Practice Essentials

Encephalitis presents as diffuse or focal neuropsychological dysfunction. Although it primarily involves the brain, it often involves the meninges as well (meningoencephalitis). From an epidemiologic and pathophysiologic perspective, encephalitis is distinct from meningitis, though on clinical evaluation both can be present, with signs and symptoms of meningeal inflammation. It is also distinct from cerebritis.

Signs and symptoms

The viral prodrome typically consists of fever, headache, nausea and vomiting, lethargy, and myalgias. Manifestations associated with specific types of encephalitis include the following:

The classic presentation is encephalopathy with diffuse or focal neurologic symptoms, including the following:

The signs of encephalitis may be diffuse or focal. Typical findings include the following:

Findings of herpes simplex virus (HSV) infection in neonates may include the following:

Encephalitis may be associated with a number of complications, including the following:

See Clinical Presentation for more detail.


Blood and urine tests that may be helpful include the following:

A lumbar puncture (LP) should be performed in all cases of suspected viral encephalitis.

Studies that may be ordered to identify the infectious agent include the following:

Imaging modalities that may be helpful include the following:

CSF analysis is essential. Parameters to be evaluated include the following:

Brain biopsy is the diagnostic standard (96% sensitivity, 100% specificity).

See Workup for more detail.


Management in the prehospital setting includes the following:

In the emergency department (ED), beyond supportive care, viral encephalitides are not treatable, with the exceptions of HSV and VZV encephalitis. Important initial measures include the following:

Additional treatment considerations include the following:

Clinical practice guidelines for treatment of encephalitis have been published by the Infectious Diseases Society of America (IDSA).[1]

See Treatment and Medication for more detail.


Encephalitis, an inflammation of the brain parenchyma, presents as diffuse and/or focal neuropsychological dysfunction. Although it primarily involves the brain, the meninges are frequently involved (meningoencephalitis).

From an epidemiologic and pathophysiologic perspective, encephalitis is distinct from meningitis, though on clinical evaluation both can be present, with signs and symptoms of meningeal inflammation, such as photophobia, headache, or stiff neck. It is also distinct from cerebritis. Cerebritis describes the stage preceding abscess formation and implies a highly destructive bacterial infection of brain tissue, whereas acute encephalitis is most commonly a viral infection with parenchymal damage varying from mild to profound.

Although bacterial, fungal, and autoimmune disorders can produce encephalitis, most cases are viral in origin. The incidence of encephalitis is 1 case per 200,000 population in the United States, with herpes simplex virus (HSV) being the most common cause. Considering the subacute and chronic encephalopathies, the emergency department (ED) physician is most likely to encounter toxoplasmosis in an immune-compromised host.

The relatively common acute arboviral encephalitides vary widely in epidemiology, mortality, morbidity, and clinical presentation, and no satisfactory treatment exists for these infections. However, attempts to distinguish these acute arboviral encephalitides from the treatable acute viral encephalitides due to herpes simplex or varicella are important.

Herpes simplex encephalitis (HSE), which occurs sporadically in healthy and immune-compromised adults is also encountered in neonates infected at birth during vaginal delivery and is potentially lethal if not treated. Varicella-zoster virus encephalitis (VZVE) is life threatening in immune-compromised patients. Swift identification and immediate treatment of HSE or VZVE can be lifesaving. From a risk-benefit standpoint, most authorities recommend initiating ED treatment with acyclovir in any patient whose central nervous system (CNS) presentation is suggestive of viral encephalitis, especially in the presence of fever, encephalopathy, or focal findings, and in all neonates who appear ill for whom a CNS infection is being considered.

See the following for more information:

West Nile encephalitis

In 1999, a late summer outbreak of West Nile encephalitis (WNE), an arbovirus not previously found in the United States, was implicated in several deaths in New York. By late summer 2002, West Nile virus had been identified throughout the eastern and southeastern United States. Following bird migration, the virus began to extend westward, and by April 2003, virus activity had been detected in 46 states and the District of Columbia.

An updated Centers for Disease Control and Prevention (CDC) report for 2007 (West Nile Virus Update) included information regarding viremic blood donors. Throughout the world, outbreaks of WNE have been associated with severe neurologic disease, though, in general, only 1 in 150 affected patients develop symptomatic WNE. By 2008, the number of cases reported to the CDC had dropped dramatically throughout the United States, owing to the decimation of the US crow bird population, a common host of the WNV, which is lethal to the American crow.[2]

For more information, see the CDC fact sheet on West Nile virus, links to state and local government web sites on West Nile virus, and the Environmental Protection Agency (EPA)/CDC article on mosquito control.

For clinical information on the Internet, see West Nile Virus: A Primer for the Clinician, from the August 6, 2002, issue of Annals of Internal Medicine. The Canadian equivalent, West Nile Virus: Primer for Family Physicians, was published on June 10, 2005, in Canadian Family Physician.[3]


Portals of entry are virus specific. Many viruses are transmitted by humans, though most cases of HSE are thought to be reactivation of HSV lying dormant in the trigeminal ganglia. Mosquitoes or ticks inoculate arbovirus, and rabies virus is transferred via an infected animal bite or exposure to animal secretions. With some viruses, such as varicella-zoster virus (VZV) and cytomegalovirus (CMV), an immune-compromised state is usually necessary to develop clinically apparent encephalitis.

In general, the virus replicates outside the CNS and gains entry to the CNS either by hematogenous spread or by travel along neural pathways (eg, rabies virus, HSV, VZV). The etiology of slow virus infections, such as those implicated in the measles-related subacute sclerosing panencephalitis (SSPE) and progressive multifocal leukoencephalopathy (PML), is poorly understood.

Once across the blood-brain barrier, the virus enters neural cells, with resultant disruption in cell functioning, perivascular congestion, hemorrhage, and a diffuse inflammatory response that disproportionately affects gray matter over white matter. Regional tropism associated with certain viruses is due to neuron cell membrane receptors found only in specific portions of the brain, with more intense focal pathology in these areas. A classic example is the HSV predilection for the inferior and medial temporal lobes.

In contrast to viruses that invade gray matter directly, acute disseminated encephalitis and postinfectious encephalomyelitis (PIE), most commonly due to measles infection and associated with Epstein-Barr virus (EBV) and CMV infections, are immune-mediated processes that result in multifocal demyelination of perivenous white matter.


The cause of encephalitis is usually infectious in nature. Viral agents, such as HSV types 1 and 2 (the latter much more common in neonates than adults), VZV, EBV, measles virus (PIE and SSPE), mumps virus, and rubella virus, are spread through person-to-person contact. Human herpesvirus 6 may also be a causative agent.[4] The CDC has confirmed that WNV can be transmitted by means of organ transplantation and via blood transfusions.

Important animal vectors include mosquitoes and ticks, which spread the arbovirus group, and warm-blooded mammals, which are vectors for rabies and lymphocytic choriomeningitis (LCM).

Bacterial pathogens, such as Mycoplasma species and those causing rickettsial disease or catscratch disease, are rare and invariably involve inflammation of the meninges out of proportion to their encephalitic components. Encephalitis due to parasites and fungi other than Toxoplasma gondii are covered elsewhere.

Noninfectious causes include the demyelinating process in acute disseminated encephalitis.


United States statistics

Determining the true incidence of encephalitis is impossible, because reporting policies are neither standardized nor rigorously enforced. In the United States, several thousand cases of viral encephalitis are reported to the CDC each year, with an additional 100 cases a year attributed to PIE. These figures probably represent a fraction of the actual number of cases.

HSE, the most common cause of sporadic encephalitis in Western countries, is relatively rare; the overall incidence is 0.2 per 100,000, with neonatal HSV infection occurring in 2-3 per 10,000 live births.

The arbovirus group is the most common cause of episodic encephalitis, with a reported incidence similar to that of HSV. These statistics may be misleading in that most people bitten by arbovirus-infected insects do not develop clinically apparent illness and, of those who do, less than 10% develop overt encephalitis.

Arboviruses require an insect vector, which is generally present between June and October. The 2 most common arboviruses result in (1) St Louis encephalitis, found throughout the United States but principally in urban areas around the Mississippi River, and (2) the geographically misnamed California virus encephalitis (CE)—in particular, LaCross encephalitis (LAC)—which affects children in rural areas in states of the upper Midwest and North East.

Among the other arbovirus-caused encephalitides, the deadliest (and, fortunately, rarest) is eastern equine encephalitis (EEE), which is encountered in New England and surrounding areas; western equine encephalitis (WEE), a milder disease, is most common in rural communities west of the Mississippi River. Powassan virus is the only well-documented arbovirus transmitted by ticks.

Less common causes of viral encephalitis include VZV encephalitis, with an incidence of roughly 1 in 2000 infected persons. Measles produces 2 devastating forms of encephalitis: PIE, which occurs in about 1 in 1000 infected persons, and SSPE, occurring in about 1 in 100,000 infected patients. Rarest in the United States are the 0-3 unrelated annual cases of rabies encephalitis, typically a consequence of the immigration of an infected person from Mexico or Central America during the long incubation period of the rabies virus but prior to the onset of clinically apparent disease.

International statistics

Japanese virus encephalitis (JE), occurring principally in Japan, Southeast Asia, China, and India, is the most common viral encephalitis outside the United States.

Age-related differences in incidence

Individuals at the extremes of age are at highest risk, particularly for HSE. Neonatal HSE is a manifestation of disseminated infection type 1 or 2, whereas older infants, children, and adults are much more likely to have localizing CNS infection almost exclusively due to type 1, in a bimodal distribution of patients aged 5-30 years or older than 50 years.

St Louis encephalitis and WNE are more common and are most severe in patients older than 60 years; conversely, LAC is more common and is most severe in children younger than 16 years. EEE and WEE disproportionately affect infants while EEE disproportionately affects children and elderly persons.


The prognosis is dependent on the virulence of the virus and the patient’s health status. Extremes of age (< 1 y or >55 y), immune-compromised status, and preexisting neurologic conditions are associated with poorer outcomes.

Untreated HSE has a mortality of 50-75%, and virtually all untreated or late-treatment survivors have long-term motor and mental disabilities. The mortality in treated HSE averages 20%, and the neurologic outcome correlates with the neurological disability present at the time of the first dose of acyclovir or comparable antiviral agents. Approximately 40% of survivors have minor-to-major learning disabilities, memory impairment, neuropsychiatric abnormalities, epilepsy, fine-motor-control deficits, and dysarthria.

Outcomes in arboviral JE and EEE are catastrophic, similar to untreated HSE, with high mortality and severe morbidity, including mental retardation, hemiplegia, and seizures. Other arboviruses cause substantially less morbidity and mortality. For example, St Louis encephalitis and WNE have a mortality rate of 2-20%, the higher rates found in patients older than 60 years. Long-term sequelae with St Louis encephalitis include behavioral disorders, memory loss, and seizures.

WEE is associated with few deaths and much less morbidity, although developmental delay, seizure disorder, and paralysis occasionally occur in children, and postencephalitic parkinsonism may occur in adults. CE is typically associated with mild illness, and most patients make a full recovery; however, the minority of patients with severe disease have a 25% chance of focal neurologic dysfunction. Death rates from WEE and LAC are less than 5%.

PIE secondary to measles is associated with a mortality rate approaching 40% of cases, with a high rate of neurologic sequelae in survivors. SSPE is uniformly fatal, although the disease course may last anywhere from several weeks to 10 years.

VZVE has a mortality of 15% in immune-competent patients and virtually 100% in immune-suppressed patients. The mortality for EBV encephalitis is 8%, with substantial morbidity found in approximately 12% of survivors.

Rabies encephalitis and acute disseminated encephalitis are virtually 100% fatal, although there are rare survivors reported in the medical literature.

Patient Education

For patient education resources, see the Brain and Nervous System Center and the Bacterial and Viral Infections Center, as well as Brain Infection, West Nile Virus, Encephalitis, and Ticks.


The clinical presentation and course can be markedly variable. The acuity and severity of the presentation correlate with the prognosis. A history of mosquito or tick bites or exposure to mouse/rat droppings should be sought. Recognizing certain mammalian animal bite(s) associated with rabies or exposure to a bat in an enclosed space for which antirabies treatment was not obtained is very important.

The viral prodrome is typically several days and consists of fever, headache, nausea and vomiting, lethargy, and myalgias. The specific prodrome in encephalitis caused by varicella-zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), measles virus, or mumps virus includes rash, lymphadenopathy, hepatosplenomegaly, and parotid enlargement. Dysuria and pyuria are reported with St Louis encephalitis. Extreme lethargy has been noted with West Nile encephalitis (WNE).

The classic presentation is encephalopathy with diffuse or focal neurologic symptoms, including the following:

Of note, severe headache is not always found. Less common is the complaint of paraspinal backache.

Symptoms of herpes simplex virus (HSV) infection in neonates (aged 1-45 d) may include localized skin, eye, or mouth lesions in the early phase of illness with encephalitis. Diminished alertness, irritability, seizures, and poor feeding develop later in the course of illness, and disseminated disease and shock are late findings.

Herpes simplex encephalitis (HSE) in older children and adults is not typically associated with active herpetic eruptions and is characterized by the acute onset of more severe symptoms of encephalitis early in the course of illness.

Toxoplasma encephalopathy accounts for as many as 40% of HIV-positive patients with neurologic disease who present with a subacute headache, findings of subtle to remarkable encephalopathy, and, often, focal neurological complaints/findings. Rarely, this may be the presenting symptom complex of profound immune suppression due to HIV infection.

Physical Examination

Look for supporting evidence of viral infection. The signs of encephalitis may be diffuse or focal. At the extremes, 80% of patients with HSE present with focal findings. Typical findings include the following:

Findings of HSV infection in neonates (aged 1-45 d) may include the following:

As noted above, Toxoplasma infection causing encephalitis is found in immune-suppressed patients. They exhibit significant encephalopathy with lethargy or personality changes, and 75% present may present with focal neuropathology.


Encephalitis may be associated with a number of complications, including the following:

Approach Considerations

Although bacterial, fungal, and autoimmune disorders can produce encephalitis, most cases are viral in origin. Accordingly, in addition to standard blood and urine tests, studies may be performed to identify the infectious agent causing the encephalitis.[5] It is important, when possible, to distinguish acute arboviral encephalitides from potentially treatable acute viral encephalitides, especially herpes simplex encephalitis (HSE) and varicella-zoster encephalitis, as a high suspicion for these disorders and prompt treatment can reduce the severity of neurological sequelae and can be lifesaving.

Blood and Urine Tests

A complete blood count (CBC) with differential should be performed, although findings are often within the normal range.

Serum electrolyte levels are usually normal unless dehydration is present; the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) occurs in 25% of patients with St Louis encephalitis.

The serum glucose level should be determined to rule out confusion due to treatable hypoglycemia and to compare with the cerebrospinal fluid (CSF) glucose value. Low serum results are found in nutritionally deprived patients, while diabetic patients may present with elevated glucose levels compatible with complicating hyperosmolar state or diabetic ketoacidosis.

Blood urea nitrogen (BUN) and creatinine levels are helpful to assess hydration status, and liver function tests should be performed to assess for end-organ dysfunction or the need to adjust antimicrobial therapy dosing regimens.

A lumbar puncture (LP) should be performed on all patients suspected of having a viral encephalitis. A platelet count and coagulation profile are indicated in patients who are chronic alcohol users, have liver disease, and those in whom disseminated intravascular coagulation (DIC) is suspected. The patient may require platelets or fresh frozen plasma (FFP) before LP.

A urinary electrolyte test should be performed if SIADH is suspected. Urine or serum toxicology screening may be indicated in selected patients presenting with a toxic delirium or confusional state.

Studies to Identify Infectious Agent

Herpes simplex virus (HSV) cultures of suspicious lesions and a Tzanck smear should be obtained. Viral cultures of CSF, including HSV, should be performed, although the incidence of the latter being positive is rare. Blood cultures for bacterial pathogens should be obtained.

Complement fixation antibodies are useful in identifying arbovirus. Cross-reactivity exists among a subgroup of arboviruses, the flaviviruses (eg, viruses that cause St Louis encephalitis, Japanese virus encephalitis [JE], and West Nile encephalitis [WNE]), and the antibodies found in persons inoculated with yellow fever vaccine.

Heterophile antibody and cold agglutinin testing for Epstein-Barr virus (EBV) may be helpful.

Serologic tests for toxoplasmosis can be helpful in light of an abnormal computed tomography (CT) scan, particularly in the case of single lesions. However, the overlap in titer levels between exposed but currently uninfected and reactivated groups may complicate interpretation.

Computed Tomography, Magnetic Resonance Imaging, and Electroencephalography

Performance of a head CT scan with and without contrast agent should be performed in virtually all patients with encephalitis. This should be done prior to LP if there are focal complaints or findings, signs to search for evidence of elevated intracranial pressure (ICP), obstructive hydrocephalus, or mass effect due to focal brain infection. Head CT scanning also helps exclude brain hemorrhage or infarction as a cause of an encephalopathic state. Magnetic resonance imaging (MRI) is more sensitive than CT scanning in demonstrating brain abnormalities earlier in the disease course.

In HSE, MRI may show several foci of increased T2 signal intensity in medial temporal lobes and inferior frontal gray matter. Head CT commonly shows areas of edema or petechial hemorrhage in the same areas. EEE and tick-borne encephalitis may show similar increased MRI signal intensity in the basal ganglia and thalamus.

In toxoplasmosis, contrast-enhanced head CT typically reveals several nodular or ring-enhancing lesions. Because lesions may be missed without contrast, MRI should be performed in patients for whom use of contrast material is contraindicated.

In HSE, electroencephalography (EEG) often documents characteristic paroxysmal lateral epileptiform discharges (PLEDs), even before neuroradiography changes. Eventually, PLEDs are positive in 80% of cases; however, the presence of PLEDs is not pathognomonic for HSE.

Analysis of Cerebrospinal Fluid

CSF analysis is essential. Typical patterns of findings in the CSF pressure and CSF analysis follow in the Table 1 regarding bacterial versus viral versus fungal (including cryptococcal) meningitis or encephalitis.

Table. Cerebrospinal Fluid Findings by Type of Organism

View Table

See Table

The most important diagnostic test in the emergency department (ED) to rule out bacterial meningitis is prompt Gram staining and, if available, polymerase chain reaction (PCR) of the CSF in patients with suspected HSV encephalitis. PCR for HSV DNA is 100% specific and 75-98% sensitive within the first 25-45 hours. Types 1 and 2 cross-react, but no cross-reactivity with other herpes viruses occurs. Arguably, a series of quantitative PCRs documenting the decline of viral load with acyclovir treatment is strongly supportive of the diagnosis of HSV, and selected patients my avoid need for brain biopsy.

Brain Biopsy

Although most histologic features are nonspecific, brain biopsy is the criterion standard because of its 96% sensitivity and 100% specificity.

The presence of Negri bodies in the hippocampus and cerebellum are pathognomonic of rabies, as are HSV Cowdry type A inclusions with hemorrhagic necrosis in the temporal and orbitofrontal lobes.

Approach Considerations

Prehospital care

In the prehospital setting, evaluate and treat for shock or hypotension. Administer crystalloid infusion in patients with evidence of circulatory compromise. Consider airway protection in patients with an altered mental status. Seizure precautions are indicated. Treat seizures according to usual protocols (ie, lorazepam 0.1 mg/kg given intravenously [IV]). All patients should receive oxygen and have intravenous access secured en route to the emergency department (ED). See the following for more information:

Emergency Department Care

With the important exceptions of HSE and varicella-zoster encephalitis, the viral encephalitides are not treatable beyond supportive care. Treatments for T gondii and cytomegalovirus (CMV) encephalitis are available but generally not initiated in the ED.

The goal of treatment for acutely ill patients is administration of the first dose or doses of acyclovir, with or without antibiotics or steroids, as quickly as possible. The standard for acute bacterial meningitis is the initiation of treatment within 30 minutes of arrival. Consider instituting an ED triage protocol to identify patients at risk for HSE.

Collect laboratory samples and blood cultures before the start of IV therapy. Even in uncomplicated cases of encephalitis, most authorities recommend a neuroimaging study (eg, magnetic resonance imaging [MRI] or, if that is not available, a contrast-enhanced head computed tomography [CT] scan) before lumbar puncture (LP).

Management of hydrocephalus and increased intracranial pressure

In patients with hydrocephalus and increased intracranial pressure (ICP), general measures include management of fever and pain, control of straining and coughing, and prevention of seizures and systemic hypotension.

In otherwise stable patients, elevating the head and monitoring neurologic status usually are sufficient. When more aggressive maneuvers are indicated, early use of diuresis (eg, furosemide 20 mg IV, mannitol 1 g/kg IV) may be helpful, provided that circulatory volume is protected. Dexamethasone 10 mg IV q6h helps in managing edema surrounding space-occupying lesions. Hyperventilation (arterial CO2 tension [PaCO2] 30 mm Hg) may cause a disproportional decrease in cerebral blood flow (CBF), but it is used to control increasing ICP on an emergency basis.

Intraventricular ICP monitoring is controversial. Some authorities believe that dangerous focal edema with a pressure gradient between the temporal lobe and the subtentorial space usually is not detected by the monitor and that this failure of detection can lead to a false sense of security. In fact, monitor placement may potentially aggravate a pressure gradient.

Treatment of systemic complications

Look for and treat systemic complications (eg, hypotension or shock, hypoxemia, hyponatremia, and exacerbation of chronic diseases), particularly in herpes simplex encephalitis (HSE), eastern equine encephalitis (EEE), Japanese virus encephalitis (JE).

Empiric treatment of HSV meningoencephalitis and VZV encephalitis

Empiric adult emergency treatment for herpes simplex virus (HSV) meningoencephalitis and varicella-zoster virus (VZV) encephalitis consists of acyclovir 10 mg/kg (infused over 1 h) q8h for 14-21 days. Give acyclovir 10-15 mg/kg IV q8h for neonatal HSV; for HSV encephalitis in the pediatric population, give acyclovir 10 mg/kg IV q8h.

In HIV-positive patients, consider foscarnet, given the increased incidence of acyclovir-resistant HSV and herpes zoster virus (HZV).

Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications. Antivirals are used to manage treatable viral encephalitides. Corticosteroids may be considered for postinfectious or noninfectious encephalitis.

Acyclovir (Zovirax)

Clinical Context:  Acyclovir has demonstrated inhibitory activity directed against both herpes simplex virus type 1 (HSV-1) and HSV-2, and infected cells selectively take it up.

Foscarnet (Foscavir)

Clinical Context:  Foscarnet is an organic analogue of inorganic pyrophosphate. It inhibits replication of known herpes viruses, including cytomegalovirus, CMV, HSV-1, and HSV-2. It exerts antiviral activity by inhibiting viral replication at pyrophosphate-binding sites on virus-specific DNA polymerases at concentrations that do not affect cellular DNA polymerases.

Patients who have poor clinical response or experience persistent viral excretion during therapy, especially HIV-positive patients, may be resistant to acyclovir. Patients who tolerate foscarnet may benefit from maintenance-level administration of 120 mg/kg/d early in treatment. Dosing should be individualized on the basis of the patient's renal function.

Class Summary

The goal of the use of antivirals for herpes simplex encephalitis (HSE) and varicella-zoster encephalitis is to shorten the clinical course, prevent complications, prevent the development of latency and/or subsequent recurrences, decrease transmission, and eliminate established latency.


Clinical Context:  Dexamethasone is used to treat various allergic and inflammatory diseases. It may decrease inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Class Summary

Corticosteroids are anti-inflammatory agents used for treatment of postinfectious encephalitis and acute disseminated encephalitis. These drugs are commonly presented as treatment alternatives, though supporting data are limited.

Furosemide (Lasix)

Clinical Context:  Furosemide is a loop diuretic that increases excretion of water by interfering with the chloride-binding co-transport system, which, in turn, inhibits sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. It increases renal blood flow without increasing the filtration rate. The onset of action generally is within 1 hour. It increases potassium, sodium, calcium, and magnesium excretion.

The proposed mechanism for furosemide in lowering intracranial pressure include (1) lowering cerebral sodium uptake, (2) affecting water transport into astroglial cells by inhibiting the cellular membrane cation-chloride pump, and (3) decreasing cerebrospinal fluid production by inhibiting carbonic anhydrase.

The dose must be individualized to the patient. Depending on the response, administer at increments of 20-40 mg, no sooner than 6-8 hours after the previous dose, until desired diuresis occurs. When treating infants, titrate with 1-mg/kg/dose increments until a satisfactory effect is achieved.

Mannitol (Osmitrol)

Clinical Context:  Mannitol may reduce pressure in the subarachnoid space by creating an osmotic gradient between cerebrospinal fluid in the arachnoid space and plasma. This agent is not intended for long-term use.

Initially assess for adequate renal function in adults by administering a test dose of 200 mg/kg, given IV over 3-5 minutes. This should produce a urine flow of at least 30-50 ml/h of urine over 2-3 hours.

In children, assess for adequate renal function by administering a test dose of 200 mg/kg, given IV over 3-5 minutes. This should produce a urine flow of at least 1 mL/kg over 1-3 hours.

Class Summary

These agents are used in patients with hydrocephalus and increased intracranial pressure (ICP) when more aggressive diuresis is desired.

Lorazepam (Ativan)

Clinical Context:  Lorazepam is a sedative hypnotic with a short onset of effects and relatively long half-life.

By increasing the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, lorazepam may depress all levels of the CNS, including limbic and reticular formation.

It is important to monitor the patient's blood pressure after administering a dose. Adjust the dose as necessary.

Class Summary

These agents are used to treat seizures associated with encephalitis.

What is encephalitis?How do the signs and symptoms of encephalitis vary by specific type?What is the classic presentation of encephalitis?Which physical findings suggest encephalitis?Which findings suggest herpes simplex virus (HSV) infection in neonates with encephalitis?What are complications of encephalitis?Which tests are performed in the diagnosis of encephalitis?Which studies may be performed to identify the infectious agent causing encephalitis?Which imaging studies may be helpful in the diagnosis of encephalitis?What are the parameters of cerebrospinal fluid (CSF) analysis for encephalitis?What is included in prehospital care for encephalitis?What is included in the initial emergency department (ED) care for encephalitis?What is encephalitis?Which conditions are associated with encephalitis?What is West Nile encephalitis?What is the pathophysiology of encephalitis?What causes encephalitis?What is the prevalence of encephalitis in the US?What is the most common type of viral encephalitis outside the US?How does the incidence of encephalitis vary by age?What is the prognosis of encephalitis?Where are patient education resources for encephalitis found?What is the clinical presentation of encephalitis?What are the classic signs and symptoms of encephalitis?What are the symptoms of herpes simplex encephalitis (HSE)?What are the symptoms of toxoplasma encephalopathy?Which physical findings suggest encephalitis?What are physical findings of herpes simplex virus (HSV) infection in neonates?What are complications of encephalitis?Which conditions should be included in the differential diagnoses for encephalitis?What are the differential diagnoses for Encephalitis?Why is it important to distinguish between types of encephalitis?What is the role of blood and urine tests in the diagnosis of encephalitis?Which studies are performed to identify the infectious agent causing encephalitis?What is the role of imaging in the diagnosis of encephalitis?What is the role of cerebrospinal fluid (CSF) analysis in the diagnosis of encephalitis?What is the role of Gram staining and polymerase chain reaction (PCR) in the diagnosis of encephalitis?What is the role of brain biopsy in the diagnosis of encephalitis?What is included in prehospital care of patients with encephalitis?What is the initial emergency department (ED) care for encephalitis?How are hydrocephalus and increased intracranial pressure treated in patients with encephalitis?Which systemic complications of encephalitis should be treated in the emergency department (ED)?What are empiric treatments for HSV meningoencephalitis and VZV encephalitis?What are the goals of drug treatment for encephalitis?Which medications in the drug class Benzodiazepines are used in the treatment of Encephalitis?Which medications in the drug class Diuretics are used in the treatment of Encephalitis?Which medications in the drug class Corticosteroids are used in the treatment of Encephalitis?Which medications in the drug class Antivirals are used in the treatment of Encephalitis?


David S Howes, MD, Professor of Medicine and Pediatrics, Residency Program Director Emeritus, Section of Emergency Medicine, University of Chicago, University of Chicago, The Pritzker School of Medicine

Disclosure: Nothing to disclose.


Marjorie Lazoff, MD, Editor-in-Chief, Medical Computing Review

Disclosure: Nothing to disclose.

Chief Editor

Barry E Brenner, MD, PhD, FACEP, Professor of Emergency Medicine, Professor of Internal Medicine, Program Director for Emergency Medicine, Sanz Laniado Medical Center, Netanya, Israel

Disclosure: Nothing to disclose.


Steven A Conrad, MD, PhD Chief, Department of Emergency Medicine; Chief, Multidisciplinary Critical Care Service, Professor, Department of Emergency and Internal Medicine, Louisiana State University Health Sciences Center

Steven A Conrad, MD, PhD is a member of the following medical societies: American College of Chest Physicians, American College of Critical Care Medicine, American College of Emergency Physicians, American College of Physicians, International Society for Heart and Lung Transplantation, Louisiana State Medical Society, Shock Society, Society for Academic Emergency Medicine, and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Robin R Hemphill, MD, MPH Associate Professor, Director, Quality and Safety, Department of Emergency Medicine, Emory University School of Medicine

Robin R Hemphill, MD, MPH is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

J Stephen Huff, MD Associate Professor of Emergency Medicine and Neurology, Department of Emergency Medicine, University of Virginia School of Medicine

J Stephen Huff, MD is a member of the following medical societies: American Academy of Emergency Medicine, American Academy of Neurology, American College of Emergency Physicians, and Society for Academic Emergency Medicine

Disclosure: Nothing to disclose.

Todd Pritz, MD Intensivist, St Anthony's Medical Center and St John's Mercy Medical Center

Todd Pritz, MD is a member of the following medical societies: Massachusetts Medical Society and Society of Critical Care Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Reference Salary Employment


  1. [Guideline] Tunkel AR, Glaser CA, Bloch KC, Sejvar JJ, Marra CM, Roos KL, et al. The management of encephalitis: clinical practice guidelines by the Infectious Diseases Society of America. Clin Infect Dis. 2008 Aug 1. 47(3):303-27. [View Abstract]
  2. Final 2008 West Nile Virus Activity in the United States. Centers for Disease Control and Prevention. Available at http://bit.ly/fATcE1. Accessed: April 26, 2009.
  3. MacDonald RD, Krym VF. West Nile virus. Primer for family physicians. Can Fam Physician. 2005 Jun. 51:833-7. [View Abstract]
  4. Yao K, Honarmand S, Espinosa A, Akhyani N, Glaser C, Jacobson S. Detection of human herpesvirus-6 in cerebrospinal fluid of patients with encephalitis. Ann Neurol. 2009 Mar. 65(3):257-67. [View Abstract]
  5. Bloch KC, Glaser C. Diagnostic approaches for patients with suspected encephalitis. Curr Infect Dis Rep. 2007 Jul. 9(4):315-22. [View Abstract]
  6. Hayasaka D, Aoki K, Morita K. Development of simple and rapid assay to detect viral RNA of tick-borne encephalitis virus by reverse transcription-loop-mediated isothermal amplification. Virol J. 2013 Mar 4. 10(1):68. [View Abstract]
CSF Finding (Normal) Bacterial Meningitis Viral Meningitis* Fungal Meningitis
Pressure (5-15 cm water)
  • Increased
  • Normal or mildly increased
  • Normal or mildly increased in most fungal and tuberculous CNS infections
  • Patients with AIDS and cryptococcal meningitis are at increased risk of blindness and death unless pressure maintained at < 30 cm
Cell counts, mononuclear cells/µL

Preterm (0-25)

Term (0-22)

6 mo+ (0-5)

  • Normal cell count excludes bacterial meningitis
  • Typically thousands of polymorphonuclear cells, but counts may not change dramatically or even be normal (classically in very early meningococcal meningitis or in extremely ill neonates)
  • Lymphocytosis with normal CSF chemistry results observed in 15-25% of patients, especially if counts < 1000 or if patient is partially treated
  • About 90% of patients with ventriculoperitoneal shunts and CSF WBC count >100 cells/µL are infected, though CSF glucose level often normal, and bacteria often less pathogenic
  • Cell count and chemistry levels normalize slowly (days) with antibiotics
  • Usually < 500, nearly 100% mononuclear
  • < 48 hours, clinically significant polymorphonuclear pleocytosis may be indistinguishable from early bacterial meningitis, particularly with EEE
  • Nontraumatic RBCs in 80% of patients with HSV meningoencephalitis, though 10% have normal CSF results
  • 100s of mononuclear cells
Microorganisms (none)
  • Gram stain 80% effective
  • Inadequate decolorization may cause Haemophilus influenzae to be mistaken for gram-positive cocci
  • Pretreatment with antibiotics may affect stain uptake, causing gram-positive species to appear to be gram-negative and decrease culture yield by an average of 20
  • No organism
  • India ink 80-90% effective for detecting fungi
  • AFB stain 40% effective for TB; increase yield by staining supernatant from at least 5 mL of CSF

Euglycemia (>50% serum)

Hyperglycemia (>30% serum)

  • Decreased
  • Normal
  • Sometimes decreased
  • In addition to fulminant bacterial meningitis, TB, primary amebic meningoencephalitis, and neurocysticercosis cause low glucose levels

Preterm (65-150 mg/dL)

Term (20-170 mg/dL

6 mo+ (15-45 mg/dL)

  • Usually >150 mg/dL
  • May be >1000 mg/dL
  • Mildly increased
  • Increased >1000 mg/dL, with relatively benign clinical presentation suggestive of fungal disease
*Some bacteria (eg, Mycoplasma, Listeria, Leptospira, Borrelia burgdorferi [Lyme disease]) cause alterations in spinal fluid that resemble the viral profile. An aseptic profile is also typical of partially treated bacterial infections (>33%, especially those in children, are treated with antimicrobials) and of the 2 most common causes of encephalitis—the arboviruses and the potentially curable HSV.

Wait 4 hours after glucose load.

AFB—acid-fast bacillus; CSF—cerebrospinal fluid; EEE-eastern equine encephalitis; HSV—herpes simplex virus; RBC—red blood cell; TB—tuberculosis; WBC—white blood cell.