Mechanisms of tremor-modulating effects of primidone and propranolol in essential tremor

Vogelnik Žakelj, Katarina (avtor), Prezelj, Neža (avtor), Gregorič Kramberger, Milica (avtor), Kojović, Maja (avtor)

Introduction: Primidone and propranolol are primary treatments for essential tremor, however the exact mechanisms underlying their efficacy are not fully elucidated. Understanding how these medications alleviate tremor may guide the development of additional pharmacologic treatments. Our prospective observational study employed transcranial magnetic stimulation (TMS) to explore mechanisms of primidone and propranolol effects in essential tremor. Eyeblink classical conditioning (EBCC) was tested as a potential predictor of treatment response. Methods: Patients with essential tremor underwent two evaluations: prior to commencing primidone or propranolol and following a minimum of three months of treatment. Tremor severity was assessed using accelerometry and clinically. TMS was employed to study changes in corticospinal excitability - resting and active motor thresholds, resting and active input/output curves and intracortical excitability - cortical silent period (CSP), short interval intracortical inhibition intensity curve (SICI), long interval intracortical inhibition (LICI), intracortical facilitation (ICF), and short afferent inhibition (SAI). EBCC, a marker of cerebellar function, was studied at baseline. Results: Of the 54 enrolled patients (28 primidone, 26 propranolol), 35 completed both visits. Primidone effect on decreasing hand tremor was associated with decreased corticospinal excitability, prolongation of CSP, increased LICI, increased SAI and decreased SICI. Propranolol effect on hand tremor was associated with decreased corticospinal excitability and increased SAI. Better EBCC at baseline predicted better response to primidone. Conclusions: Primidone exerts its therapeutic effects by blocking voltage-gated sodium channels and by modulating GABA-A and GABA-B intracortical circuits. Propranolol's central effects are likely mediated via noradrenergic modulation of GABA outflow.

• Jezik: Angleški jezik
• Ključne besede: essential tremor, primidone, propranolol, treatment, pharmacotherapy
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: MF - Medicinska fakulteta
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: 11 str.
• Številčenje: Vol. 128, art. 107151
• PID: 20.500.12556/RUL-168870
• UDK: 61
• ISSN pri članku: 1353-8020
• DOI: 10.1016/j.parkreldis.2024.107151
• COBISS.SI-ID: 234623491
• Datum objave v RUL: 05.05.2025

Gradivo je del revije

• Naslov: Parkinsonism & related disorders
• Skrajšan naslov: Parkinsonism relat. disord.
• Založnik: Elsevier
• ISSN: 1353-8020
• COBISS.SI-ID: 11416793

Licence

• Licenca: CC BY-NC 4.0, Creative Commons Priznanje avtorstva-Nekomercialno 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by-nc/4.0/deed.sl
• Opis: Licenca Creative Commons, ki prepoveduje komercialno uporabo, vendar uporabniki ne rabijo upravljati materialnih avtorskih pravic na izpeljanih delih z enako licenco.

Projekti

• Financer: University Medical Centre Ljubljana
• Program financ.: Developmental-research tertiary project
• Številka projekta: 20170057