EDITORS: FABRICE CHRÉTIEN, MD, PhD is Head of Neuropathology at the Sainte Anne Hospital, Paris; Professor of Neuropathology at the Paris University, Paris; and Unit Director at the Experimental Neuropathology Unit, Pasteur Institute, Paris, France. KUM THONG WONG, MBBS, MPath, FRCPath, MD is Professor of Pathology, Faculty of Medicine at the University of Malaya, Kuala Lumpur, Malaysia. LEROY R. SHARER, MD is Professor of Anatomic Pathology and Neuropathology, Department of Pathology, Immunology, and Laboratory Medicine at the Rutgers New Jersey Medical School and University Hospital, Newark, NJ, USA. SERIES EDITORS: CATHERINE (KATY) KEOHANE, MB, BCh, BAO, FRCPath, FFPath is a Neuropathologist and Professor at the School of Medicine, University College Cork, Brookfield Health Science Complex, Cork, Ireland. FRANÇOISE GRAY, MD, PhD is Professor of Pathology (retired) at the Lariboisière Hospital, APHP, Paris; and University Paris Diderot (Paris 7), Paris, France.

• List of Contributors ix1 Introduction and Classification of Infections of the CNS According to the Agent 1Fabrice Chrétien, Kum Thong Wong, Leroy R. Sharer, Catherine (Katy) Keohane, and Françoise Gray2 Sepsis‐Associated Encephalopathy 11Franck Verdonk, Aurelien Mazeraud, Fabrice Chrétien, and Tarek Sharshar3 Variation of CNS Infections According to the Host 21Leroy R. Sharer, Catherine (Katy) Keohane, and Françoise Gray4 Clinical Approach to the Adult Patient with CNS Infection 29Michel Wolff, Romain Sonneville, and Tarek Sharshar5 Herpes Simplex Virus Infections of the CNS 43Bette K. Kleinschmidt‐DeMasters, Catherine (Katy) Keohane, and Françoise Gray6 Varicella‐Zoster Virus and Epstein‐Barr Virus Infections of the CNS 55Catherine (Katy) Keohane and Françoise Gray7 Cytomegalovirus Infections of the CNS 65Homa Adle‐Biassette and Natacha Teissier8 Adenovirus Meningoencephalitis 77Harry V. Vinters and Xinhai R. Zhang9 Polyomavirus Infections of the CNS 83Susan Morgello10 Measles Virus Infection of the CNS 95Catherine (Katy) Keohane, Leroy R. Sharer, and Françoise Gray11 Rubella Virus 105Bette K. Kleinschmidt‐DeMasters12 Henipavirus Encephalitis 113Kum Thong Wong and Kien Chai Ong13 Rabies 121Guilherme Dias de Melo, Perrine Parize, Grégory Jouvion, Laurent Dacheux, Fabrice Chrétien, and Hervé Bourhy14 Flaviviruses 1: General Introduction and Tick‐Borne Encephalitis 131Herbert Budka15 Flaviviruses 2: West Nile, St. Louis Encephalitis, Murray Valley Encephalitis, Yellow Fever, and Dengue 147Edward S. Johnson and Juan M. Bilbao16 Flaviviruses 3: Zika Virus Infection of the CNS 163Leila Chimelli17 Flaviviruses 4: Japanese Encephalitis 169Shankar Krishna Susarla, Anita Mahadevan, Bishan Radotra, Masaki Takao, and Kum Thong Wong18 CNS Disorders Caused by Hepatitis C and Hepatitis E Viruses 177Melissa Umphlett, Clare Bryce, and Susan Morgello19 Alphaviral Equine Encephalomyelitis (Eastern, Western, and Venezuelan) 183Kum Thong Wong20 Chikungunya Virus 189Cássia Shinotsuka, Michael Blatzer, Grégory Jouvion, and Fabrice Chrétien21 Poliovirus Infection and Postpolio Syndrome 195Catherine (Katy) Keohane, Leila Chimelli, and Aisling Ryan22 Enterovirus A71 Infection 205Kum Thong Wong, Kien Chai Ong, Thérèse Couderc, and Marc Lecuit23 Human Immunodeficiency Virus Infection of the CNS 215Françoise Gray and Leroy R. Sharer24 HTLV‐1 and Neurological‐Associated Disease 231Antoine Gessain, Olivier Cassar, and Philippe V. Afonso25 Parechovirus A 243Clayton A. Wiley26 Acute Disseminated Encephalomyelitis and Acute Hemorrhagic Leukoencephalomyelitis 251Romana Höftberger and Hans Lassmann27 Miscellaneous Inflammatory Disorders of the CNS of Possible Infectious Origin 259Mari Perez‐Rosendahl, Jamie Nakagiri, Xinhai R. Zhang, and Harry V. Vinters28 Mycoplasmal and Rickettsial Infections of the CNS 267Roy H. Rhodes29 Pathogenesis and Pathophysiology of Bacterial Infections of the CNS 279Loic Le Guennec and Sandrine Bourdoulous30 Pyogenic Infections of the CNS 1: Acute Bacterial Meningitis 295Loic Le Guennec and Sandrine Bourdoulous31 Pyogenic Infections of the CNS 2: (Brain Abscess, Subdural Abscess or Empyema, Epidural Abscess, Septic Embolism, and Suppurative Intracranial Phlebitis) 309Arnault Tauziede‐Espariat, Alexandre Roux, Megan Still, Marc Zanello, Gilles Zah‐Bi, Ghazi Hmeydia, Catherine Oppenheim, Michel Wolff, Johan Pallud, and Fabrice Chrétien32 Pyogenic Infections of the CNS 3: Following Neurosurgical Procedures 319Alexandre Roux, Megan Still, Marc Zanello, Gilles Zah‐Bi, Arnault Tauziede‐Espariat, Ghazi Hmeydia, Catherine Oppenheim, Michel Wolff, Fabrice Chrétien, and Johan Pallud33 CNS Involvement in Tropheryma whipplei Infection 331Emmanuèle Lechapt‐Zalcman34 Cerebral Actinomycosis 337Arnault Tauziede‐Espariat35 Cerebral Nocardiosis 343Arnault Tauziede‐Espariat and Leroy R. Sharer36 CNS Tuberculosis 349Michael A. Farrell, Eoin R. Feeney, and Jane B. Cryan37 Non‐Tuberculous Mycobacterial Infections 357Leroy R. Sharer38 Spirochetal Infections of the CNS 363Françoise Gray and Catherine (Katy) Keohane39 Neurobrucellosis 379Marine Le Dudal, Fabrice Chrétien, and Grégory Jouvion40 Legionellosis 383Edward S. Johnson41 Neurosarcoidosis 393Michael A. Farrell and Alan Beausang42 Hypertrophic Pachymeningitis 403Françoise Gray and Leroy R. Sharer43 Toxin‐Induced Neurological Diseases 411Pierre L. Goossens, Cédric Thépenier, and Michel R. Popoff44 Fungal Infections of the CNS 419Michael Blatzer, Fanny Lanternier, Jean‐Paul Latgé, Anne Beauvais, Stéphane Bretagne, Fabrice Chrétien, and Grégory Jouvion45 Cerebral Malaria 437Patrícia Reis, Vanessa Estato, and Hugo Caire de Castro Faria Neto46 Toxoplasma Infection of the CNS 449Stéphane Bretagne, Catherine (Katy) Keohane, and Homa Adle‐Biassette47 Other Protozoal Infections 463Leila Chimelli and Catherine (Katy) Keohane48 Helminth Infections of the CNS 475Marine Le Dudal, Stéphane Bretagne, David Hardy, Fabrice Chrétien, and Grégory JouvionAppendix: CASE EXAMPLE: Schistosoma mekongi Neuroschistosomiasis 500Edward S. Johnson49 Brain Myiasis 503Arnault Tauziede‐Espariat50 Emerging CNS Infections 505Kum Thong WongIndex 515

EDITORS: FABRICE CHRÉTIEN, MD, PhD is Head of Neuropathology at the Sainte Anne Hospital, Paris; Professor of Neuropathology at the Paris University, Paris; and Unit Director at the Experimental Neuropathology Unit, Pasteur Institute, Paris, France. KUM THONG WONG, MBBS, MPath, FRCPath, MD is Professor of Pathology, Faculty of Medicine at the University of Malaya, Kuala Lumpur, Malaysia. LEROY R. SHARER, MD is Professor of Anatomic Pathology and Neuropathology, Department of Pathology, Immunology, and Laboratory Medicine at the Rutgers New Jersey Medical School and University Hospital, Newark, NJ, USA. SERIES EDITORS: CATHERINE (KATY) KEOHANE, MB, BCh, BAO, FRCPath, FFPath is a Neuropathologist and Professor at the School of Medicine, University College Cork, Brookfield Health Science Complex, Cork, Ireland. FRANÇOISE GRAY, MD, PhD is Professor of Pathology (retired) at the Lariboisière Hospital, APHP, Paris; and University Paris Diderot (Paris 7), Paris, France.

• List of Contributors ix1 Introduction and Classification of Infections of the CNS According to the Agent 1Fabrice Chrétien, Kum Thong Wong, Leroy R. Sharer, Catherine (Katy) Keohane, and Françoise Gray2 Sepsis‐Associated Encephalopathy 11Franck Verdonk, Aurelien Mazeraud, Fabrice Chrétien, and Tarek Sharshar3 Variation of CNS Infections According to the Host 21Leroy R. Sharer, Catherine (Katy) Keohane, and Françoise Gray4 Clinical Approach to the Adult Patient with CNS Infection 29Michel Wolff, Romain Sonneville, and Tarek Sharshar5 Herpes Simplex Virus Infections of the CNS 43Bette K. Kleinschmidt‐DeMasters, Catherine (Katy) Keohane, and Françoise Gray6 Varicella‐Zoster Virus and Epstein‐Barr Virus Infections of the CNS 55Catherine (Katy) Keohane and Françoise Gray7 Cytomegalovirus Infections of the CNS 65Homa Adle‐Biassette and Natacha Teissier8 Adenovirus Meningoencephalitis 77Harry V. Vinters and Xinhai R. Zhang9 Polyomavirus Infections of the CNS 83Susan Morgello10 Measles Virus Infection of the CNS 95Catherine (Katy) Keohane, Leroy R. Sharer, and Françoise Gray11 Rubella Virus 105Bette K. Kleinschmidt‐DeMasters12 Henipavirus Encephalitis 113Kum Thong Wong and Kien Chai Ong13 Rabies 121Guilherme Dias de Melo, Perrine Parize, Grégory Jouvion, Laurent Dacheux, Fabrice Chrétien, and Hervé Bourhy14 Flaviviruses 1: General Introduction and Tick‐Borne Encephalitis 131Herbert Budka15 Flaviviruses 2: West Nile, St. Louis Encephalitis, Murray Valley Encephalitis, Yellow Fever, and Dengue 147Edward S. Johnson and Juan M. Bilbao16 Flaviviruses 3: Zika Virus Infection of the CNS 163Leila Chimelli17 Flaviviruses 4: Japanese Encephalitis 169Shankar Krishna Susarla, Anita Mahadevan, Bishan Radotra, Masaki Takao, and Kum Thong Wong18 CNS Disorders Caused by Hepatitis C and Hepatitis E Viruses 177Melissa Umphlett, Clare Bryce, and Susan Morgello19 Alphaviral Equine Encephalomyelitis (Eastern, Western, and Venezuelan) 183Kum Thong Wong20 Chikungunya Virus 189Cássia Shinotsuka, Michael Blatzer, Grégory Jouvion, and Fabrice Chrétien21 Poliovirus Infection and Postpolio Syndrome 195Catherine (Katy) Keohane, Leila Chimelli, and Aisling Ryan22 Enterovirus A71 Infection 205Kum Thong Wong, Kien Chai Ong, Thérèse Couderc, and Marc Lecuit23 Human Immunodeficiency Virus Infection of the CNS 215Françoise Gray and Leroy R. Sharer24 HTLV‐1 and Neurological‐Associated Disease 231Antoine Gessain, Olivier Cassar, and Philippe V. Afonso25 Parechovirus A 243Clayton A. Wiley26 Acute Disseminated Encephalomyelitis and Acute Hemorrhagic Leukoencephalomyelitis 251Romana Höftberger and Hans Lassmann27 Miscellaneous Inflammatory Disorders of the CNS of Possible Infectious Origin 259Mari Perez‐Rosendahl, Jamie Nakagiri, Xinhai R. Zhang, and Harry V. Vinters28 Mycoplasmal and Rickettsial Infections of the CNS 267Roy H. Rhodes29 Pathogenesis and Pathophysiology of Bacterial Infections of the CNS 279Loic Le Guennec and Sandrine Bourdoulous30 Pyogenic Infections of the CNS 1: Acute Bacterial Meningitis 295Loic Le Guennec and Sandrine Bourdoulous31 Pyogenic Infections of the CNS 2: (Brain Abscess, Subdural Abscess or Empyema, Epidural Abscess, Septic Embolism, and Suppurative Intracranial Phlebitis) 309Arnault Tauziede‐Espariat, Alexandre Roux, Megan Still, Marc Zanello, Gilles Zah‐Bi, Ghazi Hmeydia, Catherine Oppenheim, Michel Wolff, Johan Pallud, and Fabrice Chrétien32 Pyogenic Infections of the CNS 3: Following Neurosurgical Procedures 319Alexandre Roux, Megan Still, Marc Zanello, Gilles Zah‐Bi, Arnault Tauziede‐Espariat, Ghazi Hmeydia, Catherine Oppenheim, Michel Wolff, Fabrice Chrétien, and Johan Pallud33 CNS Involvement in Tropheryma whipplei Infection 331Emmanuèle Lechapt‐Zalcman34 Cerebral Actinomycosis 337Arnault Tauziede‐Espariat35 Cerebral Nocardiosis 343Arnault Tauziede‐Espariat and Leroy R. Sharer36 CNS Tuberculosis 349Michael A. Farrell, Eoin R. Feeney, and Jane B. Cryan37 Non‐Tuberculous Mycobacterial Infections 357Leroy R. Sharer38 Spirochetal Infections of the CNS 363Françoise Gray and Catherine (Katy) Keohane39 Neurobrucellosis 379Marine Le Dudal, Fabrice Chrétien, and Grégory Jouvion40 Legionellosis 383Edward S. Johnson41 Neurosarcoidosis 393Michael A. Farrell and Alan Beausang42 Hypertrophic Pachymeningitis 403Françoise Gray and Leroy R. Sharer43 Toxin‐Induced Neurological Diseases 411Pierre L. Goossens, Cédric Thépenier, and Michel R. Popoff44 Fungal Infections of the CNS 419Michael Blatzer, Fanny Lanternier, Jean‐Paul Latgé, Anne Beauvais, Stéphane Bretagne, Fabrice Chrétien, and Grégory Jouvion45 Cerebral Malaria 437Patrícia Reis, Vanessa Estato, and Hugo Caire de Castro Faria Neto46 Toxoplasma Infection of the CNS 449Stéphane Bretagne, Catherine (Katy) Keohane, and Homa Adle‐Biassette47 Other Protozoal Infections 463Leila Chimelli and Catherine (Katy) Keohane48 Helminth Infections of the CNS 475Marine Le Dudal, Stéphane Bretagne, David Hardy, Fabrice Chrétien, and Grégory JouvionAppendix: CASE EXAMPLE: Schistosoma mekongi Neuroschistosomiasis 500Edward S. Johnson49 Brain Myiasis 503Arnault Tauziede‐Espariat50 Emerging CNS Infections 505Kum Thong WongIndex 515

EDITORS: FABRICE CHRÉTIEN, MD, PhD is Head of Neuropathology at the Sainte Anne Hospital, Paris; Professor of Neuropathology at the Paris University, Paris; and Unit Director at the Experimental Neuropathology Unit, Pasteur Institute, Paris, France. KUM THONG WONG, MBBS, MPath, FRCPath, MD is Professor of Pathology, Faculty of Medicine at the University of Malaya, Kuala Lumpur, Malaysia. LEROY R. SHARER, MD is Professor of Anatomic Pathology and Neuropathology, Department of Pathology, Immunology, and Laboratory Medicine at the Rutgers New Jersey Medical School and University Hospital, Newark, NJ, USA. SERIES EDITORS: CATHERINE (KATY) KEOHANE, MB, BCh, BAO, FRCPath, FFPath is a Neuropathologist and Professor at the School of Medicine, University College Cork, Brookfield Health Science Complex, Cork, Ireland. FRANÇOISE GRAY, MD, PhD is Professor of Pathology (retired) at the Lariboisière Hospital, APHP, Paris; and University Paris Diderot (Paris 7), Paris, France.

• List of Contributors ix1 Introduction and Classification of Infections of the CNS According to the Agent 1Fabrice Chrétien, Kum Thong Wong, Leroy R. Sharer, Catherine (Katy) Keohane, and Françoise Gray2 Sepsis‐Associated Encephalopathy 11Franck Verdonk, Aurelien Mazeraud, Fabrice Chrétien, and Tarek Sharshar3 Variation of CNS Infections According to the Host 21Leroy R. Sharer, Catherine (Katy) Keohane, and Françoise Gray4 Clinical Approach to the Adult Patient with CNS Infection 29Michel Wolff, Romain Sonneville, and Tarek Sharshar5 Herpes Simplex Virus Infections of the CNS 43Bette K. Kleinschmidt‐DeMasters, Catherine (Katy) Keohane, and Françoise Gray6 Varicella‐Zoster Virus and Epstein‐Barr Virus Infections of the CNS 55Catherine (Katy) Keohane and Françoise Gray7 Cytomegalovirus Infections of the CNS 65Homa Adle‐Biassette and Natacha Teissier8 Adenovirus Meningoencephalitis 77Harry V. Vinters and Xinhai R. Zhang9 Polyomavirus Infections of the CNS 83Susan Morgello10 Measles Virus Infection of the CNS 95Catherine (Katy) Keohane, Leroy R. Sharer, and Françoise Gray11 Rubella Virus 105Bette K. Kleinschmidt‐DeMasters12 Henipavirus Encephalitis 113Kum Thong Wong and Kien Chai Ong13 Rabies 121Guilherme Dias de Melo, Perrine Parize, Grégory Jouvion, Laurent Dacheux, Fabrice Chrétien, and Hervé Bourhy14 Flaviviruses 1: General Introduction and Tick‐Borne Encephalitis 131Herbert Budka15 Flaviviruses 2: West Nile, St. Louis Encephalitis, Murray Valley Encephalitis, Yellow Fever, and Dengue 147Edward S. Johnson and Juan M. Bilbao16 Flaviviruses 3: Zika Virus Infection of the CNS 163Leila Chimelli17 Flaviviruses 4: Japanese Encephalitis 169Shankar Krishna Susarla, Anita Mahadevan, Bishan Radotra, Masaki Takao, and Kum Thong Wong18 CNS Disorders Caused by Hepatitis C and Hepatitis E Viruses 177Melissa Umphlett, Clare Bryce, and Susan Morgello19 Alphaviral Equine Encephalomyelitis (Eastern, Western, and Venezuelan) 183Kum Thong Wong20 Chikungunya Virus 189Cássia Shinotsuka, Michael Blatzer, Grégory Jouvion, and Fabrice Chrétien21 Poliovirus Infection and Postpolio Syndrome 195Catherine (Katy) Keohane, Leila Chimelli, and Aisling Ryan22 Enterovirus A71 Infection 205Kum Thong Wong, Kien Chai Ong, Thérèse Couderc, and Marc Lecuit23 Human Immunodeficiency Virus Infection of the CNS 215Françoise Gray and Leroy R. Sharer24 HTLV‐1 and Neurological‐Associated Disease 231Antoine Gessain, Olivier Cassar, and Philippe V. Afonso25 Parechovirus A 243Clayton A. Wiley26 Acute Disseminated Encephalomyelitis and Acute Hemorrhagic Leukoencephalomyelitis 251Romana Höftberger and Hans Lassmann27 Miscellaneous Inflammatory Disorders of the CNS of Possible Infectious Origin 259Mari Perez‐Rosendahl, Jamie Nakagiri, Xinhai R. Zhang, and Harry V. Vinters28 Mycoplasmal and Rickettsial Infections of the CNS 267Roy H. Rhodes29 Pathogenesis and Pathophysiology of Bacterial Infections of the CNS 279Loic Le Guennec and Sandrine Bourdoulous30 Pyogenic Infections of the CNS 1: Acute Bacterial Meningitis 295Loic Le Guennec and Sandrine Bourdoulous31 Pyogenic Infections of the CNS 2: (Brain Abscess, Subdural Abscess or Empyema, Epidural Abscess, Septic Embolism, and Suppurative Intracranial Phlebitis) 309Arnault Tauziede‐Espariat, Alexandre Roux, Megan Still, Marc Zanello, Gilles Zah‐Bi, Ghazi Hmeydia, Catherine Oppenheim, Michel Wolff, Johan Pallud, and Fabrice Chrétien32 Pyogenic Infections of the CNS 3: Following Neurosurgical Procedures 319Alexandre Roux, Megan Still, Marc Zanello, Gilles Zah‐Bi, Arnault Tauziede‐Espariat, Ghazi Hmeydia, Catherine Oppenheim, Michel Wolff, Fabrice Chrétien, and Johan Pallud33 CNS Involvement in Tropheryma whipplei Infection 331Emmanuèle Lechapt‐Zalcman34 Cerebral Actinomycosis 337Arnault Tauziede‐Espariat35 Cerebral Nocardiosis 343Arnault Tauziede‐Espariat and Leroy R. Sharer36 CNS Tuberculosis 349Michael A. Farrell, Eoin R. Feeney, and Jane B. Cryan37 Non‐Tuberculous Mycobacterial Infections 357Leroy R. Sharer38 Spirochetal Infections of the CNS 363Françoise Gray and Catherine (Katy) Keohane39 Neurobrucellosis 379Marine Le Dudal, Fabrice Chrétien, and Grégory Jouvion40 Legionellosis 383Edward S. Johnson41 Neurosarcoidosis 393Michael A. Farrell and Alan Beausang42 Hypertrophic Pachymeningitis 403Françoise Gray and Leroy R. Sharer43 Toxin‐Induced Neurological Diseases 411Pierre L. Goossens, Cédric Thépenier, and Michel R. Popoff44 Fungal Infections of the CNS 419Michael Blatzer, Fanny Lanternier, Jean‐Paul Latgé, Anne Beauvais, Stéphane Bretagne, Fabrice Chrétien, and Grégory Jouvion45 Cerebral Malaria 437Patrícia Reis, Vanessa Estato, and Hugo Caire de Castro Faria Neto46 Toxoplasma Infection of the CNS 449Stéphane Bretagne, Catherine (Katy) Keohane, and Homa Adle‐Biassette47 Other Protozoal Infections 463Leila Chimelli and Catherine (Katy) Keohane48 Helminth Infections of the CNS 475Marine Le Dudal, Stéphane Bretagne, David Hardy, Fabrice Chrétien, and Grégory JouvionAppendix: CASE EXAMPLE: Schistosoma mekongi Neuroschistosomiasis 500Edward S. Johnson49 Brain Myiasis 503Arnault Tauziede‐Espariat50 Emerging CNS Infections 505Kum Thong WongIndex 515