Clinicopathological findings of an MM2-cortical-type sporadic Creutzfeldt-Jakob disease patient with cortical blindness during a course of glaucoma and age-related macular degeneration

Iwasaki

Waza³

et al. 2020

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The clinical characteristics of genetic Creutzfeldt-Jakob disease (gCJD) with a V180I mutation in the PRNP gene (V180I gCJD) are unique: elderly-onset, gradual progression, sporadic fashion, and cortical oedematous hyper-intensity on diffusion-weighted MRI (DW-MRI). This phenotype may become a potential target of future clinical therapeutic trials. The average disease duration of V180I gCJD patients is 23-27 months; however, considerably long-term survivors are also reported. The factors influencing survival and the clinicopathological characteristics of long-term survivors remain unknown. Herein, we report clinicopathological findings of a long-term survivor of V180I gCJD. A 78year old woman was admitted to our hospital due to dementia and left hand tremor approximately 1.5 months after symptom onset. Neurological examination revealed dementia, frontal signs, and left hand tremor at admission. She had no family history of dementia or other neurological disease. DW-MRI revealed cortical oedematous hyper-intensities in the bilateral frontal lobes and the right temporal and parietal lobes. PRNP gene analysis indicated a V180I mutation with methionine homozygosity at codon 129. The symptoms gradually progressed, and she died of aspiration pneumonia 61 months after symptom onset. Neuropathological examination revealed severe cerebral atrophy with moderate to severe gliosis, but the brainstem was well preserved. Various-sized and nonconfluent vacuole type spongiform changes were extensively observed in the cerebral cortices. Prion protein (PrP) immunostaining revealed weak and synaptic-type PrP deposits in the cerebral cortices. We consider that long-term tube feeding, and very mild brainstem involvement may be associated with the long-term survival of our V180I gCJD patient. ARTICLE HISTORY

Section: Discussionmentioning

confidence: 99%

Clinicopathological findings of a long-term survivor of V180I genetic Creutzfeldt-Jakob disease

Iwasaki

Waza³

et al. 2020

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“…All patients were confirmed by genetic analysis to have homozygosity for methionine at codon 129 and no prion protein gene mutation. Two patients in the MM2c-sCJD group, one of whom we previously reported [10], and three patients in the MM1-sCJD group, underwent autopsy.…”

Section: Resultsmentioning

confidence: 99%

“…To confirm the type of PrP res , brain homogenates were analysed by Western blotting using the 3F4 antibody as well as type 1 and type 2 PrP Sc -specific antibodies [10]. Histopathological analyses of the brains of patients with MM2c-sCJD revealed spongiform changes comprised of large confluent vacuoles, and perivascular-and rough plaque-type PrP Sc deposition in the cerebral cortices with preserved inferior olivary nuclei [10]. Spongiform changes with small vacuoles and synaptic-type PrP Sc deposition in the cerebral cortices were identified in the brains of patients with MM1-sCJD.…”

Section: Resultsmentioning

confidence: 99%

Focal sharp waves are a specific early-stage marker of the MM2-cortical form of sporadic Creutzfeldt-Jakob disease

Matsubayashi

Akaza

et al. 2020

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Periodic sharp wave complexes (PSWCs), identified using electroencephalography, are observed in less than half of patients with the methionine homozygosity type 2 cortical (MM2c) form of sporadic Creutzfeldt-Jakob disease (sCJD), and only at a later stage of the disease. In this study, we identified early and specific markers on the electroencephalograms (EEGs) of patients with MM2c-sCJD. We retrospectively investigated the clinical records, EEGs, and magnetic resonance imaging (MRI) scans of patients diagnosed with sCJD and compared the EEG findings of MM2c-sCJD and MM1/classic sCJD groups. The records of six patients with MM2c-sCJD and eight with MM1/classic sCJD were included. The median ages of onset in the MM2c-and MM1/ classic sCJD groups were 75.0 (range, 60-83) and 72.5 (range, 51-74) years, respectively, and the average durations between disease onset and the first EEG were 9.17 (range, 4-15) and 1.88 (range, 1-4) months, respectively. Focal sharp waves and/or focal spike-and-wave complexes in the brain regions corresponding with cortical hyperintensities on MRI scans were identified on the EEGs of patients with MM2c-sCJD in the early stages of disease progression. In contrast, EEGs of patients in the early stages of MM1/classic sCJD showed lateralized or generalized diffuse sharp waves and spike-and-wave complexes, which were not limited to cortical hyperintensities identified with MRI scans. Our findings indicate that focal sharp waves and/or focal spike-and-wave complexes on the EEGs of patients in the early phase of MM2c-sCJD are characteristic of the disease, suggesting the possible usefulness of this characteristic for early diagnosis.

“…The frequency of MM2Ctype sCJD is reportedly 2.0% and 6.7% in Caucasian and Japanese sCJD populations, respectively [1]. The average disease duration of MM2C-type sCJD is 15.7--20.6 months [1][2][3]; however, long-term survivors (more than 3 years) have also been reported [4,5]. The implementation of appropriate care for dysphagia is an important factor that enables long-term survival in patients with MM2C-type sCJD [5], and genetic CJD with V180I mutation in PRNP (V180I gCJD) [6].…”

Section: Introductionmentioning

confidence: 99%

Long-term preservation of pharyngeal swallowing function in MM2-cortical-type sporadic Creutzfeldt-Jakob disease

Kunieda

Kudo

et al. 2021

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Swallowing function in long-term survivors of Creutzfeldt-Jakob disease (CJD) has not been elucidated. Herein, we report a patient with MM2-cortical-type sporadic CJD (MM2C-type sCJD) with long-term preservation of pharyngeal swallowing function using videofluoroscopic (VF) examination of swallowing. A 55-year-old woman was admitted to hospital because of dyscalculia and memory disturbance 3 years after the onset of these symptoms. Neurological examination revealed dementia, extrapyramidal signs, and delusion. Diffusion-weighted MRI revealed bilateral hyperintensity in the basal ganglia and frontal, temporal, and parietal cortices. No mutation with the methionine homozygote at codon 129 was found on PRNP gene analysis. VF was performed 68 months after the onset. Although bolus transport from the oral cavity to the pharynx worsened, the pharyngeal swallowing function was preserved even 68 months after onset. Serial MRI examinations revealed no apparent atrophy of the brainstem. Single photon emission computed tomography revealed that the regional cerebral blood flow in the brainstem was preserved. These findings suggest that pseudobulbar palsy is the pathophysiology underlying dysphagia in long-term survivors of MM2C-type sCJD, probably owing to preserved brainstem function even in a state of akinetic mutism.