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Lessons learned from fatal progressive multifocal leukoencephalopathy in a patient with multiple sclerosis treated
Aaron L Boster1, Jacqueline A Nicholas, Ilir Topalli
1Departments of Neurology and Neuroscience, The Ohio State University, 460 W 12th Ave, Columbus, OH 43210 , USA.
Objective:
To describe the clinical, radiological, and histopathological features of a fatal case of progressive multifocal leukoencephalopathy (PML) in a patient with multiple sclerosis treated with natalizumab. We will use this case to review PML risk stratification and diagnosis.
Design:
Case report.
Setting:
Tertiary referral center hospitalized care.
Patient:
A 55-year-old, JC virus (JCV) antibody-positive patient with multiple sclerosis who died of PML after receiving 45 infusions of natalizumab.
Main Outcome Measures:
Brain magnetic resonance imaging and cerebrospinal fluid JCV DNA polymerase chain reaction results.
Results:
The patient developed subacute onset of bilateral blindness following his 44th dose of natalizumab. Ophthalmologic examination was normal, the brain magnetic resonance imaging was not suggestive of PML, and cerebrospinal fluid analysis did not reveal the presence of JCV DNA. The patient was subsequently treated for a presumed multiple sclerosis relapse with high-dose corticosteroids. Two weeks after his 45th dose of natalizumab, he developed hemiplegia that evolved into quadriparesis. Repeated magnetic resonance imaging and cerebrospinal fluid studies were diagnostic for PML. Postmortem histopathological analysis demonstrated PML-associated white matter and cortical demyelination.
Conclusions:
The risks and benefits of natalizumab must be reassessed with continued therapy duration. When there is high clinical suspicion for PML in the setting of negative test results, close clinical vigilance is indicated, natalizumab treatment should be suspended, and JCV polymerase chain reaction testing and brain magnetic resonance imaging scans should be repeated.
Insights
A fatal case of progressive multifocal leukoencephalopathy (PML) in a multiple sclerosis patient treated with natalizumab highlights diagnostic challenges. Early vigilance and repeat testing are crucial when PML is suspected despite initial negative results.
Area of Science:
- Neurology
- Immunology
- Infectious Diseases
Background:
- Natalizumab is an effective disease-modifying therapy for multiple sclerosis.
- Progressive multifocal leukoencephalopathy (PML) is a rare but serious opportunistic infection associated with natalizumab treatment.
- JC virus (JCV) is the causative agent of PML.
Observation:
- A 55-year-old JCV antibody-positive multiple sclerosis patient received 45 natalizumab infusions.
- The patient developed neurological symptoms including blindness and quadriparesis.
- Initial diagnostic tests (MRI, CSF JCV PCR) were negative for PML.
Findings:
- Despite negative initial tests, repeated MRI and CSF JCV PCR confirmed PML.
- Histopathology revealed PML-associated demyelination.
- The patient died from PML.
Implications:
- The risk-benefit profile of natalizumab necessitates careful consideration, especially with prolonged therapy.
- High clinical suspicion for PML warrants repeated diagnostic testing and potential treatment suspension.
- Early and accurate diagnosis of PML is critical for patient outcomes.
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