Antibodies to the aquaporin-4 (AQP4) water channel in neuromyelitis optica spectrum disorder (NMOSD) are reported to trigger the complement cascade, which is implicated in astrocyte damage and subsequent neuronal injury. The PREVENT study demonstrated that the terminal complement inhibitor eculizumab reduces adjudicated relapse risk in patients with anti-AQP4 immunoglobulin G-positive (AQP4+) NMOSD. The objective of this analysis was to evaluate the efficacy of eculizumab in reducing relapse risk and its safety in AQP4+ NMOSD across clinically relevant subgroups in PREVENT.In the randomized, double-blind, time-to-event, phase 3 PREVENT trial, 143 adults received eculizumab (maintenance dose, 1200 mg/2 weeks) or placebo (2:1), with stable-dose concomitant immunosuppressive therapy (IST) permitted (except rituximab and mitoxantrone). Post hoc analyses of relapses and adverse events were performed for prespecified and post hoc subgroups based on concomitant IST and prior rituximab use, demographic and disease characteristics, and autoimmune comorbidity.The significant reduction in relapse risk observed for eculizumab versus placebo in the overall PREVENT population was consistently maintained across subgroups based on concomitant IST and previous rituximab use, age, sex, region, race, time since clinical onset of NMOSD, historical annualized relapse rate, baseline Expanded Disability Status Scale score, and history of another autoimmune disorder. The serious infection rate was lower with eculizumab than placebo regardless of rituximab use in the previous year, concomitant IST use, or history of another autoimmune disorder.Across a wide range of clinically relevant AQP4+ NMOSD patient subgroups in PREVENT, eculizumab therapy was consistently effective versus placebo in reducing relapse risk, with no apparent increase in serious infection rate.NCT01892345 (ClinicalTrials.gov).
A 72-year-old man was admitted for examination of dyspnea and pitting edema of the lower legs in July, 1996. His hemoglobin level was 6.9 g/dl, and myelodysplastic syndrome (MDS) was revealed by bone marrow aspiration, and frequent transfusions were needed. His renal function rapidly deteriorated in the middle of August (BUN 45 mg/dl, Cr 4.8 mg/dl) and IgA nephropathy (IgAN) with marked intestinal nephritis was disclosed by renal biopsy. In November, joint manifestations of warmth and pain, which suggested arthritis, appeared at the bilateral wrist and ankle joints. Soon after receiving prednisolone (20 mg/day), the arthritis was relieved. Renal function also improved (BUN 41 mg/dl, Cr 21 mg/dl) and frequent transfusions were no longer necessary. This is a case with various clinical manifestations of MDS, IgAN, and arthritis, and appears to be the first MDS case complicated with IgAN. A number of case reports have identified immune abnormalities in patients with MDS. Immune and bone marrow abnormalities have been reported to be involved in the pathogenesis of IgAN. Thus, MDS could be complicated by IgAN. Their pathogenetic association is discussed in this paper.
Malformations caused by abnormalities of cortical development, or cortical dysplasias, were examined in surgical specimens from 108 patients with medically intractable epilepsy to determine the scope of histopathologic changes. The relevance of the clinical findings was also evaluated. Various types and degrees of dysplastic features were observed in various combinations, including architectural abnormalities, an increased number of neurons in the molecular layer and/or cortical layer II, neuronal clustering, an increased number of satellite oligodendrocytes, abnormal gyration, single and/or aggregates of heterotopic neurons in the white matter, and the appearance of cytologically abnormal cells, such as giant or dysmorphic neurons and balloon cells. In the temporal lobe specimens, microdysgenesis (corresponding to mild malformations caused by abnormalities of cortical development and type IA/B focal cortical dysplasias) was more frequently observed than Taylor-type focal cortical dysplasia (type IIA/B), whereas in the frontal lobe specimens, the frequency of occurrence of both types was even. The ages at seizure onset and surgery of patients with the latter type were significantly lower than those of patients with the former. On the other hand, prominent astrocytosis in the cortex and white matter was evident in all cases, and many corpora amylacea and neurofibrillary tangle—like inclusions were observed in a subset of cases. An ultrastructural investigation revealed dilatation of the postsynaptic dendritic spines and shafts in the cortex and features indicating the occurrence in the white matter of demyelination followed by remyelination. Thus, with regard to the epileptogenic lesions, although dysplastic changes constitute the pathogenetic basis, the overlapping subsequent degenerative processes involving synapses, dendrites, and axons might contribute to the development of epileptogenic processes. Astrocytes might also actively participate in the development of the pathogenesis of epilepsy. ( J Child Neurol 2005;20:341—350).
Abstract We report a case of frontotemporal dementia and parkinsonism linked to chromosome 17 of 5 years' duration in an 81‐year‐old man whose brother had died at age 86 years with dementia. In this patient, we found frontal and temporal neuronal loss, glial‐predominant tau deposits, progressive supranuclear palsy‐like straight tubules, accumulation of 4‐repeat‐predominant Sarkosyl‐insoluble tau, and a novel exon 1 (Arg5His) tau gene mutation. This mutation decreased microtubule‐promoting capacity and increased fibrillation of tau in vitro. Thus, we consider that the Arg5His mutation is an authentic tau gene abnormality responsible for the patient's tau pathology and late‐onset dementia.
Additional file 1. Mineral assemblages of altered rock fragments in the volcanic ash. All of mineral assemblages we obtained from the volcanic ash are shown. †: Minerals name are abbreviated as: Si: Silica mineral, Pyr: pyrite, Anh: anhydrite, Gyp: gypsum, Alu: alunite, Kao: 7 Å-kaolin-group mineral, Pyl: pyrophyllite, Mus: muscovite, Chl: chlorite, Bi: biotite, Grt: garnet, Kfs(Or): potassic feldspar with orthoclase percent in the bracket, Ab(Ab): albite with albite percent the bracket, Pl(An): plagioclase with anorthite percent in the bracket, Ano(Ab): anorthoclase with albite percent the bracket, Px: pyroxene, and. Rul: rutile. ††: Samples named “coarse” is a grain in the coarse fraction and “med” is a grain in the medium fraction.
