title: Detection of infectious agents in brain of patients with acute hemorrhagic leukoencephalitis.
abstract: Acute hemorrhagic leukoencephalitis (AHL) is a rare and usually fatal disorder characterized clinically by an acute onset of neurologic abnormalities. It may occur in association with a viral illness or vaccination. Radiology and brain biopsy are essential for the diagnosis. The etiology of AHL is unclear. We postulated that viral/bacterial infection might be responsible, directly or through an immune-mediated mechanism, for this acute inflammatory myelinopathy. Fifteen cases of AHL were studied. Infectious agents, including varicella zoster virus (VZV), herpes simplex virus (HSV), human herpes virus-6 (HHV-6), cytomegalovirus, Epstein-Barr virus, and Mycoplasma, were investigated in brain specimens using the polymerase chain reaction (PCR), reverse transcriptase (RT)-PCR, and immunohistochemistry. Using PCR, HSV DNA was found in four cases, VZV DNA in two, and HHV-6 DNA in one. Among the control cases, two were HSV DNA positive. Further investigation to detect HSV RNA and antigens in HSV DNA-positive cases revealed that two cases with AHL were both HSV RNA and antigen positive. AHL is a hyperacute disease, which is considered the most acute form of acute disseminated encephalomyelitis (ADEM). Our findings suggests that a viral infection may be implicated in its pathogenesis, most likely through an indirect mechanism; however, as only a few cases of this rare disease were examined, statistical significance was not achieved. As a number of patients with disorders of the ADEM group may progress to develop multiple sclerosis (MS), we argue that an organism that has produced the former may remain in the brain tissue and be subsequently involved in the production of a self-sustained disorder such as MS.
authors.affiliation: Department of Molecular Pathogenesis, Division of Neuropathology, Institute of Neurology, University College London, London, United Kingdom. S.An@ion.ucl.ac.uk
authors.forename: Shu F
authors.initials: SF
authors.lastname: An
authors.forename: Michael
authors.initials: M
authors.lastname: Groves
authors.forename: Lillian
authors.initials: L
authors.lastname: Martinian
authors.forename: Lu T
authors.initials: LT
authors.lastname: Kuo
authors.forename: Francesco
authors.initials: F
authors.lastname: Scaravilli
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000956:Antigens, Viral / Q000032:analysis; D001921:Brain / Q000382:microbiology / Q000473:pathology / Q000821:virology*; D002648:Child; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification; D004269:DNA, Bacterial / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D014645:Herpesvirus 3, Human / Q000302:isolation & purification; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D015654:Herpesvirus 6, Human / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D004684:Leukoencephalitis, Acute Hemorrhagic / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009174:Mycoplasma / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D018139:Simplexvirus / Q000302:isolation & purification
chemical_list: D000956:Antigens, Viral; D004269:DNA, Bacterial; D004279:DNA, Viral