What treatment approach should be taken for a patient with Multiple Sclerosis (MS) and a history of COVID-19 who is experiencing a pseudo MS flare?

Management of Pseudo MS Flare in a Patient with MS and COVID-19 History

In a patient with MS experiencing a pseudo MS flare following COVID-19 infection, do not treat with high-dose corticosteroids or disease-modifying therapy escalation; instead, provide supportive care and symptomatic management while monitoring for true relapse, as pseudo-relapses resolve spontaneously without immunosuppressive intervention. 1, 2

Distinguishing Pseudo-Relapse from True Relapse

The critical first step is differentiating a pseudo-relapse from a true MS relapse, as treatment approaches differ fundamentally:

Pseudo-relapse characteristics:

• Worsening of pre-existing MS symptoms without new neurological deficits 2
• Triggered by systemic stressors such as infection, fever, or metabolic disturbances 1, 3
• Symptoms fluctuate with body temperature and resolve as the underlying trigger improves 2
• No new gadolinium-enhancing lesions or T2 lesions on MRI 3

True relapse characteristics:

• New neurological symptoms or objective worsening lasting >24 hours 3
• New gadolinium-enhancing lesions or T2 lesions on brain/spine MRI 3
• Occurs in absence of fever or infection 2

Evidence-Based Management Approach

For Pseudo-Relapse (Most Likely Scenario Post-COVID-19)

Primary management strategy:

• Treat the underlying trigger (COVID-19 infection or its sequelae) rather than the neurological symptoms 2, 3
• Provide symptomatic relief through cooling measures, hydration, and fever control 1
• Continue current disease-modifying therapy without interruption unless contraindicated by severe COVID-19 4, 5

Critical caveat: Approximately 37% of MS patients experience neurological worsening post-COVID-19, with pseudo-relapses accounting for 46% of these cases 2. However, COVID-19 severity and incomplete systemic recovery are the primary predictors of neurological worsening, not the MS disease itself 2.

For True Relapse (If Confirmed by MRI)

If MRI demonstrates new inflammatory activity suggesting a true relapse:

Corticosteroid therapy:

• Methylprednisolone 160 mg IV daily for 7 days, followed by 64 mg every other day for 1 month 6
• This regimen has been shown effective for acute MS exacerbations, though it does not alter long-term disease progression 6

Important consideration: High-dose corticosteroids should be used cautiously in the context of recent COVID-19, as they may be needed for COVID-19-associated cytokine release syndrome 4. The timing and indication must be carefully weighed.

Disease-Modifying Therapy Considerations

Continue current DMT in most cases:

• Interferon-β, glatiramer acetate, teriflunomide, dimethyl fumarate, natalizumab, and sphingosine-1-phosphate receptor modulators can be continued during COVID-19 infection 1, 4
• These therapies do not increase COVID-19 severity and should not be interrupted for pseudo-relapses 4, 5

Special consideration for anti-CD20 therapies (rituximab, ocrelizumab):

• Rituximab has been associated with increased risk of severe COVID-19 outcomes and mortality 7
• However, discontinuing effective therapy risks disease reactivation 8
• For patients on ocrelizumab with stable disease, continuation is generally recommended unless severe COVID-19 develops 8
• If vaccination is needed, complete the regimen at least 4-6 weeks before the next ocrelizumab infusion, or wait at least 4-6 months after the last dose 1, 9

Monitoring and Follow-Up

Essential monitoring parameters:

• Serial neurological examinations to document symptom trajectory 2
• Temperature monitoring and assessment of systemic COVID-19 recovery 2
• MRI with gadolinium if symptoms persist beyond expected pseudo-relapse duration (typically days to 2 weeks) 3
• Assessment for post-COVID-19 neurological syndrome if symptoms persist beyond 4 weeks 4

Common pitfall to avoid: Do not empirically treat with high-dose corticosteroids based on clinical symptoms alone without MRI confirmation of new inflammatory activity 6, 3. This exposes patients to unnecessary immunosuppression during or shortly after viral infection.

Vaccination Recommendations

COVID-19 vaccination is strongly recommended for all MS patients to prevent future infections and reduce risk of neurological worsening 1, 10, 9:

• Complete primary series and boosters according to national guidelines 10, 9
• Vaccination does not trigger MS relapses or exacerbate symptoms 4
• Timing should be optimized based on current DMT (see above for anti-CD20 therapies) 1, 9