Fatal familial insomnia

Prion diseases uniquely manifest in three distinct forms: inherited, sporadic, and infectious. Wild-type prions are responsible for the sporadic and infectious versions, while mutant prions cause inherited variants like fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). Although some drugs can prolong prion incubation times up to four-fold in rodent models of infectious prion diseases, no effective treatments for FFI and fCJD have been found. In this study, we evaluated the efficacy of various anti-prion drugs on newly-developed knock-in mouse models for FFI and fCJD...

Human spongiform encephalopathies are rare transmissible neurodegenerative diseases of the brain and the nervous system that are caused by misfolding of the physiological prion protein into a pathological form and its deposition in the central nervous system (CNS). Prion diseases include Creutzfeldt-Jakob disease (CJD, sporadic or familial), Gerstmann-Straussler-Scheinker syndrome (GSS) and fatal familial insomnia (FFI). Prion diseases can be differentiated into three etiological categories: spontaneous (sporadic CJD), inherited (familial CJD, FFI, and GSS) and acquired (variant CJD and iatrogenic CJD)...

Fatal familial insomnia,an autosomal dominant prion disease,is rare.We reported the clinical symptoms,examination results,diagnosis,treatment,and prognosis of a patient who was diagnosed with fatal familial insomnia.Furthermore,we described the unique clinical manifestations that involuntary movements and laryngeal stridor were significantly correlated with postural changes,aiming to provide reference for the clinical diagnosis,treatment,and research of the disease in the future.

Neurodegenerative diseases (NDs) manifest a wide variety of clinical symptoms depending on the affected brain regions. Gaining insights into why certain regions are resistant while others are susceptible is vital for advancing therapeutic strategies. While gene expression changes offer clues about disease responses across brain regions, the mixture of cell types therein obscures experimental results. In recent years, methods that analyze the transcriptomes of individual cells (e.g., single-cell RNA sequencing or scRNAseq) have been widely used and have provided invaluable insights into specific cell types...

Fatal familial insomnia (FFI) is a rare autosomal dominant genetic neurodegenerative disease. Generally, FFI patients will develop rapidly progressive dementia, sleep disturbance, autonomic dysfunction, and so on. Cerebrospinal fluid examination of FFI patients normally shows no obvious abnormalities. Here, we report a young male patient who was diagnosed with FFI during the COVID-19 epidemic. Clinical symptoms include psychobehavioral abnormality, cognitive decline, sleep disturbance, and autonomic dysfunction...

It is increasingly evident that the association of glycans with the prion protein (PrP), a major post-translational modification, significantly impacts the pathogenesis of prion diseases. A recent bioassay study has provided evidence that the presence of PrP glycans decreases spongiform degeneration (SD) and disease-related PrP (PrPD) deposition in a murine model. We challenged (PRNPN181Q/197Q) transgenic (Tg) mice expressing glycan-free human PrP (TgGlyc-), with isolates from sCJDMM2, sporadic fatal insomnia, and familial fatal insomnia, three human prion diseases that are distinct but share histotypic and PrPD features...

Prion diseases and the prion protein are only partially understood so far in many aspects. This explains the continued research on this topic, calling for an overview on the current state of knowledge. The main objective of the present review article is to provide a comprehensive up-to-date presentation of all major features of human prion diseases bridging the gap between basic research and clinical aspects. Starting with the prion protein, current insights concerning its physiological functions and the process of pathological conversion will be highlighted...

Prion diseases uniquely manifest in three distinct forms: inherited, sporadic, and infectious. Wild-type prions are responsible for the sporadic and infectious versions, while mutant prions cause inherited variants like fatal familial insomnia (FFI) and familial Creutzfeldt-Jakob disease (fCJD). Although some drugs can prolong prion incubation times up to four-fold in rodent models of infectious prion diseases, no effective treatments for FFI and fCJD have been found. In this study, we evaluated the efficacy of various anti-prion drugs on newly-developed knock-in mouse models for FFI and fCJD...

BACKGROUND: Prion diseases or TSE diseases are a group of neurodegenerative disorders that manifest in several forms in humans, such as Kuru disease, Creutzfeldt‒Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome (GSS) and fatal familial insomnia. OBJECTIVE: In this study, we propose a multimodular hypothesis of prion diseases. According to this hypothesis, a prion disease manifests because of the interaction of two genetic modules, such as the PRNP gene module and that of the gene or genes responsible for one or more chaperones, with one or some chemical module on whose structure the products of the genes or genetic modules interact...

Fatal familial insomnia (FFI) is a rare autosomal-dominant inherited prion disease with a wide variability in age of onset. Its causes are not known. In the present study, we aimed to analyze genetic risk factors other than the prion protein gene ( PRNP ), in FFI patients with varying ages of onset. Whole-exome sequencing (WES) analysis was performed for twenty-five individuals with FFI (D178N-129M). Gene ontology enrichment analysis was carried out by Reactome to generate hypotheses regarding the biological processes of the identified genes...

BACKGROUND: Gerstmann-Sträussler-Scheinker (GSS) is a rare prion disease with heterogeneous clinical presentation. Although sleep-related abnormalities are prominent and well-known in other prion diseases such as fatal familial insomnia and Creutzfeldt-Jakob disease, information on sleep is limited in GSS. METHODS: We evaluated sleep in three genetically confirmed GSS cases using clinical history, sleep scales and video-polysomnography. In addition, patients underwent neurological assessment, neurological scales, neuropsychological testing, lumbar puncture, brain MRI and brain 18 F-FDG-PET...

Genetic Creutzfeldt-Jakob disease (gCJD) with a V180I mutation (V180I gCJD) is the most common type of gCJD in Japan, characterized by an older age at onset, slower progression, and moderate to severe cortical degeneration with spongiform changes and sparing of the brainstem and cerebellum. Degeneration of the inferior olivary nucleus (IO) is rarely observed in patients with CJD but is known to occur in fatal familial insomnia (FFI) and MM2-thalamic-type sporadic CJD (sCJD-MM2T) involving type 2 prion protein (M2T prion)...

Prion diseases are a group of neurodegenerative diseases. The disease-causing agent is a protein (PrP), that is normally produced in the nervous system, aggregated in an abnormal form. The abnormal protein, known as prion (PrPSc ), is capable of self-propagation promoting the misfolding of the normal protein (PrP). These conditions can be acquired sporadically, genetically, or infectiously either by eating meat contaminated with prions or from iatrogenic exposure. The diagnosis of these diseases is often challenging...

The diagnostic approach to sleep-related movements disorders is seldom discussed. We report a case of fatal familial insomnia who initially presented with persistent limb movements in sleep, which later progressed to a state of agrypnia excitata. Here, the evaluation of abnormal movements in sleep is discussed using a step-by-step diagnostic approach. Although no cure is available for fatal familial insomnia, prompt recognition of this condition is important to facilitate proper management, including the involvement of interdisciplinary neuropalliative care...

Fatal familial insomnia (FFI) is a rare neurodegenerative disease caused by a dominantly inherited single amino acid substitution (D178N) within the prion protein (PrP). No in vitro human brain tissue model for this disease has previously been available. Consequently, how this mutation exerts its damaging effect on brain cells is still unknown. Using CRISPR-Cas9 engineered induced pluripotent stem cells, we made D178N cerebral organoids and compared these with isotype control organoids. We found that, in the absence of other hallmarks of FFI, the D178N organoids exhibited astrogliosis with cellular oxidative stress...

OBJECTIVE: 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 was 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...

Prion gene (PRNP) mutations are associated with diverse disease phenotypes, including familiar Creutzfeldt-Jakob Disease (CJD), Gerstmann-Sträussler-Scheinker disease (GSS), and fatal familial insomnia (FFI). Interestingly, PRNP mutations have been reported in patients diagnosed with Alzheimer's disease, dementia with Lewy bodies, Parkinson's disease, and frontotemporal dementia. In this review, we describe prion mutations in Asian countries, including Republic of Republic of Korea, China, and Japan. Clinical phenotypes and imaging data related to these mutations have also been introduced in detail...

STUDY OBJECTIVES: Although sympathetic hyperactivity with preserved parasympathetic activity has been extensively recognized in fatal familial insomnia (FFI), the symptoms of parasympathetic nervous system failure observed in some patients are difficult to explain. Using heart rate variability (HRV), this study aimed to discover evidence of parasympathetic dysfunction in patients with FFI and the difference of parasympathetic activity between patients with FFI and Creutzfeldt-Jakob disease (CJD)...

Fatal familial insomnia (FFI) is a rare prionopathy with unusually high incidence in the Basque Country. We report detailed data on clinical, diagnostic, histopathological, and biochemical characteristics of a recent FFI case series. The Basque Brain Bank database was screened for patients diagnosed from 2010 to 2021 with standard genetic and/or neuropathological criteria. This series includes 16 patients, 25% without family history, with 12 cases from 9 unrelated (but geographically-linked, Basque country) kindreds, onset ranging from 36 to 70 years, and disease course from 7 to 11...

Human prion diseases are rapidly progressive and fatal neurodegenerative conditions caused by a disease-causing isoform of the native prion protein. The prion protein gene ( PRNP ) encodes for the cellular prion protein, which is the biological substrate for prion disease transmission and neurotoxicity. Human prion diseases have three etiologies: sporadic, genetic, and acquired. PRNP polymorphisms and pathogenic variants play a large role in the frequency, age at onset, and clinicopathologic phenotype of prion diseases...