Preserved regional cerebral blood flow in the occipital cortices, brainstem, and cerebellum of patients with V180I-129M genetic Creutzfeldt-Jakob disease in serial SPECT studies

Self Cite

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: Clinical Summarysupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

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

Hayashi

Iwasaki

Waza³

et al. 2020

Self Cite

“…1,2 In addition, cortical hyper-intensity in diffusion-weighted MR images (DW-MRI) is observed during the acute phases of status eplepticus 3 and CJD. Furthermore, V180I genetic CJD (gCJD) exhibits cortical-edematous hyper-intensities on DW-MRI, 4,5 which is similar to the acute phase of status epilepticus. Thus, non-prion encephalitis/encephalopathy with convulsion is an important differential diagnosis of prion disease.…”

Section: Introductionmentioning

confidence: 99%

“…3 Moreover, this duration is shorter than the duration in V180I gCJD in serial MRI studies. 5 Therefore, CSF samples and/or MRI from the acute phase of status epilepticus or convulsion state may confound the diagnosis of prion disease.…”

Section: Introductionmentioning

confidence: 99%

An autopsy-verified case of steroid-responsive encephalopathy with convulsion and a false-positive result from the real-time quaking-induced conversion assay

Hayashi

Iwasaki

Yagi

et al. 2017

Self Cite

We report an autopsy-verified case of steroid-responsive encephalopathy with convulsion and a false-positive result from the real-time quaking-induced conversion (RT-QUIC) assay. A 61-year-old Japanese man presented with acute onset of consciousness disturbance, and convulsions, but without a past medical or family history of progressive dementia, epilepsy, or prion disease. Brain diffusion and fluid-attenuated inverted recovery MR images revealed edematous cortical hyper-intensity, which diminished after the acute phase. Steroid pulse therapy was partially effective, although he continued to have dementia with myoclonus and psychiatric symptoms, despite resolution of the consciousness disturbance. Cerebrospinal fluid (CSF) analysis revealed a normal cell count, with significantly elevated levels of 14-3-3 protein and total tau protein. In addition, prion protein in the CSF was slowly amplified by the RT-QUIC assay. PRNP gene analysis revealed methionine homozygosity at codon 129 without mutation. The patient died of sudden cardiac arrest at 3 months after the onset of symptoms. The positive result from the RT-QUIC assay led us to suspect involvement of prion disease, although a postmortem assessment revealed that he had pathological changes after convulsion, and no prion disease. This case indicates that convulsion may cause false-positive RT-QUIC results, and that a postmortem evaluation remains the gold standard for diagnosing similar cases.

“…1 The point mutation c.538G>A that replaces valine for isoleucine at 180 (V180I) is one of the major causes of gCJD in Japan and extremely rare in other populations. 2,3 Clinical features of gCJD with V180I mutation include late-onset; slower progression; lower odds of developing myoclonus; cerebellar and pyramidal signs compared with classical sporadic CJD (sCJD) symptoms. 2 To our knowledge, we reported the first Brazilian case of gCJD with V180I mutation.…”

Section: Introductionmentioning

confidence: 99%

First case of V180I rare mutation in a Brazilian patient with Creutzfeldt-Jakob disease

Souza

Josviak

Batistela

et al. 2017

Here, we report the first case of V180I rare mutation in a Brazilian woman whose clinical condition started with memory impairment for recent events and insomnia with 2 months of evolution, without any other alterations in neurological examination. Both the electroencephalogram (EEG) and the routine biochemical examination of cerebrospinal fluid (CSF) were normal. CSF 14-3-3 protein search was positive. Magnetic resonance imaging (MRI) of the encephalon showed findings suggestive of Creutzfeldt-Jakob disease, confirmed by sequencing of PRNP gene that reveal V180I mutation also homozygosity for methionine at codon 129 (M129M).