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Management and outcome of CSF-JC virus PCR-negative PML in a natalizumab-treated patient with MS
1Department of Biomedicine and Neurology, University Hospital Basel, Basel, Switzerland.
Objective:
To describe the diagnosis and management of a 49-year-old woman with multiple sclerosis (MS) developing a progressive hemiparesis and expanding MRI lesion suspicious of progressive multifocal leukoencephalopathy (PML) 19 months after starting natalizumab.
Results:
Polyomavirus JC (JCV)-specific qPCR in CSF was repeatedly negative, but JCV-specific antibodies indicated intrathecal production. Brain biopsy tissue taken 17 weeks after natalizumab discontinuation and plasmapheresis was positive for JCV DNA with characteristic rearrangements of the noncoding control region, but histology and immunohistochemistry were not informative except for pathologic features compatible with immune reconstitution inflammatory syndrome. A total of 22 months later, the clinical status had returned close to baseline level paralleled by marked improvement of neuroradiologic abnormalities.
Conclusions:
This case illustrates diagnostic challenges in the context of incomplete suppression of immune surveillance and the potential of recovery of PML associated with efficient immune function restitution.
Insights
A multiple sclerosis (MS) patient developed progressive multifocal leukoencephalopathy (PML) despite negative initial tests. Recovery occurred with immune reconstitution, highlighting diagnostic challenges and treatment potential.
Area of Science:
- Neuroimmunology
- Viral Neurology
Background:
- Natalizumab is an effective MS therapy, but carries a risk of progressive multifocal leukoencephalopathy (PML).
- Early diagnosis of natalizumab-associated PML is crucial for management and prognosis.
Observation:
- A 49-year-old woman with MS developed hemiparesis and an expanding MRI lesion 19 months after starting natalizumab.
- Initial cerebrospinal fluid (CSF) testing for JC polyomavirus (JCV) was negative, but intrathecal antibody production was detected.
Findings:
- Brain biopsy confirmed JCV DNA with characteristic noncoding control region rearrangements, despite negative CSF qPCR.
- Histology suggested immune reconstitution inflammatory syndrome (IRIS).
- Clinical and radiological recovery occurred 22 months after natalizumab discontinuation and plasmapheresis.
Implications:
- This case highlights diagnostic difficulties with incomplete immune suppression and the potential for PML recovery with immune function restoration.
- It underscores the importance of considering PML even with negative initial tests in natalizumab-treated patients.
Related Concept Videos
Cytomegalovirus Disease
Multiple Sclerosis l: Introduction
Acute Pyelonephritis II: Diagnostic Studies and Management
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Encephalitis ll: Pathophysiology

