Objective: To explain central mechanisms of propranolol and primidone action and to study pathophysiology of essential tremor (ET).

Background: Neurophysiological studies suggest that both motor cortex and cerebellum are involved in pathophysiology of ET.  Although the beneficial effect of β-blockers and primidone on ET is well known, the mechanism of their central action is poorly understood.

Method: Thirty-six patient with clinical diagnosis of ET were studied prior to treatment with propranolol or primidone and 17 thus far repeated the assessment 3 months after treatment initiation. We used transcranial magnetic stimulation to study motor cortex excitability, including resting and active recruitment curves (RC), short interval intracortical inhibition (SICI), cortical silent period (CSP) and short afferent inhibition (SAI). Eyeblink classical conditioning (EBCC) paradigm was performed at baseline to asses if degree of cerebellar impairment may predict treatment response. Tremor was assessed clinically and by EMG and accelerometry recordings. Positive treatment response was defined as 30% or more decrease in tremor amplitude.

Results: Propranolol significantly more increased SICI than primidone. On the contrary, primidone was significantly more effective in decreasing the stepness of resting RC and in prolonging  CSP comparing to propranolol. Decrease in the steepness of active RC, an increase of SAI and increase of ICF were present in propranolol group only and among responders only. There was a significant correlation between improvement of both SAI and ICF and tremor improvement. EBCC did not predict response to treatment in neither propranolol nor primidone group.

Conclusion: Propranol and primidone have different effect on TMS measures of cortical excitability in ET. Propranolol effect may be associated with increase of GABA-a and cholinergic cortical inhibition, as measured by SICI and SAI respectively and with increase in intracortical facilitiation, which is presumably mediated by glutaminergic transmission. Primidone effect may be related to increase in GABA-b intracortical inhibition and increase in membrane resting potential, as measured by CSP and resting RC, respectively. TMS may help to define mechanism of action of pharmacological agents in ET, which may eventually lead to development of novel therapeutics.

« Back to 2019 International Congress

MDS Abstracts - https://www.mdsabstracts.org/abstract/the-mechanism-of-tremor-modulating-properties-of-propranolol-and-primidone-in-essential-tremor-a-study-with-transcranial-magnetic-stimulation-and-eye-blink-classical-conditioning-paradigm/