ObjectiveTo investigate the clinical characteristics and prognosis of anti-gamma-aminobutyric acid-B (GABA-B) receptor encephalitis.MethodsThis retrospective study enrolled nineteen patients with anti-GABA-B receptor encephalitis. Clinical manifestations, radiological and electroencephalogram features, treatment and outcomes were collected and analyzed. The neurological function was evaluated according to the modified Rankin Scale (mRS).ResultsThere were eleven patients in the favorable-prognosis group (mRS ≤ 2) and eight patients in the poor-prognosis group (mRS > 2). In the favorable-prognosis group, clinical symptoms included memory deterioration (n = 10; 90.9%), epileptic seizures (n = 9; 81.8%), psychiatric disorders (n = 9; 81.8%), and conscious disturbance (n = 5; 45.5%); magnetic resonance imaging (MRI) indicated an involvement of the limbic system in three (27.3%) cases in this group. Lung cancer was detected in one patient (9.1%). After an average follow-up period of 11.7 months, four (36.4%) patients were cured, and seven (63.6%) patients showed significant improvements. In the poor-prognosis group, all patients presented with memory deterioration, epileptic seizures, psychiatric disorders, and conscious disturbance; five (62.5%) patients had convulsive status epilepticus, and five (62.5%) patients developed respiratory failure; MRI indicated an involvement of the limbic system in seven (87.5%) cases. Malignant tumors were detected in five (62.5%) patients. After an average follow-up period of 14.8 months, seven (87.5%) patients died and one (12.5%) patient remained dependent in daily life.ConclusionsThe clinical manifestations of anti-GABA-B receptor encephalitis include epileptic seizures, cognitive impairment and psychiatric disorders. Patients with convulsive status epilepticus or respiratory failure have poor outcomes. In anti-GABA-B receptor encephalitis, limbic system involvement is associated with a poor prognosis in and radiological examinations can reflect disease progression. Early diagnosis and appropriate treatment should be highlighted.
Inflammasomes are multiprotein complexes that can sense pathogen-associated molecular patterns and damage-associated molecular signals. They are involved in the initiation and development of inflammation via activation of IL-1β and IL-18. Many recent studies suggest a strong correlation between inflammasomes and neurological diseases, such as multiple sclerosis (MS), Alzheimer's disease (AD), and Parkinson's disease (PD). Several components of inflammasomes, such as nucleotide-binding oligomerization domain- (NOD-) like receptor, absent in melanoma 2- (AIM2-) like receptors (ALRs), apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1, as well as the upstream factors and downstream effectors, are associated with the initiation and development of MS and its animal model, experimental autoimmune encephalomyelitis. Additionally, inflammasomes affect the efficacy of interferon-β therapy in patients with MS. Finally, the strong association of inflammasomes with AD and PD needs to be further studied. In this review of latest literatures, we comprehensively tease out diverse roles of different kinds of inflammasomes in neuroimmune and neurodegenerative diseases, especially in the perspective of double roles involved in pathogenesis, and identify future research priorities.
Cerebral venous sinus thrombosis (CVST) is a central nervous system disease characterised by thrombosis in cerebral venous or dural sinuses. Autoimmune diseases, a series of diseases caused by immune responses to autoantigens, are important causes of CVST. The most common diseases that lead to CVST are Behçet’s syndrome, systemic lupus erythematosus, antiphospholipid syndrome, and Sjögren’s syndrome. Each of these diseases have different clinical and imaging manifestations and treatment for CVST varies by aetiology. This review summarises the characteristics and the current management strategies for autoimmune disease-associated CVST and emphasises controversial therapeutic strategies to provide informative reference information for diagnosis and treatment. Risk factors of autoimmune antigens should not be neglected when unconventional CVST occurs, and both drugs and interventional therapy need further standardisation and discussion with more prospective clinical studies.
Previous studies have revealed that the infectious scrapie isoform of prion protein (PrPSc) harbored in the skin tissue of patients or animals with prion diseases can be amplified and detected through the serial protein misfolding cyclic amplification (sPMCA) or real-time quaking-induced conversion (RT-QuIC) assays. These findings suggest that skin PrPSc-seeding activity may serve as a biomarker for the diagnosis of prion diseases; however, its utility as a biomarker for prion therapeutics remains largely unknown. Cellulose ethers (CEs, such as TC-5RW), widely used as food and pharmaceutical additives, have recently been shown to prolong the lifespan of prion-infected mice and hamsters. Here we report that in transgenic (Tg) mice expressing hamster cellular prion protein (PrPC) infected with the 263K prion, the prion-seeding activity becomes undetectable in the skin tissues of TC-5RW-treated Tg mice by both sPMCA and RT-QuIC assays, whereas such prion-seeding activity is readily detectable in the skin of untreated mice. Notably, TC-5RW exhibits an inhibitory effect on the in vitro amplification of PrPSc in both skin and brain tissues by sPMCA and RT-QuIC. Moreover, we reveal that TC-5RW is able to directly decrease protease-resistant PrPSc and inhibit the seeding activity of PrPSc from chronic wasting disease and various human prion diseases. Our results suggest that the level of prion-seeding activity in the skin may serve as a useful biomarker for assessing the therapeutic efficacy of compounds in a clinical trial of prion diseases and that TC-5RW may have the potential for the prevention/treatment of human prion diseases.
Prion is an infectious protein (PrPSc) that is derived from a cellular glycoprotein (PrPC) through a conformational transition and associated with a group of prion diseases in animals and humans. Characterization of proteinase K (PK)-resistant PrPSc by western blotting has been critical to diagnosis and understanding of prion diseases including Creutzfeldt-Jakob disease (CJD) and Gerstmann-Sträussler-Scheinker (GSS) disease in humans. However, formation as well as biochemical and biological properties of the glycoform-selective PrPSc in variably protease-sensitive prionopathy (VPSPr) remain poorly understood. Here we reveal that formation of the ladder-like PrPSc in VPSPr is a PK-dependent two-step process, which is enhanced by basic pH. Two sets of PrPSc fragments can be identified with antibodies directed against an intermediate or a C-terminal domain of the protein. Moreover, antibodies directed against specific PrP glycoforms reveal faster electrophoretic migrations of PrP fragments mono-glycosylated at residue 181 and 197 in VPSPr than those in sporadic CJD (sCJD). Finally, RT-QuIC assay indicates that PrPSc-seeding activity is lower and its lag time is longer in VPSPr than in sCJD. Our results suggest that the glycoform-selective PrPSc in VPSPr is associated with altered glycosylation, resulting in different PK-truncation and aggregation seeding activity compared to PrPSc in sCJD.
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