sodium-oxybate and Essential-Tremor

Patients with essential tremor, vocal tremor, torticollis, myoclonus-dystonia and posthypoxic myoclonus often benefit in a surprisingly rapid and robust manner from ingestion of a modest amount of alcohol (ethanol). Despite considerable investigation, the mechanism of ethanol's ability to produce this effect remains a mystery. In this paper, we review the pharmacology of ethanol and its analogue GHB (or sodium oxybate), summarize the published literature of alcohol-responsive hyperkinetic movement disorders, and demonstrate videos of patients we have treated over the last fifteen years with either an ethanol challenge or with chronic sodium oxybate therapy. We then propose a novel explanation for this phenomenon-namely, that ingestion of

Topics: Adjuvants, Anesthesia; Alcoholic Beverages; Animals; Behavior, Animal; Central Nervous System Depressants; Cerebellar Nuclei; Dystonic Disorders; Essential Tremor; Ethanol; Humans; Hypoxia, Brain; Movement Disorders; Myoclonus; Neural Pathways; Purkinje Cells; Sodium Oxybate; Torticollis; Voice Disorders

Many movement disorders, including tics, chorea, tremor, myoclonus and parkinsonism, may result from substance abuse. However, alcohol in particular is associated in a more complex manner with two specific movement disorders, essential tremor (ET) and myoclonus-dystonia (M-D). In this review we discuss the comorbidity of alcohol abuse in both ET and M-D, the ameliorative effects of alcohol in both diseases, and review the data evaluating alcohol abuse secondary to self-medication. We also discuss shared pathophysiologic mechanisms in the understanding of both of these disorders, as the elucidation of the mechanisms by which alcohol exerts its effects may lead to novel therapeutic approaches.

Topics: Adjuvants, Anesthesia; Alcohol Drinking; Brain; Comorbidity; Dystonic Disorders; Essential Tremor; Ethanol; Exons; gamma-Aminobutyric Acid; Humans; Movement Disorders; Myoclonus; Phenotype; Point Mutation; Self Medication; Sodium Oxybate

Essential tremor of voice (ETv) is characterized by involuntary oscillations of laryngeal and upper airway muscles, causing rhythmic alterations in pitch and loudness during both passive breathing and active laryngeal tasks, such as speaking and singing. Treatment of ETv is challenging and typically less effective compared with treatment of ET affecting extremities.. We conducted a proof-of-concept, open-label phase II study to examine the efficacy and central effects of sodium oxybate in patients with alcohol-responsive ETv.. All subjects received 1.0 to 1.5 g of oral sodium oxybate and underwent brain functional magnetic resonance imaging. The primary endpoint was the number of patients (% from total) with reduced ETv symptoms by at least 10% at about 40 to 45 minutes after sodium oxybate intake based on the combined visual analog scale score of ETv symptom severity. The secondary endpoint included changes in brain activity after sodium oxybate intake compared to baseline.. Sodium oxybate reduced ETv symptoms on average by 40.8% in 92.9% of patients. Drug effects were observed about 40 to 45 minutes after intake, lasting about 3.5 hours, and gradually wearing off by the end of the fifth hour. The central effects of sodium oxybate were associated with normalized activity in the cerebellum, inferior/superior parietal lobules, inferior frontal gyrus, and insula and re-established functional relationships between these regions.. Sodium oxybate showed high efficacy in ETv patients, with a likely central action on disorder pathophysiology. Sodium oxybate may be an effective novel oral drug for treatment of alcohol-responsive ETv patients. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Topics: Essential Tremor; Ethanol; Humans; Sodium Oxybate; Treatment Outcome

The authors performed an open-label, rater-blinded, add-on study of sodium oxybate in 20 patients with ethanol-responsive myoclonus or essential tremor. Blinded ratings of videotaped examinations showed improvements in myoclonus at rest, stimulus-sensitive myoclonus, action myoclonus, functional performance, and postural and kinetic tremor. Tolerability was acceptable, and more than half of the patients chose to continue treatment after the trial. Double-blind placebo-controlled studies in these disorders are warranted.

Topics: Adjuvants, Anesthesia; Adult; Affective Symptoms; Aged; Brain; Dizziness; Dose-Response Relationship, Drug; Essential Tremor; Ethanol; Female; Headache; Humans; Male; Middle Aged; Myoclonus; Nausea; Patient Compliance; Patient Dropouts; Sodium Oxybate; Treatment Outcome

Sodium oxybate is currently approved in the United States exclusively for the treatment of cataplexy in narcoleptic patients. In a prior article published in this journal, we reported a patient with severe posthypoxic myoclonus whose myoclonus improved with ethanol and also with treatment with sodium oxybate. We extend this preliminary observation to five other patients with ethanol-responsive movement disorders in an open-label, dose-titration, add-on, 8-week trial. All five patients (one with severe alcohol-responsive posthypoxic myoclonus, two with epsilon-sarcoglycan-linked myoclonus-dystonia, and two with essential tremor) experienced improvement from baseline of 50% or greater as measured by blinded videotape review. Tolerability was satisfactory, with dose-dependent sedation as the most common side effect. Further studies of this drug in hyperkinetic movement disorders are warranted.

Topics: Adjuvants, Anesthesia; Adult; Aged; Central Nervous System Depressants; Drug Administration Schedule; Drug Therapy, Combination; Dystonia; Essential Tremor; Ethanol; Female; Humans; Male; Myoclonus; Pilot Projects; Severity of Illness Index; Sodium Oxybate; Treatment Outcome