Efficacy and safety of onabotulinumtoxinA with standardized physiotherapy for the treatment of pediatric lower limb spasticity: A randomized, placebo-controlled, phase III clinical trial.

BACKGROUND: Spasticity is common in cerebral palsy and can result in pain and diminished health-related quality of life. OBJECTIVE: To evaluate the safety and efficacy of onabotulinumtoxinA for lower limb spasticity treatment in children with cerebral palsy. METHODS: In this registrational phase 3, multinational, randomized, double-blind, placebo-controlled trial (NCT01603628), children (2-< 17 years) with cerebral palsy and ankle spasticity (Modified Ashworth Scale-Bohannon [MAS] score≥2) were randomized 1 : 1 : 1 to standardized physical therapy and onabotulinumtoxinA (4 or 8 U/kg), or placebo. Primary endpoint was average change from baseline at weeks 4 and 6 in MAS ankle score. Secondary endpoints included the Modified Tardieu Scale (MTS) and Global Attainment Scale (GAS). RESULTS: 381 participants were randomized. MAS scores averaged at weeks 4 and 6 were significantly reduced with both onabotulinumtoxinA doses (8 U/kg: -1.06, p = 0.010; 4 U/kg: -1.01, p = 0.033) versus placebo (-0.8). Significant improvements in average dynamic component of spasticity, measured by MTS, and in function, measured by GAS, were observed at several time points with both onabotulinumtoxinA doses versus placebo. Most adverse events were mild or moderate. CONCLUSIONS: OnabotulinumtoxinA was well tolerated and effective in reducing lower limb spasticity and improving functional outcomes versus placebo in children.

Sleep and physical activity patterns in adults and children with Bardet-Biedl syndrome.

BACKGROUND: Overweight and obesity are common features of the rare disease Bardet-Biedl syndrome (BBS). Sleep and physical activity are behaviors that might impact overweight and obesity and thus may play a key role in the health and well-being of people with BBS. Objectively-measured sleep and physical activity patterns in people with BBS are not well known. We evaluated objectively-measured sleep and physical activity patterns in the largest cohort to date of people with BBS. RESULTS: Short sleep duration, assessed using wrist-worn accelerometers, was common in both children and adults with BBS. Only 7 (10%) of adults and 6 (8%) of children met age-specific sleep duration recommendations. Most adults 64 (90%) achieved recommended sleep efficiency. The majority of children 26 (67%) age 6-12 years achieved recommended sleep efficiency, but among children age 13-18, only 18 (47%). In both adults and children, sleep duration was significantly negatively correlated with duration of prolonged sedentary time. In children age 6-12 sleep duration was also significantly related to total activity score, children with lower sleep duration had lower total activity scores. CONCLUSIONS: Insufficient sleep duration is very common in people with BBS. Prolonged sedentary time and short sleep duration are both potentially important health-related behaviors to target for intervention in people with BBS.

The effect of botulinum toxin A (Botox) injections used to treat limb spasticity on speech patterns in children with dysarthria and cerebral palsy: A report of two cases.

Botulinum toxin A (Btx-A) injections are used to treat limb spasticity in children with cerebral palsy (CP) resulting in improved gross and fine motor control. This treatment has also been reported to have additional functional effects, but the effect of treatment on speech has not been reported. This report presents results of longitudinal speech evaluation of two children with CP given injections of Btx-A for treatment of limb spasticity. Speech evaluations were accomplished at baseline (date of injections) and 4- and 10-weeks post-injections. Improvements in production of consonants, loudness control, and syllables produced per breath were found. Parental survey also suggested improvements in subjects' speech production and willingness to speak outside the testing situation. Future larger studies are warranted to assess the nature of the changes observed related to Btx-A.

Long-Term Follow-up to a Randomized Controlled Trial Comparing Peroneal Nerve Functional Electrical Stimulation to an Ankle Foot Orthosis for Patients With Chronic Stroke.

BACKGROUND: Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle foot orthoses (AFO) for treatment of foot drop poststroke, but few long-term, randomized controlled comparisons exist. OBJECTIVE: Compare changes in gait quality and function between FES and AFOs in individuals with foot drop poststroke over a 12-month period. METHODS: Follow-up analysis of an unblinded randomized controlled trial (ClinicalTrials.gov #NCT01087957) conducted at 30 rehabilitation centers comparing FES to AFOs over 6 months. Subjects continued to wear their randomized device for another 6 months to final 12-month assessments. Subjects used study devices for all home and community ambulation. Multiply imputed intention-to-treat analyses were utilized; primary endpoints were tested for noninferiority and secondary endpoints for superiority. Primary endpoints: 10 Meter Walk Test (10MWT) and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test (6MWT), GaitRite Functional Ambulation Profile, and Modified Emory Functional Ambulation Profile (mEFAP). RESULTS: A total of 495 subjects were randomized, and 384 completed the 12-month follow-up. FES proved noninferior to AFOs for all primary endpoints. Both FES and AFO groups showed statistically and clinically significant improvement for 10MWT compared with initial measurement. No statistically significant between-group differences were found for primary or secondary endpoints. The FES group demonstrated statistically significant improvements for 6MWT and mEFAP Stair-time subscore. CONCLUSIONS: At 12 months, both FES and AFOs continue to demonstrate equivalent gains in gait speed. Results suggest that long-term FES use may lead to additional improvements in walking endurance and functional ambulation; further research is needed to confirm these findings.

The effects of peroneal nerve functional electrical stimulation versus ankle-foot orthosis in patients with chronic stroke: a randomized controlled trial.

BACKGROUND: Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle-foot orthoses (AFO) for treatment of foot drop poststroke, but few randomized controlled comparisons exist. OBJECTIVE: To compare changes in gait and quality of life (QoL) between FES and an AFO in individuals with foot drop poststroke. METHODS: In a multicenter randomized controlled trial (ClinicalTrials.gov #NCT01087957) with unblinded outcome assessments, 495 Medicare-eligible individuals at least 6 months poststroke wore FES or an AFO for 6 months. Primary endpoints: 10-Meter Walk Test (10MWT), a composite of the Mobility, Activities of Daily Living/Instrumental Activities of Daily Living, and Social Participation subscores on the Stroke Impact Scale (SIS), and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test, GaitRite Functional Ambulation Profile (FAP), Modified Emory Functional Ambulation Profile (mEFAP), Berg Balance Scale (BBS), Timed Up and Go, individual SIS domains, and Stroke-Specific Quality of Life measures. Multiply imputed intention-to-treat analyses were used with primary endpoints tested for noninferiority and secondary endpoints tested for superiority. RESULTS: A total of 399 subjects completed the study. FES proved noninferior to the AFO for all primary endpoints. Both the FES and AFO groups improved significantly on the 10MWT. Within the FES group, significant improvements were found for SIS composite score, total mFEAP score, individual Floor and Obstacle course time scores of the mEFAP, FAP, and BBS, but again, no between-group differences were found. CONCLUSIONS: Use of FES is equivalent to the AFO. Further studies should examine whether FES enables better performance in tasks involving functional mobility, activities of daily living, and balance.

Tolerability and effectiveness of a neuroprosthesis for the treatment of footdrop in pediatric patients with hemiparetic cerebral palsy.

OBJECTIVE: To assess the tolerability and efficacy of a commercially available footdrop neuroprosthesis for treatment of footdrop in children with hemiparetic cerebral palsy. DESIGN: A prospective, observational pilot study. SETTING: Marshfield Clinic, Department of Physical Medicine. PARTICIPANTS: Ten children, ages 7-12 years, with hemiparetic cerebral palsy, who use an ankle foot orthosis (AFO) for correction of footdrop. METHODS: Children replaced their AFO with a transcutaneous peroneal (fibular) nerve stimulation neuroprosthesis for 3 months. MAIN OUTCOME MEASUREMENTS: The ability to tolerate fitting and programming of the device, device-recorded wear time, a daily-use diary, satisfaction survey, and secondary measures, including passive range of motion and gait laboratory measurement of gait velocity and ankle kinematics. RESULTS: All 10 participants (100%) tolerated fitting and programming of the neuroprosthesis and wore the device for 6 weeks. Seven of 10 (70%) wore the device for the entire 3-month study period; 6 of 10 (60%) continued to use the device after study completion. Wear time varied from 2 to 11 hours per day. Tolerability and satisfaction were high; although 6 participants complained of "size" and "bulkiness" of the device, and 2 reported skin irritation. Gait velocity increased in 5 subjects (50%). Seven participants (70%) preferred the neuroprosthesis to their AFO. CONCLUSION: Analysis of the preliminary evidence suggests that electrical stimulation by a footdrop neuroprosthesis is tolerated well by children and is effective for the treatment of footdrop in children with hemiparetic cerebral palsy. Commercially available neuroprostheses may offer a promising alternative treatment option for children with footdrop.