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Neuroimmunology

Multiple Sclerosis

Diagnosis, relapse treatment, and DMTs

Multiple sclerosis (MS) is diagnosed by dissemination in space and time. Relapses are treated with high-dose steroids; DMTs reduce relapses and disability.

1.Diagnosis

Dissemination in space and time (McDonald 2017). MRI, CSF (OCBs). Exclude NMO, ADEM, sarcoid, infection.[+]

2.MS Relapse

Definition

New or worse deficit, demyelinating pattern, >24 h, no fever/infection. Pseudo-relapse: do not treat with steroids.[+]

Treatment

High-dose steroids: Methylprednisolone 500–1000 mg IV × 3–5 days. Speeds recovery; minimal effect on long-term disability. Use for disabling relapses. Mild, non-disabling: often observe.[+]

Steroid failure or very severe: PLEX (5–7 exchanges). Consider for transverse myelitis, severe optic neuritis.[+]

3.Disease-Modifying Therapy

DMT reduces relapses and disability. Start early in RRMS. Choice by efficacy, safety, pregnancy. Injectables, orals, infusions — discuss with patient and neuro.[+]

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Frequently asked questions

How are the McDonald 2017 criteria used to diagnose multiple sclerosis?

McDonald 2017 criteria diagnose MS by demonstrating dissemination in space (DIS) and dissemination in time (DIT). DIS requires ≥1 T2 lesion in ≥2 of 4 CNS locations: periventricular, cortical/juxtacortical, infratentorial, or spinal cord. DIT requires either simultaneous gadolinium-enhancing and non-enhancing lesions on a single MRI, a new T2 or gadolinium-enhancing lesion on follow-up MRI, or CSF-specific oligoclonal bands. For a typical clinically isolated syndrome (CIS), MS can be diagnosed at the first clinical event if DIS is met on MRI plus either DIT on MRI or positive CSF oligoclonal bands. The 2017 revision added cortical lesions and symptomatic lesions as contributors to DIS and lowered the threshold to first attack with appropriate paraclinical evidence.

What is the treatment for an acute multiple sclerosis relapse?

Acute MS relapses with new disabling neurologic deficit are treated with high-dose corticosteroids: methylprednisolone 1 g IV daily for 3–5 days, or oral methylprednisolone 1000 mg daily for 3–5 days (oral and IV are equivalent per multiple RCTs and the 2018 AAN guideline). An oral prednisone taper is not routinely required. Steroids shorten the duration of relapse but do not alter long-term disability. Plasma exchange (5–7 exchanges over 10–14 days) is the standard of care for steroid-refractory, severely disabling relapses (AAN 2011, Class I, Level A) — particularly tumefactive demyelination, severe optic neuritis, or transverse myelitis with paraplegia. IVIG is not recommended for acute MS relapse treatment.

What are the high-efficacy disease-modifying therapies for multiple sclerosis?

High-efficacy DMTs for relapsing MS include the anti-CD20 monoclonals ocrelizumab and ofatumumab, natalizumab (anti-VLA-4), alemtuzumab (anti-CD52), and cladribine. Recent evidence — including the TREAT-MS trial and large registry analyses — supports an early high-efficacy strategy (starting one of these agents at diagnosis) over the traditional escalation approach (starting an injectable platform therapy and escalating only after breakthrough activity). Choice among high-efficacy agents balances efficacy, safety monitoring requirements (JC virus serology for natalizumab, immunoglobulin levels for anti-CD20s, autoimmunity surveillance for alemtuzumab), and patient factors (pregnancy planning, infection risk, vaccination status).

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