Clinical Variability in P102L Gerstmann–Sträussler–Scheinker Syndrome

Tesař, Adam; Matěj, Radoslav; Kukal, Jaromír; Johanidesová, Silvie; Rektorová, Irena; Vyhnálek, Martin; Keller, Jiří; Eliasova, Ilona; Parobková, Eva; Smětáková, Magdalena; Mušová, Zuzana; Rusina, Robert

doi:10.1002/ana.25579

Cited by 25 publications

(31 citation statements)

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“…The greatest variability of results was observed in the GSS group. This phenomenon has been described in the literature and was also evident in our archival samples [14,26]. On the positive side, all archived GSS BHs tested positive, even after long-term storage.…”

Section: Discussionsupporting

confidence: 87%

Detection of Prions in Brain Homogenates and CSF Samples Using a Second-Generation RT-QuIC Assay: A Useful Tool for Retrospective Analysis of Archived Samples

et al. 2021

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The possibilities for diagnosing prion diseases have shifted significantly over the last 10 years. The RT-QuIC assay option has been added for neuropsychiatric symptoms, supporting biomarkers and final post-mortem confirmation. Samples of brain homogenates used for final diagnosis, archived for many years, provide the possibility for retrospective studies. We used a second-generation RT-QuIC assay to detect seeding activity in different types of sporadic and genetic prion diseases in archival brain homogenates and post-mortem CSF samples that were 2 to 15 years old. Together, we tested 92 archival brain homogenates: 39 with definite prion disease, 28 with definite other neurological disease, and 25 with no signs of neurological disorders. The sensitivity and specificity of the assay were 97.4% and 100%, respectively. Differences were observed in gCJD E200K, compared to the sporadic CJD group. In 52 post-mortem CSF samples—24 with definite prion disease and 28 controls—we detected the inhibition of seeding reaction due to high protein content. Diluting the samples eliminated such inhibition and led to 95.8% sensitivity and 100% specificity of the assay. In conclusion, we proved the reliability of archived brain homogenates and post-mortem CSF samples for retrospective analysis by RT-QuIC after long-term storage, without changed reactivity.

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Section: Discussionsupporting

confidence: 87%

Detection of Prions in Brain Homogenates and CSF Samples Using a Second-Generation RT-QuIC Assay: A Useful Tool for Retrospective Analysis of Archived Samples

et al. 2021

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“…This is also the case for the Pro102Leu mutation. In contrast, carriers of apolipoprotein E variants present with late onset of symptoms [18,19].…”

Section: Gerstmann-straussler-scheinker Syndromementioning

confidence: 97%

THαβ Immunological Pathway as Protective Immune Response against Prion Diseases: An Insight for Prion Infection Therapy

Tsou

Chen

et al. 2022

Viruses

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Prion diseases, including Creutzfeldt–Jakob disease, are mediated by transmissible proteinaceous pathogens. Pathological changes indicative of neuro-degeneration have been observed in the brains of affected patients. Simultaneously, microglial activation, along with the upregulation of pro-inflammatory cytokines, including IL-1 or TNF-α, have also been observed in brain tissue of these patients. Consequently, pro-inflammatory cytokines are thought to be involved in the pathogenesis of these diseases. Accelerated prion infections have been seen in interleukin-10 knockout mice, and type 1 interferons have been found to be protective against these diseases. Since interleukin-10 and type 1 interferons are key mediators of the antiviral THαβ immunological pathway, protective host immunity against prion diseases may be regulated via THαβ immunity. Currently no effective treatment strategies exist for prion disease; however, drugs that target the regulation of IL-10, IFN-alpha, or IFN-β, and consequently modulate the THαβ immunological pathway, may prove to be effective therapeutic options.

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“…Though most cases of prion disease converge toward progressive dementia, akinetic mutism, and ultimately, terminal illness, early symptoms vary widely in a manner not faithfully predicted by genotype. Diverse presentations have been reported not only within variants [15][16][17][18][19][20][21] but even within the same affected family 13,22,23 and between affected monozygotic twins. [24][25][26] However, despite its erosion over time, it is useful to be aware of the classical genotype-phenotype correlation (Table 1).…”

Section: Classical Phenotypesmentioning

confidence: 99%