Harika Yalamanchili PGY-3 PML Harika Yalamanchili PGY-3

Progressive multifocal leukoencephalopathy Severe demyelinating disease of the CNS caused by reactivation of the JC polyomavirus Asymptomatic primary infection occurs in childhood and antibodies can be found in 86% of adults The virus remains latent in kidneys and lymphoid organs unless development of profound cellular immunosuppression where it reactivates and spreads to the brain Induces a lytic infection of oligodendrocytes, CNS myelin- producing cells

Manifestations Symptoms vary and depend on location of lesions Typically spares the optic nerves and the spinal cord Subacute neurologic deficits AMS Motor deficits (hemiparesis or monoparesis) Limb ataxia Gait ataxia Visual symptoms (hemianopia or diplopia) Aphasia Seizures

Imaging Symmetric or asymmetric multifocal areas of white matter demyelination that do not conform to cerebrovascular territories and exhibit neither mass effect nor contrast enhancement CT: hypodense patchy or confluent white matter regions MRI: lesions with decreased signal intensity on T1, T2, and FLAIR with hyperintensity on diffusion-weighted sequences Bilateral and localized preferentially to the periventricular areas and the subcortical white matter

Diagnosis Diagnosis Gold standard is brain biopsy Histopathologic triad of demyelination, bizarre astrocytes, and enlarged oligodendroglial nuclei Compatible clinical and neuroimaging features + JC virus DNA in the CSF Differential includes HIV encephalopathy, primary CNS lymphoma, CNS vasculitis, reversible posterior leukoencephalopathy, and VZV encephalopathy

Treatment No specific treatment Initiate or optimize ART High risk for IRIS Withdraw immunosuppressive agents if possible Progressive and fatal Non-HIV: 3 months HIV without ART: 4-5 months HIV with ART: 1.8 years