Viral Meningitis- 6 Interesting Facts

Viral Meningitis in Adults

Viral meningitis is an infection of the tissues (meninges) that cover the brain and spinal cord. Many common viruses can cause viral meningitis.

Most people with viral meningitis get better without treatment in about 10 days. However, it is important to be evaluated by your health care provider to make sure you do not have bacterial meningitis.

Bacterial meningitis has similar symptoms, but it is much more dangerous and must be treated quickly with antibiotics.

Interesting Facts

  1. Viral meningitis is a viral infection of the meninges and cerebrospinal fluid, usually evolving acutely over a few hours to several days
  2. Enteroviruses cause 80% to 90% of viral meningitis cases; other common causes are HSV, varicella-zoster virus, mumps virus, lymphocytic choriomeningitis virus, HIV, and arboviruses (eg, West Nile virus)
  3. Presentation varies with age, but generally includes fever, headache, and neck stiffness; neonates may develop severe multisystem disease, presenting with irritability, poor feeding, vomiting, diarrhea, hypotension, tachycardia, seizures, and respiratory distress
  4. Diagnosis is made by lumbar puncture and analysis of cerebrospinal fluid; typical findings include a lymphocytic pleocytosis and cerebrospinal fluid/serum glucose ratio of 0.50 to 0.66 or slightly lower 1
    • Tests to identify a specific causative virus in cerebrospinal fluid include polymerase chain reaction assays (for enteroviruses, HSV types 1 and 2, and varicella-zoster virus) and IgM assays (for mumps virus and West Nile virus)
    • Other tests may provide evidence of the causative virus, such as polymerase chain reaction assay on nasopharyngeal or rectal swabs (for enteroviruses), on saliva or urine (for mumps virus), and on fluid from vesicles on skin or mucus membranes (for HSV or varicella-zoster virus); acute and convalescent serology may aid diagnosis of some viral causes
  5. Treatment of viral meningitis is usually supportive and symptomatic and includes fluids, analgesics, and antiemetics. Guidelines differ on whether to administer antiviral therapy (eg, acyclovir, valacyclovir) in absence of encephalitis, but many authorities recommend it
  6. Prognosis is good in most cases, with uneventful recovery and no long-term sequelae; exceptions include neonates, older adults with West Nile virus infection, and those with untreated hypo- or agammaglobulinemia

Urgent Action

  • Administer empiric antibiotics to all patients in whom bacterial meningitis (including partially treated) cannot be quickly excluded

What are the causes of Viral Meningitis ?

Many common viruses can cause viral meningitis, including:

  • Enteroviruses. These types of viruses are the most common cause of viral meningitis.
  • Herpes.
  • HIV (human immunodeficiency virus).
  • Measles.
  • Mumps.
  • Chicken pox (varicella-zoster).
  • Flu (influenza) viruses.

These viruses can be spread in different ways, such as through contact with:

  • Stool. This means that you could get sick by touching something that has been contaminated with infected stool and then touching your eyes, nose, or mouth.
  • Respiratory secretions. This means that you could get sick from coughs or sneezes of an infected person, similar to the spreading of the common cold.
  • Infected blood or infected bodily fluids.
  • Rodents.
  • Mosquito bites or tick bites.

When a virus enters your system, it can spread through the blood to reach the brain and spinal cord.

What increases the risk?

You may be at higher risk for meningitis if you have a weakened disease-fighting system (immune system).

What are the signs or symptoms?

Symptoms of viral meningitis may be similar to symptoms of a cold or flu. Signs and symptoms may include:

  • Fever.
  • Headache.
  • Stiff neck.
  • Muscle aches.
  • Nausea and vomiting.
  • Sensitivity to light.
  • Tiredness.
  • Cough.

How is this diagnosed?

This condition may be diagnosed based on your symptoms, your medical history, and a physical exam. You may be asked to touch your chin to your neck to see if this causes pain. You may have tests, such as:

  • Lumbar puncture. In this procedure, also called a spinal tap, a small amount of fluid from your spinal canal (cerebrospinal fluid) is removed and analyzed.
  • Blood tests.
  • Other fluid or tissue samples.
  • CT scan.
  • MRI.

How is this treated?

Most types of viral meningitis go away without treatment. You may be given antibiotic medicine through an IV tube until your health care provider is sure that you do not have bacterial meningitis. The antibiotic will be stopped as soon as viral meningitis is diagnosed.

Depending on the type of virus that caused your meningitis, you may be given:

  • Antiretroviral medicine.
  • Antiviral medicine.
  • Medicines that reduce fever and pain.
  • Medicines that reduce swelling (steroids).

Follow these instructions at home:

  • Take over-the-counter and prescription medicines only as told by your health care provider.
  • If you are taking a medicine for viral meningitis, do not stop taking the medicine even if you start to feel better.
  • Drink enough fluid to keep your urine clear or pale yellow.
  • Rest at home until you feel better. Return to your normal activities as told by your health care provider.
  • Keep all follow-up visits as told by your health care provider. This is important.

How is this prevented?

  • Get a flu shot (influenza vaccination) every year. This will help prevent meningitis that is caused by flu viruses.
  • Wash your hands often with soap and water. If soap and water are not available, use hand sanitizer.
  • Avoid touching your hands to your face when you have not washed your hands recently.
  • Avoid close contact with people who are sick.
  • Disinfect counters and other surfaces if someone in your home is sick.
  • Stay home while you are sick, and try to stay away from others as much as possible to avoid spreading the infection.
  • Cover your nose and mouth when you sneeze or cough.
  • Use insect repellent to prevent mosquito bites.

Contact a health care provider if:

  • Your symptoms do not improve after 7–10 days.
  • You have a fever that does not get better with medicine.

Get help right away if:

  • Your symptoms get worse.
  • You become confused.
  • You become very sleepy.

Viral Meningitis in Children

Most children with viral meningitis get better without treatment in about 10 days. Infants are most likely to have a more severe infection.

It is important to have your child evaluated by a health care provider to make sure your child does not have bacterial meningitis.

What are the signs or symptoms?

Symptoms of viral meningitis may be similar to symptoms of a cold or flu. Signs and symptoms may include:

  • Fever.
  • Headache.
  • Stiff neck.
  • Muscle aches.
  • Nausea and vomiting.
  • Sensitivity to light.
  • Tiredness.
  • Cough.
  • Irritability.
  • Fatigue.
  • Mental confusion.
  • Seizures.

Common symptoms in infants include:

  • Fever.
  • Poor feeding.
  • Lack of energy.
  • Irritability.
  • Sleepiness.

How is this diagnosed?

This condition may be diagnosed based on your child’s symptoms, his or her medical history, and a physical exam. Your child may be asked to touch his or her chin to his or her neck to see if this causes pain. Your child may have tests, such as:

  • Lumbar puncture. In this procedure, also called a spinal tap, a small amount of fluid from your child’s spinal canal (cerebrospinal fluid) is removed and analyzed.
  • Blood tests.
  • Other fluid or tissue samples.
  • Imaging tests to check for inflammation in your child’s brain (encephalitis). These tests may include:
    • CT scan.
    • MRI.

How is this treated?

Most types of viral meningitis go away without treatment. Your child may be given:

  • Antibiotic medicine through an IV tube. This may be given until your child’s health care provider is sure that your child does not have bacterial meningitis. The antibiotic will be stopped as soon as viral meningitis is diagnosed.
  • Medicines that reduce fever and pain.
  • Medicines that reduce swelling (steroids), if your child has signs of encephalitis.

Follow these instructions at home:

  • Give your child over-the-counter and prescription medicines only as told by your child’s health care provider.
  • If your child is taking an antibiotic, make sure that your child does not stop taking the medicine even if he or she starts to feel better.
  • Have your child drink enough fluid to keep his or her urine clear or pale yellow.
  • Have your child rest at home until he or she feels better. Your child may return to normal activities as told by his or her health care provider.
  • Keep all follow-up visits as told by your child’s health care provider. This is important.

How is this prevented?

  • Have your child:
  • Get a flu shot (influenza vaccination) every year. This will help prevent meningitis that is caused by flu viruses. A yearly (annual) flu shot is recommended for every child who is 6 months of age or older.
    • Wash his or her hands often with soap and water. If soap and water are not available, your child should use hand sanitizer.
    • Avoid touching his or her face when he or she has not washed hands recently.
    • Avoid close contact with people who are sick.
    • Stay home while he or she is sick, and try to have him or her stay away from others as much as possible to avoid spreading the infection.
    • Cover his or her nose and mouth when he or she sneezes or coughs.
    • Use insect repellent to prevent mosquito bites.
  • Disinfect counters and other surfaces if someone in your home is sick.

Contact a health care provider if:

  • Your child has a fever that does not get better with medicine.
  • Your child’s symptoms do not improve after 7–10 days.

Get help right away if:

  • Your child who is younger than 3 months old has a temperature of 100°F (38°C) or higher.
  • Your child’s heart is beating very quickly.
  • Your child has trouble breathing.
  • Your child becomes confused.
  • Your child becomes very sleepy.
  • Your child has a seizure.
  • Your child has nausea and vomiting that do not go away.

Detailed Information

Pitfalls

  • Partially treated bacterial meningitis may mimic viral meningitis; obtain a careful history of recent and current antibiotic use

Terminology

Clinical Clarification

  • Viral meningitis is a viral infection of the meninges and cerebrospinal fluid 2
    • Although distinguished from encephalitis (ie, inflammation of brain parenchyma), overlap (meningoencephalitis) occurs in some cases
    • Additionally, some viral agents can cause concurrent meningitis, encephalitis, and/or myelitis (ie, inflammation of spinal cord)
  • Most common form of meningitis

Diagnosis

Clinical Presentation

History

  • Evolution is usually acute, evolving over several hours to several days
  • Presentations may vary somewhat by age
    • Infants
      • In infants, especially neonates, there may be a history of maternal fever during the perinatal period
      • Fever, irritability, high-pitched crying, poor feeding, vomiting, diarrhea, cough or nasal stuffiness, lethargy, or altered sleep pattern may be noted
      • Neonates may present with severe systemic illness, including seizures or respiratory distress
    • Children, adolescents, and adults
      • Illness may be biphasic, with nonspecific constitutional symptoms (eg, fever, fatigue, malaise, nausea) that resolve and are followed by recurrent fever associated with:
        • Headache, typically severe and frontal
        • Photophobia
        • Stiff neck
      • There may be associated nausea, vomiting, diarrhea, cough, or sore throat
      • Some viruses cause characteristic extraneural manifestations, for example:
        • Rashes or enanthema
        • Pleurodynia (pleuritic chest pain)
        • Pericarditis, which is characterized by substernal chest pain that is relieved by sitting up and leaning forward
    • Older adults (eg, those aged 65 years or older) and immunocompromised patients
      • Typical symptoms may not occur
      • Presenting symptoms may be limited to confusion, lethargy, and inanition
  • Elicit thorough history of recent travel and household, medical, occupational, and recreational exposures
    • Exposure to illness (eg, mumps, mononucleosis)
      • Knowledge of community outbreaks (eg, enterovirus, West Nile virus, mumps) may provide clues
    • Exposure to human blood or other bodily fluids
      • Consider HIV risk factors
    • Exposure to mosquitoes, ticks, or rodents (especially mice)
      • Arboviruses 3
        • Mosquitoborne: West Nile virus, St Louis encephalitis virus, and Murray Valley encephalitis
        • Tickborne: tickborne encephalitis, Colorado tick virus, and Powassan virus
      • Exposure to house mice droppings may lead to infection with lymphocytic choriomeningitis virus
    • Travel within and outside home country
      • Geographic distribution of arboviruses varies from region to region, between and within continents 4
        • North America: West Nile virus and St Louis encephalitis virus
        • South and Central America: West Nile virus, dengue, and chikungunya virus
        • Asia: tickborne encephalitis (central and west Asia), West Nile (west Asia), dengue, chikungunya virus, and Japanese encephalitis virus
        • Africa: West Nile virus and dengue
        • Australia: Murray Valley encephalitis and West Nile virus
        • Europe: tickborne encephalitis, West Nile virus, and Toscana virus (southern Europe)
      • Travelers may be exposed to other causes of viral meningitis in certain areas (eg, mumps in areas with low immunization rates)
    • Immunizations
      • Rarely, disease may be caused by live virus vaccine strains (eg, mumps) in a recent immunization 5
      • Conversely, lack of immunization may heighten suspicion for causes such as measles, mumps, rubella, varicella, and herpes zoster
  • Careful history of current and recent medication use is important
    • Some medications (eg, NSAIDs, sulfa drugs) can cause drug-induced aseptic meningitis; clinical presentation and cerebrospinal fluid pattern are similar to those of viral meningitis
    • Antibiotics, both prescribed and self-medicated, may alter the course of bacterial meningitis and cause it to mimic viral meningitis

Physical examination

  • Fever is almost invariably present in children, but adults are frequently afebrile 6
  • Infants
    • Irritable and fussy
    • Bulging fontanelle may or may not be evident
    • Neck may be stiff but more often is not
    • Exanthem and/or enanthema may be detected
    • Neonates may present with severe systemic illness, including hypotension, tachycardia, seizures, and respiratory distress (eg, tachypnea, nasal flaring, wheezing, apnea)
  • Children, adolescents, and adults
    • Incidence of nuchal rigidity increases with age, and is usually present in patients older than infants
    • Brudzinski and Kernig signs have low sensitivity and may not be elicited
      • Kernig sign
        • Hip is flexed at 90° in the supine position; passive knee extension causes resistance in lower back and posterior thigh
      • Brudzinski sign
        • Passive neck flexion in a supine patient causes knee or hip flexion
    • Neurologic examination findings are usually normal; there are no focal neurologic signs and mental status is intact
    • Additional findings sometimes suggest the cause:
      • Generalized lymphadenopathy and/or pharyngitis: HIV or Epstein-Barr virus
      • Vesicular ulcers in the posterior oropharynx: herpangina, usually due to coxsackievirus or other enteroviruses
      • Vesicular stomatitis accompanied by a papular or vesicular rash of hands and feet: coxsackievirus or other enteroviral cause
      • Swollen salivary glands (most commonly parotid glands) or testes: mumps
      • Pleural or pericardial rub: coxsackievirus
      • Genital or perianal vesicles: HSV
      • Unilateral vesicular rash in dermatomal distribution: varicella-zoster virus
        • Note that varicella-zoster virus may cause meningitis even when there are no skin lesions

Causes and Risk Factors

Causes

  • When a causal agent is identified, enteroviruses account for 80% to 90% of cases 2 4
    • Primarily coxsackievirus and echovirus in children
    • Parechovirus has been associated with severe disease in neonates, including organ system involvement 5
  • Other commonly identified causes include:
    • HSV (type 2 more often than type 1)
    • Varicella-zoster virus
    • HIV
    • Lymphocytic choriomeningitis virus
    • Mumps virus (a significant cause in areas where mumps is endemic)
    • Arboviruses
      • In the United States, West Nile virus and St Louis encephalitis virus are the most commonly implicated arboviruses
      • Other arboviruses known to cause viral meningitis include Colorado tick fever virus, Murray Valley encephalitis virus, Venezuelan encephalitis virus, and dengue virus
    • Less common causes:
      • Several other human herpesviruses:
        • Epstein-Barr virus
        • Cytomegalovirus
        • Human herpesvirus 6

Risk factors and/or associations

Age
  • Most common in infants and young children
  • Neonates are at risk for more severe manifestations of parechovirus infections
Sex
  • Mumps meningitis is 3 times more common in males than in females 7
Other risk factors/associations
  • Seasonality (in temperate climates): 7
    • Enteroviral infections are more common in summer and fall
    • Mumps tends to occur in late winter and early spring
    • Lymphocytic choriomeningitis virus infection is more common in winter
    • Arboviral infections are more common in summer and fall
  • Immunodeficiency
    • Increases the risk for cytomegalovirus meningitis

Diagnostic Procedures

Primary diagnostic tools

  • Primary diagnostic tools are history, physical examination, and cerebrospinal fluid analysis
  • Diagnostic challenges include:
    • Differentiating viral meningitis from bacterial and fungal meningitis
    • Identifying treatable causes of viral meningitis (primarily HSV and varicella-zoster virus)
  • Perform a lumbar puncture in all patients in whom meningitis is suspected, unless there is a clear contraindication (eg, uncorrected coagulopathy, uncontrolled seizures) or unless CT imaging is required to ensure that the tap can be done without risk of brain herniation 4
    • Indications for CT imaging include: 8
      • Immunocompromised state
      • New onset of seizures
      • History of central nervous system disorder (eg, stroke, mass lesion, focal infection)
      • New focal neurologic finding
      • Papilledema
      • Decreased level of consciousness (ie, Glasgow Coma Scale score less than 12, or fluctuation of score by 2 points or more)
    • If parenchymal brain involvement (ie, encephalitis) is suspected, perform an MRI 9
  • Cerebrospinal fluid analysis should include cell count and differential; protein, glucose, and lactate levels; Gram stain; and culture 2 4
    • When viral meningitis is suspected, tests should include polymerase chain reaction for enteroviruses, HSV types 1 and 2, and varicella-zoster virus
    • Add tests for other causative agents based on epidemiology (eg, mumps virus, West Nile virus, HIV)
  • In all patients, using blood specimen drawn concurrently with lumbar puncture, obtain serum chemistry panel including liver function tests, CBC with differential cell count, coagulation tests, and blood cultures 1 2
    • Serum procalcitonin level may be helpful in differentiating bacterial from viral meningitis
  • Obtain and store a blood specimen in case acute and convalescent serologic tests are needed for diagnosis (eg, for mumps, lymphocytic choriomeningitis, or rickettsial infections) 1 2
  • Other tests to consider based on epidemiology and clinical presentation include: 4
    • Polymerase chain reaction:
      • For enterovirus on throat and/or rectal swabs
      • For HSV and/or varicella-zoster virus on fluid from skin or mucosal vesicles
      • For mumps virus in saliva or urine
    • Monospot test for Epstein-Barr virus infection
    • HIV test
  • Numerous other tests of blood and cerebrospinal fluid may be appropriate to exclude other entities in the differential diagnosis, including: 2
    • Cerebrospinal fluid VDRL test
    • Cerebrospinal fluid and serum cryptococcal antigen
    • Mycobacterial and fungal studies on cerebrospinal fluid
    • Serum Lyme antibody

Laboratory

  • CBC
    • Absolute neutrophil count of 10,000 cells/μL or higher argues against a viral cause 3
  • Coagulation tests
    • Levels outside reference range suggest nonviral cause (eg, bacterial sepsis, meningococcal meningitis, rickettsial infection)
    • It is not necessary to await results before performing lumbar puncture unless a coagulopathy is suspected 1
  • Blood cultures
    • Obtained early in diagnostic work-up as a precaution in case the clinical evaluation and cerebrospinal fluid analysis do not clearly distinguish between bacterial and viral disease; results are positive in 50% to 75% of bacterial meningitis cases 10
  • Serum chemistry panel
    • Ratio of cerebrospinal fluid glucose level to concurrent serum glucose level helps differentiate bacterial from nonbacterial causes of meningitis 4
  • Serum procalcitonin level
    • Elevated procalcitonin levels are associated with bacterial infection, and measurement has been found to be highly accurate in discriminating between viral and bacterial meningitis; however, reference values vary among test manufacturers and no standard cutoff has been defined 11 12

Imaging

  • CT or MRI
    • Scan is indicated before lumbar puncture when clinical criteria suggest raised intracranial pressure, which contraindicates lumbar puncture. CT without contrast agent is preferred for this indication in most cases, but it is of little diagnostic value 13
      • Fourth ventricle effacement and cerebellar tonsillar herniation are CT signs of increased intracranial pressure
    • MRI is more sensitive for encephalitis and is the test of choice if brain involvement is suspected

Procedures

Lumbar puncture
General explanation
  • Insertion of a hollow-bore needle between the vertebral bodies into the subarachnoid space to do 1 of the following:
    • Obtain a specimen of cerebrospinal fluid
    • Measure cerebrospinal fluid opening pressure in the subarachnoid space
  • Patient is either in the lateral recumbent position (preferable for measuring opening pressure) or sitting upright
Indication
  • Suspected meningitis
Contraindications
  • Uncontrolled coagulopathy
  • Skin infection at site of needle insertion
  • Patient at risk of brain herniation 14
    • Best predictors of precipitating herniation (even with normal CT result) include:
      • Deteriorating level of consciousness (particularly to a Glasgow Coma Scale score of 11 or less)
      • Brainstem signs (eg, pupillary changes, abnormal posturing, irregular respirations)
      • Very recent seizure
Complications 15
  • Post–dural puncture headache
  • Back pain
  • Radicular injury
  • Infection
    • Epidural abscess
    • Meningitis (superimposed)
    • Diskitis
    • Vertebral osteomyelitis
  • Epidural hematoma
  • Cerebral herniation
  • Epidermoid tumor formation
Interpretation of results
  • Cerebrospinal fluid findings typical of viral meningitis: 1
    • Opening pressure: within reference range to mildly elevated (reference range, 12-20 cm)
    • Appearance: clear
    • Leukocyte count: mildly elevated (5-1000 cells/µL); most often has lymphocyte predominance, although may be neutrophilic early in course
    • Glucose: cerebrospinal fluid/serum glucose ratio is usually 0.50 to 0.66
    • Protein level: within reference range (less than 40 mg/dL) to mildly increased
    • Lactate level: lower than 35 mg/dL
    • Gram stain: negative
    • Bacterial culture: negative
    • Polymerase chain reaction test: may demonstrate enterovirus, HSV type 1 or 2, or varicella-zoster virus
    • IgM antibodies for mumps or West Nile virus may be detected in appropriate epidemiologic setting
  • Other cerebrospinal fluid tests recommended under some circumstances to rule out alternative diagnoses
    • Polymerase chain reaction, acid-fast stain, and culture for Mycobacterium tuberculosis
    • Lyme antibody index (also requires serum)
    • Cryptococcal antigen
    • Histoplasma antigen
    • Fungal culture
    • VDRL test or fluorescent treponemal antibody test
    • Cytology

Differential Diagnosis

Most common

  • Bacterial meningitis
    • Life-threatening bacterial infection of the meninges and cerebrospinal fluid
    • Clinical features are similar to those of viral meningitis (eg, fever, headache, stiff neck, photophobia)
    • In general, there are no reliable clinical distinctions between viral and bacterial meningitis that apply to the full spectrum of disease
      • Patients with meningococcal meningitis may have a petechial or purpuric rash, whereas patients with viral meningitis may have a maculopapular or vesicular rash
      • Patients with bacterial meningitis tend to be more severely ill and may have altered mental status, seizures, focal neurologic deficits, and/or hypotension; however, these signs indicate advanced disease and may not be present early in the course
    • Characterized by neutrophilic pleocytosis of cerebrospinal fluid, usually accompanied by elevated cerebrospinal fluid protein level and low ratio of cerebrospinal fluid glucose level to serum glucose level; bacteria may be identified by Gram stain, culture, and/or polymerase chain reaction
      • Lactate level lower than 35 mg/dL is typical of viral meningitis 1
  • Encephalitis
    • Acute brain inflammation, often caused by viral infection or inflammatory response after acute systemic viral infection
      • May overlap with viral meningitis (ie, meningoencephalitis)
    • Similarities include fever and headache, with or without meningismus; cerebrospinal fluid analysis may find lymphocytic pleocytosis and chemistry findings similar to those of viral meningitis
    • Unlike most cases of viral meningitis, encephalitis is usually characterized by altered mental status (eg, personality change, confusion, stupor); seizures may occur
    • Diagnosis is made by CT or MRI demonstrating cerebral inflammation; etiologic agent may be identified by polymerase chain reaction or antibody testing of cerebrospinal fluid, or by serologic testing of acute and convalescent serum specimens
  • Nonviral aseptic meningitis syndromes
    • Partially treated bacterial meningitis
      • Bacterial meningitis in a patient who has received antibiotics during course of infection, either prescribed or self-medicated
        • Whether or not the antibiotic is effective against the bacterial agent, it may alter the cerebrospinal fluid pattern and render bacterial cultures negative
      • Clinical presentation (eg, headache, fever, meningismus) may be similar, and cerebrospinal fluid test may find a lymphocytic pleocytosis characteristic of viral meningitis
      • Diagnosis may be suspected if a history of antibiotic use can be elicited, and in some cases diagnosis may be confirmed by identifying bacterial cause using polymerase chain reaction test
    • Tuberculous meningitis
      • As with viral meningitis, fever and headache are common presenting complaints
      • Onset is often more subacute than in viral meningitis; seizures and altered mental status occur more often than in viral meningitis
      • As in viral meningitis, cerebrospinal fluid is characterized by lymphocytic pleocytosis; however, glucose levels are generally lower
      • Brain imaging may find cerebral tuberculomas and basilar arachnoiditis; there may be radiographic evidence of pulmonary tuberculosis
      • Positive results for acid-fast stain, polymerase chain reaction assay for Mycobacterium tuberculosis, and/or culture confirm the diagnosis
    • Fungal meningitis
      • Cryptococcosis
        • Symptoms include fever and headache
        • Onset tends to be more insidious than viral meningitis, and altered mental status is common
        • May occur in normal hosts but more common in patients with immunocompromising illnesses, such as advanced HIV
        • Cerebrospinal fluid demonstrates a lymphocytic pleocytosis; protein levels are elevated, sometimes markedly
        • Positive cryptococcal antigens in serum or cerebrospinal fluid and/or culture confirm diagnosis
      • Coccidioidomycosis
        • Fungal infection endemic in arid areas of the southwestern and south central United States and parts of Mexico and Central and South America
        • Patients with meningeal involvement have fever, headache, and meningeal signs, similar to viral meningitis
        • Onset tends to be more subacute than viral infection; altered mental status is more common
        • May be associated with evidence of involvement elsewhere (eg, lungs, bones, joints, skin)
        • Cerebrospinal fluid analysis finds lymphocytic pleocytosis
        • Diagnosis is made by detection of spherules through special staining of cerebrospinal fluid, antigen testing of cerebrospinal fluid, serum antibody testing, or culture
      • Histoplasmosis
        • Patients with meningeal involvement have fever, headache, and meningeal signs, similar to viral meningitis
        • May be associated with pulmonary involvement; lymphadenopathy and hepatosplenomegaly may be evident on examination
        • Cerebrospinal fluid analysis finds lymphocytic pleocytosis with elevated protein level and low glucose level
        • Diagnosis is made by detecting histoplasma antigen in cerebrospinal fluid, serum, or urine and/or by culture of cerebrospinal fluid
    • Carcinomatous or lymphomatous meningitis
      • Headache (with or without fever) and mild meningismus are common
      • Process may be more indolent and subacute than viral meningitis; altered sensorium is common
      • Cerebrospinal fluid demonstrates lymphocytic pleocytosis and elevated protein levels
      • Differentiated by demonstration of malignant cells on cytology of cerebrospinal fluid

Treatment

Goals

  • In most cases, specific therapy is not available and treatment is primarily supportive and aimed at reducing fever and headache
  • Antiviral treatment of herpes simplex meningitis (without encephalitis) and varicella-zoster meningitis is controversial

Disposition

Admission criteria

  • Admission for empiric antibiotics and close observation is recommended for all patients in whom bacterial meningitis has not been excluded
  • When antiviral therapy is elected for patients with herpes zoster or primary herpes simplex infection who have associated meningitis, it is reasonable to admit and to start antiviral therapy parenterally, although expert opinion supports oral administration if there is no suggestion of encephalitis 2
  • Otherwise, admission is often necessary to provide analgesia, administer fluids, and closely observe patient until clinical improvement occurs

Recommendations for specialist referral

  • Consult infectious disease specialist and/or neurologist if diagnosis is uncertain

Treatment Options

Administer empiric antibiotics to all patients in whom bacterial meningitis (including partially treated) has not been excluded 1 8 16

Only available treatment in most cases of viral meningitis is analgesia and other symptomatic measures (eg, antiemetics) as needed; fluids generally are advised and may need to be given by IV if nausea and vomiting preclude oral intake 1

In herpes simplex and varicella-zoster meningitis, specific antiviral therapy may speed resolution of symptoms, although evidence that it does so is lacking (despite proven benefit of antiviral therapy for encephalitis due to these agents)

  • British guidelines recommend against antiviral therapy unless there are signs or symptoms that suggest associated encephalitis 1
  • In the setting of meningitis associated with a primary herpes simplex infection, US guidelines recommend antiviral therapy to shorten duration of primary infection 17
  • International expert panel guidance recommends treating meningitis caused by varicella-zoster virus 18
  • If infection due to HSV or varicella-zoster virus is suspected clinically, it is reasonable to start antiviral treatment empirically if laboratory confirmation cannot be obtained promptly

Drug therapy

  • Antiviral agents for HSV infections
    • Parenteral regimens 9
      • Acyclovir Sodium Solution for injection; Infants 1 to 2 months: 10 mg/kg/dose IV every 8 hours for 7 to 14 days.
      • Acyclovir Sodium Solution for injection; Infants, Children and Adolescents: 10 mg/kg/dose IV every 8 hours. AAP recommends treating for 7 to 14 days. Use ideal body weight when dosing in obese patients.
      • Acyclovir Sodium Solution for injection; Adults: 10 mg/kg/dose IV every 8 hours until clinical improvement, then oral therapy to complete at least 10 total days of therapy. Use ideal body weight when dosing in obese patients.
    • Oral regimen (may be used initially or after parenteral therapy)
      • Valacyclovir Hydrochloride Oral tablet; Adults: 1 g PO 3 times a day for 7 to 14 days. 2
  • Antiviral therapy for varicella-zoster virus infections
    • Parenteral regimens
    • Acyclovir Sodium Solution for injection; Adults: 10 mg/kg/dose IV every 8 hours until clinical improvement, then oral therapy to complete at least 10 total days of therapy. Manufacturer recommends using ideal body weight when dosing in obese adult patients. 2
    • Oral regimen (may be used initially or after parenteral therapy)
      • Valacyclovir Hydrochloride Oral tablet; Adults: 1 g PO 3 times a day for 7 to 14 days. 2

Nondrug and supportive care

Fluid support to maintain adequate hydration

Complications and Prognosis

Complications

  • Most patients recover from viral meningitis without complications; a minority develop chronic headaches 2
  • Neonates are at risk for severe complications (eg, hepatic necrosis, necrotizing enterocolitis, myocarditis), stemming from multiorgan involvement 3
  • Older adults with West Nile virus meningitis or meningoencephalitis may experience persistent fatigue, cognitive deficits, or movement disorders
  • Immunocompromised patients (particularly those with hypo- or agammaglobulinemia) may develop chronic enterovirus infection that progresses over months or years 19
    • Manifestations may include slow, progressive mental status changes with decline in cognitive function, generalized weakness, or paralysis
    • Some patients develop a syndrome that resembles dermatomyositis
    • It is not clear that administration of immunoglobulin is effective as treatment, although incidence of chronic enteroviral infection appears to have declined since institution of routine immunoglobulin treatment in this patient population 7 19

Prognosis

  • In immunocompetent patients, prognosis is generally good and full recovery occurs within a few days to a few weeks
    • Patients at extremes of age or who are immunocompromised may experience complications or incomplete recovery
  • Recurrence of meningitis associated with subsequent episodes of herpes simplex is uncommon

Screening and Prevention

Prevention

  • As most cases are caused by enterovirus infections, handwashing and good personal hygiene are the primary preventive measures 3
  • For vectorborne viral meningitis, prevention relies on controlling vector populations and avoiding exposure 20
    • Public health authorities may monitor vector activity in endemic areas and start applying pesticides if resources permit
    • Remove standing water (eg, in old tires, cans, gutters, and wading pools), which serves as mosquito breeding ground
    • Ensure window screens are in good repair
    • Wear protective clothing and apply mosquito and tick repellent for outdoor activities
      • DEET (diethyltoluamide), picaridin, oil of lemon eucalyptus, and ethyl butylacetylaminopropionate (IR3535) are effective
    • Apply permethrin to clothing and camping equipment
  • Immunization is effective in preventing some cases (eg, those caused by mumps virus, which may cause meningitis in up to 15% of those infected) 4
  • Routine administration of immunoglobulin to patients with hypo- or agammaglobulinemia may prevent enterovirus infection (or complications) 7 19

Sources

1: McGill F et al: The UK joint specialist societies guideline on the diagnosis and management of acute meningitis and meningococcal sepsis in immunocompetent adults. J Infect. 72(4):405-38, 2016
Cross Reference