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This article discusses a case of Creutzfeldt-Jakob disease (CJD), a rare and fatal prion disease, specifically focusing on the MV2K subtype. The MV2K subtype is particularly rare in Asia due to the low prevalence of the MV genotype in the Asian population. The article presents the case of a Chinese patient with probable MV2K sCJD, highlighting the unique involvement of the midbrain and the dynamic progression of MRI changes. The study contributes to the understanding of this subtype and may aid in early diagnosis. [Extracted from the article]

Objective: To assess the proportion of clinically diagnosed MM2‐type sporadic Creutzfeldt–Jakob disease (sCJD) in a Chinese cohort, describe the clinical features of MM2‐cortical (MM2C) and MM2‐thalamic (MM2T) type sCJD to improve the early detection of MM2‐type sCJD. Methods: A total of 209 patients with sCJD admitted to the Xuanwu Hospital between February 2012 and August 2022 were reviewed. The patients were classified into probable MM2C, MM2T‐type sCJD, and other types of sCJD according to current clinical diagnostic criteria. Clinical and ancillary data were compared between the groups. Results: Fifty‐one (24.4%) patients were clinically diagnosed with MM2‐type sCJD, of which 44 were diagnosed with MM2C‐type sCJD and 7 with MM2T‐type sCJD. In the absence of RT‐QuIC, 27 (61.3%) patients of MM2C‐type sCJD did not meet the US CDC sCJD criteria for possible sCJD on admission, even though the mean period from onset to admission was 6.0 months. However, all of these patients had cortical hyperintensity on DWI. Compared to the other types of sCJD, MM2C‐type sCJD was associated with slower disease progression and the absence of the typical clinical features of sCJD; the MM2T‐type sCJD group had a higher proportion of males, earlier age of onset, longer duration of disease, and a higher incidence of bilateral thalamic hypometabolism/hypoperfusion. Interpretation: In the absence of multiple typical sCJD symptoms within 6 months, the presence of cortical hyperintensity on DWI should raise concerns for MM2C‐type sCJD after excluding other etiologies. Bilateral thalamic hypometabolism/hypoperfusion may be more helpful in the clinical diagnosis of MM2T‐type sCJD. [ABSTRACT FROM AUTHOR]

Background: The Heidenhain variant of Creutzfeldt–Jakob disease (HvCJD), as a rare phenotype of CJD, has been under-recognized. We aim to elucidate the clinical and genetic features of HvCJD and investigate the differences of clinical features between genetic and sporadic HvCJD to improve our understanding of this rare subtype. Method: HvCJD patients admitted to the Xuanwu Hospital from February 2012 to September 2022 were identified, and published reports on genetic HvCJD cases were also reviewed. The clinical and genetic features of HvCJD were summarized, and the clinical features between genetic and sporadic HvCJD were compared. Results: A total of 18 (7.9%) HvCJD patients were identified from 229 CJD cases. Blurred vision was the most common visual disturbance at the disease's onset, and the median duration of isolated visual symptoms was 30.0 (14.8–40.0) days. DWI hyperintensities could appear in the early stage, which might help with early diagnosis. Combined with previous studies, nine genetic HvCJD cases were identified. The most common mutation was V210I (4/9), and all patients (9/9) had methionine homozygosity (MM) at codon 129. Only 25% of cases had a family history of the disease. Compared to sporadic HvCJD, genetic HvCJD cases were more likely to present with non-blurred vision visual symptoms at onset and develop cortical blindness during the progression of the disease. Conclusions: HvCJD not only could be sporadic, but also, it could be caused by different PRNP mutations. Sporadic HvCJD was more likely to present with blurred vision visual symptoms at onset, and genetic HvCJD was more likely to develop cortical blindness with the disease's progression. [ABSTRACT FROM AUTHOR]

Background and purpose: This study was undertaken to elucidate the clinical profile of sporadic fatal insomnia (sFI), assess the similarities and differences between sFI and fatal familial insomnia (FFI), and evaluate the influence of ethnicity on the phenotype of sFI patients. Methods: The data of sFI and FFI patients were retrieved from our case series and through literature review. The clinical and diagnostic features of sFI and FFI were compared, as were the phenotypes of Asian and Caucasian sFI patients. Results: We identified 44 sFI and 157 FFI cases. The prevalence of sleep‐related, neuropsychiatric, and autonomic symptoms among the sFI patients were 65.9%, 100.0%, and 43.2%, respectively. Compared to FFI, sFI exhibited longer disease duration and a higher proportion of neuropsychiatric symptoms, whereas FFI was characterized by a higher incidence of sleep‐related and autonomic symptoms in the early stages of the disease or throughout its course. In addition, a higher proportion of the sFI patients showed hyperintensity on magnetic resonance imaging (MRI) and periodic sharp wave complexes on electroencephalography compared to the FFI patients, especially those presenting with pathological changes associated with MM2‐cortical type sporadic Creutzfeldt–Jakob disease. The Asian sFI patients had a higher proportion of males and positivity for cerebrospinal fluid 14‐3‐3 protein, and fewer sleep‐related symptoms compared to Caucasian sFI patients. The age at onset and duration of sFI differed between ethnic groups, but the difference failed to reach statistical significance. Conclusions: Despite its similarities to FFI, sFI is characterized by longer disease duration, higher proportion of neuropsychiatric symptoms, and hyperintensity on MRI, along with differences in the clinical characteristics based on ethnicity. [ABSTRACT FROM AUTHOR]

Abbreviations CJD Creutzfeldt-Jakob disease CSF Cerebrospinal fluid DWI Diffusion-weighted image EEG Electroencephalogram FLAIR Fluid-attenuated inversion recovery HLA Human leukocyte antigen MRI Magnetic resonance imaging PCR Polymerase chain reaction PRNP Prion protein gene PrP SP Sc sp Scrapie isoform of the prion protein PSWC Periodic sharp wave complexes RT-QuIC Real-time quaking-induced conversion RBD Rapid eye movement sleep behavioral disorder Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. We hypothesize that the scrapie isoform of the prion protein deposits in this patient triggered phosphorylated tau deposition, which coupled with a genetic susceptibility to anti-IgLON5 disease, eventually resulted in the positive of anti-IgLON5 antibody. However, given that this patient is a carrier of I HLA-DQB1 i SP I * i sp I 05:01 i , which is recognized in approximately 90% of patients with anti-IgLON5 antibodies and in only 3.38% of the Chinese population [[9]], and the prolonged disease course, the possibility of coexistence of the two diseases cannot be completely ruled out. Less than 5% of CJD patients could produce autoantibodies, including those specific for NMDAR, GluR 2, VGKC complex, CASPR2, and GLyR; those antibodies may also be a factor in the development of the disease's clinical symptoms. [Extracted from the article]

Background: The 14-3-3 protein in cerebrospinal fluid (CSF) is a suitable biomarker for the diagnosis of Creutzfeldt-Jakob disease (CJD). However, it has also been detected in various non-prion-related rapidly progressive dementia (RPD), which affected its diagnostic performance and clinical utilization. Objective: To investigate the general disease distribution with positive 14-3-3 result and to evaluate the association between CSF 14-3-3 protein and the clinical features in patients with non-prion RPD. Methods: A total of 150 patients with non-prion RPD were enrolled. The clinical data were collected and CSF 14-3-3 test was performed for all patients. The distribution of various diseases with a positive 14-3-3 result was analyzed and the association of CSF 14-3-3 with clinical features was tested. Results: The CSF 14-3-3 protein was detected in 23.3% of non-prion RPD patients, and the most frequent diagnoses were autoimmune encephalitis (22.9%) and neurodegenerative disease (22.9%). CSF 14-3-3 protein was more common in older patients (p = 0.028) and those presenting myoclonus (p = 0.008). In subgroup analysis, the positive 14-3-3 test was more common in neurodegenerative disease with a long time from the symptom onset to CSF 14-3-3 test (p = 0.014). Conclusion: CSF 14-3-3 protein could be detected in a broad spectrum of non-prion RPD. In particular, patients with autoimmune encephalitis and rapidly progressive neurodegenerative diseases and those with myoclonus have a greater likelihood of a positive 14-3-3 result. These results could help clinicians interpret the results of CSF 14-3-3 protein more reasonably. [ABSTRACT FROM AUTHOR]

The majority of seven-octapeptide repeat insertion (7-OPRI) carriers exhibit relatively early onset and a slowly progressive course. We have presented three cases of 7-OPRI, including two that are rapidly progressing, and compared the clinical and ancillary characteristics of the short-term and long-term disease course, as well as factors that influence disease course. The clinical and ancillary features of three new 7-OPRI patients in a Chinese pedigree were analyzed. Global data on 7-OPRI cases were then collected by reviewing the literature, and the cases were grouped according to clinical duration as per the WHO sCJD criteria, with a two-year cut-off. A Chinese pedigree has a glycine-to-glutamate substitution within the 7-OPRI insertion, which enhances the hydrophilicity of the prion protein. Two cases in this pedigree had a short disease course (consistent with the typical clinical and ancillary features of sCJD). In addition, the members of this pedigree had a later onset (p < 0.001) and shorter disease course (p < 0.001) compared to previously reported 7-OPRI cases with 129 cis-M and a similar age of onset and disease course to that of cases with 129 cis-V. The 7-OPRI cases with a shorter clinical course (n = 4) had a later onset (p = 0.021), higher rate of hyperintensity on MRI (p = 0.029) and higher frequency of 129 cis-V (p = 0.066) compared to those with a longer clinical course (n = 13). The clinical presentation of 7-OPRI is significantly heterogeneous. Codon 129 cis-V and amino acid substitution within repeat insertions are possible contributors to the short-term disease course of 7-OPRI. [ABSTRACT FROM AUTHOR]

Background: Creutzfeldt-Jakob disease (CJD) can be difficult to distinguish clinically from some non-prion neurological diseases. Previous studies have reported markedly increased levels of α-synuclein in cerebrospinal fluid (CSF) of CJD patients, indicating that it is a potential diagnostic biomarker.Objective: The aim of this study was to assess the diagnostic power of CSF α-synuclein in discriminating CJD from non-prion disorders.Methods: The Ovid MEDLINE, Cochrane, and Embase databases were searched for articles published on or before February 25, 2022, using the search term (prion diseases OR Creutzfeldt-Jakob syndrome) AND (synuclein OR α-synuclein). The difference in CSF α-synuclein levels between CJD and non-prion diseases was calculated using random-effects models (I2 > 50%) or fixed-effects models (I2 < 50%) in terms of standardized mean difference (SMD) and 95% confidence interval (CI). The publication bias was estimated using funnel plots and the Egger's test.Results: Ten studies were included in this study. The concentrations of CSF α-synuclein were significantly higher in CJD patients compared to total non-prion controls (SMD = 1.98, 95% CI 1.60 to 2.36, p < 0.00001), tauopathies (SMD = 1.34, 95% CI 0.99 to 1.68, p < 0.00001), synucleinopathies (SMD = 1.78, 95% CI 1.11 to 2.44, p < 0.00001), or Alzheimer's (SMD = 1.14, 95% CI 0.95 to 1.33, p < 0.00001). CSF α-synuclein could distinguish CJD from non-prion diseases with overall sensitivity of 89% (95% CI 80-95%), specificity of 92% (95% CI 86-95%), and AUC of 0.96 (95% CI: 0.94-0.97).Conclusion: CSF α-synuclein has excellent diagnostic value in discriminating CJD from non-prion neurological diseases. Given the high heterogeneity among the included studies, further studies are needed to confirm its clinical utility. [ABSTRACT FROM AUTHOR]

To elucidate and compare the genetic, clinical, ancillary diagnostic, and pathological characteristics across different Gerstmann-Sträussler-Scheinker disease (GSS) phenotypes and explore the underlying causes of the phenotypic heterogeneities. The genetic, clinical, ancillary diagnostic, and pathological profiles of GSS patients reported in the literature were obtained and analyzed. Additionally, 3 patients with genetically confirmed GSS from our unit were included. Based on clinical presentation, patients were classified into typical GSS, Creutzfeldt-Jakob disease (CJD)-like GSS, GSS with dementia, and other categories. A total of 329 GSS cases were included with a 1.13:1 female-to-male ratio, median onset age 44, and median duration 4 years. Of the 294 categorized patients, 50.7% had typical GSS, 24.8% showed CJD-like GSS, and 16.3% presented with GSS with dementia. Clinical classification varied significantly based on genotype, with P102L more common in typical GSS and A117V prevalent in CJD-like GSS. Polymorphism at codon 129 has no effect on GSS phenotype, but the 129 M allele acts as a protective factor in GSS patients in Asia and North America. Moderate to severe spongiform degeneration and the presence of PK-resistant small fragments migrating at <11 kDa on electrophoretic gels along with PrP27–30 fragments were more prevalent in CJD-like GSS phenotype, while hyperphosphorylated tau protein co-deposition tends to be characteristic of typical GSS and GSS with dementia. This study reveals GSS's intricate nature, showing significant variations in clinical presentations, diagnostic findings, and pathological features. Mutation sites and pathological changes play crucial roles in determining the GSS clinical heterogeneity. • GSS exhibits diverse clinical, diagnostic, and pathological variations. • Typical GSS only makes up about half of all GSS patients. • Mutation sites and pathological changes determine GSS clinical heterogeneity. • Polymorphism at codon 129 doesn't affect GSS phenotype • 129 M allele acts as a protective factor in Asia/North America GSS patients. [ABSTRACT FROM AUTHOR]

Background: Creutzfeldt–Jakob disease (CJD) is a devastating neurodegenerative disease caused by propagation of abnormally folded prion proteins (PrPSc). Some fluid biomarkers have been reported to be associated with disease duration in CJD. Based on studies which have found that prion protein (PrPC) played a role in erythrocytic hematopoiesis, we evaluated the association between peripheral red blood cell indices and survival time in CJD. Methods: We retrospectively collected data on peripheral red blood cell indices, including red blood cell (RBC) count, hemoglobin (Hb), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), and red cell distribution width (RDW), from 125 CJD patients. Cox proportional hazard models were generated to determine whether red cell indices correlated with survival time of patients with CJD. Results: Of the 125 included participants, 70 (56%) were male, and the mean age at diagnosis (SD) was 60.3 (9.5) years. Hemoglobin levels (hazard ratio 1.710, 95% CI 1.124–2.600, p = 0.012) and HCT (hazard ratio 1.689, 95% CI 1.112–2.565, p =0.014) were significantly associated with survival time after controlling for sex, age, and Barthel Index. Red blood cell count, MCV, MCH, MCHC, and RDW were not associated with survival time before or after adjusting for covariates. Conclusions: Our study found that Hb and HCT were significantly associated with survival time in patients with CJD. These results may inform evaluation of the mechanisms of interaction between prion disease and hematopoiesis, and indicate that Hb and HCT may be potential prognostic biomarkers. [ABSTRACT FROM AUTHOR]