Viral Meningitis


Article Author:
Rebecca Cantu


Article Editor:
Joe M Das


Editors In Chief:
Ishwarlal Jialal


Managing Editors:
Avais Raja
Orawan Chaigasame
Khalid Alsayouri
Kyle Blair
Radia Jamil
Erin Hughes
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Navid Mahabadi
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Abbey Smiley
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beenish Sohail
Hajira Basit
Phillip Hynes
Sandeep Sekhon


Updated:
7/26/2019 11:56:16 PM

Introduction

Meningitis is the inflammation of the meninges with an associated abnormal cell count in the cerebrospinal fluid (CSF).[1] Aseptic meningitis, defined by the lack of bacterial growth in cultures, is the most common form, with viruses being a frequent cause.[2] 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.[3] 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.[1][4]  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.[1] 

Etiology

Enteroviruses (Coxsackie or Echovirus groups) are the most common cause of viral meningitis across all age groups; parechoviruses are also common in children.[5][6] 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.[3][6] Arboviruses that can cause viral meningitis include West Nile virus (WNV), Zika, chikungunya, dengue, LaCross, Saint Louise encephalitis, Powassan, and eastern equine encephalitis virus.[4]

Epidemiology

Viral meningitis most commonly occurs in young children, with the incidence decreasing with age.[1] 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.[6] 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.[3] 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.[4] 

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.[7] 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.[8] 

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.[1][8] 

VZV can cause viral meningitis, more commonly with reactivation than in primary infection. Varicella meningitis can occur without cutaneous lesions.[1] 

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.[4] HSV reaches the central nervous system via the cranial nerves.[8] 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.[4] 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.[1][9]

Pathophysiology

Meningitis is an inflammatory pathology of the meninges surrounding the brain.[3] 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.[3][4] As a virus reaches the central nervous system (CNS) and spreads through the subarachnoid space, it causes an inflammatory response resulting in meningitis.[8] Encephalitis occurs when there is inflammation of the brain parenchyma and is associated with a worse prognosis.[1][3] The mumps virus is highly neurotropic and can directly infect the epithelium of the choroid plexus.[4] Enteroviruses replicate outside the CNS and reach the CNS via hematogenous spread.[8]

History and Physical

The clinical findings of viral meningitis can vary by age and immune status.[9] 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.[1] 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.[9]

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.[9][7] 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.[10] Consider WNV meningitis in adults presenting with CSF pleocytosis and lower motor neuron involvement; WNV is more common in adults than children.[9][10]

It is important to obtain a travel history in patients with suspected viral meningitis, as many viruses have specific geographical distributions.[8]

Evaluation

A lumbar puncture is necessary unless there are contraindications such as focal neurologic deficits, papilledema, recent seizures, age 60 or greater.[1][11] 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.[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.[1] This neutrophilic predominance is not limited to the first 24 hours of illness and is not a reliable indicator between viral and bacterial meningitis.[1][13] 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.[1] CSF C-reactive protein and procalcitonin have not been shown to differentiate viral vs. bacterial meningitis compared to serum levels.[14] 

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.[15] The BMS has also undergone validation in adults with meningitis.[16]

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.[17] CSF lactate has been shown to be a good indicator to differentiate bacterial from aseptic meningitis.[18][19] The combination of CSF results, such as enterovirus and lactate, with the BMS, can increase sensitivity and specificity.[20][21]

Treatment / Management

Most viruses causing meningitis have no specific treatment other than supportive care.[3][4][9] 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.[9] 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.[17] If encephalitis is suspected, empiric antiviral treatment with intravenous acyclovir should be a consideration.[1] 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.[4][8][12]

Differential Diagnosis

Partially-treated bacterial meningitis should merit consideration scenario if the patient received prior antibiotic exposure.[9] Other infectious etiologies to consider include mycoplasma, spirochetes, mycobacteria, Brucella, and fungal meningitis or encephalitis.[1][9] Noninfectious etiologies include drugs (NSAIDs, trimethoprim-sulfamethoxazole, intravenous immune globulin), heavy metals, neoplasms, neurosarcoidosis, systemic lupus erythematosus, Behcet's syndrome, and vasculitis.[4][9] In children, Kawasaki disease can present similarly to bacterial or viral meningitis.[22] 

Prognosis

The prognosis of viral meningitis without associated encephalitis is generally good.[23] 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.[9] While viral meningitis is usually self-limiting, there can be morbidity.[1]

Complications

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.[7][23] In children, neurologic complications of enteroviral infection can include acute flaccid paralysis and rhombencephalitis.[24][7] Neuropsychological impairments after viral meningitis are measurable but typically not as severe as those sustained after bacterial meningitis.[25] Some studies have noted impaired sleep as a long-term sequela of meningitis.[26]

Deterrence and Patient Education

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.[4] 

Pearls and Other Issues

Infants and young children may present with fever, irritability, and non-specific symptoms such as lethargy and decreased oral intake, with a lack of meningeal signs.[1][23] 

Utilization of PCR tests to diagnosis viruses such as enterovirus, HSV, and VZV can decrease the length of stay and reduce antibiotic administration.[1]

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.[15][21] 

Enhancing Healthcare Team Outcomes

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]


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Viral Meningitis - Questions

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A 3-year-old boy is evaluated in the emergency department for fever. He had fever and malaise several days prior, then developed fever, headache, and neck pain one day prior to presentation. He is suspected to have viral meningitis. What is the most common cause of viral meningitis in children?



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An 8-year-old previously healthy boy from Montana develops encephalitis after returning from a trip to Japan. He has fever, headache, vomiting, and diarrhea. On examination, he is lethargic, with left upper extremity twitching and eye deviation to the left. Which of the following is most likely to diagnose the etiology of his illness?



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A 27-year-old male is transported to the emergency department after having his first seizure. Prior to the seizure, he had complained of headache and neck pain and had one episode of emesis. On arrival, he is febrile and unresponsive, with a GCS of 11. His examination is notable for several insect bites. Which of the following is the next best step in evaluation?



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A 16-year-old male presents to the hospital with a history of fever and myalgias for the past three days. He has normal mental status on examination. Signs of meningeal irritation are absent, except for neck stiffness. A head CT is unremarkable. Lumbar puncture was performed and cerebrospinal fluid results are notable for a white blood cell count of 350 per cubic milliliter, protein 95 mg/dL, and polymerase chain reaction test positive for enterovirus. Which of the following would also be expected in his cerebrospinal fluid results?



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A 7-year-old female is admitted to the hospital with presumed viral meningitis. Her cerebrospinal fluid studies showed pleocytosis with 300 white blood cells/mm3, mildly elevated protein, normal glucose, and a negative Gram stain. Polymerase chain reaction testing is positive for enterovirus. Which of the following complications is associated with her illness?



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A 4-year-old male presents to the emergency department with a 2-day history of fever, neck pain, and malaise. On examination, he is lethargic and has a positive Brudzinski's sign. Due to suspicion for meningitis, a lumbar puncture is performed. Cerebrospinal fluid (CSF) results include 175 cells per mm3, protein 100 mg/dL, glucose 75 mg/dL, CSF lactate 2 mmol/L, with a negative gram stain. Which of the following is the most useful indicator in differentiating bacterial from aseptic meningitis?



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A 5-year-old girl presents to the hospital with a history of fever, malaise, and headache for the past three days. Physical examination is remarkable for neck stiffness and a temperature of 102F. Kernig's and Budzinski's sign are negative. Cerebrospinal fluid shows 135 white blood cells per cubic millimeter, glucose 60 mg/dl, and protein 80 mg/dL, with no organisms visualized on gram stain. Polymerase chain reaction viral tests are pending. Which of the following viruses is most likely to cause meningitis in this patient?



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An 8-year-old boy is discharged from the hospital after being diagnosed with enteroviral meningitis. His cerebrospinal fluid was notable for positive enterovirus polymerase chain reaction test and negative bacterial culture. Which of the following is the recommended management?



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A 10-year-old female presents to the emergency department with a fever of 104 Farheinheit and altered mental status. A head computed tomography scan is ordered immediately and is unremarkable. She undergoes a lumbar puncture; cerebrospinal fluid (CSF) results show 180 white blood cells/mm3, CSF protein 100 mg/dL, and CSF glucose 35 mg/dL. CSF Gram stain and viral polymerase chain reaction tests are pending. Which of the following additional findings would increase the likelihood of bacterial meningitis?



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A 28-year-old, previously healthy male presents with a three-day history of fever, headache, nausea, and vomiting. There are nuchal rigidity and fever, but otherwise, the exam and CT of the head are normal. Lumbar puncture shows mild elevation of protein, lymphocytic pleocytosis, and normal glucose. Select the most likely diagnosis.



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A 7 year old girl is brought to the emergency department of the emergency department with fever, nuchal rigidity, and sores on the mouth, feet, and hands. CSF gram stain is negative, protein is 100 mg/dL, glucose is 80 mg/dL, and there are 100 WBC/L, and latex antigen testing is negative. Select appropriate management.



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A 17-year-old male presented with fever, neck stiffness, and fatigue in early summer. Imaging of his brain was unremarkable. He underwent lumbar puncture. Which of the following cerebrospinal fluid profiles is most consistent with viral meningitis?

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A 42-year-old male in the northeast United States presents to the emergency department with confusion and leg weakness. On exam, he is noted to have a fever of 39 C, diminished strength in bilateral lower extremities, and altered mental status. A head CT is unremarkable. Cerebrospinal fluid is notable for pleocytosis (250 white blood cells/mm3), with no red blood cells, mildly elevated protein, and normal glucose. There are no organisms seen on Gram stain, and bacterial culture has no growth. Which of the following is the most likely vector of his illness?



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A 16-year-old female is admitted to the hospital with presumed viral meningitis. Her cerebrospinal fluid showed 200 white blood cells/mm3 with a predominance of mononuclear cells, slightly elevated protein, normal glucose, and a negative Gram stain. The cerebrospinal fluid has no growth to date. PCR testing is not available at this hospital. She is fully vaccinated. Which of the following is the most appropriate management of the most likely cause of her symptoms?



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A 6-year-old unvaccinated male is brought to the hospital with headache, fatigue, and facial swelling. On examination, he has bilateral parotid gland swelling. He undergoes a lumbar puncture due to his severe headache. Cerebrospinal fluid results show 250 white blood cells per mm3, protein 150 mg/dL, glucose 65 mg/dL, and a negative Gram stain. Which of the following is the most likely etiology for his symptoms?



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A 16-year-old female who works in a pet store is admitted to the hospital with presumed viral meningitis. She presented with one week of fever, headache, malaise, and nausea. After extensive evaluation, she is diagnosed with lymphocytic choriomeningitis virus. Which of the following is the most likely vector of her illness?



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Viral Meningitis - References

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The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Pathology-Chemistry. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Pathology-Chemistry, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Pathology-Chemistry, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Pathology-Chemistry. When it is time for the Pathology-Chemistry board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Pathology-Chemistry.