Viral Meningitis

Updated: Jul 17, 2018
Author: Cordia Wan, MD; Chief Editor: Niranjan N Singh, MBBS, MD, DM, FAHS, FAANEM 



Viral meningitis is inflammation of the leptomeninges as a manifestation of central nervous system (CNS) infection. Viral names the causative agent, and the term meningitis implies lack of parenchymal and spinal cord involvement (otherwise called encephalitis and myelitis, respectively). Viral meningitis is also often referred to as aseptic meningitis. 

In uncomplicated viral meningitis, the clinical course is usually self-limited, with complete recovery in 7-10 days. However, when the viral pathogen causes a more involved meningoencephalitis or meningomyelitis, the course can be significantly more protracted. A magnetic resonance imaging (MRI) scan of a patient with meningoencephalitis is seen below.

T1-weighted MRI of brain demonstrates diffuse enha T1-weighted MRI of brain demonstrates diffuse enhancement of the meninges in viral meningoencephalitis.

Currently, more than 85% of viral meningitis cases are caused by nonpolio enteroviruses. Disease characteristics, clinical manifestations, and epidemiology generally mimic those of enteroviral infections.

Mumps, polio, and lymphocytic choriomeningitis viruses (LCMVs) are now rare offenders in developed countries. However, polio remains a major cause of debilitating myelitis in some regions of the world.

As discussed below, many viruses are capable of causing meningitis. This discussion attempts to simplify the microbiology of each viral family with emphasis on disease manifestations and risk factors. Note that in as many as one third of cases, no causative agents are identified. This number is improving with new testing methodologies.


Enteroviruses account for more than 85% of all cases of viral meningitis. They are part of the viral family Picornaviridae ("pico" for small, "rna" for ribonucleic acid) and include echoviruses, coxsackieviruses A and B, polioviruses, and the numbered enteroviruses. Nonpolio enteroviruses are common viruses; they are nearly as prevalent as rhinoviruses (which cause the common cold).[1]

The overwhelming majority of meningitis cases are caused by serotypes of coxsackievirus and echovirus. Coxsackievirus B subgroups alone account for more than 60% of meningitis cases in children younger than age 3 months.

Enteroviruses enter the human host usually via the oral-fecal route, but can also spread through the respiratory route.

Enteroviruses are ubiquitous in the summer and early fall; their propensity to cause infection during the warmer months is the major factor in the higher incidence of aseptic meningitis during that time.

The associated clinical findings in enteroviral infections may include pharyngitis, pleurodynia, rash, and pericarditis.

Expectant mothers infected with coxsackievirus B may remain minimally symptomatic, but their infants can acquire the infection perinatally and develop a potential fatal illness, with the infection targeted mainly toward the heart.

Enteroviruses 70 and 71, which exhibit strong neurotropism, are associated with meningoencephalitis, poliolike paralytic syndromes, and Guillain-Barre syndrome, as well as aseptic meningitis.


Arboviruses account for about 5% of cases in North America.

Arboviruses consist of more than 500 viruses from different viral families, all given the common name "ar-bo," for arthropod-borne disease. Blood-sucking arthropods, usually mosquitoes, serve as vectors for transmission.

Because exposure to mosquitoes or ticks is the risk factor for transmission, the number of infections is highest in summer and early fall, in concordance with high mosquito populations.

Some of the important arboviruses include the eastern and western equine encephalitis viruses, from the Togavirus family; St. Louis encephalitis’ West Nile, Japanese B, and Murray Valley viruses, from the Flavivirus family; and California group and Jamestown Canyon viruses, from the Bunyaviridae family. Colorado tick fever is caused by a coltivirus in the western regions of the United States.

The most common clinical manifestation is meningoencephalitis rather than pure meningitis.

Seizures are more common with arboviral meningitis than with any other group of viruses.

Some agents preferentially infect certain age groups, such as St. Louis encephalitis, which affects the extremes of age, and California virus, which infects young children. Children with St. Louis or California group encephalitis viruses may not exhibit any neurologic signs or altered mental status.

St. Louis encephalitis (SLE) virus is the most common cause of arboviral meningitis, and is also the most common mosquito-transmitted disease in the United States. Internationally, Japanese B virus is the biggest offender in this group.

Of the arboviruses, West Nile virus caused much attention, as it was first recognized in the United States only in 1999 and quickly became an epidemic in 2002, with more than 4,000 reported cases. In 2008, 1,356 cases were reported.[2]

Infection with the West Nile virus is usually asymptomatic or manifests as mild symptoms of nonspecific fever, myalgia, and fatigue. However, 1 in 150 cases develop into severe disease involving the nervous system, with encephalitis reported more than meningitis. In 2008, 687 cases of West Nile neuroinvasive disease were reported to the US Centers for Disease Control and Prevention (CDC) from all across the United States.[2]

Neuroinvasive West Nile disease occurs more often in elderly persons.


A member of the Paramyxovirus family, mumps virus was one of the first known causative agents of meningitis and meningoencephalitis.[3]

The incidence of mumps in the vaccination era has decreased significantly to 1 per 100,000 population in the United States.

Nonetheless, outbreaks have occurred in vaccinated populations, including a large epidemic in the United Kingdom that peaked in 2005 and several outbreaks in the American Midwest in 2006.[4, 18] In addition, mumps continues to cause 10-20% of meningitis and meningoencephalitis cases in parts of the world where vaccines are not readily accessible.

Males 16-21 years of age are at highest risk for developing this infection, with a 3:1 male/female ratio.

Clusters of cases occur in schools and colleges in the winter months.

Concomitant parotitis is a helpful clinical tool, but it may be absent in as many as half of cases with CNS involvement.

A cohort study of 12,000 unvaccinated children from northern Finland revealed that mumps meningoencephalitis accounted for 40.9% of all viral CNS infections. Mumps also remains an important cause of aseptic meningitis in England and Japan.[15]

In 2003, epidemics of aseptic meningitis following measles, mumps, rubella (MMR) vaccination campaigns in various nations (including Brazil and the UK) prompted the Global Advisory Committee on Vaccine Safety to conduct a review of vaccine-derived mumps meningitis.[5] At the time, the committee stated that certain strains of the mumps vaccine (Urabe, Leningrad-Zagreb, and Leningrad-3 strains) were associated with higher incidences of postvaccination aseptic meningitis.

In 2006, the committee determined that the international literature reviewed was actually inconclusive and that further studies were needed.[6] Even so, replacement mumps components were developed and vaccines were reformulated worldwide.

Herpes family viruses

Herpes simplex virus (HSV)-1, HSV-2, varicella-zoster virus (VZV), Ebstein-Barr virus (EBV), cytomegalovirus (CMV), and human herpesvirus-6 collectively cause approximately 4% of cases of viral meningitis, with HSV-2 being the most common offender. The viruses may attack at any time of the year.

Meningitis caused by these viruses is often self-limited. When associated with encephalitis, however, the mortality rate can be high. Early treatment with acyclovir can significantly reduce morbidity.

HSV-1 remains the most common cause of sporadic encephalitis, while HSV-2 infections of CNS mostly are restricted to aseptic meningitis.

HSV-2 genital infection may precede meningitis; sexual contact with actively infected individuals is one of the known risk factors.

In one review, however, only 3 of 23 patients with HSV-2 meningitis had a history of prior genital herpes or had genital lesions noted at the time of presentation.[7] Maternal-fetal transmission of HSV-2 can occur, leading to significant systemic sequelae, including infantile septicemia and death.

EBV, HSV-1, and especially HSV-2 have been associated with Mollaret meningitis, a rare, benign, recurrent meningitis that resolves spontaneously. Mollaret cells (activated monocytes with an atypical appearance of enlarged, bilobed nuclei and amorphous cytoplasm) are found in the CSF usually on the first day of symptoms. Herpesvirus-6, EBV, and the human immunodeficiency virus (HIV; which is not a member of the herpes family) have also been implicated. These viruses are all known to remain latent within the nervous system.

CMV infections occur mostly in immunocompromised hosts. CMV may cause subacute encephalitis in patients with AIDS. Congenital CMV, which is a much more serious form of infection, has significant associated morbidity and mortality.

Childhood or adult chickenpox infections by VZV rarely are complicated by meningitis. Adult zoster involving any dermatome may lead to meningitis or meningoencephalitis.

Lymphocytic choriomeningitis virus

LCMV belongs to the family of arenaviruses. Now a rare cause of meningitis, the virus is transmitted to humans by contact with rodents (eg, hamster, rats, mice) or their excreta. Persons at highest risk of infection are laboratory workers, pet owners, or persons living in nonhygienic areas.


Adenovirus is a rare cause of meningitis in immunocompetent individuals but a major cause in patients with acquired immunodeficiency syndrome (AIDS). The infection may occur simultaneously with an upper respiratory infection.


This Morbillivirus is another cause of meningitis that has become rare. The characteristic maculopapular rash aids in the diagnosis. Most cases occur in younger people in schools and colleges. Still a worldwide health threat, measles has the highest attack rate of any infection.

From January 1 through April 24, 2015, the United States experienced 5 outbreaks, with 166 cases reported.[19] Preliminary investigations of a large multistate outbreak that originated in California revealed 45% of the infected were unvaccinated, and 43% had unknown vaccination status.[19]

Eradication of measles is an important goal of the World Health Organization (WHO).


HIV may be a cause of atypical meningitis characterized by chronicity and recurrence. About the time of seroconversion, patients may present with CSF pleocytosis, elevated protein level and, occasionally, high intracranial pressure.

Reports have suggested that as many as 5-10% of HIV infections can be heralded by meningitis. Aside from the usual meningeal signs, HIV infections may also cause global encephalopathy, seizures, and focal neurologic deficits. Some patients develop chronically abnormal CSF findings with mild or no symptoms. HIV often can be isolated from the CSF.

Nonviral causes of meningitis

Tuberculous, fungal, and mycoplasmal organisms are among the important nonviral causes of aseptic meningitis and should be suspected in the appropriate clinical setting.

For example, Lyme borreliosis causes a significant number of cases of aseptic meningitis in the Northeast and Mid-Atlantic states. The diagnosis is suggested by the history of tick bite or outdoor activity in these areas of endemic disease, and the presence of erythema chronicum migrans at the site of tick bite is pathognomonic. Lyme meningitis has a predilection to cause focal cranial nerve palsies, with the seventh nerve most commonly affected.

Clinicians must consider partially-treated bacterial meningitis as a possible etiology for the aseptic nature of their patient's disease; for example, patients with bacterial otitis and sinusitis who have been taking antibiotics may present with meningitis and CSF findings identical to those of viral meningitis.

The clinician should also realize that the picture of aseptic meningitis is created not only by infectious agents, but also by chemical irritation (chemical meningitis), neoplasm (meningitis carcinomatous), granulomatous disorders, and other inflammatory conditions. This discussion, however, focuses on meningitis caused by viral agents.


Some controversy exists as to the long-term effects of viral meningitis on children, with some studies attributing learning disabilities, neuromuscular impairments (ie, mild paresis or loss of coordination), and deafness to viral meningitis. Investigators believe that most of these cases must involve the CNS parenchyma, causing encephalitis or encephalomyelitis.

Communicating hydrocephalus is a rare complication of viral meningitis and is due to obstruction of arachnoid granulations by inflammatory debris. The usual time of onset is within weeks of the original symptoms. Less common is acute hydrocephalus, with onset within hours to days of the original symptoms.


Viral pathogens may gain access to the CNS via either of 2 main routes: hematogenous and neural. The hematogenous route is more common for penetration of most known viral pathogens. Neural penetration refers to spread along nerve roots and is usually limited to herpes viruses (HSV-1, HSV-2, VZV B) and possibly some enteroviruses.

Multiple host defenses prevent viral inoculum from causing clinically significant infection. These include local and systemic immune responses, skin and mucosal barriers, and the blood-brain barrier (BBB).

The virus replicates in the initial organ system (ie, respiratory or gastrointestinal mucosa) and gains access to the bloodstream. Primary viremia introduces the virus to the reticuloendothelial organs (liver, spleen, lymph nodes). If the replication persists despite immunologic defenses, secondary viremia occurs, which is thought to be responsible for seeding of the CNS. Rapid viral replication likely plays a major role in overcoming the host defenses.

The actual mechanism of viral penetration into the CNS is not well understood. The virus may cross the BBB directly at the capillary endothelial level or through natural defects, such as the area postrema and other sites that lack a BBB.

The inflammatory response is seen in the form of pleocytosis; polymorphonuclear leukocytes (PMNs) lead the differential cell count in the first 24-48 hours, followed later by increasing numbers of monocytes and lymphocytes. The CSF lymphocytes have been recognized as T cells, although B cell immunity is also important in defending against some viruses.

Evidence exists that some viruses gain access to the CNS by retrograde transport along nerve roots. For example, the likely pathway for HSV-1 encephalitis is via the olfactory or trigeminal nerve roots, with the virus being transported by the olfactory fibers to the basal frontal and anterior temporal lobes.

Examples of modes of transmission in viral meningitis include the following (see Background):

  • Enteroviruses - Usually through the oral-fecal route, but also sometimes through the respiratory route

  • Arboviruses - Via blood-sucking arthropods, usually mosquitoes

  • Lymphocytic choriomeningitis virus - Through contact with rodents (eg, hamster, rats, mice) or their excreta


Incidence of viral meningitis in the United States

More than 10,000 cases of viral meningitis are reported annually, but the actual incidence may be as high as 75,000. Lack of reporting is due to the uneventful clinical outcome of most cases and the inability of some viral agents to grow in culture.

According to reports from the Centers for Disease Control and Prevention (CDC), inpatient hospitalizations resulting from viral meningitis range from 25,000-50,000 each year. An incidence of 11 per 100,000 population per year has been estimated in some reports.

International incidence of viral meningitis

Obtaining accurate international prevalence and incidence of this clinically heterogenous and often benign disease is difficult. Worldwide causes of viral meningitis include enteroviruses, mumps virus, measles virus, VZV, and HIV. Meningitis symptoms may develop in as few as 1 in 3,000 cases of infection by these agents.

Mumps causes 10-20% of meningitis and meningoencephalitis cases in parts of the world where vaccines are not readily accessible.

Japanese B encephalitis virus, the most common pathogen in epidemic viral meningitis worldwide, accounts for more than 35,000 infections annually throughout Asia but is estimated to cause 200-300 times that number of subclinical infections.

Viral meningitis is a notifiable disease in England and Wales, but many cases go unreported.[16] This is also true in Ireland.[17]  

Age predilection

The incidence of viral meningitis drops with age, with the incidence during the first year of life being 20 times greater than it is in older children and adults.

Studies from Finland have estimated the incidence of viral meningitis to be 19 per 100,000 population in children aged 1-4 years. This is in significant contrast to 219 cases per 100,000 population estimated for children younger than age 1 year.[15]

Most arboviruses have diverse attack characteristics that affect both sexes, but at different ages. Some agents preferentially infect certain age groups, such as St. Louis encephalitis, which affects the extremes of age, and California virus, which infects young children.

In neonates older than 7 days, enteroviruses are the most common cause of aseptic meningitis. Vaccination has greatly reduced the incidence of meningitis from mumps, polio, and measles viruses.

Some of the arboviruses strike at the extremes of age, with the elderly at greater risk of infection, while mumps and measles peak in the later teenage years.

Males 16-21 years of age are at highest risk of developing mumps. Clusters of cases occur in schools and colleges in the winter months.

Most cases of measles occur in younger people in schools and colleges.

Sex predilection

Depending on the type of viral pathogen, the ratio of affected males to females can vary. Enteroviruses are thought to affect males 1.3-1.5 times more often than females. Mumps virus is known to affect males 3 times more often than females.

Morbidity and mortality in viral meningitis

Long-term neurologic sequelae from uncomplicated viral meningitis are rare. Sequelae in children (especially infants and young children), as reported in the literature, include the following:

  • Seizure disorders

  • Hydrocephalus

  • Sensorineural hearing loss

  • Weakness

  • Paralysis

  • Cranial nerve palsy

  • Learning disabilities

  • Blindness

  • Behavior disorders

  • Speech delay

Physicians must realize that viruses capable of causing meningitis can also cause more serious infections of the CNS and other organs. Complications, such as brain edema, hydrocephalus, and seizures, can occur in the acute period.

WHO statistical reports from 1997 reported enteroviral meningitis with sepsis as the fifth most frequent cause of neonatal mortality.

Excluding the neonatal period, the mortality rate associated with viral meningitis is less than 1%; the morbidity rate is also low.


The prognosis for viral meningitis is usually excellent, with most cases resolving in 7-10 days. Implicit in the diagnosis is the self-limited nature of this disease. The exception falls with the neonatal patients, in whom viral meningitis can be fatal or associated with significant morbidity.

Concomitant encephalitis adds significant potential for adverse outcomes. Concurrent systemic manifestations, such as pericarditis and hepatitis, are other indicators of poor prognosis.

Patient Education

Pregnant women should avoid exposure to rodents, rats, and house mice, which carry LCMV. Some investigators even suggest avoidance of young children and public pools by pregnant women in the third trimester, in order to decrease the risk of enteroviral colonization and transmission to the fetus. Infected pets also pose a risk to pregnant women.

Neonates should be kept away from exposure to mosquitoes, for the prevention of arboviral infection.

Vaccination remains the most potent means of combating infections by polio, measles, mumps, and varicella viruses.

Strict handwashing is effective in controlling the spread of enterovirus-related infections, but maintaining public hygiene remains a problem in some developing countries.

The education of sex partners about the use of barrier devices can significantly decrease the incidence of HSV-2 infections.

Protection against mosquito exposure (using insect sprays, netting, and eradication of breeding sites) should be exercised to prevent arbovirus infection and is especially important in vulnerable patients, such as the young.

Avoidance of exposure to rodents can decrease the incidence of LCMV meningoencephalitis. Infected pets, house mice, and rats pose a risk to pregnant women.

For patient education information, visit eMedicineHealth's Brain and Nervous System Center and Children's Health Center. Also, see eMedicineHealth's patient education articles Meningitis in Adults, Meningitis in Children, Encephalitis, and Ticks.




Upon presentation, most patients report fever, headache, irritability, nausea, vomiting, stiff neck, rash, or fatigue within the previous 18-36 hours. Constitutional symptoms of vomiting, diarrhea, cough, and myalgias appear in more than 50% of patients.

For several weeks or longer, children may experience irritability, incoordination, and an inability to concentrate.

Headache is almost always present in patients with viral meningitis and is often reported as severe. However, the classic description of abrupt onset of the "worst headache of my life," attributable to aneurysmal subarachnoid hemorrhage, is uncommon.

History of temperature elevation occurs in 76-100% of patients who come to medical attention. A common pattern is low-grade fever in the prodromal stage and higher temperature elevations at the onset of neurological signs.

Younger children may not report headache and may simply be irritable.

Newborns may present with poor feeding and lethargy.

Some viruses cause rapid onset of the above symptoms, while others manifest as nonspecific viral prodromes, such as malaise, myalgia, and upper respiratory symptoms. In many cases, symptoms have a biphasic pattern; the nonspecific flu-like symptoms and low-grade fever precede neurologic symptoms by approximately 48 hours. With the onset of neck stiffness and headache, the fever usually returns.

Meticulous history taking is essential and must include evaluation of exposure to ill contacts, mosquitoes, ticks, outdoor activity in areas of endemic Lyme disease, travel history with possible exposure to tuberculosis, as well as history of medication use, intravenous drug use, and sexually transmitted disease risk.

An important part of the history is prior antibiotic use, which may alter the clinical picture of bacterial meningitis.

Physical Examination

Some general physical findings in viral meningitis are common to all causative agents.

The classically taught triad of meningitis consists of fever, nuchal rigidity, and altered mental status, but not all patients have all 3 symptoms.

Fever is common (80-100% of cases) and usually ranges from 38°-40°C.

Nuchal rigidity or other signs of meningeal irritation (Brudzinski or Kernig sign) may be seen in more than half of patients, but these symptoms are generally less severe than they are in bacterial meningitis. Pediatric patients, especially neonates, tend not to exhibit nuchal rigidity on examination.

Irritability, disorientation, and altered mentation may be seen.

Severe lethargy or bulging fontanelle in neonates is a sign of increased intracranial pressure but may be absent in more than half of all cases. The neonate may exhibit hypotonia, irritability, and poor feeding. The clinical picture can mimic neonatal bacterial septicemia accompanied by multiple organ system involvement.

Headache is common and is characteristically severe.

Photophobia is relatively common but may be mild. Phonophobia may also be present.

Seizures occur occasionally and are usually a result of the fever, although the involvement of brain parenchyma (encephalitis) should be considered.

Global encephalopathy and focal neurologic deficits are rare but can be present. Deep tendon reflexes are usually normal but may be brisk.

Various signs of specific viral infection can aid in diagnosis. These include the following:

  • Pharyngitis and pleurodynia in enteroviral infections

  • Skin manifestations, such as zoster eruption from VZV, maculopapular rash from measles and enteroviruses, vesicular eruption from herpes simplex, and herpangina from coxsackievirus A infections

  • Pharyngitis, lymphadenopathy, and splenomegaly, which suggest EBV infection

  • Immunodeficiency and pneumonia, which should suggest adenovirus, CMV, or HIV as the causative agent

  • Parotitis and orchitis, from mumps

  • Gastroenteritis and rash, which occur with most enteroviral infections



Diagnostic Considerations

In very young patients, the signs and symptoms of viral meningitis are not "textbook," and a high index of suspicion is required for accurate diagnosis and management. The elderly may also present with atypical signs and symptoms.

For the clinician, as previously mentioned, consideration of other pathogens, such as bacteria, mycoplasma, and fungi, is crucial. Partially untreated bacterial meningitis in particular can manifest similarly to viral meningitis. These are treatable pathogens that can have devastating outcomes if misdiagnosed.

The clinician should also realize that the picture of aseptic meningitis is created not only by infectious agents, but also by chemical irritation (chemical meningitis), neoplasm (meningitis carcinomatous), granulomatous disorders, and other inflammatory conditions.

In addition to the differentials listed in the next section, mimics of viral meningitis include the following:

  • Partially treated bacterial meningitis

  • Parameningeal infection

  • Coccidioides immitis infection

  • Cryptococcus neoformans infection

  • Histoplasma capsulatum infection

  • Candida species infection

  • Blastomyces dermatitidis infection

  • Mycoplasma infection

  • Listeria infection

  • Leptospira infection

  • Drugs

  • Heavy metals

  • Surgically implanted materials

  • Sjögren syndrome

  • Behçet disease

  • Electroencephalogram in neurologic infections

  • Cytomegalovirus encephalitis

  • Abnormal neonatal electroencephalogram

  • Low-grade astrocytoma

  • Lumbar puncture (CSF Examination)

  • Electroencephalogram in status epilepticus

  • Leptomeningeal carcinomatosis

  • Migraine variants

  • Neurocysticercosis

  • Neurosarcoidosis

  • Subdural empyema

  • Varicella zoster

  • Hydrocephalus

  • Brucellosis

  • Lyme disease

  • Neurosyphilis

  • Brucellosis

Differential Diagnoses



Approach Considerations

Routine chemistry and hematology tests should be performed.

In neonatal and severe cases of viral meningitis, arterial blood gas analysis, coagulation studies, and liver function tests should also be considered.

The serum white blood cell (WBC) count is not a sensitive indicator of the severity of infection, especially in the immunocompromised, neonatal, or elderly patient.

The serum sodium level may be abnormal because of dehydration or the rare occurrence of syndrome of inappropriate antidiuretic hormone secretion (SIADH).

The serum amylase level may be elevated in cases of viral meningitis that are caused by mumps, even in the absence of parotitis.

Reports have shown high C-reactive protein (CRP) levels in the serum of children with bacterial meningitis whose CSF Gram stain findings were negative for bacteria. However, a comparable group of children with viral meningitis did not have similar elevations in serum CRP (ie, 50-150 in bacterial meningitis group vs < 20 in the viral meningitis group).

All patients whose condition is not improving clinically within 24-48 hours should have a more extensive workup to discern the cause of meningitis.

Blood, feces, and throat swabs may be sent for viral serology and cultures.

Acid-fast staining of CSF should be performed, and the remaining fluid should be sent for testing, using the polymerase chain reaction (PCR), for HIV and CMV.[8]

Serum titers of antibodies against HIV and toxoplasma should be obtained.

Additional serum collection 10-21 days later may aid in discerning rising titers in the antibodies against specific viral pathogens; a 4-fold increase in viral antibodies confirms the diagnosis. This is particularly useful for arboviral and LCMV cases, but it also is helpful in ruling out toxoplasmosis, leptospirosis, borreliosis, and rickettsial infections. Although some of these studies do not yield an immediate result for clinical decision making, they may be useful for prognostication.

In patients in whom encephalitis is suspected, MRI with contrast enhancement and adequate visualization of the basal frontal and temporal areas is necessary

Electroencephalography (EEG) may be performed if encephalitis or subclinical seizures are suspected in the altered patient. Periodic lateralized epileptiform discharges (PLEDs) are often seen in herpetic encephalitis.

CSF Studies

CSF examination is the most important test in differentiating the cause of meningitis. Prior to lumbar puncture (LP), a computed tomography (CT) scan should be performed in patients with any abnormal neurologic sign, to exclude an intracranial lesion or obstructive hydrocephalus.[20] CSF culture remains the criterion standard in discerning bacterial or pyogenic from aseptic meningitis. Again, a partially-treated bacterial meningitis may present with a negative Gram stain result and thus appear aseptic.

Consider saving CSF for less common tests (ie, PCR for HIV and CMV) if the cause of meningitis is not certain after initial tests.

The exact sequence of testing for these agents depends on the patient’s clinical condition and on suggestive facts in his or her history and examination. For example, most cases of viral meningitis do not require PCR testing for HIV.

A high WBC count in the CSF (especially neutrophils), a high protein level, and a low glucose level should suggest a diagnosis of a bacterial meningitis, although some viral pathogens may produce similar CSF profiles.

PCR testing

Real-time PCR testing for enterovirus was first cleared for marketing in 2007 by the US Food and Drug Administration (FDA) and is now available through commercial laboratories.[9] Results are available in approximately 3 hours, as opposed to days to weeks in traditional PCR studies.

In clearing the test, the FDA cited a multicenter study in which 96% of patients who tested positive did have viral meningitis, and 97% of patients who tested negative did not have viral meningitis.

In a retrospective study of routine PCR testing of CSF for enterovirus—using a test with turnaround time of 23 hours—confirmation of enteroviral meningitis by PCR decreased the length of hospitalization and the duration of antibiotic use among infants aged 90 days or younger.[10]


A retrospective multicenter study found that neither the presence nor quantity of immature neutrophils (bands) in CSF independently predicted bacterial meningitis among children with CSF pleocytosis.[11]

Pleocytosis with WBC counts in the range of 50 to more than 1000 x 109/L of blood has been reported in viral meningitis. Mononuclear cell predominance is the rule, but PMNs may make up most cells in the first 12-24 hours; the cell count is usually then dominated by lymphocytes in the classic CSF pattern of viral meningitis. This helps to distinguish viral from bacterial meningitis, which has a much higher cell count and a predominance of PMNs in the cell differential; this is by no means an absolute rule, however.

Protein levels

The CSF protein level usually is only slightly elevated, but it can range from normal to as high as 200 mg/dL.

Glucose levels

The glucose level is normal in most cases, but severe hypoglycorrhachia has been reported, especially with LCMV or the mumps virus. Very low glucose levels with a lymphocytic pleocytosis may be seen in tuberculous meningitis.


CSF latex antigen testing helps to rule out bacterial causes of meningitis, such as Haemophilus influenzae and Neisseria meningitidis. The addition of a drop of CSF sediment to an India ink preparation may aid in the diagnosis of cryptococcal meningitis, although antigen assay testing for cryptococci is the preferred test.

Other tests

Culture, Gram stain, and acid-fast stain tests should be performed.

Tests in the absence of clinical improvement

If the CSF Gram stain result is negative but moderate-to-severe pleocytosis is noted (WBC >1000 x 109/L), a repeat LP should be considered in 12-18 hours if the patient has not improved clinically. All patients with suspected bacterial meningitis should be treated empirically with appropriate antibiotics.

After the bacterial Gram stain, latex antigen tests, and cultures return negative, antibacterial therapy can be discontinued. If the results of PCR testing of the CSF and the viral culture for herpes simplex are negative, acyclovir can be discontinued; otherwise, a 10-day course is recommended.

If no clinical improvement in the patient is noted and all the common bacterial and viral pathogens have been ruled out, the following tests should be performed and the therapy modified depending on their results:

  • CSF - Venereal Disease Research Laboratories test (VDRL), PCR for CMV, acid-fast stain

  • Skin - Purified protein derivative (PPD) to help exclude tuberculosis

Blood - HIV antibody and PCR, rapid plasma reagent (RPR), Lyme antibody (in areas of endemic disease or if history suggests), toxoplasmosis antibody (especially in infants and newborns)

CT Scanning

Imaging for suspected viral meningitis and encephalitis may include CT scanning of the head, with and without contrast, or MRI of the brain, with gadolinium.

CT scanning with contrast helps to rule out intracranial pathology. Contrasted scans should be obtained to evaluate for any enhancement along the meninges and to exclude cerebritis, intracranial abscess, subdural empyema, and other lesions.


MRI with contrast is the criterion standard in visualizing intracranial pathology in viral encephalitis. HSV-1 commonly affects the basal frontal and temporal lobes with a typical picture of diffusely enhancing bilateral lesions. An MRI scan of a patient with meningoencephalitis is seen below.

T1-weighted MRI of brain demonstrates diffuse enha T1-weighted MRI of brain demonstrates diffuse enhancement of the meninges in viral meningoencephalitis.

Lumbar Puncture

LP is the most important procedure used in the diagnosis of viral meningitis. Other potential procedures, depending on individual indications and disease severity, include intracranial pressure monitoring, brain biopsy, and ventricular drainage or shunting.[12]

CT scanning is usually performed prior to LP to rule out intracranial hematoma, mass effect, or obstructive hydrocephalus. The LP itself may provide significant symptomatic relief, presumably due to the decrease in intracranial pressure. LP should be performed in the standard sterile fashion, and the CSF opening pressure should be measured. Coagulopathy due to intrinsic or extrinsic factors (eg, warfarin) is a relative contraindication to LP. The clinician should exercise caution and, as for all medical procedures, weigh the risks and benefits associated with each individual case.

Intracranial Pressure Monitoring

Intracranial pressure monitoring is rarely needed in patients with meningoencephalitis complicated by cerebral edema. The risks of intracranial hemorrhage in cases with coagulopathy often outweigh the diagnostic benefit of the monitor. The monitor should be placed under strictly sterile conditions by a neurosurgeon or neurointensivist.

Operative Brain Biopsy

Operative brain biopsy for confirmation of herpetic encephalitis largely has been replaced by PCR testing for viral DNA. In some cases, however, encephalomalacia due to an unknown viral infection may be confused with vascular infarction or, rarely, a tumor; in these cases, a biopsy may be helpful. With the use of stereotactic localization and a needle biopsy, morbidity is minimal.

Histologic Examination

Because of the low mortality rate associated with acute viral meningitis, pathologic features other than lymphocytic response within the CSF are generally not in evidence. The leptomeninges undergo inflammation with PMNs and later mononuclear cells in the acute phase of the disease. Perivascular cuffing, neuronophagia, and an increased number of microglial cells have been noted in specimens from patients who died of viral encephalitis.

Bacterial/Viral Meningitis Score

In 2007, the Pediatric Emergency Medicine Collaborative Research Committee of the American Academy of Pediatrics published a Bacterial Meningitis Score that clinically predicts whether patients are at high or low risk for having bacterial meningitis versus aseptic meningitis.[13] According to the score, patients have a very low risk for bacterial meningitis if all of the following are absent:

  • Positive CSF Gram stain

  • CSF absolute neutrophil count (ANC) of ≥1000

  • CSF protein of ≥80 mg/dL

  • Peripheral ANC of ≥10,000 cells/mcL

  • Seizure before or at time of presentation

The higher number of criteria present, the higher the chance is that the patient has bacterial meningitis.



Approach Considerations

Treatment for viral meningitis is mostly supportive. Rest, hydration, antipyretics, and pain or anti-inflammatory medications may be given as needed. The most important decision is whether to initiate antimicrobial therapy empirically for bacterial meningitis while waiting for the cause to be identified. Intravenous (IV) antibiotics should be administered promptly if bacterial meningitis is suspected.[14]

No surgical therapy is usually indicated in patients with viral meningitis. In rare patients in whom viral meningitis is complicated by hydrocephalus, a CSF diversion procedure, such as ventriculoperitoneal (VP) or LP shunting, may be required. Ventriculostomy with an external collection system is indicated in the rare cases of acute hydrocephalus.

Pharmacologic Treatment and Medical Procedures

Patients with signs and symptoms of meningoencephalitis should receive acyclovir early to possibly curtail HSV encephalitis. Therapy can be modified as the results of Gram stain, cultures, and PCR testing become available. Patients in unstable condition need critical care unit admission for airway protection, neurologic checks, and the prevention of secondary complications.

Enteroviruses and HSV are each capable of causing viral septic shock in newborns and infants. In these young patients, broad-spectrum antibacterial coverage and acyclovir should be instituted as soon as the diagnosis is suspected. Special attention should be paid to fluid and electrolyte balance (especially sodium), since SIADH has been reported. Fluid restriction, diuretics, and, rarely, hypertonic saline infusion may be used to correct the hyponatremia. Prevention of secondary infections of urinary tract and pulmonary systems is of paramount importance.

Waiting for LP results should not delay administration of antibiotics when warranted on clinical grounds. Broad-spectrum coverage is attained with ampicillin and a third-generation cephalosporin (ceftriaxone or cefotaxime; ceftazidime can also be used). Aminoglycosides are used in severe infections in neonates or children. Antituberculous, antifungal, and antiretroviral medications are reserved for clinically suggested or laboratory-confirmed cases.

Seizures should be treated immediately with IV anticonvulsants, such as lorazepam, phenytoin, midazolam, or a barbiturate. Unconscious patients with viral encephalitis may be in nonconvulsive status epilepticus, and EEG is used to reveal and monitor subclinical seizures.

Cerebral edema does occur in cases of severe encephalitis and may require intracranial pressure control by infusion of mannitol (1 g/kg initial dose followed by 0.25-0.5 g/kg q6h), IV dexamethasone, or intubation and mild hyperventilation, with arterial PCO2 around 28-30 mm Hg. Placement of an intracranial pressure monitor with transduced intraparenchymal pressure is recommended in these cases.

Multiple antiviral medications are currently being tested in the general population; their impact on preventing the potential, rare sequelae of viral meningitis has not yet been established. In herpetic viral infections, acyclovir is significantly beneficial only if given very early in the course of the infection. Suspected cases should be treated as soon as possible; in cases complicated by seizures, encephalitis is assumed and acyclovir should be initiated.

Anti-HIV therapy is initiated when the patient’s history or associated risk factors suggest the early phases of HIV meningoencephalitis.

Ganciclovir for CMV-related infections is reserved for severe cases with positive CMV culture or when a congenital infection or an AIDS-related infection is strongly suspected.

Administration of IVIg to neonates with overwhelming enteroviral meningitis has met with occasional success and is reserved for severe cases lacking other therapeutic options.

Patient Activity

A patient’s activity limitations should be individualized based on each patient's clinical picture. Bed rest is recommended for the acute phase of infection.

Patient Transfer

Patients with focal signs, severe lethargy, or headache should be transferred to the closest institution with CT-scanning capability. Children younger than age 1 year and neonates should be transferred to a hospital equipped with pediatric intensive care capability.

Medications should be instituted prior to transfer in select cases, particularly agents being used in empiric therapy for bacterial meningitis, if indicated.

Outpatient Treatment and Follow-up

Although most patients with signs of meningitis are hospitalized, a subgroup with aseptic meningitis is treated appropriately in an ambulatory setting. Absolute criteria for discharge of these patients from the emergency department (ED) have not been established, but investigations in children suggest that age greater than 1 year, nontoxic clinical appearance, normal serum WBC count, mild CSF pleocytosis, negative CSF Gram stain, adequate control of symptoms, and a reliable family setting may serve as some useful factors in the decision to discharge.

Prospective studies would aid in further delineating guidelines for patient discharge and follow-up. Most admissions are for IV hydration, empiric antibiotics, and observation, or they occur if a diagnosis other than viral meningitis is being considered.

Arrange follow-up with the primary care physician in 1-3 days, with explicit instructions to return to the ED in case of any clinical worsening. A follow-up call in a day to report on the status of the patient seems like a common-sense recommendation.

In select patients, additional serum specimens 10-21 days later may reveal a specific viral antibody titer rise, which is useful in arboviral, LCMV, and some nonviral causes of aseptic meningitis.

In cases complicated by seizures, outpatient anticonvulsants should be continued and close follow-up should be considered in the first week after discharge.

Outpatient supplies of antipyretics, such as acetaminophen, and antiemetics, such as promethazine, may be given to ambulatory patients who do not appear clinically toxic. No strict criteria exist for discharging patients with viral meningitis.


Consultations may be sought from clinicians in the following fields:

  • Neurology - Seizure control, EEG, management of brain edema in refractory cases, neurointensive care

  • Neurosurgery - Placement of intracranial pressure monitor, CSF shunting or temporary drainage in patients with hydrocephalus, neurointensive care

  • Infectious disease - Control of epidemics, isolation of patient and contacts, choice of antibiotics in refractory or atypical cases

  • Neonatology - Any newborn or infant with severe viral meningitis requiring intensive care



Medication Summary

Symptomatic control with antipyretics, analgesics, and antiemetics is usually all that is needed in the management of uncomplicated viral meningitis.

The decision to start antibacterial therapy for treatment of possible bacterial meningitis is the most crucial; empiric antibacterial therapy for likely pathogens should be considered in the context of the clinical setting.

Acyclovir should be used in cases suspicious for HSV (patients with herpetic lesions), and is usually used empirically in more severe cases complicated by encephalitis or sepsis.

Anti-HIV therapy is initiated when the patient’s history strongly suggests the presence of HIV infection and/or confirmatory tests have proven that an infection exists. Ganciclovir for CMV-related infections is reserved for severe cases with positive CMV culture or congenital infection, or for immunocompromised patients.

Administration of IVIg to neonates with overwhelming enteroviral meningitis has met with only occasional success and is not covered in this section.

Antiemetic Agents

Class Summary

These agents are used mostly to prevent chemotherapy-induced nausea and vomiting.

Ondansetron (Zofran, Zofran ODT, Zuplenz)

This is a selective 5-HT3-receptor antagonist that blocks serotonin peripherally and centrally. It has efficacy in patients who do not respond well to other antiemetics.

Droperidol (Inapsine)

Droperidol is a neuroleptic agent that may reduce emesis by blocking dopamine stimulation of the chemoreceptor trigger zone. It also has antipsychotic and sedative properties.

Promethazine (Phenergan, Promethegan)

Promethazine is used for symptomatic treatment of nausea in vestibular dysfunction. It is an antidopaminergic agent effective in treating emesis. It blocks postsynaptic mesolimbic dopaminergic receptors in the brain and reduces stimuli to brainstem reticular system.

Antiviral Agents

Class Summary

Antienteroviral therapy is under investigation for viral meningitis and may soon become available. Anti-HIV and antituberculosis regimens are not covered here, but they should be instituted if infection with HIV or tuberculosis is strongly suggested clinically or is confirmed by testing. Empiric therapy can be discontinued once the cause of viral meningitis has been established and bacterial meningitis excluded.

Acyclovir (Zovirax)

Acyclovir is to be started as soon as the diagnosis of herpetic meningoencephalitis is suspected. The drug inhibits the activity of HSV-1 and HSV-2.


Class Summary

Symptomatic control with antipyretics and analgesics is needed in the management of uncomplicated viral meningitis.

Acetaminophen (Tylenol, FeverAll)

Acetaminophen inhibits action of endogenous pyrogens on heat-regulating centers. It reduces fever by a direct action on the hypothalamic heat-regulating centers, which, in turn, increase the dissipation of body heat via sweating and vasodilation.

Ibuprofen (Motrin, Advil)

Ibuprofen is the drug of choice for patients with mild-to-moderate pain. It inhibits inflammatory reactions and pain by decreasing prostaglandin synthesis.

Naproxen (Aleve, Naprosyn)

Naproxen is used for relief of mild-to-moderate pain. It inhibits inflammatory reactions and pain by decreasing activity of cyclo-oxygenase, which results in a decrease of prostaglandin synthesis.


Class Summary

Empiric therapy for likely pathogens should be considered in the context of the clinical setting. Broad-spectrum coverage is attained with ampicillin and a third-generation cephalosporin (ceftriaxone or cefotaxime; ceftazidime can also be used). Aminoglycosides are used in severe infections in neonates or children.


Ampicillin is a broad-spectrum penicillin. It interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms. It is an alternative to amoxicillin when unable to take medication orally. It is indicated for L monocytogenes and S agalactiae meningitis, usually in combination with gentamicin.

Ceftriaxone (Rocephin)

Ceftriaxone is a third-generation cephalosporin with broad-spectrum, gram-negative activity. It has lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. Bactericidal activity results from inhibiting cell wall synthesis by binding to one or more penicillin binding proteins. It exerts antimicrobial effect by interfering with synthesis of peptidoglycan, a major structural component of bacterial cell wall. Bacteria eventually lyse due to the ongoing activity of cell wall autolytic enzymes while cell wall assembly is arrested.

Cefotaxime (Claforan)

Cefotaxime is a third-generation cephalosporin with broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. It arrests bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins, which in turn inhibits bacterial growth. Safety profile is more favorable than aminoglycosides. It is used to treat suspected or documented bacterial meningitis caused by susceptible organisms such as H influenzae or N meningitides.

Ceftazidime (Fortaz, Tazicef)

Ceftazidime is a third-generation cephalosporin with broad-spectrum, gram-negative activity, including pseudomonas; lower efficacy against gram-positive organisms and higher efficacy against resistant organisms. It arrests bacterial growth by binding to one or more penicillin-binding proteins, which, in turn, inhibit the final transpeptidation step of peptidoglycan synthesis in bacterial cell wall synthesis, thus inhibiting cell wall biosynthesis. The condition of the patient, severity of the infection, and susceptibility of the microorganism should determine the proper dose and route of administration.


Gentamicin is an aminoglycoside antibiotic that inhibits protein synthesis by irreversibly binding to 30s ribosome. Aminoglycosides are used in severe infections in neonates or children.


Class Summary

Seizures should be treated immediately with IV anticonvulsants, such as lorazepam, phenytoin, midazolam, or a barbiturate.

Lorazepam (Ativan)

Lorazepam is a benzodiazepine and sedative hypnotic with short onset of effects and relatively long half-life. It increases the action of gamma-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter in the brain, and may depress all levels of CNS, including limbic and reticular formation. It is important to monitor patient's blood pressure after administering dose and adjust as necessary.


Midazolam is a shorter-acting benzodiazepine sedative-hypnotic useful in patients requiring acute and/or short-term sedation.


Phenytoin is a hydantoin that may act in motor cortex, where it may inhibit spread of seizure activity. Activity of brain stem centers responsible for tonic phase of grand mal seizures may also be inhibited. Phenytoin doses should be individualized.


Phenobarbital is a barbiturate that elevates seizure threshold, limits the spread of seizure activity, and has sedative effects.


Questions & Answers


What is viral meningitis?

How long is the clinical course of viral meningitis?

What is the cause of viral meningitis?

What is the role of enteroviruses in the etiology of viral meningitis?

What is the role of arboviruses in the etiology of viral meningitis?

What is the role of Rubulavirus (mumps virus) in the etiology of viral meningitis?

What is the role of herpes viruses in the etiology of viral meningitis?

What is the role of LCMV in the etiology of viral meningitis?

What is the role of adenovirus in the etiology of viral meningitis?

What is the role of morbillivirus in the etiology of viral meningitis?

What is the role of HIV in the etiology of viral meningitis?

What are nonviral causes of aseptic meningitis?

What are the possible complications and long-term sequelae of viral meningitis?

What is the pathogenesis of viral meningitis?

How is viral infection transmitted in viral meningitis?

How prevalent is viral meningitis in the US?

How prevalent is viral meningitis globally?

How does the prevalence of viral meningitis vary by age?

How does the prevalence of viral meningitis vary by sex?

What are long-term neurologic sequelae in children with viral meningitis?

What are possible complications during the acute phase of viral meningitis?

What is the mortality rate for viral meningitis?

What is the prognosis of viral meningitis?

How can viral meningitis be prevented?


What are the signs and symptoms of viral meningitis?

What should be the focus of patient history in suspected viral meningitis?

Which physical findings suggest viral meningitis?

Which signs of specific viral infection can aid in diagnosis of viral meningitis?


What alternative etiologies should be considered in the evaluation of viral meningitis?

Which conditions should be included in the differential diagnoses of viral meningitis?

What are the differential diagnoses for Viral Meningitis?


Which lab tests are used in the diagnosis of viral meningitis?

How is cerebrospinal fluid (CSF) testing used to differentiate the cause of viral meningitis?

What is the role of polymerase chain reaction (PCR) testing in the workup of viral meningitis?

What does a finding of pleocytosis indicate in the workup of viral meningitis?

Which CSF protein levels suggest viral meningitis?

Which CSF glucose levels suggest viral meningitis?

What is the role of CSF latex antigen testing in the workup of viral meningitis?

When are culture, Gram stain, and acid-fast stain tests indicated in the workup of viral meningitis?

Which tests should be performed in the absence of clinical improvement of viral meningitis?

What is the role CT scanning in the diagnosis of viral meningitis?

What is the role of MRI in the diagnosis of viral meningitis?

What is the role of lumbar puncture in the diagnosis of viral meningitis?

What is the role of intracranial pressure monitored in the management of viral meningitis?

When is operative brain biopsy indicated in the diagnosis of viral meningitis?

Which histologic findings suggest viral meningitis?

What is the Bacterial Meningitis Score and how is it used in the diagnosis of viral meningitis?


What are the treatment options for viral meningitis?

When is surgery indicated for viral meningitis?

How is meningoencephalitis caused by viral meningitis treated?

How is septic shock caused by viral meningitis treated in newborns and infants?

When should medications be initiated for the treatment of viral meningitis?

How are seizures caused by viral meningitis treated?

What is the treatment for cerebral edema caused by viral meningitis?

Which antiviral medications are used in the treatment of viral meningitis?

What activity restrictions are included in the treatment of viral meningitis?

When should a patient be transferred for treatment of viral meningitis?

When is viral meningitis treated in an outpatient setting?

What monitoring is needed following treatment of viral meningitis?

What is the role of antipyretics in the treatment of viral meningitis?

Which specialist consultations are needed for the management of viral meningitis?


Which medication is used in the treatment of viral meningitis?

Which medications in the drug class Anticonvulsants are used in the treatment of Viral Meningitis?

Which medications in the drug class Antibiotics are used in the treatment of Viral Meningitis?

Which medications in the drug class Analgesics are used in the treatment of Viral Meningitis?

Which medications in the drug class Antiviral Agents are used in the treatment of Viral Meningitis?

Which medications in the drug class Antiemetic Agents are used in the treatment of Viral Meningitis?