From the Guidelines
Progressive Multifocal Leukoencephalopathy (PML) typically presents with subacute neurological symptoms, including cognitive dysfunction, motor weakness, visual disturbances, speech abnormalities, ataxia, and incoordination, which progressively worsen over weeks to months. These symptoms reflect the areas of demyelination in the brain and are often associated with immunocompromised states, such as HIV/AIDS, hematologic malignancies, or treatment with immunosuppressive medications like natalizumab or rituximab 1. The disease results from reactivation of the JC virus (John Cunningham virus) in immunocompromised states, leading to infection of oligodendrocytes and subsequent demyelination.
Clinical Presentations
- Cognitive dysfunction
- Motor weakness (hemiparesis or monoparesis)
- Visual disturbances (hemianopsia or cortical blindness)
- Speech abnormalities (dysarthria or aphasia)
- Ataxia and incoordination
- Headaches, seizures, and behavioral or personality changes
Diagnostic Considerations
Diagnosis of PML is based on clinical presentation, MRI findings, and detection of JCV DNA in the cerebrospinal fluid (CSF) 1. MRI features of PML include diffuse, large lesions in a subcortical location, with irregular borders and no mass effect. The presence of anti-JCV antibodies is a well-characterized factor for the development of PML, and anti-JCV antibody testing is recommended every 6 months for patients on natalizumab therapy 1.
Management and Prognosis
There is no effective prevention or specific treatment for PML, and management is focused on restoring the host adaptive immune response, which may prolong survival and minimize CNS injury 1. Early detection of PML and rapid cessation of immunosuppressive therapy, followed by plasma exchange to restore immune function, may be associated with a good prognosis 1. However, the prognosis for PML remains poor, and prompt recognition and management of the disease are critical to improving outcomes.
From the Research
Clinical Presentations of Progressive Multifocal Leukoencephalopathy (PML)
The clinical presentations of PML can vary, but common manifestations include:
- Weakness
- Gait abnormalities
- Speech disturbance
- Cognitive disorders
- Headache
- Visual impairment 2 These symptoms can occur in patients with impaired cellular immunity, such as those with HIV infection or those undergoing immunosuppressive treatments.
Demographic Characteristics
PML can affect individuals of various ages, with a range of 5 to 68 years reported in one study 2. The disease has been found to affect more men than women, with homosexuality being a common AIDS risk factor among men, and heterosexual transmission and intravenous drug abuse being common among women 2.
Diagnostic Features
Diagnostic features of PML may include:
- Involvement of posterior fossa structures evident on cranial magnetic resonance imaging (MRI) studies 2
- Contrast enhancement, typically faint and peripheral, on computed tomography (CT) scans or MRI studies 2
- JC virus (JCV) reactivation in the setting of impaired cellular immunity 3, 4
Disease Course and Outcome
The disease course and outcome of PML can be severe, with a median survival of 6 months and survival exceeding 1 year in only 9% of cases 2. However, with the development of new immunotherapeutic approaches, there is hope for improved outcomes and management of the disease 3. Additionally, early identification and prompt treatment of PML can lead to better outcomes 5.