Search

• Our study included 30 patients of NMOSD followed up over two years. • Isolated ON was the most common symptom at disease onset. • Serostatus of patients did not significantly affect EDSS score and ARR. • Only quadriparesis at disease onset predicted a worse disease outcome. • Rituximab was most effective in preventing relapse and reduction of EDSS. To study the clinical presentation and response to immunosuppressives in patients with Neuromyelitis Optica Spectrum Disorder (NMOSD) in a tertiary care hospital of eastern India. There was a female preponderance of the disease (6.5:1) with mean age of disease onset 26.6 years. Isolated ON was the most common presentation at disease onset (60 %). Among motor symptoms at disease onset, only quadriparesis predicted a worse EDSS outcome at last follow up (p = 0.003). Visual acuity ≤6/60 and bilateral involvement was more common in the seropositive patients than in seronegative patients. Anti MOG Antibody was tested in 64.2 % of seronegative patients and was negative. Rituximab was most effective in preventing relapses (no relapses) followed by azathioprine (reduction of ARR of 90.1 %) and mycophenolate (reduction of ARR of 58.6 %). Also the reduction in median EDSS score and median FSS score for vision was greatest for the patients who received rituximab (52.9 % and 33.3 % respectively). Relapsing course of the disease was frequently observed with isolated optic neuritis being the most common symptom at disease onset. Among the motor features only quadriparesis at disease onset predicted a worse disease outcome. Rituximab was most effective in reducing the median EDSS score on follow up and preventing relapse. [ABSTRACT FROM AUTHOR]

Neuromyelitis Optica (NMO) is an autoimmune inflammatory disease that affects the optic nerves and spinal cord. The autoantibody is generated against the abundant water channel protein of the brain, Aquaporin 4 (AQP4). Of the two isoforms of AQP4, the shorter one (M23) often exists as a supramolecular assembly known as an orthogonal array of particles (OAPs). There have been debates about the fate of these AQP4 clusters upon binding to the antibody, the exact mechanism of its turnover, and the proteins associated with the process. Recently several clinical cases of NMO were reported delineating the effect of Rituximab (RTX) therapy. Extending these reports at the cell signaling level, we developed a glioma based cellular model that mimicked antibody binding and helped us track the subsequent events including a variation of AQP4 levels, alterations in cellular morphology, and the changes in downstream signaling cascades. Our results revealed the extent of perturbations in the signaling pathways related to stress involving ERK, JNK, and AKT1 together with markers for cell death. We could also decipher the possible routes of degradation of AQP4, post-exposure to antibody. We further investigated the effect of autoantibody on AQP4 transcriptional level and involvement of FOXO3a and miRNA-145 in the regulation of transcription. This study highlights the differential outcome at the cellular level when treated with the serum of the same patient pre and post RTX therapy and for the first time mechanistically describes the effect of RTX. [Display omitted] • AQP4 is internalized and degraded upon exposure to NMO patient serum. • Prior to RTX therapy and after AQP4 I g G seropositive NMO patient serum exposure, AQP4 levels are regulated by miRNA 145. • Post RTX therapy and NMO serum exposure, the AQP4 increases as the level of miRNA 145 decreases. • The degradation of cellular AQP4 prior to RTX therapy occurs predominantly via the proteasomal pathway. [ABSTRACT FROM AUTHOR]

Abstract: A 3-year-old boy receiving valproate for 1.5 months presented with sudden-onset unprovoked seizures and unconsciousness. Hypoketotic hypoglycemia, hyperammonemia, and deranged liver function were detected. Elevated medium-chain urinary acylglycines and plasma acylcarnitine were detected. His serum valproate level was elevated. Valproate toxicity had been precipitated in presence of medium-chain acyl-CoA dehydrogenase deficiency. Cranial magnetic resonance imaging brain indicated unilateral basal ganglia ischemia instead of the bilateral changes expected in metabolic disease. [Copyright &y& Elsevier]