Nucleic acid detection as a diagnostic tool in polyomavirus JC induced progressive multifocal leukoencephalopathy

Procedures involved in the diagnosis of JC virus central nervous system infection range from detection of virus specific products in biopsy material to demonstration of viral DNA in cerebrospinal fluid by PCR. Despite the fact that PCR is the most sensitive method for the detection of virus in clinical specimens, diagnostic evaluation is increasingly difficult in view of the possible subclinical activation of persistent JCV infection in the central nervous system of high risk patients. Therefore, PML diagnosis by molecular detection of JCV DNA in biopsy material was compared with diagnosis by PCR on CSF of patients with and without PML. Evaluation of the diagnostic techniques revealed that stereotactic biopsy based PCR diagnosis at present combines speed and sensitivity with the highest specificity available. Although the non invasive technique of JCV detection in CSF by PCR is even more sensitive leading to detection of about 20 genome equivalents per 1 microl of CSF, the specificity of the method is limited by subclinical presence of JCV DNA in CSF of neurologically asymptomatic HIV infected patients. Additionally, autopsy proven PML cases remaining JCV negative in PCR on CSF become a common finding. Therefore, in cases where biopsy is not performed, diagnosis of PML can only be achieved in combination with neurological and radiological diagnosis.