The Aspects and Mechanisms of Cognitive Alterations in Epilepsy: The Role of Antiepileptic Medications

Abstract

Epilepsy is a major health problem. Several studies suggest a significant influence of epilepsy and its treatment on dynamic and functional properties of brain activity. Epilepsy can adversely affect mental development, cognition, and behavior. Epileptic patients may experience reduced intelligence, attention, and problems in memory, language, and frontal executive functions. Neuropsychological, functional, and quantitative neuroimaging studies revealed that epilepsy affect the brain as a whole. Mechanisms of epilepsy-related cognitive dysfunction are poorly delineated. Cognitive deficits with epilepsy may be transient, persistent, or progressive. Transient disruption of cognitive encoding processes may occur with paroxysmal focal or generalized epileptic discharges, whereas epileptogenesis-related neuronal plasticity, reorganization, sprouting, and impairment of cellular metabolism are fundamental determinants for progressive cognitive deterioration. Also antiepileptic drugs (AEDs) have differential, reversible, and sometimes cumulative cognitive adverse consequences. AEDs not only reduce neuronal irritability but also may impair neuronal excitability, neurotransmitter release, enzymes, and factors critical for information processing and memory. The present article serves as an overview of recent studies in adult and childhood epilepsy literatures present in PubMed that highlighted cognitive evaluation in epilepsy field (publications till 2008 were checked). We also checked the reference lists of the retrieved studies for additional reports of relevant studies, in addition to our experience in this field. Our search revealed that although the aspects of cognitive dysfunction, risk factors, and consequences have been explored in many studies; however, the mechanisms of contribution of epilepsy-related variables, including AEDs, to patients' cognition are largely unexplored. In this review, we discussed the differential effect of AEDs in mature and immature brains and the known mechanisms underlying epilepsy and AEDs adverse effects on cognition. The nature, timing, course, and mechanisms of cognitive alteration with epilepsy and its medications are of considerable clinical and research implications.

Memory, executive function and language function are similarly impaired in both temporal and extra temporal refractory epilepsy—A prospective study

“…underlying pathology, high frequency of seizures, medications and also, surgery. Studies indicate the association of cognitive impairment with factors like age of onset, seizure type, seizure frequency and localization of the seizure focus, however, there is variation in the strength of association of these factors, reported in different studies (Lah et al, 2006;Hamed, 2009). Recent literature suggests transition from a long-standing focus on the relationship between cognitive function and clinical epilepsy features to one linking cognitive impairment to underlying anatomic, metabolic, and other neurobiologic correlates of the epilepsies (Hermann et al, 2009).…”

Cognitive Disorders in Juvenile Myoclonic Epilepsy

“…[40,41] It can be concluded that CDs in JME patients may at least partially be caused by side effects of medication. The basic mechanisms underlying AED-induced cognitive impairments require further investigation.…”

“…[39] In general, the deleterious effect of AEDs on cognition could be attributed to: (1) Na+ channel blockade, (2) enhanced GABAergic activity, and (3) decrement in glutamate-mediated excitation. [40] Simultaneously, there are also studies that describe a positive effect of AEDs on cognitive disorders. In general, the beneficial effects of AEDs on cognition could be due to:…”

Cochlear Function in Adults with Epilepsy and Treated with Carbamazepine

“…While epilepsy is defined by the presence of recurrent seizures, it can be complicated by a number of comorbidities which impact the patient's overall quality of life. Individuals with chronic epilepsy may experience cognitive impairment and reduced intelligence [Hamed, 2009], behavioral complications such as depression, anxiety, obsessive compulsive symptoms and psychosis [Kobau et al, 2006;Hamed et al, 2013], and a wide variety of somatic disorders such as vascular risks and events [Hamed et al, 2007] and metabolic and endocrine side effects [Hamed, 2015]. These comorbid conditions have been attributed to epilepsy itself, the underlying etiology of remote or symptomatic epilepsy and as a complication of long-term AED therapy.…”