Definitive diagnosis utilizes brain biopsy:
(1) multifocal demyelination in any part of the white matter
(2) hyperchromatic enlarged oligodendrocytic nuclei showing viral inclusions (on immunohistochemistry, in situ hybridization, electron microscopy)
(3) enlarged, bizarre astrocytes with lobulated, hyperchromatic nuclei
Diagnosis without brain biopsy - all of the following:
(1) clinical findings (cognitive deficits, speech deficits, visual deficits, hemiparesis, gait difficulties, incoordination, other focal deficits)
(2) multiple nonenhancing white matter lesions on imaging studies
(3) positive PCR for JC virus in cerebrospinal fluid (CSF)
Neuroimaging findings in the white matter:
(1) CT scans show hypodense areas that do not enhance and which do not show a mass effect.
(2) MRI shows hypointensity on T1-weighted and hyperintense on T2-weighted images.