No abstract

No abstract

Background: There are still insufficient quantitative comparisons of phase-dependent blood-brain barrier permeability among inflammatory central nervous system disorders. Aim: By using the Reibergram (2-D diagram of the quotient of albumin and quotient of immunoglobulin G), we visually compared the extent of blood-brain barrier permeability among inflammatory central nervous system disorders. Methods: Both the quotient of albumin and that of immunoglobulin G in the acute and chronic phase were calculated in non-herpetic meningitis, septic meningitis, multiple sclerosis and neuromyelitis optica, and were plotted on the Reibergram. As controls, samples from non-inflammatory patients without pleocytosis were collected. The correlation coefficient between each cerebrospinal fluid biomarker and disease severity index in each disorder was also studied. Results: In the controls, the distribution differed between males and females, suggesting a sex-dependent difference in blood-brain barrier-function, in addition to the age-related compromise. A compromised blood-brain barrier was confirmed in the acute phase of meningitis and neuromyelitis optica, but not in the acute phase of multiple sclerosis. However, blood-brain barrier permeability significantly correlated with the severity and disability in multiple sclerosis. In meningitis, a compromised blood-brain barrier correlated well with the length of hospitalization rather than cerebrospinal fluid cell count. Conclusion: Visualization of the blood-brain barrier permeability with a Reibergram indicated distinct pathophysiology in each disorder. The quotient of albumin and quotient of immunoglobulin G would be useful for estimating the pathophysiology in each disorder, and the severity of ongoing inflammation or damage in the central nervous system.

The terminal complement inhibitor eculizumab was shown to improve myasthenia gravis-related symptoms in the 26-week, phase 3, randomized, double-blind, placebo-controlled REGAIN study (NCT01997229). In this 52week sub-analysis of the open-label extension of REGAIN (NCT02301624), eculizumab's efficacy and safety were assessed in 11 Japanese and 88 Caucasian patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis. For patients who had received placebo during REGAIN, treatment with openlabel eculizumab resulted in generally similar outcomes in the Japanese and Caucasian populations. Rapid improvements were maintained for 52 weeks, assessed by change in score from open-label extension baseline to week 52 (mean [standard error]) using the following scales (in Japanese and Caucasian patients, respectively): Myasthenia Gravis Activities of Daily Living (−2.4 [1.34] and − 3.3 [0.65]); Quantitative Myasthenia Gravis (−2.9 [1.98] and − 4.3 [0.79]); Myasthenia Gravis Composite (−4.5 [2.63] and − 4.9 [1.19]); and Myasthenia Gravis Quality of Life 15-item questionnaire (−8.6 [5.68] and − 6.5 [1.93]). Overall, the safety of eculizumab was consistent with its known safety profile. In this interim sub-analysis, the efficacy and safety of eculizumab in Japanese and Caucasian patients were generally similar, and consistent with the overall REGAIN population.