Adult-onset mitochondrial movement disorders: a national picture from the Italian Network

J Neurol. 2022 Mar;269(3):1413-1421. doi: 10.1007/s00415-021-10697-1. Epub 2021 Jul 14.

Abstract

Introduction: Both prevalence and clinical features of the various movement disorders in adults with primary mitochondrial diseases are unknown.

Methods: Based on the database of the "Nation-wide Italian Collaborative Network of Mitochondrial Diseases", we reviewed the clinical, genetic, neuroimaging and neurophysiological data of adult patients with primary mitochondrial diseases (n = 764) where ataxia, myoclonus or other movement disorders were part of the clinical phenotype.

Results: Ataxia, myoclonus and movement disorders were present in 105/764 adults (13.7%), with the onset coinciding or preceding the diagnosis of the mitochondrial disease in 49/105 (46.7%). Ataxia and parkinsonism were the most represented, with an overall prevalence at last follow-up of 59.1% and 30.5%, respectively. Hyperkinetic movement disorders were reported in 15.3% at last follow-up, being the less common reported movement disorders. The pathogenic m.8344A > G and POLG variants were always associated with a movement disorder, while LHON variants and mtDNA single deletions were more commonly found in the subjects who did not present a movement disorder. The most common neuroimaging features were cortical and/or cerebellar atrophy, white matter hyperintensities, basal ganglia abnormalities and nigro-striatal degeneration. Almost 70% of patients with parkinsonism responded to dopaminergic therapy, mainly levodopa, and 50% with myoclonus were successfully treated with levetiracetam.

Conclusion: Movement disorders, mainly ataxia and parkinsonism, are important findings in adult primary mitochondrial diseases. This study underlies the importance of looking for a mitochondrial etiology in the diagnostic flowchart of a movement disorder and may help direct genetic screening in daily practice.

Keywords: Ataxia; Mitochondrial disorders; Movement disorders; Parkinsonism.

MeSH terms

  • Humans
  • Mitochondrial Diseases* / complications
  • Mitochondrial Diseases* / epidemiology
  • Mitochondrial Diseases* / genetics
  • Movement Disorders* / diagnosis
  • Movement Disorders* / epidemiology
  • Movement Disorders* / genetics
  • Myoclonus*
  • Parkinsonian Disorders* / complications
  • Parkinsonian Disorders* / epidemiology
  • Parkinsonian Disorders* / genetics
  • Phenotype