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

Detailed Summary

Pathophysiology of tremor-modulating mechanisms of propranolol and primidone in essential tremor (ET) will be studied using accelerometry with electromyography (EMG), transcranial magnetic stimulation (TMS), and eyeblink conditioning paradigm (EBCC). TMS is a well-established experimental method for studying the effects of drugs on motor cortex excitability. EBCC is a learning paradigm that can be used for studying cerebellar dysfunction since only brainstem and cerebellar functions seem to be needed for this paradigm. The investigators will use TMS to study the mechanisms of primidone and propranolol action in ET, EBCC paradigm to evaluate cerebellar dysfunction in ET patients and to show whether cerebellar dysfunction influences the effectiveness of propranolol and primidone. The investigators will clinically assess patients using The Essential Tremor Rating Assessment Scale (TETRAS) and the Scale for the Assessment and Rating of Ataxia (SARA) scales. Patients with ET will be studied prior to treatment with propranolol or primidone and re-tested 3-6 months after treatment initiation. On each visit, the investigators will clinically assess the patients and perform accelerometry, TMS measurements, and the eyeblink classical conditioning (EBCC) paradigm. The investigators hypothesize that in ET patients, baseline electrophysiological parameters will differ between responders and non-responders to propranolol and primidone and that propranolol and primidone will cause a different pattern of change in electrophysiological parameters among responders. It is hypothesized that cerebellar dysfunction will negatively correlate with patients' response to treatment.

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