Botulinum toxin A injection for post-stroke upper limb spasticity and rehabilitation practices from centers across Asian countries.

Purpose: Describe real-life practice and outcomes in the management of post-stroke upper limb spasticity with botulinum toxin A (BoNT-A) in Asian settings. Methods: Subgroup analysis of a prospective, observational study (NCT01020500) of adult patients (≥18 years) with post-stroke upper limb spasticity presenting for routine spasticity management, including treatment with BoNT-A. The primary outcome was goal attainment as assessed using goal-attainment scaling (GAS). Patients baseline clinical characteristics and BoNT-A injection parameters are also described. Results: Overall, 51 patients from Asia were enrolled. Rates of comorbid cognitive and emotional problems were relatively low. Patients tended to have more severe distal limb spasticity and to prioritize active over passive function goals. Most (94.1%) patients in the subgroup were treated with abobotulinumtoxinA. For these patients, the median total dose was 500 units, and the most frequently injected muscles were the biceps brachii (83.3%), flexor carpi radialis (72.9%), and flexor digitorum profundus (66.7%). Overall, 74.5% achieved their primary goal and the mean GAS T score after one treatment cycle was 56.0 ± 13.0, with a change from baseline of 20.9 ± 14.3 (p < 0.001). The majority (96.1%) of Asian patients were rated as having improved. Conclusion: In the Asian treatment setting, BoNT-A demonstrated a clinically significant effect on goal attainment for the real-life management of upper limb spasticity following stroke.

Early AbobotulinumtoxinA (Dysport®) in Post-Stroke Adult Upper Limb Spasticity: ONTIME Pilot Study.

The ONTIME study investigated whether early post-stroke abobotulinumtoxinA injection delays appearance or progression of upper limb spasticity (ULS) symptoms. ONTIME (NCT02321436) was a 28-week, exploratory, double-blind, randomized, placebo-controlled study of abobotulinumtoxinA 500U in patients with ULS (Modified Ashworth Scale [MAS] score ≥ 2) 2⁻12 weeks post-stroke. Patients were either symptomatic or asymptomatic (only increased MAS) at baseline. Primary efficacy outcome measure: time between injection and visit at which re-injection criteria were met (MAS ≥ 2 and ≥1, sign of symptomatic spasticity: pain, involuntary movements, impaired active or passive function). Forty-two patients were randomized (abobotulinumtoxinA 500U: n = 28; placebo: n = 14) with median 5.86 weeks since stroke. Median time to reach re-injection criteria was significantly longer for abobotulinumtoxinA (156 days) than placebo (32 days; log-rank: p = 0.0176; Wilcoxon: p = 0.0480). Eleven (39.3%) patients receiving abobotulinumtoxinA did not require re-injection for ≥28 weeks versus two (14.3%) in placebo group. In this exploratory study, early abobotulinumtoxinA treatment significantly delayed time to reach re-injection criteria compared with placebo in patients with post-stroke ULS. These findings suggest an optimal time for post-stroke spasticity management and help determine the design and sample sizes for larger confirmatory studies.

Effect of early use of AbobotulinumtoxinA after stroke on spasticity progression: Protocol for a randomised controlled pilot study in adult subjects with moderate to severe upper limb spasticity (ONTIME pilot).

INTRODUCTION: Approximately 15 million people suffer a stroke annually, up to 40% of which may develop spasticity, which can result in impaired limb function, pain and associated involuntary movements affecting motor control.Robust clinical data on spasticity progression, associated symptoms development and functional impairment is scarce. Additionally, maximal duration of muscle tone reduction following botulinum toxin type A (BoNT-A) injections remains undetermined. The ONTIME pilot study aims to explore these issues and evaluate whether abobotulinumtoxinA 500 U (Dysport®; Ipsen) administered intramuscularly within 12 weeks following stroke delays the appearance or progression of symptomatic (disabling) upper limb spasticity (ULS). METHODS: ONTIME is a 28-week, phase 4, randomised, double-blind, placebo-controlled, exploratory pilot study initiated at four centres across Malaysia, the Philippines, Singapore and Thailand. Subjects (n = 42) with moderate to severe ULS (modified Ashworth scale [MAS] score ≥2) in elbow flexors or pronators, wrist flexors, or finger flexors will be recruited. Subjects will be randomised 2:1 to abobotulinumtoxinA 500 U or placebo (single dose 2-12 weeks after first-ever stroke).Primary efficacy will be measured by time between initial injection and visit at which reinjection criteria (MAS score ≥2 in the primary targeted muscle group and appearance or reappearance of symptomatic ULS) are met. Follow-up visits will be 4-weekly to a maximum of 28 weeks. DISCUSSION: This pilot study will facilitate the design and sample size calculation of further confirmatory studies, and is expected to provide insights into the optimal management of post-stroke patients, including timing of BoNT-A therapy and follow-up duration.

Feasibility of video clip analysis on effect of botulinum toxin-A injection for post-stroke upper limb spasticity.

Existing functional evaluation tools do not accurately reveal the improved function following botulinum toxin A (BTX-A) injection for post-stroke upper limb spasticity. With the aim of developing an alternate method of measuring functional improvement following BTX-A injection, this study tested the feasibility, validity and reliability of video clip analysis performed by the clinicians. Seventy-nine patients administered BTX-A due to post-stroke upper limb spasticity, were retrospectively evaluated using video clip analysis. Pre- and post-injection video clips recorded at 1-month intervals were randomly allocated and sent to three blinded physician evaluators who were asked to choose the one that seemed more improved in terms of hand motion and associated upper limb reaction during gait. The three physicians chose the post-injection video clip as depicting improved hand motion (82.3%, 79.7%, and 72.2%) and associated upper limb reaction during gait (73.4%, 70.9%, and 70.9%). Kappa and intraclass correlation coefficient as a measure of interrater reliability among the three physicians was 0.86 and 0.79 for the hand, and 0.92 and 0.92 for associated upper limb reaction during gait, respectively. The percent overall agreement of the physicians was 78.1% and 71.7% for hand function and associated upper limb reaction, respectively. Retrospective pre- and post-BTX-A injection video clip analyses is a clinically feasible alternative method to evaluate the improvement following BTX-A injection for post-stroke upper limb spasticity, especially in busy clinical practice setting.

Surgical outcomes of microsurgical selective peripheral neurotomy for intractable limb spasticity.

BACKGROUND: The authors frequently employed selective peripheral neurotomy (SPN) as the primary treatment of severe intractable focal and multifocal spastic hypertonia. We occasionally operated SPN in diffuse spastic disorders. OBJECTIVE: To study surgical outcome of SPN in terms of severity of spasticity and functional condition. METHODS: Patients harboring refractory harmful spasticity of various origins were enrolled into the present study. They were clinically evaluated by using the Modified Ashworth Scale (MAS), passive range of motion (PROM) and functional status. These variables were compared between pre- and postsurgery by using the paired t test and the Wilcoxon signed-rank matched-pairs test. RESULTS: One hundred and forty-one SPNs were accomplished in 33 patients. Overall mean pre- and postoperative MAS and PROM were 3.0 and 0.7 (p < 0.001) and 78.3 and 102.3° (p < 0.001), respectively. Analysis of individual SPN subgroups also demonstrated statistically significant improvement of both parameters. Furthermore, we found significant gait improvement among 10 ambulatory subjects. Nine bed-bound cases attained significant enhancement of sitting competency and ambulatory condition. CONCLUSION: SPN is an efficacious neurosurgical intervention in the treatment of spasticity. It is apparently beneficial in the reduction of spasticity, amelioration of functional status, facilitation of patient care and prevention of long-term musculoskeletal sequelae.

Utilization of intraoperative electromyography for selecting targeted fascicles and determining the degree of fascicular resection in selective tibial neurotomy for ankle spasticity.

BACKGROUND: Selective tibial neurotomy (STN) is an effective neurosurgical intervention for treating ankle spasticity. The authors use intraoperative electromyography (EMG) for selecting targeted fascicles and determining the degree of fascicular resection in STN. This study reports surgical techniques and outcomes of the operation. METHODS: Participants who underwent STN with utilization of intraoperative EMG were recruited. Modified Ashworth Scale (MAS), passive range of motion (PROM) of the ankle in plantar flexion and dorsiflexion, Massachusetts General Hospital Functional Ambulatory Classification (MGHFAC) and ability to attain full plantigrade stance were assessed pre- and postoperatively. RESULTS: Twenty-one STNs were performed in 15 patients. The mean pre- and postoperative MAS and PROM were 2.8 and 0.4 (p < 0.001), 39.5(o) and 66.0(o) (p < 0.001), respectively. The mean level of MGHFAC was improved from 3.3 preoperatively to 4.9 postoperatively (p < 0.01). Six non-ambulators had significant amelioration in MGHFAC level. Postoperatively, 19 of 21 lower limbs achieved full plantigrade, and 6 patients could perform selective voluntary motor control of the ankle. CONCLUSION: STN is an effective procedure for spastic ankle in well-selected cases. Intraoperative EMG helps in selection of targeted fascicles, increases objectivity in neurotomy and prevents excessive denervation.

Current considerations for the management of musculoskeletal pain in Asian countries: a special focus on cyclooxygenase-2 inhibitors and non-steroid anti-inflammation drugs.

Chronic pain is a complex problem that eludes precise definition and can be clinically difficult to diagnose and challenging to treat. In the Asia-Pacific region, prevalence estimates that chronic pain ranges from 12% to 45% of the population, with musculoskeletal, rheumatic or osteoarthritis pain making up the majority of the disease burden. Implementation of current management guidelines into routine clinical practice has been challenging and as a result, patients with musculoskeletal pain are often poorly managed. For these reasons, a multidisciplinary Chronic Pain Advisory Board of leading physicians from various Asian countries was convened to explore ways to improve treatment and compliance, especially among patients with osteoarthritis and rheumatoid arthritis. We have identified a number of unmet therapeutic needs and prioritized initiatives with the potential to contribute toward a more integrated approach to chronic pain management. Key priorities included using evidence-based interventions as recommended by current guidelines, particularly those aspects pertinent to addressing treatment priorities in Asia (e.g., patient compliance), and the incorporation of cyclooxygenase-2 inhibitors and non-steroid anti-inflammation drugs into the management algorithms for osteoarthritis and rheumatoid arthritis. Treatment must be individualized for each patient based on efficacy, side-effect profile and drug accessibility. Further studies are required to examine head-to-head comparisons among analgesics, combinations of analgesics and long-term efficacy outcomes. Our increasing understanding of the problem combined with the promise of new therapy options offers hope for improved management of musculoskeletal pain in Asian countries.

Improvement of sitting ability and ambulation status after selective peripheral neurotomy of the sciatic hamstring nerve together with obturator branches for severe spasticity of the lower extremities.

BACKGROUND: The authors used selective peripheral neurotomy (SPN) on the sciatic and obturator nerves to restore the sitting posture and ambulation in bedridden patients suffering from severe proximal lower limb spasticity. OBJECTIVE: To study the surgical outcome of sciatic and obturator neurotomies. METHODS: All patients with refractory hamstring spasticity who encountered SPN on the hamstring nerve were recruited. Obturator neurotomy was undertaken in some individuals. The clinical assessment included modified Ashworth scale (MAS), passive range of motion (PROM), sitting competency and ambulatory condition. These parameters were compared between before and after the surgery by using the Wilcoxon signed-rank test. RESULTS: Among the sciatic neurotomy group (n = 15), the mean pre- and postoperative MAS and PROM were 3.3 and 0.8 (p < 0.01) and 78.3 and 121.7° (p < 0.01), respectively. Those measurements of the obturator nerve surgery group (n = 11) were 3.7 and 1.1 (p < 0.01) as well as 21.0 and 45.0° (p < 0.01), respectively. Seven and 8 of a total of 9 patients had statistically significant improvement in sitting ability (p = 0.016) and ambulation status (p < 0.01), respectively. CONCLUSION: Bedridden patients who suffer from severe proximal lower limb spasticity have an optimum to return to sitting and ambulate with a wheelchair after SPN of the sciatic and obturator nerves.

Botulinum toxin injection for hypertonicity of the upper extremity within 12 weeks after stroke: a randomized controlled trial.

BACKGROUND: Botulinum neurotoxin type A (BoNT-A) reduces upper-extremity poststroke spasticity when given 6 or more months after stroke. Effects on functional use of the arm and hand are less apparent. OBJECTIVE: To determine the effect and safety of very early use of BoNT-A for patients with upper-limb spasticity. METHODS: The Asia Botulinum Toxin-A Clinical Trial DESIGN: ed for Early Post-stroke Spasticity (ABCDE-S; NCT00234546) was a multicenter, randomized, placebo-controlled trial conducted in patients recruited within 2 -12 weeks of first-ever stroke. Participants with a Modified Ashworth Scale (MAS) score of 1+ or above received BoNT-A (Dysport) 500 U or placebo to one or more wrist and elbow mover muscles, plus unstructured rehabilitation. The primary outcome was the MAS score in the most affected joint 4 weeks after first injection. Follow-up was 24 weeks. RESULTS: A total of 163 patients were enrolled and assigned to placebo (n = 83) or BoNT-A (n = 80). Mean time since stroke was about 7 weeks. At 4 weeks postinjection, BoNT-A significantly improved MAS scores. Treatment effect-size estimates increased with higher baseline MAS scores from 0.45 (Q1) to 0.70 (Q3). MAS scores for all secondary end points improved with BoNT-A versus placebo at all time points (P < .0001, all visits). The Functional Motor Assessment Scale did not reveal clinically significant differences. No group differences in adverse events were found. Interpretation. BoNT-A 500 U can provide a sustained reduction in poststroke upper-limb spasticity when combined with rehabilitation in Asian patients who have mild-to-moderate hypertonicity and voluntary movement, within 2 -12 weeks of stroke. Functional use of the arm and hand was not affected.

Combined ablative neurosurgical procedures in a patient with mixed spastic and dystonic cerebral palsy.

BACKGROUND: Harmful generalized spasticity is an obstacle in rehabilitation and caregiving. Neurosurgical intervention is a therapeutic option for patients with severe spasticity who do not respond to nonoperative management. Currently, intrathecal baclofen therapy (ITB) is a good alternative treatment for such patients. However, the ITB device is costly and the intrathecal drug is not available in Thailand. CASE DESCRIPTION: We report a combined use of ablative neurosurgical procedures in a patient with severe generalized spasticity and disabling cervical dystonia (CD). The assembled operations including selective peripheral denervation for CD, microsurgical dorsal root entry zone lesion for upper limb spasticity, and selective dorsal rhizotomy for lower limb spasticity were conducted in a single session. Furthermore, recurrent spasticity of the upper extremities was subsequently treated by selective peripheral neurotomy. RESULTS: The spasticity and CD totally disappeared after all operations. The patient became able to sit and perform head turning. Additionally, we also found an improvement in swallowing and the voluntary movement of the lower limbs.