title: Revisiting the Heidenhain Variant of Creutzfeldt-Jakob Disease: Evidence for Prion Type Variability Influencing Clinical Course and Laboratory Findings.
abstract: The Heidenhain variant defines a peculiar clinical presentation of sporadic Creutzfeldt-Jakob disease (sCJD) characterized by isolated visual disturbances at disease onset and reflecting the early targeting of prions to the occipital cortex. Molecular and histopathological typing, thus far performed in 23 cases, has linked the Heidenhain variant to the MM1 sCJD type. To contribute a comprehensive characterization of cases with the Heidenhain variant, we reviewed a series of 370 definite sCJD cases. Eighteen patients (4.9%) fulfilled the selection criteria. Fourteen of them belonging to sCJD types MM1 or MM1+2C had a short duration of isolated visual symptoms and overall clinical disease, a high prevalence of periodic sharp-wave complexes in EEG, and a marked increase of cerebrospinal fluid proteins t-tau and 14-3-3 levels. In contrast, three cases of the MM 2C or MM 2+1C types showed a longer duration of isolated visual symptoms and overall clinical disease, non-specific EEG findings, and cerebrospinal fluid concentration below threshold for the diagnosis of "probable" CJD of both 14-3-3 and t-tau. However, a brain DWI-MRI disclosed an occipital cortical hyperintensity in the majority of examined cases of both groups. While confirming the strong linkage with the methionine genotype at the polymorphic codon 129 of the prion protein gene, our results definitely establish that the Heidenhain variant can also be associated with the MM 2C sCJD type in addition to the more common MM1 type. Likewise, our results highlight the significant differences in clinical evolution and laboratory findings between cases according to the dominant PrPSc type (type 1 versus type 2).
authors.affiliation: Dipartimento di Scienze Biomediche e Neuromotorie (DiBiNeM), Università di Bologna, Bologna, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Baiardi
authors.affiliation: Dipartimento di Scienze Biomediche e Neuromotorie (DiBiNeM), Università di Bologna, Bologna, Italy.|IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy.
authors.forename: Sabina
authors.initials: S
authors.lastname: Capellari
authors.affiliation: Dipartimento di Biologica Cellulare e Neuroscienze, Istituto Superiore di Sanità, Roma, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Ladogana
authors.affiliation: UOC di Neurologia, Ospedale Morgagni-Pierantoni, Forlì, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Strumia
authors.affiliation: UOC di Neurologia, Ospedale Ramazzini, Carpi, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Santangelo
authors.affiliation: Dipartimento di Biologica Cellulare e Neuroscienze, Istituto Superiore di Sanità, Roma, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pocchiari
authors.affiliation: Dipartimento di Scienze Biomediche e Neuromotorie (DiBiNeM), Università di Bologna, Bologna, Italy.|IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy.
authors.forename: Piero
authors.initials: P
authors.lastname: Parchi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D007562:Creutzfeldt-Jakob Syndrome / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011328:Prions / Q000235:genetics / Q000378:metabolism*
chemical_list: D011328:Prions
keywords: Dementia; molecular typing; neurodegenerative diseases; occipital cortex; prion diseases; prion protein