Recommendations
Key Recommendations
Always refer a patient with suspected acute viral meningitis to hospital for a thorough assessment.[2][27]
Take blood cultures as soon as possible from a patient with signs of meningism in case they have bacterial meningitis.[2] Do this even if antibiotics have been given in the community.[2] Bacterial meningitis is a life-threatening condition that requires urgent management. Treat all patients in line with guidelines on bacterial meningitis until the diagnosis of bacterial meningitis is excluded or deemed unlikely. See Bacterial meningitis in adults and Bacterial meningitis in children.
Do a lumbar puncture (LP), if deemed safe and appropriate for the individual patient, to obtain cerebrospinal fluid (CSF) from all patients with suspected meningitis.[2] Do an LP, if indicated, even if antibiotics have been given in the community.[2] If you suspect a viral cause based on the the CSF examination, test the CSF by polymerase chain reaction (PCR) for viral pathogens.[2]
Always refer a patient with suspected acute viral meningitis to hospital for a thorough assessment.[2][27] This is because there are no reliable clinical indicators to differentiate between viral meningitis and bacterial meningitis, which carries a serious prognosis and requires immediate life-saving treatment.[27]
Practical tip
Think 'Could this be sepsis?' based on acute deterioration in an adult patient in whom there is clinical evidence or strong suspicion of infection.[28][29][30]
The patient may present with non-specific or non-localised symptoms (e.g., acutely unwell with a normal temperature) or there may be severe signs with evidence of multi-organ dysfunction and shock.[28][29][30]
Remember that sepsis represents the severe, life-threatening end of infection.[31]
The signs and symptoms of viral meningitis are similar to those of bacterial meningitis, which can cause serious and potentially fatal sepsis and critical illness.[4]
Use a systematic approach (e.g., National Early Warning Score 2 [NEWS2]), alongside your clinical judgement, to assess the risk of deterioration due to sepsis.[28][30][32][33] Consult local guidelines for the recommended approach at your institution.
Arrange urgent review by a senior clinical decision-maker (e.g., ST4 level doctor in the UK) if you suspect sepsis:[34]
Within 30 minutes for a patient who is critically ill (e.g., NEWS2 score of 7 or more, evidence of septic shock, or other significant clinical concerns)
Within 1 hour for a patient who is severely ill (e.g., NEWS2 score of 5 or 6).
Follow your local protocol for investigation and treatment of all patients with suspected sepsis, or those at risk. Start treatment promptly. Determine urgency of treatment according to likelihood of infection and severity of illness, or according to your local protocol.[33][34]
In the community: refer for emergency medical care in hospital (usually by blue-light ambulance in the UK) any patient who is acutely ill with a suspected infection and is:[29]
Deemed to be at high risk of deterioration due to organ dysfunction (as measured by risk stratification)
At risk of neutropenic sepsis.
See Sepsis in adults.
Patients with viral meningitis typically present with acute onset of meningism: neck stiffness, headache, and photophobia.[2]
Headache is the most common presenting feature.[2][35]
In a large multicentre cohort study in the UK, 99% of patients with viral meningitis had a headache on admission to hospital.[6]
Fever may be present.[2]
Other non-specific symptoms (e.g., diarrhoea, vomiting, muscle pain, sore throat) are sometimes seen.[2]
Take particular care when assessing young children, in whom meningitis tends to present with fever and irritability but without evidence of meningism.[16][27] Neck stiffness and photophobia may also be absent in adults.[27][36]
Differential diagnoses
Adults with viral meningitis tend not to present with reduced levels of consciousness. A change in the patient’s conscious level suggests an alternative diagnosis.[2] For more information, see Differentials.
More info: Important differential diagnoses
It is crucial to consider these alternative diagnoses:[2]
Bacterial meningitis
It is difficult to differentiate viral meningitis from bacterial meningitis on clinical grounds alone.
Therefore, all patients with suspected meningitis of unconfirmed aetiology should immediately receive empirical antibiotics.[2][37][38] Use lumbar puncture to confirm a diagnosis of viral meningitis before stopping antibiotics.[38]
See Bacterial meningitis in adults and Bacterial meningitis in children .
Encephalitis
Seizures, reduced Glasgow Coma Scale score, or focal neurological signs suggest encephalitis and should prompt empirical antiviral treatment, alongside further tests to establish the cause.[27]
See Encephalitis.
Encephalopathy due to metabolic factors or infection outside the central nervous system
Other intracranial pathology such as a subarachnoid haemorrhage or a space occupying lesion.
Take a detailed history to determine:
Onset of symptoms: may be sudden or gradual
Illness in contacts (in the family or at work): children are a common source, particularly of enteroviral infection
Travel history: may identify a history of exposure to rodents, mosquitoes, or ticks[27]
Sexual history: may reveal risk factors for recent HIV infection or a recent episode of genital herpes
Vaccination history: to ensure immunity to mumps[27]
Compromised immunity.[27]
Bear in mind that examination findings in viral meningitis may be similar to those in acute bacterial meningitis and it may be difficult to differentiate the two conditions. See Bacterial meningitis in adults and Bacterial meningitis in children .
A diffuse maculopapular rash is often seen with enteroviral infection but may also be seen in meningococcal disease.[39] Conversely, petechiae similar to that seen with meningococcal sepsis may be seen in enteroviral meningitis.[40]
The presence of genital herpetic lesions may suggest herpes simplex virus type 2 (HSV-2) as the aetiological agent; however, the majority of patients with proven HSV-2 meningitis do not have genital lesions.[41]
Recent shingles or chickenpox is suggestive of varicella zoster viral (VZV) meningitis. Bear in mind, however, that not all people with VSV meningitis will have cutaneous lesions.
Kernig's and Brudzinski's signs are uncommon in viral meningitis.
Blood tests
Take blood cultures as soon as possible when a patient presents with signs of meningism in case they have bacterial meningitis. Do this even if antibiotics have been given in the community.[2] Promptly start empirical antibiotics, if they have not already been started.[2]
If subsequent testing identifies a viral pathogen, stop the antibiotics.[2]
Also take bloods for:[2][37][38]
Full blood count and differential
Measure the peripheral white blood cell (WBC) count (may be normal or mildly raised in patients with viral meningitis)
C reactive protein (may be normal or mildly raised in patients with viral meningitis)
Procalcitonin
Elevated in bacterial meningitis; may be normal or mildly raised in patients with viral meningitis[42]
Serum procalcitonin >0.5 nanograms/mL has a positive predictive value of 100% for bacterial meningitis and negative predictive value of >93%, and is useful for distinguishing viral from bacterial meningitis[42][43][44][45]
Serum urea, creatinine, and electrolytes
Blood gases
Blood glucose
Compare this with CSF glucose. In viral meningitis there is a normal or mildly lowered ratio of CSF:blood glucose.
Lumbar puncture
Do a lumbar puncture (LP), if deemed safe and appropriate for the individual patient, to obtain CSF for examination and analysis in all patients with suspected meningitis.[2]
Do an LP, if indicated, even if antibiotics have been given in the community.[2]
Do not arrange neuroimaging before LP unless there are signs suggestive of a shift of brain compartments (e.g., focal neurological signs, presence of papilloedema, continuous or uncontrolled seizures, Glasgow Coma Scale score ≤12).[2]
Delaying LP for a CT scan can cause delays in antibiotic administration, which can in turn lead to an increase in mortality[48][49]
Most patients will have LP without the need for prior neuroimaging.[2]
Regardless of decisions about pre-LP neuroimaging, delay/avoid LP in the following situations:[2]
Respiratory or cardiac compromise
Signs of severe sepsis or a rapidly evolving rash
Infection at the site of the LP
A coagulopathy.
Use features from the history and examination (e.g., immune compromise and travel history) to guide further PCR testing of CSF, or serological assays, for other viruses.[2]
CSF examination and biochemistry
Examine the CSF for:[2]
Opening pressure (cm CSF)
Appearance
CSF WBC count (cells/microlitre)
Predominant cell type
In early infection there may be a neutrophil predominance, but this evolves to a more typical lymphocytic picture over the first 2 days of infection.
CSF protein (g/L)
CSF glucose (mmol)
CSF/plasma glucose ratio
CSF lactate (only if LP has been done before antibiotics)
A low CSF lactate (<35 mg/dL) is useful in distinguishing viral from bacterial meningitis, particularly if it is measured prior to antibiotics being administered.
Sensitivity is reduced if antibiotics have been started.[50]
A meta-analysis of 25 studies found that, as a single marker, CSF lactate concentration had better diagnostic accuracy in distinguishing bacterial from aseptic meningitis when compared to CSF glucose, CSF/plasma glucose quotient, CSF protein, and CSF total number of leukocytes.[51]
Classic CSF features of the different causes of meningitis (reproduced with permission).[2] | |||||
Normal | Bacterial | Viral | Tuberculosis | Fungal | |
Opening pressure (cm CSF) | 12 to 20 | Raised | Normal/mildly raised | Raised | Raised |
Appearance | Clear | Turbid, cloudy, purulent | Clear | Clear or cloudy | Clear or cloudy |
CSF WBC count (cells/microlitre) | <5 | Raised (typically >100)a | Raised (typically 5 to 1000)a | Raised (typically 5 to 500)a | Raised (typically 5 to 500)a |
Predominant cell type | n/a | Neutrophilsb | Lymphocytesc | Lymphocytesd | Lymphocytes |
CSF protein (g/L) | <0.4 | Raised | Mildly raised | Markedly raised | Raised |
CSF glucose (mmol) | 2.6 to 4.5 | Very low | Normal/slightly low | Very low | Low |
CSF/plasma glucose ratio | >0.66 | Very low | Normal/slightly low | Very low | Low |
Local laboratory ranges for biochemical tests should be consulted and may vary from those quoted here. A traumatic lumbar puncture will affect the results by falsely elevating the white cells due to excessive red cells. A common correction factor used is 1:1000. aOccasionally the CSF WBC count is normal (especially in immunodeficiency or tuberculous meningitis). bMay be lymphocytic if antibiotics given before lumbar puncture (partially treated bacterial meningitis), or with certain bacteria (e.g., Listeria monocytogenes). cMay be neutrophilic in enteroviral meningitis (especially early in disease). dMay be neutrophils early in the course of disease. | |||||
Practical tip
If the lumbar puncture is carried out with the patient sitting, discount the CSF opening pressure which will be artificially raised because of the patient’s position.
Bacterial culture and Gram stain of the CSF should be negative.
Practical tip
Send a further sample of CSF to the laboratory for storage. If lymphocytosis is identified, the stored CSF can be used for PCR testing.
CSF PCR
If you suspect a viral cause based on the CSF examination, test the CSF by PCR for viral pathogens:[2]
Enteroviruses
Herpes simplex viruses type 1 and 2 (HSV-1 and HSV-2)
Varicella zoster virus (VZV).
CSF PCR is the gold standard diagnostic test for confirmation of viral meningitis.[2][52]
Isolation of virus from the CSF by cell culture is time-consuming and expensive, and so is not available in the majority of laboratories.
PCR methods are able to detect enteroviruses and herpes viruses in the CSF more rapidly than cell culture and with greater sensitivity and specificity.[53][54]
Tests for lymphocytic choriomeningitis virus (LCMV) and many of the arboviruses are less widely available and often rely on serological techniques as well as nucleic acid amplification.[55]
Highly accurate, rapid diagnostic viral PCR-based tests for specific organisms (e.g., enterovirus and tuberculosis) are widely available and can provide an accurate diagnosis within hours.[56][57]
Practical tip
A negative PCR test does not necessarily exclude viral meningitis. Some people with viral meningitis won’t have a positive PCR test.
If you identify a viral pathogen, stop any empirical antibiotics that may have been started.[2]
This approach reduces the number of investigations performed and the duration of hospital stay.[58][59][60]
Practical tip
Bear in mind that a diagnosis of HSV meningitis and possible associations with genital herpes may be upsetting for the patient. Initiate a sensitive discussion about this at the earliest opportunity.[27] A diagnosis of HSV-2 meningitis does not necessarily suggest recent infection and may reflect reactivation of latent infection from many years previously.
Other tests
Test stool and/or throat swabs for enterovirus by PCR.[2]
Test all patients for HIV.
Although fourth-generation ELISAs have reduced the interval between infection and testing antibody-positive to under 1 month, it may be necessary to request viral load testing if HIV seroconversion is suspected and HIV serology is negative.
Computed tomography (CT) or magnetic resonance imaging (MRI) of the brain may be used in some centres to exclude cerebral abscess.
Meningeal enhancement may be seen with tuberculous or bacterial meningitis.
MRI is more sensitive than CT for detecting changes associated with viral encephalitis.
Encephalitis due to herpes simplex typically causes lesions in the temporal lobe. Many of the other viral encephalitides also have suggestive appearances on MRI.
Emerging tests
While serum testing of procalcitonin is more widely available than CSF, CSF procalcitonin >0.5 nanograms/mL also has a positive predictive value of 100% for bacterial meningitis and negative predictive value of >93%, and is useful for distinguishing viral from bacterial meningitis.[42][43][44][45]
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