Fingolimod-associated PML with mild IRIS in MS: A clinicopathologic study

Area of Science:

• Neurology
• Virology
• Immunology

Background:

• Fingolimod is an immunomodulatory drug used for multiple sclerosis (MS).
• Progressive multifocal leukoencephalopathy (PML) is a rare, serious opportunistic infection of the brain.
• JC virus (JCV) is the causative agent of PML.

Purpose of the Study:

• To describe the clinical, neuropathologic, and virologic features of PML and PML-IRIS in a patient treated with fingolimod.
• To highlight diagnostic challenges and clinical course in fingolimod-associated PML.

Main Methods:

• A single case study of a 34-year-old female patient with MS.
• Clinical assessment, serial MRI, cerebrospinal fluid (CSF) analysis, and brain biopsy.
• Quantitative PCR and in situ hybridization for JCV DNA detection.

Main Results:

• The patient presented with hemiparesis and aphasia, initially showing a white matter lesion on MRI.
• Cessation of fingolimod and subsequent MRI changes suggested PML-IRIS.
• Low CSF JCV DNA and absence of viral inclusions on initial biopsy complicated diagnosis; JCV DNA was detected in active inflammatory demyelinating lesions.
• Patient showed gradual symptom improvement with methylprednisolone and mefloquine treatment.

Conclusions:

• Low CSF JCV DNA and initial lack of viral inclusions can impede PML diagnosis.
• Fingolimod-associated PML may present with a milder immune reconstitution pattern.
• Early detection and management are crucial for improving outcomes in fingolimod-associated PML.