Progressive multifocal leukoencephalopathy: causes, symptoms, diagnosis, treatment

Progressive multifocal leukoencephalopathy (subcortical encephalopathy) is a slow viral infection of the central nervous system that develops in immunodeficiency states. The disease leads to subacute progressive demyelination of the central nervous system, multifocal neurological deficits, and death, usually within a year. Diagnosis is based on contrast-enhanced CT or MRI data, as well as CSF PCR results. Treatment is symptomatic.

ICD-10 code

A81.2. Progressive multifocal leukoencephalopathy.

Epidemiology of progressive multifocal leukoencephalopathy

The source of the pathogen is a person. The transmission routes have not been sufficiently studied, it is believed that the pathogen can be transmitted both by airborne droplets and by the feco-oral route. In the vast majority of cases, the infection is asymptomatic. Antibodies are found in 80-100% of the population.

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What causes progressive multifocal leukoencephalopathy?

Progressive multifocal leukoencephalopathy is caused by the JC virus of the Papovaviridae family, Polyomavirus genus . The viral genome is represented by circular RNA. Progressive multifocal leukoencephalopathy (PMLE) is most likely caused by reactivation of the widespread JC virus of the papovavirus family, which usually enters the body in childhood and remains latent in the kidneys and other organs and tissues (e.g., CNS mononuclear cells). The reactivated virus has a tropism for oligodendrocytes. Most patients with the disease have suppression of cellular immunity due to AIDS (the most common risk factor), lympho- and myeloproliferative (leukemia, lymphoma) or other diseases and conditions (e.g., Wiskott-Aldrich syndrome, organ transplantation). The risk of developing progressive multifocal leukoencephalopathy in patients with AIDS increases with increasing viral load; the incidence of progressive multifocal leukoencephalopathy has now decreased due to the widespread availability of more effective antiretroviral drugs.

Pathogenesis of progressive multifocal leukoencephalopathy

CNS damage occurs in individuals with immunodeficiencies due to AIDS, lymphoma, leukemia, sarcoidosis, tuberculosis, and pharmacological immunosuppression. The JC virus exhibits pronounced neurotropism and selectively infects neuroglial cells (astrocytes and oligodendrocytes), which leads to disruption of myelin synthesis. Multiple foci of demyelination are found in the brain tissue in the cerebral hemispheres, brainstem, and cerebellum, with maximum density at the border of gray and white matter.

Symptoms of progressive multifocal leukoencephalopathy

The onset of the disease is gradual. The disease may debut with the patient's awkwardness and clumsiness, subsequently movement disorders worsen to the point of hemiparesis. Multifocal damage to the cerebral cortex leads to the development of aphasia, dysarthria, hemianopsia, as well as sensory, cerebellar and brainstem insufficiency. In some cases, transverse myelitis develops. Dementia, mental disorders and personality changes are noted in 2/3 of patients. Headaches and seizures are typical for AIDS patients. Progressive progression of the disease leads to death, usually 1-9 months after the onset. The course is progressive. Neurological symptoms of progressive multifocal leukoencephalopathy reflect diffuse asymmetric damage to the cerebral hemispheres. Hemiplegia, hemianopsia or other changes in the visual fields, aphasia, dysarthria are typical. The clinical picture is dominated by disturbances of higher brain functions and disorders of consciousness followed by severe dementia. Progressive multifocal leukoencephalopathy ends in death within 1-6 months.

Diagnosis of progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy should be considered in cases of unexplained progressive brain dysfunction, especially in patients with underlying immunodeficiency. PMLE is suggested by single or multiple white matter lesions detected on contrast-enhanced CT or MRI. T2-weighted images show a high-intensity signal from the white matter, with contrast accumulation at the periphery in 5-15% of abnormal lesions. CT usually shows multiple asymmetric confluent foci of low density that do not accumulate contrast. Detection of JC virus antigen in CSF using PCR in combination with characteristic changes on MRI confirm the diagnosis of progressive multifocal leukoencephalopathy. Standard examination of the CSF is usually normal, serological studies are uninformative. Sometimes, for the purpose of differential diagnosis, a stereotactic brain biopsy is performed, which, however, is rarely justified.

CT and MRI reveal areas of low density in the white matter of the brain; viral particles are detected in brain tissue biopsies (electron microscopy), the viral antigen is detected by immunocytochemistry, and the viral genome (by PCR). JC virus replicates in primate cell culture.

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Treatment of progressive multifocal leukoencephalopathy

There is no effective treatment for progressive multifocal leukoencephalopathy. Treatment is symptomatic. Cidofovir and other antiviral drugs are in clinical trials and do not appear to provide the desired results. Aggressive antiretroviral therapy is indicated for HIV-infected patients, which improves the prognosis for patients with progressive multifocal leukoencephalopathy due to a decrease in viral load.