title: Parkinsonian features in hereditary diffuse leukoencephalopathy with spheroids (HDLS) and CSF1R mutations.
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.
authors.affiliation: Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA.
authors.forename: Christina
authors.initials: C
authors.lastname: Sundal
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Fujioka
authors.forename: Jay A
authors.initials: JA
authors.lastname: Van Gerpen
authors.forename: Christian
authors.initials: C
authors.lastname: Wider
authors.forename: Alexandra M
authors.initials: AM
authors.lastname: Nicholson
authors.forename: Matt
authors.initials: M
authors.lastname: Baker
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Shuster
authors.forename: Jan
authors.initials: J
authors.lastname: Aasly
authors.forename: Salvatore
authors.initials: S
authors.lastname: Spina
authors.forename: Bernardino
authors.initials: B
authors.lastname: Ghetti
authors.forename: Sigrun
authors.initials: S
authors.lastname: Roeber
authors.forename: James
authors.initials: J
authors.lastname: Garbern
authors.forename: Alex
authors.initials: A
authors.lastname: Tselis
authors.forename: Russell H
authors.initials: RH
authors.lastname: Swerdlow
authors.forename: Bradley B
authors.initials: BB
authors.lastname: Miller
authors.forename: Anne
authors.initials: A
authors.lastname: Borjesson-Hanson
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Uitti
authors.forename: Owen A
authors.initials: OA
authors.lastname: Ross
authors.forename: A Jon
authors.initials: AJ
authors.lastname: Stoessl
authors.forename: Rosa
authors.initials: R
authors.lastname: Rademakers
authors.forename: Keith A
authors.initials: KA
authors.lastname: Josephs
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Dickson
authors.forename: Daniel
authors.initials: D
authors.lastname: Broderick
authors.forename: Zbigniew K
authors.initials: ZK
authors.lastname: Wszolek
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use; D018070:Biological Specimen Banks; D001921:Brain / Q000473:pathology; D005190:Family; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology; D005911:Gliosis / Q000150:complications / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D006801:Humans; D018476:Hypokinesia / Q000209:etiology; D007091:Image Processing, Computer-Assisted; D056784:Leukoencephalopathies / Q000150:complications / Q000235:genetics* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009127:Muscle Rigidity / Q000209:etiology / Q000503:physiopathology; D009154:Mutation / Q000235:genetics* / Q000502:physiology*; D059906:Neuroimaging; D010300:Parkinson Disease / Q000209:etiology / Q000235:genetics* / Q000473:pathology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000235:genetics* / Q000502:physiology; D014202:Tremor / Q000209:etiology; D006113:United Kingdom; D055815:Young Adult
chemical_list: D000978:Antiparkinson Agents; D016186:Receptor, Macrophage Colony-Stimulating Factor
keywords: Autosomal dominant; CSF1R mutation; HDLS; Parkinsonism; White matter disorders