833 e2 virus and pigs for Nipah Human infection is acquired via expo sure to secretions from infected animals Outbreaks have occurred in Australia for Hendra virus; outbreaks of Nipah virus have oc cu[.]
833.e2 • eFig 67.9 Brain axial T2-weighted magnetic resonance image of Zika virus central nervous system infection showing right-sided white matter changes and cortical volume loss virus and pigs for Nipah Human infection is acquired via exposure to secretions from infected animals Outbreaks have occurred in Australia for Hendra virus; outbreaks of Nipah virus have occurred in Bangladesh, India, and Southeast Asia Mortality can be as high as 70% for both viruses.137 Rabies, while now rare in the United States, remains a significant public health issue in the developing world, primarily in Asia and Africa.142 Infection occurs via a bite from an infected animal, with the virus traveling from the bitten area to the CNS transsynaptically In the developing world, bites from stray canines are the primary source of infection Reservoirs for the virus in the United States are primarily bats and wild carnivorous mammals, such as raccoons, skunks, and foxes The incubation period for rabies is typically quite long (20–60 days) but can be as short as days or as long as months Prodromal symptoms include nonspecific fever, headache, weakness, and possibly discomfort/ tingling/itching to the site of the bite Confusion, agitation, and other signs of encephalitis progress to excessive salivation, pharyngeal spasm, and hydrophobia Once symptoms begin to manifest, the disease is nearly universally fatal and management is supportive Rabies is preventable with prompt postexposure administration of human rabies immunoglobulin.142 LCMV typically causes mild disease in humans and is caused by a rodent-borne arenavirus LCMV is transmitted via exposure to infected animal secretions or inhalation of aerosolized virus Human illness is biphasic, with an early nonspecific syndrome consistently presenting with fever, headache, myalgia, malaise, and lymphadenopathy, with or without a rash This is followed by a brief period of improvement, then development of CNS involvement (meningitis or encephalitis).143 Most influenza virus strains are not thought to be neurotropic; however, neurologic complications occur, more commonly with influenza A CNS involvement can be severe, with mortality 30%, and residual deficit noted in 30% to 40% The CSF in patients with influenza and neurologic symptoms typically does not demonstrate pleocytosis Additionally, the virus is rarely identified, either by CSF PCR or isolation Much of the CNS disease in these cases is thought to be secondary to host response Neurologic symptoms will follow the acute illness and can include • eFig 67.10 Brain coronal fluid-attenuation inversion recovery magnetic resonance image sequence of H1N1 influenza infection demonstrating acute necrotizing encephalopathy • eFig 67.11 Brain diffusion-weighted magnetic resonance image showing acute necrotizing encephalopathy in H1N1 central nervous system infection encephalopathy, seizure, ataxia, and focal neurologic deficits A more severe presentation, known as acute necrotizing encephalopathy, shows a characteristic pattern of bilateral, multifocal thalamic lesions on MRI that are often hemorrhagic in nature (eFigs 67.10 and 67.11) Though many of the cases of influenza-associated encephalopathy in children are in Asia and Australia, cases have been reported in Europe and North America.144–146 In addition to the infectious causes of encephalitis, autoimmune encephalitis—namely, anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis—is increasingly clinically relevant for the pediatric intensivist While first described in 2005 in women with ovarian teratomas, a recent 2017 review demonstrated an average age at diagnosis of 10 years.147 Clinically, anti-NMDAR encephalitis is described in three stages: (1) a prodromal stage suggestive of upper respiratory infection, including fever, nausea, and vomiting; (2) an early stage in which psychosis and seizures are prominent features; and (3) a hyperkinetic phase that includes increasing 833.e3 irritability/hyperactivity and deterioration of speech and language skills progressing to mutism, decreased responsiveness, and catatonia.148 Progression through the stages of disease takes weeks and presentation to medical attention is often with the appearance of seizures, which can be refractory to treatment, or psychotic features.149 The diagnosis is made by presence of antibodies directed against the NR1 subunit of the NMDAR on CSF analysis Neuroimaging is often normal but may show T2 intensity in the frontotemporal region, hippocampus, basal ganglia, brainstem, or spinal cord 833.e4 eTABLE Epidemiology, Clinical Features, Diagnosis, and Treatment of Selected Viral Causes of Encephalitis 67.4 Etiology Epidemiology Clinical Features/Diagnosis Treatment Adenoviridae Adenovirus Children and immunocompromised patients; sporadic Associated pneumonia Diagnosis: PCR of respiratory site, PCR of CSF or brain specimen Supportive Bunyaviridae La Crosse virus Mosquito vector; Midwestern and Eastern US; school-aged children Most cases subclinical; fatality rare; fulminant onset with seizure, paralysis, focal weakness Diagnosis: Serologic testinga and CSF IgM Supportive Flaviviridae Japanese encephalitis virus Mosquito vector; most common cause worldwide of epidemic encephalitis; Japan, China, Korea, Taiwan, Southeast Asia, India, Nepal, Northern Australia Seizures and parkinsonian features common; acute flaccid paralysis; case fatality rate 20%–30% Diagnosis: Serologic testinga and CSF IgM and antigen Supportive Powassan virus Tick vector; New England states, Canada, Asia Case fatality rate 10%–15%; focal findings in 50% of patients Diagnosis: Serologic testinga and CSF IgM Supportive St Louis encephalitis virus Mosquito vector; North America (endemic in western US, large periodic outbreaks in eastern US), Central and South America; adults 50 y Most severe in elderly; tremors, seizure, headache, nausea, vomiting, stupor, paresis; urinary symptoms may be early features; SIADH; case fatality rate 3%–30% Diagnosis: Serologic testinga and CSF IgM Supportive; consider IFN-a2b West Nile virus Mosquito vector; North and Central America, Africa, parts of Asia, Middle East, and southern Europe; increased incidence in age 50 y and immunocompromised Abrupt-onset fever, headache, neck stiffness and vomiting; meningitis, encephalitis, or acute flaccid paralysis Diagnosis: Serologic testing,a CSF IgM and CSF PCR Supportive Herpesviridae Cytomegalovirus (CMV) Immunocompromised patients; rare in immunocompetent; congenital infection in 1% of neonates Evidence of widespread CMV disease (e.g., retinitis, pneumonitis, adrenalitis, myelitis, polyradiculopathy) Diagnosis: CSF PCR Ganciclovir plus foscarnet Epstein-Barr virus (EBV) Exposure to saliva from those with asymptomatic shedding Seizure, coma, personality changes, cerebellar ataxia, cranial nerve palsies; transverse myelitis Diagnosis: Serologic testing and CSF PCR (may be false positive) Supportive; consider corticosteroids; acyclovir not recommended Herpes simplex virus (HSV-1 and HSV-2) 5%–10% of all cases; one of the most common causes of identified sporadic encephalitis worldwide; all age groups; all seasons; HSV-1 more common in adults; HSV-2 more common in neonates Fever, hemicranial headache, language and behavioral abnormalities, memory impairment, seizures; less commonly, a brainstem syndrome; SIADH Diagnosis: CSF PCR; bilateral temporal lobe involvement on MRI nearly pathognomonic Acyclovir; foscarnet in acyclovir resistant Human Herpes virus-6 (HHV-6) Immunocompromised (reactivation), particularly in transplant recipients; role in immunocompetent hosts unclear; no seasonal predilection Recent exanthem; seizures Diagnosis: Serologic testing, culture, CSF PCR Ganciclovir or foscarnet in immunocompromised; weaker evidence for use in immunocompetent Varicella zoster virus (VZV) All age groups, but highest incidence in adults; all seasons; recrudescent disease (herpes zoster) seen in immunocompetent persons but more often in immunocompromised; can occur in patients without rash, especially if immunocompromised Primary cerebellar involvement in children, usually self-limited or severe encephalitis; delirium common; seizure unusual; vasculitis reported; reactivation leads to encephalitis with focal neurologic deficits and seizures; large-vessel granulomatous arteritis presents with delayed contralateral hemiplegia weeks to months after reactivation in the ophthalmic division of the trigeminal nerve (herpes zoster ophthalmicus) Diagnosis: DFA of skin lesion; serum IgM for primary varicella, CSF PCR, CSF IgM Acyclovir; ganciclovir; foscarnet (acyclovir resistant); consider corticosteroids 833.e5 eTABLE Epidemiology, Clinical Features, Diagnosis, and Treatment of Selected Viral Causes of Encephalitis—cont’d 67.4 Etiology Epidemiology Clinical Features/Diagnosis Treatment Orthomyxoviridae Influenza virus Worldwide; sporadic; rare cause of encephalitis; often affects children; Reye syndrome (now uncommon) Prior or concomitant respiratory tract symptoms; may be associated with bilateral thalamic necrosis (ANE) Diagnosis: Antigen detection and PCR of respiratory tract specimen Oseltamivir Paramyxoviridae Hendra virus Australia; natural host, fruit bats; horses infected from secretions of bats, humans infected from body fluids/ excretions from horses Fever, drowsiness, seizures, and coma accompanying severe flulike illness Diagnosis: Contact Special Pathogens Branch at CDC Supportive Measles virus Unvaccinated children and adults; worldwide; sporadic; measles inclusion body encephalitis within 1–6 mo; SSPE has variable incubation, most cases seen 4–8 y after primary infection (most important risk factor is acquisition of measles before yo) Decline of consciousness; focal neurologic signs and seizures are common; SSPE has insidious onset, with subtle personality changes and declining intellectual performance progressing to mental deterioration, seizures, myoclonic jerks, motor signs, coma, and death Diagnosis: Serologic testing,a viral culture of nasopharynx and urine, PCR of nasopharynx, urine, CSF Ribavirin (investigational for life-threatening disease); intrathecal ribavirin for SSPE Mumps virus Unvaccinated persons Previous parotitis (50%); headaches and vomiting, seizures, altered consciousness; sensorineural hearing loss Diagnosis: Serologic testing,a culture of saliva specimens, CSF culture/PCR Supportive Nipah virus Close exposure to infected pigs; bat reservoir; exposure to infected bats or bat roosting sites; close contact exposure to infected humans; South Asia Fever, headache, altered mental status, dizziness and vomiting; myoclonus, dystonia, areflexia, and hypotonia; pneumonitis Diagnosis: Serologic testing,a CSF culture, Contact Special Pathogens Branch at CDC Supportive; consider ribavirin Picornaviridae Nonpolio enteroviruses Echoviruses, coxsackieviruses, and enterovirus 71 and various other numbered enteroviruses; peak incidence late summer–early fall; worldwide distribution Aseptic meningitis more common than encephalitis; severe illness in neonates; syndrome of chronic enteroviral meningoencephalitis in agammaglobulinemia (rare); enterovirus 71 outbreak in children with rhombencephalitis (myoclonus, tremors, ataxia, cranial nerve deficits) Diagnosis: Stool and throat culture/PCR, CSF PCR Supportive; IVIG for chronic and/or severe disease Poliovirus Principally in infants; Africa and Asia; unvaccinated in developed countries; fecal-oral spread; related to administration of oral vaccine Disturbances in consciousness, seizures; flaccid paralysis Diagnosis: Serologic testing,a throat and stool culture/PCR, CSF PCR Supportive Retroviridae Human immunodeficiency virus (HIV) Risk factors for HIV infection; worldwide Acute encephalopathy with seroconversion; most commonly presents as HIV dementia (forgetfulness, loss of concentration, cognitive dysfunction, psychomotor retardation) Diagnosis: HIV serologic testing, HIV RNA (viral load), CSF PCR HAART Rhabdoviridae Rabies virus Transmitted by bite of infected animal; may be transmitted after unrecognized bite from bat; organ donation (few recognized cases); rare and sporadic in the US, but worldwide in distribution (50,000–100,000 deaths annually) Furious form (most common): agitation, hydrophobia, bizarre behavior, and delirium progressing to disorientation, stupor, and coma Paralytic form: ascending paralysis and later cerebral involvement Diagnosis: Serum antibodies in unvaccinated patients,a culture and PCR of saliva specimens, immunofluorescent detection of viral antigen in nuchal biopsy, CSF antibodies in unvaccinated patients, CSF PCR, antigen detection and histopathologic examination of brain biopsy (Negri bodies) Supportive; postexposure prophylaxis with rabies immunoglobulin and vaccine (ineffective after onset of disease) Continued 833.e6 eTABLE Epidemiology, Clinical Features, Diagnosis, and Treatment of Selected Viral Causes of Encephalitis—cont’d 67.4 Etiology Epidemiology Clinical Features/Diagnosis Treatment Togaviridae Eastern equine encephalitis virus Mosquito vector; North America (especially Atlantic and Gulf states), Central and South America (uncommon); mainly affects children and elderly; sporadic Most infections presumed to be subclinical; abrupt onset with fulminant course; seizures common; headache, altered consciousness; case fatality rate 50%–70% with high frequency of sequelae among survivors Diagnosis: Serologic testing,a culture or antigen detection in brain Supportive Rubella virus More common in adults; unvaccinated Rash followed within 1–6 d by headache, dizziness, behavioral abnormalities; seizures Diagnosis: Serologic testing,a CSF IgM Supportive Western equine encephalitis virus Mosquito vector; North America (west of the Mississippi and in prairie provinces in Canada); Central and South America; mainly affects children and adults 50 yo; epidemic, but no human cases in US since 1994 Most infections presumed to be subclinical; headache, altered consciousness, seizures; case fatality rate ,5% Diagnosis: Serologic testinga with detection of IgM in serum, CSF IgM; viral antigen detection in brain Supportive a A 4-fold increase in convalescent-phase IgG antibody titers may be necessary to establish the diagnosis ANE, Acute necrotizing encephalopathy; CDC, Centers for Disease Control and Prevention; CSF, cerebrospinal fluid; DFA, direct fluorescent antibody; HAART, highly active antiretroviral therapy; IgG, immunoglobulin G; IgM, immunoglobulin M; IFN-a2b, interferon-a2b; IVIG, intravenous immunoglobulin; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; RNA, ribonucleic acid; SIADH, syndrome of inappropriate antidiuretic hormone secretion; SSPE, subacute sclerosing panencephalitis ... virus Unvaccinated children and adults; worldwide; sporadic; measles inclusion body encephalitis within 1–6 mo; SSPE has variable incubation, most cases seen 4–8 y after primary infection (most important... detection in brain Supportive Rubella virus More common in adults; unvaccinated Rash followed within 1–6 d by headache, dizziness, behavioral abnormalities; seizures Diagnosis: Serologic testing,a