Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations |
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Authors: | 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 Zbigniew K. Wszolek |
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Affiliation: | 1. Department of Neurology, Mayo Clinic, Jacksonville, FL, USA;2. Department of Clinical Neuroscience and Rehabilitation, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden;3. Department of Neuroscience, Mayo Clinic Florida, Jacksonville, FL, USA;4. Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway;5. Department of Pathology and Laboratory Medicine and Indiana Alzheimer Disease Center, Indiana University School of Medicine, Indianapolis, USA;6. Center for Neuropathology and Prion Research, Ludwig-Maximilians University Munich, Munich, Germany;7. Department of Neurology, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA;8. Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA;9. Department of Neurology, University of Kansas School of Medicine, Kansas City, USA;10. Department of Pathology, Texas Tech University Health Sciences Center, Lubbock, TX, USA;11. Pacific Parkinson''s Research Centre, University of British Columbia & Vancouver Coastal Health, Vancouver, BC, Canada;12. Department of Neurology, Mayo Clinic Rochester, MT, USA;13. Department of Neuroradiology, Mayo Clinic Florida, Jacksonville, FL, USA |
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Abstract: | 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. |
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Keywords: | HDLS Parkinsonism Autosomal dominant White matter disorders |
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