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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.

Cervical dystonia is a neurological movement disorder causing abnormal posture of the head. It may be accompanied by involuntary movements which are sometimes tremulous. The condition has marked effects on patients’ self-image, and adversely affects quality of life, social relationships and employment. Botulinum neurotoxin (BoNT) is the treatment of choice for CD and its efficacy and safety have been extensively studied in clinical trials. However, current guidelines do not provide enough practical information for physicians who wish to use this valuable treatment in a real-life setting. In addition, patients and physicians may have different perceptions of what successful treatment outcomes should be. Consequently, an international group of expert neurologists, experienced in BoNT treatment, met to review the literature and pool their extensive clinical experience to give practical guidance about treatment of CD with BoNT. Eight topic headings were considered: the place of BoNT within CD treatment options; patient perspectives and desires for treatment; assessment and goal setting; starting treatment with BoNT-A; follow-up sessions; management of side effects; management of non-response; switching between different BoNT products. One rapporteur took responsibility for summarising the current literature for each topic, while the consensus statements were developed by the entire expert group. These statements are presented here along with a discussion of the background information.

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IncobotulinumtoxinA treatment resulted in significant improvements in facial symmetry in patients with facial nerve injury following neurosurgical interventions. Treatment was effective for the correction of the compensatory hyperactivity of mimic muscles on the unaffected side that develops in the acute period of facial nerve palsy, and for the correction of synkinesis in the affected side that develops in the long-term period. Appropriate dosing and patient education to perform exercises to restore mimic muscle function should be considered in multimodal treatment.

LAY ABSTRACTSpastic hemiparesis is a condition in which the muscles on one side of the body become weak and stiff, often after a stroke. One treatment involves injecting botulinum toxin (e.g. abobotulinumtoxinA) into the affected muscles. Patients may find walking difficult, but repeated injections of abobotulinumtoxinA into the legs have been associated with improved walking speed. How ever, it is not known whether improvements in walking speed are maintained when the dose of abobo-tulinumtoxinA is split to treat other affected areas, such as the arms. This study shows that splitting the dose of abobotulinumtoxinA across the arms and legs does not hamper walking speed, compared with injecting into the legs only. This suggests that doctors can split the dose across the arms and legs as needed to best treat the symptoms of spastic hemiparesis. Objective: To compare walking speed in patients with spastic hemiparesis who received abobotuli-numtoxinA either in the lower limb or simultaneously in both the lower and upper limbs. Design: Post hoc analysis from a phase 3 study of abobotulinumtoxinA (Dysport®, NCT01251367). Patients: Adult patients with spastic hemiparesis causing gait dysfunction. Methods: Comfortable barefoot walking speed over 10 m was evaluated in 127 patients receiving lower limb vs lower and upper limb injections over ≤4 treat ment cycles; 1,000 U or 1,500 U in lower limb for cycle 1/2; optional upper limb injections from cycle 3 (500 U: upper limb, 1,000 U: lower limb). Results: Mean (standard deviation; SD) lower limb cycle 3/4 doses were lower in the lower plus upper limb group vs lower limb only (1,000 U (SD 50), 1,000 U (SD 50) vs 1,380 U (SD 210), 1,360 U (SD 220). Baseline comfortable barefoot walking speed was similar between groups. Changes at cycle 3 week 4, in m/s, were: lower and upper limb: +0.063 (SD 0.131); lower limb only: +0.078 (SD 0.114), and cycle 4 week 4: lower and upper limb: +0.086 (SD 0.166); lower limb only: +0.086 (SD 0.123). Conclusion: Simultaneous lower and upper limb abobotulinumtoxinA treatment does not hamper improvement in walking speed compared with lower limb treatment alone. Thus, physicians may split the 1,500 U abobotulinumtoxinA dose as needed to best treat patients with spastic paresis.

Botulinum toxins, such as abobotulinumtoxinA, are used to treat spasticity (muscle overactivity) in arm muscles. Spasticity in shoulder muscles occurs in many patients following a stroke. Shoulder spasticity can be painful and limit limb movement. This paper compares the results from patients who did and those who did not receive abobotulinumtoxinA injections in shoulder muscles (among other arm muscles) in 2 studies. In both studies, the results showed that more patients receiving treatment in shoulder muscles chose pain as a key goal for treatment and had reduced pain following treatment compared with patients not treated in the shoulder. In addition, patients receiving shoulder injections showed further improvement in arm movement compared with those not receiving shoulder injections. Overall, these results suggest that abobotulinumtoxinA treatment in shoulder muscles may improve outcomes for patients with arm spasticity involving the shoulder. Objective: To compare patients with upper limb spasticity who did or did not receive abobotulinum-toxinA (Dysport®) in shoulder muscles during 2 international clinical studies. Design: Phase 4 Upper Limb International Spasticity Study-II (ULIS-II; NCT01020500) endpoints: primary goal selection and achievement. Phase 3 Adult Upper Limb (AUL) open-label study (NCT01313299) endpoints: Disability Assessment Scale principal target of treatment and mean (standard deviation) change from baseline to week 4 (last cycle involving shoulder muscles) for pain, Modified Frenchay Scale (active function), and Tardieu Scale parameters. Patients: Shoulder population: patients receiving abobotulinumtoxinA injections in shoulder muscles (n = 82 and n = 96 in ULIS-II and AUL open-label study, respectively); non-shoulder population: patients not injected in shoulder muscles (n = 239 and n = 158, respectively). Results: ULIS-II: primary treatment goal was pain in 25.6% vs 8.4% patients (3-fold higher) in shoulder vs non-shoulder populations, with high goal-achievement for pain reduction (85.7%). AUL open-label study: Disability Assessment Scale pain selection was 9.5% vs 5.1% (almost double); pain improvements were -0.7 (0.9) vs -0.4 (0.7); active function improvements were +0.60 (0.80) vs +0.33 (0.79), in shoulder vs non-shoulder populations, respectively. Tardieu scale parameters were improved. Conclusion: High goal achievement rates for pain reduction and improved active function were observed in patients receiving abobotulinumtoxinA in shoulder muscles.

A.I. Burnazyan Federal Medical and Biological Center, FMBA of Russia; 23 Marshala Novikova St., Moscow 123098, Russia; 3