Meningitis is the inflammation of the meninges with an associated abnormal cell count in the cerebrospinal fluid (CSF). Aseptic meningitis, defined by the lack of bacterial growth in cultures, is the most common form, with viruses being a frequent cause. Viral causes of meningitis have become more common as the prevalence of bacterial meningitis has decreased due to vaccinations, and viral meningitis is the most common form of meningitis in many countries. Viral meningitis typically presents with the acute onset of fever, headache, photophobia, neck stiffness, and often nausea and vomiting, although younger children may not show signs of meningeal irritation. Appropriate and timely evaluation is critical as there are no reliable initial clinical indicators to differentiate bacterial and viral etiologies of meningitis. Viral meningitis is usually a self-limiting illness with a good prognosis.
Enteroviruses (Coxsackie or Echovirus groups) are the most common cause of viral meningitis across all age groups; parechoviruses are also common in children. Herpesviruses that cause meningitis include herpes simplex virus (HSV) 1 and 2, varicella-zoster virus (VZV), cytomegalovirus, Epstein-Barr virus, and human herpesvirus 6. Other viral causes include adenovirus, lymphocytic choriomeningitis virus (LCMV), influenza, parainfluenza, and mumps. Arboviruses that can cause viral meningitis include West Nile virus (WNV), Zika, chikungunya, dengue, LaCross, Saint Louise encephalitis, Powassan, and eastern equine encephalitis virus.
Viral meningitis most commonly occurs in young children, with the incidence decreasing with age. In countries with high rates of immunization coverage, viral meningitis is more common than bacterial meningitis, with an estimated 3 to 18% of childhood meningitis being bacterial in origin. Vaccinations for Haemophilus influenza type B, Streptococcus pneumoniae, and Neisseria meningitidis have significantly decreased cases of bacterial meningitis. The incidence of viral meningitis has been estimated to range from 0.26 to 17 cases per 100000 people. In the United States, there are up to 75000 cases of enteroviral meningitis annually. In temperate climates, viral meningitis is most common in the summer and autumn months, while it is present year-round in tropical and subtropical areas.
Enteroviruses rank as the most common cause of viral meningitis in many places in the world, with up to 12 to 19 cases per 100000 population annually in some high-income countries. WNV, which is spread by mosquitoes, can cause meningitis and encephalitis. It is now endemic in North America and carries a 4 to 13% fatality rate. Mortality is higher in patients who are elderly, immunosuppressed, or have diabetes.
Half of the patients with WNV encephalitis have long-term neurological or psychological sequelae.
Human immunodeficiency virus (HIV) meningitis can be present during seroconversion, occurring in 10 to 17% of symptomatic seroconversion illnesses, with a small number progressing to chronic meningitis.
VZV can cause viral meningitis, more commonly with reactivation than in primary infection. Varicella meningitis can occur without cutaneous lesions.
HSV 1 and 2 can cause viral meningitis. HSV-1 is more commonly associated with sporadic encephalitis, while HSV-2 can cause a benign recurrent viral meningitis; meningitis usually occurs in the absence of genital lesions or a history of prior genital herpes infection. HSV reaches the central nervous system via the cranial nerves. LCMV is a rodent-borne virus, usually spread via inhalation of aerosolized urine or droppings, through vertical transmission and transmission via infected corneal, liver, and kidney transplants is also possible. It is more common in winter and early spring. Mumps was previously a common cause of viral meningitis in the United States but has decreased recently due to the widespread use of measles, mumps, and rubella (MMR) vaccination. It is more common in male patients.
Meningitis is an inflammatory pathology of the meninges surrounding the brain. Viruses can reach the meninges in a variety of ways, including spread via the bloodstream, retrograde spread from nerve endings, and reactivation from a dormant state within the nervous system. As a virus reaches the central nervous system (CNS) and spreads through the subarachnoid space, it causes an inflammatory response resulting in meningitis. Encephalitis occurs when there is inflammation of the brain parenchyma and is associated with a worse prognosis. The mumps virus is highly neurotropic and can directly infect the epithelium of the choroid plexus. Enteroviruses replicate outside the CNS and reach the CNS via hematogenous spread.
The clinical findings of viral meningitis can vary by age and immune status. Viral meningitis typically presents with acute onset of fever, headache, photophobia, neck stiffness, and nausea/vomiting. Young children may present with fever and irritability without evidence of meningeal irritation. In the initial presentation, there are no reliable clinical indicators to differentiate viral versus bacterial meningitis. Neonates with enteroviral meningitis can present similarly to bacterial sepsis and may also have systemic involvement such as hepatic necrosis, myocarditis, necrotizing enterocolitis, seizures, or focal neurologic findings.
Older infants and children may have a biphasic fever, first peaking with systemic constitutional symptoms and a second febrile phase with the onset of neurological signs. Viral meningitis in adults is more likely to present with meningeal symptoms and a higher CSF protein. Children with viral meningitis are more likely to have a fever, respiratory symptoms, and leukocytosis. Consider WNV meningitis in adults presenting with CSF pleocytosis and lower motor neuron involvement; WNV is more common in adults than children.
It is important to obtain a travel history in patients with suspected viral meningitis, as many viruses have specific geographical distributions.
A lumbar puncture is necessary unless there are contraindications such as focal neurologic deficits, papilledema, recent seizures, age 60 or greater. Indications for imaging before performing a lumbar puncture include focal neurological signs, papilledema, continuous or uncontrolled seizures, or a Glasgow Coma Score less than 12. Cerebrospinal fluid (CSF) analysis, including cell count and differential, glucose, protein, culture, and molecular diagnostics as available, should be performed. Viral meningitis characteristically has a CSF mononuclear pleocytosis, although there may initially be a neutrophilic predominance. This neutrophilic predominance is not limited to the first 24 hours of illness and is not a reliable indicator between viral and bacterial meningitis. Polymerase chain reaction (PCR) tests can be used to diagnose some causes of viral meningitis, such as enterovirus, VZV, and HSV. Serum white blood cell count and C-reactive protein do not reliably distinguish viral and bacterial meningitis. CSF C-reactive protein and procalcitonin have not been shown to differentiate viral vs. bacterial meningitis compared to serum levels.
Because of the lack of clinical findings to help distinguish between viral and bacterial meningitis and the risk of untreated bacterial meningitis, there has been much interest in identifying predictors of bacterial meningitis. The bacterial meningitis score (BMS) was originally developed for and validated in children with meningitis. The score is comprised of four laboratory predictors (positive Gram stain, CSF protein over 80 mg/dL, peripheral absolute neutrophil count greater than 10000 cells/mm3, CSF absolute neutrophil count over 1000 cells/mm3) and one clinical predictor (seizure at or before the presentation). A positive Gram stain is worth 2 points, and the other predictors are worth 1 point each if present. The negative predictive value for a score of 0 was 100%; a score of more than 2 predicted bacterial meningitis with 87% sensitivity. The BMS has also undergone validation in adults with meningitis.
In adults, researchers have studied individual predictors of bacterial rather than viral meningitis. In one study, these predictors included CSF glucose less than 34 mg/dL, CSF WBC over 2000 cells/mm3, CSF neutrophils greater than 1180, CSF protein over 220 mg/dL, and a ratio of CSF to blood glucose less than 0.23.15. CSF lactate has been shown to be a good indicator to differentiate bacterial from aseptic meningitis. The combination of CSF results, such as enterovirus and lactate, with the BMS, can increase sensitivity and specificity.
Most viruses causing meningitis have no specific treatment other than supportive care. Fluid and electrolyte management and pain control are the mainstays of management of viral meningitis. Patients should undergo observation for neurological and neuroendocrine complications, including seizures, cerebral edema, and SIADH.
Because of the difficulty in differentiating viral from bacterial meningitis initially, empiric antibiotic therapy is usually indicated until bacterial meningitis is ruled out. In patients aged one month and older, empiric therapy for bacterial meningitis can be provided with vancomycin in combination with either ceftriaxone or cefotaxime while culture results are pending. If encephalitis is suspected, empiric antiviral treatment with intravenous acyclovir should be a consideration. Acyclovir should be the choice for suspected or proven HSV or VZV infections, although it has been shown to provide benefits in HSV encephalitis, not meningitis.
Partially-treated bacterial meningitis should merit consideration scenario if the patient received prior antibiotic exposure. Other infectious etiologies to consider include mycoplasma, spirochetes, mycobacteria, Brucella, and fungal meningitis or encephalitis. Noninfectious etiologies include drugs (NSAIDs, trimethoprim-sulfamethoxazole, intravenous immune globulin), heavy metals, neoplasms, neurosarcoidosis, systemic lupus erythematosus, Behcet's syndrome, and vasculitis. In children, Kawasaki disease can present similarly to bacterial or viral meningitis.
The prognosis of viral meningitis without associated encephalitis is generally good. Viral meningitis typically has a spontaneous recovery, compared to bacterial meningitis in which progressive mental status deterioration may occur. Older infants and children are often ill for greater than a week but usually, have a full recovery. Adults with enterovirus meningitis can have symptoms for several weeks, but the illness is typically less severe than in children. While viral meningitis is usually self-limiting, there can be morbidity.
Enterovirus meningitis typically has a benign course, while enterovirus encephalitis can result in long-term neurological sequelae. Significant morbidity and mortality follow enteroviral meningitis in neonates and immunocompromised patients. Some subtypes of enterovirus, such as EV71 and EV68, are associated with more severe neurological disease and worse outcomes. The most common severe complications of enteroviral meningitis are meningoencephalitis, myocarditis, and pericarditis. In children, neurologic complications of enteroviral infection can include acute flaccid paralysis and rhombencephalitis. Neuropsychological impairments after viral meningitis are measurable but typically not as severe as those sustained after bacterial meningitis. Some studies have noted impaired sleep as a long-term sequela of meningitis.
The spread of pathogens causing viral meningitis is commonly through the fecal-oral route, so good hand hygiene is essential in prevention. Some causes of meningitis are preventable by vaccination.
Utilization of PCR tests to diagnosis viruses such as enterovirus, HSV, and VZV can decrease the length of stay and reduce antibiotic administration.
There are no reliable clinical indicators to distinguish bacterial from viral meningitis, though certain laboratory and clinical predictors can help identify patients at low risk for bacterial meningitis.
Viral meningitis can occur at age any but is most common in younger age groups. Because of the lack of apparent distinguishing features between viral and bacterial meningitis on initial presentation, an interprofessional team with strong medical knowledge and open communication is essential in providing appropriate care to these patients. Pharmacists can recommend empiric antibiotic coverage until there is confirmation of a diagnosis of viral meningitis. Nurses who look after patients with viral meningitis should know the disorder, what potential complications can arise, and when to call the clinician. The treatment of viral meningitis, for the most part, is supportive but residual sequelae of the disease are not uncommon; hence follow up with the primary care provider, and nurse practitioner is necessary. Interprofessional collaboration is crucial for optimal results in the management of viral meningitis, as with any condition. [Level V]
|||Logan SA,MacMahon E, Viral meningitis. BMJ (Clinical research ed.). 2008 Jan 5; [PubMed PMID: 18174598]|
|||Mount HR,Boyle SD, Aseptic and Bacterial Meningitis: Evaluation, Treatment, and Prevention. American family physician. 2017 Sep 1 [PubMed PMID: 28925647]|
|||McGill F,Griffiths MJ,Solomon T, Viral meningitis: current issues in diagnosis and treatment. Current opinion in infectious diseases. 2017 Apr; [PubMed PMID: 28118219]|
|||Wright WF,Pinto CN,Palisoc K,Baghli S, Viral (aseptic) meningitis: A review. Journal of the neurological sciences. 2019 Mar 15; [PubMed PMID: 30731305]|
|||Sadarangani M,Willis L,Kadambari S,Gormley S,Young Z,Beckley R,Gantlett K,Orf K,Blakey S,Martin NG,Kelly DF,Heath PT,Nadel S,Pollard AJ, Childhood meningitis in the conjugate vaccine era: a prospective cohort study. Archives of disease in childhood. 2015 Mar; [PubMed PMID: 25256088]|
|||Mijovic H,Sadarangani M, To LP or not to LP? Identifying the Etiology of Pediatric Meningitis. The Pediatric infectious disease journal. 2019 Jun [PubMed PMID: 31205243]|
|||Rudolph H,Schroten H,Tenenbaum T, Enterovirus Infections of the Central Nervous System in Children: An Update. The Pediatric infectious disease journal. 2016 May; [PubMed PMID: 26862675]|
|||Chadwick DR, Viral meningitis. British medical bulletin. 2005; [PubMed PMID: 16474042]|
|||Irani DN, Aseptic meningitis and viral myelitis. Neurologic clinics. 2008 Aug; [PubMed PMID: 18657719]|
|||Shukla B,Aguilera EA,Salazar L,Wootton SH,Kaewpoowat Q,Hasbun R, Aseptic meningitis in adults and children: Diagnostic and management challenges. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology. 2017 Sep [PubMed PMID: 28806629]|
|||Mirrakhimov AE,Gray A,Ayach T, When should brain imaging precede lumbar puncture in cases of suspected bacterial meningitis? Cleveland Clinic journal of medicine. 2017 Feb; [PubMed PMID: 28198685]|
|||Griffiths MJ,McGill F,Solomon T, Management of acute meningitis. Clinical medicine (London, England). 2018 Mar; [PubMed PMID: 29626023]|
|||Negrini B,Kelleher KJ,Wald ER, Cerebrospinal fluid findings in aseptic versus bacterial meningitis. Pediatrics. 2000 Feb; [PubMed PMID: 10654948]|
|||Santotoribio JD,Cuadros-Muñoz JF,García-Casares N, Comparison of C Reactive Protein and Procalcitonin Levels in Cerebrospinal Fluid and Serum to Differentiate Bacterial from Viral Meningitis. Annals of clinical and laboratory science. 2018 Jul; [PubMed PMID: 30143494]|
|||Nigrovic LE,Kuppermann N,Malley R, Development and validation of a multivariable predictive model to distinguish bacterial from aseptic meningitis in children in the post-Haemophilus influenzae era. Pediatrics. 2002 Oct [PubMed PMID: 12359784]|
|||McArthur R,Edlow JA,Nigrovic LE, Validation of the bacterial meningitis score in adults presenting to the ED with meningitis. The American journal of emergency medicine. 2016 Jul [PubMed PMID: 27139257]|
|||Tunkel AR,Hartman BJ,Kaplan SL,Kaufman BA,Roos KL,Scheld WM,Whitley RJ, Practice guidelines for the management of bacterial meningitis. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America. 2004 Nov 1 [PubMed PMID: 15494903]|
|||Sakushima K,Hayashino Y,Kawaguchi T,Jackson JL,Fukuhara S, Diagnostic accuracy of cerebrospinal fluid lactate for differentiating bacterial meningitis from aseptic meningitis: a meta-analysis. The Journal of infection. 2011 Apr [PubMed PMID: 21382412]|
|||Huy NT,Thao NT,Diep DT,Kikuchi M,Zamora J,Hirayama K, Cerebrospinal fluid lactate concentration to distinguish bacterial from aseptic meningitis: a systemic review and meta-analysis. Critical care (London, England). 2010 [PubMed PMID: 21194480]|
|||Pires FR,Franco ACBF,Gilio AE,Troster EJ, Comparison of enterovirus detection in cerebrospinal fluid with Bacterial Meningitis Score in children. Einstein (Sao Paulo, Brazil). 2017 Apr-Jun [PubMed PMID: 28767914]|
|||[PubMed PMID: 29185620]|
|||Dengler LD,Capparelli EV,Bastian JF,Bradley DJ,Glode MP,Santa S,Newburger JW,Baker AL,Matsubara T,Burns JC, Cerebrospinal fluid profile in patients with acute Kawasaki disease. The Pediatric infectious disease journal. 1998 Jun; [PubMed PMID: 9655538]|
|||Drysdale SB,Kelly DF, Fifteen-minute consultation: enterovirus meningitis and encephalitis-when can we stop the antibiotics? Archives of disease in childhood. Education and practice edition. 2017 Apr; [PubMed PMID: 27789515]|
|||Huang CC,Liu CC,Chang YC,Chen CY,Wang ST,Yeh TF, Neurologic complications in children with enterovirus 71 infection. The New England journal of medicine. 1999 Sep 23; [PubMed PMID: 10498488]|
|||Schmidt H,Heimann B,Djukic M,Mazurek C,Fels C,Wallesch CW,Nau R, Neuropsychological sequelae of bacterial and viral meningitis. Brain : a journal of neurology. 2006 Feb; [PubMed PMID: 16364957]|
|||Schmidt H,Cohrs S,Heinemann T,Goerdt C,Djukic M,Heimann B,Wallesch CW,Nau R, Sleep disorders are long-term sequelae of both bacterial and viral meningitis. Journal of neurology, neurosurgery, and psychiatry. 2006 Apr; [PubMed PMID: 16543543]|