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Pn0607 Meningitis.Pdf Accurate diagnosis and an extensive work-up can avoid unnecessary treatments. As the meningitis season heats up, here’s how to be ready. iral meningitis is a significant cause of morbidi- nective tissue diseases, partially treated bacterial meningitis, ty and mortality. There are over 100,000 cases of parameningeal infections and drug-induced meningitis.2 aseptic meningitis annually in the United Some viral pathogens may cause “pure” meningitis in which States.1 The term “aseptic meningitis” refers to the signs of brain involvement and spinal cord inflammation both infectious and noninfectious causes of are absent. Viral infection may also result in a combined syn- meningitisV for which no etiology is identified after routine drome of menigoencephalitis or encephalomyelitis.3 The clini- evaluation and culture of the cerebrospinal fluid (CSF). The cal features associated with viral meningitis are often non-spe- differential diagnosis for aseptic meningitis is quite broad. cific, so awareness of epidemiology, including seasonality and Although viruses are the major cause of acute meningitis, the geographic distribution of the various pathogens, becomes clinical presentation and CSF findings are often indistinguish- important in establishing a diagnosis. Given the paucity of able from other causes of aseptic meningitis, presenting a diag- effective therapies for viral meningitis, preventive measures nostic challenge. Therefore, knowledge of unique clinical fea- have an important role in reducing morbidity and mortality. A tures and epidemiology for the causative agents of viral menin- detailed look at the unique characteristics of the common gitis is especially important for diagnosis, treatment and pre- pathogens in viral meningitis will aid in clinical recognition. vention of disease. In this article we have reviewed the major causes of viral meningitis, including diagnosis of and Enteroviruses available therapies for these pathogens. Enteroviruses are the most common cause of aseptic meningi- tis for all ages. In the United States, enteroviruses cause over Identifying the Pathogen 75,000 cases of aseptic meningitis annually.4,5 With the advent The annual number of cases of meningitis due to of polymerase chain reaction (PCR) analysis, detection of viruses surpasses that of all other etiologies of aseptic enteroviral RNA in the CSF has improved dramatically. meningitis. Nevertheless, in addition to viral etiolo- Enteroviruses are classified into five groups: coxsackie A, gies, possible causes of aseptic meningitis include coxsackie B, echoviruses, polioviruses and the newer, num- bacteria that are not easily detected on Gram’s stain bered enteroviruses. Certain serotypes are more strongly asso- or culture such as mycobacteria and spirochetes as ciated with meningitis than others.6 As many as 85 to 95 per- well as fungi, protozoa, helminths, neoplasms, con- cent of acute viral meningitis cases have been attributed to By Bevin Sell, MD and Lawrence L. Livornese Jr. MD June 2007 Practical Neurology 45 Viral Meningitis enteroviral infection.7 The incidence of enteroviral meningitis but available therapies have included immune serum globulin is five to eight times higher in infants than in the adult popu- and pleconaril. Immune serum globulin has been used prima- lation.8 rily in neonates and immunocompromised patients.13,14 In temperate climates, enteroviral infections arise most Pleconaril is an oral antiviral agent that inhibits enteroviral often in the summer and early fall. Sporadic cases, however, replication.9 There is some data to suggest that Pleconaril may may appear at any time of year.9 The typical clinical presenta- reduce the duration of symptoms associated with enteroviral tion of enteroviral meningitis varies with age. Neonates and meningitis. However, the Food and Drug Administration young children will often present with fever and other non- denied licensure due to equivocal data regarding efficacy and specific findings, while headache is a prominent complaint concern for drug interactions.15 among adults and older children. Photophobia, nausea and vomiting are common; however, Arboviruses nuchal rigidity is found in less than 70 percent of patients. In Arboviruses are a commonly recognized cause of encephalitis some cases, clinical findings can be suggestive of infection with throughout the world. A number of these viruses, including a particular enteroviral serotype. For example, hand-foot- Saint Louis encephalitis virus, Tick-borne encephalitis virus, mouth syndrome has been associated with enterovirus 71 Colorado tick fever virus and West Nile virus, may also cause infection; herpangina is typically seen with coxsackie virus A meningitis as a manifestation of disease. Saint Louis infection; a maculopapular rash has been linked to echovirus 9 Encephalitis virus (SLE) is one of the most common causes of infection.3,5 Symptoms will usu- vector-transmitted aseptic menin- ally resolve within a week but Because enteroviruses are gitis in the United States. Cases of can occasionally persist for sev- SLE have been reported from most eral weeks.10 cleared via antibody-mediated of the continental United States, Because enteroviruses are sparing only a few of the north- cleared via antibody-mediated mechanisms, patients with eastern states.16 mechanisms, patients with Birds are the primary reservoir agammaglobulinemia are at agammaglobulinemia are at for infection and mosquitos serve greater risk for developing as the vector for transmission. chronic enteroviral meningoen- greater risk for developing Symptoms of meningitis occur in cephalitis, which may last for approximately 15 percent of symp- several years. The prognosis in chronic enteroviral menin- tomatic individuals.3 Colorado these patients is poor, with five- goencephalitis, which may last tick fever virus (CTFV) is a tick- year mortality rates approach- borne coltivirus that has been iso- ing 50 percent.3,5,9 for several years. The prognosis lated from patients with meningi- Historically, polioviruses tis in the Rocky Mountain region have been an important cause in these patients is poor, with of the United States and Canada. of viral meningitis, with large CTFV can cause a prolonged epidemics involving the United five-year mortality rates viremia, lasting up to four States and Europe in the first months.17 Meningoencephalitis half of the 20th century. In approaching 50 percent. develops in about five to 10 per- 1988 the World Health cent of infected individuals. Assembly initiated the public health initiative to eradicate Treatment for SLE and CTFV is primarily supportive, polio and, the burden of disease was reduced by over 99 per- although there are reports of experimental use of Ribavirin for cent. However, despite worldwide vaccination efforts, there CTFV infection.18 Tick-borne encephalitis (TBE) is a flavivirus were still 2,001 cases of polivirus infection in the year 2006.11,12 that is transmitted by ticks and has been increasingly recog- Although the rates of poliovirus meningitis have decreased nized as an important cause of viral meningitis in Europe and markedly in past years, the burden of disease caused by non- Asia.19 Neurological symptoms of infection can include menin- polio enteroviruses remains considerable. gitis, encephalitis, myelitis or a combined syndrome. CSF polymerase chain reaction (PCR) can be used for diag- Meningitis accounts for approximately 50 percent of reported nosis of enteroviral meningitis and has been found to be faster, central nervous system disease. There is no known treatment more sensitive and more specific than culture of the CSF. for TBE. An inactivated, whole virus vaccine has been used in Treatment for enteroviral meningitis is primarily supportive, some endemic areas, but is not available in the United States.20 46 Practical Neurology June 2007 The West Nile virus (WNV) was first isolated in the West nant water should be avoided as these can serve as a breeding Nile province of Uganda in 1937. The first recognized case in ground for mosquitoes, and a thorough check for ticks should the United States occurred in 1999 after an epidemic of be done after time spent outdoors. Finally, local and govern- meningitis and encephalitis in New York City.21 The virus has ment programs for insect control can be helpful in reducing since spread to the Western United States and is now found the risk of exposure. nationwide. WNV is a flavivirus and a member of the Japanese encephalitis virus serocomplex, which contains Japanese Herpes viruses encephalitis, SLE, Murray valley, Kunjin and Usutu viruses.22 Herpes simplex types 1 and 2, cytomegalovirus, Epstein-Barr Transmission to humans occurs most commonly through virus and human herpes virus type 6 have all been associated the bite of an infected culicine mosquito. Birds serve as the nat- with aseptic meningitis. Meningitis due to HSV-1 and HSV-2 ural host for the virus. Humans and other mammals typically infection, however, is much more common than that caused by have low-level viremia and, therefore, mammal-to-mammal the other herpes viruses and accounts for approximately one to transmission by mosquitoes is unlikely. Additional modes of three percent of all cases of aseptic meningitis.3 While both transmission include blood transfusion, organ transplantation, HSV-1 and HSV-2 have been reported to cause meningitis, breast-feeding, transplacental and occupational exposure in HSV-2 is a more common cause of pure meningitis, whereas laboratory workers.23 The majority of
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