CEREBELLAR CONTINUOUS THETA BURST STIMULATION IN ESSENTIAL TREMORG Leodori (1), M Bologna (2), L Rocchi (1), G Paparella (1), A Conte (1-2), A Berardelli (1-2)

(1) Department of Neurology and Psychiatry, Sapienza University of Rome, Rome, Italy; (2) Neuromed Institute IRCCS, Pozzilli (IS), Italy

INTRODUCTION: An abnormal cerebello-thalamo-cortical connectivity is thought to be involved in the pathophysiology of essential

tremor (ET). In the present study we aimed to investigate whether continuous theta-burst stimulation (cTBS) of the cerebellum

modulate severity of postural tremor and the cerebello-thalamo-cortical connectivity (CTC) in patients with ET.

METHODS: Fifteen Patients with ET and 10 healthy controls underwent two

experimental sessions: (i) cTBS of the right cerebellarhemisphere (real cerebellar cTBS) and (ii) cTBS over the neckmuscles (sham cerebellar cTBS).

The two sessions were performed at least one week apart.Postural tremor was rated clinically and objectively measuredusing kinematic techniques – FIGURE 1 before and aftercerebellar cTBS. Primary motor cortex excitability was assessedby recording the input/output curve of the motor evokedpotentials from the right first dorsal interosseous muscle –FIGURE 2.

FIGURE 1: Kinematicassessment of posturaltremor.

FIGURE 2: Experimental design.Electrophysiological and kinematic measurements were performed at three different time points, before stimulation and 5 min and 45 min thereafter.

RESULTS: There were no significant changes in clinical tremor rating after real and sham cerebellar cTBS in patients with ET;

cerebellar cTBS did not modify the postural tremor mean frequency and tremor magnitude assessed with kinematictechniques in patients – FIGURE 3.

Real cerebellar cTBS, but not sham cerebellar cTBS, reduced the excitability in the controlateral primary motor cortexonly in healthy subjects but not in patients with ET – FIGURE 4.

Figure 4: Cortical excitability measurements (input-output curves of the Motor Evoked Potentials); Y axis indicates MEPs amplitude in mV and X axis indicates the stimulation intensities (from100% to 150% resting motor threshold – RMT) in the two experimental sessions (real cerebellar cTBS– upper panels; sham cerebellar cTBS –lower panels), in healthy controls (left panels) and in patients with ET (right panels) during the three measurement time points (baseline-T0 circular black indicators, 5 min after cTBS-T1 circular white indicators, and 45 min after cTBS-T2, triangular black indicators).

CONCLUSIONS: The present study provide provide information on the possible therapeutic implications of non-invasive cerebellar

stimulation in ET. The lack of tremor reduction after a single session of cerebellar cTBS in ET raises the question as tohow it may be possible to modify this stimulation paradigm in order to obtain a clinically or neurophysiologicallysignificant effect.

Further studies are warranted to clarify the pathophysiological relevance of the reduced LTD-like mechanisms of theCTC pathways in ET.

Figure 3: Clinical rating of tremor (upper panel); tremor frequency (central panel) and tremor amplitude (lower panel) during the three measurement time points (baseline-T0, 5min after cTBS-T1 and 45min after cTBS-T2) in patients with ET. Black histograms indicate measurements in the real cerebellar cTBS session. White histograms indicate measurements in the sham cerebellar cTBS session.

REFERENCESDeuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord 1998; 13(Suppl 3): S2–S23.Deuschl G, Bergman H. Pathophysiology of nonparkinsonian tremors. Mov Disord 2002; 17 (Suppl 3):S41-S48.Chen R. Repetitive transcranial magnetic stimulation as a treatment for essential tremor? Clin Neurophysiol 2012; 123:850-851.

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