Antibody-mediated inflammatory diseases of the CNS, including aquaporin-4 antibody neuromyelitis optica spectrum disorder (AQP4-Ab NMOSD) and myelin oligodendrocyte glycoprotein antibody–associated disease (MOGAD), have undergone major therapeutic transformation with the advent of sensitive antibody assays and targeted immunotherapies. These advances have markedly reduced relapse rates and improved long-term outcomes. With improved disease control, questions regarding optimal treatment duration and the possibility of de-escalation or discontinuation are increasingly relevant. In AQP4-Ab NMOSD, relapses are typically severe and disabling, and most observational studies show a high risk of reactivation after tapering or withdrawal. Thus, discontinuation is never recommended. Successful de-escalation has been reported in selected patients with prolonged remission, although relapse risk persists, underscoring the need for individualized decisions and close monitoring. In contrast, MOGAD is clinically heterogeneous. Many patients, particularly children, experience a monophasic illness with good recovery, whereas relapse risk in adults appears to decline after several years. De-escalation strategies can thus be applied for anti-CD20 and IVIG. Recent cohort studies suggest that even discontinuation may be feasible after 2 to 5 years of remission in children and adults, especially in those who become seronegative for myelin oligodendrocyte glycoprotein immunoglobulin G. In seronegative NMOSD, the evidence base is limited and prognosis uncertain; attacks can be severe, no therapies are specifically approved, and although some experts suggest that discontinuation may be considered after 5 years of stability, this remains guided by expert opinion alone. Treatment de-escalation is sometimes necessary because of adverse effects, comorbidities, infections, treatment fatigue, or life circumstances such as pregnancy. In pregnancy, management requires balancing maternal disease control with fetal safety, with strategies ranging from continuation of selected therapies to temporary tapering or deferral. Monitoring with MRI, OCT, and emerging fluid biomarkers offers potential to detect early recurrence of disease activity, although none are validated for routine use. Prospective studies, real-world registry data, and dedicated trials are urgently needed to inform safe and patient-centered de-escalation/discontinuation strategies.
Y. Hacohen, G. Androdias, G. Arrambide et al.· Neurology· 0 citations
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the central nervous system, characterized by severe attacks. Optic neuritis is the most common clinical manifestation, leading to a rapid and often severe loss of vision, which is sometimes bilateral, with frequent sequelae and a risk of very low visual acuity in the long-term. Magnetic resonance imaging (MRI) reveals extensive lesions of the optic nerve, mostly involving the posterior part of the nerve and sometimes extending to the optic chiasm. Myelitis manifests as longitudinally extensive and centrally located spinal cord lesions, which may lead to tetraplegia, sensory disturbances, neuropathic pain and sphincter dysfunction. Area postrema syndrome presents with nausea, vomiting, and severe hiccups, which are often resistant to conventional treatments and may require hospitalization. Diagnosis is confirmed by the detection of anti-aquaporine 4 (AQP4) antibodies in the serum. Attacks should be treated as an emergency, with intravenous (IV) corticosteroids and plasma exchange, without waiting for antibody confirmation. Maintenance therapy includes monoclonal antibodies targeting B lymphocytes, interleukin-6 receptor, complement C5 and non-selective immunosuppressive treatments, according to profile of tolerance. Conventional treatments such as azathioprine or mycophenolate are less commonly used as first-line therapies but remain possible depending on the clinical context. Follow-up is multidisciplinary, with neurological, and according to the symptoms ophthalmological, neuropsychological, urodynamic or sequellar disability consultations. Therapeutic patient education and support from patient organizations are essential for improving quality of life and treatment adherence. Pregnancy is considered high-risk, requiring regular neurological and obstetric monitoring, as the risk of attack increases in the postpartum period. Finally, the rapid and individualized management of attacks as well as the prevention of relapses is crucial to limit functional sequelae and disability.
L. Giorgi, R. Marignier, J. Pique et al.· Revue neurologique (Paris)· 0 citations
A review of current evidence on established and emerging fluid biomarkers in NMOSD and MOGAD, with emphasis on analytical performance, biological relevance, and clinical utility, and outlines priorities for future research.
S. Mariotto, Á. Cobo-Calvo, Michael Khalil et al.· Neurology(R) neuroimmunology...· 0 citations