Agrypnia excitata and obstructive apnea in a patient with fatal familial insomnia from China: A case report
Rationale:
Fatal familial insomnia (FFI) linked to a D178N/129M haplotype mutation in the PRNP gene is the most common genetic prion disease in the Han Chinese population. Here, we describe a Han Chinese patient with FFI who exhibited agrypnia excitata and obstructive apnea.
Patient concerns:
A 46-year-old man displayed involuntary movements during sleep time, snoring, autonomic nervous system dysfunction, cognitive deficit, brainstem symptoms, myoclonus and ataxia in order within 8 months. The electroencephalogram (EEG) and Magnetic Resonance Imaging (MRI) revealed abnormal changes but without the typical prion disea...
Source: Medicine - December 1, 2017 Category: Internal Medicine Tags: Research Article: Clinical Case Report Source Type: research
[PERSPECTIVES] Experimental Models of Inherited PrP Prion Diseases
The inherited prion protein (PrP) prion disorders, which include familial Creutzfeldt–Jakob disease, Gerstmann–Sträussler–Scheinker disease, and fatal familial insomnia, constitute ~10%–15% of all PrP prion disease cases in humans. Attempts to generate animal models of these disorders using transgenic mice expressing mutant PrP have produced variable results. Although many lines of mice develop spontaneous signs of neurological illness with accompanying prion disease–specific neuropathological changes, others do not. Furthermore, demonstrating the presence of protease-resistant PrP spe...
Source: Cold Spring Harbor perspectives in medicine - November 1, 2017 Category: Research Authors: Watts, J. C., Prusiner, S. B. Tags: Prion Diseases PERSPECTIVES Source Type: research
Chapter 28 Prion diseases
Publication date: 2017 Source:Handbook of Clinical Neurology, Volume 145 Author(s): James W. Ironside, Diane L. Ritchie, Mark W. Head The human prion diseases comprise Creutzfeldt–Jakob disease, variably protease-sensitive prionopathy, Gerstmann–Sträussler–Scheinker disease, fatal familial insomnia, and kuru. Each is a uniformly fatal rare neurodegenerative disease in which conformational changes in the prion protein are thought to be the central pathophysiologic event. The majority of cases of human prion diseases occur worldwide in the form of sporadic Creutzfeldt–Jakob disease and a minority of around 10...
Source: Handbook of Clinical Neurology - October 4, 2017 Category: Neurology Source Type: research
Genetic human prion disease modelled in PrP transgenic Drosophila
Inherited human prion diseases, such as fatal familial insomnia (FFI) and familial Creutzfeldt–Jakob disease (fCJD), are associated with autosomal dominant mutations in the human prion protein gene PRNP and accumulation of PrPSc, an abnormal isomer of the normal host protein PrPC, in the brain of affected individuals. PrPSc is the principal component of the transmissible neurotoxic prion agent. It is important to identify molecular pathways and cellular processes that regulate prion formation and prion-induced neurotoxicity. This will allow identification of possible therapeutic interventions for individuals with, or...
Source: Biochemical Journal - September 20, 2017 Category: Biochemistry Authors: Thackray, A. M., Cardova, A., Wolf, H., Pradl, L., Vorberg, I., Jackson, W. S., Bujdoso, R. Tags: Research Articles Source Type: research
Fatal familial insomnia with abnormal signals on routine MRI: a case report and literature review
We report a patient with FFI presentin... (Source: BMC Neurology)
Source: BMC Neurology - May 26, 2017 Category: Neurology Authors: Tingting Lu, Yuhang Pan, Lisheng Peng, Feng Qin, Xiaobo Sun, Zhengqi Lu and Wei Qiu Source Type: research
Fatal Familial Insomnia: Clinical Aspects and Molecular Alterations
This article reviews recent research on the clinical and molecular aspects of the disease.Recent FindingsNew clinical and biomarker tools have been implemented in order to assist in the diagnosis of the disease. In addition, the generation of mouse models, the availability of ‘omics’ data in brain tissue and the use of new seeding techniques shed light on the molecular events in FFI pathogenesis. Biochemical studies in human samples also reveal that neuropathological alterations in vulnerable brain regions underlie severe impairment in key cellular processes such as mitochondrial and protein synthesis machinery.Summary...
Source: Current Neurology and Neuroscience Reports - March 20, 2017 Category: Neuroscience Source Type: research
Fatal Familial Insomnia: a video-polysomnographic case report
Fatal familial insomnia (FFI) is a rare neurodegenerative hereditary autosomal dominant prion disease that affects patients between the fifth and sixth decades, with a rapid fatal outcome [1, 2]. It is caused by a missense mutation at codon 178 (p.D178N) of the prion protein gene (PRNP) [3]. Clinical hallmarks of the disease are sleep disturbances, motor disorders, dysautonomia and dementia [1]. Pathology includes a typical prominent thalamo-olivaric involvement [4]. Here, we report a video-documented polysomnography (PSG) of a 49-year-old woman with molecularly proven FFI. (Source: Sleep Medicine)
Source: Sleep Medicine - March 9, 2017 Category: Sleep Medicine Authors: Thomas Megelin, Benjamin Thomas, Xavier Ferrer, Imad Ghorayeb Tags: Video-Clinical Corners Source Type: research
Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Correlation of Histopathology and MRI in Prion Disease.
This study includes 11 cases of definite prion disease in which FDG-PET scans were obtained. There were 8 sporadic CJD cases, 2 genetic CJD cases, and 1 fatal familial insomnia case. Automated FDG-PET analysis revealed parietal region hypometabolism in all cases. Surprisingly, limbic and mesolimbic hypermetabolism were also present in the majority of cases. When FDG-PET hypometabolism was compared with neuropathologic changes (neuronal loss, astrocytosis, spongiosis), hypometabolism was predictive of neuropathology in 80.6% of cortical regions versus 17.6% of subcortical regions. The odds of neuropathologic changes were 2....
Source: Alzheimer Disease and Associated Disorders - January 26, 2017 Category: Psychiatry Tags: Alzheimer Dis Assoc Disord Source Type: research
Neuroradiology of human prion diseases, diagnosis and differential diagnosis
AbstractHuman transmissible spongiform encephalopathies (TSEs), or prion diseases, are invariably fatal conditions associated with a range of clinical presentations. TSEs are classified as sporadic [e.g. sporadic Creutzfeldt –Jakob disease (sCJD), which is the most frequent form], genetic (e.g. Gerstmann–Straussler–Scheinker disease, fatal familial insomnia, and inherited CJD), and acquired or infectious (e.g. Kuru, iatrogenic CJD, and variant CJD). In the past, brain imaging played a supporting role in the diagno sis of TSEs, whereas nowadays magnetic resonance imaging (MRI) plays such a prominent role that MRI find...
Source: La Radiologia Medica - January 20, 2017 Category: Radiology Source Type: research
Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Correlation of Histopathology and MRI in Prion Disease
This study includes 11 cases of definite prion disease in which FDG-PET scans were obtained. There were 8 sporadic CJD cases, 2 genetic CJD cases, and 1 fatal familial insomnia case. Automated FDG-PET analysis revealed parietal region hypometabolism in all cases. Surprisingly, limbic and mesolimbic hypermetabolism were also present in the majority of cases. When FDG-PET hypometabolism was compared with neuropathologic changes (neuronal loss, astrocytosis, spongiosis), hypometabolism was predictive of neuropathology in 80.6% of cortical regions versus 17.6% of subcortical regions. The odds of neuropathologic changes were 2....
Source: Alzheimer Disease and Associated Disorders - January 1, 2017 Category: Geriatrics Tags: Original Articles Source Type: research
Genetic prion disease: Experience of a rapidly progressive dementia center in the United States and a review of the literature
We present the UCSF gPrD cohort, including 129 symptomatic patients referred to and/or seen at UCSF between 2001 and 2016, and compare the clinical features of the gPrDs from 22 mutations identified in our cohort with data from the literature, as well as perform a literature review on most other mutations not represented in our cohort. E200K is the most common mutation worldwide, is associated with gJCD, and was the most common in the UCSF cohort. Among the GSS‐associated mutations, P102L is the most commonly reported and was also the most common at UCSF. We also had several octapeptide repeat insertions (OPRI), a rare n...
Source: American Journal of Medical Genetics Part B: Neuropsychiatric Genetics - December 11, 2016 Category: Genetics & Stem Cells Authors: Leonel T. Takada, Mee ‐Ohk Kim, Ross W. Cleveland, Katherine Wong, Sven A. Forner, Ignacio Illán Gala, Jamie C. Fong, Michael D. Geschwind Tags: Review Article Source Type: research
Clinical and Neuroimaging Features of A Chinese Patient with Fatal Familial Insomnia
Fatal familial insomnia (FFI) is a rare inherited human prion-protein disease characterized by progressive sleep abnormalities, dysautonomia, motor disturbances, and cognitive decline [1, 2]. FFI cases without clinical insomnia were rarely reported [3, 4]. Herein we report a patient with FFI who presented with rapidly progressive dementia and motor signs, but without typical wake-sleep abnormalities. (Source: Sleep Medicine)
Source: Sleep Medicine - December 6, 2016 Category: Sleep Medicine Authors: Lulu Liu, Chun Li, Qin Yang, Wenwen Zhang, Yonglei Liu, Hongcan Zhu Tags: Letter to the Editor Source Type: research
Oxidative stress and mitochondrial dysfunction-linked neurodegenerative disorders.
Authors: Islam MT
Abstract
Reactive species play an important role in physiological functions. Overproduction of reactive species, notably reactive oxygen (ROS) and nitrogen (RNS) species along with the failure of balance by the body's antioxidant enzyme systems results in destruction of cellular structures, lipids, proteins, and genetic materials such as DNA and RNA. Moreover, the effects of reactive species on mitochondria and their metabolic processes eventually cause a rise in ROS/RNS levels, leading to oxidation of mitochondrial proteins, lipids, and DNA. Oxidative stress has been considered to be lin...
Source: Neurological Research - November 6, 2016 Category: Neurology Tags: Neurol Res Source Type: research
Proteomic Analyses for the Global S -Nitrosylated Proteins in the Brain Tissues of Different Human Prion Diseases
We described the first proteomic analysis of globalS-nitrosylation in brain tissues of sporadic Creutzfeldt –Jakob disease (sCJD), fatal familial insomnia (FFI), and genetic CJD with a substitution of valine for glycine at codon 114 of the prion protein gene (G114V gCJD) accompanying with normal control with isobaric tags for relative and absolute quantitation (iTRAQ) combined with a nano-HPLC/Q-Exactiv e mass spectrometry platform. In parallel, we used several approaches to provide quality control for the experimentally definedS-nitrosylated proteins. A total of 1509S-nitrosylated proteins (SNO-proteins) were identified...
Source: Molecular Neurobiology - September 6, 2016 Category: Neurology Source Type: research
Towards authentic transgenic mouse models of heritable PrP prion diseases
Abstract
Attempts to model inherited human prion disorders such as familial Creutzfeldt–Jakob disease (CJD), Gerstmann–Sträussler–Scheinker (GSS) disease, and fatal familial insomnia (FFI) using genetically modified mice have produced disappointing results. We recently demonstrated that transgenic (Tg) mice expressing wild-type bank vole prion protein (BVPrP) containing isoleucine at polymorphic codon 109 develop a spontaneous neurodegenerative disorder that exhibits many of the hallmarks of prion disease. To determine if mutations causing inherited human prion disease alter this phenotype, we gene...
Source: Acta Neuropathologica - June 27, 2016 Category: Neurology Source Type: research
