Objective: To examine the central effects of sodium oxybate in patients with alcohol-responsive (EtOH+) laryngeal dystonia (LD).

Background: LD is a task-specific form of isolated dystonia characterized by involuntary spasms in the laryngeal muscles during speech production. A recent phase IIb randomized, double-blind, placebo-controlled clinical trial demonstrated that a single dose of 1.5g of oral sodium oxybate is superior to placebo in patients with EtOH+ LD but not in alcohol-non-responsive (EtOH-) LD. An average of 40.8% of symptom improvement was observed in EtOH+ LD patients¹.

Method: A total of 31 LD patients (25 female/6 male, age 59.1 ± 11.6) who benefited from sodium oxybate with at least 16% symptom improvement and 31 healthy controls (HC, 19 female/12 male, mean age 56.9 ± 13.6) participated in the pharmacological fMRI study over three consecutive days. Whole-brain activity during symptomatic speech production in LD patients was examined following sodium oxybate, placebo, and alcohol intake and compared to brain activity during normal speaking in HC at family-wise error-corrected p ≤ 0.05 with voxelwise threshold ≥ 0.01 and cluster size threshold ≥ 640 mm³.

Results: The baseline comparison between EtOH+ LD patients and HC showed a typical pattern of increased brain activity in the primary sensorimotor, premotor, inferior parietal, insular, prefrontal, and occipital cortices, basal ganglia, and cerebellum. Following sodium oxybate intake, LD patients compared to HC showed largely normalized brain activity in these regions, except for a region in the right occipital cortex that remained hyperactive. Given the similarities of action between sodium oxybate and alcohol and the strong association between sodium oxybate efficacy and alcohol-responsiveness of dystonic symptoms¹, brain activity in LD patients after alcohol intake was found to be modulated similarly, albeit to a lesser degree, with regions in the inferior parietal, prefrontal, and premotor cortices remaining hyperactive, compared to HC. In contrast, brain activity in LD patients following placebo intake remained mostly unchanged, except for the cerebellum, which showed normal activity compared to HC.

Conclusion: Sodium oxybate, similar to alcohol but unlike placebo, exhibits direct modulatory effects on LD pathophysiology by normalizing abnormally increased brain activity within the dystonic neural network.

References: 1. Simonyan K, O’Flynn LC, Hamzehei Sichani A, et al. Efficacy and Safety of Sodium Oxybate in Isolated Focal Laryngeal Dystonia: A Phase IIb Double-Blind Placebo-Controlled Cross-Over Randomized Clinical Trial. Ann Neurol. 2024 Nov 20.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/central-neuromodulatory-effects-of-sodium-oxybate-in-laryngeal-dystonia-a-pharmacological-fmri-study/