Seizures in encephalitis

A large number of viruses can result in encephalitis. However, certain viruses are more prevalent in certain geographical regions. For example, Japanese encephalitis (JE) and dengue in South East Asia and West Nile in Middle East whereas Herpes simplex encephalitis (HSE) occurs all over the world without any seasonal or regional variation. Encephalitis can result in acute symptomatic seizures and remote symptomatic epilepsy. Risk of seizures after 20 years is 22% following encephalitis and 3% after meningitis with early seizures. Amongst the viruses, HSE is associated with most frequent and severe epilepsy. Seizures may be presenting feature in 50% because of involvement of highly epileptogenic frontotemporal cortex. Presence of seizures in HSE is associated with poor prognosis. HSE can also result in chronic and relapsing form of encephalitis and may be an aetiology factor in drug resistant epilepsy. Amongst the Flaviviruses, Japanese encephalitis is the most common and is associated with seizures especially in children. The frequency of seizures in JE is reported to be 6.9% to 46%. Associated neurocysticercosis in JE patients may aggravate the frequency and severity of seizures. Other flaviviruses such as equine, St Louis, and West Nile encephalitis can also produce seizures. In Nipah encephalitis, seizures are commoner in relapsed and late-onset encephalitis as compared to acute encephalitis (50% vs 24%). Other viruses like measles, varicella, mumps, influenza and enteroviruses may result in encephalitis and seizures. Status epilepticus can also occur in encephalitis. It may be refractory to medication and require aggressive treatment. Single or discrete seizures in encephalitis should be treated as any other acute symptomatic seizures. Neurology Asia 2008; 13 : 1 – 13 Address for correspondence: U K Misra, Professor and Head, Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow226014, India. FAX: 091-0522-2668017, Email: [email protected], [email protected] INTRODUCTION Encephalitis refers to acute inflammatory process affecting the brain. Viral infections are the most important cause of encephalitis. There are over 00 viruses that can result in encephalitis. The patients present with fever and varying degree of alteration in sensorium which may be associated with focal neurological signs or seizures. In such patients, malaria, bacterial meningitis and non infectious causes of encephalopathy must be carefully excluded. Viral encephalitis generally results in nonspecific clinical picture with some specific features of anatomical involvement such as behavioral changes, aphasia or partial complex seizure in herpes simplex encephalitis (HSE) because of characteristic frontotemporal involvement. There are numerous viruses responsible for viral encephalitis. While precise estimates about the incidence of encephalitis following these viral infections are not available; there are estimates that HSE is the most important cause of treatable viral encephalitis with an incidence of case/million population/year. Certain viruses are prevalent in certain regions. Japanese encephalitis (JE) in South East Asia, West Nile encephalitis is Middle East, St. Luis encephalitis and equine encephalitis in America are some examples. Lately West Nile encephalitis from USA and Nipah virus encephalitis from Malaysia have been reported. The incidence of clinically diagnosable encephalitis is between 3.5-7.4/ 00,000 population/year; however in children the incidence is much higher. Encephalitis may occur in sporadic or epidemic form. Establishing the diagnosis of viral encephalitis may be challenging. The likelihood of a virus depends upon the geographical location, timing of the epoch studied and method or rigor of investigation. In a recent study in Finland, cerebrospinal fluid (CSF) polymerase chain reaction (PCR) was used to diagnose over 3,000 REVIEW ARTICLES Neurology Asia June 2008 2 patients with CNS infections, such as encephalitis, meningitis and myelitis. In this study, Vericella zoster was the most common infection (29%), followed by herpes and entero viruses in % each, and influenza A virus in 7% of patients.2 This study suggests that HSV is probably over estimated and Varicella zoster underestimated. HSE however, remains a critical diagnosis because specific treatment is available for this encephalitis. In USA, the most important encephalitides are HSE and arbovirus encephalitides, but 73% encephalitis is of undetermined etiology.3 Encephalitis and meningoencephalitis are important causes of acute symptomatic seizures and remote symptomatic epilepsy. Long-term risk of seizures following CNS infection was studied in a large population based study. Twenty year risk of unprovoked seizures was 6.8%; 22% for encephalitis with early seizures, and 3% for bacterial meningitis with early seizures.4 In the present review, the seizures in HSE, Flavivirus (Japanese encephalitis, eastern equine and western equine, dengue), and other viruses including Nipah virus encephalitis will be discussed. HERPES SIMPLEX ENCEPHALITIS Herpes simplex virus is a neurotropic virus and is the most important cause of sporadic encephalitis in children above 6 months and in adults.5 No seasonal or gender related preference occurs in HSE. It has a high mortality of 70% if untreated and prognosis is poor. Only a minority of patients return to normal functions. There is a bimodal distribution of HSE with one third cases occurring before 20 years of age and half in those above 50 year of age. In a recent PCR study on 5 6 patients with clinical evidence of encephalitis, 7.4% patients were due to HSE and most of these HSE patients were above 40 year of age.6 The bimodal distribution of HSE may reflect primary HSV infection in younger age group and reactivation of latent HSV infection in older patients. In immunocompetent patients, more than 90% of HSE occurs due to infection with HSVand the remainder due to HSV-2.7 More than two-third cases of HSE due to HSV infection appears to result from reactivation of endogenous latent HSVinfection in the individuals previously exposed to the virus. HSVhas remarkable capability for producing latency, persistent infection and for reactivation.8 Primary HSV infection results in axoplasmic transport to the trigeminal sensory ganglion where it establishes latency. Latent HSV1 virus is detectable in trigeminal ganglia of nearly all seropositive individuals.8 Reactivation results in retrograde transport of virus resulting in herpes labialis amongst other clinical manifestations. However the pathway by which HSV reaches the CNS in humans to produce encephalitis remains unknown. In Primary infection, virus could invade the olfactory bulbs through the nose and spread via olfactory pathway to orbitofrontal and medial temporal lobes.9 Affinity of HSV-1 for basifrontal and medial temporal (limbic) cortex and sparing of the most other cortices, grey matter, nuclear masses and white matter is interesting and mysterious. The affinity for the specialized areas is attributed to intranasal inoculation and spread via olfactory nerve of HSV.9 Proximity of dural nerves to basifrontal and temporal lobes, virus lies dormant in anterior and middle cranial fossa which renders these areas more susceptible to HSV. The virus may travel by cell to cell contact across the meninges into adjacent cortices. The structures involved in HSE are part of limbic system and these boundaries are respected by HSV . 0 This affinity is attributed to distinctive anatomical, neurochemical and immunological properties of these cortices.