Meningoencephalitis due to Enteroviral Infection – An Often Overlooked Etiology

Introduction Meningoencephalitis due to Enteroviral Infection – An Often Overlooked Etiology McBath A and Antony SJ* Texas Tech University School of Medicine, El Paso, Texas *Corresponding author: Antony SJ, 1205 N Oregon, El Paso, Texas 79902, Fax: 915-533-4902, Tel: 15-5334900, E-mail: suresh.antony@att.net Citation: McBath A, Antony SJ (2015) Meningoencephalitis due to Enteroviral Infection – An Often Overlooked Etiology. J Immunol Infect Dis 2(1): 104. doi: 10.15744/2394-6512.1.204 Case Report Open Access

Related to our case series, we also present some epidemiological and statistical data gathered from national enteroviral surveillance, including data from the Centers for Disease Control and Prevention.We also discuss several manifestations of enteroviral infection as well as clinical findings and diagnostic methods.Finally, because of its propensity to spread from person to person, we discuss transmission and reference published cases in which enteroviruses have been found to spread among patients in close contact, such as shared homes or classrooms.

Case Reports Index Case
Our presumed index case is the husband of the patient presented in Case 1.We were unable to evaluate him directly because he was deployed overseas at the time of our first patient's presentation; thus our patient is the source of our data regarding this presumed index case.According to our patient, her husband began to feel sick and have headaches several days before being deployed, and he did not seek medical attention until he arrived at his destination.He was diagnosed with viral meningitis after a spinal tap was done.The exact viral etiology was not determined.According to the wife, he recovered after 72-96 hours and continued to stay well.

Case 1
Our first patient is a 30-year-old female who presented with headache, nausea, vomiting, and diarrhea.According to the patient, her symptoms began several days after her husband started showing symptoms.On admission her temperature was 98.2F, BP113/68 mmHg, and pulse 78 beats per minute.On physical exam she was alert and oriented with mild nuchal rigidity; otherwise, the rest of the examination was unremarkable.The serum white blood count was 11,000 cells/mm 3 , hemoglobin 13 g/dL, hematocrit 40% and platelets 301,000 cells/mm 3 .Spinal fluid analysis revealed 8 leukocytes/mm 3 with 18% neutrophils and 81% lymphocytes, and glucose of 54 mg/dL.CSF culture was negative, as were coagglutinins for Haemophilus influenza type B, Streptococcus pneumoniae, Group B streptococcus, and Neisseria meningitidis.HSV PCR was negative.Viral cultures were negative.MRI was unremarkable.A cerebrospinal fluid (CSF) sample sent for enteroviral RT-PCR analysis came back positive.Serotype was not done.She was treated with pain medications and intravenous fluids and recovered well.Follow up in 4 weeks was unremarkable.Journal of Immunology and Infectious Diseases This patient is the 29-year-old female roommate of the patient described above who presented with severe headaches around the same time the previously described patient had headaches.She also complained of a low grade fever and pain in the neck associated with photophobia and nausea but no vomiting.

Additional Cases
Her temperature was 99 F, BP 123/64 mmHg, and pulse 72 beats per minute.Physical exam was significant for a young lady who looked uncomfortable due to neck pain, but she was alert and oriented.The rest of the physical examination was unremarkable.Her white blood cell count was 10,400 cells/mm 3 , hemoglobin 11 g/dl, hematocrit 34%, and platelets 298,000 cells/ mm 3 .CSF analysis showed 65 leukocytes/mm 3 with 87% lymphocytes and 7% neutrophils, and a protein of 63 mg/dL.Viral cultures and HSV PCR were negative.Spinal fluid culture and coagglutinin assays were negative as above.Enteroviral RT-PCR came backpositive.She received similar treatment as the previous case and her recovery was unremarkable.
In addition to the patients described above, two children (ages 5 and 7) in the household had similar symptoms (headaches, low grade fever, cough, and mild diarrhea) and were thought to have a viral illness.Many of their symptoms cleared up in 72 hours, but one of the children required admission for dehydration while the other child was treated at home.Both children were treated conservatively and did well (Table 1).

Discussion
Enteroviruses are members of the family Picornaviridae and are responsible for a wide range of clinical manifestations, ranging from asymptomatic infection, mild febrile illness, conjunctivitis, and respiratory tract infections to more serious conditions such as meningoencephalitis and myocarditis [1][2][3].The exact incidence of infection is difficult to appreciate due to the propensity of enteroviral infections to be asymptomatic [2], particularly in adults [4].According to the CDC, an average of 1,467 cases per year were reported during surveillance from 1970-2005, with nearly half of infections being in children under one year old [5].The true numbers, however, are certainly much higher because enteroviral infections are not nationally reportable; the CDC estimates that there are 10-15 million symptomatic enteroviral infections in the United States each year [5].
Enteroviruses are a common cause of meningitis, an infection of the protective membranes that surround the brain and spinal cord.Clinical manifestations usually have a sudden onset and are characterized by biphasic fever, headache, photophobia, vomiting, rash, and myalgia [3,6].Infection may also spread to the brain parenchyma, a condition known as encephalitis, which may have focal neurologic signs or altered mental status in addition to the aforementioned symptoms.According to one 7-year observational study, enteroviruses were the most frequently identified viral cause of central nervous system infection in the cases analyzed [8].Infection patterns follow a temporal approach, with most enteroviral infections, including those responsible for meningitis, occurring during the summer months.According to national surveillance, states in the Southern United States have the highest rates of diagnosis [1].Spread of infection may occur by either the fecal-oral or respiratory route [6].In addition, the virus can be transmitted via fomites, facilitating transmission to those in close contact with infected individuals [7].For this reason, transmission within households is relatively common [4].In one study that examined household members of patients positively identified to have enteroviral infection, high rates of simultaneous infection were found in family members; for instance, there was an 84% transmission rate among siblings of infected individuals [4].This same study also illustrates the increased likelihood of transmission between adults and children who are in close contact with each other: for children identified with enteroviral infection, 41% of parents were found to also be infected along with 28% of grandparents and 26% of aunts or uncles [4].These findings are consistent with the cases described above with spread of infection between adults and children who share the same living space.Journal of Immunology and Infectious Diseases An additional tool with great utility in the diagnosis of viral meningitis that has become widely available is polymerase chain reaction testing (PCR).Prior to PCR, viral meningitis was more or less a diagnosis of exclusion once a bacterial cause had been ruled out [6].PCR is faster, more sensitive, and more reliable than viral culture in detecting enteroviruses [3].Additionally, PCR is useful as a diagnostic tool because it can detect the presence of enteroviral RNA in cerebrospinal fluid that may have had leukocyte counts, protein levels, and glucose levels within normal limits [3].The widespread availability of PCR has shown to save both time and money in the management of viral meningitis.PCR results can be obtained the same day the CSF is collected, whereas a bacterial culture may take several days and a viral culture even longer [10].Patients who are rapidly diagnosed as having viral meningitis have also been shown to have shorter hospital stays and shorter duration of empiric treatment with antibiotics and/or acyclovir [8,10].
PCR is not without its limitations, however.First, enteroviruses are present in the CSF only transiently; thus, they can only be detected for a short time [2].Additionally, if the infection involves only the brain parenchyma (encephalitis) and not the meninges, PCR may fail [2].Next, the utility of PCR testing in diagnosis of viral meningitis may be affected by temporal factors.One study found that the diagnostic yield of PCR in viral meningitis dropped if the fluid was collected more than two days after the onset of symptoms.The same study also found that using stool as the source for PCR provided a higher diagnostic yield after two days and up to weeks after symptom onset.However, because enteroviruses are a common cause of asymptomatic infections [11], detection of enteroviral RNA outside the cerebrospinal fluid could represent an incidental finding not necessarily related to the patient's clinical symptoms [11].
In conclusion, the case series we report here involving three adults and two children is consistent with current evidence that enteroviruses are capable of causing meningoencephalitis that is easily transmitted among close contacts.We use the presentation of the patients shown here with a review of the literature to remind clinicians of the role that enteroviruses play in various infections, their presentation and clinical findings, and that they should be kept in mind as a potential source of outbreaks.Journal of Immunology and Infectious Diseases Submit your manuscript to Annex Publishers and benefit from: Submit your manuscript at http://www.annexpublishers.com/paper-submission.php→ Convenient online submission → Rigorous peer review → Open access: articles freely available online → Immediate publication on acceptance → Better discount for your subsequent articles → High visibility within the field

Table 1 :
Summary of blood and cerebrospinal fluid lab work from each patient