Progressive Multifocal Leukoencephalopathy in an HIV Patient

Progressive multifocal leukoencephalopathy is an AIDS defining disease often arising in HIV patients with low CD4 T cell count, and rarely among those with more than 500 CD4 T cell/mm 3 . Definite diagnosis requires JC Virus (JCV) isolation in cerebrospinal fluid (CSF) or in brain tissue. JCV PCR sensitivity in highly active antiretroviral therapy (HAART) era is lower, making progressive multifocal leukoencephalopathy (PML) definite diagnosis difficult. A 48-year-old woman was diagnosed with HIV1 in 1998, never having had any AIDS-defining illness. Combined antiretroviral therapy was started in 2004. In January 2009 she presented a tandem gait and gait ataxia. Her HIV viral load was undetectable and the CD4 T cell count was of 533/mm 3 . Brain CT scan was normal. In the following months a bilateral cerebellar syndrome installed and brain MRI was done showing asymmetrical demyelinating lesions. Normal cerebrospinal fluid (CSF) findings other than mononuclear pleocytosis and a negative JCV PCR were documented. PML was suspected, combined antiretroviral therapy (cARV) was altered, and cidofovir and mirtazapine were prescribed, associated with physiotherapy. She was clinically stable for some months. Almost one year later her neurological state got worse, CD4 T cell count was of 478/mm 3 , brain lesions progressed, and finally, JCV PCR became positive (5th determination). PML definite diagnosis was made. The patient died in June 2010 due to PML progression. Sensitivity of JCV PCR in CSF lowers under HAART with high CD4 T cell count, making definite PML diagnosis difficult even when a high grade of suspicion exists, based on clinical presentation and magnetic resonance imaging (MRI) findings. Differential diagnosis of demyelinating diseases should be considered, and HIV-leukoencephalitis should be taken in consideration when HIV replication exists in the brain. PML may arise in a patient under cARV and good immunological status. Treatment should not be delayed when a probable diagnosis exists even if CD4 T cell count is above 500/mm 3 . Repeated lumbar puncture with JCV determinations should be done in the advent of new/worsen neurological symptoms and evidence of demyelination showed in MRI. Sensitivity of JCV PCR increases with lower CD4 T cell count. doi:10.4021/jmc78w

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