1/22. Stealth virus epidemic in the Mohave Valley: severe vacuolating encephalopathy in a child presenting with a behavioral disorder.An infectious illness, attributed to atypically structured cytopathic "stealth" viruses, occurred in 1996 in the Mohave Valley region of the united states. A stealth virus-infected child from this region has developed a severe noninflammatory, vacuolating (spongiform) en cephalopathy. The illness initially presented as a behavioral problem without overt neurological signs. Extensive investigations, including repeated magnetic resonance imaging, two brain biopsies, and stealth virus cultures, have helped define the disease process occurring in this child. Significant clinical benefit with apparent retardation of disease progression occurred during a 6-week course of ganciclovir therapy. The potential contributing role of stealth virus infections in children presenting with behavioral problems needs to be addressed.- - - - - - - - - - ranking = 1keywords = spongiform, encephalopathy (Clic here for more details about this article) |
2/22. Inherited prion encephalopathy associated with the novel PRNP H187R mutation: a clinical study.OBJECTIVE: To describe a variant of prion encephalopathy associated with the recently identified H187R mutation in the prion protein (PRNP) gene. methods: The authors studied a multigenerational American family with nine affected individuals. Clinical examination included imaging, EEG, and CSF analysis with 14-3-3 protein testing. Histopathology was characterized by examination of a brain biopsy from an H187R mutation-positive patient. RESULTS: The disease in this family is caused by the PRNP H187R mutation and characterized by autosomal dominant inheritance, median age at disease onset of 42 years (range 33 to 50 years), and median duration of illness of 12 years (range 8 to 19 years). Clinical signs include progressive dementia, ataxia, myoclonus, and seizures. Histopathologic features consist of distinctive "curly" prion protein deposits with a strictly laminar distribution in the cerebral cortex and minimal astrogliosis in the absence of amyloid plaques or spongiosis. CONCLUSION: A variant of prion encephalopathy associated with the novel H187R mutation in the PRNP gene displays distinctive clinical and immunostaining characteristics that further expand the boundaries of human prion disease.- - - - - - - - - - ranking = 0.01056948112491keywords = encephalopathy (Clic here for more details about this article) |
3/22. Inherited prion disease caused by the V210I mutation: transmission to transgenic mice.OBJECTIVE: To describe the clinical and neuropathologic profile and determine the strain characteristics of familial Creutzfeldt-Jakob disease (fCJD) caused by a point mutation of the PRNP gene at codon 210 that results in a valine-to-isoleucine substitution in the prion protein (PrP). methods: The clinicopathologic features of four individuals from the united states who died of fCJD(V210I) were compared. Transgenic (Tg) mice expressing a chimeric human-mouse PrP transgene were inoculated with brain extracts from three fCJD(V210I) cases, sporadic CJD (sCJD), fCJD(E200K), and fatal familial insomnia (FFI), to compare prion strain characteristics. RESULTS: The clinicopathologic profile of fCJD(V210I) was variable among cases but shared similarities with sCJD. The pattern of PrP(Sc) deposition in the brains of Tg mice was similar to that caused by sCJD but different from that associated with fCJD(E200K) or FFI. CONCLUSIONS: Each of these prion diseases is characterized by a rapidly progressive dementia with myoclonus, periodic complexes on EEG, and spongiform change without PrP plaque deposition in the brain. The occurrence of a different PrP(Sc) phenotype with each PRNP mutation argues that each respective amino acid sequence substitution produces a different prion strain.- - - - - - - - - - ranking = 0.99295367925006keywords = spongiform (Clic here for more details about this article) |
4/22. The use of antioxidants in transmissible spongiform encephalopathies: a case report.BACKGROUND: Transmissible spongiform encephalopathies (TSE), which include Creutzfeldt-Jakob disease and new variant Creutzfeldt-Jakob disease, are diseases characterized by progressive deterioration in the central nervous system with neuronal degeneration, vacuolatization of the neuropil, and gliosis. Little is known about the pathogenic mechanisms of infection, and controversy exits around the inciting infective agent. It has been shown that an important factor in pathogenesis is the immune system. CASE: The reported case points to beneficial effects when antioxidant therapies are used in transmissible spongiform encephalopathies. The case revealed an early reversal in cognitive decline and subsequent improvements in myoclonus, apnea and rigidity. Although death was the ultimate outcome, the patient succumbed to the illness over 22 months after the onset of symptoms when the early rapid decline predicted demise within a few months. CONCLUSION: It is possible that strategies blocking the effect of proinflammatory cytokines and the resulting oxidative damage may stem the progressive damage to the neuropil that occurs in spongiform encephalopathies. Further investigation into the use of antioxidants and other types of agents quelling inflammation needs to be undertaken. If antioxidants could be combined with treatments for the inciting infective agent, a new direction could be taken in the outcome of transmissible spongiform encephalopathies including CJD and vCJD.- - - - - - - - - - ranking = 7.9436294340005keywords = spongiform (Clic here for more details about this article) |
5/22. Novel prion protein insert mutation associated with prolonged neurodegenerative illness.BACKGROUND: Mutations in the prion protein gene (PRNP) are found in approximately 13 to 15% of persons classified as dying from a transmissible spongiform encephalopathy. Point and octapeptide repeat insert and deletion mutations are described in the open reading frame (ORF) of PRNP. The authors present a clinicopathologic study of a patient with a family history of a lengthy and progressive neurodegenerative disorder associated with a novel large octapeptide repeat insert mutation. methods: Neuropathologic examination, including immunohistochemistry for the prion protein, was undertaken. The ORF of PRNP was amplified by PCR, cloned, and sequenced. Homogenate of cerebral tissue underwent Western blot analysis for the prion protein before and after proteinase K treatment. RESULTS: The proband died after a 16-year illness commencing at age 29 years. Confident premortem clinical diagnosis was not achieved despite a brain biopsy. autopsy examination of the brain confirmed a spongiform encephalopathy. Prion protein immunohistochemistry revealed occasional granular deposits in the cerebellar granular layer. The proband was found to harbor a novel PRNP 168 base pair (bp) insert mutation. CONCLUSION: The authors have identified a novel 168 bp octapeptide repeat insert mutation. Prion protein immunohistochemistry differs from previous cases harboring seven octapeptide repeat and other long insert mutations. Optimization of PRNP analysis, especially PCR conditions, is essential to avoid overlooking this type of mutation and delay the correct molecular genetic diagnosis.- - - - - - - - - - ranking = 20.099793941786keywords = spongiform encephalopathy, spongiform, encephalopathy (Clic here for more details about this article) |
6/22. Loss of glycosylation associated with the T183A mutation in human prion disease.A heterozygous T183A mutation in the prion protein (PrP) gene, PRNP, was identified in a patient with histopathologically confirmed spongiform encephalopathy. Clinically, this form of prion disease was characterized by early-onset dementia as the predominant sign, along with global cerebral atrophy and hypometabolism. The age at onset was 40 years and the disease duration was 4 years. Additional neurological signs including cerebellar ataxia and EEG abnormalities were absent until late stages of the disease. The T183A mutation was not found in non-affected family members. This mutation results in the removal of one of the two consensus sites for glycosylation of PrP. Neuropathological examination revealed severe spongiform degeneration and neuronal loss in the neocortex, putamen and claustrum, small plaque-like PrP-immunoreactive deposits in the molecular layer of the cerebellum, and faint intracellular cytoplasmic PrP immunoreactivity. Western blot analysis of the patient's brain tissue showed protease K-resistant PrP with a definite preponderance of the monoglycosylated form. The additional appearance of a band representing diglycosylated PrPSc strongly suggests that non-mutated PrP also acquires protease resistance in the present setting. Cell culture experiments confirmed previous reports on intracellular retention of the mutant protein in vitro. This is the second report of a disease-causing T183A mutation of PrP, and the clinical, histological and genetic observations strongly suggest that T183A is a disease-causing mutation.- - - - - - - - - - ranking = 11.042850650143keywords = spongiform encephalopathy, spongiform, encephalopathy (Clic here for more details about this article) |
7/22. Prion disease with a 144 base pair insertion: unusual cerebellar prion protein immunoreactivity.Sporadic, acquired, and genetic human prion diseases are characterized neuropathologically by distinct deposition patterns of the abnormal, disease-associated form of the prion protein (PrP(sc)). In addition to mutations in the prion protein gene (PRNP), PrP(sc) immunostaining patterns correlate with molecular phenotypes of prion diseases defined by the PRNP polymorphism at codon 129 and with protease-resistant PrP classified by Western blotting. Some point or insertional PRNP mutations share similar clinical and neuropathological phenotypes, whereas others show great variability even within the same family. Here we report a patient who presented clinically as sporadic Creutzfeldt-Jakob disease (CJD). Histologically moderate spongiform change was seen in cerebral and cerebellar cortical areas. Neuronal loss was restricted mainly to the occipital cortex and the basal ganglia. Surprisingly, numerous eosinophilic globular structures were noted in the molecular layer and the parahippocampal gyrus. These globules showed intense PrP immunopositivity using anti-PrP antibodies against different epitopes. They were stained with PAS but lacked congophilia and birefringence in polarized light. Ultrastructurally, globules were composed of 21-nm-thick intermingled filaments without dense core. Genetic analysis revealed a PRNP 144 base pair insertion. Our case reinforces the importance of molecular genetic diagnosis, especially in those patients who lack a family history of prion disease and show unusual neuropathological changes. It also widens the phenotypic spectrum of prion diseases. The phenotypic variability within the same mutation suggests further, yet uncharacterized, genetic or epigenetic influence on phenotype in these diseases.- - - - - - - - - - ranking = 0.99295367925006keywords = spongiform (Clic here for more details about this article) |
8/22. Intracerebral distribution of infectious amyloid protein in spongiform encephalopathy.We studied the regional distribution of infectious amyloid protein by western immunoblots of brain tissue extracts from 37 patients with different forms of spongiform encephalopathy, i.e., 16 sporadic cases, 18 familial cases with a variety of mutations, and 3 iatrogenic cases. In sporadic and familial Creutzfeldt-Jakob disease, amyloid protein concentrations were usually highest in the frontotemporal regions of the cerebral cortex, whereas iatrogenic Creutzfeldt-Jakob disease and Gerstmann-Straussler-Scheinker syndrome had as high or higher concentrations in the deep cerebral nuclei and cerebellum. As a group, familial cases had lower amyloid protein concentrations than either sporadic or iatrogenic cases, and fatal familial insomnia patients had the lowest concentrations found in any form of disease. This hierarchy of amyloid protein concentrations corresponds to the experimental transmission rates observed for each form of disease and is consistent with the concept that the protein molecule is an integral component of the infectious agent. Regional amyloid protein pattern analysis of brain and spinal cord may help to distinguish sporadic from environmentally acquired infections, as for example, cases of human disease suspected to have arisen from exposure to sheep or cows infected with scrapie or bovine spongiform encephalopathy.- - - - - - - - - - ranking = 60.299381825357keywords = spongiform encephalopathy, spongiform, encephalopathy (Clic here for more details about this article) |
9/22. Spongy encephalopathy in ketotic hyperglycinemia.Three cases of ketotic hyperglycinemia are described. Spongy encephalopathy was present in white as well as gray matter. The cell type that predominantly exhibited swelling was the astrocyte. glycine binding is required for activation of the NMDA receptor. By constant excitation a surplus of glycine could disturb the ion balance. This might provide the pathogenetic principle of seizures and cytotoxic edema in hyperglycinemia.- - - - - - - - - - ranking = 0.0088079009374252keywords = encephalopathy (Clic here for more details about this article) |
10/22. Inherited Creutzfeldt-Jakob disease in a British family associated with a novel 144 base pair insertion of the prion protein gene.A case of familial Creutzfeldt-Jakob disease associated with a 144 base pair insertion in the open reading frame of the prion protein gene is described. Sequencing of the mutated allele showed an arrangement of six octapeptide repeats, distinct from that of a recently described British family with an insertion of similar size. Thirteen years previously the brother of the proband had died from "Huntington's disease", but re-examination of his neuropathology revealed spongiform encephalopathy and anti-prion protein immunocytochemistry gave a positive result. The independent evolution of at least two distinct pathological 144 base pair insertions in Britain is proposed. The importance of maintaining a high index of suspicion of inherited Creutzfeldt-Jakob disease in cases of familial neurodegenerative disease is stressed.- - - - - - - - - - ranking = 10.049896970893keywords = spongiform encephalopathy, spongiform, encephalopathy (Clic here for more details about this article) |
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