Worsening MS Symptoms During a UTI and Heat Exposure
Mrs. L, 38, has relapsing-remitting MS and receives natalizumab every 4 weeks. She presents with 2 days of worsening left leg heaviness, blurred vision in the right eye, and fatigue. She has had a urinary tract infection for 3 days, temp 38.4°C, and spent the afternoon at a hot outdoor festival. Exam: left iliopsoas 4/5, right eye visual acuity 20/40 (baseline 20/20), no sensory level. Her MRI from 3 months ago was stable, and she has been on natalizumab for 30 months.
1. Distinguish pseudoexacerbation from relapse in this patient. What features favor each?
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Pseudoexacerbation is favored by the UTI, fever, and heat exposure, which slow demyelinated conduction (Uhthoff phenomenon). Symptoms often fluctuate, worsen with heat or fatigue, and improve within 24–48 hours after the trigger resolves, without new MRI lesions.
Relapse is favored by new, objective, persistent deficits lasting more than 24–48 hours that are not explained by triggers, especially monocular visual loss (optic neuritis) or new motor weakness. A new contrast-enhancing lesion on MRI confirms it.
This case is ambiguous: the fever and heat support pseudoexacerbation, but monocular acuity loss and leg weakness could be a true relapse. Do not assume either; treat the trigger and obtain MRI with contrast.
2. What is your immediate management, and would you give IV methylprednisolone now?
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Treat the trigger first: urine culture and culture-guided antibiotics, antipyretics, cooling, and hydration. Reassess the neurologic exam in 24–48 hours after the infection and heat exposure resolve.
Do not give IV methylprednisolone during an active infection unless a true relapse is confirmed and the benefit outweighs the risk. Steroids can worsen infection and mask evolving PML. If the deficit persists or MRI shows a new enhancing lesion, treat relapse with IV methylprednisolone 500–1,000 mg daily for 3–5 days (or equivalent oral), with GI and glucose precautions. Plasma exchange is reserved for severe steroid-refractory relapse.
3. What natalizumab-specific safety concerns affect your plan?
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Natalizumab carries a risk of progressive multifocal leukoencephalopathy (PML), which rises with longer duration (especially beyond 24 months), prior immunosuppression, and a high JCV antibody index (>1.5). At 30 months, she is in a higher-risk group.
New neurologic symptoms require MRI with contrast and consideration of CSF JCV PCR to exclude PML before giving the next dose. Hold natalizumab until PML is excluded. Steroids can obscure MRI findings, so obtain imaging first. Also counsel her that stopping natalizumab carries a rebound relapse risk, so any change should be coordinated with neurology.