Atypical parkinsonism and cerebrotendinous xanthomatosis: Report of a family with corticobasal syndrome and a literature review§

Authors

  • Ignacio Rubio-Agusti MD,

    1. Sobell Department for Movement Disorders and Motor Neuroscience, UCL Institute of Neurology, London, United Kingdom
    2. Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, United Kingdom
    3. Movement Disorders Unit, Department of Neurology, Hospital Universitari La Fe, Valencia, Spain
    Search for more papers by this author
  • Maja Kojovic MD,

    1. Sobell Department for Movement Disorders and Motor Neuroscience, UCL Institute of Neurology, London, United Kingdom
    Search for more papers by this author
  • Mark J. Edwards MRCP, PhD,

    1. Sobell Department for Movement Disorders and Motor Neuroscience, UCL Institute of Neurology, London, United Kingdom
    Search for more papers by this author
  • Elaine Murphy MRCP, FRCPath,

    1. Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, United Kingdom
    Search for more papers by this author
  • Hoskote S. Chandrashekar MD,

    1. Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom
    Search for more papers by this author
  • Robin H. Lachmann MRCP, PhD,

    1. Charles Dent Metabolic Unit, National Hospital for Neurology and Neurosurgery, London, United Kingdom
    Search for more papers by this author
  • Kailash P. Bhatia MRCP, FRCP

    Corresponding author
    1. Sobell Department for Movement Disorders and Motor Neuroscience, UCL Institute of Neurology, London, United Kingdom
    • Institute of Neurology, UCL, 12 Queen Square, London WC1N 3BG, United Kingdom

    Search for more papers by this author

  • Funding agencies: This work was undertaken at UCLH/UCL, which received a proportion of funding from the Department of Health's NIHR Biomedical Research Centres funding scheme.

  • Relevant conflicts of interest/financial disclosures: Nothing to report.

  • §

    Full financial disclosures and author roles may be found in the online version of this article.

Abstract

Cerebrotendinous xanthomatosis is an autosomal recessive inborn error of cholesterol metabolism. It presents with systemic and neurological symptoms, rarely including parkinsonism. Presented here are a clinical description of a new family with cerebrotendinous xanthomatosis and parkinsonism and a review of 13 additional cases reported in the literature. The index case developed corticobasal syndrome, previously not reported in cerebrotendinous xanthomatosis. His brother had parkinsonism with cerebellar features and cognitive impairment. In a literature review, median age of onset of parkinsonism was found to be 40 years. Nearly all patients had other neurological symptoms: cognitive (93%), pyramidal (93%), or cerebellar (53%). All patients had walking difficulties, with falls in 27%. Systemic features were common: cataracts (93%) or tendon xanthomata (87%). Frequent MRI abnormalities included cerebellar atrophy (100%), cerebral atrophy (80%), and dentate nuclei signal changes (80%). Functional dopaminergic imaging often demonstrated presynaptic denervation. Improvement with levodopa was frequent (91%) but mild. Progressive neurological decline occurred in 92% of patients despite treatment with chenodeoxycholic acid. Cerebrotendinous xanthomatosis should be considered in the differential diagnosis of atypical parkinsonism, including corticobasal syndrome, particularly with early age of onset and in the context of a complex neurological phenotype. Tendon xanthomata, early-onset cataracts, and radiological findings of cerebellar atrophy with lesions of the dentate nuclei are useful clinical clues. Symptomatic treatment with levodopa may help, but progressive neurological decline is frequent despite treatment with chenodeoxycholic acid. © 2012 Movement Disorder Society

Ancillary