Progressive multifocal leukoencephalopathy: causes, symptoms, diagnosis, treatment

Progressive multifocal leukoencephalopathy (subcortical encephalopathy) is a slow viral infection of the central nervous system, which develops in immunodeficient states. The disease leads to subacute progressive demyelination of the central nervous system, a multifocal neurologic deficit and death, usually within a year. The diagnosis is based on CT data with contrast enhancement or MPT, as well as PCR CSF result. 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 pathways have not been studied sufficiently, it is believed that the causative agent can be transmitted by both airborne and fecal-oral routes. In most cases, the infection is asymptomatic. Antibodies were found in 80-100% of the population.

[1], [2], [3], [4], [5], [6], [7], [8], [9]

What causes progressive multifocal leukoencephalopathy?

Progressive multifocal leukoencephalopathy is caused by the JC virus of the Papovaviridae family , the genus Polyomavirus. The genome of the virus is represented by ring RNA. The cause of progressive multifocal leukoencephalopathy (PMLE) is most likely the reactivation of a widespread family of papovaviruses in the JC virus population, which usually enters the body in childhood and is latent in the kidneys and other organs and tissues (eg CNS mononuclear cells). Reactivated virus has a tropism for oligodendrocytes. Most of the patients noted oppression of cellular immunity against AIDS (the most frequent risk factor), lympho- and myeloproliferative (leukemia, lymphoma) or other diseases and conditions (for example, Wiskott-Aldrich Syndrome, organ transplantation). The risk of developing progressive multifocal leukoencephalopathy in AIDS patients increases with the increase in viral load; the incidence of progressive multifocal leukoencephalopathy has declined due to the proliferation of more effective antiretroviral drugs.

Pathogenesis of progressive multifocal leukoencephalopathy

CNS lesion occurs in individuals with immunodeficiencies against AIDS, lymphoma, leukemia, sarcoidosis, tuberculosis, and pharmacological immunosuppression. The JC virus exhibits pronounced neurotropism and selectively infects the cells of the neuroglia (astrocytes and oligodendrocytes), which leads to a disruption of myelin synthesis. In the brain substance, multiple foci of demyelination in the hemispheres of the brain, trunk and cerebellum with maximum density at the boundary of gray and white matter are detected.

Symptoms of progressive multifocal leukoencephalopathy

The onset of the disease is gradual. The disease can make its debut with the appearance of the patient's awkwardness and clumsiness, and then the motor disorders are aggravated until the development of hemiparesis. Multifocal lesion of the cerebral cortex leads to the development of aphasia, dysarthria, hemianopsia, as well as sensory, cerebellar and stenal insufficiency. In some cases, a transverse myelitis develops. In 2/3 patients, dementia, mental disorders and personality changes are noted. People with AIDS are characterized by headaches and convulsive seizures. The prograde progression of the disease leads to death, usually 1 to 9 months after the debut. The course is progressive. Neurological symptoms of progressive multifocal leukoencephalopathy reflect a diffuse asymmetric lesion of the cerebral hemispheres. Characteristic hemiplegia, hemianopia or other changes in the fields of vision, aphasia, dysarthria. In the clinical picture, disorders of higher cerebral functions and disorders of consciousness predominate, followed by gross dementia. Progressive multifocal leukoencephalopathy ends with a lethal outcome 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 background immunodeficiency states. In favor of PMLE, single or multiple pathological changes in the white matter of the brain revealed on CT or MRI with contrast enhancement. On T2-weighted images, a signal of increased intensity from white matter is detected, the contrast accumulates around the periphery in 5-15% of pathologically altered foci. CT scans usually identify multiple asymmetric foci of reduced density that do not accumulate contrast. Detection of the JC virus antigen in the CSF using PCR in combination with the characteristic changes in KTMRT confirm the diagnosis of progressive multifocal leukoencephalopathy. With a standard CSF study, it is often not changed, serological studies are not informative. Sometimes, for the purpose of differential diagnosis, a stereotactic brain biopsy is performed, which, however, rarely justifies itself.

CT and MRI reveal foci of reduced density in the white matter of the brain; In biopsies of the brain tissue, virus particles (electron microscopy) are detected, the virus antigen is immunocytochemically detected, the viral genome (PCR method). The JC virus multiplies in the culture of primate cells.

[10], [11], [12], [13], [14], [15], [16]

Treatment of progressive multifocal leukoencephalopathy

Effective treatment of progressive multifocal leukoencephalopathy is absent. Treatment is symptomatic. Cidofovir and other antiviral drugs are in clinical trials and, apparently, do not give the desired result. HIV-infected patients are shown aggressive antiretroviral therapy, improving the prognosis for a patient with progressive multifocal leukoencephalopathy due to a decrease in viral load.