sodium-oxybate and Dystonic-Disorders

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

Oral medications for the treatment of dystonia are not established. Currently, symptoms of focal dystonia are managed with botulinum toxin injections into the affected muscles. However, the injection effects are short-lived and not beneficial for all patients. We recently reported significant clinical improvement of symptoms with novel investigational oral drug, sodium oxybate, in patients with the alcohol-responsive form of laryngeal focal dystonia. Understanding the mechanism of action of this promising oral agent holds a strong potential for the development of a scientific rationale for its use in dystonia. Therefore, to determine the neural markers of sodium oxybate effects, which may underlie dystonic symptom improvement, we examined brain activity during symptomatic speech production before and after drug intake in patients with laryngeal dystonia and compared to healthy subjects. We found that sodium oxybate significantly attenuated hyperfunctional activity of cerebellar, thalamic and primary/secondary sensorimotor cortical regions. Drug-induced symptom improvement was correlated with decreased-to-normal levels of activity in the right cerebellum. These findings suggest that sodium oxybate shows direct modulatory effects on disorder pathophysiology by acting upon abnormal neural activity within the dystonic network.

Topics: Botulinum Toxins; Brain; Dystonic Disorders; Ethanol; Female; Humans; Male; Middle Aged; Nerve Net; Sodium Oxybate; Voice