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Progressive multifocal leucoencephalopathy

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Abstract

Progressive multifocal leucoencephalopathy (PML) is a rarely occurring demyelinating disease of the central nervous system caused by a neurotropic papovavirus named JC virus (JCV). The most frequently affected regions are the cerebral hemispheres, especially the parietooccipital region, followed by the cerebellum and brain stem.

The disease occurs predominantly in individuals with an immunocompromised state and impaired cellular mediated immunity (CMI) due to other underlying illness. More extensive use of irradiation and immunosuppressive therapy in relation to increased transplantational activities as well as treatment of autoimmune diseases and malignancies, in addition to the appearance of the acquired immunodeficiency syndrome (AIDS) as a consequence of infection with the human immunodeficiency virus (HIV), has caused a considerable increase in the occurrence of PML. The course of the disease is still most often rapidly progressive and fatal, but several cases with prolonged survival and even remission have been reported, and various antiviral treatments have been tried. The only drug that until now has shown favourable results is cytosine arabinoside. In HIV-infected PML-patients immunomodulation with AZT/zidovudine may alleviate the course and improve the prognosis in some patients.

Suspicion of PML should lead to an extensive immunological investigation before considering of brain biopsy, which is still the only specific test.

On the basis of the increased frequency of PML in relation to HIV-infection, it is likely that our knowledge of the pathogenetic aspects will increase, which, hopefully, may lead to an effective therapeutic strategy.

Sommario

La leucoencefalopatia progressiva multifocale (PML) è una rara malattia demienilizzante del sistema centrale causata da un papovavirus neurotropo denominato virus JC (JCV). Le regioni più frequentemente interessate sono gli emisferi cerebrali, con particolare riguardo alla regione parieto-occipitale, seguiti da cervelletto e troncoencefalo.

La malattia si manifesta prevalentemente nel corso di malattie che determinano immunodepressione con alterazione della immunità cellulare (CMI). L'aumentato impiego di terapie radianti e immunosoppressive in relazione al diffondersi delle tecniche di trapianto o per il trattamento di malattie autoimmuni e tumorali, oltre alla comparsa della sindrome di immunodeficienza acquisita (AIDS), determinata dal virus della immunodeficienza umana (HIV), hanno determinato un considerevole incremento di frequenza della PML. IL decorso della malattia è il più delle volte rapido e fatale, tuttavia sono stati segnalati parecchi casi con sopravvivenza prolungata o addirittura remissione, cosa che ha indotto a sperimentare l'efficacia di vari trattamenti antivirali. Il solo farmaco dimostratosi finora efficace è la citosina arabinoside. In alcuni pazienti HIV positivi con PML la terapia immunomodulante con AZT/zidovudina può alleviare il decorso della malattia e migliorare la prognosi.

Il sospetto di PML deve indurre ad uno studio immunologico completo prima di ricorrere alla biopsia cerebrale che rappresenta l'unico test diagnostico specifico. L'aumentata frequenza di osservazione della PML in relazione all'infezione HIV porterà probabilmente ad un miglioramento delle nostre conoscenze sulla patogenesi, con conseguente sperabile messa a punto di strategie terapeutiche efficaci.

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Authors and Affiliations

  1. Neurological Department N, Copenhagen County Hospital, Glostrup, Ndr. Ringvej, DK-2600, Glostrup, Denmark

    Dalsgaard Hansen N. J. & Madsen C.

  2. Esbjerg Centralsygehus, Neurological Department, Denmark

    Stenager E.

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This article is based on an original article first published in the Danish Ugeskrift for Læger 157: 284–288, 1995.

This article is based upon a more comprehensive review of the literature than the numbered references.

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Dalsgaard Hansen, N.J., Madsen, C. & Stenager, E. Progressive multifocal leucoencephalopathy. Ital J Neuro Sci 17, 393–399 (1996). https://doi.org/10.1007/BF01997713

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