Deep brain stimulation reduces (nocturnal) dyskinetic exacerbations in patients with ADCY5 mutation: a case series

Ana Luísa de Almeida Marcelino,Werner Poewe,Andrea A. Kühn,Patricia Krause,Tina Mainka,Christos Ganos

doi:10.1007/s00415-020-09871-8

Abstract

Mutations in the ADCY5 gene can cause a complex hyperkinetic movement disorder. Episodic exacerbations of dyskinesia are a particularly disturbing symptom as they occur predominantly during night and interrupt sleep. We present the clinical short- and long-term effects of pallidal deep brain stimulation (DBS) in three patients with a confirmed pathogenic ADCY5 mutation. Patients were implanted with bilateral pallidal DBS at the age of 34, 20 and 13 years. Medical records were reviewed for clinical history. Pre- and postoperative video files were assessed using the “Abnormal Involuntary Movement Scale” (AIMS) as well as the motor part of the “Burke Fahn Marsden Dystonia Rating Scale” (BFMDRS). All patients reported subjective general improvement ranging from 40 to 60%, especially the reduction of nocturnal episodic dyskinesias (80–90%). Objective scales revealed only a mild decrease of involuntary movements in all and reduced dystonia in one patient. DBS-induced effects were sustained up to 13 years after implantation. We demonstrate that treatment with pallidal DBS was effective in reducing nocturnal dyskinetic exacerbations in patients with ADCY5-related movement disorder, which was sustained over the long term.

Highlights

The phenotypic presentation of patients carrying pathogenic ADCY5 gene mutations includes a wide range of movement disorders, most notably chorea, dystonia and myoclonus [1,2,3]
Three patients with genetically confirmed ADCY5-related hyperkinetic movement disorder treated with deep brain stimulation (DBS) of the Globus pallidus pars interna (GPi) at Charité—Universitätsmedizin Berlin were identified
All cases showed mixed movement disorder phenotypes comprising chorea, dystonia and myoclonus, in line with previous descriptions of this genetic entity [1, 3, 5, 6]. Core features such as axial hypotonia, facial dyskinesia and episodic exacerbations of the generalized movement disorder were present in all patients [2]

Summary

Introduction

The phenotypic presentation of patients carrying pathogenic ADCY5 gene mutations includes a wide range of movement disorders, most notably chorea, dystonia and myoclonus [1,2,3]. Two further core features are axial hypotonia and episodic exacerbations of hyperkinesias often referred to as “ballistic bouts” or “spells”, which predominantly occur during drowsiness or sleep [1, 3, 4]. Even though these episodic exacerbations are often clinically misdiagnosed as nocturnal frontal lobe or other types of focal epilepsy, ictal EEG abnormalities are absent in most cases. Since the discovery of the mutated gene responsible for this phenotype in 2012 by whole exome sequencing within this same family [7], more than 70 cases have been described until today.

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Conclusion