Antibodies to aquaporin-4 (AQP4) are found in a number of Japanese opticospinal multiple sclerosis (OSMS) patients. Whether anti-AQP4 antibody-positive and -negative OSMS patients are afflicted with an identical disease remains unknown. To clarify immunological differences between the two groups of patients, we studied serum antibody titres against AQP4 in 191 patients with idiopathic central nervous system demyelinating diseases and clarified any relationships with immunological parameters. The anti-AQP4 antibody positivity rate was higher in patients with OSMS (36.2%), idiopathic recurrent myelitis (23.5%), and recurrent optic neuritis (26.9%) than in conventional MS patients (8.0%), and those with other diseases (0%). Anti-AQP4 antibody titre was significantly higher in patients with SS-A/B antibodies than in those without. Anti-AQP4 antibody-negative OSMS patients showed significantly higher CD4+ IFN-γ+ IL-4- T cell percentages and intracellular IFN-γ/IL-4 ratios than anti-AQP4 antibodypositive patients, anti-AQP4 antibody-negative conventional MS patients, and healthy controls. As well, CD4+ IFN-γ+ IL-4- T cell percentages were negatively correlated with anti-AQP4 antibody titres. In CSF, OSMS patients had significantly higher levels of IFN-γ and granulocyte colony-stimulating factor levels than patients with non-inflammatory neurological diseases and other causes of myelitis. A significant increase of IL-17 compared with non-inflammatory neurological diseases patients was only found in OSMS patients, irrespective of the presence or absence of anti-AQP4 antibody. These findings suggest that high titres of anti-AQP4 antibodies are produced as a result of heightened humoral autoimmunity, and that they are likely to contribute to extensive lesion development through disturbed resolution of vasogenic oedema. Moreover, since intrathecal up-regulation of IL-17 and IFN-γ is characteristic of OSMS, Th17/Th1 cells may be critical for the initiation of inflammation and the disruption of blood-brain barrier (BBB); rendering anti-AQP4 antibody get across the BBB.

Background: We previously reported that, in Japanese patients with multiple sclerosis (MS), the frequency of chronic headaches was signifi cantly higher after administration of interferon beta (IFNβ). However, the mechanisms underlying IFNβ-related chronic headaches were unknown. Objective: To clarify the mechanisms underlying IFNβ-induced chronic headaches in MS patients by analyzing cytokine levels in cerebrospinal fl uid (CSF). Methods: We measured the levels of 27 CSF cytokines and growth factors using a fl uorescent bead-based immunoassay, during a headache-free period, in 34 MS patients enrolled in our previous survey on chronic headaches. Results: There were no signifi cant differences in CSF cytokine levels between the 21 MS patients with chronic headaches and the 13 without chronic headaches. Among the 14 patients receiving IFNβ therapy, the 5 patients with chronic headaches showed signifi cantly lower levels of interleukin (IL) 15, IL17 and chemokine (C-C motif) ligand 2 (CCL2) (also known as monocyte chemoattractant protein 1; MCP1) compared with the 9 patients without chronic headaches (P < 0.05). Conclusions: The present survey revealed that in MS, chronic headache sufferers on IFNβ therapy had decreased levels of IL15, IL17 and CCL2 in CSF. This suggests that chronic headaches may tend to develop in good responders to IFNβ.

Although cardiac rehabilitation (CR) has been shown to improve exercise tolerance and prognosis in patients with cardiovascular diseases, there remains low participation in outpatient CR. This may be attributed to the patients’ busy schedules and difficulty in visiting the hospital due to distance, cost, avoidance of exercise, and severity of coronary disease. To overcome these challenges, many countries are exploring the possibility of remote CR. Specifically, there is increasing attention on the development of remote CR devices, which allow transmission of vital information to the hospital via a remote CR application linked to a wearable device for telemonitoring by dedicated hospital staff. In addition, remote CR programs can support return to work after hospitalization. Previous studies have demonstrated the effects of remote CR on exercise tolerance. However, the preventive effects of remote CR on cardiac events and mortality remain controversial. Thus, safe and effective remote CR requires exercise risk stratification for each patient, telenursing by skilled staff, and multidisciplinary interventions. Therefore, quality assurance of telenursing and multi-disciplinary interventions will be essential for remote CR. Remote CR may become an important part of cardiac management in the future. However, issues such as costeffectiveness and insurance coverage still persist.