Movement disorders in genetically confirmed mitochondrial disease and the putative role of the cerebellum

TY - JOUR

T1 - Movement disorders in genetically confirmed mitochondrial disease and the putative role of the cerebellum

AU - Schreglmann, Sebastian R

AU - Riederer, Franz

AU - Galovic, Marian

AU - Ganos, Christos

AU - Kägi, Georg

AU - Waldvogel, Daniel

AU - Jaunmuktane, Zane

AU - Schaller, Andre

AU - Hidding, Ute

AU - Krasemann, Ernst

AU - Michels, Lars

AU - Baumann, Christian R

AU - Bhatia, Kailash

AU - Jung, Hans H

N1 - © 2017 International Parkinson and Movement Disorder Society.

PY - 2018/1

Y1 - 2018/1

N2 - BACKGROUND: Mitochondrial disease can present as a movement disorder. Data on this entity's epidemiology, genetics, and underlying pathophysiology, however, is scarce.OBJECTIVE: The objective of this study was to describe the clinical, genetic, and volumetric imaging data from patients with mitochondrial disease who presented with movement disorders.METHODS: In this retrospective analysis of all genetically confirmed mitochondrial disease cases from three centers (n = 50), the prevalence and clinical presentation of video-documented movement disorders was assessed. Voxel-based morphometry from high-resolution MRI was employed to compare cerebral and cerebellar gray matter volume between mitochondrial disease patients with and without movement disorders and healthy controls.RESULTS: Of the 50 (30%) patients with genetically confirmed mitochondrial disease, 15 presented with hypokinesia (parkinsonism 3/15), hyperkinesia (dystonia 5/15, myoclonus 3/15, chorea 2/15), and ataxia (3/15). In 3 patients, mitochondrial disease presented as adult-onset isolated dystonia. In comparison to healthy controls and mitochondrial disease patients without movement disorders, patients with hypo- and hyperkinetic movement disorders had significantly more cerebellar atrophy and an atrophy pattern predominantly involving cerebellar lobules VI and VII.CONCLUSION: This series provides clinical, genetic, volumetric imaging, and histologic data that indicate major involvement of the cerebellum in mitochondrial disease when it presents with hyper- and hypokinetic movement disorders. As a working hypothesis addressing the particular vulnerability of the cerebellum to energy deficiency, this adds substantially to the pathophysiological understanding of movement disorders in mitochondrial disease. Furthermore, it provides evidence that mitochondrial disease can present as adult-onset isolated dystonia. © 2017 International Parkinson and Movement Disorder Society.

AB - BACKGROUND: Mitochondrial disease can present as a movement disorder. Data on this entity's epidemiology, genetics, and underlying pathophysiology, however, is scarce.OBJECTIVE: The objective of this study was to describe the clinical, genetic, and volumetric imaging data from patients with mitochondrial disease who presented with movement disorders.METHODS: In this retrospective analysis of all genetically confirmed mitochondrial disease cases from three centers (n = 50), the prevalence and clinical presentation of video-documented movement disorders was assessed. Voxel-based morphometry from high-resolution MRI was employed to compare cerebral and cerebellar gray matter volume between mitochondrial disease patients with and without movement disorders and healthy controls.RESULTS: Of the 50 (30%) patients with genetically confirmed mitochondrial disease, 15 presented with hypokinesia (parkinsonism 3/15), hyperkinesia (dystonia 5/15, myoclonus 3/15, chorea 2/15), and ataxia (3/15). In 3 patients, mitochondrial disease presented as adult-onset isolated dystonia. In comparison to healthy controls and mitochondrial disease patients without movement disorders, patients with hypo- and hyperkinetic movement disorders had significantly more cerebellar atrophy and an atrophy pattern predominantly involving cerebellar lobules VI and VII.CONCLUSION: This series provides clinical, genetic, volumetric imaging, and histologic data that indicate major involvement of the cerebellum in mitochondrial disease when it presents with hyper- and hypokinetic movement disorders. As a working hypothesis addressing the particular vulnerability of the cerebellum to energy deficiency, this adds substantially to the pathophysiological understanding of movement disorders in mitochondrial disease. Furthermore, it provides evidence that mitochondrial disease can present as adult-onset isolated dystonia. © 2017 International Parkinson and Movement Disorder Society.

KW - Journal Article

U2 - 10.1002/mds.27174

DO - 10.1002/mds.27174

M3 - SCORING: Journal article

C2 - 28901595

VL - 33

SP - 146

EP - 155

JO - MOVEMENT DISORD

JF - MOVEMENT DISORD

SN - 0885-3185

IS - 1

ER -