A 44-year-old male patient presented with dysphasia, confusion, and memory impairment that developed following a generalized seizure. He had been living in Jakarta, Indonesia, for the last 6 years. He was diagnosed as AIDS during a routine health examination in 2011. However, he willingly did not seek any medical treatment. Two months prior to presentation, an unremitting diarrhea developed and he returned to his hometown for medical evaluation. A diagnosis of cytomegalovirus (CMV) colitis was made through colonoscopic biopsy. The titer of reverse transcriptase-PCR (RT-PCR) against HIV at the time of admission was 126,629 copies/ml and absolute count of CD4 was 10/UL. Ganciclovir (antiviral agent for CMV) and highly active antiretroviral therapy (HAART, comprising lopinavir, ritonavir, tenofovir, and emtricitabine) were started. After recovery from CMV colitis, his condition was stable. Despite the improvement of his diarrhea, a generalized seizure followed by dysphasia and memory impairment developed 2 months later. He denied any homosexual behavior and his medical history was unremarkable, including transfusion or drug addiction.
Magnetic resonance imaging (MRI) of the brain revealed multiple confluent subcortical lesions with high signal intensity on T2-weighted image, involving bilateral frontal, right temporal and parietal lobes, and left thalamic and subcapsular regions [Figure 1a and b]. Irregular marginal enhancement on gadolinium was evident [Figure 1c]. Laboratory findings were as follows: hemoglobin of 15.1 g/dL, white blood cell (WBC) count of 4.62 x 109/L, platelet count of 293 x 109/L, erythrocyte sedimentation ratio of 27 mm/h, and C-reactive protein level of 0.17 mg/dL. CSF examination showed WBC count of 2 cells/UL, red blood cell count of 1 cell/UL, protein level of 33.5 mg/dL, glucose of 51 mg/dL, and chloride of 124 mEq/L. HIV titer was 80,148 copies/mL and CD4 count was 35/UL. The results of the CSF PCR examination for toxoplasmosis, tuberculosis, and polyoma viruses including BK and JCV were negative.
To confirm the pathology of the brain lesion, a brain biopsy was requested. Under three-dimensional MRI guidance, small craniotomy of the left frontal was performed. Portions of the middle frontal gyrus and subcortical white matter showing enhancement on MRI were taken for pathologic examination [Figure 1d]. The histologic examination revealed multifocal demyelinated areas with reactive astrocytosis and perivascular lymphocytic cuffing. Several large infected oligodendrocytes with inclusion-bearing dark nuclei or clear nucleoplasm having marginated chromatin were present in the periphery of demyelinated area [Figure 2a]. The demyelinated areas revealed small round lesions with myelin breakdown in the luxol-fast blue staining for myelin [Figure 2b]. Numerous macrophages had infiltrated and phagocytosis containing fragmented myelin was apparent. The hyperchromatic, inclusion-bearing oligodendrocytes displayed high ki-67 proliferative index [Figure 2c] and intense p53 nuclear immunostaining. Electron microscopy revealed infected oligodendrocytes filled by viral particles evident as spheres measuring up to 40 nm in diameter [Figure 2d]. JCV DNA was detected in brain tissue by PCR. Therefore, the final diagnosis of PML was confirmed and HAART was continued. His neurologic status was stable despite continued memory impairment. A generalized seizure developed 3 weeks after brain biopsy and his mentality became stuporous. Epileptiform discharges over the left frontocentral lobes were found on electroencephalography, and anticonvulsants (levetiracetam 2000 mg/day and valproate 900 mg/day) were added. Despite anticonvulsants and HAART, his mentality did not improve. Recurrent seizures developed and additional anticonvulsants were prescribed (levetiracetam 2000 mg/day, valproate 1200 mg/day, topiramate 600 mg/day, and clobazam 20 mg/day). The patient died 3 months from the onset of neurological symptoms.