20.500.12556/DiRROS-24512 Mechanisms of tremor-modulating effects of primidone and propranolol in essential tremor 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 essential tremor primidone and propranolol treatments true false true Angleški jezik Ni določen Neznano 2025-12-03 13:43:07 2025-12-03 13:43:07 2025-12-04 03:46:31 0000-00-00 00:00:00 2024 0 0 str. 1-11 Vol. 128 2024 0000-00-00 Zaloznikova Objavljeno apc 0000-00-00 0000-00-00 0000-00-00 61 1353-8020 10.1016/j.parkreldis.2024.107151 234623491 RAZ_Vogelnik_Zakelj_Katarina_2024.pdf RAZ_Vogelnik_Zakelj_Katarina_2024.pdf 1 30758D45DF7E9375F0FF8107719ECEB8 5096fe4a3f3b994c64d57080562e0c2f3e4db8a5d5d8c8d3a45454828f4f7997 c44f6751-d045-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=36538 https://www.sciencedirect.com/science/article/pii/S1353802024011635 0 9fd94faa-d045-11f0-94a7-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=36537 Univerzitetni klinični center Ljubljana 0 0 0