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Chapter 1 : Pathological Features of Encephalitis in Humans
Authors:
John Booss1,
Margaret M. Esiri2
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Affiliations:
1: National Director of Neurology, Department of Veterans Affairs, VA Connecticut, West Haven, and Professor of Neurology and of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut;
2: Professor of Neuropathology, Department of Clinical Neurology, University of Oxford, and Honorary Consultant Neuropathologist, Oxford Radcliffe NHS Trust, Oxford, United Kingdom
Content Type: Monograph
Publication Year:
2003
Category: Viruses and Viral Pathogenesis
Book DOI:
10.1128/9781555817831
Chapter DOI:
10.1128/9781555817831.ch1
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Abstract:
This chapter provides an overview of the pathology of human encephalitis. It describes procedures that are of value in examining central nervous system (CNS) tissues from cases of suspected encephalitis, and histopathological features common to most forms of viral encephalitis. The chapter discusses factors that confer specificity in the case of particular viral infections of the CNS, such as selectivity with regard to a host cell type that a virus may show, the character of the immune response, and the tempo of the disease. The association of a virus with its natural host species is generally a very close and specific one, and it is therefore only with caution that findings in animals can be applied to humans. Naked-eye examination and light microscopy are the classical techniques of pathological examination that formed the basis of the early studies of encephalitis. A variety of techniques is available to search in histological material for specific viral antigens. Immunofluorescence was the first of these to be developed and has been in routine use for many years. The appearance of the characteristic inflammatory infiltrate in encephalitis is dependent on the presence of an intact immune response. The relative contributions of cellular and humoral immunity, both in eliminating virus and in contributing to the damage produced, remain relatively ill-defined in human encephalitis. In recent decades, the autopsy rates in most hospitals have dropped dramatically. There are few conditions for which the autopsy is more important than viral encephalitis.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
Figures
Pathological Features of Encephalitis in Humans
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-1
FIGURE 1.1
Summary chart of recommended procedures when dealing with autopsy or biopsy specimens from a case of suspected encephalitis. IPX, immunoperoxidase; ISH, in situ hybridization; EM, electron microscopy; HE, hematoxylin and eosin.
10.1128/9781555817831/fig1-1_thmb.gif
10.1128/9781555817831/fig1-1.gif
FIGURE 1.1
Summary chart of recommended procedures when dealing with autopsy or biopsy specimens from a case of suspected encephalitis. IPX, immunoperoxidase; ISH, in situ hybridization; EM, electron microscopy; HE, hematoxylin and eosin.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-2
FIGURE 1.2
Astrocytic reaction in white matter demonstrated by GFAP immunostaining in a case of HIV encephalitis.
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10.1128/9781555817831/fig1-2.gif
FIGURE 1.2
Astrocytic reaction in white matter demonstrated by GFAP immunostaining in a case of HIV encephalitis.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-3
FIGURE 1.3
(a) Plasma cells immunostained by an antibody to immunoglobulin G in a case of herpes simplex encephalitis, (b) Macrophages immunostained by an antibody to CD68 surrounding a small vein in acute hemorrhage leukoencephalitis.
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10.1128/9781555817831/fig1-3.gif
FIGURE 1.3
(a) Plasma cells immunostained by an antibody to immunoglobulin G in a case of herpes simplex encephalitis, (b) Macrophages immunostained by an antibody to CD68 surrounding a small vein in acute hemorrhage leukoencephalitis.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-4
FIGURE 1.4
Examples of immunostaining for viral antigens in formalin-fixed paraffin-embedded tissue, (a) HIV in the processes of a multinucleated macrophage in HIV encephalitis (arrows), (b) Herpes simplex virus in the hippocampus in herpes simplex encephalitis, (c) Cytomegalovirus in ependymal and subependymal cells in a case of necrotizing ventriculo-encephalitis with AIDS, (d) Rabies virus in negri bodies of hippocampal neurons (arrows). (Courtesy of G. Gosztonyi.)
10.1128/9781555817831/fig1-4_thmb.gif
10.1128/9781555817831/fig1-4.gif
FIGURE 1.4
Examples of immunostaining for viral antigens in formalin-fixed paraffin-embedded tissue, (a) HIV in the processes of a multinucleated macrophage in HIV encephalitis (arrows), (b) Herpes simplex virus in the hippocampus in herpes simplex encephalitis, (c) Cytomegalovirus in ependymal and subependymal cells in a case of necrotizing ventriculo-encephalitis with AIDS, (d) Rabies virus in negri bodies of hippocampal neurons (arrows). (Courtesy of G. Gosztonyi.)
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-5
FIGURE 1.5
Demonstration of JC virus DNA using in situ hybridization in a case of progressive multifocal leukoencephalopathy. The positively reacting nuclei (arrows) mainly surround a small locus of demyelination indicated by the dashed line.
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10.1128/9781555817831/fig1-5.gif
FIGURE 1.5
Demonstration of JC virus DNA using in situ hybridization in a case of progressive multifocal leukoencephalopathy. The positively reacting nuclei (arrows) mainly surround a small locus of demyelination indicated by the dashed line.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-6
FIGURE 1.6
Foci of neuronophagia seen at low power in (a) and (b) and at higher power in (c). In (c), there is a central degenerate neuron in the dentate nucleus of the cerebellum. The neuron contains an intranuclear inclusion body suggestive of cytomegalovirus infection. Sample was collected from a patient with encephalitis with microglial nodules following renal transplantation. Panels (a) and (c) hematoxylin and eosin stain; (b) immunostain for macrophages using Ricinus communis agglutinin.
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10.1128/9781555817831/fig1-6.gif
FIGURE 1.6
Foci of neuronophagia seen at low power in (a) and (b) and at higher power in (c). In (c), there is a central degenerate neuron in the dentate nucleus of the cerebellum. The neuron contains an intranuclear inclusion body suggestive of cytomegalovirus infection. Sample was collected from a patient with encephalitis with microglial nodules following renal transplantation. Panels (a) and (c) hematoxylin and eosin stain; (b) immunostain for macrophages using Ricinus communis agglutinin.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-7
FIGURE 1.7
Neurofibrillary tangle in a substantia nigra neuron from a case of postencephalitic parkinsonism. Congo red stain.
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10.1128/9781555817831/fig1-7.gif
FIGURE 1.7
Neurofibrillary tangle in a substantia nigra neuron from a case of postencephalitic parkinsonism. Congo red stain.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-8
FIGURE 1.8
Bizarre multinucleated astrocytes in the cerebellum of a young man with progressive multifocal leukoen cephalopathy complicating a severe congenital immunodeficiency syndrome. Hematoxylin and eosin stain.
10.1128/9781555817831/fig1-8_thmb.gif
10.1128/9781555817831/fig1-8.gif
FIGURE 1.8
Bizarre multinucleated astrocytes in the cerebellum of a young man with progressive multifocal leukoen cephalopathy complicating a severe congenital immunodeficiency syndrome. Hematoxylin and eosin stain.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-9
FIGURE 1.9
Typical perivascular cuffs of mononuclear inflammatory cells surrounding a small vein in a case of brain stem encephalitis resembling encephalitis lethargica.
10.1128/9781555817831/fig1-9_thmb.gif
10.1128/9781555817831/fig1-9.gif
FIGURE 1.9
Typical perivascular cuffs of mononuclear inflammatory cells surrounding a small vein in a case of brain stem encephalitis resembling encephalitis lethargica.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-10
FIGURE 1.10
(a) CD68+ cells extending into parenchyma from small veins in a case of brain stem encephalitis. In contrast, (b) immunostained B cells (arrows) remain in perivascular spaces. Both panels counterstained with hematoxylin.
10.1128/9781555817831/fig1-10_thmb.gif
10.1128/9781555817831/fig1-10.gif
FIGURE 1.10
(a) CD68+ cells extending into parenchyma from small veins in a case of brain stem encephalitis. In contrast, (b) immunostained B cells (arrows) remain in perivascular spaces. Both panels counterstained with hematoxylin.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-11
FIGURE 1.11
(a) Negri bodies (arrows) in the cytoplasm of cortical pyramidal neurons in rabies, (b) Cowdry type A inclusion bodies (arrows) in neuronal nuclei in a case of immunosuppressive measles encephalitis. Both panels, hematoxylin and eosin stain.
10.1128/9781555817831/fig1-11_thmb.gif
10.1128/9781555817831/fig1-11.gif
FIGURE 1.11
(a) Negri bodies (arrows) in the cytoplasm of cortical pyramidal neurons in rabies, (b) Cowdry type A inclusion bodies (arrows) in neuronal nuclei in a case of immunosuppressive measles encephalitis. Both panels, hematoxylin and eosin stain.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-12
FIGURE 1.12
Examples of diffetences in topographical location of damage found in different forms of viral encephalitis (ventricular system stippled).
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10.1128/9781555817831/fig1-12.gif
FIGURE 1.12
Examples of diffetences in topographical location of damage found in different forms of viral encephalitis (ventricular system stippled).
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-13
FIGURE 1.13
Acute hemorrhagic leukoencephalitis showing a small vein at the center surrounded by leukocytes. Beyond these, there is a zone of red blood cells and demyelinated white matter parenchyma. Luxol fast blue stain.
10.1128/9781555817831/fig1-13_thmb.gif
10.1128/9781555817831/fig1-13.gif
FIGURE 1.13
Acute hemorrhagic leukoencephalitis showing a small vein at the center surrounded by leukocytes. Beyond these, there is a zone of red blood cells and demyelinated white matter parenchyma. Luxol fast blue stain.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-14
FIGURE 1.14
Cerebral white matter from a case of perivenous encephalitis. Venules are surrounded by an intense inflammatory cell infiltrate. Nissl stain.
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10.1128/9781555817831/fig1-14.gif
FIGURE 1.14
Cerebral white matter from a case of perivenous encephalitis. Venules are surrounded by an intense inflammatory cell infiltrate. Nissl stain.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-15
FIGURE 1.15
Adjacent section to that shown in Fig. 1.14, stained for myelin and showing perivenous myelin pallor. Weil's stain.
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10.1128/9781555817831/fig1-15.gif
FIGURE 1.15
Adjacent section to that shown in Fig. 1.14, stained for myelin and showing perivenous myelin pallor. Weil's stain.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-16
FIGURE 1.16
Cerebellar tonsillar herniation, particularly marked on the right side (left side in photograph).
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10.1128/9781555817831/fig1-16.gif
FIGURE 1.16
Cerebellar tonsillar herniation, particularly marked on the right side (left side in photograph).
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
/content/10.1128/9781555817831.chap1.fig1-17
FIGURE 1.17
Venous infarction secondary to sagittal sinus thrombosis in a case of encephalitis of undiagnosed cause.
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10.1128/9781555817831/fig1-17.gif
FIGURE 1.17
Venous infarction secondary to sagittal sinus thrombosis in a case of encephalitis of undiagnosed cause.
Citation:
Booss J, Esiri M.
2003.
Pathological Features of Encephalitis in Humans,
p 3-19.
In
Viral Encephalitis in Humans.
ASM Press, Washington, DC.
doi: 10.1128/9781555817831.ch1
References
/content/book/10.1128/9781555817831.chap1
1.
Adams, D. H.,, and A. R. Lloyd. 1997. Chemokines: leucocyte recruitment and activation cytokines. Lancet 349: 490– 495.
2.
Advisory Committee on Dangerous Pathogens. 1994. Precautions for work with human and animal transmissible spongiform encephalopathies. H.M. Stationery Office, London, United Kingdom.
3.
Advisory Committee on Dangerous Pathogens. 1995a. Protection against Bfood-Borne Infections in the Workplace: HIV and Hepatitis. H.M. Stationery Office, London, United Kingdom.
4.
Advisory Committee on Dangerous Pathogens. 1995b. Categorisation of Biological Agents According to Hazard and Categories of Containment. H.M. Stationery Office, London, United Kingdom.
5.
Advisory Committee on Dangerous Pathogens. 1998. Transmissible Spongiform Encephalopathy Agents: Safe Working and the Prevention of Infection. H.M. Stationery Office, London, United Kingdom.
6.
Allsopp, T. E.,, and J. K. Fazakerley. 2000. Altruistic cell suicide and the specialized case of the virus-infected nervous system. Trends Neurosci. 23: 284– 290.
7.
Anderson, J. R.,, and H. J. Field. 1983. The distribution of herpes simplex type 1 antigen in mouse central nervous system after different routes of inoculation. J. Neurol. Sci. 60: 181– 195.
8.
Atenasiu, P., 1973. Laboratory Techniques in Rabies, p. 338. In M. M. Kaplan, and H. Koprowski (ed.), WHO Monograph Series. World Health Organization, Geneva, Switzerland.
9.
Bell, J. E.,, S. M. Gentleman,, J. W. Ironside,, L. McCardle,, P. L. Lantos,, L. Doey,, J. Lowe,, J. Fergusson,, P. Luthert,, S. McQuaid,, and St. V. Allen. 1997. Prion protein immunocytochemistry—UK five centre consensus report. Neuropathol. Appl. Neurobiol. 23: 26– 35.
10.
Benjamin, D. R.,, and C. G. Ray. 1975. Use of immunoperoxidase on brain tissue for the rapid diagnosis of herpes encephalitis. Am. J. Clin. Pathol. 64: 472– 476.
11.
Berger, D. P.,, D. Homann,, and M. B. A. Oldstone,. 2000. Im-munocyrotherapy of persistent viral infection, p. 289– 295. In P. K. Peterson, and J. Remington (ed.), New Concepts in the hn-munopathogenesis of CNS Infections. Blackwell Science, Oxford, United Kingdom.
12.
Blinzinger, K.,, J. Simon,, D. Magrath,, and L. Boulger. 1969. Po-liovirus crystals within the endoplasmic reticulum of endothelial and mononuclear cells in the monkey spinal cord. Science 163: 1336– 1337.
13.
Blumberg, B. M.,, D. J. Mock,, J. M. Powers,, M. Ito,, J. G. As-souline,, J. V. Baker,, B. Chen,, and A. D. Goodman. 2000. The HHV6 paradox: ubiquitous commensal or insidious pathogen? A two-step in situ PCR approach. J. Clin. Virol. 16: 159– 178.
14.
Bodian, D.,, and H. A. Howe. 1941. The rate of progression of poliomyelitis virus in nerves. Bull. Johns Hopkins Hosp. 69: 7985.
15.
Booss, J.,, P. R. Dann,, B. P. Griffith,, and J. H. Kim. 1989. Host defense response to cytomegalovirus in the central nervous system. Predominance of the monocyte. Am. J. Pathol. 134: 71– 78.
16.
Bouteille, M.,, R. Houdart,, and G. Delarue. 1965. Ultrastructural arguments in favor of the histogenetic oneness of astrocytomas, glioblastoma multiforme and oligodendrogliomas. Rev. Neurol. (Paris) 112: 69– 71.
17.
Breitfeld, V.,, Y. Hashida,, F. E. Sherman,, K. Odagiri,, and E. J. Yunis. 1973. Fatal measles infection in children with leukemia. Lab. Invest. 28: 279– 291.
18.
Brightman, M. W. 1968. The intracerebral movement of proteins injected into blood and cerebrospinal fluid of mice. Prog. Brain Res. 29: 19– 40.
19.
Brown, C. 1998. Antigen retrieval methods for immunohisto-chemistry. Toxicol. Pathol. 26: 830– 831.
20.
Brown, P.,, C. J. Gibbs, Jr.,, H. L. Amyx,, D. T. Kingsbury,, R. G. Rohwer,, M. P. Sulima,, and D. C. Gajdusek. 1982. Chemical disinfection of Creutzfeldt-Jakob disease virus. N. Engl. J. Med. 306: 1279– 1282.
21.
Buchmeier, M. J.,, R. M. Welsh,, E. J. Dutko,, and M. B. Oldstone. 1980. The virology and immunobiology of lymphocytic choriomeningitis virus infection. Adv. Immunol. 30: 275– 331.
22.
Budka, H.,, and T. Popow-Kraupp. 1981. Rabies and herpes simplex virus encephalitis. An immunohistological study on site and distribution of viral antigens. Virchows Arch. A. Pathol. Anat. Histol. 390: 353– 364.
23.
Budka, H.,, H. Lassmann,, and T. Popow-Kraupp. 1982. Measles virus antigen in panencephalitis. An immunomorphological study stressing dendritic involvement in SSPE. Acta Neu-ropathol. 56: 52– 62.
24.
Buzzard, E. E.,, and J. G. Greenfield. 1919. Lethargic encephalitis; its sequelae and morbid anatomy. Brain 42: 305– 388.
25.
Centers for Disease Control and Prevention. 1999. Biological Safety Level 4 Agents. Biosafety in Microbiological and Biomedical Laboratories, 4th ed. Centers for Disease Control and Prevention and National Institutes of Health, U.S. Department of Health and Human Services. U.S. Government Printing Office, Washington, D.C.
26.
Centers for Disease Control and Prevention. 2002. Draft Guidelines for Disinfection and Sterilization in Health Care Facilities. Centers for Disease Control and Prevention, Atlanta, Ga.
27.
Chao, C. C.,, S. Hu,, W. S. Sheng,, D. Bu,, M. I. Bukrinsky,, and P. K. Peterson. 1996. Cytokine-stimulated astrocytes damage human neurons via a nitric oxide mechanism. Glia 16: 276– 284.
28.
COSHH. 1999. Regulations on control of substances hazardous to health. H. M. Stationery Office, London, United Kingdom.
29.
Dayan, A. D.,, and J. D. Almeida,. 1975. The morphologist's contribution to the study of viral encephalitis, p. 32– 55. In L. S. Illis (ed.), Viral Diseases of the Nervous System. Bailliere Tindall, London, United Kingdom.
30.
DeBiasi, R. L.,, and K. L. Tyler. 1999. Polymerase chain reaction in the diagnosis and management of central nervous system infections. Arch. Neurol. 56: 1215– 1219.
31.
de la Torre, J. C.,, M. Mallory,, M. Brot,, L. Gold,, G. Koob,, M. B. Oldstone,, and E. Masliah. 1996. Viral persistence in neurons alters synaptic plasticity and cognitive functions without destruction of brain cells. Virology 220: 508– 515.
32.
Duriez, P. J.,, and G. M. Shah. 1997. Cleavage of poly(ADP-ribose) polymerase: a sensitive parameter to study cell death. Biochem. Cell Biol. 75: 337– 349.
33.
Esiri, M. M. 1982. Herpes simplex encephalitis. An immunohistological study of the distribution of viral antigen within the brain. J. Neurol. Sci. 54: 209– 226.
34.
Esiri, M. M.,, D. R. Oppenheimer,, B. Brownell,, and M. Haire. 1982. Distribution of measles antigen and immunoglobulin-containing cells in the CNS in subacute sclerosing panencephalitis (SSPE) and atypical measles encephalitis. J. Neurol. Sci. 53: 29– 43.
35.
Gauczynski, S.,, J. M. Peyrin,, S. Haik,, C. Leucht,, C. Hundt,, R. Rieger,, S. Krasemann,, J. P. Deslys,, D. Dormont,, C. I. Lasmezas,, and S. Weiss. 2001. The 37-kDa/67-kDa laminin receptor acts as the cell-surface receptor for the cellular prion protein. EMBO J. 20: 5863– 5875.
36.
Glasgow, L. A., 1979. Biology and pathogenesis of viral infections, p. 39– 76. In G. J. Galasso,, T. C. Merigan,, and R. A. Buchanan (ed.), Viral Agents and Viral Diseases in Man. Raven Press, New York, N.Y.
37.
Gosztonyi, G., 1979. Possible mechanisms of spread of fixed rabies virus along neural pathways, p. 323– 345. In P. A. Bachmann (ed.), Proc. 4th Munich Symposium on Microbiology. (Mechanisms of Viral Pathogenesis and Virulence.).>
38.
Gosztonyi, G.,, and M. Terborg. 1992. In situ hybridization histochemistry in the diagnosis of viral infections of the central nervous system. Acta Histochem. Suppl. 42: 123– 130.
39.
Graf stein, B.,, and D. S. Forman. 1980. Intracellular transport in neurons. Physiol. Rev. 60: 1167– 1283.
40.
Grcevic, N.,, and V. Vince. 1976. p. 127– 149. In Vesenjak-Hirjan (ed.), Tick-Borne Encephalitis in Croatia (Yugoslavia). Jugoslaven-ska Akademige 327, Zagreb, Yugoslavia.
41.
Griffin, D. E.,, and J. M. Hardwick. 1997. Regulators of apopto-sis on the road to persistent alphavirus infection. Annu. Rev. Microbiol. 51: 565– 592.
42.
Gutewa, J.,, and E. Osetowska,. 1961. A chronic form of subacute sclerosing panencephalitis (a case with a history of 5 years); clinical and pathological study, p. 386– 404. In L. van Bogaert,, J. Radermecker,, J. Hozay,, and A. Lowenthal (ed.), Encephalitides. Elsevier, Amsterdam, The Netherlands.
43.
Hallervorden, J. 1935. Anatomische Untersungen zur Patho-genese des postencephalitischen Parkinsonismus. D.Z. Nerven-heilk 136: 68– 77.
44.
Haymaker, W.,, M. G. Smith,, L. van Bogaert,, and C. de Chenar,. 1958>. Pathology of viral disease in man characterised by nuclear inclusions, p. 95– 104. In W. S. Field, and R. L. Blattner (ed.), Viral Encephalitis. Charles C. Thomas Co., Springfield, III.
45.
Horten, B.,, R. W. Price,, and D. Jimenez. 1981. Multifocal varicella-zoster virus leukoencephalitis temporally remote from herpes zoster. Ann. Neurol. 9: 251– 266.
46.
Hummel, M.,, I. Anagnostopoulos,, P. Korbjuhn,, and H. Stein. 1995. Epstein-Barr virus in B-cell non-Hodgkin's lymphomas: unexpected infection patterns and different infection incidence in low- and high-grade types. J. Pathol. 175: 263– 271.
47.
Ironside, J. W.,, and J. E. Bell. 1996. The 'high-risk' neu-ropathological autopsy in AIDS and Creutzfeldt-Jakob disease: principles and practice. Neuropathol. Appl. Neurobiol. 22: 388– 393.
48.
Itoyama, Y.,, H. D. Webster,, N. H. Sternberger,, E. P. Richardson, Jr.,, D. L. Walker,, R. H. Quarles,, and B. L. Padgett. 1982. Distribution of papovavirus, myelin-associated glycoprotein, and myelin basic protein in progressive multifocal leukoencephalopathy lesions. Ann. Neurol. 11: 396– 407.
49.
Johnson, A. J.,, M. Rodriquez,, and L. R. Pease,. 2000. Class I major histocompatibility molecules play a critical role in resistance to Theiler's virus infection, p. 296– 316. In P. K. Peterson and J. S. Remington (eds.), New Concepts in the Pathogenesis of CNS Infections. Blackwell Science, Oxford, United Kingdom.
50.
Johnson, R. T. 1965. Virus invasion of the central nervous system. A study of Sindbis virus infection in the mouse using im-munofluorescent antibody. Am. J. Pathol. 46: 929– 943.
51.
Johnson, R. T. 1980. Selective vulnerability of neural cells to viral infections. Brain 103: 447– 472.
52.
Jubelt, B.,, G. Gallez'Hawkins,, O. Narayan,, and R. T. Johnson. 1980. Pathogenesis of human poliovirus infection in mice. I. Clinical and pathological studies. J. Neuropathol. Exp. Neurol. 39: 138– 148.
53.
Kerschensteiner, M.,, E. Gallmeier,, L. Behrens,, V. V. Leal,, T. Misgeld,, W. E. Klinkert,, R. Kolbeck,, E. Hoppe,, R. L. Oropeza^Wekerle,, I. Bartke,, C. Stadelmann,, H. Lassmann,, H. Wekerle,, and R. Hohlfeld. 1999. Activated human T cells, B cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J. Exp. Med. 189: 865– 870.
54.
Kleinschmidt'DeMasters, M. D.,, R. L. DeBiasi,, and K. L. Tyler. 2001. Polymerase chain reaction as a diagnostic adjunct in herpes virus infections of the nervous system. Brain Pathol. 11: 452– 464.
55.
Knobler, R. L.,, L. A. Tunison,, P. W. Lampert,, and M. B. Oldstone. 1982. Selected mutants of mouse hepatitis virus type 4 (JHM strain) induce different CNS diseases. Pathobiology of disease induced by wild type and mutants ts8 and tsl5 in BALB/c and SJL/J mice. Am. J. Pathol 109: 157– 168.
56.
Krakauer, D. C. 2000. Evolving cell death in the virus-infected nervous system. Trends Neurosci. 23: 611– 612.
57.
Kristensson, K.,, E. Lycke,, and J. Sjostrand. 1974. Spread of herpes simplex virus in peripheral nerves. Acta Neuropathol. 17: 44– 53.
58.
Kumanishi, X.,, and A. Hirano. 1978. An immunoperoxidase study on herpes simplex virus encephalitis. J. Neuropathol. Exp. Neurol. 37: 790– 795.
59.
Kumanishi, T.,, and I. Seichii. 1979. SSPE: immunohistochemical demonstration of measles virus antigen(s) in paraffin sections. Acta Neuropathol. (Berlin) 48: 161– 163.
60.
Kure, K.,, W. D. Lyman,, K. M. Weidenheim,, and D. W. Dickson. 1990. Cellular localization of an HIV-1 antigen in subacute AIDS encephalitis using an improved double-labeling immunohistochemical method. Am. J. Pathol. 136: 1085– 1092.
61.
Lawson, L. J., 1995. Leukocyte migration into the central nervous system, p. 27– 60. In N. Rothwell (ed.), Immune Responses in the Nervous System. Bios, Oxford, United Kingdom.
62.
Lebon, P.,, G. Ponsot,, J. Gony,, and J. Hors. 1986. HLA antigens in acute measles encephalitis. Tissue Antigens 27: 75– 77.
63.
Lee, S. C.,, D. W. Dickson,, W. Liu,, and C. E Brosnan. 1993. Induction of nitric oxide synthase activity in human astrocytes by interleukin-1 beta and interferon-gamma. J. Neuroimmunol. 46: 19– 24.
64.
Levine, B.,, Q. Huang,, J. T. Isaacs,, J. C. Reed,, D. E. Griffin,, and J. M. Hardwick. 1993. Conversion of lytic to persistent alphavirus infection by the bcl-2 cellular oncogene. Nature 361: 739– 742.
65.
Lewis, J.,, S. L. Wesselingh,, D. E. Griffin,, and J. M. Hardwick. 1996. Alphavirus-induced apoptosis in mouse brains correlates with neurovirulence. J. Virol. 70: 1828– 1835.
66.
Liou, M. L.,, and C. Y. Hsu. 1998. Japanese encephalitis virus is transported across the cerebral blood vessels by endocytosis in mouse brain. Cell Tissue Res. 293: 389– 394.
67.
Lohler, J. 1982. Virus infections of the central nervous system. Demonstration of viral antigens in paraffin-embedded autopsy material by the PAP technic (Sternberger). Acta Histochem. Suppl. 25: 107– 111.
68.
Long, A. A.,, P. Komminoth,, E. Lee,, and H. J. Wolfe. 1993. Comparison of indirect and direct in-situ polymerase chain reaction in cell preparations and tissue sections. Detection of viral DN A, gene rearrangements and chromosomal translocations. Histochemistry 99: 151– 162.
69.
Mahley, R. W.,, and S. C. Rail, Jr. 2000. Apolipoprotein E: far more than a lipid transport protein. Annu. Rev. Genomics Hum. Genet. 1: 507– 537.
70.
Mandybur, T. I.,, A. S. Nagpaul,, Z. Pappas,, and W. J. Niklowitz. 1977. Alzheimer neurofibrillary change in subacute sclerosing panencephalitis. Ann. Neurol. 1: 103– 107.
71.
Mathur, A.,, N. Khanna,, and U. C. Chaturvedi. 1992. Breakdown of blood-brain barrier by virus-induced cytokine during Japanese encephalitis virus infection. Int. J. Exp. Pathol. 73: 603– 611.
72.
Monath, T. P.,, C. B. Cropp,, and A. K. Harrison. 1983. Mode of entry of a neurotropic arbovirus into the central nervous system. Reinvestigation of an old controversy. Lab. Invest. 48: 399– 410.
73.
Moore, G. R.,, U. Traugott,, L. C. Scheinberg,, and C. S. Raine. 1989. Tropical spastic paraparesis: a model of virus-induced, cytotoxic T-cell-mediated demyelination? Ann. Neurol. 26: 523– 530.
74.
Morris, C. S.,, M. M. Esiri,, T. J. Sprinkle,, and N. Gregson. 1994 - Oligodendrocyte reactions and cell proliferation markers in human demyelinating diseases. Neuropathol. Appl. Neurobiol. 20: 272– 281.
75.
Mrak, R. E.,, and L. Young. 1994. Rabies encephalitis in humans: pathology, pathogenesis and pathophysiology. J. Neuropathol. Exp. Neurol. 53: 1– 10.
76.
Murphy, E. A.,, and S. G. Whitfield. 1970. Eastern equine encephalitis virus infection: electron microscopic studies of mouse central nervous system. Exp. Mol. Pathol. 13: 131– 146.
77.
Murphy, E. A.,, S. P. Bauer,, A. K. Harrison,, and W. C. Winn, Jr. 1973. Comparative pathogenesis of rabies and rabies-like viruses. Viral infection and transit from inoculation site to the central nervous system. Lab. Invest. 28: 361– 376.
78.
Neumann, H. 2001. Control of glial immune function by neurons. Glia 36: 191– 199.
79.
Oldstone, M. B.,, J. Holmstoen,, and R. M. Welsh, Jr. 1977. Alterations of acetylcholine enzymes in neuroblastoma cells persistently infected with lymphocytic choriomeningitis virus. J. Cell Physiol. 91: 459– 472.
80.
Pathak, S.,, and H. E. Webb. 1974. Possible mechanisms for the transport of Semliki forest virus into and within mouse brain. An electron-microscopic study. J. Neurol. Sci. 23: 175– 184.
81.
Paula-Barbosa, M. M.,, R. Brito,, C. A. Silva,, R. Faria,, and C. Cruz. 1979. Neurofibrillary changes in the cerebral cortex of a patient with subacute sclerosing panencephalitis (SSPE). Acta Neuropathol. (Berlin) 48: 157– 160.
82.
Piyasirisilp, S.,, B. J. Schmeckpeper,, D. Chandanayingyong,, T. Hemachudha,, and D. E. Griffin. 1999. Association of HLA and T-cell receptor gene polymorphisms with Semple rabies vaccine-induced autoimmune encephalomyelitis. Ann. Neurol. 45: 595– 600.
83.
Ransohoff, R. M., 1999. Chemokines and central nervous system inflammation, p. 413– 436. In R. R. Ruffolo,, G. Z. Fenerstein,, A. J. Hunter,, and G. Poste (ed.), Inflammatory Cells and Mediators in CNS Diseases. Harwood, Taylor & Francis Group, London, United Kingdom.
84.
Rao, L.,, M. Debbas,, P. Sabbatini,, D. Hockenbery,, S. Korsmeyer,, and E. White. 1992. The adenovirus El A proteins induce apoptosis, which is inhibited by the E1B 19-kDa and Bcl-2 proteins. Proc. NatL Acad. Sci. USA 89: 7742– 7746.
85.
Reinacher, M.,, J. Bonin,, O. Narayan,, and C. Scholtissek. 1983. Pathogenesis of neurovirulent influenza A virus infection in mice. Route of entry of virus into brain determines infection of different populations of cells. Lab. Invest. 49: 686– 692.
86.
Rosenberg, G., 1999. Cytokines and matrix metalloproteinases in inflammation of the blood brain barrier, p. 413– 436. In R. R. Ruffolo,, G. Z. Fenerstein,, A. J. Hunter,, and G. Poste (ed.), Inflammatory Cells and Mediators in CNS Diseases. Harwood, Taylor & Francis Group, London, United Kingdom.
87.
Sherriff, F. E.,, L. R. Bridges,, and S. Sivaloganathan. 1994. Early detection of axonal injury after human head trauma using im-munocytochemistry for beta-amyloid precursor protein. Acta Neuropathol. 87: 55– 62.
88.
Simbulan-Rosenthal, C. M.,, D. S. Rosenthal,, S. Iyer,, A. H. Boulares,, and M. E. Smulson. 1998. Transient poly(ADP-ribosyl)ation of nuclear proteins and role of poly(ADP-ribose) polymerase in the early stages of apoptosis. J. Biol. Chem. 273: 13703– 13712.
89.
Springer, T. A. 1994. Traffic signals for lymphocyte recirculation and leukocyte emigration: the multistep paradigm. Cell 76: 301– 314.
90.
Sternberger, L. A. 1979. Immunocytochemistry, 2nd ed. John Wiley, New York, N.Y.
91.
Summers, B. A.,, H. A. Greisen,, and M. J. Appel. 1978. Possible initiation of viral encephalomyelitis in dogs by migrating lymphocytes infected with distemper virus. Lancet ii: 187– 189.
92.
Venters, H. D.,, Q. Tang,, Q. Liu,, R. W. VanHoy,, R. Dantzer,, and K. W. Kelley. 1999. A new mechanism of neurodegener-ation: a proinflammatory cytokine inhibits receptor signaling by a survival peptide. Proc. Natl. Acad. Sci. USA 96: 9879– 9884.
93.
von Andrian, U. H.,, and C. R. Mackay. 2000. T-cell function and migration. Two sides of the same coin. N. Engl. J. Med. 343: 1020– 1034.
94.
Walker, R.,, C. Bedel,, O. Boucher,, M. C. Dauge,, C. Vissuzaine, and E Potet. 1995. In situ gene amplification on tissue sections (in situ PCR). A new technique for pathologists. Ann. Pathol. 15: 459– 465.
95.
Webb, H. E.,, and J. G. Hall. 1972. An assessment of the role of the allergic response in the pathogenesis viral diseases. Symp. Soc. Gen. Microbiol. 22: 383.
96.
Westendorp, M. O.,, R. Frank,, C. Ochsenbauer,, K. Strieker,, J. Dhein,, H. Walczak,, K. M. Debatin,, and P. H. Krammer. 1995. Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gpl20. Nature 375: 497– 500.
97.
Williams, K. C.,, and W. F. Hickey,. 1996. Traffic of lymphocytes into the CNS during inflammation and HIV infection, p. 31– 55. In R. W. Price, and J. J. Sidris (ed.), The Cellular Basis of Central Nervous System HIV-J Infection and the AIDS Dementia Complex. Haworth Medical Press, New York, N.Y.
98.
Wolinsky, J. S.,, T. Klassen,, and J. R. Baringer. 1976. Persistence of neuroadapted mumps virus in brains of newborn hamsters after intraperitoneal inoculation. J. Infect. Dis. 133: 260– 267.
99.
Wong, K. T.,, K. B. Chua,, and S. K. Lam. 1999. Immunohistochemical detection of infected neurons as a rapid diagnosis of enterovirus 71 encephalomyelitis. Ann. Neurol. 45: 271– 272.
100.
Wyatt, H. V. 1982. Any questions? Tropical Doctor 12: 218.
101.
Zlotnik, I.,, C. E. Smith,, D. P. Grant,, and S. Peacock. 1970. The effect of immunosuppression on viral encephalitis, with special reference to cyclophosphamide. Br. J. Exp. Pathol. 51: 434– 439.
102.
Zu Rhein, G. M.,, and S. M. Chou. 1965. Particles resembling papovaviruses in human cerebral demyelinating disease. Science 148: 1477– 1479.