From the Guidelines
Progressive multifocal leukoencephalopathy (PML) is diagnosed through a combination of clinical evaluation, imaging studies, and laboratory testing, with the most definitive diagnosis based on the presence of JC virus DNA in the cerebrospinal fluid (CSF) or characteristic histopathological changes on brain biopsy 1. The diagnostic approach begins with recognizing risk factors such as immunosuppression and characteristic symptoms including cognitive impairment, motor weakness, visual disturbances, and personality changes.
- Key clinical features that may suggest PML include subacute onset, progressive evolution, and symptoms such as aphasia, behavioral and neuropsychological alterations, retrochiasmal visual deficits, hemiparesis, and seizures 1.
- Brain MRI is essential and typically shows asymmetric, non-enhancing white matter lesions predominantly in the subcortical regions without mass effect, with features such as diffuse hyperintensity on T2-weighted sequences, irregular shape, and ill-defined borders toward the white matter 1.
- CSF analysis using PCR to detect JC virus DNA is the most definitive laboratory test, with a sensitivity of approximately 80% and specificity over 95% 1. In cases where CSF PCR is negative but clinical suspicion remains high, brain biopsy may be necessary to confirm the diagnosis by demonstrating characteristic histopathological changes and the presence of JC virus.
- Early diagnosis is critical as PML has high mortality rates, and management focuses on immune reconstitution when possible, such as optimizing antiretroviral therapy in HIV patients or withdrawing immunosuppressive medications in other cases 1. Some key points to consider in the diagnostic workup of PML include:
- The importance of routine surveillance MRI in asymptomatic patients to enable early detection and treatment of suspected PML 1.
- The use of fluid-attenuated inversion recovery (FLAIR) and diffusion-weighted imaging (DWI) to detect PML-associated lesions 1.
- The potential for gadolinium-enhancing lesions to be present in some cases of PML, although this is not diagnostic 1.
- The need for careful monitoring and repeated CSF testing in patients with suspected PML, as a negative CSF result does not exclude the diagnosis 1.
From the FDA Drug Label
For diagnosis of PML, an evaluation including a gadolinium-enhanced MRI scan of the brain and, when indicated, cerebrospinal fluid analysis for JC viral DNA are recommended. The diagnostic criteria for Progressive Multifocal Leukoencephalopathy (PML) include:
- A gadolinium-enhanced MRI scan of the brain
- Cerebrospinal fluid analysis for JC viral DNA, when indicated If the initial evaluations for PML are negative but clinical suspicion for PML remains, continue to withhold TYSABRI dosing, and repeat the evaluations 2
From the Research
Diagnostic Criteria for Progressive Multifocal Leukoencephalopathy (PML)
The diagnostic criteria for PML include:
- Distinguishing neurological features at presentation 3
- Characteristic brain MRI changes 4, 5, 6, 7
- Presence of JCV DNA in cerebrospinal fluid 4, 5, 3, 7 Key imaging features of PML on MRI include:
- Areas of T2 hyperintensity with involvement of the subcortical U-fibers 5
- Restricted diffusion in all patients 5
- Contrast enhancement, which may indicate an inflammatory response and herald immunologic virus elimination 5 Other imaging modalities that may be used to evaluate PML include:
- Diffusion-weighted imaging (DWI) 5, 7
- Diffusion tensor imaging (DTI) 5, 7
- MR spectroscopy 4, 7
- Computed tomography (CT) 7
- Single photon-emission computed tomography (SPECT) 7
- Positron-emission tomography (PET) 6, 7