Three cases of Creutzfeldt–Jakob disease with prion protein gene codon180 mutation presenting with pathological laughing and crying

An autopsy case of Creutzfeldt‐Jakob disease with a prion protein gene codon 180 mutation presenting with pathological laughing and an exaggerated startle reaction

“…The clinical diagnosis of CJD in the present case was largely based on MRI findings in the early disease stage. Previous reports have indicated that cases of V180I gCJD exhibit characteristic swelling in the cerebral cortex on T2‐weighted and FLAIR images as well as widespread cortical hyperintensity on diffusion‐weighted images, except in the medial occipital and cerebellar cortices . Based on the present case, we corroborate the hypothesis that characteristic MRI findings in the cerebral neocortex can provide a foundation for suspecting V180I gCJD.…”

“…In the present case, pathological laughing appeared and fluctuated in tandem with the startle reaction; additionally, both symptoms resolved simultaneously before the patient reached an akinetic mutism state. As previously described, the authors have not identified pathological laughing in any CJD patients except for the V180I gCJD cases . Furthermore, pathological laughing was not noticed in our previous research on the clinical findings of CJD .…”

“…Recently, pathological laughing (pathological laughter) and an exaggerated startle reaction (startle reflex) have been proposed as pathognomonic findings in V180I gCJD; however, the pathological basis of these symptoms is unclear. Here, we report the clinicopathological findings of a patient with V180I gCJD who presented with conspicuous pathological laughing and a prominent startle reaction.…”

“…Here, we report the clinicopathological findings of a patient with V180I gCJD who presented with conspicuous pathological laughing and a prominent startle reaction. Previously, we reported three cases of V180I gCJD with these key symptoms; in the present report, we provide an update on the case corresponding to the previously published case 1 . When the case was last published, the patient was still alive at 18 months post‐symptom onset.…”

“…CJD with point mutation of valine to isoleucine at codon 180 of PrP (V180I gCJD) is the most frequent form of gCJD in Japan, whereas this variant is extremely rare in Europe and North America . According to several previous reports, the clinical features of V180I gCJD are relatively uniform but differ from those of sporadic CJD as follows: (i) an older age of onset; (ii) prolonged disease duration with a slower course of progression; (iii) cerebral cortical symptoms such as aphasia, apraxia and hemiparesis in the early stage of disease; (iv) a lower positive rate of brain‐specific proteins such as neuron‐specific enolase, total tau protein, and 14–3‐3 protein in cerebrospinal fluid (CSF); (v) the absence of PSWCs on EEG throughout the disease course; (vi) less prominent myoclonus with a later time of onset; and (vii) a lack of affected family members and thus appearance as a sporadic neurodegenerative disorder. These clinical features make it difficult to diagnosis V180I gCJD without knowledge of the underlying PrP gene mutation, such that cases are sometimes misdiagnosed as neurodegenerative disorders such as corticobasal degeneration and Alzheimer's disease (AD) …”