Neurology · Topic 22 of 22

Multiple Sclerosis Relapse

Neurology · demyelinating disease

Multiple Sclerosis Relapse

A new deficit for 24 hours without fever or infection is a relapse; rule out pseudo-relapse, then give high-dose methylprednisolone for disabling attacks.

Key numbers

New deficit lasting ≥ 24 hours≥ 24 h

Methylprednisolone 1 g daily, 3–5 days1 g × 3–5 days

Fingolimod first dose: 6-hour bradycardia watch≥ 6 h observation

01 · What it isNew deficit lasting ≥ 24 hours

A relapse is a new or worsening neurologic deficit lasting ≥ 24 hours without fever, infection or other acute illness, starting ≥ 30 days after the previous episode began.

02 · Don't confusePseudo-relapse: infection, fever or heat

Pseudo-relapse: old symptoms resurfacing with infection (often UTI), fever, heat or stress and no new MRI activity; check temperature, CBC and urinalysis with culture, and treat the trigger, not with steroids.

03 · GiveMethylprednisolone 1 g daily, 3–5 days

Treat disabling relapses with high-dose methylprednisolone 1 g IV (or oral) daily for 3–5 days; it speeds recovery but does not change long-term disability.

Presentation

What you'll see

Uhthoff phenomenon: heat worsens old deficitsHeat from fever, exercise, hot weather or a hot bath temporarily worsens existing MS deficits (Uhthoff phenomenon) — treat the fever and cool the patient.

Diagnosis & monitoring

Work-up

MRI with gadolinium, ideally before steroidsGadolinium-enhancing lesions confirm new activity; image ideally within 72 hours and before steroids, which shorten enhancement. Add spinal MRI for cord symptoms.

Natalizumab: check JC virus antibodyBefore and during natalizumab, check JC virus antibodies to stratify PML risk; seronegative patients are retested every 6 months.

Fingolimod first dose: 6-hour bradycardia watchFingolimod requires first-dose monitoring for bradycardia and AV block (≥ 6 hours with ECGs), fundus exams for macular edema, and warns of severe disability rebound after stopping.

Anti-CD20 therapy: screen for hepatitis BBefore ocrelizumab or other anti-CD20 therapy, screen for hepatitis B (active HBV is a contraindication) and check immunoglobulins; premedicate with steroid and antihistamine for infusion reactions.

Do right now

In this order

First moves

Pseudo-relapse: infection, fever or heat

→

MRI with gadolinium, ideally before steroids

→

Methylprednisolone 1 g daily, 3–5 days1 g × 3–5 days

Why each step

Pseudo-relapse: infection, fever or heatPseudo-relapse: old symptoms resurfacing with infection (often UTI), fever, heat or stress and no new MRI activity; check temperature, CBC and urinalysis with culture, and treat the trigger, not with steroids.

Methylprednisolone 1 g daily, 3–5 daysTreat disabling relapses with high-dose methylprednisolone 1 g IV (or oral) daily for 3–5 days; it speeds recovery but does not change long-term disability.

Management

Orders

Steroid-refractory severe relapse: plasma exchangeFor a severe relapse that fails high-dose steroids, use plasma exchange — typically 5 exchanges on alternate days.

Red flags & don'ts

Avoid harm

New deficits on natalizumab: think PML complicationNew cognitive change, aphasia, hemianopia or ataxia on natalizumab (also fingolimod or anti-CD20 drugs) suggests progressive multifocal leukoencephalopathy: hold the drug, get MRI, then CSF JC virus PCR.

High-dose steroids: glucose, insomnia, mood, infection complicationWarn about insomnia, mood change, GI upset, metallic taste and infection risk; monitor glucose (closely in diabetes) and add gastroprotection for prior ulcer or reflux.

The rules

Know these

Mild sensory relapses usually go untreatedMild relapses, especially purely sensory ones, are usually not treated with steroids unless they significantly affect function or quality of life.

Relapse or pseudo-relapse?

Commonly confused

Cause	New CNS inflammation
Duration	≥ 24 hours
Symptoms	New or worsening deficit
MRI	New gadolinium-enhancing lesions
Treatment	High-dose methylprednisolone if disabling

Commonly confused

Tell apart

Exclude cord compression and strokeBefore calling it a relapse, consider spinal cord compression, stroke and functional disorders, which can mimic an MS attack.

More detail

Reference

Show 5 reference facts

Alemtuzumab raises the risk of secondary autoimmune disease, serious infusion reactions and some cancers; it is reserved for disease failing ≥ 2 other drugs.

Relapse risk rises in the first 3 months postpartum and after stopping an effective disease-modifying therapy; anti-TNF agents can also trigger relapses.

Brief stereotyped paroxysmal symptoms (trigeminal neuralgia, tonic spasms, paroxysmal dysarthria) recurring many times a day usually respond to carbamazepine rather than steroids.

If PML is confirmed on natalizumab, plasma exchange removes the drug; immune reconstitution inflammatory syndrome that follows is treated with glucocorticoids.

Most patients have bladder dysfunction; retention and intermittent catheterization predispose to UTI, a common pseudo-relapse trigger.

Pearl

Fever, infection or heat first — a pseudo-relapse needs the trigger treated, not steroids.

Sources · Ramo-Tello C et al. Recommendations for the Diagnosis and Treatment of Multiple Sclerosis Relapses. J Pers Med 2021;12:6 · Merck Manual Professional — Multiple Sclerosis (MS) · Gilenya (fingolimod) prescribing information — DailyMed · Ocrevus (ocrelizumab) prescribing information — DailyMed · Hudak NM. Identifying and Managing MS Relapse. Clinician Reviews 2018;28(9):e9–e10 (MS Consult, Duke MS division) · Starter sheet built from the verified AGACNP fact map (facts reviewed 2026-10-15).