Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations

Christina Sundal, Shinsuke Fujioka, Jay A. Van Gerpen, Christian Wider, Alexandra M. Nicholson, Matt Baker, Elizabeth A. Shuster, Jan Aasly, Salvatore Spina, Bernardino Ghetti, Sigrun Roeber, James Garbern, Alex Tselis, Russell H. Swerdlow, Bradley B. Miller, Anne Borjesson-Hanson, Ryan J. Uitti, Owen A. Ross, A. Jon Stoessl, Rosa RademakersKeith A. Josephs, Dennis W. Dickson, Daniel Broderick, Zbigniew K. Wszolek

Research output: Contribution to journalArticlepeer-review

45 Scopus citations


Atypical Parkinsonism associated with white matter pathology has been described in cerebrovascular diseases, mitochondrial cytopathies, osmotic demyelinating disorders, leukoencephalopathies leukodystrophies, and others. Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal dominant disorder with symptomatic onset in midlife and death within a few years after symptom onset. Neuroimaging reveals cerebral white matter lesions that are pathologically characterized by non-inflammatory myelin loss, reactive astrocytosis, and axonal spheroids. Most cases are caused by mutations in the colony-stimulating factor 1 receptor (CSF1R) gene. We studied neuropathologically verified HDLS patients with CSF1R mutations to assess parkinsonian features. Ten families were evaluated with 16 affected individuals. During the course of the illness, all patients had at least some degree of bradykinesia. Fifteen patients had postural instability, and seven had rigidity. Two patients initially presented with parkinsonian gait and asymmetrical bradykinesia. These two patients and two others exhibited bradykinesia, rigidity, postural instability, and tremor (two with resting) early in the course of the illness. Levodopa/carbidopa therapy in these four patients provided no benefit, and the remaining 12 patients were not treated. The mean age of onset for all patients was about 45 years (range, 18-71) and the mean disease duration was approximately six years (range, 3-11).We also reviewed HDLS patients published prior to the CSF1R discovery for the presence of parkinsonian features. Out of 50 patients, 37 had gait impairments, 8 rigidity, 7 bradykinesia, and 5 resting tremor. Our report emphasizes the presence of atypical Parkinsonism in HDLS due to CSF1R mutations.

Original languageEnglish (US)
Pages (from-to)869-877
Number of pages9
JournalParkinsonism and Related Disorders
Issue number10
StatePublished - Oct 2013


  • Autosomal dominant
  • CSF1R mutation
  • HDLS
  • Parkinsonism
  • White matter disorders

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology


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