Third year medical students Faculty of medicine, Mutah University Viral Meningitis Dr. Amin Aqel NS I Third year medical students Faculty of medicine, Mutah University

Introduction * Meningitis is one of the most terrifying disease. * It can be fatal in hours. * Early symptoms resemble self-limiting conditions (flu and colds).

Meningitis…… Definition Meningitis is an infection which causes inflammation of the membranes covering the brain and spinal cord. Non-bacterial meningitis is often referred to as ‘aseptic meningitis’ – eg. viral meningitis Bacterial meningitis may be referred to as ‘purulent meningitis’. Common causes and risks The most common causes of meningitis are viral infections that usually resolve without treatment. Bacterial infections of the meninges are extremely serious illnesses, and may result in death or brain damage even if treated.

Symptoms of meningitis…. Adults and children Babies Neonates and the elderly often present atypically .

Viral (aseptic) Meningitis Definition: A syndrome characterized by acute onset of meningeal symptoms, fever, and cerebrospinal fluid pleocytosis, with bacteriologically sterile cultures. Laboratory criteria for diagnosis: No evidence of bacterial or fungal meningitis Case classification Confirmed: a clinically compatible illness diagnosed by a physician as aseptic meningitis, with no laboratory evidence of bacterial or fungal meningitis Comment Aseptic meningitis is a syndrome of multiple etiologies, but most cases are caused by a viral agent.

Viral Meningitis Etiological Agents: Reservoirs: Enteroviruses (Coxsackie's and echovirus): most common. Adenovirus Measles virus Herpes Simplex Virus Varicella Arbovirus Reservoirs: Humans for Enteroviruses, Adenovirus, Measles, HS, and Varicella Natural reservoir for arbovirus not known but may be birds, rodents etc. Modes of transmission: Primarily person to person and arthropod vectors for Arboviruses Incubation Period: Variable. For enteroviruses 3-6 days, for arboviruses 2-15 days Treatment: No specific treatment available. Most patients recover completely on their own.

Properties of enteroviruses Property Enteroviruses Size (nm) Capsid form Polypeptide RNA type Virus replication the Acid Optimal temperature for growth(oC) Non enveloped 22-30 Icosahedral VP1, VP2, VP3, VP4 +SS-RNA cytoplasm Stable*pH 3 to 9 37

Symptoms Brain Day 0 4-14 7 - 9 10 GUT Oral Infection viral infections of the central nervous system viral meningitis (‘aseptic meningitis’) > enteroviruses Common – usually benign GUT Brain Oral Infection Replication in Gut Viraemia Infection of CNS Symptoms Day 0 4-14 7 - 9 10 enterovirus meningitis

Transmission Fecal – oral route: poor hygiene, dirty diapers(especially in day-care settings) Ingestion via contaminated food and water Contact with infected hands Inhalation of infectious aerosols

Viral Meningitis 75% caused by enteroviruses Other viruses Poliovirus Coxsackie virus (A and B groups) Echo virus Enterovirus Other viruses HSV2 (HSV1 causes encephalitis) HIV Lymphocytic choriomeningitis virus Mumps Varicella Zoster

Viral meningitis Summer, fall Severe headache Vomiting Fever Stiff neck CSF - pleocytosis (mainly mononuclear cells), Normal protein, Normal glucose CSF pleocytosis (mainly mononuclear cells) Normal to slightly elevated CSF protein 18% Normal to slightly low CSF glucose 12% Most not reported, so true incidence not known

Viral Meningitis Cannot distinguish initially from bacterial meningitis May be preceded by a few weeks by viral gastroenteritis Almost never involves brain (meningoencephalitis) Patient never obtunded, no History of seizure Disease is self-limited, resolves after 7 to 10 days without treatment No serious sequelae

CSF Low numbers of WBCs : 10 to 500 PMNs predominate early, Monos or Lymphocytes later CSF to serum glucose ratio usually = 50% Protein may be high Gram stain, culture and bacterial antigens negative Enteroviral PCR positive about 70% of time

Laboratory Diagnosis Molecular Virus Isolation Mainstay of diagnosis of enterovirus infection Coxsackie B and Echoviruses can be readily grown in cell culture from throat swabs, faeces, and rectal swabs. They can also be isolated from the CSF Coxsackie A viruses cannot be easily isolated in cell culture. They can be isolated readily in suckling mice but this is not offered by most diagnostic laboratories because of practical considerations. Molecular techniques may provide a better alternative. Serology Neutralization tests or EIAs are used but are very cumbersome and thus not offered by most diagnostic laboratories Molecular PCR

Approach Treat like bacterial meningitis until the 72 hrs culture comes back negative But HSV meningitis: Behavioral and personality changes Ct scan Temporal lobe Aciclovir iv

Viral meningitis - Treatment Supportive No antibiotics Analgesia Fever control Often feel better after LP No isolation - Standard precautions Not clear why sometimes feel better after diagnostic LP

Viral meningitis - Outcomes Adverse outcomes rare Infants <1 year have higher incidence of speech & language delay Neurological complications are rare Encephalitis may develop, though this is rare.

Meningoencephalitis - etiology Herpes simplex type 1 Rabies Arthropod-borne St. Louis encephalitis La Crosse encephalitis Eastern equine encephalitis Western equine encephalitis West Nile

herpes simplex encephalitis > haemorrhagic encephalitis Sporadic Acute e.g. human rabies, herpes simplex virus, herpes simplex encephalitis > haemorrhagic encephalitis mortality (without antivirals) 70-90% residual serious morbidity 95% occurs at all ages

encephalitis Subacute sclerosing panencephalitis (measles), + inflammatory reaction Chronic subacute sclerosing panencephalitis (SSPE) occurs in about 1 in100,000 to 1,000,000 cases of measles virus infection. SSPE develops years (typically 6-10) following infection with measles virus and has an almost invariably fatal outcome.

Japanese Encephalitis Leading cause of viral encephalitis in Asia with 30-50,000 cases reported annually case-fatality ratio: 30% serious neurologic sequelae: 30%