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.

Wide-awake local anesthesia has many advantages. We describe a new method to use wide-awake local anesthesia with more flexibility. A 32-year-old man with a severe right-hand contracture after an iatrogenic tourniquet accident during an anterolateral thigh flap for a partial hand amputation underwent contracture release using external fixation after proximal row carpectomy and subsequent tenolysis. We performed most of the tenolysis procedure under general anesthesia and the final stage with an intraoperative assessment of active finger movement and dissection under local anesthesia. He regained his grip strength 2.5 years post-injury. General anesthesia is useful to treat a surgical site with extensive hard scars, whereas local anesthesia is useful for adjusting tension in an awake patient. The indication for wide-awake surgery is yet to be established; our method of combining general and local anesthesia in the tenolysis procedure illustrates the possibilities in expanding this method.
Adult ; Anesthesia, General ; Anesthesia, Local ; Brain Neoplasms ; Contracture/surgery* ; Dissection ; External Fixators ; Fracture Fixation ; Humans ; Male ; Wakefulness