While spasticity is commonly treated with oral agents or botulinum neurotoxin (BoNT) injection, these treatments have not been systematically compared. This study performed a randomised, double-blind, placebo-controlled trial to compare injection of BoNT-Type A into spastic upper limb muscles versus oral tizanidine (TZD), or placebo, in 60 subjects with upper-limb spasticity due to stroke or traumatic brain injury (TBI). Wrist flexors were systematically injected, while other upper limb muscles were injected as per investigator judgement. Participants were randomised into three groups: (1) intramuscular BoNT plus oral placebo; (2) oral TZD plus intramuscular placebo; (3) intramuscular placebo plus oral placebo. The primary outcome was the difference in change in wrist flexor modified Ashworth score (MAS) between groups. Other outcome measures included MAS at elbow and finger joints, Disability Assessment Scale (DAS) and adverse events (AE). BoNT produced greater tone reduction than TZD or placebo in finger and wrist flexors at week 3 (por=0.09). The incidence of AE related to study treatment was higher with TZD than in the BoNT (p<0.01) or placebo groups (p = 0.001). BoNT is safer and more effective than TZD in reducing tone and disfigurement in upper-extremity spasticity, and may be considered as first-line therapy for this disorder.

Objective: To demonstrate single abobotulinumtoxinA injection efficacy in lower limb vs placebo for adults with chronic hemiparesis and assess long-term safety and efficacy of repeated injections. Methods: In a multicenter, double-blind, randomized, placebo-controlled, single-cycle study followed by a 1-year open-label, multiple-cycle extension, adults ≥6 months after stroke/brain injury received one lower limb injection (abobotulinumtoxinA 1,000 U, abobotulinumtoxinA 1,500 U, placebo) followed by ≤4 open-label cycles (1,000, 1,500 U) at ≥12-week intervals. Efficacy measures included Modified Ashworth Scale (MAS) in gastrocnemius–soleus complex (GSC; double-blind primary endpoint), physician global assessment (PGA), and comfortable barefoot walking speed. Safety was the open-label primary endpoint. Results: After a single injection, mean (95% confidence interval) MAS GSC changes from baseline at week 4 (double-blind, n = 381) were as follows: −0.5 (−0.7 to −0.4) (placebo, n = 128), −0.6 (−0.8 to −0.5) (abobotulinumtoxinA 1,000 U, n = 125; p = 0.28 vs placebo), and −0.8 (−0.9 to −0.7) (abobotulinumtoxinA 1,500 U, n = 128; p = 0.009 vs placebo). Mean week 4 PGA scores were as follows: 0.7 (0.5, 0.9) (placebo), 0.9 (0.7, 1.1) (1,000 U; p = 0.067 vs placebo), and 0.9 (0.7, 1.1) (1,500 U; p = 0.067); walking speed was not significantly improved vs placebo. At cycle 4, week 4 (open-label), mean MAS GSC change reached −1.0. Incremental improvements in PGA and walking speed occurred across open-label cycles; by cycle 4, week 4, mean PGA was 1.9, and walking speed increased +25.3% (17.5, 33.2), with 16% of participants walking >0.8 m/s (associated with community mobility; 0% at baseline). Tolerability was good and consistent with the known abobotulinumtoxinA safety profile. Conclusions: In chronic hemiparesis, single abobotulinumtoxinA (Dysport Ipsen) administration reduced muscle tone. Repeated administration over a year was well-tolerated and improved walking speed and likelihood of achieving community ambulation. Clinicaltrial.gov identifiers: NCT01249404, NCT01251367. Classification of evidence: The double-blind phase of this study provides Class I evidence that for adults with chronic spastic hemiparesis, a single abobotulinumtoxinA injection reduces lower extremity muscle tone.

Introduction: The efficacy of single injections of abobotulinumtoxinA (Dysport) is established in adults with upper limb spasticity. In this study we assessed the effects of repeated injections of abobotulinumtoxinA over 1 year. Methods: Patients (n = 258, safety population) received 500 U, 1,000 U, or 1,500 U (1,500‐U dose included 500‐U shoulder injections) for up to 4 or 5 treatment cycles. Assessments included treatment‐emergent adverse events (TEAEs), muscle tone, passive and active range of motion (X_V1, X_A), angle of catch (X_V3), Disability Assessment Scale (DAS) score, Modified Frenchay Scale (MFS) score, and Physician Global Assessment (PGA) score. Results: The incidence of TEAEs decreased across cycles. Muscle tone reduction and X_V1 remained stable across cycles, whereas X_V3 and X_A continued to improve at the finger, wrist, and elbow flexors. DAS and PGA improved across cycles. MFS improved best with 1,500 U. Discussion: A favorable safety profile and continuous improvements in active movements and perceived and active function were associated with repeated abobotulinumtoxinA injections in upper limb muscles. Muscle Nerve 57: 245–254, 2018

When increasing ambulation speed in Parkinson’s disease, step cadence increases more than stride length, indicating movement scaling difficulties that affect step generation in particular. We investigated whether step length variation when increasing ambulation speed was related to disease progression. Patients with Parkinson’s disease (N = 39) and controls (N = 152) performed two timed ambulation tasks: at a 'free' (self-selected) pace and then at 'maximal' speed. The total number of steps (including during turns) and time to complete the task were clinically measured. The relative contribution of step length and cadence to increased ambulation speed was determined using two methods: the ratios of change in step length or in cadence to the change in ambulation speed, and the step length index. While the relative contribution of step length and cadence to increased ambulation speed was independent of age in both control and patient groups, in Parkinson’s disease there was a negative correlation between time from diagnosis and the ratio of change in step length to change in ambulation speed (R = 0.54; p = 0.0004) and the step length index (R = 0.56, p = 0.0002). In parallel, there was a positive correlation between time since diagnosis and the ratio of change in cadence to change in ambulation speed (R = 0.57; p = 0.0002). The relative contribution of step length and cadence to increased ambulation speed is age invariant but a marker of Parkinson's disease advancement, and can be easily determined in the clinical setting.

The continuous, accurate and reliable estimation of gait parameters as a measure of mobility is essential to assess the loss of functional capacity related to the progression of disease. Connected insoles are suitable wearable devices which allow precise, continuous, remote and passive gait assessment. The data of 25 healthy volunteers aged 20 to 77 years were analysed in the study to validate gait parameters (stride length, velocity, stance, swing, step and single support durations and cadence) measured by FeetMe^® insoles against the GAITRite^® mat reference. The mean values and the values of variability were calculated per subject for GAITRite^® and insoles. A t-test and Levene’s test were used to compare the gait parameters for means and variances, respectively, obtained for both devices. Additionally, measures of bias, standard deviation of differences, Pearson’s correlation and intraclass correlation were analysed to explore overall agreement between the two devices. No significant differences in mean and variance between the two devices were detected. Pearson’s correlation coefficients of averaged gait estimates were higher than 0.98 and 0.8, respectively, for unipedal and bipedal gait parameters, supporting a high level of agreement between the two devices. The connected insoles are therefore a device equivalent to GAITRite^® to estimate the mean and variability of gait parameters.