Zolpidem improves task-specific dystonia : a randomized clinical trial integrating exploratory transcranial magnetic stimulation and [18F] FDG-PET imaging

Vogelnik Žakelj, Katarina (author), Trošt, Maja (author), Tomše, Petra (author), Petrović, Igor N. (author), Tomić Pešić, Aleksandra (author), Radovanović, Saša (author), Kojović, Maja (author)

Background: Task-specific dystonia (TSFD) is a disabling movement disorder. Effective treatment options are currently limited. Zolpidem was reported to improve primary focal and generalized dystonia in a proportion of patients. The mechanisms underlying its therapeutic effects have not yet been investigated. Methods: We conducted a randomized, double-blind, placebo-controlled, crossover trial of single-dose zolpidem in 24 patients with TSFD. Patients were clinically assessed using Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS), Writers’ Cramp Rating Scale (WCRS), and Visual Analogue Scale (VAS), before and after receiving placebo and zolpidem. Transcranial magnetic stimulation was conducted on placebo and zolpidem to compare corticospinal excitability – active and resting motor thresholds (AMT and RMT), resting and active input/output curves and intracortical excitability - cortical silent period (CSP), short-interval intracortical inhibition curve (SICI), long-interval intracortical inhibition (LICI) and intracortical facilitation (ICF). Eight patients underwent brain FDG-PET imaging on zolpidem and placebo. Results: Zolpidem treatment improved TSFD. Zolpidem compared to placebo flattened rest and active input/output curves, reduced ICF and was associated with hypometabolism in the right cerebellum and hypermetabolism in the left inferior parietal lobule and left cingulum. Correlations were found between changes in dystonia severity on WCRS and changes in active input/output curve and in brain metabolism, respectively. Patients with lower RMT, and higher rest and active input/output curves exhibited better response to zolpidem compared to placebo. Conclusions: Zolpidem improved TSFD by reducing corticomotor output and influencing crucial nodes in higher-order sensory and motor networks.

• Language: English
• Keywords: zolpidem, writer's cramp, musician's dystonia, TMS, FDG-PET
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine
• Publication status: Published
• Publication version: Version of Record
• Year: 2024
• Number of pages: 9 str.
• Numbering: Vol. 124, art. 107014
• PID: 20.500.12556/RUL-158995
• UDC: 616.8
• ISSN on article: 1353-8020
• DOI: 10.1016/j.parkreldis.2024.107014
• COBISS.SI-ID: 199949571
• Publication date in RUL: 27.06.2024

Record is a part of a journal

• Title: Parkinsonism & related disorders
• Shortened title: Parkinsonism relat. disord.
• Publisher: Elsevier
• ISSN: 1353-8020
• COBISS.SI-ID: 11416793

Licences

• License: CC BY 4.0, Creative Commons Attribution 4.0 International
• Link: http://creativecommons.org/licenses/by/4.0/
• Description: This is the standard Creative Commons license that gives others maximum freedom to do what they want with the work as long as they credit the author.

Projects

• Funder: ARRS - Slovenian Research Agency
• Project number: J3-7310
• Name: Novi ciljni receptorji pri distoniji: elektrofiziološki in slikovni korelati učinka zolpidema, selektivnega agonista benzodiazepinskega podtipa receptorja alfa-1, pri različnih oblikah primarne žariščne distonije