The evolution of multiple sclerosis (MS) diagnostic criteria over the past 4 decades has shortened the time to diagnosis of MS, enabling earlier institution of immunomodulatory therapy and therefore improved clinical outcomes. In response to a recent expansion of knowledge related to approaches and paraclinical tools that may aid diagnosis of MS and identify causes of MS misdiagnosis, the 2024 McDonald criteria reflect substantive changes and introduce new pathways to MS diagnosis. These revisions carry potential for both earlier and more accurate diagnosis of MS, yet require expertise for their appropriate application in clinical practice and introduce new challenges for global implementation. These changes include expansion of anatomical locations that represent dissemination in space, new paraclinical findings that can substitute for dissemination in time, inclusion of patients with asymptomatic or nonspecific clinical presentations, and recommendations for diagnostic approaches in specific patient populations. These changes also incorporate new paraclinical tools for the first time, including MRI central vein sign and paramagnetic rim lesions, CSF kappa free light chains, and optical coherence tomography. The revised criteria have now unified the diagnostic pathway for clinical presentations typical of MS with attack or progressive onset, and established a new pathway for patients without symptoms or with nonspecific clinical presentations accompanied by MRI findings typical of MS. The 2024 revisions continue to rely on recognition of typical clinical and MRI findings of MS, and additionally recommend specific approaches to pediatric patients, patients with vascular comorbidities, and older patients to further reduce the risk of misdiagnosis. Previous data suggest barriers to implementation, and misunderstanding and misapplication of prior revisions to MS diagnostic criteria that may be associated with misdiagnosis. Implementation of the revised 2024 McDonald criteria globally, particularly in low and low-middle income countries, will require educational outreach, leveraging and maximizing existing resources, and engagement of health care systems to improve access to new technology. This review contextualizes the implications of key revisions in the 2024 criteria for routine clinical care, while providing accessible guidance for its appropriate application with a lens toward nonspecialist clinicians and trainees globally, to ensure early and accurate MS diagnosis.
A. J. Solomon, W. Brownlee, Shanthi Viswanathan et al.· Neurology· 0 citations
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
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