Case report
Myoclonus and tremor response to thalamic deep brain stimulation parameters in a patient with inherited myoclonus–dystonia syndrome

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Abstract

We present a 74-year-old woman with inherited myoclonus–dystonia, with predominant myoclonus and a novel mutation in the ɛ-sarcoglycan gene. The patient reports a life-long history of rapid, jerking movements, most severe in the upper extremities as well as a postural and action tremor. Bilateral deep brain stimulation (DBS) of the ventral intermediate nucleus of the thalamus was performed, and the patient demonstrated moderate clinical improvement in myoclonus. We studied the effects on myoclonus and tremor of varying DBS frequency and amplitude. The frequency tuning curve for myoclonus was similar to that of tremor, suggesting similar mechanisms by which DBS alleviates both disorders.

Introduction

Myoclonus refers to sudden, shock-like involuntary movements associated with brief bursts of muscle activity. Myoclonus is commonly inherited as an autosomal dominant trait, termed inherited myoclonus–dystonia (M–D) [1]. Clinical characteristics of M–D include myoclonic jerks affecting the neck, shoulders, and arms, and dystonic symptoms such as torticollis [1]. The M–D phenotype is clinically heterogeneous with variable expression of myoclonus and dystonia [1], and many cases are due to mutations in the ɛ-sarcoglycan (SGCE) gene [2], [3]. M–D has an onset in childhood or adolescence, a benign clinical course, and occurs in the absence of other neurological deficits [1], [4], [5].

Deep brain stimulation (DBS) is an effective treatment for several movement disorders. DBS of the internal segment of the globus pallidus is effective for generalized dystonia [6], [7], [8] and alleviates dystonia and myoclonus in M–D [9], [10], [11]. Amelioration of myoclonic, but not dystonic, symptoms of M–D has been reported with DBS of the ventral intermediate nucleus (Vim) of the thalamus. In a 61-year-old man, involuntary movements were reduced by 65% with unilateral stimulation [12] and by 80% with bilateral stimulation [13], and in a second case myoclonus was reduced by 90% with unilateral thalamic stimulation in a 21-year-old man [14].

We present a patient with an action and postural tremor and inherited M–D, with severe myoclonus and mild action-induced dystonia, resulting from a novel mutation in the SGCE gene. We quantify the effects of the Vim DBS frequency and amplitude on myoclonus and tremor. Tremor was suppressed and myoclonus was moderately controlled.

Section snippets

Case report

This was a 74-year-old woman with a history of tremor and myoclonic jerks. Her myoclonus was most prominent in her head and upper extremities. In addition to prominent action myoclonus, she exhibited bilateral postural and action tremor in the upper extremities. Over the last 5 years, she had moderate worsening of symptoms including a pronounced and constant jerking of her mouth, upper extremities, neck, torso, and sometimes legs. She recently lost the ability to write and feed herself. Her

Results

Myoclonus was alleviated, but not completely suppressed, and tremor was completely suppressed by intraoperative high frequency stimulation of the Vim, and the response to stimulation was immediate. Two weeks post-implant initial stimulation parameters were selected for the left (contacts 0–1+ with 1.5 V, 60 μs, and 185 Hz) and right (contacts 5–4+ with 2.8 V, 90 μs, and 185 Hz) electrodes, with continuous bilateral stimulation. Paresthesias in the contralateral hands were transient and myoclonic

Discussion

This patient has inherited M–D and a postural and action tremor. A diagnosis of M–D was genetically supported with the identification of a novel deletion mutation in the SGCE gene. Due to a poor response to medication, bilateral Vim DBS was performed and the effect of DBS was quantified. Vim was selected as the anatomical target for this case because the patient had tremor and a myoclonus predominant M–D phenotype. Vim DBS has been shown to improve myoclonus [12], [13], [14] and is a

Conflict of interest

The authors have reported no conflicts of interest.

Acknowledgements

This work was supported by NIH Grant R01-NS40894.

Thanks to Dr. Burton Scott, Dr. Valerie Street, and Dr. David Sommer for performing the blinded ratings.

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