Progressive Multifocal Leukoencephalopathy in a Child with Hyperimmunoglobulin E Recurrent Infection Syndrome and Review of the Literature

Abstract

Progressive multifocal leukoencephalopathy (PML) is a fatal demyelinating disease due to infection with polyomavirus JC (JCV). PML occurs almost exclusively in immunocompromised patients, and although it has increased markedly in relation to AIDS, remains exceptional in children. We present the case of an immunocompromised child with hyperimmunoglobulin E recurrent infection syndrome (HIES) and pathologically-proven PML. HIES is a rare congenital immunodeficiency that to our knowledge has never before been reported in association with neurological complications. Following a recurrence of bronchopneumonia, the child's motor and cognitive functions deteriorated progressively in parallel with alterations on cerebral MRI. The neurological onset coincided with lymphocyte subset changes. PCR for JCV DNA did not detect the virus in CSF, and brain biopsy was required to secure the diagnosis. Antiviral treatment with cidofovir produced no benefit. Autopsy revealed the typical neuropathological findings of PML which were associated with inflammatory eosinophilic infiltrate (a marker of HIES). In accordance with the few pediatric PML cases reported and here reviewed, the child died five months after neurological onset.

Pediatric PML - Hyperimmunoglobulin E syndrome (HIES)

References

• 1 Araujo A P, Pereira H S, Oliveira R H, Frota A C, Esperanca J C, Duarte F. Progressive multifocal leukoencephalopathy in a child with acquired immunodeficiency syndrome (AIDS).  Arq Neuropsiquiatr. 1977;  55 122-125
• 2 Aström K E, Mancall E L, Richardson E P. Progressive multifocal leukoencephalopathy. A hitherto unrecognized complication of chronic lymphatic leukemia and Hodgkin's disease.  Brain. 1958;  81 93-111
• 3 Berger J R, Kaszovitz B, Post J D, Dickinson G. Progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection: a review of the literature with a report of 16 cases.  Ann Intern Med. 1987;  107 78-87
• 4 Berger J R, Levy R M, Flomenhoft D, Dobbs M. Predictive factors for prolonged survival in AIDS-associated PML.  Ann Neurol. 1998;  44 341-349
• 5 Berger J R, Pall L, Lanska D, Whiteman M. Progressive multifocal leukoencephalopathy in patients with HIV infection.  J Neurovirol. 1998;  4 59-68
• 6 Bezrodnik L, Samara R, Krasovec S, Erro M G, Sevlever G. Progressive multifocal leukoencephalopathy in a patient with hypogammaglobulinemia.  Clin Infect Dis. 1998;  27 181-184
• 7 Borges W G, Augustin N H, Hill H R. Defective interleukin-12/interferon-gamma pathway in patients with hyperimmunoglobulinemia E syndrome.  J Pediatr. 2000;  136 176-180
• 8 Brooks B R, Walker D L. Progressive multifocal leukoencephalopathy.  Neurol Clin. 1984;  2 299-313
• 9 Buckley R H, Wray B B, Belmaker E Z. Extreme hyperimmunoglobulinemia E and undue susceptibility to infection.  Pediatrics. 1972;  49 59-70
• 10 Buckley R H. Disorders of the IgE System. Stiehm ER Immunologic Disorders in Infants and Children. Philadelphia; W. B. Saunders Company 1996: 409-422
• 11 Castaigne P, Rondot P, Escourolle R, Ribadeau Dumas J L, Cathala F, Hauw J J. Leucoencephalopathie multifocale progressive et “gliomes multiples”.  Rev Neurol (Paris). 1974;  130 379-392
• 12 Cavanagh J B, Greenbaum D, Marshall A. Cerebral demyelination associated with disorders of reticuloendothelial system.  Lancet. 1959;  II 524-529
• 13 Cinque P, Vago L, Dahl H, Brytting M, Terreni M R, Fornara C. et al . Polymerase chain reaction on cerebrospinal fluid for diagnosis of virus-associated opportunistic diseases of the central nervous system in HIV-infected patients.  AIDS. 1996;  10 951-958
• 14 Cinque P, Casari S, Bertelli D. Prolonged survival and clearance of JCV-DNA from the cerebrospinal fluid of patients with progressive multifocal leukoencephalopathy receiving highly active antiretroviral therapy.  N Engl J Med. 1998;  339 848-849
• 15 De Luca A, Giancola M L, Ammassari A, Grisetti S, Cingolani A, Paglia M G. et al . The effect of potent antiretroviral therapy and JC virus load in cerebrospinal fluid on clinical outcome of patients with AIDS-associated progressive multifocal leukoencephalopathy.  J Infect Dis. 2000;  182 1077-1083
• 16 Del Prete G, Tiri A, Maggi E, De Carli M, Macchia D, Parronchi P. et al . Defective in vitro production of gamma-interferon and tumor necrosis factor-alpha by circulating T cells from patients with the hyper-immunoglobulin E syndrome.  J Clin Invest. 1989;  84 1830-1835
• 17 Dozic S, Suvakovic V, Cvetkovic D, Jetovic D, Skender M. Neoplastic angioendotheliomatosis (NAE) of the CNS in a patient with AIDS subacute encephalitis, diffuse leukoencephalopathy and meningo-cerebral cryptococcosis.  Clin Neuropathol. 1990;  9 284-289
• 18 Epstein L G, Sharer L R, Joshi W, Fojas M M, Koenigsberger M R, Oleske J M. Progressive multifocal leukoencephalopathy in children with acquired immunodeficiency syndrome.  Ann Neurol. 1985;  17 488-496
• 19 Grimbacher B, Shaffer A A, Holland S M, Davis J, Gallin J I, Malech H L. et al . Genetic linkage of hyper-IgE syndrome to chromosome 4.  Am J Hum Genet. 1999;  65 735-744
• 20 Hall C D, Dafni U, Simpson D, Clifford D, Wetherill P E, Cohen B. et al . Failure of cytarabine in progressive multifocal leukoencephalopathy associated with human immunodeficiency virus infection.  N Engl J Med. 1998;  338 1345-1351
• 21 Holman R C, Janssen R S, Buehler J W, Zelasky M T, Hooper W C. Epidemiology of progressive multifocal leukoencephalopathy in the United States: analysis of national mortality and AIDS surveillance data.  Neurology. 1991;  41 1733-1736
• 22 Inui K, Miyagawa H, Sashihara J, Miyoshi H, Tanaka-Taya K, Nishigaki T. et al . Remission of progressive multifocal leukoencephalopathy following highly active antiretroviral therapy in a patient with HIV infection.  Brain Dev. 1999;  21 416-419
• 23 Katz D A, Berger J R, Hamilton B, Major E O, Donovan Post M J. Progressive multifocal leukoencephalopathy complicating Wiskott-Aldrich syndrome.  Arch Neurol. 1994;  51 422-426
• 24 Krasinki K, Borkowsky W, Holtzman R S. Prognosis of human immunodeficiency virus infection in children and adolescents.  Pediatr Infect Dis. 1989;  8 216-220
• 25 Lang C, Jacobi G, Kreuz W, Hacker H, Herrmann G, Keul H G. et al . Rapid development of giant aneurysm at the base of the brain in an 8-year-old boy with perinatal HIV infection.  Acta Histochem. 1992;  XLII (Suppl) 83-90
• 26 Major E O, Amemiya E E, Tornatore C S, Houff S A, Berger J R. Pathogenesis and molecular biology of progressive multifocal leukoencephalopathy, the JC virus-induced demyelinating disease of the human brain.  Clin Microbiol. 1992;  5 49-73
• 27 Miller J, Barret R, Britton C. Progressive multifocal leukoencephalopathy in a male homosexual with T-cell immune deficiency.  New Engl J Med. 1982;  307 1436-1438
• 28 Morriss M C, Rustein R M, Rudy B, Desrochers C, Hunter J V, Zimmermann R A. Progressive multifocal leukoencephalopathy in an HIV-infected child.  Neuroradiology. 1997;  39 142-144
• 29 Padgett B L, Walker D L, Zu Rhein G, Eckroade R J, Dessel B H. Cultivation of papova-like virus from human brain with progressive multifocal leukoencephalopathy.  Lancet. 1971;  1 1257-1260
• 30 Padgett B L, Walker D L. Virologic and serologic studies of progressive multifocal leukoencephalopathy. Sever JL, Madden DL Polyoma Viruses and Human Neurological Disease. New York; Alan R. Liss 1983: 107-171
• 31 Paganelli R, Scala E, Capobianchi M R, Fanales-Belasio E, D'Offizi G, Fiorilli M. et al . Selective deficiency of interferon-gamma production in the Hyper-Ig E syndrome. Relationship to in vitro IgE synthesis.  Clin Exp Immunol. 1991;  84 28-33
• 32 Redfearn A, Pennie R A, Mahony J B, Dent P. Progressive multifocal leukoencephalopathy in a child with immunodeficiency and hyperimmunoglobulinemia M.  Pediatr Infect Dis J. 1993;  12 399-401
• 33 Rhiza H J, Bornkamm G, Zur Hausen H. Seroepidemiological studies and serologic response to viral infection.  Med Microbiol Immunol. 1978;  165 73-92
• 34 Singer C, Berger J R, Bowen B D, Bruce J H, Weiner W J. Akinetic-rigid syndrome in a 13-year-old girl with HIV-related progressive multifocal leukoencephalopathy.  Mov Disord. 1993;  8 113-116
• 35 Vandersteenhoven J J, Dbaibo G, Boyko O B, Hulette C M, Antony D C, Kenny J F. et al . Progressive multifocal leukoencephalopathy in pediatric acquired immunodeficiency syndrome.  Pediatr Infect Dis J. 1992;  11 232-237
• 36 Walker D L. Progressive multifocal leukoencephalopathy: an opportunistic infection of the central nervous system. Vinken PJ, Bruyn GW Handbook of Clinical Neurology: vol 34. New York; Elsevier 1978: 307-329
• 37 Wrzolek M A, Brudkowska J, Kozlowski P B. et al . Opportunistic infections of the central nervous system in children with HIV infection: report of 9 autopsy cases and review of literature.  Clin Neuropathol. 1995;  14 187-196
• 38 Zu Rhein G M, Padgett B L, Walker D L, Chun R WM, Horowitz S D, Hong R. Progressive multifocal leukoencephalopathy in a child with severe combined immunodeficiency.  N Engl J Med. 1978;  299 256-257