The Progression of Epilepsy

Abstract

Summary: Prognosis for seizure control and cognitive development varies considerably among syndromes. Several factors may interact to influence outcome of an epilepsy including a causative etiology, ictal and interictal discharges, seizure‐related trauma or systemic perturbations, and antiepileptic drug (AED) effects. Clinical evidence convincingly supporting Gowers' hypothesis that seizures beget seizures is lacking. Short‐term seizure suppression by early treatment does not appear to influence long‐term prognosis. Malignant epilepsy syndromes usually begin in infancy or childhood, have a high seizure frequency, resist the initial AED, and are often associated with progressive cognitive dysfunction. Prompt management of some severe epilepsy syndromes may lessen cognitive decline. However, aggressive AEDs therapy must be balanced against the potential for cognitive side effects, particularly if multiple AEDs are used. Several experimental paradigms closely parallel human TLE as both have an initial precipitating injury (IPI), a latent period, then recurrent spontaneous seizures. In humans, an IPI is any medical event with neurological implications. Although transition from a latent period to a seizure disorder certainly constitutes “progression” of the disorder, convincing clinical evidence of subsequent worsening has not emerged. Substantial clinical and experimental evidence indicates some cognitive regression and focal atrophy with time for TLE and other intractable syndromes. However, seizure frequency and severity, established early in the disorder, appear stable in most patients, and even regress in benign syndromes. Factors mitigating or extinguishing epilepsies need to be further sought.

Excitatory/Inhibitory Balance and Circuit Homeostasis in Autism Spectrum Disorders

“…For example, if inhibitory transmission is reduced, this is likely to enhance the ability of excitatory synapses to undergo Hebbian LTP which will in turn create a further imbalance in activity making compensation all the more difficult. This nonlinear interaction could contribute to the frequent switch-like onset and subsequent persistence of seizures, although the question of how or even whether “seizures beget seizures” is controversial (Ben-Ari, 2008; Blume, 2006; Hauser and Lee, 2002). Perhaps more importantly, compensation mechanisms may themselves be targets of the underlying pathology.…”

Ionotropic Glutamate Receptors & CNS Disorders

“…Although epilepsy exists in various forms [287,288], the role of KARs in the initiation and maintenance of epileptic seizures primarily comes from work on temporal lobe epilepsy (TLE) [289][290][291][292]. Two main types are internationally recognized (i) mesial TLE which occurs in the hippocampus, parahippocampal gyrus and amygdala regions of the CNS Fig.…”

Convulsive status epilepticus duration as determinant for epileptogenesis and interictal discharge generation in the rat limbic system

“…The pre-epileptic state-which presumably reflects an epileptogenic process-is known as latent period while the epileptic condition is commonly defined as chronic period (Blume, 2006;Cavalheiro et al, 2006). TLE patients are often unresponsive to antiepileptic drugs (Wiebe et al, 2001), and present with a typical pattern of brain damage known as Ammon's horn sclerosis (or mesial temporal sclerosis) that is characterized by neuronal loss in hippocampus and parahippocampal structures such as the entorhinal cortex (EC) and amygdala (Engel, 2001;Gloor, 1991).…”