The syndrome of progressive encephalopathy with limb rigidity has been historically termed progressive encephalomyelitis with rigidity and myoclonus (PERM) or stiff-person syndrome plus.
The case is ...presented of a previously healthy 28-year-old man with a rapidly fatal form of PERM developing over 2 months.
Serum antibodies to both NMDA receptors (NMDAR) and glycine receptors (GlyR) were detected postmortem, and examination of the brain confirmed an autoimmune encephalomyelitis, with particular involvement of hippocampal pyramidal and cerebellar Purkinje cells and relative sparing of the neocortex. No evidence for an underlying systemic neoplasm was found.
This case displayed not only the clinical features of PERM, previously associated with GlyR antibodies, but also some of the features associated with NMDAR antibodies. This unusual combination of antibodies may be responsible for the particularly progressive course and sudden death.
Paraneoplastic autoimmune diseases associate occasionally with small cell lung cancers and gynecologic tumors. However, myasthenia gravis (MG) occurs in at least 30% of all patients with thymomas ...(usually present at MG diagnosis). These epithelial neoplasms almost always have numerous admixed maturing polyclonal T cells (thymocytes). This thymopoiesis-and export of mature CD4+T cells-particularly associates with MG, though there are rare/puzzling exceptions in apparently pure epithelial WHO type A thymomas. Other features potentially leading to inefficient self-tolerance induction include defective epithelial expression of the autoimmune regulator (AIRE) gene and/or of major histocompatibility complex class II molecules in thymomas, absence of myoid cells, failure to generate FOXP3+ regulatory T cells, and genetic polymorphisms affecting T-cell signaling. However, the strong focus on MG/neuromuscular targets remains unexplained and suggests some biased autoantigen expression, T-cell selection, or autoimmunization within thymomas. There must be further clues in the intriguing serological and cellular parallels in some patients with late-onset MG but without thymomas-and in others with AIRE mutations-and in the contrasts with early-onset MG, as discussed here.
To report an association of myelin-oligodendrocyte glycoprotein (MOG) antibodies with aquaporin-4 (AQP4) antibody-seronegative neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder ...(NMOSD) in adults.
We describe the clinical and serologic features of 4 adult patients with an NMO/NMOSD phenotype who had antibodies to MOG.
Twenty-seven adult AQP4-seronegative NMO/NMOSD patients were tested for MOG antibodies. Four patients (3 male, 1 female) with severe optic neuritis and/or longitudinally extensive transverse myelitis were positive. All 4 made good recoveries with steroids or plasma exchange. Two patients experienced recurrence of symptoms when corticosteroids were withdrawn quickly but none have experienced further relapses over a mean follow-up of 12 months, although 3 patients remain on treatment. Imaging abnormalities resolved fully following clinical recovery and MOG antibody titers fell in all 4 patients. MOG antibodies were not found in 44 AQP4 antibody-positive NMO/NMOSD patients, 75 adult patients with multiple sclerosis, or 47 healthy individuals.
MOG antibody-associated NMO/NMOSD could account for some cases thought previously to be AQP4-seronegative NMO/NMOSD. Our 4 patients appear to have more favorable clinical outcomes than those with typical AQP4 antibody-mediated disease. However, further studies of NMO/NMOSD and other demyelinating conditions are required to help clarify the diagnostic and prognostic relevance of MOG antibodies.
Abstract We studied the longitudinal relation between disease severity and titers of antigen-specific IgG subclasses in sera of patients with myasthenia gravis and antibodies to Muscle Specific ...Kinase (MuSK MG). Six patients were included of whom 55 samples had been collected during 2.5–13.4 years. Anti-MuSK antibodies were determined by ELISA and with a cell-based immunofluorescence assay. Disease severity was scored on a semi continuous scale. Only antigen-specific IgG4, and not IgG1, titers were significantly associated with disease severity in a linear mixed effect model ( p = 0.036). Levels of IgG4 antibodies were above IgG1 in all samples except in one patient who went into clinical remission while switching from IgG4 to IgG1. The results support an important role for IgG4 in the pathogenesis of MuSK MG, in contrast to MG with anti-acetylcholine receptor antibodies.
The identification of high-performance indicator taxa that combine practical feasibility and ecological value requires an understanding of the costs and benefits of surveying different taxa. We ...present a generic and novel framework for identifying such taxa, and illustrate our approach using a large-scale assessment of 14 different higher taxa across three forest types in the Brazilian Amazon, estimating both the standardized survey cost and the ecological and biodiversity indicator value for each taxon. Survey costs varied by three orders of magnitude, and dung beetles and birds were identified as especially suitable for evaluating and monitoring the ecological consequences of habitat change in our study region. However, an exclusive focus on such taxa occurs at the expense of understanding patterns of diversity in other groups. To improve the cost-effectiveness of biodiversity research we encourage a combination of clearer research goals and the use of an objective evidence-based approach to selecting study taxa.
Highlights • STZ-icv induced dysfunction in CA1-mPFC plasticity and recognition memory. • Nicotine was effective to prevent prefrontal LTP and memory deficits induced by STZ-icv. • Modulation of ...nicotinic receptor might be an alternative approach for AD treatment.
Background
Xeroderma pigmentosum (XP) patients present a high risk of developing skin cancer and other complications at an early age. This disease is characterized by mutations in the genes related ...to the DNA repair system.
Objectives
To describe the clinical and molecular findings in a cohort of 32 Brazilian individuals who received a clinical diagnosis of XP.
Methods
Twenty‐seven families were screened for germline variants in eight XP‐related genes.
Results
All patients (N = 32) were diagnosed with bi‐allelic germline pathogenic or potentially pathogenic variants, including nine variants previously undescribed. The c.2251‐1G>C XPC pathogenic variant, reported as the founder mutation in Comorian and Pakistani patients, was observed in 15 cases in homozygous or compound heterozygous. Seven homozygous patients for POLH/XPV variants developed their symptoms by an average age of 7.7 years. ERCC2/XPD, DDB2/XPE and ERCC5/XPG variants were found in a few patients. Aside from melanoma and non‐melanoma skin tumours, a set of patients developed skin sebaceous carcinoma, leiomyosarcoma, angiosarcoma, mucoepidermoid carcinoma, gastric adenocarcinoma and serous ovarian carcinoma.
Conclusions
We reported a high frequency of XPC variants in 32 XP Brazilian patients. Nine new variants in XP‐related genes, unexpected non‐skin cancer lesions and an anticipation of the clinical manifestation in POLH/XPV cases were also described.
Myelin oligodendrocyte-antibody-associated disease (MOGAD) often presents with severe optic neuritis (ON) but tends to recover better than in aquaporin-4 antibody neuromyelitis optica spectrum ...disorder (AQP4-NMOSD). We measured OCT and VEP in MOGAD and AQP4-NMOSD eyes with good visual function, with or without previous ON episodes. Surprisingly, OCT and/or VEPs were abnormal in 84% MOGAD-ON versus 38% AQP4-NMOSD-ON eyes (p = 0.009) with good vision, compared with 18% and 17% respectively of eyes with no previous ON. A sub-group with macular OCT performed as part of a research study confirmed both retinal and macular defects in visually-recovered MOGAD eyes. These findings have implications for investigation and management of MOGAD patients.
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