MM2 subtype of sporadic Creutzfeldt-Jakob disease may underlie the clinical presentation of progressive supranuclear palsy
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The classical presentation of sporadic Creutzfeldt-Jakob disease (sCJD) is rapid progressive dementia often associated with myoclonus and ataxia followed by death in less than a year from diagnosis. The few patients in the literature who presented with parkinsonism and who were suspected to have progressive supranuclear palsy (PSP) all ran a malignant course and most of them died within 3 years of diagnosis. We screened the Queen Square Brain Bank database and, among 213 patients with a clinical diagnosis of PSP, we found ten patients with 3 years or less disease duration, including one patient with CJD pathology. We report this patient and review other similar cases from the literature. Ten additional cases with similar presentation were identified in the literature. The mean disease duration was 24.2 months. The classical clinical, radiological and laboratory findings for sCJD were absent in the majority of these cases. Clinical presentation of these patients consists of: early falls, prominent dementia, early vertical supranuclear gaze palsy and symmetric akinetic syndrome. In the patients who were subtyped at post-mortem, all four represented the MM2 subtype of sCJD. A rapidly progressive course of PSP with early falls, cognitive impairments and vertical supranuclear gaze palsy should raise suspicion of underlying sCJD pathology regardless of absence of supportive findings on ancillary tests. This case and the literature support the notion that biochemical properties of the prion protein can influence the clinical presentation of sCJD.
KeywordsCreutzfeldt-Jakob disease Prion MM2 Progressive supranuclear palsy Neuropathology
Dr Igor Petrovic is funded by the Ministry of Science; Republic of Serbia (projects no.175090). The Reta Lila Weston Trust for Medical Research funded this project and Dr Silveira-Moriyama and Dr Helen Ling are beneficiaries of Reta Lila Weston fellowships. Dr Luke Massey has been funded by a grant from the PSP (Europe) Association.
Conflicts of interest
The authors declare that they have no conflict of interest.
All human studies must have been approved by an ethics committee and have, therefore, been performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki.
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