Updates in Multiple Sclerosis: AAN Annual Meeting 2026

Authors: *Andrew Dugue,1 Tyler Ellis Smith1 1. Department of Neurology, NYU Grossman School of Medicine, New York City, USA *Correspondence to [email protected] Disclosure: Smith has received research funding from PCORI and is set to receive research funding from Neurogenesis; is set to receive royalties from Es- sential Neurology Board Review Q&A, a book published through Springer; and has participated on the TREAT-MS Trial Study Advisory Committee, funded by PCORI. Dugue has declared no conflicts of interest. Keywords: Biomarker, central vein sign (CVS), disease-modifying therapy (DMT), McDonald Criteria, multiple sclerosis (MS). Citation: Neurol AMJ. 2026;3[1]:23-28. https://doi.org/10.33590/neurolamj/G2763DH3 ACROSS the spectrum of multiple sclerosis (MS) care, the American Academy of Neurology (AAN) Annual Meeting 2026 highlighted changes in the diagnosis of MS, impacting both asymptomatic and symptomatic patients. Additionally, a new mechanism of action for the treatment of MS, targeting Bruton’s tyrosine kinase (BTK), showed positive results in both progressive and relapsing MS. Together, these changes, along with updates in biomarkers and upcoming studies on the approach to treatment of MS, underscore the rapid state of change in MS care and opportunities for patients. INTRODUCTION Aaron Miller, Icahn School of Medicine at Mount Sinai, New York, USA, reviewed the latest 2024 McDonald Criteria, noting that it was developed through a consensus methodology. The 2024 McDonald Criteria incorporates clinical and radiographic data, as well as biomarkers, to make the diagnosis of MS earlier and in more individuals. Miller emphasized that these criteria maintain accuracy to ultimately reduce the burden of disability among individuals with MS.1 Highlighting a key change to the McDonald Criteria, Laura Balcer, NYU Grossman School of Medicine, New York, USA, presented the inclusion of the optic nerve as the fifth topographical region when evaluating for dissemination in space. Both asymptomatic and symptomatic optic nerve lesions are now included and can be detected with orbital MRI with gadolinium, and optical coherence tomography, along with visual evoked potentials (Table 1).

The addition of iron-sensitive MRI techniques to detect the presence of a central vein sign (CVS) and paramagnetic rim lesions (PRL) in the 2024 Revised McDonald Criteria were reviewed. The CVS enables the identification of white matter lesions with a central vein, which has demonstrated high sensitivity and specificity for MS, when using the ‘Select 6’ method to identify a sufficient number of CVSs to be consistent with MS. PRLs are thought to indicate chronic inflammation in demyelinating lesions, related to iron-laden macrophages and microglia at the lesion edge. While PRLs have not been as sensitive for the diagnosis of MS as a CVS, they remain highly specific. Together, these biomarkers can increase diagnostic specificity for MS. In addition to substituting oligoclonal bands unique to the cerebrospinal fluid to fulfil the dissemination in time criteria (present in the 2017 McDonald Criteria), the updated MS diagnostic criteria also allow for the use of kappa free light chains to substitute for dissemination in time. Balcer highlighted the advantages of kappa free light chains: high concordance with oligoclonal bands, while remaining rater-independent. Furthermore, if sufficient criteria are met, dissemination in time is no longer required to diagnose MS in the 2024 McDonald Criteria. The updated criteria also renovate the diagnosis of asymptomatic patients. As discussed by Miller and Jiwon Oh, University of Toronto, Canada, individuals who would have been diagnosed with radiologically isolated syndrome under the prior criteria will now be diagnosed with MS if they meet the appropriate criteria, despite being asymptomatic. Miller and Oh both emphasized the importance of applying these latest criteria in an individual with a typical syndrome (such as unilateral optic neuritis, partial myelopathy, focal supratentorial, brainstem, or cerebellar syndrome), and to use caution when examining atypical presentations (e.g., encephalopathy, isolated fatigue). While these updated criteria can be applied across diverse situations, Oh emphasized the need to confirm additional features of MS, such as spinal cord lesions, presence of oligoclonal bands and/or kappa free light chains, and the CVS, in individuals with a higher chance of misdiagnosis (e.g., older patients, younger patients, and those with vascular and headache comorbidities). Validation of the updated criteria was reviewed by Miller, who presented early data from Brownlee et al.3 demonstrating a substantial increase (28%) in the ability of the 2024 McDonald Criteria to diagnose MS with high accuracy, when compared to the 2017 criteria. Importantly, individuals who met the prior McDonald Criteria4 will continue to maintain the diagnosis of MS under the 2024 criteria. The latest McDonald Criteria also maintain that the presentation must not be better explained by another disorder. For further reading on a consensus approach to the differential diagnosis of MS, see Solomon et al.5 Ludwig Kappos, University Hospital Basel, Switzerland, presented his thoughts on the inclusion of a spectrum of biomarkers in trials, including blood-derived biomarkers (neurofilament light chain, glial fibrillary acidic protein), imaging biomarkers (quantitative MRI, optical coherence tomography, PET), and digital biomarkers. Additionally, Kappos highlighted the role of progression in MS and advocated for the inclusion of progression independent of relapse activity as a clinical endpoint. Gloria von Geldern, University of Washington School of Medicine, Seattle, USA, elaborated on the concept of progression independent of relapse activity, characterized by “microglial activation and dysfunctional astrocytes, … [resulting] in [central nervous system]-centric inflammation and neurodegeneration” and leading to a progressive decline in symptoms and function without distinct relapse activity, that has characterized the endpoints of trials focused on relapsing MS. Annette Wundes, University of Washington School of Medicine, Seattle, USA, presented defective oligodendrocyte progenitor cell recruitment as the primary reason that remyelination fails in chronic MS. Remyelination trials are ongoing to look at exercise and vagus nerve stimulation, as well a number of molecules that may be helpful in affecting remyelination. TREATMENTS Veronica Cipriani, University of Chicago Medicine, Illinois, USA, presented the importance of high efficacy disease-modifying therapy (DMT) in preventing irreversible disability and decreasing the number of relapses, MRI activity, and atrophy. Based on work by Langer-Gould et al.,6 Cipriani highlighted some key risk factors for long-term disability, including bowel and bladder symptoms at onset, incomplete recovery from first relapse, short interval between first and second relapses, early accumulation of disability, and Black or Hispanic race/ethnicity (Table 2). In addition to preventing relapses, Cipriani presented data supporting the association of higher efficacy treatments with a delay to the development of secondary progressive MS.