This is a healthy 11 year old male who is taken to his PMD for persistent headaches for the last 4 days despite treatment with acetaminophen and ibuprofen at home. He has had intermittent emesis and tactile fever for the last three days and has had minimal oral intake over the last 36 hours. There was no history of trauma, but he has had recent URI symptoms 2 weeks ago. After evaluation by his PMD, he is sent to the lab for tests when his mother notes that he is more sleepy and unresponsive. While going to the lab for tests, he develops shaking movements on the left side of his body. 911 is called and he is taken to an emergency department via ambulance. An IV is started and he is given diazepam IV which promptly stops the seizure activity.
VS: T 38.6, P 136, R 15 (shallow), BP 108/65, oxygen saturation 100% with mask. Wt 40kg. He is unresponsive to voice commands and he has shallow respirations. His head shows no signs of trauma. His pupils are equal at 3 mm and reactive to light. No papilledema on funduscopic exam is noted. His oral mucosa is moist with no oral lesions. His neck is supple without adenopathy. Heart is regular. Lungs are clear with shallow aeration. His abdomen is normal. His pulses, color and perfusion are good. He has several bug bites on his extremities without signs of cellulitis, petechiae, or bruises. He has increased tone to the left side of his body and brisk reflexes L>R. He is nonresponsive to voice commands, but he withdraws to pain. He exhibits no purposeful movements or signs of posturing. His corneal reflex, oculocephalic, and oculovestibular responses intact.
Encephalitis is suspected. He is given IV loading doses of fosphenytoin, acyclovir, and ceftriaxone. Lab studies show a normal CBC, chemistry, and liver function studies. Urine and serum toxicology screens are pending. A head CT without contrast shows no evidence of intracranial mass, ventriculomegaly, or intracranial bleed. A lumbar puncture is done. Opening pressure is 10 cm H20. CSF analysis shows 58 WBC (65% segs, 26% lymphs, 9% mono), protein 95, glucose 40, 4th tube on hold. Gram stain of the CSF shows few WBCs, but no organisms seen.
He is transferred to the PICU for further management.
Encephalitis is defined as an acute infection with focal or diffuse inflammation of brain parenchyma usually from viral etiologies, but it may also be associated with bacterial, fungal, protozoan, and autoimmune processes. Most often, encephalitis is an unusual complication of common systemic infections. Clinical manifestations reflect damage to neural cells that impair neural cell function through immune responses (1). The probability and severity of encephalitis can often be determined by: seasonality, age of infected groups, geographic distribution, availability of vaccines, animal or insect vector involvement, and immune-competency of the host.
The estimated incidence of viral encephalitis in the United States according to the Center for Disease Control (CDC) is 20,000 cases per year (5). It is an infrequent disease, occurring predominantly in children (16 per 100,000), elderly, and immunocompromised hosts (1). The incidence is highest in the second year of life (17 per 100,000 child years) and declines to 1 per 100,000 at age 15 (2). Overall mortality is 3 to 4% and morbidity is 7 to 10%. Endemic causes of encephalitis in the United States include herpes simplex virus (HSV), rabies virus, and La Cross virus. HSV is the most common cause of severe encephalitis in children and accounts for approximately 10% of all cases of encephalitis in the United States (2,4,5). Neonatal HSV-2 encephalitis with treatment, has a mortality of 14% (compared to 85% without treatment) and severe neurological dysfunction is found in 50 to 70% of affected individuals (2). HSV-1 encephalitis in older children represents the commonest cause of nonepidemic fatal viral encephalitis with a mortality of 30 to 50% and major neurological sequelae in 40 to 50% (2,6). Rabies virus infection accounts for several thousand deaths per year in Asian countries. In contrast, rabies virus is a rare cause of death or encephalitis in the United States due to the mandatory vaccination program of domestic canines. There are less than 5 indigenous cases of human rabies per year in the United States. One article, however, has suggested that the incidence in the United States may be increasing because of the changing epidemiology of infection in animal populations (5).
Arthropod-borne viruses (arboviruses) are agents of several virus families that can replicate in both invertebrate and vertebrate cells. Replication and infection of the hematophagous host must occur prior to injection of the vertebrate host. Over 400 arboviruses produce four major clinical syndromes associated with human arboviral infections: 1) encephalitis, 2) yellow fever, 3) hemorrhagic fevers, and 4) undifferentiated tropical fevers (6). La Cross virus is the most common cause of endemic arboviral encephalitis. St. Louis encephalitis is geographically the most widespread arbovirus in the United States and the commonest cause of epidemic viral encephalitis. The CDC receives reports of 200-500 cases of arboviral encephalitis per year. Encephalitis due to La Cross virus characteristically affects males (male:female ratio 2:1) 5-15 years of age in Wisconsin and Ohio, occurs from June to early October, and has less than 1% mortality (2,4,5). St. Louis encephalitis, in contrast, causes large urban epidemics among the elderly and occurs more frequently in the lower socioeconomic groups in the Midwestern and southeastern United States in late August and September following heavy spring rains and summer droughts. The virus is more common in urban environments where there is stagnant water with high organic content, particularly poorly draining sewage (6). Mortality ranges from 3 to 20%. Worldwide, Japanese encephalitis is the most common cause of arthropod-borne encephalitis with over 50,000 cases reported per year in China, Southeast Asia, and India (5). During epidemics, mortality ranges from 20 to 40%, with death usually occurring in the first week of illness (4). Eastern Equine encephalitis has peak activity from August to September and is geographically located along the eastern coast from Massachusetts to Florida. Compared to other arboviral encephalitides, Eastern Equine encephalitis symptoms are more severe and mortality is greatest at 50 to 75%. Mosquito-borne viruses peak in late summer in temperate regions, whereas tick-borne diseases occur in spring and early summer.
Post-infectious encephalomyelitis is an acute, inflammatory, demyelinating disease affecting multiple levels of the central nervous system (brain, optic nerves, and spinal cord) and occurs after a respiratory tract infection, viral exanthem, or an immunization. Synonymous names include: acute disseminated encephalomyelitis, acute demyelinating encephalomyelitis, and postviral encephalomyelitis. Occurrence is rare before 1 year of age, and it accounts for 10-15% of acute encephalitis cases in the United States (1) with peak incidence at 5 to 6 years of age. Historically, postinfectious encephalomyelitis was a complication of vaccinia immunization and measles virus infections; however, the discontinuation of vaccination against smallpox has eliminated the former, and immunization against measles has greatly reduced the later. Currently, post-infectious encephalitis in the United States is most commonly associated with varicella-zoster virus and influenza virus (5); although true postinfectious encephalomyelitis as a complication of varicella or influenza are rare (6). Other infections associated with postinfectious encephalomyelitis include: rubella, Mycoplasma pneumoniae, EBV, mumps, and human herpes virus 6 (HHV-6) (2,6). Worldwide there are over 100,000 cases that occur secondary to measles infection (5). Encephalitis from measles in the United States, in contrast, occurs in one per thousand cases (2). The incidence of post-infectious encephalitis has declined precipitously in countries following implementation of vaccination against measles, mumps, and rubella.
Viral encephalitis can be transmitted in one of two ways: via animal or insect vectors that transmit viruses maintained in environmental reservoirs or by human transmission via direct contact with human blood or body fluids. Epidemiologically, this is important since environmentally derived viral pathogens display relatively uniform epidemiologic characteristics. Furthermore, human disease correlates with the life cycle of the vector (spring and summer) and exhibits a geographic distribution that parallels with the habitat of the vector. In contrast, viruses transmitted human-to-human display few seasonal, temporal, or geographic predilections.
Central nervous system (CNS) infection depends, in large measure, on the magnitude and duration of the viremia, which reflect, in turn, the efficiency of the viral replication at extraneural locations and the ability to evade host defense mechanisms. The spectrum and severity of neurological signs and symptoms depends on neurovirulence (the capacity to cause disease within the CNS) and neurotropism (the propensity to infect specific cell groups of the CNS) (1). In human disease, the difference in neurovirulence between viruses is striking. For example, mumps is very highly neuroinvasive, but its neurotropism appears limited to ependymal cells, which may account for the low level of neurovirulence. In contrast, herpes simplex virus is thought to be relatively nonneuroinvasive, but when the CNS is infected, neurons, glial cells, pia-arachnoid cells, and endothelial cells are all affected and, without appropriate treatment, a 70% mortality bespeaks a very high degree of neurovirulence (6).
Infectious encephalitis is the result of direct invasion of any cell type in the brain and gains entry via hematogenous or neuronal routes. Most viral CNS infections are acquired hematogenously and current evidence indicates that most viruses grow at some extraneural site (usually the reticuloendothelial system), establish a viremia, and cross from blood to brain or cerebrospinal fluid by varied pathways: 1) via cerebral capillaries, 2) transfer via pinocytotic vesicles across capillary endothelial cells, and 3) via the fenestrated vascular endothelial cells of the choroid plexus (6). Hematogenous spread is exemplified by neonatal (HSV-2) herpes encephalitis and arthropod-born viral disease. Transmission of virus into the brain through neural pathways include 1) bidirectional axonal transport, and 2) cell-to-cell infection (6). Rabies, HSV-1, and varicella-zoster virus exemplify neural transmission of viruses into the CNS.
Post-infectious encephalitis is likely an autoimmune cell-mediated immune process characterized by perivenulitis and contiguous demyelination (1) caused by derangement and dysregulation of the immune system following either respiratory or intestinal tract infections. A viral infection may activate myelin-reactive T-cells that migrate to the CNS. These cells may activate other mediators of inflammation, including inflammatory cytokines that trigger demyelination.
Clinical manifestations of encephalitis in the neonatal period are often nonspecific and include: fever, poor feeding, irritability, lethargy, and sepsis. Apnea, focal or generalized seizures, paralysis, or coma may appear with progressive neonatal herpes simplex encephalitis. The mean age at onset of neonatal HSV encephalitis is 11-14 days after birth. HSV-2 is usually the etiological agent in 3/4 of cases and is acquired either by intrapartum contact of the fetus with maternal genital secretions (85-95%) or in utero (5-15%). Primary maternal genital HSV infection poses a much greater risk to the fetus than recurrent genital infection, since the initial viremia and the lack of protective antibodies against HSV are more likely to result in disease. The risk of transmission from mother to fetus is 30-50% with maternal primary infection, as compared with <3% with recurrent infection (4). Overall, 50% of infants with neonatal HSV infection will have encephalitis as a component of their disease (1,2). The presence of microcephaly, hydranencephaly, microphthalmia, chorioretinitis, cataracts, intracranial calcifications, intrauterine growth retardation, and vesicular rash are characteristic of in utero acquisition of HSV-2. This latter presentation is due to congenital infection (hematogenous exposure during early gestation usually from primary maternal HSV), as opposed to the former presentation which is a perinatal infection acquired close to the time of delivery.
In older children, the clinical manifestations of the inflammatory response are initially subtle and diverse. Specific neurological findings vary according to which areas of brain parenchyma are affected and also the degree of increased intracranial pressure. Some features of acute encephalitis are similar to those found in aseptic meningitis and include headache, stiff neck, photophobia, fever, vomiting, and irritability; however, the hallmark of disease is alteration of higher cerebral function, characterized by change in level of consciousness, psychiatric and behavioral abnormalities, and/or seizure activity. Predominant cortical involvement may lead to disorientation and confusion. Basal ganglia involvement may lead to movement disorders and brainstem involvement may lead to cranial nerve dysfunction. Occasionally, spinal cord involvement (myelitis) may accompany the encephalitis with findings of flaccid paraplegia and abnormalities of the deep tendon reflexes.
HSV encephalitis in the older child may represent primary infection, reinfection, or reactivation of latent infection. Most cases (about 70%) are the due to reactivation in the olfactory bulb or trigeminal ganglia and resultant spread into the CNS. Encephalitis may begin suddenly or after a brief influenza-like prodrome. Initial symptoms include: fever (always present) with headache, vomiting, malaise, behavioral changes, and speech difficulties. Consciousness decreases with progression and focal seizures are prominent (40%). Focal neurological signs, such as hemiparesis, dysphagia, or visual field defects develop and likely reflect selective involvement of the temporal or frontal lobes. The clinical course of HSV encephalitis can be rapidly progressive, with refractory seizures (status epilepticus), coma, increased ICP, and death within 2 weeks. The clinical course, however, may become more chronic and result in seizures, memory loss, and behavioral disturbances. Pathological studies have shown localized inflammation, necrosis, and inclusion bodies, with strikingly unilateral frontal-temporal localization (6). This pathologic finding suggests that the virus is spread from cell to cell along the base of the brain within the middle and anterior fossae.
Of the nearly 100 known herpesviruses of non-humans, eight human herpesviruses (HSV 1 & 2, cytomegalovirus (CMV), varicella-zoster virus, Epstein-Barr virus (EBV), and human herpesvirus 6, 7, & 8) are prevalent in all human populations and seven are capable of persisting for life. All eight human herpesvirus infections are associated with acute encephalitis. Acquired cytomegalovirus (CMV) infections in immunocompetent hosts are rarely associated with neurological complications, but when they occur, the encephalitis is often mild, and self-limited. Encephalitis from varicella-zoster virus usually appears 3-7 days after onset of the rash and consists of headache, fever, seizures, paralysis, and coma (1). Epstein-Barr virus (EBV) encephalitis accounts for 5% of cases of acute encephalitis and is the most common infectious agent mimicking HSV encephalitis (1). Clinical manifestations of acute encephalitis include: fever, headache, altered consciousness, and seizures, including status epilepticus. EBV infection also produces the "Alice-in-Wonderland" syndrome characterized by bizarre personality changes and perceptual misinterpretation (metamorphosia of size, shape, and or distance) (1). Human herpes virus type 6 and 7 (HHV-6 and HHV-7) causes roseola (exanthem subitum) in young children and account for a substantial proportion of febrile seizures of childhood. HHV-6 or HHV-7 have been linked with acute encephalopathy and encephalitis in young children with symptomatic infections having high fevers and seizures that are usually generalized. Hemiparesis (transient or permanent) and coma may be additional clinical features (1).
Encephalitis from arboviruses in pediatrics are usually the result of La Cross virus, a California serogroup virus, which is transmitted from the vector, Aedes triseriatus, a forest dwelling mosquito residing in wooded areas of the midwestern and mid-Atlantic United States. The virus is maintained in the wild through a mosquito and small woodland mammal (chipmunks, rabbits, and squirrels) cycle. Unlike eastern, western, and St. Louis encephalitis, the transmission cycles do not involve an avian reservoir (6). There are approximately 100 cases per year in children 5 to 11 years of age. The clinical course is mild and characterized by headache, fever, malaise, abdominal pain, and vomiting for 3 to 7 days after exposed to the virus. Lethargy, behavioral changes, and/or brief seizures follow with clinical improvement over a 7 to 8 day period. Focal neurological signs are present in 16 to 25%, suggesting a diagnosis of HSV encephalitis and may necessitate initiation of treatment. Fifty percent develop seizures and 10 to 15% of children develop status epilepticus. Mortality is less than 1% (4).
St. Louis encephalitis virus is endemic in the midwestern United States and is maintained in a mosquito-bird cycle involving Culex tarsalis mosquitoes, pigeons, sparrows, and doves. Most infections are asymptomatic; however, two-thirds of symptomatic infections present with encephalitis. Children have a biphasic illness first with low-grade fever, diarrhea, vomiting, and malaise followed by the rapid onset of headache, vomiting, fever (as high as 41 C), neck stiffness, lethargy, and/or agitation. Tremors may be present, but focal neurological findings are infrequent. Clinical improvement begins within 7 to 10 days of disease onset. Syndrome of inappropriate antidiuretic hormone (SIADH) with hyponatremia, dysuria with pyuria, opsoclonus, myoclonus, and oculomotor paralysis are unique clinical features of this form of encephalitis (6). Mortality ranges from 8 to 20% with most deaths within the first 2 weeks. Approximately 10% of survivors experience sequelae of memory loss, chronic fatigue, sleeplessness, headaches, and occasionally seizures or motor deficits.
Japanese encephalitis causes more neurologic morbidity and mortality than all of the other arboviruses combined and is the most common arthropod-borne encephalitis worldwide with over 50,000 cases per year in Asia. The virus is maintained in a bird-vertebrate cycle involving Culex tritaeniorhynchus mosquitoes that breed in rice fields, domestic pigs, young water buffalo, herons and other wading birds (1,6). Children affected are usually under 15 years of age and have an abrupt, fulminant illness with rapid depression of consciousness, fever, vomiting, increased muscle tone, convulsions, and coma. The virus may infect brain stem nuclei, leading to acute respiratory failure and death. Infection of the basal ganglia and thalamus presents as tremors during the acute disease and result in parkinsonian mask-like facies, rigidity, tremor, and dystonia in survivors (4). Decorticate and decerebrate posturing are notorious clinical features in Japanese encephalitis. Mortality ranges from 25 to 40% with the majority of survivors having mental retardation, seizures, motor deficits, or subtle behavioral and intellectual abnormalities. Infection may be prevented with an inactivated Japanese encephalitis virus vaccine prepared by infected mouse brains.
Eastern equine encephalitis virus has the lowest incidence in North America, but has the highest mortality rate. Geographically, the eastern encephalitis virus is found in the eastern half of the United States primarily along the freshwater marshes of the Atlantic and Gulf coasts from Massachusetts to Florida. Peak activity occurs in August and September. The rarity of human disease is explained by the cycle of the virus that is usually transmitted between marsh birds and Culiseta melanura mosquitoes, which do not feed on large vertebrates. Only with alterations in the conditions of the marshes, changes in rainfall, different bird populations, and variations in mosquito breeding, can the virus spill over into other mosquito vectors that feed on mammals. Human outbreaks usually are heralded by deaths among horses and pheasants (4,6). Although the disorder usually begins with abrupt onset high fever, lethargy, vomiting, and convulsions, some have a prodromal phase of fever, headache, malaise, and myalgia. Signs are usually diffuse, but some may have focal findings suggesting focal encephalitides, such as HSV. Mortality ranges from 50 to 75% with neurological sequelae of mental retardation, seizures, spastic paralysis, and behavioral abnormalities (1). The Asian Tiger mosquito (Aedes albopictus) was imported into Houston, Texas in 1985 in a shipment of used tires. In 1991, Eastern encephalitis virus was recovered in the Asian Tiger mosquito and has raised major concerns since the mosquito is an aggressive biter of humans which thrives in suburban and forest habitats and could become a treacherous host for the eastern encephalitis virus (6).
The differential diagnosis for acute encephalitis includes: bacterial meningitis, Rocky Mountain spotted fever, brain abscesses, drug intoxication, lead encephalopathy, Reye's syndrome, hepatic coma, uremia, organic acidemias, amino acidemias, urea cycle defects, intracranial neoplasms, systemic lupus erythematosus, cerebrovascular accidents, pseudotumor cerebri, trauma, and post-infectious encephalopathies. The presence of fever is helpful in distinguishing encephalitis from encephalopathies due to toxins or inborn errors of metabolism.
Evaluation of an infant, child, or adolescent with signs of neurological dysfunction with or without fever requires a thorough neurodiagnostic assessment that may include: cerebrospinal fluid (CSF) examination, electroencephalogram (EEG), and imaging studies of the brain and/or spinal cord. The sequence of these studies will depend on severity of condition and concerns regarding possibility of CNS mass lesion, presence of increased intracranial pressure, or other acute neurological conditions requiring specific intervention.
In general, there is little correlation of CSF abnormalities with clinical or histologic severity of encephalitis. The CSF is usually clear and colorless, but may be xanthochromic when blood has been in the CSF for some time. The CSF cell count and protein are frequently normal or slightly elevated, and the glucose concentration remains normal. In the early phase of viral infection, there is often a mixed pleocytosis with both polymorphonuclear (PMN) and mononuclear cells that typically shifts to a lymphocytic pleocytosis over time (1,2). Subsequent lumbar punctures can be helpful in demonstrating pleocytosis. Eastern equine encephalitis has CSF parameters which appear more "bacterial" than "viral," with a predominance of PMN pleocytosis that persists throughout the illness (1,2). Although HSV-1 typically produces lytic infection of neuronal cells and causes hemorrhagic necrosis of the brain (1), the presence of red blood cells in the CSF is a late and inconsistent indicator of HSV encephalitis. Consideration must also be given to subarachnoid hemorrhage from occult trauma or vascular malformation. Vasculitis or tissue necrosis elicits CSF leukocytosis with increased PMN cells and also causes extravasation of red blood cells into CSF (2).
Cell culture provides direct evidence of infection by detecting viral pathogens from CSF, blood, or other body fluids. Viruses that can be detected via this diagnostic approach include herpesvirus, enterovirus, adenovirus, HIV, and rabies. Yields typically are very poor: viral CSF cultures are positive in less than 30% of neonatal HSV encephalitis or disseminated disease (5). Additionally, CSF viral cultures for HSV-1 are almost always negative (4) for older children with HSV encephalitis (2). As for the arboviruses, La Cross virus, St. Louis, and eastern equine encephalitis virus are not typically isolated.
Polymerase chain reaction (PCR) is an inexpensive, rapid, molecular genetic assay that detects specific organism DNA sequences and provides confirmatory viral isolation and thus a specific etiologic diagnosis. PCR affords rapid diagnosis of infections with HSV, CMV, EBV, enterovirus, JC virus, HHV-6, varicella-zoster virus, B. burgdorferi (Lyme disease), Bartonella henselae (cat scratch disease), and HIV. The specificity of PCR in HSV encephalitis approaches 100% and the sensitivity ranges from 75 to 95% depending on the quality of the laboratory (1). PCR has become the gold standard for evaluation of infants and children with suspected HSV encephalitis.
Immunoglobulins and antibodies have limited usefulness for early diagnosis because of poor specificity and sensitivity. Additionally, the antibody response in the CSF does not appear before the fifth day of illness. Finally, acute and convalescent serum antibody titers generally take 3 to 6 weeks to develop.
Electroencephalography (EEG) is usually abnormal in infants and children with encephalitis and shows slowing and epileptiform discharges that can be diffuse or focal. HSV encephalitis classically produces slowing, sharp-wave discharges, or periodic lateralizing epileptiform discharges localized to the temporal or frontal lobe (2). EEG however, is not specific for HSV encephalitis since only 50% exhibit the classic EEG findings. Similar EEG findings have been found with infectious mononucleosis.
Neuroimaging studies, such as computed tomography (CT) or magnetic resonance imaging (MRI), have major roles in evaluating infants and children with presumed or proven CNS infections. Large mass lesions, such as tumors, hemorrhages, and brain abscesses, can be excluded reliably with CT, especially when obtained with contrast enhancement. CT is a better imaging modality for infants with suspected intrauterine viral infections, since small intracranial calcifications are better detected by CT compared to MRI or ultrasound (1). MRI is the preferred imaging modality in children with suspected viral encephalitis and post-infectious encephalomyelitis (1). Herpes simplex encephalitis in older children reveals T2 prolongation on MRI in the medial temporal lobe, orbitofrontal region, or cingulate gyrus, as well as cortical enhancement in these regions when gadolinium is administered intravenously (1,2). In contrast, neonatal herpes simplex encephalitis in the acute stages reveals diffuse brain edema that is consistent with the hematogenous transmission of the virus to the brain. Subsequent imaging shows atrophy, parenchymal calcifications, or cystic encephalomalacia (1).
The definitive diagnostic test of encephalitis, however, is brain biopsy for tissue histology and culture. The utility, however, of routine brain biopsies in children is controversial. Improved neuroimaging techniques and low adverse effects from current antiviral therapy have made empiric therapy the usual practice. Brain biopsy has utility if patients have atypical features or the disease progresses despite empiric therapy (1,2).
Encephalitis and other non-infectious conditions that suggest the presence of CNS infection severe enough to alter the state of consciousness, should be admitted to a Pediatric Intensive Care Unit (PICU) for initial evaluation and supportive care. Severe encephalitis can lead to extensive areas of perivascular infiltrates and diffuse cerebral edema with elevation in ICP and cerebral herniation (2). Frequent assessments of responsiveness, neurological exam, anticipatory monitoring for seizures, and signs of increased intracranial pressure can all be provided in the PICU.
Since antiviral therapy has decreased the mortality for HSV infections by nearly 40% from the pre-antiviral era, acyclovir is the treatment of choice for herpes simplex encephalitis. Antivirals inhibit viral infection by binding with viral nucleic acid and prevent viral replication. The currently approved dose is 30 mg/kg/day IV divided every 8 hours for 14 to 21 days, but some experts recommend increasing the total daily dose to 45-60 mg/kg/day IV divided every 8 hours. Acyclovir has also been effective against varicella zoster virus, while other antiviral agents such as ganciclovir and foscarnet have been used for CMV infections. Unfortunately, antiviral therapy has essentially no impact on morbidity among survivors of CNS disease. Approximately two-thirds still suffer neurological impairment such as major motor and sensory deficits, aphasia, and amnestic syndrome (Korsakoff's psychosis) despite antiviral agents during the acute CNS infection.
Encephalitis from arthropod-borne viruses cannot be treated with specific therapy and typically resolve with conservative management, antipyretics, intravenous fluids, and antiepileptic drugs. Seizures, a frequent complication of viral encephalitis, can be treated acutely with lorazepam and may need maintenance antiepileptic drug therapy with phenobarbital or phenytoin in standard doses.
Potentially life-threatening complications of encephalitis are increased intracranial pressure (ICP), seizures refractory to antiepileptic therapy, and neuronal destruction of the brainstem leading to respiratory compromise or hemodynamic instability. Treatment for increased ICP often requires routine head positioning, osmotic diuresis, fluid restriction, and assisted mechanical ventilation with hyperventilation. Long-acting neuromuscular paralytics for intubation and mechanical ventilation should be avoided since clinical manifestations of seizures will not be evident. Furthermore, neuromuscular blocking agents in patients with impairment of consciousness does not permit repetitive neurological exams and the development of raised ICP may not be evident until intracranial hypertension causes Cushing's triad and possible herniation (2).
Overall, the mortality and morbidity for encephalitis is 3 to 4% and 7 to 10%, respectively. Severity is inversely correlated with the age of onset. Children under the age of one year have a mortality of 40 to 50% (2). Death usually results from cerebral edema or vasomotor instability. Generally, improvement occurs over days to weeks, while focal deficits resolve over a period of months. Neurological morbidity includes: personality changes, behavior disorders, mental retardation, blindness, movement disorders, paretic syndromes, spasticity, and persistent ataxia (1-4). Significant neurological sequelae are more likely to occur if the patient presents with lethargy, coma, or with seizures. Mortality for neonatal HSV encephalitis is 14% with treatment and the outcome is worse for infants with HSV-2 infection (1,3). Older children with HSV encephalitis have mortality at 28% and 40-50% have significant neurological impairment. Of all arboviral encephalitides, Eastern equine encephalitis has the greatest mortality at 50 to 75% with neurological damage in most survivors. In contrast, La Cross encephalitis has the lowest mortality, but seizures develop in 10% of survivors (2).
1. Encephalitis is usually the result of which of the following:
. . . . . a. viral
. . . . . b. bacterial
. . . . . c. protozoa
. . . . . d. autoimmune
. . . . . e. fungal
. . . . . f. all of the above
2. What are the endemic forms of encephalitis in the United States?
3. Which viral infection involving the CNS is likely to present with focal neurological findings?
. . . . . a. HSV
. . . . . b. Coxsackievirus
. . . . . c. Enterovirus
. . . . . d. Rabies virus
. . . . . e. St. Louis virus
4. Match the following encephalitis (first column) with the appropriate clinical characteristic (second column):
5. Polymerase chain reaction (PCR) is the diagnostic method of choice for confirming the cause of encephalitis for all of the following except:
. . . . . a. Cytomegalovirus
. . . . . b. Enteroviruses
. . . . . c. HHV-6 and HHV-7
. . . . . d. HSV 1 and 2
. . . . . e. Rabies virus
6. True/False: Antiviral therapy has decreased the morbidity and mortality for HSV encephalitis.
Herpes encephalitis case: Higashigawa KH, Yamamoto LG. A Toxic Infant with Aseptic Meningitis. In: Yamamoto LG, Inaba AS, DiMauro R (eds). Radiology Cases In Pediatric Emergency Medicine, 2002, volume 7, case 9. Available online at: www.hawaii.edu/medicine/pediatrics/pemxray/v7c09.html
1. Bale JF Jr. Chapter 64 - Viral Infections of the Nervous System. In: Swaiman KF, Ashwai S (eds). Pediatric Neurology Principles and Practice, third edition. 1999, St. Louis: Mosby, pp. 1001-1024
2. Berkowitz ID, et al. Chapter 32 - Meningitis, Infectious Encephalopathies, and Other Central Nervous System Infections. In: Rogers MC, et al (eds). Textbook of Pediatric Intensive Care, third edition. 1996, Baltimore: Williams & Wilkins, pp. 1062-1089.
3. Bingham AC, Saiman L. Short Course Viral Encephalitis. Office and Emerg Pediatr 2000;13(5/6):184-189.
4. Roos KL. Central Nervous System Infections. Neurol Clin 1999;17(4):813-833.
5. Whitley RJ, Kimberlin DW. Viral Encephalitis. Ped Rev 1999;20(6):192-198.
6. Johnson, R.T. Viral Infections of the nervous system, second edition. 1998, Philadelphia: Lippincott-Raven
Answers to questions
1. a. viral
2. HSV, St. Louis encephalitis, and rabies virus.
3. a. HSV
4. Japanese encephalitis-decorticate or decerebrate posturing, Eastern equine encephalitis-highest mortality, Post-infectious encephalitis-involvement of multiple CNS levels, St. Louis encephalitis-SIADH, La Cross encephalitis-Aedes triseriatus.
5. e. Rabies virus
6. False. Antiviral therapy has only decreased mortality, NOT morbidity.