Treatment of Essential Tremor with Long-chain Alcohols: Still Experimental or Ready for Prime Time?

Haubenberger, Dietrich; Nahab, Fatta B.; Voller, Bernhard; Hallett, Mark

doi:10.7916/d8rx991r

Cited by 7 publications

(1 citation statement)

References 58 publications

(60 reference statements)

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“…Importantly, delta-subunit containing GABA receptors including the alpha6delta GABA receptors, which are expressed in cerebellar granule cells, are nonsensitive to benzodiazepines and have been shown to be sensitive to ethanol. These cerebellar GABA-A receptors therefore may facilitate the effect of ethanol in ET 41 and have been identified as potential targets for treatment development in ET. 24 Lastly, we highlight a few limitations in our study.…”

Section: Discussionmentioning

confidence: 99%

Objective response to ethanol in essential tremor: results from a standardized ethanol challenge study

McGurrin,

Norato,

Thompson‐Westra

et al. 2023

Ann Clin Transl Neurol

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Background and ObjectivesEthanol has been reported to improve tremor severity in approximately two thirds of patients with essential tremor (ET), but the accuracy of that proportion is not certain and the mechanism of action is unknown. The goal of this study was to investigate alcohol response on tremor by applying an a priori objective response definition and subsequently to describe the responder rate to a standardized ethanol dose in a cohort of 85 ET patients. A secondary analysis evaluated other tremor and nontremor features, including demographics, tremor intensity, breath alcohol concentration, nontremor effects of alcohol, self‐reported responder status to ethanol, and prior ethanol exposure.MethodsThis was a prospective, open‐label, single‐dose challenge of oral ethanol during which motor and nonmotor measurements were obtained starting immediately prior to ethanol administration and subsequently every 20 min for 120 min. We defined tremor reduction as a 35% decline in power in the patient's tremor frequency recorded during spiral drawing 60 min after ethanol administration.ResultsIn total, 80% of patients were considered alcohol responsive using our objective definition. Responder status and change in the objective tremor metrics were significantly correlated with the change in breath alcohol concentration levels after ethanol administration, but no other relationships to nontremor metrics were found.DiscussionA high percentage of patients actually respond to acute ethanol. However, their self‐reported response does not correlate well with their objective response. Objective response correlates with breath alcohol level but not with sedation, indicating a specific effect of ethanol on tremor.

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Section: Discussionmentioning

confidence: 99%

Objective response to ethanol in essential tremor: results from a standardized ethanol challenge study

McGurrin,

Norato,

Thompson‐Westra

et al. 2023

Ann Clin Transl Neurol

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An open-label study of sodium oxybate in Spasmodic dysphonia

et al. 2016

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Objective Spasmodic dysphonia (SD) is a task-specific laryngeal dystonia that affects speech production. Co-occurring voice tremor (VT) often complicates the diagnosis and clinical management of SD. Treatment of SD and VT is largely limited to botulinum toxin injections into laryngeal musculature; other pharmacological options are not sufficiently developed. Study Design and Methods We conducted an open-label study in 23 SD and 22 SD/VT patients to examine the effects of sodium oxybate (Xyrem®), an oral agent with therapeutic effects similar to those of alcohol in these patients. Blinded randomized analysis of voice and speech samples assessed symptom improvement before and after drug administration. Results Sodium oxybate significantly improved voice symptoms (p = 0.001) primarily by reducing the number of SD-characteristic voice breaks and severity of VT. Sodium oxybate further showed a trend for improving VT symptoms (p = 0.03) in a subset of patients who received successful botulinum toxin injections for the management of their SD symptoms. The drug’s effects were observed approximately 30–40 min after its intake and lasted about 3.5–4 hours. Conclusion Our study demonstrated that sodium oxybate reduced voice symptoms in 82.2% of alcohol-responsive SD patients both with and without co-occurring VT. Our findings suggest that the therapeutic mechanism of sodium oxybate in SD and SD/VT may be linked to that of alcohol and as such sodium oxybate might be beneficial for alcohol-responsive SD and SD/VT patients.

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Milestones in Tremor Research: 10 Years Later

Erro

Fasano

Barone

et al. 2022

Movement Disord Clin Pract

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Major progress has occurred during the last decade in the field of tremor. From the clinical standpoint, a new classification has completely revised the nosology of tremor syndromes and has re‐conceptualized essential tremor as a syndrome rather than a single disease entity, fueling an ongoing enlightened debate. Significant advances have been obtained in terms of instrumental measurement of tremor, remarking on the possibility of developing novel treatment strategies based on tremor characteristics, namely tremor‐phase. Moreover, a better understanding of the pathophysiological mechanisms has further led to the suggestion of refining the classification of tremor syndromes according to their driving underpinnings. Finally, surgical options such as deep brain stimulation and focused ultrasound thalamotomy are now part of the therapeutic portfolio for tremor, but several oral drugs, including long‐chain alcohols, T‐channel blockers, allosteric modulators of potassium channels, and of GABA‐A receptors, are currently being tested and hold promise. This review will discuss the key milestones in tremor research of the last 10 years, with a focus on the most common tremor syndromes, namely essential tremor, dystonic tremor, and Parkinsonian tremor.

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Treatment of Essential Tremor with Long-chain Alcohols: Still Experimental or Ready for Prime Time?

Cited by 7 publications

References 58 publications

Objective response to ethanol in essential tremor: results from a standardized ethanol challenge study

Objective response to ethanol in essential tremor: results from a standardized ethanol challenge study

An open-label study of sodium oxybate in Spasmodic dysphonia

Milestones in Tremor Research: 10 Years Later

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