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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.

IntroductionChemotherapy‐induced neuropathies are one of the most common side effects of cancer treatment, surpassing bone marrow suppression and kidney dysfunction. Chemotherapy effects on the nervous system vary between different classes of drugs and depend on specific chemical and physical properties of the drug used. The three most neurotoxic classes of anti‐cancer drugs are: platinum‐based drugs, taxanes, and thalidomide and its analogs; other, less neurotoxic but also commonly used drugs are: bortezomib, ixabepilone, and vinca alkaloids.MethodsHere, in this paper, based on our experience and current knowledge, we provide a short review of the most common, neuropathy‐inducing anti‐cancer drugs, describe the most prevalent neuropathy symptoms produced by each of them, and outline preventive measures and treatment guidelines for cancer patients suffering from neuropathy and for their health care providers.ResultsPatients should be encouraged to report any signs of neuropathic pain, alteration in sensory perception, tingling, numbness, burning, increased hot/cold sensitivity and motor dysfunctions as early as possible. If known neurotoxic chemotherapeutics are used, a neurological examination with electrophysiological evaluation should be implemented early in the course of treatment so, both patients and physicians would be better prepared to cope with possible neurotoxic effects.ConclusionsThe use of neurotoxic chemotherapeutics should be closely monitored and if clinically permitted, that is, if a patient shows signs of cancer regression, drug doses should be reduced or combined with other less neurotoxic anti‐cancer medication. If not counteractive, the use of over the counter antineuropathic supplements such as calcium or magnesium might be encouraged. If physically possible, patients should also be encouraged to exercise regularly and avoid factors that might increase nerve damage such as excessive drinking, smoking, or sitting in a cramped position.

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ObjectiveThis pivotal phase III study, SIAXI, investigated the efficacy and safety of incobotulinumtoxinA for the treatment of chronic sialorrhea due to Parkinson disease (PD), atypical parkinsonism, stroke, or traumatic brain injury (TBI).MethodsAdult patients with PD (70.7%), atypical parkinsonism (8.7%), stroke (19.0%), or TBI (2.7%) were randomized (2:2:1) to double-blind treatment with placebo (n = 36), or total doses of incobotulinumtoxinA 75 U (n = 74) or 100 U (n = 74), in a single treatment cycle. The coprimary endpoints were change in unstimulated salivary flow rate from baseline to week 4, and patients' Global Impression of Change Scale score at week 4. Adverse events were recorded throughout.ResultsA total of 184 patients were randomized. Both incobotulinumtoxinA dose groups showed reductions in mean unstimulated salivary flow rate at week 4, with a significant difference vs placebo in the incobotulinumtoxinA 100 U group (p = 0.004). Patients' Global Impression of Change Scale scores also improved at week 4, with a significant difference vs placebo in the incobotulinumtoxinA 100 U group (p = 0.002). A lasting effect was observed at week 16 post injection. The most frequent treatment-related adverse events in the incobotulinumtoxinA 75 U and 100 U groups were dry mouth (5.4% and 2.7% of patients) and dysphagia (2.7% and 0.0% of patients).ConclusionsIncobotulinumtoxinA 100 U is an effective and well-tolerated treatment of chronic sialorrhea in adults.ClinicalTrials.gov identifierNCT02091739.Classification of evidenceThis study provides Class I evidence that incobotulinumtoxinA reduces salivary flow rates in patients with chronic sialorrhea due to PD, atypical parkinsonism, stroke, or TBI.