Objective: To report a novel prion disease characterized by distinct histopathological and immunostaining features, and associated with an abnormal isoform of the prion protein (PrP) that, contrary to the common prion diseases, is predominantly sensitive to protease digestion. Methods: Eleven subjects were investigated at the National Prion Disease Pathology Surveillance Center for clinical, histopathological, immunohistochemical, genotypical, and PrP characteristics. Results: Patients presented with behavioral and psychiatric manifestations on average at 62 years, whereas mean disease duration was 20 months. The type of spongiform degeneration, the PrP immunostaining pattern, and the presence of microplaques distinguished these cases from those with known prion diseases. Typical protease-resistant PrP was undetectable in the cerebral neocortex with standard diagnostic procedures. After enrichment, abnormal PrP was detected at concentrations 16 times lower than common prion diseases; it included nearly 4 times less protease-resistant PrP, which formed a distinct electrophoretic profile. The subjects examined comprised about 3% of sporadic cases evaluated by the National Prion Disease Pathology Surveillance Center. Although several subjects had family histories of dementia, no mutations were found in the PrP gene open reading frame. Interpretation: The distinct histopathological, PrP immunohistochemical, and physicochemical features, together with the homogeneous genotype, indicate that this is a previously unidentified type of disease involving the PrP, which we designated "protease-sensitive prionopathy" (or PSPr). Protease-sensitive prionopathy is not rare among prion diseases, and it may be even more prevalent than our data indicate because protease-sensitive prionopathy cases are likely also to be classified within the group of non-Alzheimer's dementias.
Myasthenia gravis (MG) is still a disease of young women and old men, as reflected by the hospital admission rates. In-hospital mortality of MG is low. Hospital utilization of i.v. immunoglobulin has significantly increased compared to plasma exchange and thymectomy.
Five phenotypically distinct subtypes have been identified in sporadic Creutzfeldt-Jakob disease (sCJD), based on the methionine/valine polymorphic genotype of codon 129 of the prion protein (PrP) gene and the presence of either one of the two protease K-resistant scrapie prion protein (PrP(Sc)) types identified as 1 and 2. The infrequent co-existence of both PrP(Sc) types in the same case has been known for a long time. Recently, it has been reported, using type-specific antibodies, that the PrP(Sc) type 1 is present in all cases of sCJD carrying PrP(Sc) type 2. The consistent co-occurrence of both PrP(Sc) types complicates the diagnosis and the current classification of sCJD, and has implications for the pathogenesis of naturally occurring prion diseases. In the present study, we investigated the prevalence of PrP(Sc) types 1 and 2 co-occurrence, along with its effects on the disease phenotype and PrP(Sc) strain characteristics, comparatively analysing 34 cases of sCJD, all methionine homozygous at codon 129 of the PrP gene (sCJDMM). To minimize overestimating the prevalence of the sCJDMM cases carrying PrP(Sc) types 1 and 2 (sCJDMM1-2), we used proteinase K concentrations designed to hydrolyse all fragments resulting from an incomplete digestion, while preserving the protease-resistant PrP(Sc) core. Furthermore, we used several antibodies to maximize the detection of both PrP(Sc) types. Our data show that sCJDMM cases associated exclusively with either PrP(Sc) type 1 (sCJDMM1) or PrP(Sc) type 2 (sCJDMM2) do exist; we estimate that they account for approximately 56% and 5% of all the sCJDMM cases, respectively; while in 39% of the cases, both PrP(Sc) types 1 and 2 are present together (sCJDMM1-2) either mixed in the same anatomical region or separate in different regions. Clinically, sCJDMM1-2 had an average disease duration intermediate between the other two sCJDMM subtypes. The histopathology was also intermediate, except for the cerebellum where it resembled that of sCJDMM1. These features, along with the PrP immunostaining pattern, offer a diagnostic clue. We also observed a correlation between the disease duration and the prevalence of PrP(Sc) type 2 and sCJDMM2 phenotypes. The use of different antibodies and of the conformational stability immunoassay indicated that the co-existence of types 1 and 2 in the same anatomical region may confer special conformational characteristics to PrP(Sc) types 1 and 2. All of these findings indicate that sCJDMM1-2 should be considered as a separate entity at this time.
Inducible nitric oxide synthase (iNOS) is a transcriptionally regulated enzyme that synthesizes nitric oxide from L-arginine that has a key role in the pathophysiology of systemic inflammation and sepsis. Transgenic animals with a null mutation for the iNOS gene are resistant to hypotension and death caused by Escherichia coli lipopolysaccharide (LPS). The regulation of peripheral iNOS has been well studied in sepsis, but little is known about iNOS regulation in the brain during systemic inflammation or sepsis. We know that at baseline there is no detectable iNOS gene expression in the brain, but a detailed neuroanatomical study reveals that early in the course of systemic inflammation there is a profound induction of iNOS messenger RNA in vascular, glial and neuronal structures of the rat brain, accompanied by the production of nitric oxide (NO) metabolites in brain parenchyma and cerebrospinal fluid (CSF). We propose that the spillover of nitrite into the CSF has the potential to be a diagnostic marker for systemic inflammation and sepsis. Pharmacological interventions aimed at regulating iNOS function in the brain might represent a new treatment strategy in sepsis. Brain iNOS may be relevant to the pathophysiology, diagnosis and treatment of systemic inflammation and sepsis.
The mortality rate in Guillain-Barré syndrome is low, and predictors of death are similar to those predicting poor disability outcome. The disease incidence was stable over the 5 years included in this study.
ContributorsGIW wrote and revised the manuscript in response to co-author comments. He finalized all the figures and tables, performed the literature search, and assisted with data interpretation. HJK critically reviewed the manuscript and made important suggestions to improve it. He assisted with data interpretation. IBA performed the data analysis, constructed the figures and tables, and made important suggestions to improve the manuscript. H-CK assisted with the data analysis and also reviewed the manuscript. GRC critically reviewed the manuscript and made important suggestions to improve it. He assisted with data interpretation. All other authors were given the opportunity to review the manuscript and make suggestions which GIW received, either revising the paper or providing explanations. All who are not deceased were involved with approval of the manuscript.
Compared to PLEX, IVIG appears of similar clinical (mortality and complications) and perhaps of superior economic (length of stay and total inpatient charges) outcomes in the treatment of MG. Elderly and those with complex comorbid diseases including acute respiratory failure may be better treated with IVIG.
Electrodiagnostic procedures are routinely performed in patients with a variety of neuromuscular disorders. These studies are generally well tolerated and rarely thought to be associated with any significant side effects. However, needle electromyography is an invasive procedure and under certain situations has the potential to be associated with iatrogenic complications, including bleeding, infection, nerve injury, pneumothorax, and other local trauma. Similar complications are possible if needles are used for either stimulating or recording. In addition, like all other electrical devices and monitoring equipment connected to patients, electrodiagnostic testing carries the risk of stray leakage currents that under certain circumstances can result in electrical injury, especially in patients in the intensive care setting. Similarly, certain precautions are required during nerve conduction studies (NCS) in patients with pacemakers and other similar cardiac devices. In this review, we address the known and theoretical complications of NCS and needle electrode examination, and the possible methods to avoid such hazards.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.