Fulminant Course in a Case of Diffuse Myelinoclastic Encephalitis - A Case Report

We report on a 10-year old previously healthy boy who exhibited a fulminant and nearly monophasic clinical course of demyelinating encephalitis with relapsing intracranial hypertension syndrome. Histologic examination of a diagnostic brain biopsy revealed an inflammatory demyelinating process with perivascular T lymphocytic infiltration and axonal damage reminiscent of multiple sclerosis-like lesions. In the brain, the DNA of human Herpes virus 6 (HHV6) was detectable. Eleven months after the initial symptoms and on maintainance with oral steroids, MRI showed demyelination of both hemispheres as well as demyelination of the brain stem and Wallerian degeneration. The boy exhibited a severe neurologic defect syndrome. The clinical and radiological course is unusual because of the asymmetric progression of the encephalitis and the extensive confluent lesions without demarcated border or enhancement of the rim after injection of gadolinium. The clinical course showed no definite steroid response. The pathogenetic relevance of HHV6 remains elusive. Although single patients with HHV6-associated encephalomyelitis have been reported, HHV6 DNA is occasionally detected in brains of healthy individuals.

Myelinoclastic diffuse encephalitis - Schilder disease - HHV6 - Demyelination - Steroids - ADEM

References

• 1 Afifi A K, Bell W E, Menezes A H, Moore S A. Myelinoclastic diffuse sclerosis (Schilder's diease): report of a case and review of the literature.  J Child Neurol. 1994;  9 398-403
• 2 Bethge W, Beck R, Jahn G, Mundinger P, Kanz L, Einsele H. Successful treatment of human herpesvirus-6 encephalitis after bone marrow transplantation.  Bone Marrow Transpl. 1999;  11 1245-1248
• 3 Bonsack T A, Robertson R L, Lacson A, Casadonte J A, Buonomo C. Pediatric case of the day.  Radiographics. 1996;  16 1509-1511
• 4 Carrigan D R, Harrington D, Knox K. Subacute leukoencephalitis caused by CNS infection with human herpesvirus-6 manifesting as acute multiple sclerosis.  Neurology. 1996;  47 145-149
• 5 Challoner P B, Smith K T, Parker J D, MacLeod D L, Coulter S N, Rose T M. et al . Plaque-associated expression of human herpes virus 6 in multiple sclerosis.  P Natl Acad Sci. 1995;  92 7440-7444
• 6 Dressler L P, Tourian A Y, Anthony D C. A case of myelinoclastic sclerosis in an adult.  Neurology. 1991;  41 589-595
• 7 Eblen F, Poremba M, Grodd W, Opitz H, Roggendorf W, Dichgans J. Myelinoclastic diffuse sclerosis (Schilder's disease): cliniconeuroradiologic correlations.  Neurology. 1991;  41 589-591
• 8 Friedmann J E, Lyons M J, Cu G, Ablashl D V, Whitman J E, Edgar M. et al . The association of the human herpesvirus-6 and MS.  Mult Scler. 1999;  5 355-362
• 9 Kepes J J. Large focal tumor-like demyelinating lesions of the brain: intermediate entity between multiple sclerosis and acute disseminated encephalomyelitis? A study of 31 patients.  Ann Neurol. 1993;  33 18-27
• 10 Klotman M E, Lusso P, Bacchus D, Corbellino M, Jarrett R F, Berneman Z N. Detection of human herpesvirus 6 and human herpesvirus 7 by PCR amplification. Persing DH, Smith TF, Tenover FC, White TJ Diagnostic Molecular Microbiology, Principles and Applications. Washington, D. C.; American Society for Microbiology 1993: 501-510
• 11 Lassmann H. Pathology of multiple sclerosis. Compston A, Ebers G, Lassmann H, McDonald I, Matthews B, Wekerle H McAlpine's Multiple Sclerosis. London; Churchill Livingstone 1998: 323-358
• 12 Leuzzi V, Lyon G, Cilio M R, Pedepan J M, Fontan D, Chateil J F. et al . Childhood demyelinating disease with a prolonged remitting course and their relation to Schilder's disease: report of two cases.  J Neurol Neurosur Ps. 1999;  3 407-408
• 13 Luppi M, Barozzi P, Maiorana A, Marasca R, Toelli G. Human herpesvirus 6 infection in normal human brain tissue.  J Infect Dis. 1994;  169 943-944
• 14 Mehler M F, Rabinowich L. Inflammatory myelinoclastic diffuse sclerosis.  Ann Neurol. 1988;  23 413-415
• 15 Novoa L J, Nagra R M, Nakawatase T, Edwards-Lee T, Tourtellote W W, Cornford M E. Fulminant demyelinating encephalomyelitis associated with productive HHV-6 infection in an immunocompetent adult.  J Med Virol. 1997;  52 301-308
• 16 Poser C M, Goutières F, Carpentier M A, Aicardi J. Schilder's myelinoclastic diffuse sclerosis.  Pediatrics. 1986;  77 107-112
• 17 Pretorius M L, Loock D B, Ravenscroft A, Schoeman J F. Demyelinating disease of Schilder type in three young South African children: dramatic response to corticosteroids.  J Child Neurol. 1998;  13 197-201
• 18 Reymen D, Naesen L, Balzarini J, Holy A, Dvorakoa H, De Clercq E. Antiviral activity of selected acyclic nucleoside analogues against human herpesvirus 6.  Antivir Res. 1995;  4 343-357
• 19 Rodesch G, Avni E F, Parizel P, Determann D, Szliwowski H, Brotchi J. et al . Schilder's disease: Neuroradiological findings.  J Neuroradiol. 1988;  15 386-393
• 20 Schilder P. Zur Kenntnis der sogenannten diffusen Sklerose.  Z Ges Neurol Psychiatr. 1912;  10 1-60
• 21 Suga S, Yoshikawa T, Asano Y, Kozawa R, Nakashima T, Kobayashi I. et al . Clinical and virological analyses of 21 infants with exanthema subitum (roseola infantum) and central nervous system complications.  Ann Neurol. 1993;  33 597-603
• 22 Van der Knaap M S. Multiple sclerosis. Van der Knaap MS, Valk J Magnetic Resonance of Myelin, Myelination, and Myelin Disorders. 2nd ed. Berlin, Heidelberg, New York; Springer Verlag 1995: 296-313