Article Text

Concomitant fragile X-associated tremor ataxia syndrome and Parkinson's disease: a clinicopathological report of two cases
  1. Eduardo De Pablo-Fernandez1,2,
  2. Karen M Doherty1,2,
  3. Janice L Holton1,2,3,
  4. Tamas Revesz1,2,
  5. Atbin Djamshidian1,
  6. Patricia Limousin3,4,
  7. Kailash P Bhatia3,4,
  8. Thomas T Warner1,2,3,
  9. Andrew J Lees1,2,
  10. Helen Ling1,2
  1. 1 Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, London, UK
  2. 2 Queen Square Brain Bank for Neurological Disorders, UCL Institute of Neurology, London, UK
  3. 3 National Hospital for Neurology and Neurosurgery, Queen Square, UCL Hospitals NHS Foundation Trust, London, UK
  4. 4 Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London, UK
  1. Correspondence to Dr Helen Ling, Reta Lila Weston Institute of Neurological Studies, UCL Institute of Neurology, 1 Wakefield Street, London WC1N 1PJ, UK; h.ling{at}

Statistics from


Parkinsonism is common in fragile X-associated tremor/ataxia syndrome (FXTAS) but its underlying pathophysiology remains unknown. Our group reported a patient with FXTAS and parkinsonism, and in vivo evidence of presynaptic and postsynaptic nigrostriatal dysfunction.1 We report the histological findings of this case (case 1) and another case with dual pathologies of FXTAS and Lewy body Parkinson's disease (PD).


Genetic testing for FXTAS was requested in seven cases from the Queen Square Brain Bank for Neurological Disorders (QSBB) based on the characteristic radiological ‘middle cerebellar peduncle’ (MCP) sign (case 1, diagnosis confirmed in life) and histological findings of round, eosinophilic p62-positive neuronal intranuclear inclusions in the hippocampus or unexplained cerebellar degeneration (6 postmortem cases were tested). Two cases were positive for FMR1 premutation and both showed histological features of FXTAS and PD. The QSBB brain donor programme was approved by a Research Ethics Committee and written consent for research was obtained from all cases.

Case reports

Case 1

A 68-year-old man presented with a 10-year history of slowly progressive right-hand tremor. There was no family history of neurological disorders or mental retardation. Examination showed hypomimia, asymmetric rest and kinetic tremor, rigidity, mild bradykinesia and inability to tandem walk. The patient was diagnosed with tremor-predominant PD but did not respond to L-dopa (600 mg/day). Over the next few years he developed mild cognitive impairment, gait ataxia and intention tremor. Brain MRI demonstrated the MCP sign and diffuse atrophy. Genetic analysis confirmed FMR1 premutation with 87 CGG expansion. 123I-FP-CIT SPECT revealed …

View Full Text

Supplementary materials

  • Supplementary Data

    This web only file has been produced by the BMJ Publishing Group from an electronic file supplied by the author(s) and has not been edited for content.

    Files in this Data Supplement:

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.