INFECTIOUS ETIOLOGIES

OVERVIEW

The commonest etiology for epilepsy worldwide is infectious, especially in developing countries. Infections in the central nervous system can cause both acute symptomatic (provoked) seizures (which occur closely related to the timing of the initial infection) and epilepsy. Infectious etiologies include tuberculosis, HIV, cerebral malaria, neurocysticercosis, subacute sclerosing panencephalitis, cerebral toxoplasmosis. These infections sometimes have a structural correlate, however the primary cause of the epilepsy is conceptualized as the infectious process. An infectious etiology may have specific treatment implications. There are also public health implications as prevention of such infections may reduce the burden of epilepsy, particularly in developing countries.

BACTERIAL MENINGITIS OR MENINGOENCEPHALITIS

The commonest etiologies for bacterial meningitis are meningococus, pneumococcus and haemophilus influenza B. Acute seizures may occur related to fever or to complications such as subdural collections, cerebritis or cerebral infarction. Immunization programs may reduce the incidence of specific bacterial meningitides.

CEREBRAL MALARIA

Plasmodium falciparum in sub-Saharan Africa can cause neurologic complications in half of affected individuals. This infection is the most important cause of epileptic seizures in these regions. Cerebral malaria with related coma may be fatal, especially in children. Plasmodium vivax in Asia causes similar neurological complications and epilepsy.

CEREBRAL TOXOPLASMOSIS

Toxoplasmosis, found worldwide, is caused by Toxoplasma gondii. Immunocompetent persons with primary infection are usually asymptomatic, but latent infection can occur. In immunosuppressed patients, especially those with HIV, reactivation can cause disease (usually when CD4 lymphocyte count falls below 100 cells/mm3). Most patients with cerebral toxoplasmosis have multiple, ring-enhancing, brain lesions often associated with edema and with predilection for involvement of the basal ganglia.

CMV

CMV is the commonest fetal viral infection. Fetal CNS infection after 20 weeks gestation can cause malformations of cortical development (including polymycrogyria and schizencephaly), and intracranial calcification in the developing brain. Direct perinatal CNS CMV infection can also occur, with clinical signs manifesting after an incubation period of 2-6 weeks. Overall, 90% of affected infants are asymptomatic at birth, resulting in challenges in early correct diagnosis of CMV neuroinfection. Some of these infants may only present with sensorineural hearing loss at a later date. However, 10% of infants may have early symptoms which may include microcephaly, anaemia, thrombocytopenia, hepatitis, chorioretinitis, neurological impairment and sensorineural hearing impairment. Diagnosis is by detection of CMV DNA in CSF. CMV DNA may also be detected in in urine. Seizures may have onset in the first month of life, in the first year or rarely later. Treatment with gancyclovir may ameliorate the clinical course.

HIV

Seizures can result from primary cerebral HIV infection, especially in children. In adults, most seizures are cause by related opportunistic central nervous system infections such as toxoplasmosis, cryptococcal meningitis and tuberculomas; or due to secondary neoplastic lesions.

NEUROCYSTERICOSIS

Neurocysticercosis is caused by ingestion of food contaminated with Taenia solium eggs. Eggs hatch in the intestine, larvae migrate to the central nervous system and then form cysts. Cysts have four phases: 1) vesicular (asymptomatic); 2) colloidal (degeneration and inflammation); 3) granular nodular; and 4) calcification. Although seizures are most often associated with cyst degeneration, they can occur at any stage. Although neurocysticercosis is more prevalent in developing countries (Latin-America, India and Africa), individuals in developed countries may be affected, if they have had foreign travel to endemic areas.

The diagnosis of neurocysticercosis is complex; no diagnostic test identifies all cases. The diagnosis depends on supportive clinical history (including exposure history), laboratory results and imaging findings. In most patients, neuroimaging findings are not pathognomonic. If an eccentric scolex is seen within the cyst, neurocystericosis may be diagnosed confidently. During the degeneration of the cyst, contrast-enhancing lesions with surrounding edema may be observed on imaging. Enzyme-linked immunotransfer blotting is the most accurate serologic test. A negative serologic result does not exclude neurocysticercosis. The sensitivity of this test is higher early in the course of infection (when individuals are often asymptomatic) and lower late in the disease course (when individuals are symptomatic, and lesions calcified). The sensitivity in the presence of multiple intracranial cysts is higher (90-100%) but lower (20-30%) when inflammation is absent or in the presence of a single cyst.

TUBERCULOSIS

Seizures can occur in meningo-tuberculosis due to cerebral vasculitis and infarction, especially in young children and in people co-infected with HIV. Seizures with focal features may also occur as a consequence of tuberculomas, identified as ring-enhancing lesions on neuroimaging.

VIRAL ENCEPHALITIS

Encephalitis is a recognized complication of infections with a number of viruses. Herpes simplex virus type 1 is the most common viral cause. Affected individuals present with acute encephalopathy and seizures, epilepsy develops in around 50% of cases. Other less common etiologies for viral encephalitis include human herpes virus 6 (associated with acute limbic encephalitis and febrile status epilepticus), influenza B, varicella, measles, mumps and rubella viruses. In certain countries or regions there is a predominance of specific viral etiologies for encephalitis, examples include Japanese and enterovirus 71 in Asia, West Nile virus in the USA, arbovirus in Europe and Dengue virus in some African and Latin-American countries.

Sub-acute sclerosing panencephalitis is a rare progressive chronic encephalitis, seen predominantly in children and young adults as a consequence of chronic measles infection (typically with the initial infection occurring before the age of 2 years). Affected individuals show progressive cognitive deterioration, seizures (myoclonus), ataxia, photosensitivity, and a characteristic EEG (periodic discharges).

OTHER INFECTIONS

Other less common infectious causes of epilepsy include toxocariasis, schistosomiasis and Lyme disease (neuroborreliosis).