Objective: To describe the prevalence and phenotype of movement disorders (MDs) in patients with mitochondrial cytopathy (MC) and corresponding pattern of cerebral atrophy.

Background: MCs encompass a group of syndromes that are caused by respiratory chain dysfunction resulting in a variable neurological phenotype.

Methods: Retrospective analysis of all genetically confirmed MC cases (n=60) from three European MDs centers. We assessed the prevalence and clinical presentation of video-documented MDs in patients with genetically confirmed MC. In all patients with available high-resolution MR imaging (n=14), voxel-based morphometry (VBM) was used to quantify grey matter in patients with (n=6) and without MDs (n=8) and compared with healthy controls (n=110).

Results: 14/60 MC patients (24%) presented relevant MDs during the course of their disease. Phenotypes included dystonia (6/14), parkinsonism (3/14), myoclonus (3/14) and chorea (2/14). Three cases initially presented as isolated, task-specific dystonia. In comparison to all other MC cases, MC patients with MDs significantly more often showed clinical vestibulocochlear (χ2 = 9.74, p=0.004) and cerebellar signs (χ2 = 30.5, p<0.001). Cerebellar atrophy was not reported more often on routine scans. On autopsy one MC case presenting with myoclonus showed marked dentate nucleus atrophy with preserved cerebellar cortical architecture. Age-corrected volumetric analysis revealed no difference in overall grey matter volume (GMV) between MC patients and controls, while cerebellar GMV was significantly reduced (0.31±0.08; n=14; vs. 0.39±0.05; n=110; p=0.001). Voxel-wise analysis showed a consistent atrophy of cerebellar lobule 6 in MC patients with MDs when compared to controls (p<0.05, multiple corrections) and also when compared to MC patients without MDs (p<0.005, uncorrected), which was irrespective of motor phenotype.

Conclusions: This series documents the prevalence (24%) and spectrum of MDs in genetically confirmed MC patients. It provides evidence that MC can present as isolated dystonia. Converging evidence from clinical, histological and morphometric data points to an involvement of the cerebellum in the pathophysiology of MDs in MC patients. The mechanism connecting this atrophy pattern with both hypo- and hyperkinetic phenotypes remains to be studied further.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/same-cerebellar-atrophy-pattern-in-hyper-and-hypokinetic-movement-disorders-due-to-mitochondrial-cytopathy/