The risk factors for epilepsy are many but for the purpose of this review may be divided into infectious and noninfectious conditions. The noninfectious causes include traumatic brain injury, cerebrovascular disease, tumors and genetic factors. The infectious risk factors differ inherently from noninfectious conditions because of their biological nature as opposed to chemical, environmental, or genetic nature of the latter. The biological nature of agents that cause infections confer certain special epidemiological characteristics to epilepsy associated with CNS infections as opposed to posttraumatic and poststroke epilepsy. These characteristics are outlined below.
A complex interaction exists among the infectious agent, the host, and the environment (Fig. 1). An understanding of this epidemiological triad is vital for appreciation of the mechanisms by which infective agents produce clinical symptoms and signs (e.g., seizures or epilepsy). Infective agents include prions, viruses, bacteria, fungi, and helminths. The biological life cycle of the infective agent, which may in certain cases, be rather complex, the mode and dynamics of transmission, and the natural history of the infectious disorder it produces in the human host determine the epidemiological proportions of the infectious disease.
In population studies, exposure to the infectious agent is not necessarily synonymous with clinical disease and may not lead to infection at all. On the other hand, it may lead to subclinical disease with no overt clinical manifestations. The iceberg analogy (Fig. 2) is often used to describe the clinical spectrum of a variety of infectious disorders, including both epidemic encephalitides and more chronic endemic disorders such as Taenia solium-cysticercosis. For instance, during an epidemic of Japanese-B-encephalitis (JE) infection, symptomatic illness occurs in only 1 in 250 cases (Grossman et al., 1973). Furthermore, the majority of the symptomatic cases have only mild manifestations. Those that present with neurological manifestations and sequelae (including epilepsy) represent merely the tip of the iceberg. Likewise, in the case of cysticercosis, caused by the larval stage of the tapeworm, T. solium, community-based serological surveys reveal high levels of seropositivity in endemic populations. The majority of the seropositive individuals in the populations surveyed do not have epilepsy or other neurological symptoms due to cysticercosis or evidence of neurocystcercosis (NCC) on imaging studies (e.g., computed tomography [CT]). In the community, therefore, there is a large pool of individuals who are seropositive, suggesting exposure to the parasite, T. solium but no manifestations of NCC (Montano et al., 2005). Conversely, there are individuals in the community, who demonstrate evidence of neurological infestation by the parasite (i.e., NCC) on imaging studies but have no symptoms (or seizures). A study undertaken in an endemic community in Guatemala found evidence of NCC on imaging studies in 47% of those with seizures as well as 24% of asymptomatic individuals (Garcia-Noval et al., 1996). Indeed, CT undertaken in asymtomatic individuals in T. solium–endemic communities may frequently reveal single- or multiple-calcified specks (Montano et al., 2005). These calcified specs signify dead cysticerci, which presumably were live and active in the past but nonetheless did not manifest with symptoms (i.e., seizures) and hence remained subclinical. Thus, both, in the case of endemic infections and during epidemics, there is a proportion of individuals in the community, who are exposed to the infective organism but do not develop the infection (asymptomatic seroposivity) as well as those who get infected but do not develop symptoms and signs (subclinical cases) in addition to those who manifest with symptoms (seizures) in addition to imaging evidence of neurological involvement by the infecting organism as well as demonstrate immunological evidence of exposure (i.e., seropositivity correlating with symptoms). Finally, there may be individuals who present with seizures due to neurological infection but are seronegative (Montano et al., 2005). Presumably, the immunological response to the infective agent is insufficient to be detected by the serological assays in these individuals.