830 SECTION VI Pediatric Critical Care Neurologic Drainage of the abscess fluid is typically the initial approach to patient management Material obtained by surgery or aspiration should be sent for ae[.]
830 S E C T I O N V I Pediatric Critical Care: Neurologic • Fig 67.5 Axial diffusion-weighted magnetic resonance image of brain showing abscess in right frontal lobe • Fig 67.6 Axial magnetic resonance image apparent diffusion coefficient image of right frontal brain abscess showing hypointensity characteristic of cerebral abscess Drainage of the abscess fluid is typically the initial approach to patient management Material obtained by surgery or aspiration should be sent for aerobic, anaerobic, mycobacterial, and fungal cultures Additional workup of a patient with a CNS abscess should include echocardiography to rule out endocarditis or underlying congenital heart disease; chest radiograph to identify lung infections; and evaluation of ear, nose, throat, and teeth for foci of infection (sinusitis, mastoiditis, tooth abscess) Blood cultures can be helpful in a small percentage of patients, especially in those in whom the abscess is thought to result from hematogenous spread If blood cultures are positive, identification of underlying foci should be a priority Lumbar puncture to obtain CSF may be contraindicated in a patient with a brain abscess as raised ICP may lead to brainstem herniation in these patients Additionally, CSF culture does not contribute significantly to the identification of the organism The microorganisms cultured from the brain abscess are variable and often depend on the original source Sterile cultures are seen in up to one-third of patients regardless of prior antibiotic exposure When a pathogen is isolated, it is most frequently a single organism Streptococci (both aerobic and anaerobic) are the most common organisms cultured from abscess fluid, followed by S aureus and gram-negative anaerobic bacilli When cultured, anaerobes are typically members of the oropharyngeal flora and often associated with sinus infections or tooth abscesses Citrobacter and Enterobacter sakazakii are frequently associated with brain abscesses in neonates Mixed aerobic and anaerobic flora are less commonly isolated but often associated with children who have chronic otitis and sinusitis.105 The most important cause of brain abscess in patients with HIV is Toxoplasma gondii, which typically present with multiple small abscesses Other causes of HIV-related brain abscesses include Nocardia species and M tuberculosis.106 Patients who receive immunosuppression following solid-organ or hematopoietic stem-cell transplantation, or chemotherapy, are at risk for fungal abscesses due to Aspergillus, Candida, or Mucorales species Treatment of brain abscesses involves a multidisciplinary approach Neurosurgery, radiology, and infectious disease involvement in the ICU management is recommended The therapeutic approach to brain abscesses should consider the neurologic status of the patient, location of the abscess, number and size of the abscesses, and the stage of abscess formation Obtaining material for culture is often important This can often be accomplished with stereotactic CT-guided needle aspiration Even in the critically ill ICU patient, a stereotactic CT-guided aspiration of the abscess is minimally invasive and the risk-benefit profile typically supports its use Aspiration of the abscess allows both removal of infected nidus and likely identification of the causative organism Excision of the abscess may also be considered Excision of the abscess cavity may be useful when it is located in a periventricular or posterior fossa distribution, is loculated, or contains a foreign body Excision should also be considered for abscesses that enlarge after weeks of antibiotic therapy or that fail to shrink after to weeks of antibiotics.107 Primary excision may be the procedure of choice for lesions located in the cerebellum One study reported a lower mortality, decreased development of obstructive hydrocephalus, and shorter hospital stay if primary excision was chosen over stereotactic aspiration.108 A 2016 meta-analysis comparing resection to aspiration showed that patients undergoing resection of superficial abscesses in nonvital areas of the brain had a lower rate of reoperation, a higher rate of postoperative abscess clearance, and better neurologic improvement after month However, there were no differences in mortality or long-term neurologic recovery.109 There are few indications for the nonoperative management of brain abscesses These include patients with surgically inaccessible lesions, early cerebritis, multiple small abscesses, or medical comorbidities that would classify the patient as high risk Antibiotic management alone may be considered in abscesses smaller than 2.5 cm or when multiple small abscesses are present.105,110 Long-term antimicrobial therapy is the mainstay of treatment and should not be delayed A combination of a third- or fourthgeneration cephalosporin, vancomycin, and metronidazole is a reasonable choice for initial antibiotic therapy in brain abscesses There are no prospective studies in children to guide antibiotic therapy Duration of treatment is typically based on clinical response Duration can be as short as to weeks in surgically drained abscesses and up to weeks for those managed by antibiotics alone.103,111 Mortality attributed to brain abscess was 60% before 1970 Since the advent of newer radiologic procedures, such has CHAPTER 67 Central Nervous System Infections and Related Conditions high-resolution head CT or MRI, detection of brain abscesses is more efficient With earlier detection, mortality has dropped to 4% to 12% in children and 8% to 25% in adults.89,112 Long-term neurologic morbidity attributed to the abscess and therapy ranges from 10% to 30% depending on both size and location of the lesion as well as response to therapy.100 Brain abscesses resulting from a contiguous focus of infection and those developing after a traumatic injury tend to have a better prognosis Poorer prognosis is associated with delayed diagnosis, immunocompromised status, rupture of the abscess into the ventricular space, fungal etiology, and pretreatment neurologic compromise Viral Meningoencephalitis Viral meningoencephalitis is a common neurologic problem for the PICU Due to the effectiveness of vaccines and subsequent decline in acute bacterial meningitis, viral encephalitis may soon be the most prevalent CNS infection encountered in the PICU Presenting signs and symptoms are often indistinguishable from bacterial meningitis A key distinguishing factor between meningitis and encephalitis is the presence or absence of neurologic dysfunction Meningitis implies that the meninges are primarily involved Patients typically have fever, meningeal signs, CSF pleocytosis, and no associated neurologic dysfunction unless related to seizures or elevated ICP Encephalitis involves the brain parenchyma; therefore, focal neurologic signs, cranial nerve deficits, motor and sensory deficits, difficulties with speech, changes in mental status, and seizures are more common Morbidity and mortality rates from CNS infections not necessarily decrease if the etiology is viral versus bacterial Given the difficulty discerning between meningitis and encephalitis, some prefer to use the term “meningoencephalitis.” This better describes those patients who present with evidence of both meningeal and parenchymal involvement Epidemiology A review of the Nationwide Inpatient Sample from 1998 to 2010 reported the overall US hospitalization rate for encephalitis at about per 100,000 The average hospital length of stay was 11.2 days, and a fatal outcome occurred in 5.8% of hospitalizations This was three times higher than the mortality rate for all inpatient stays during the same study period.113,114 Children under the age of year had the second highest risk for hospitalization due to encephalitis, behind elderly patients However, they were most likely to be admitted with a known cause of encephalitis given the high prevalence of viral etiologies in this age group Although a definitive cause can be elusive in patients with encephalitis, most identifiable cases are viral in origin with enteroviruses, herpesviruses, and arboviruses causing the greatest burden of disease in children.113,114 Pathophysiology/Pathogenesis of Viral Meningoencephalitis Viral meningoencephalitis often begins with replication of the virus at the mucosal surfaces of the skin, gastrointestinal tract, or respiratory tract Extension into the CNS occurs by several mechanisms: (1) direct invasion across cerebral capillary endothelial cells of the blood-brain barrier, (2) direct infection of cerebral microvascular endothelial cells before infection of adjacent glia and neurons, (3) direct transportation through a disrupted 831 blood-brain barrier via infected leukocytes, (4) primary glial infection without evidence of adjacent endothelial infection, (5) choroid plexus epithelial invasion, or (6) spread along neural pathways.115 Once within the CNS, viruses attack susceptible neurons or glial cells and induce cellular and inflammatory processes that manifest as meningitis and/or encephalitis Clinical Evaluation A comprehensive approach to an encephalopathic child should entertain all potential causes, both infectious and noninfectious, given the significant overlap between presenting symptoms In addition to bacterial and viral meningoencephalitis, trauma, hepatic failure, metabolic derangements, and toxins need to be considered A thorough history will help guide subsequent testing and management This should include immunization status, recent infections, history of immune disorders, recent travel, season of the year, tick or mosquito exposure, and history of maternal infection for neonates In addition to a complete neurologic exam with fundoscopy, a directed physical exam should focus on skin and mucous membranes to evaluate for signs of trauma or portal of entry for infection Care should also be taken to evaluate the other organ systems—respiratory and cardiovascular—as additional support in the acute setting may be required Serial neurologic examinations are a must in the encephalopathic patient in order to remain vigilant for the development of cerebral edema and herniation In all cases of suspected meningoencephalitis, antibiotic and/or antiviral medication should not be delayed by laboratory testing or imaging Laboratory Manifestations Obtaining CSF for testing is essential when considering a diagnosis of meningoencephalitis Children presenting with signs concerning for elevated ICP or mass lesion (papilledema, pupillary abnormalities, focal neurologic exam findings, and so on) may warrant neuroimaging prior to lumbar puncture If imaging reveals evidence of increased ICP or mass lesion, lumbar puncture should be delayed until these have been managed appropriately Evaluation of CSF should, at a minimum, include cell count, protein, glucose, and bacterial culture with Gram stain Opening pressure should be obtained when feasible.116 Pleocytosis in the 10 to 200 cells/mL range are usually seen in viral encephalitis Early in infection, CSF differential may show polymorphonuclear cell predominance, with mononuclear cells being more common later in the course CSF protein is usually at least mildly elevated and glucose is often normal or minimally decreased.117 Increased CSF RBC count may indicate a traumatic tap; however, this can also be seen in herpesvirus CNS infections Blood should also be obtained for routine laboratory studies (complete blood count, electrolyte panels, and transaminases), markers of inflammation (erythrocyte sedimentation rate, C-reactive protein) and bacterial culture Additional testing of CSF, serum, and/or other body fluid may be indicated based on history Molecular diagnostic methods have become widely available for many neurotropic organisms and have become the test of choice for several viruses, including enteroviruses and herpes simplex virus (HSV).117 Likewise, PCR is the most available and studied method of detecting human herpesvirus (HHV-6), a common etiology of encephalitis in immunocompromised children, especially following allogenic hematopoietic cell transplant.118 Multiplex PCR technology can simultaneously test for 832 S E C T I O N V I Pediatric Critical Care: Neurologic numerous pathogens (viral, bacterial, and fungal) from a single sample with a faster turnaround time than conventional microbiological methods and with relatively high sensitivity and specificity.119,120 However, multiplex panels may show decreased sensitivity when compared with individual assays of their component targets.121 Despite the increasing popularity of multiplex PCR testing for numerous viral pathogens, arbovirus infections remain best identified by CSF and serum immunoglobulins G and M antibody testing.117 Many states offer surveillance programs for arboviral infections These programs, in addition to local health departments and the CDC, can provide guidance related to specific serologic testing Though not often performed, brain biopsy remains the gold standard for definitive diagnosis of CNS viral infection and should be considered in severe cases when no clear etiology is identified Neuroimaging Many patients presenting with meningoencephalitis will receive a noncontrasted head CT as part of their initial workup because of the clinical overlap between infectious and noninfectious causes of encephalopathy Much of the time, this initial study may be helpful only in ruling out large mass lesions or intracranial hemorrhage In severe or late presentations, initial CT may demonstrate cerebral edema or more worrisome evidence of uncal or transtentorial herniation Brain MRI is a more sensitive study to detect regional or diffuse inflammation and edema; therefore, it is the preferred neuroimaging modality in evaluating meningoencephalitis Standard protocol should include T1 and T2 spin-echo sequences as well as fluid-attenuation inversion recovery (FLAIR) sequence for detection of subtle early changes.122 Exam findings suspicious for brainstem or spinal cord involvement should prompt inclusion of the spine in MRI investigation Certain infections can show specific patterns on MRI, potentially guiding treatment prior to confirmatory molecular or microbiological diagnosis In general, viral encephalitis will show T2 and FLAIR hyperintensity with gadolinium enhancement that is diffuse, multifocal, or with areas of confluence Inflammation is often shown involving the meninges and causing edema Hemorrhage and mass effect may also be present HSV and HHV-6 infections often include bilateral hemorrhagic inflammation of the temporal lobes, typically sparing the basal ganglia (Figs 67.7 and 67.8).123,124 Neonates with HSV infection often show more widespread MRI findings, with involvement of the periventricular white matter.125 CNS infection by varicella zoster virus (VZV) causes a cerebral vasculopathy involving large and/or small arteries and can result in multifocal ischemic lesions varying in size and location depending on the size of vessel involved High-resolution sequences are capable of showing vessel wall enhancement and arterial stenosis in large artery disease.126 Myelitis is also a common finding with VZV, with hemorrhage less commonly seen.127 Cytomegalovirus (CMV) typically shows T2 hyperintensity and contrast enhancement of the ependyma of the lateral ventricles consistent with ventriculitis but may require utilization of DWI sequences.128 Several mosquito-borne viruses—including West Nile, St Louis encephalitis, Japanese encephalitis, and Eastern and Western equine encephalitis—demonstrate T2 signal intensities in the subcortical white matter and deeper structures of the thalamus, basal ganglia, substantia nigra, pons, and midbrain.123 Encephalitis secondary to enterovirus does not necessarily have a consistent pattern of MRI findings However, subtype Enterovirus 71 has demonstrated a predilection for brainstem and spinal • Fig 67.7 Brain axial T2-weighted magnetic resonance image of herpes simplex virus encephalitis • Fig 67.8 Brain axial fluid-attenuation inversion recovery magnetic reso- nance image sequence of herpes simplex virus encephalitis showing asymmetric temporal lobe tropism cord involvement with T2 and FLAIR signal intensity with or without restricted diffusion in the midbrain, pons, medulla, and dentate nucleus of the cerebellum and a relative lack of involvement of supratentorial structures.129,130 Clinical Presentation and Course Viral meningitis, encephalitis, and meningoencephalitis can all present with prodromal symptoms of fever, headache, malaise, irritability, nausea, vomiting, and possibly neck stiffness or pain Rashes may also be present and can provide clues suggesting etiologic organism In addition to irritability, children with encephalitis show a significant decline in their mental status ranging from confusion or aphasia to coma Other neurologic signs can include focal motor/sensory deficits, pupillary abnormalities and visual changes, ataxia, hemiparesis, and seizures.131 Autonomic dysfunction, diabetes insipidus, and syndrome of inappropriate antidiuretic hormone secretion (SIADH) can also develop in the setting CHAPTER 67 Central Nervous System Infections and Related Conditions of viral encephalitis.129,132 Their presence and course are variable and can range from relatively mild disease with complete recovery to long-term neurologic morbidity or death HSV continues to be the most commonly identified and most likely fatal cause of viral encephalitis in children and adults.113,114 It also remains one of the few viral causes of encephalitis with specific antiviral therapy, making early identification and treatment paramount to optimizing outcome Presentation can vary from hypothermia, poor feeding, and lethargy in neonates to nonspecific neurologic findings and altered mental status in older children and adolescents Seizures are common with CNS HSV infection in the neonate but can occur in all age groups A recent cross-sectional study of North American pediatric emergency department visits showed the median age of HSV infection at any site (skin-eye-mucosa, CNS, or disseminated) at 14 days.133 Skin lesions are commonly present at presentation; however, absence of characteristic vesicular lesions does not rule out HSV infection In neonates, HSV-2 causes the majority of encephalitis cases with transmission related to shedding of virus in the maternal genital tract during either primary infection or recrudescence.124 Older children and adults primarily have HSV-1 infection CNS HSV disease may demonstrate characteristic temporal lobe findings on MRI and the electroencephalogram (EEG) will frequently demonstrate periodic epileptiform spike and slow-wave discharges corresponding to injury of that area.123,124 Factors associated with increased morbidity and mortality from HSV include disseminated disease (mortality rate up to 50%) and delayed diagnosis/ treatment.124 Along with herpesviruses, enteroviruses are another major cause of CNS viral infection in children Presentation is variable but often involves fever, nausea, vomiting, headache, irritability, and malaise Unlike HSV, enteroviruses generally not have characteristic findings on MRI or EEG The majority of cases are relatively mild; however, hospitalization is frequently required for more severe presentations that involve significant alterations in mental status.134 While many viral causes of encephalitis not have a particular seasonal predilection, enteroviruses and arboviruses are seen most frequently in summer and autumn Detailed discussion of Enterovirus 71, parechovirus, arbovirus, zoonotic virus, influenza, and autoimmune causes of meningoencephalitis can be found on ExpertConsult.com Treatment Specific antiviral treatment regimens are outlined in eTable 67.4 Unfortunately, with the exception of the herpesviruses HSV and VZV, the vast majority of viral causes of encephalitis have no definitive antiviral therapy and management is mostly symptomatic and supportive As in other diseases in which neurologic dysfunction and seizures can be severe and refractory, patients may require intubation for airway protection and mechanical ventilation The need for cardiovascular support, ranging from volume resuscitation in systemic inflammatory response syndrome to mechanical circulatory support in myocarditis, is not uncommon given that systemic infection with nonneurologic manifestations commonly occurs with many of these viruses Some clinical syndromes may also have profound autonomic dysfunction that can have significant effects on hemodynamics Seizures, both convulsive and subclinical, are frequent and can require active surveillance with continuous EEG as well as aggressive use of anticonvulsant medications Refractory status epilepticus in the setting of viral encephalitis has been associated with poor 833 outcomes and prognosis.150,151 Electrolyte abnormalities from SIADH, diabetes insipidus, and cerebral salt wasting can all occur as a complication of CNS infection, requiring meticulous fluid management and electrolyte monitoring In some cases with related intracranial hypertension, ICP monitor use is described.152 Therapies directed at lowering ICP—including hyperosmolar therapy, CSF diversion, and decompressive craniectomy—have not demonstrated consistent results in children with viral encephalitis.152,153 Antiviral medication is indicated in treatment of HSV encephalitis Acyclovir is the standard therapy The current recommended treatment is IV acyclovir (20 mg/kg every hours) given for 21 days for both encephalitis and disseminated HSV in patients younger than months For patients between months and 12 years of age, recommended dosing is 10 to 15 mg/kg per dose every hours Those older than 12 years should receive acyclovir at 30 mg/kg per day in three divided doses for 21 days Acyclovirresistant HSV infections have been reported and should be treated with foscarnet.154 Acyclovir is also used in VZV encephalitis However, the window of opportunity to affect the course may be brief Infants born to mothers who contract primary VZV infection within days prior to delivery to days after delivery are at increased risk for severe varicella CNS disease Exposed newborns may be candidates for acyclovir and VZV-specific immunoglobulin prophylaxis (VariZIG) Data are limited, but the recommended course of acyclovir for neonates with clinical signs of varicella is the same as that for HSV IV acyclovir therapy is also recommended for other pediatric patients with varicella encephalitis Children with varicella should not receive salicylates owing to the increased risk for Reye syndrome, and those on chronic salicylate therapy for other conditions should have their salicylate stopped Like HSV, acyclovir-resistant varicella has been treated with foscarnet.154 Treatment for enteroviral CNS infections is largely supportive Anecdotal evidence may support use of IV immunoglobulin (IVIG) and/or high-dose steroids with Enterovirus 71 CNS disease.129,135 Several different groups are working on preventive enteroviral vaccines.155 Encephalitis secondary to HHV-6 in the immunocompromised and transplant patient populations may be caused by either a primary infection or reactivation Serology is considered unreliable, particularly in immunocompromised patients, and diagnosis should be made via PCR Foscarnet and/or ganciclovir at high doses are recommended first-line therapies.118 CMV, typically a cause of encephalitis in immunocompromised patients and particularly fatal in HIV disease, has been treated with ganciclovir and foscarnet, though with limited success.137,154 Influenza encephalitis is likely related more to host response than to systemic infection As it is not a true CNS infection, it is unclear whether the neuraminidase inhibitor oseltamivir or the ion channel blocker amantadine will change either course or outcome Nevertheless, these medications are commonly given to patients despite limited data supporting their use Therapy for anti-NMDAR encephalitis should start once clinical suspicion is raised and laboratory testing has been obtained, as outcomes may be improved with earlier treatment Several studies demonstrate that symptom severity correlates with antibody titer and decreases in antibody titer are associated with clinical improvement.149 First-line therapies include high-dose steroids, IVIG, and therapeutic plasma exchange, with use of rituximab, cyclophosphamide, and—rarely—electroconvulsive therapy in refractory cases For those patients with tumor-associated 833.e1 Enterovirus 71, Parechovirus, Arbovirus, Zoonotic Virus, Influenza, and Autoimmune Causes of Meningoencephalitis Enterovirus 71 (EV71), a common cause of hand-foot-andmouth disease (HFMD) in children, typically causes fever and flulike symptoms with the characteristic oral ulcers and erythematous rash to hands, feet, and buttocks Neurologic manifestations— including meningitis, acute flaccid myelitis, and potentially fatal brainstem encephalitis—can occur in a small proportion of patients.129 Cardiovascular complications, including myocarditis and heart failure, are also reported EV71 has been linked to outbreaks in Asia, Australia, Europe, and the United States, and is gaining more attention worldwide given the severity of presentation and significant long-term morbidity and mortality In a recent study, the clinical characteristics and outcomes were described in 61 children with EV71 neurologic disease during a 2013 outbreak Four patients died within hours of presentation related to cardiopulmonary collapse Of the remaining, 40% had encephalomyelitis, 35% brainstem encephalitis, 11% encephalitis, and 7% each with acute flaccid myelitis and autonomic dysregulation with pulmonary edema The most common presenting symptoms were fever (100%), myoclonus (86%), ataxia (54%), and emesis (54%) Other presenting neurologic symptoms included limb and/or truncal weakness (40% each) with less than 30% of patients presenting with urinary retention, seizure, autonomic dysfunction, or cranial nerve deficits.129 Long-term sequelae are common, with 10% of the patients demonstrating residual abnormalities at 12-month follow-up In addition to residual motor deficits, developmental and cognitive outcomes are also poorer in children with EV71 brainstem encephalitis when associated with cardiopulmonary failure The 2011 WHO guidelines on HFMD specifically address EV71 neurologic disease and recommend collecting throat, vesicle (if available), and stool/rectal swabs for PCR diagnosis to increase yield as CSF positivity is usually low.135 Diagnostic findings in the Australia outbreak similarly showed the highest positivity rates in feces/rectal swabs (95%) and throat swabs (85%), with yields much lower in CSF (24%) Those with encephalitis were more likely to have a positive CSF PCR.129 A total of 63% of the Australian cohort, not just those with encephalitis, demonstrated characteristic inflammation in the dorsal brainstem and dentate nuclei of the cerebellum on FLAIR and T2-weighted sequences and approximately 80% had abnormal spine MRI with involvement of the anterior horns or nerve roots Human parechovirus type (HPeV3), a member of the Picornaviridae family, is increasingly associated with CNS disease, especially in the young infant population.136 Like enteroviruses, HPeV3 seems to have a summer-autumn seasonality with outbreaks occurring approximately every other year Clinical presentation is typically indistinguishable from other viral causes of encephalitis It can cause a severe, sepsis-like picture with components of coagulopathy, hepatopathy, and/or myocarditis Seizure can also be a presenting symptom and difficult to control CSF pleocytosis is not a common finding in HPeV3 CNS infection; however, protein levels may be mildly elevated On MRI, inflammatory subcortical white matter changes can be seen and are more common in those infants who have seizure as part of their clinical course.136 Neuroinvasive arboviruses are a large group of arthropod vectorborne viruses that display diagnostically significant geographic distribution and seasonal variation depending on vector (mosquito or tick) activity, often peaking in summer months In North America, the most common are West Nile virus, the California serogroup, La Crosse encephalitis virus, Eastern and Western equine viruses, St Louis encephalitis virus, and Powassan and Jamestown Canyon viruses Outside North America, Japanese encephalitis virus is the most common cause of arboviral encephalitis, occurring primarily in southern and eastern Asia Dengue, Chikungunya and Zika viruses are found typically in Central and South America, Central Africa, Southeast Asia, and India.137 In addition to meningoencephalitis, these viruses can also less commonly affect the anterior horn cells of the spinal cord or peripheral nerves, presenting as acute flaccid paralysis Neurologic symptoms, ranging from altered mental status to acute flaccid paralysis or coma, can follow a flulike prodrome West Nile virus is known to preferentially affect the brainstem, with resultant early presentation of coma MRI often depicts involvement of the deep gray structures (basal ganglia and thalamus) and cerebellum, making movement disorders a common long-term morbidity.138 Arboviral diseases are reportable conditions According to the most recent published review from ArboNET (the national arbovirus surveillance system), there were 1200 cases of neuroinvasive (encephalitis, meningitis, or acute flaccid paralysis) arboviral infection in children, including 22 deaths, from 2003 to 2012 La Crosse virus was the most common arboviral cause of neuroinvasive disease in children (50% of reported cases) The highest pediatric case fatality rate was seen in eastern equine encephalitis (10 deaths in 30 cases) West Nile was reported throughout the United States while La Crosse was primarily confined to regions around the Appalachian Mountains (Ohio, West Virginia, Tennessee, and North Carolina) Eastern equine encephalitis is noted mostly in the Atlantic and Gulf Coast areas.139 Zika virus has emerged as a clinically significant pathogen in North America, primarily because of the devastating effects that congenital and perinatal infections can have on the fetus and newborn In addition to transmission via its arthropod vector (Aedes species mosquitos), Zika virus can also be transmitted from human to human sexually, via blood transfusions, or from mother to newborn across the placenta Nonperinatal infections appear to be relatively mild, consisting of nonspecific symptoms of rash, fever, arthralgia, and conjunctivitis The CDC recently published a series of 141 postnatally acquired Zika virus infections in children up to 18 years of age None of the reported cases had neurologic signs or symptoms as part of their disease.140 This is in stark contrast to the significant neurologic sequelae seen in congenital and perinatal infection One Brazilian study reported on 102 infants who were microcephalic at birth and born to mothers with evidence of Zika virus infection within the first two trimesters These infants all had brain abnormalities noted on neuroimaging, including cerebral atrophy, ventriculomegaly, cortical malformation, and cortical/subcortical calcifications (eFig 67.9) Greater than 90% of these patients had hypertonia and neurodevelopmental delay, and more than 50% had EEG evidence of seizure activity Visual and hearing impairments were also seen in nearly 20% of the patients.141 Other zoonoses known to cause encephalitis include rabies, Hendra virus, Nipah virus, and lymphocytic choriomeningitis virus (LCMV) Tick exposure may suggest infection with Colorado tick fever virus or nonviral etiologies such as Lyme disease or Rocky Mountain Spotted Fever Bats serve as the reservoir for both Hendra and Nipah viruses; both are rare causes of encephalitis in humans Horses serve as an intermediate vector for Hendra ... discerning between meningitis and encephalitis, some prefer to use the term “meningoencephalitis.” This better describes those patients who present with evidence of both meningeal and parenchymal... hospital length of stay was 11.2 days, and a fatal outcome occurred in 5.8% of hospitalizations This was three times higher than the mortality rate for all inpatient stays during the same study... be admitted with a known cause of encephalitis given the high prevalence of viral etiologies in this age group Although a definitive cause can be elusive in patients with encephalitis, most identifiable