title: Clinical findings in sporadic Creutzfeldt-Jakob disease correlate with thalamic pathology.
abstract: The pathogenesis underlying the typical findings in Creutzfeldt-Jakob disease (CJD) such as periodic EEG changes or myoclonus is not fully understood. The thalamus possesses a high density of inhibitory neurones and serves as a crucial pacemaker of rhythmic EEG activity. As inhibitory neurones expressing parvalbumin (PV) are reduced in the cerebral cortex and hippocampus in sporadic CJD (sCJD), we studied the distribution and number of PV-immunoreactive neurones in sCJD thalami in order to determine whether damage to them could account for certain clinical findings. Immuno histochemical analysis was performed on the thalami from 21 sCJD patients and five controls. The number of PV+ neurones was counted in the thalamic nuclei and compared with clinical and molecular findings. In sCJD patients, PV+ neurones were significantly reduced in the ventrolateral posterior (VLp), ventrolateral anterior (VLa), anteroventral (AV), lateral dorsal (LD), mediodorsal (MD) and reticular (Re) thalamic nuclei (P < 0.05). The VLp was especially damaged in sCJD patients with homozygosity for methionine at codon 129 and scrapie prion protein (PrP(Sc)) type 1. Patients with typical EEG changes [periodic sharp wave complexes (PSWCs)] and myoclonus had a predominant loss of PV+ cells in the reticular thalamic nucleus. In conclusion, our data support the hypothesis that the damage to PV-immunoreactive neurones determines the generation of certain typical clinical features of CJD, i.e. PSWCs associated with myoclonus.
authors.affiliation: Department of Neuropathology, Georg-August University, Goettingen, Germany.
authors.forename: Henriette J
authors.initials: HJ
authors.lastname: Tschampa
authors.forename: Jochen W
authors.initials: JW
authors.lastname: Herms
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Schulz-Schaeffer
authors.forename: Brigitte
authors.initials: B
authors.lastname: Maruschak
authors.forename: Otto
authors.initials: O
authors.lastname: Windl
authors.forename: Ute
authors.initials: U
authors.lastname: Jastrow
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
authors.forename: Bernhard J
authors.initials: BJ
authors.lastname: Steinhoff
authors.forename: Sigrid
authors.initials: S
authors.lastname: Poser
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kretzschmar
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000328:Adult; D000368:Aged; D007562:Creutzfeldt-Jakob Syndrome / Q000473:pathology* / Q000503:physiopathology*; D004569:Electroencephalography; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009207:Myoclonus / Q000473:pathology* / Q000503:physiopathology*; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000473:pathology*; D010320:Parvalbumins / Q000032:analysis; D013788:Thalamus / Q000473:pathology* / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000032:analysis
chemical_list: D010320:Parvalbumins; D005680:gamma-Aminobutyric Acid