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Home , Poliovirus, Viral meningitis

Viral

Virginia A. Triant, MD, MPH

iral meningitis is a (CNS) characterized by signs and symptoms of meningeal in the absence of Vpositive bacterial cultures. The incidence varies with season, and the clinical presentation often includes , , and nuchal rigidity (stiffness of the neck) accompanied by symptoms typical of the specific causal . is usually self-limited and resolves without treatment, although case reports suggest that treatment is indicated and beneficial in certain clinical scenarios.

Viral meningitis should be differentiated Prevalence and Distribution from the broader category of . Viral meningitis occurs with a peak monthly Although patients with aseptic meningitis by defini- incidence of 1 per 100,000 persons in temperate Mother comforts tion have negative bacterial cultures, the clinical climates. Reported cases are highest during the her child despite the picture of meningitis is not always caused by a virus summer and early fall. The exact incidence is diffi- hardships of living in and is not always infectious. cult to determine since many cases of viral menin- a sparse motel room. Diagnosing viral meningitis is complex for gitis are not reported to public health authorities. Photo by two reasons. First, a multitude of can Many cases are probably undiagnosed because this David Comb cause meningitis, each with its own characteristic self-limited disorder often resolves without progres- mode of transmission, presentation, and work-up. sion of symptoms. Second, and more importantly, the presentation are the most common cause of of viral meningitis may only differ slightly from viral meningitis, accounting for 75-90% of cases. that of bacterial meningitis, a life-threatening and The genus includes , highly contagious disorder that requires immediate echovirus, , and human enteroviruses 68 recognition and treatment. to 71. Other common causes of viral meningitis include virus-2 (HSV-2), human

The Health Care of Homeless Persons - Part I - Viral Meningitis 175 Table 1: Causes of Viral Meningitis meningitis or experience a more severe illness. For example, sexually active populations are more likely Common Less common Rare to develop HSV-2 or HIV meningitis. Unvac- Enteroviruses HSV-1 cinated individuals are at risk for meningitis caused HSV-2 CMV Parainfluenza by , , or rubella. Finally, neonates HIV EBV (especially those less than 2 weeks of age) and adults with agammaglobulinemia who contract enteroviral LCMV VZV Vaccinia meningitis tend to develop more severe cases. Arbovirus Adenovirus Encephalomyocarditis Mumps Measles virus Mode of Transmission Rubella The mechanism of transmission of viral meningitis depends upon the specific viral etiology. Ninety percent of cases in which a specific virus Note: HSV=; is identified are caused by enteroviruses, which HIV=human immunodeficiency virus; are transmitted via the fecal-oral route or through LCMV= lymphocytic choriomeningitis virus; CMV=; EBV=Epstein Barr virus; infected respiratory secretions. VZV= HSV-2 is transmitted through contact with an active ulcerative lesion or contact with an infected immunodeficiency virus (HIV), lymphocytic shedding HSV from a mucosal surface. HIV choriomeningitis virus (LCMV), arbovirus, and is transmitted via sexual contact or contact with . Less commonly, HSV-1, cyto- infected blood. LCMV is contracted through megalovirus (CMV), Epstein Barr virus (EBV), contact with infected rodents or through contami- varicella zoster virus (VZV), adenovirus, measles, nated environmental surfaces. Arboviruses are and rubella cause viral meningitis. Rare causes of transmitted in the setting of tick bites, and mumps viral meningitis include influenza, parainfluenza, virus is spread via respiratory droplets. rotavirus, vaccinia, and encephalomyocarditis virus. Most cases of recurrent viral meningitis are caused Symptoms and Diagnosis by HSV-2. HSV-1 typically causes Classic symptoms of meningitis include fever, rather than meningitis. Table 1 lists the causes of headache, and nuchal rigidity. Viral meningitis viral meningitis by frequency. can present more sub-acutely than bacterial, with Enteroviruses are estimated to cause approxi- , lethargy, myalgias, anorexia, nausea, mately 75,000 cases of viral meningitis in the vomiting, abdominal pain, or diarrhea. The USA annually. The rising prevalence of HSV-2 headache in viral meningitis is often frontal or retro- in the USA has led to recognition of this virus as a orbital and can be associated with or common cause of meningitis, with some estimates ranking it the second leading cause. LCMV is Figure 1: thought to account for 10-15% of cases of viral meningitis. The incidence of mumps meningitis has fallen by more than 95% since initiation of widespread vaccination measures. In the past, as many as half of the cases of aseptic meningitis were of unknown etiology, but better laboratory techniques have resulted in improved identification of a causal agent. Some forms of viral meningitis occur with seasonal variation. Cases in the summer or early fall are most likely to be caused by enteroviruses or arboviruses. LCMV or mumps are the most probable causes during the winter months. Cases of HIV- and HSV-associated meningitis are not seasonal. Depending on risk factors, certain groups are more likely to develop a particular form of

176 The Health Care of Homeless Persons - Part I - Viral Meningitis The Health Care of Homeless Persons - Part I - Viral Meningitis 177 pain on eye movement. While nuchal rigidity is Figure 2: usually present, it is frequently mild, occurring only near the limit of neck anteflexion (bending the neck forward so that the chin touches the upper chest). Diagnosis can be confirmed by and analysis of (CSF). CSF find- ings in viral and bacterial meningitis both reflect the presence of meningeal irritation but are otherwise quite distinct. Viral meningitis is characterized by an increased WBC count with a lymphocyte predominance, slightly elevated , and normal . Early viral meningitis can show a neutrophil predominance, but the differential shifts towards lymphocytes within eight to 24 hours. Glucose is usually normal (greater than 50 percent of serum value) but can be moderately decreased in some cases of enterovirus, mumps, HSV, and LCMV. Assuming a non-traumatic tap, red blood cells are typically absent; however, they can be present in HSV-1 meningitis. In contrast, CSF findings in bacterial meningitis typically include a very high involvement in 13-36% of patients. Some studies WBC count with neutrophil predominance, higher have indicated that 25% of women and 11% of men protein, and low glucose. with initial HSV-2 infection develop meningitis. Polymerase chain reaction (PCR) is increasingly On rare occasions, HSV-2 meningitis can present used to diagnose viral meningitis when routine viral with severe but atypical symptoms of meningitis, cultures are negative. On average, CSF cultures are such as urinary retention, paresthesias, focal weak- positive in only half of aseptic meningitis cases. In ness, or signs of ascending . The majority two-thirds of culture-negative cases, the specific (85%) of patients with HSV-2 meningitis also have viral etiology can be identified by PCR. With genital lesions that typically precede CNS symp- the present technology, PCR is routinely used to toms by 7 days. While viral cultures are positive in diagnose enterovirus, HSV, CMV, EBV, and VZV 80% of cases of HSV-2 meningitis, HSV PCR is the meningitis. diagnostic test of choice. A brief discussion of the clinical presentations of some of the common viral causes of meningitis is HIV merited, as identification of a specific viral etiology In 5-10% of new HIV diagnoses, meningitis is can direct treatment. a component of the initial viral illness. This mono- nucleosis-like syndrome is characterized by fever, Enterovirus malaise, lymphadenopathy, rash, and pharyngitis. In addition to an abrupt onset of headache, In contrast to other types of viral meningitis, HIV fever, nausea, vomiting, malaise, photophobia, and meningitis can present with or cranial nerve nuchal rigidity, enteroviral meningitis may present palsies. Cranial nerves V, VII, and VIII are most with , pleuritic chest pain, conjunctivitis, commonly affected. While CSF cultures for HIV or abdominal pain. Enterovirus CSF cultures are are often positive, diagnosis is more typically made positive in 40-80% of patients who undergo by standard HIV testing. HIV meningitis tends to lumbar puncture, but incubation time ranges from be self-limited. 4-12 days. Enteroviruses can also be isolated from throat or stool specimens but can yield false positive LCMV results. CSF PCR for enterovirus, with a sensitivity In LCMV meningitis, flu-like symptoms can of over 97% and a specificity of close to 100%, is the accompany headache and meningeal signs. Rarely, diagnostic test of choice. patients can present with a rash, pulmonary infil- trates, alopecia, orchitis, parotitis, myopericarditis, HSV-2 or arthritis. CSF findings are typical of viral Primary HSV-2 infection results in meningeal

176 The Health Care of Homeless Persons - Part I - Viral Meningitis The Health Care of Homeless Persons - Part I - Viral Meningitis 177 Table 2: Differential Diagnosis of Viral Meningitis presentation and the analysis of the CSF findings are helpful in making this distinction. The presence Broad Category Example of either or both of two classical signs, called the Leptospira sp. Borrelia burgdorferi Kernig and Brudzinski signs, suggests a non-viral Treponema pallidum etiology of the meningitis. When a patient is supine Mycoplasma pneumoniae Bacterial meningitis or seated, a positive Kernig sign is the inability or Rickettsia sp. Ehrlichia sp. reluctance to fully extend the knee when the hip is Brucella sp. flexed 90 degrees as illustrated in Figure 1. Patients Chlamydia sp. who spontaneously flex the hip during passive Cryptococcus neoformans Coccidiodes immitus flexion of the neck have a positive Brudzinski Histoplasma capsulatum sign as illustrated in Figure 2. Both tests were Toxoplasma gondii Parasitic meningitis initially developed as diagnostic tools in chronic Angiostrongylus (e.g. tuberculous) meningitis but are now used to Mycobacterial meningitis demonstrate the nuchal rigidity that is characteristic Bacterial endocarditis Parameningeal Epidural or subdural of acute bacterial meningitis. Profound alterations Carcinomatous meningitis in consciousness, seizures, or focal neurological Neoplastic Leukemias deficits are suggestive of a parenchymal rather than Lymphomas meningeal process. Sarcoid Autoimmune Behcet’s disease Viral meningitis should also be differentiated SLE from West Nile . From an Nonsteroidal anti-inflammatory epidemiological perspective, the risk of contracting drugs (ibuprofen most common) Sulfa drugs increases more than twenty-fold Drug-induced Phenazopyridine in those over 50 years of age. In contrast, viral Azathioprine meningitis is common in the young as well as the Anti-CD3 monoclonal Intravenous immune globulin elderly. While West Nile virus in its mild form can present with symptoms that resemble viral meningitis, with the exception of occasionally lower meningitis – malaise, headache, and gastrointestinal glucose and higher cell counts. symptoms – it has several distinct clinical features. Unlike viral meningitis, meningoencephalitis caused Mumps by West Nile virus is characterized by severe muscle Common features of mumps infection include weakness, a diffuse flaccid paralysis, and diminished orchitis, parotitis, and laboratory evidence of reflexes. In some cases it can resemble Guillain- . However, the characteristic parotitis Barre syndrome. In addition, nearly 20% of is present in only half of patients with mumps patients with West Nile virus have an erythematous meningitis. Infection is more common in males, rash. The differential diagnosis of viral meningitis is and documented prior infection excludes the outlined in Table 2. possibility of current infection. In contrast to other viral meningitides, the CSF can show a neutrophilic Treatment and Complications pleocytosis and a decreased glucose. Most cases of viral meningitis are self-limited and require only . Hospi- Arbovirus talization is not usually necessary. Treatment with Arbovirus infections typically occur in clusters intravenous immunoglobulin is indicated in persons in a localized geographic region during the summer with humoral deficiency and neonates or fall. In addition to typical symptoms of viral with severe infection. Patients whose CSF or meningitis, a history of tick exposure is often other clinical findings are ambiguous or suggest the present. possibility of non-viral meningitis should be treated The differential diagnosis of viral meningitis is promptly with antibiotics. critical because the signs and symptoms can be very Anecdotal evidence supports the use of acyclovir similar to other forms of meningitis that are life- (Zovirax™) to treat HSV meningitis and severe threatening if not treated promptly. It is critical for EBV or VZV meningeal infection. Controlled the clinician to distinguish bacterial and non-bacte- trial data are unavailable, and whether treatment rial causes of meningitis. The severity of the clinical decreases the severity or duration of symptoms or reduces complications remains unknown. Antiviral

178 The Health Care of Homeless Persons - Part I - Viral Meningitis The Health Care of Homeless Persons - Part I - Viral Meningitis 179 therapy is considered to be appropriate in the setting attention so that bacterial meningitis can be ruled of primary HSV meningitis (versus recurrent) or out by lumbar puncture. Despite signs of systemic for patients with severe neurological symptoms viral infection, symptoms of meningitis should not and signs. Therapy consists of IV acyclovir or oral be automatically ascribed to a viral etiology, as a acyclovir (Zovirax™), famciclovir (Famvir™), or concurrent bacterial infection may still be present. valacyclovir (Valtrex™). Prophylaxis with acyclovir Shelters are unique settings that can facilitate is indicated in patients who have frequent recur- the screening of risk factors for preventable infec- rences of HSV meningitis. tions. Upon intake to a shelter, guests can be A new antiviral agent, pleconaril, is currently screened for a vaccination history and current being investigated for the treatment of enteroviral medical conditions. Depending on the risk factor meningitis. Previous trials have suggested that or medical history, guests can be offered education, pleconaril shortens the duration of symptoms. counseling, or access to vaccinations. Although a randomized placebo-controlled trial has shown the agent to be effective and safe for Summary enteroviral meningitis, indications for its use are still • The differential diagnosis of viral men- being defined. ingitis is broad: always rule out non-viral causes first, as the untreated mortality rate Prevention and Control of bacterial meningitis is very high. Prevention of viral meningitis can be achieved • If there is any question about the etiology by reduction of risk factors and by vaccination strate- of meningitis, start antibiotics. gies. The spread of HSV-2 and HIV can be reduced • Viral meningitis is usually self-limited. through education on how the viruses are transmitted • Cases vary seasonally, with enterovirus be- and the promotion of strategies for preventing ing the most common cause. transmission, such as barrier protection during sexual • A detailed history and physical exam help contact and needle exchange programs. Meningitis to hone the diagnosis. from mumps, measles, and rubella, as well as VZV, • Hallmark symptoms include fever, head- can be prevented by vaccination. ache, and stiff neck. Control of the spread of viral meningitis • Diagnosis is by lumbar puncture and CSF depends on the specific viral agent. Transmission analysis. of enterovirus meningitis, for example, can be • Viral PCR studies of the CSF are more decreased through basic hygiene techniques such as sensitive and specific than routine cultures. hand washing. • Treatment is usually not indicated. • Acyclovir (Zovirax™) is used for treat- Special Consideration for Homeless Populations ment and prophylaxis of HSV meningitis. Homeless populations living in shelters are at an • New antiviral therapies are under investi- increased risk of developing communicable diseases gation. because of the large number of individuals with • Shelter settings can increase transmission diverse exposures living in close quarters. Given of meningitis but facilitate risk factor as- the easy transmissibility of infectious diseases in sessment and prevention strategies. E shelter settings, it is imperative to identify serious and treatable infections early to prevent spread to The author of this chapter gratefully acknowledges the co-habitants. Any individual with symptoms of invaluable contribution of Jean Molloy, RN,C, MS, meningitis should be emergently directed to medical who authored this chapter in the original Manual.

Viral Meningitis Medication List

Generic Brand Name Cost

acyclovir Zovirax $

famciclovir Famvir $$$

valacyclovir Valtrex $$$$

178 The Health Care of Homeless Persons - Part I - Viral Meningitis The Health Care of Homeless Persons - Part I - Viral Meningitis 179 References Johnson RP. Aseptic meningitis. UpToDate, 2003.

Johnson RP, Gluckman SJ. Overview of viral infections of the central nervous system. UpToDate, 2003.

Petersen LR, Roehrig JT, Hughes JM. West Nile virus encephalitis. New England Journal of Medicine 2002;347(16): 1225-1226.

Redington JJ, Tyler KL. Viral infections of the nervous system 2002: update on diagnosis and treatment. Archives of 2002;59(5):712-718.

Rotbart HA, Webster AD, Pleconaril Treatment Registry Group. Treatment of potentially life threatening enterovirus infections with pleconaril. Clinical Infectious Diseases 2001;34:72-77.

Tyler KL. West Nile virus encephalitis in America. New England Journal of Medicine 2001;344(24):1858-1859.

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