Department of Otolaryngology-Head and Neck Surgery, Massachusetts Eye and Ear and Harvard Medical School, Boston, Massachusetts, USA.
Program in Speech Hearing Bioscience and Technology, Harvard University, Boston, Massachusetts, USA.
Mov Disord. 2023 Oct;38(10):1936-1944. doi: 10.1002/mds.29529. Epub 2023 Jul 14.
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.
声带震颤（ETv）的特征是喉部和上呼吸道肌肉的不自主振荡，导致在被动呼吸和主动发声任务（如说话和唱歌）期间音高和响度出现有节奏的改变。ETv 的治疗具有挑战性，与治疗影响四肢的 ET 相比，通常效果较差。
我们进行了一项概念验证、开放标签的 II 期研究，以检查口服羟丁酸钠对酒精反应性 ETv 患者的疗效和中枢作用。
所有受试者均接受 1.0 至 1.5 g 口服羟丁酸钠，并接受脑功能磁共振成像。主要终点是根据 ETv 症状严重程度的综合视觉模拟量表评分，在大约 40 至 45 分钟后，羟丁酸钠摄入后至少有 10%的患者（占总人数的百分比）ETv 症状减轻至少 10%。次要终点包括与基线相比，羟丁酸钠摄入后大脑活动的变化。
羟丁酸钠平均使 92.9%的患者 ETv 症状减轻 40.8%。药物作用在摄入后约 40 至 45 分钟出现，持续约 3.5 小时，在第五小时结束时逐渐消失。羟丁酸钠的中枢作用与小脑、下/顶叶、下额叶和脑岛的正常活动有关，并重新建立了这些区域之间的功能关系。
羟丁酸钠在 ETv 患者中显示出较高的疗效，对疾病病理生理学可能具有中枢作用。羟丁酸钠可能是一种治疗酒精反应性 ETv 患者的有效新型口服药物。
