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Altered Cortical Excitability and Inhibition in Patients with Primary Dystonia: A Transcranial Magnetic Stimulation Study
Published online by Cambridge University Press: 19 March 2025
Abstract
Background:
The literature on cortical excitability, inhibitory and facilitatory properties of the brain in patients with primary dystonia is not well elucidated. We aimed to study the changes in these neurophysiological parameters in patients with dystonia using transcranial magnetic stimulation (TMS).
Methods:
Patients with primary dystonia of presumed genetic etiology (n = 36) and an equal number of healthy controls (HC) (n = 36) were recruited from May 2021 to September 2022. TMS was done using single and paired pulse paradigms. The left motor cortex was stimulated, and responses were recorded from the contralateral first dorsal interosseus muscle. Resting motor threshold (RMT), central motor conduction time, contralateral silent period (cSP), ipsilateral silent period (iSP), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were recorded. All patients underwent whole exome sequencing.
Results:
The mean age of patients was 36.6 ± 13.5 years. There was a significant reduction of cSP (79.5 ± 33.8 vs 97.5 ± 25.4, p = 0.02) and iSP (42.3 ± 13.5 vs 53.8 ± 20.8, p = 0.003) in patients compared to HC. SICI was significantly enhanced in patients (0.38 ± 0.23) compared to HC (0.51 ± 0.24, p = 0.006). RMT was higher (42.1 ± 7.9 vs 37.1 ± 6.4%, p = 0.032) with enhanced SICI (0.36 ± 0.21 vs 0.56 ± 0.25, p = 0.004) in patients with generalized dystonia (n = 20) compared to HC. The genetically determined subgroup (n = 13) had significantly enhanced SICI compared to HC (0.23 ± 0.15 vs 0.51 ± 0.23, p = 0.001).
Conclusions:
Patients with primary dystonia have altered cortical excitability and inhibition with significantly reduced silent period and enhanced intracortical inhibition suggestive of impaired GABAergic neurotransmission.
Résumé :
Altération de l’excitabilité et de l’inhibition corticales chez les patients atteints de dystonie primaire : une étude par stimulation magnétique transcrânienne.
La littérature portant sur l’excitabilité corticale, ainsi que sur les propriétés inhibitrices et facilitatrices du cerveau chez les patients atteints de dystonie primaire, n’est pas encore bien comprise. Nous avons ainsi cherché à étudier les changements de ces paramètres neurophysiologiques chez les patients atteints de dystonie en utilisant la stimulation magnétique transcrânienne (SMT).
Des patients atteints de dystonie primaire chez lesquels on a présumé une étiologie génétique (n = 36), de même qu’un nombre égal de témoins en bonne santé (TBS) (n = 36), ont été recrutés de mai 2021 à septembre 2022. La SMT a été effectuée en utilisant des paradigmes impulsionnels uniques et appariés. À cet égard, le cortex moteur gauche a été stimulé et les réponses ont été enregistrées à partir du premier muscle interosseux dorsal controlatéral. Le seuil moteur au repos (resting motor threshold)), le temps de conduction dans le système nerveux central (central motor conduction), la période silencieuse controlatérale (PSC), la période silencieuse ipsilatérale (PSI), l’inhibition intra-corticale à intervalle court (IICIC) et la facilitation intra-corticale (FIC) ont été enregistrés. Notons enfin que tous les patients ont subi un séquençage de l’exome entier (SEE).
L’âge moyen des patients était de 36,6 ± 13,5 ans. Une réduction significative de la PSC (79,5 ± 33,8 contre 97,5 ± 25,4 ; p = 0,02) et de la PSI (42,3 ± 13,5 contre 53,8 ± 20,8 ; p = 0,003) a été observée chez les patients comparés ensuite aux TBS. L’IICIC s’est révélée significativement plus élevée chez les patients (0,38 ± 0,23) par rapport aux TBS (0,51 ± 0,24 ; p= 0,006). Le seuil moteur au repos était plus élevé (42,1 ± 7,9 contre 37,1 ± 6,4 % ; p = 0,032) avec une IICIC améliorée (0,36 ± 0,21 contre 0,56 ± 0,25 ; p = 0,004) chez les patients atteints de dystonie généralisée (n = 20) par rapport aux TBS. Finalement, le sous-groupe génétiquement déterminé (n = 13) a donné à voir une IICIC notablement plus élevée que celle des TBS (0,23 ± 0,15 contre 0,51 ± 0,23 ; p= 0,001).
Les patients atteints de dystonie primaire ont présenté une altération de l’excitabilité et de l’inhibition corticales avec une période silencieuse significativement réduite et une inhibition intra-corticale accrue, ce qui suggère une neurotransmission gabaergique altérée.
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- © The Author(s), 2025. Published by Cambridge University Press on behalf of Canadian Neurological Sciences Federation
Footnotes
†
Both authors contributed equally. Hence, both are to be considered as first authors.
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