title: Neuronal intranuclear and neuropil inclusions for pathological assessment of Huntington's disease.
abstract: To evaluate the usefulness of neuronal intranuclear inclusions and neuropil inclusions for the pathological assessment of Huntington's disease (HD), their presence in neocortex was assessed by ubiquitin and N-terminal huntingtin immunohistochemistry in a consecutive series of 195 autopsy brains of individuals with a positive or tentative clinical diagnosis of, or at risk for, HD. The findings were correlated with striatal pathology (n = 190), CAG repeat length (n = 85) and original pathological diagnosis (n = 186). The antibodies detected both these inclusions in 181 patients with HD pathology > or = Vonsattel et al's grade I, five patients lacking striatal tissue for review, and two at-risk individuals with grade 0 and grade I HD pathology, respectively. One patient with HD-like pathology and two patients and four at-risk individuals without HD pathology lacked HD inclusions. In the genetically analyzed cases, the inclusions were exclusively and consistently observed in association with repeat expansion [(CAG)(n) > or = 39, n = 81]. Thirteen inclusion-positive cases, including the grade 0 at-risk individual, had a false negative original pathological diagnosis of HD and four had an unjustly questionable diagnosis. A false positive diagnosis was made in the inclusion-negative case with HD-like pathology. These results indicate that immunohistochemical analysis for HD inclusions facilitates the pathological evaluation of HD and enhances its accuracy.
authors.affiliation: Department of Neurology, Leiden University Medical Center, The Netherlands. m.l.c.maat-schieman@lumc.nl
authors.forename: Marion
authors.initials: M
authors.lastname: Maat-Schieman
authors.forename: Raymund
authors.initials: R
authors.lastname: Roos
authors.forename: Monique
authors.initials: M
authors.lastname: Losekoot
authors.forename: Josephine
authors.initials: J
authors.lastname: Dorsman
authors.forename: Corrie
authors.initials: C
authors.lastname: Welling-Graafland
authors.forename: Ingrid
authors.initials: I
authors.lastname: Hegeman-Kleinn
authors.forename: Freerk
authors.initials: F
authors.lastname: Broeyer
authors.forename: Martijn
authors.initials: M
authors.lastname: Breuning
authors.forename: Sjoerd
authors.initials: S
authors.lastname: van Duinen
mesh_terms: D000328:Adult; D000368:Aged; D042622:DNA Repeat Expansion / Q000235:genetics; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D002479:Inclusion Bodies / Q000473:pathology*; D045586:Intranuclear Inclusion Bodies / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D019579:Neocortex / Q000473:pathology*; D017072:Neostriatum / Q000473:pathology; D019581:Neuropil / Q000473:pathology*