Post

N=6

Population: TBI=3, Stroke=3; Mean Age=50yr; Gender: Male=2, Female=4.

Intervention: Patients were surgically fitted with a programmable infusion pump into the lower abdominal wall for continuous administration of baclofen using the same methodology as Meythaler et al. (1997).

Outcome Measure: Ashworth Rigidity Scale, Spasm Frequency Scale, Deep Tendon Reflex scores.

1.       Lower extremities showed a significant reduction in Ashworth scores (p<0.0001), affected lower limb reflex score (p=0.021), normal side (p=0.0051), but not significant changes in affected lower limb spasm score (p=0.500).

2.       Upper extremities showed significant reductions in Ashworth scores on affected side (p=0.0002) but were not significant for Biceps Reflex score (affected and normal: p=0.109 and p=0.068), or spasm score (affected:  p=0.1797).

3.       No patients complained of subjective weakness on the normal side.

Meythaler et al. (1997)

USA

Pre-Post

N=12

Population: TBI=9, ABI=3; Mean Age=28yr; Gender: Male=11, Female=1.

Intervention: Patients received continuous intrathecal baclofen delivery for 3mo via an implanted infusion pump-catheter system.

Outcome Measure: Ashworth Rigidity Scale, Spasm Frequency Score, Deep Tendon Reflex Score.

1.       For the lower extremity, Ashworth Scale Scores decreased by a mean of 1.4 points, spasm frequency by 1.5, and reflex scores by 2.5 (all p<0.0001).

2.       For the upper extremity, the mean decrease in scores was 1.4 points for the Ashworth Scale (p=0.003), 1.2 for spasm frequency (p=0.007) and 1.0 for reflex (p=0.011).

Becker et al. (1997)

Germany

Case Series

N=18

Population: TBI=9, Hypoxic Brain Injury=9; Mean Age=41yr; Gender: Male=13, Female=6; Mean Time Post Injury=11.6mo.

Intervention: Patients received continuous intrathecal baclofen infusion.

Outcome Measure: Ashworth Scale, Spasm Frequency Scale.

1.       In all patients spasticity was reduced.

2.       Mean Ashworth scores reduced from 4.5 to 2.33, and the mean spasm frequency scores decreased from 2.16 to 0.94.

3.       Reduction in spasticity led to a reduction in pain.