TY - JOUR
T1 - Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations
AU - Sundal, Christina
AU - Fujioka, Shinsuke
AU - Van Gerpen, Jay A.
AU - Wider, Christian
AU - Nicholson, Alexandra M.
AU - Baker, Matt
AU - Shuster, Elizabeth A.
AU - Aasly, Jan
AU - Spina, Salvatore
AU - Ghetti, Bernardino
AU - Roeber, Sigrun
AU - Garbern, James
AU - Tselis, Alex
AU - Swerdlow, Russell H.
AU - Miller, Bradley B.
AU - Borjesson-Hanson, Anne
AU - Uitti, Ryan J.
AU - Ross, Owen A.
AU - Stoessl, A. Jon
AU - Rademakers, Rosa
AU - Josephs, Keith A.
AU - Dickson, Dennis W.
AU - Broderick, Daniel
AU - Wszolek, Zbigniew K.
N1 - Funding Information:
Work was partially supported by the NIH/NINDS ( P50 NS072187 ); Mayo Clinic Florida (MCF) Research Committee CR program ( MCF #90052030 ); and Dystonia Medical Research Foundation . CS was sponsored by The Swedish and Gothenburg Societies for the Neurologically Disabled and The Gothenburg Foundation for Neurological Research , “Rune och Ulla Amlövs” Foundation for Neurological research , Capio Research Foundation , Thuréus Foundation for Geriatric research , Stiftelsen för Gamla Tjänarinnor , the Swedish Society of Medicine Gothenburg , and the Anna – Lisa and Bror Bjornssons Foundation for neurological research 2012/2013. AMN was partially supported by the Association for Frontotemporal Degeneration Postdoctoral Fellowship .
PY - 2013/10
Y1 - 2013/10
N2 - 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.
AB - 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.
KW - Autosomal dominant
KW - CSF1R mutation
KW - HDLS
KW - Parkinsonism
KW - White matter disorders
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U2 - 10.1016/j.parkreldis.2013.05.013
DO - 10.1016/j.parkreldis.2013.05.013
M3 - Article
C2 - 23787135
AN - SCOPUS:84883277154
SN - 1353-8020
VL - 19
SP - 869
EP - 877
JO - Parkinsonism and Related Disorders
JF - Parkinsonism and Related Disorders
IS - 10
ER -