Extrapyramidal symptoms in Wilson's disease are associated with olfactory dysfunction.
Wilson's disease is a rare autosomal recessive disorder characterized by the accumulation of copper, mainly in the liver and the brain. As copper accumulation in the brain leads to disturbances in basal ganglia function, neurological-type patients typically present with hypo- and hyperkinetic extrapyramidal symptoms, with Parkinsonism being very common. Although there are numerous reports on olfactory deficits in primary neurodegenerative disorders, olfactory function has not been investigated in metabolic disorders presenting with extrapyramidal features. Twenty-four patients with Wilson's disease participated in the investigation. All patients were treated pharmacologically. They comprised patients with liver disease alone (including mild enzyme elevation in asymptomatic individuals; n = 11) and/or neurological symptoms (n = 13) at the time of testing. Twenty-one patients underwent both [18F]fluoro-2-deoxy-D-glucose positron emission tomography ([18F]FDG-PET) and magnetic resonance imaging (MRI). The severity of extrapyramidal symptoms was judged using a clinical score system ranging from 0 (no symptoms) to 3 (severe symptoms). In all patients, psychophysical testing was performed using the Sniffin' Sticks, which involved tests for odor threshold, discrimination, and identification. Results from the present study revealed that Wilson's disease patients with neurological symptoms show a significant olfactory dysfunction compared to hepatic-type patients. Individuals who are more severely neurologically affected also present with a more pronounced olfactory deficit. Of interest, there was no significant effect of long-term treatment with penicillamine on olfactory function. Olfactory function did not correlate significantly with the presence of MRI visible lesions in the basal ganglia or with any regional glucose metabolism as measured by [18]F-FDG-PET. In conclusion, these findings indicate that the underlying pathological alterations with degeneration in the basal ganglia and neuronal loss in association with a marked increase of the copper content in this brain region play a role in the olfactory deficit.
Mueller
Antje
A
Smell & Taste Clinic, Department of Otorhinolaryngology, University of Dresden Medical School, Dresden, Germany. antje.mueller@uniklinikum-dresden.de
Reuner
Ulrike
U
Landis
Basile
B
Kitzler
Hagen
H
Reichmann
Heinz
H
Hummel
Thomas
T
D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000503:physiopathology; D001480:Basal Ganglia Diseases / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D002869:Chromosome Aberrations; D003300:Copper / Q000378:metabolism; D005116:Extrapyramidal Tracts / Q000503:physiopathology; D005260:Female; D019788:Fluorodeoxyglucose F18; D005808:Genes, Recessive; D006527:Hepatolenticular Degeneration / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D019636:Neurodegenerative Diseases / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D000857:Olfaction Disorders / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D009833:Olfactory Pathways / Q000503:physiopathology; D020734:Parkinsonian Disorders / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D049268:Positron-Emission Tomography; D012684:Sensory Thresholds / Q000502:physiology; D013223:Statistics as Topic
D001786:Blood Glucose; D019788:Fluorodeoxyglucose F18; D003300:Copper