title: Non-paraneoplastic limbic encephalitis and central nervous HHV-6B reactivation: Causality or coincidence?
abstract: Autoantibody-related encephalopathies represent an important differential diagnosis in adult onset epilepsy. Here, we report the case of a 25-year-old patient with new-onset epilepsy and psychotic syndrome, who underwent biopsy resection for etiological classification. MRI analysis and neuropathological examination showed a T-lymphocytic dominated encephalitis with involvement of the limbic system. An indirect immunohistochemistry approach identified autoantibodies against glutamic acid decarboxylase (GAD) in cerebral spinal fluid and serum, which were confirmed by affinity purification / mass spectrometry analysis. Further examinations revealed evidence of chromosomally integrated human herpes virus type 6B (HHV-6B). However, astrocytic expression of HHV-6 lytic protein was detected by double immunofluorescence analysis. The cerebral expression of HHV-6 antigen, a clinical improvement under antiviral therapy as well as an initial finding of HHV-6 IgM antibodies strongly argue for an additional active HHV-6B infection. Review of the literature reveals singular reports of patients with GAD antibody-positive limbic encephalitis and central nervous system infections with HHV-6B. Since herpes simplex virus encephalitis has been recently reported as a trigger of N-methyl-D-aspartate receptor antibody encephalitis, it is tempting to speculate that HHV-6B infections may trigger a non-paraneoplastic form of limbic encephalitis in a parallel cascade.
authors.affiliation: Department of Neurology / Pathology, Oslo University Hospital, Oslo, Norway.|Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Pitt
authors.initials: P
authors.lastname: Niehusmann
authors.affiliation: Department of Epileptology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Guido
authors.initials: G
authors.lastname: Widman
authors.affiliation: Institute of Virology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Eis-Hübinger
authors.affiliation: Department of Radiology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Greschus
authors.affiliation: Department of Neurology / Pathology, Oslo University Hospital, Oslo, Norway.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Robens
authors.affiliation: Department of Neurosurgery, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Grote
authors.affiliation: Department of Neurology / Pathology, Oslo University Hospital, Oslo, Norway.|Translational Epilepsy Research Section, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Becker
mesh_terms: D000328:Adult; D001323:Autoantibodies; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D015654:Herpesvirus 6, Human / Q000472:pathogenicity*; D006801:Humans; D020363:Limbic Encephalitis / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology / Q000821:virology*
chemical_list: D001323:Autoantibodies; D005968:Glutamate Decarboxylase
keywords: autoantibody; autoimmune encephalitis; epilepsy; glutamic acid decarboxylase; human herpes virus type 6