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November 25, 2003; 61 (10) Article

Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections

D. Donati, N. Akhyani, A. Fogdell–Hahn, C. Cermelli, R. Cassiani-Ingoni, A. Vortmeyer, J. D. Heiss, P. Cogen, W. D. Gaillard, S. Sato, W. H. Theodore, S. Jacobson
First published November 24, 2003, DOI: https://doi.org/10.1212/01.WNL.0000094357.10782.F9
D. Donati
From the Neuroimmunology Branch (Dr. Donati, Fogdell–Hahn, and Cermelli, N. Akhyani and R. Cassiani Ingoni), Surgical Neurology Branch (Drs. Vortmeyer and Heiss), and Clinical Epilepsy Section (Drs. Gaillard, Sato, and Theodore), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, and Departments of Neurology (Dr. Gaillard) and Neurosurgery (Dr. Cogen), Children’s National Medical Center, George Washington University School of Medicine, Washington, DC; and Struttura Complessa di Microbiologia e Virologia (Dr. Donati), Azienda Ospedaliera Universitaria Senese, Siena, and Dipartimento di Sc. Igienistiche, Microbiologiche, e Biostatistiche (Dr. Cermelli), Università degli Studi di Modena e Reggio Emilia, Italy.
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N. Akhyani
From the Neuroimmunology Branch (Dr. Donati, Fogdell–Hahn, and Cermelli, N. Akhyani and R. Cassiani Ingoni), Surgical Neurology Branch (Drs. Vortmeyer and Heiss), and Clinical Epilepsy Section (Drs. Gaillard, Sato, and Theodore), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, and Departments of Neurology (Dr. Gaillard) and Neurosurgery (Dr. Cogen), Children’s National Medical Center, George Washington University School of Medicine, Washington, DC; and Struttura Complessa di Microbiologia e Virologia (Dr. Donati), Azienda Ospedaliera Universitaria Senese, Siena, and Dipartimento di Sc. Igienistiche, Microbiologiche, e Biostatistiche (Dr. Cermelli), Università degli Studi di Modena e Reggio Emilia, Italy.
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A. Fogdell–Hahn
From the Neuroimmunology Branch (Dr. Donati, Fogdell–Hahn, and Cermelli, N. Akhyani and R. Cassiani Ingoni), Surgical Neurology Branch (Drs. Vortmeyer and Heiss), and Clinical Epilepsy Section (Drs. Gaillard, Sato, and Theodore), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, and Departments of Neurology (Dr. Gaillard) and Neurosurgery (Dr. Cogen), Children’s National Medical Center, George Washington University School of Medicine, Washington, DC; and Struttura Complessa di Microbiologia e Virologia (Dr. Donati), Azienda Ospedaliera Universitaria Senese, Siena, and Dipartimento di Sc. Igienistiche, Microbiologiche, e Biostatistiche (Dr. Cermelli), Università degli Studi di Modena e Reggio Emilia, Italy.
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C. Cermelli
From the Neuroimmunology Branch (Dr. Donati, Fogdell–Hahn, and Cermelli, N. Akhyani and R. Cassiani Ingoni), Surgical Neurology Branch (Drs. Vortmeyer and Heiss), and Clinical Epilepsy Section (Drs. Gaillard, Sato, and Theodore), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, and Departments of Neurology (Dr. Gaillard) and Neurosurgery (Dr. Cogen), Children’s National Medical Center, George Washington University School of Medicine, Washington, DC; and Struttura Complessa di Microbiologia e Virologia (Dr. Donati), Azienda Ospedaliera Universitaria Senese, Siena, and Dipartimento di Sc. Igienistiche, Microbiologiche, e Biostatistiche (Dr. Cermelli), Università degli Studi di Modena e Reggio Emilia, Italy.
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R. Cassiani-Ingoni
From the Neuroimmunology Branch (Dr. Donati, Fogdell–Hahn, and Cermelli, N. Akhyani and R. Cassiani Ingoni), Surgical Neurology Branch (Drs. Vortmeyer and Heiss), and Clinical Epilepsy Section (Drs. Gaillard, Sato, and Theodore), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, and Departments of Neurology (Dr. Gaillard) and Neurosurgery (Dr. Cogen), Children’s National Medical Center, George Washington University School of Medicine, Washington, DC; and Struttura Complessa di Microbiologia e Virologia (Dr. Donati), Azienda Ospedaliera Universitaria Senese, Siena, and Dipartimento di Sc. Igienistiche, Microbiologiche, e Biostatistiche (Dr. Cermelli), Università degli Studi di Modena e Reggio Emilia, Italy.
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A. Vortmeyer
From the Neuroimmunology Branch (Dr. Donati, Fogdell–Hahn, and Cermelli, N. Akhyani and R. Cassiani Ingoni), Surgical Neurology Branch (Drs. Vortmeyer and Heiss), and Clinical Epilepsy Section (Drs. Gaillard, Sato, and Theodore), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, and Departments of Neurology (Dr. Gaillard) and Neurosurgery (Dr. Cogen), Children’s National Medical Center, George Washington University School of Medicine, Washington, DC; and Struttura Complessa di Microbiologia e Virologia (Dr. Donati), Azienda Ospedaliera Universitaria Senese, Siena, and Dipartimento di Sc. Igienistiche, Microbiologiche, e Biostatistiche (Dr. Cermelli), Università degli Studi di Modena e Reggio Emilia, Italy.
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J. D. Heiss
From the Neuroimmunology Branch (Dr. Donati, Fogdell–Hahn, and Cermelli, N. Akhyani and R. Cassiani Ingoni), Surgical Neurology Branch (Drs. Vortmeyer and Heiss), and Clinical Epilepsy Section (Drs. Gaillard, Sato, and Theodore), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, and Departments of Neurology (Dr. Gaillard) and Neurosurgery (Dr. Cogen), Children’s National Medical Center, George Washington University School of Medicine, Washington, DC; and Struttura Complessa di Microbiologia e Virologia (Dr. Donati), Azienda Ospedaliera Universitaria Senese, Siena, and Dipartimento di Sc. Igienistiche, Microbiologiche, e Biostatistiche (Dr. Cermelli), Università degli Studi di Modena e Reggio Emilia, Italy.
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P. Cogen
From the Neuroimmunology Branch (Dr. Donati, Fogdell–Hahn, and Cermelli, N. Akhyani and R. Cassiani Ingoni), Surgical Neurology Branch (Drs. Vortmeyer and Heiss), and Clinical Epilepsy Section (Drs. Gaillard, Sato, and Theodore), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, and Departments of Neurology (Dr. Gaillard) and Neurosurgery (Dr. Cogen), Children’s National Medical Center, George Washington University School of Medicine, Washington, DC; and Struttura Complessa di Microbiologia e Virologia (Dr. Donati), Azienda Ospedaliera Universitaria Senese, Siena, and Dipartimento di Sc. Igienistiche, Microbiologiche, e Biostatistiche (Dr. Cermelli), Università degli Studi di Modena e Reggio Emilia, Italy.
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W. D. Gaillard
From the Neuroimmunology Branch (Dr. Donati, Fogdell–Hahn, and Cermelli, N. Akhyani and R. Cassiani Ingoni), Surgical Neurology Branch (Drs. Vortmeyer and Heiss), and Clinical Epilepsy Section (Drs. Gaillard, Sato, and Theodore), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, and Departments of Neurology (Dr. Gaillard) and Neurosurgery (Dr. Cogen), Children’s National Medical Center, George Washington University School of Medicine, Washington, DC; and Struttura Complessa di Microbiologia e Virologia (Dr. Donati), Azienda Ospedaliera Universitaria Senese, Siena, and Dipartimento di Sc. Igienistiche, Microbiologiche, e Biostatistiche (Dr. Cermelli), Università degli Studi di Modena e Reggio Emilia, Italy.
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S. Sato
From the Neuroimmunology Branch (Dr. Donati, Fogdell–Hahn, and Cermelli, N. Akhyani and R. Cassiani Ingoni), Surgical Neurology Branch (Drs. Vortmeyer and Heiss), and Clinical Epilepsy Section (Drs. Gaillard, Sato, and Theodore), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, and Departments of Neurology (Dr. Gaillard) and Neurosurgery (Dr. Cogen), Children’s National Medical Center, George Washington University School of Medicine, Washington, DC; and Struttura Complessa di Microbiologia e Virologia (Dr. Donati), Azienda Ospedaliera Universitaria Senese, Siena, and Dipartimento di Sc. Igienistiche, Microbiologiche, e Biostatistiche (Dr. Cermelli), Università degli Studi di Modena e Reggio Emilia, Italy.
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W. H. Theodore
From the Neuroimmunology Branch (Dr. Donati, Fogdell–Hahn, and Cermelli, N. Akhyani and R. Cassiani Ingoni), Surgical Neurology Branch (Drs. Vortmeyer and Heiss), and Clinical Epilepsy Section (Drs. Gaillard, Sato, and Theodore), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, and Departments of Neurology (Dr. Gaillard) and Neurosurgery (Dr. Cogen), Children’s National Medical Center, George Washington University School of Medicine, Washington, DC; and Struttura Complessa di Microbiologia e Virologia (Dr. Donati), Azienda Ospedaliera Universitaria Senese, Siena, and Dipartimento di Sc. Igienistiche, Microbiologiche, e Biostatistiche (Dr. Cermelli), Università degli Studi di Modena e Reggio Emilia, Italy.
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S. Jacobson
From the Neuroimmunology Branch (Dr. Donati, Fogdell–Hahn, and Cermelli, N. Akhyani and R. Cassiani Ingoni), Surgical Neurology Branch (Drs. Vortmeyer and Heiss), and Clinical Epilepsy Section (Drs. Gaillard, Sato, and Theodore), National Institute of Neurological Disorders and Stroke, NIH, Bethesda, MD, and Departments of Neurology (Dr. Gaillard) and Neurosurgery (Dr. Cogen), Children’s National Medical Center, George Washington University School of Medicine, Washington, DC; and Struttura Complessa di Microbiologia e Virologia (Dr. Donati), Azienda Ospedaliera Universitaria Senese, Siena, and Dipartimento di Sc. Igienistiche, Microbiologiche, e Biostatistiche (Dr. Cermelli), Università degli Studi di Modena e Reggio Emilia, Italy.
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Citation
Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections
D. Donati, N. Akhyani, A. Fogdell–Hahn, C. Cermelli, R. Cassiani-Ingoni, A. Vortmeyer, J. D. Heiss, P. Cogen, W. D. Gaillard, S. Sato, W. H. Theodore, S. Jacobson
Neurology Nov 2003, 61 (10) 1405-1411; DOI: 10.1212/01.WNL.0000094357.10782.F9

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Abstract

Background: Human herpesvirus-6 (HHV-6), a ubiquitous β-herpesvirus, is the causative agent of roseola infantum and has been associated with a number of neurologic disorders including seizures, encephalitis/meningitis, and multiple sclerosis. Although the role of HHV-6 in human CNS disease remains to be fully defined, a number of studies have suggested that the CNS can be a site for persistent HHV-6 infection.

Objective: To characterize the extent and distribution of HHV-6 in human glial cells from surgical brain resections of patients with mesial temporal lobe epilepsy (MTLE).

Method: Brain samples from eight patients with MTLE and seven patients with neocortical epilepsy (NE) undergoing surgical resection were quantitatively analyzed for the presence of HHV-6 DNA using a virus-specific real-time PCR assay. HHV-6 expression was also characterized by western blot analysis and in situ immunohistochemistry (IHC). In addition, HHV-6-reactive cells were analyzed for expression of glial fibrillary acidic protein (GFAP) by double immunofluorescence.

Results: DNA obtained from four of eight patients with MTLE had significantly elevated levels of HHV-6 as quantified by real-time PCR. HHV-6 was not amplified in any of the seven patients with NE undergoing surgery. The highest levels of HHV-6 were demonstrated in hippocampal sections (up to 23,079 copies/106 cells) and subtyped as HHV-6B. Expression of HHV-6 was confirmed by western blot analysis and IHC. HHV-6 was co-localized to GFAP-positive cells that morphologically appeared to be astrocytes.

Conclusions: HHV-6B is present in brain specimens from a subset of patients with MTLE and localized to astrocytes in the absence of inflammation. The amplification of HHV-6 from hippocampal and temporal lobe astrocytes of MTLE warrants further investigation into the possible role of HHV-6 in the development of MTLE.

  • Received January 20, 2003.
  • Accepted in final form July 26, 2003.
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Letters: Rapid online correspondence

  • Detection of human herpesvirus-6 in mesial temporal lobe epilepsy surgical brain resections
    • Jonathan M Schott, Dementia Research Group, Institute of Neurology, Box 16, Institute of Neurology, Queen Square, London WC1N 3BG, UKjschott@dementia.ion.ucl.ac.uk
    • Martin N. Rossor
    Submitted January 28, 2004
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