Current McDonald criteria for multiple sclerosis (MS) rely on complex statistical metaphors—dissemination in space and time—that are prone to clinical misapplication. This manuscript proposes a clinician-centred approach that simplifies diagnosis by focusing on four fundamental immunobiological pillars: confirming the condition is a chronic, inflammatory, demyelinating disease of the CNS. By reclassifying existing markers—such as the central vein sign, paramagnetic rim lesions, and neurofilaments—into these intuitive categories, the model provides clinicians greater flexibility to triangulate evidence based on available data. Crucially, this framework introduces Immunobiological MS (IBMS) (formerly Radiologically Isolated Syndrome) and Non-active CDMS as distinct diagnostic entities. These categories acknowledge the disease's biological diversity and accommodate variable treatment decisions.

Background Integrating clinical findings with neuroradiological changes is a crucial skill in neurology, particularly for diagnosis. Multiple Sclerosis (MS) lesions in the brainstem are rarely asymptomatic, leading to unique and often localised clinical syndromes. MS lesions exhibit a characteristic perivenular distribution, which in the brainstem is imprinted by the consistent topography of the penetrating veins. Objective This review provides an integrative perspective on the anatomical patterns of MS lesions in the brainstem (midbrain, pons, and medulla). It correlates specific clinical syndromes with radiological appearances, aiding in both diagnosis and functional localisation. Methods We searched the available literature using keywords related to the three brainstem sections (midbrain, pons, medulla) and eloquent anatomical locations (medial longitudinal fasciculus, cerebellar peduncle, nerve fascicle, aqueduct, area postrema), aiming to correlate specific radiological patterns of MS lesions with their consistent clinical syndromes as reported in the literature. Summary of Key Findings Brainstem MS lesions often cause irritative symptoms rather than full functional loss. Unlike other conditions, visible MS lesions on MRI rarely disappear and usually remain as silent lesions following an acute event. The consistent venous architecture creates specific radiological patterns that link to distinct clinical presentations. In contrast, inflammatory disorders like NMOSD and MOGAD cause more aggressive and extensive dysfunction. Conclusion The visual details of MS brainstem lesions reflect their close relationship to venous anatomy, which can be anticipated even when the central vein sign is not directly visualised. Recognising these specific clinical-radiological syndromes provides a unique and insightful diagnostic tool for MS, underscoring the value of strong functional and radiological-anatomical interpretation skills in clinical neurology.

Recent studies demonstrate the efficacy of B cell-targeting therapies in managing multiple sclerosis (MS) activity, emphasizing the critical role of B cells in MS pathogenesis. CladB study aimed to quantify the temporal changes in peripheral immune cells and their activity over 96 weeks of Cladribine tablets (CladT) treatment in relapsing-remitting MS (RRMS).Ten participants (3 males, 7 females) had blood samples collected at multiple intervals (Day 0, 1, 5, then weekly for 8 weeks, biweekly for up to 24 weeks, and monthly for up to 96 weeks) for immune cell analysis, compared to a historical alemtuzumab-treated cohort. Paired cerebrospinal fluid (CSF) was also taken for various analyses, alongside clinical and brain imaging assessments.CladT depleted memory B cells, while alemtuzumab rapidly depleted T and B cells. The кFLC index decreased from 164.5 ± 227.1 to 71.3 ± 84.7 at 48 weeks (p = 0.002) and to 64.4 ± 67.3 at 96 weeks (p = 0.01). The IgG index dropped from 1.1 ± 0.5 at baseline to 0.8 ± 0.4 at 48 weeks (p = 0.014) and to 0.8 ± 0.3 at 96 weeks (p = 0.02). CSF CXCL-13 decreased from 88.6 ± 68.4 pg/mL to 39.4 ± 35.2 pg/mL at 48 weeks (p = 0.037) and 19.1 ± 11.7 pg/mL at 96 weeks (p = 0.027). CSF NfL levels were reduced at 48 weeks (p = 0.01).CladT primarily depletes memory B cells and antibody-secreting cell precursors in RRMS, leading to sustained effects on intrathecal antibody production and total IgG, and a reduction in CSF CXCL-13.

BACKGROUND:Despite increasing evidence that Epstein-Barr virus (EBV) plays a causal role in MS, no treatments have been shown to reduce EBV turnover. We studied the effect of famciclovir on salivary EBV shedding in people with MS (NCT05283551) in a pilot, proof-of-concept study. METHODS:People with MS receiving natalizumab provided weekly saliva samples for 12 weeks before starting famciclovir 500 mg twice daily for 12 weeks. Twelve saliva samples were provided on treatment and 12 following treatment. A real-time qPCR Taqman assay was used to detect EBV DNA in saliva. The proportion of saliva samples containing EBV DNA was compared using the Friedman test. RESULTS:Of 30 participants (19 F; mean age 41 years; median EDSS 3.5), 29 received famciclovir, and 24 completed the 12-week course. Twenty-one participants provided at least one usable saliva sample in all epochs. Ten of the 21 had shedding in at least one sample pre-drug; 7/21 when taking famciclovir (not significant). No difference in EBV DNA copy number was seen. There were no drug-related serious adverse events. CONCLUSION:No significant effect of famciclovir on EBV shedding was seen in this small pilot study. Given the low numbers, a small effect of famciclovir cannot be excluded. Salivary EBV shedding in this natalizumab-treated cohort was lower than in previous studies, which requires replication.