Role of complement and potential of complement inhibitors in myasthenia gravis and neuromyelitis optica spectrum disorders: a brief review.

The complement system is a powerful member of the innate immune system. It is highly adept at protecting against pathogens, but exists in a delicate balance between its protective functions and overactivity, which can result in autoimmune disease. A cascade of complement proteins that requires sequential activation, and numerous complement regulators, exists to regulate a proportionate response to pathogens. In spite of these mechanisms there is significant evidence for involvement of the complement system in driving the pathogenesis of variety of diseases including neuromyelitis optica spectrum disorders (NMOSD) and myasthenia gravis (MG). As an amplification cascade, there are an abundance of molecular targets that could be utilized for therapeutic intervention. Clinical trials assessing complement pathway inhibition in both these conditions have recently been completed and include the first randomized placebo-controlled trial in NMOSD showing positive results. This review aims to review and update the reader on the complement system and the evolution of complement-based therapeutics in these two disorders.

Treatment of MOG-IgG-associated disorder with rituximab: An international study of 121 patients.

OBJECTIVE: To assess the effect of anti-CD20 B-cell depletion with rituximab (RTX) on relapse rates in myelin oligodendrocyte glycoprotein antibody-associated disorder (MOGAD). METHODS: Retrospective review of RTX-treated MOGAD patients from 29 centres in 13 countries. The primary outcome measure was change in relapse rate after starting rituximab (Poisson regression model). RESULTS: Data on 121 patients were analysed, including 30 (24.8%) children. Twenty/121 (16.5%) were treated after one attack, of whom 14/20 (70.0%) remained relapse-free after median (IQR) 11.2 (6.3-14.1) months. The remainder (101/121, 83.5%) were treated after two or more attacks, of whom 53/101 (52.5%) remained relapse-free after median 12.1 (6.3-24.9) months. In this 'relapsing group', relapse rate declined by 37% (95%CI=19-52%, p<0.001) overall, 63% (95%CI=35-79%, p = 0.001) when RTX was used first line (n = 47), and 26% (95%CI=2-44%, p = 0.038) when used after other steroid-sparing immunotherapies (n = 54). Predicted 1-year and 2-year relapse-free survival was 79% and 55% for first-line RTX therapy, and 38% and 18% for second-/third-line therapy. Circulating CD19+B-cells were suppressed to <1% of total circulating lymphocyte population at the time of 45/57 (78.9%) relapses. CONCLUSION: RTX reduced relapse rates in MOGAD. However, many patients continued to relapse despite apparent B-cell depletion. Prospective controlled studies are needed to validate these results.

Rituximab in neurological disease: principles, evidence and practice.

Rituximab is a widely used B-cell-depleting monoclonal antibody. It is unlicensed for use in neurological disorders and there are no treatment guidelines. However, as a rapidly acting, targeted therapy with growing evidence of efficacy and tolerability in several neuroinflammatory disorders, it is an attractive alternative to conventional immunomodulatory medications. This practical review aims to explain the basic principles of B-cell depletion with therapeutic monoclonal antibodies. We present the evidence for using rituximab in neurological diseases, and describe the practical aspects of prescribing, including dosing, monitoring, safety, treatment failure and its use in special circumstances such as coexisting viral hepatitis, pregnancy and lactation. We provide an administration guide, checklist and patient information leaflet, which can be adapted for local use. Finally, we review the safety data of rituximab and ocrelizumab (a newer and recently licensed B-cell-depleting therapy for multiple sclerosis) and suggest monitoring and risk reduction strategies.

Intracranial dural arteriovenous fistula mistaken as cervical transverse myelitis.

We describe a man with an intracranial dural arteriovenous fistula that presented as a subacute longitudinally extensive cervical myelopathy. The uncommon location of the fistula and the absence of specific radiological signs resulted in initial misdiagnosis as longitudinally extensive transverse myelitis. Neurologists should have a high index of suspicion for dural arteriovenous fistula in older men, especially those with subacute or chronic symptoms, acellular cerebrospinal fluid and, particularly, if there is neurological deterioration soon after corticosteroid treatment. Patients need early angiography to identify this treatable cause of myelopathy.