In the present study, pregnancy-related attack was common in NMOSD, and unlike in multiple sclerosis, the ARR was not reduced during pregnancy. Discontinued or insufficient immunosuppression appeared to increase the risk of pregnancy-related attack.

BackgroundCognitive impairment could affect quality of life for patients with multiple sclerosis (MS), and cognitive function may be correlated with several factors such as depression and fatigue. This study aimed to evaluate cognitive function in Japanese patients with MS and the association between cognitive function and apathy, fatigue, and depression.MethodsThe Brief Repeatable Battery of Neuropsychological tests (BRB-N) was performed in 184 Japanese patients with MS and 163 healthy controls matched for age, gender, and education. The Apathy Scale (AS), Fatigue Questionnaire (FQ), and Beck Depression Inventory Second Edition (BDI-II) were used to evaluate apathy, fatigue, and depression, respectively. Student’s t-test was used to compare MS patients and healthy controls. Correlations between two factors were assessed using the Pearson correlation test, and multiple regression analysis was used to evaluate how much each factor affected the BRB-N score.ResultsIn all BRB-N tests, patients with MS scored significantly lower than controls, and the effect size of symbol digit modalities test was the highest among the 9 tests of the BRB-N. Patients with MS had higher AS (p < 0.001), FQ (p < 0.0001), and BDI-II (p < 0.0001) scores than controls. In patients with MS, scores on most of the BRB-N tests correlated with scores on the AS and BDI-II; however, there was little correlation between scores on the BRB-N tests and those on the FQ.ConclusionsCognitive function was impaired, particularly information-processing speed, and decreased cognitive function was correlated with apathy and depression in Japanese patients with MS. Despite the association between cognitive variables and depression/apathy, cognitive function was impaired beyond the effect of depression and apathy. However, subjective fatigue is not related with cognitive impairment. Taken together, this suggests that different therapeutic approaches are needed to improve subjective fatigue and cognition, and thereby quality of life, in patients with MS.

Odor impairment and its relationship with TAR DNA-binding protein 43 (TDP-43) pathology in patients with amyotrophic lateral sclerosis (ALS) have not been fully elucidated. We performed the odor stick identification test for Japanese (OSIT-J) in 18 ALS patients and in 18 controls. The score was significantly decreased (6.6 ± 2.7) in the patients versus the controls (9.2 ± 2.4) (U = 77.0, p = 0.007). This decrement of the OSIT-J score paralleled the cognitive decline. We then studied samples from a series of 42 postmortem ALS cases. Quantitative analyses demonstrated that TDP-43-positive inclusions were most frequent in the hippocampus and least abundant in the olfactory bulb and were of intermediate density in the primary olfactory cortex. This centrifugal gradient suggests that TDP-43 pathology starts in the hippocampus, spreads into the primary olfactory center, and finally reaches the olfactory bulb. TDP-43, tau, and α-synuclein accumulations appeared to be independent. These observations suggest that impaired odor discrimination in ALS patients may be related to TDP-43-positive lesions affecting predominantly secondary olfactory centers (especially the hippocampus) in contrast to decreased odor sensitivity in Parkinson disease in which α-synuclein pathology mainly involves the peripheral region (i.e., olfactory bulb). We suggest that detectable odor impairments in ALS patients are useful for predicting the presence of TDP-43 pathology in the extramotor system.

These abnormalities in IL-10 regulation were not seen in the relapsing-remitting form of MS. Thus, the defect in regulation of both IL-12 and IFNgamma production by endogenous IL-10 in progressive MS could be an important factor involved in the transition of MS from the relapsing to the progressive stage and has implications for treating MS patients with exogenous IL-10.

Multiple sclerosis (MS) is a putative autoimmune disease that is linked with HLA-DR2,w15. Proteolipid protein (PLP) is a candidate autoantigen in MS, but the disease-associated epitopes have not been determined. Using overlapping and non-overlapping PLP peptides, we have studied the T cell response to the major hydrophilic domain PLP 85-159 in the peripheral blood of MS and healthy subjects (HS). Short-term T cell lines (TCL) were selected against each peptide using microwell plates and the frequency of peptide-specific TCL was estimated. PLP 95-116-specific TCL were most efficiently generated and the frequency was significantly higher in MS compared with HS (P < 0.05). When compared between DR2,w15+ and DR2,w15- MS, TCL frequency to PLP 95-116 was significantly higher in DR2,w15+ MS (P < 0.005) and TCL reactive to the overlapping peptide 105-124 were also increased in DR2,w15+ MS (P < 0.025). Using DR gene-transfected L cells, we could show that the DRB1*1501 product of the DR2 haplotype presents PLP 95-116 to TCL selected against the peptide. These results imply that PLP 95-116 represents a major epitope for the DR2,w15+ MS.