Faculty Bibliography

Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given.

BACKGROUND: Embouchure dystonia is an unusual focal task-specific dystonia affecting the muscles that control the flow of air into the mouthpiece of a brass or woodwind instrument. The complexity of the embouchure and the relative rarity of the condition pose barriers for recognition and management of the disorder. METHODS: Case review and video survey. RESULTS: This paper presents four video compilations that illustrate the rich phenomenology of embouchure dystonia, in order to enhance recognition and diagnosis. CONCLUSION: The phenomenology of embouchure dystonia is discussed.

Therapeutic strategies in dystonia have evolved considerably in the past few decades. Three major treatment modalities include oral medications, botulinum toxin injections and surgical therapies, particularly deep brain stimulation. Although there has been a tremendous interest in the later two modalities, there are relatively few recent reviews of oral treatment. We review the medical treatment of dystonia, focusing on three major neurotransmitter systems: cholinergic, GABAergic and dopaminergic. We also provide a practical guide to medication selection, therapeutic strategy and unmet needs.

[This corrects the article DOI: 10.1186/s40734-015-0028-1.].

OPINION STATEMENT: Serotonin syndrome (SS) and neuroleptic malignant syndrome (NMS) can present similarly and range in severity from mild to life-threatening. Although they are easily misdiagnosed, each is distinct clinically and pathophysiologically. It is important to distinguish between the two, as therapeutic options differ. An accurate and thorough medication history plus knowledge of the various clinical presentations of both syndromes are the first steps in management. After this, removing the offending agents and aggressive supportive care are crucial. This includes controlling muscle rigidity and hyperthermia, providing cardiovascular support, and alleviating agitation. In severe cases, paralysis, sedation, and intubation are required. Agents to reverse either surplus serotonergic activity or dopamine blockage can be useful. However, the diagnosis must be clear, as use of these agents in the incorrect syndrome can worsen symptoms. In pharmacologically refractory cases of NMS, electroconvulsive therapy should be pursued.

OBJECTIVE: To evaluate efficacy, tolerability, and safety of adjunctive brivaracetam (BRV) in patients with Unverricht-Lundborg disease (EPM1). METHODS: Two prospective, multicenter, double-blind, phase III trials (N01187/NCT00357669; N01236/NCT00368251) in patients (>/=16 years) with genetically ascertained EPM1, showing moderate-severe myoclonus (action myoclonus score >/=30/160), randomized (1:1:1) to twice-daily BRV (N01187: 50 or 150 mg/day; N01236: 5 or 150 mg/day), or placebo. Both studies comprised a baseline period (2 weeks), 2-week up-titration period, 12-week stable-dose maintenance period, and down-titration or entry into long-term follow-up study. Symptoms of myoclonus were assessed by Unified Myoclonus Rating Scale (UMRS). Primary efficacy end point was percent reduction from baseline in action myoclonus score (UMRS section 4) at last treatment visit. Safety assessments included treatment-emergent adverse events (TEAEs). RESULTS: N01187: 50 patients randomized, 47 completed; N01236: 56 patients randomized, 54 completed. Median (min-max) percent reduction from baseline in action myoclonus score is the following-N01187: placebo 5.6 (-81.3 to 53.8), pooled BRV group (primary efficacy analysis) 21.4 (-50.0 to 73.6), BRV 50 mg/day 26.3 (-35.8 to 69.2), BRV 150 mg/day 16.9 (-50.0 to 73.6); N01236: placebo 17.5 (-170 to 61.5), BRV 5 mg/day -4.6 (-430 to 81.8), BRV 150 mg/day (primary efficacy analysis) 12.3 (-58.3 to 96.9). Estimated differences versus placebo were not statistically significant. TEAEs were reported by 72-75% placebo-treated and 56-83% BRV-treated patients. SIGNIFICANCE: Effect of BRV on action myoclonus was not statistically significant. However, action myoclonus score showed wide intrapatient variability and may not have been the optimal tool to measure severity of myoclonus in EPM1. Both studies had very high completion rates (95.3% overall), and a high percentage of patients (88.7% overall) entered long-term follow-up; both likely to be influenced by good tolerability. These studies demonstrate the feasibility of rigorous trials in progressive myoclonic epilepsy.

OBJECTIVES/HYPOTHESIS: Our aims are to 1) illustrate the complexity and phenomenological richness of the embouchure; 2) delineate the main clinical features of non-dystonic embouchure problems (NED) versus embouchure dystonia (ED); and 3) provide a practical framework for physicians who may encounter a patient with embouchure dysfunction. STUDY DESIGN: We performed retrospective chart and video review and report 139 instrumentalists with embouchure dysfunction evaluated over a 15-year period. RESULTS: Included in this group are 109 ED patients (20 newly reported and 89 previously published) and 30 NED patients. Non-dystonic embouchure problems included the overuse syndrome, infraorbital neuropathy, and orbicularis oris tears, among others. CONCLUSIONS: Based on this experience, the largest series presented to date, we propose a practical guide to help evaluate patients with embouchure dysfunction in the office. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1327-1333, 2016.

BACKGROUND: Myoclonus-dystonia is a condition that manifests predominantly as myoclonic jerks with focal dystonia. It is genetically heterogeneous with most mutations in the epsilon sarcoglycan gene (SGCE). In medically refractory cases, deep brain stimulation (DBS) has been shown to provide marked sustainable clinical improvement, especially in SGCE-positive patients. We present two patients with myoclonus-dystonia (one SGCE positive and the other SGCE negative) who have the isolated myoclonus phenotype and had DBS leads implanted in the bilateral globus pallidus internus (GPi). METHODS: We review their longitudinal Unified Myoclonus Rating Scale scores along with their DBS programming parameters and compare them with published cases in the literature. RESULTS: Both patients demonstrated complete amelioration of all aspects of myoclonus within 6-12 months after surgery. The patient with the SGCE-negative mutation responded just as well as the patient who was SGCE positive. High-frequency stimulation (130 Hz) with amplitudes greater than 2.5 V provided therapeutic benefit. DISCUSSION: This case series demonstrates that high frequency GPi-DBS is effective in treating isolated myoclonus in myoclonus-dystonia, regardless of the presence of SGCE mutation.