Cognitive side-effects of antiepileptic drugs in children

Abstract

Although the causes of cognitive impairment in patients with epilepsy have not been completely elucidated, three factors are clearly involved: the underlying etiology of epilepsy, the effects of seizures or the epileptiform EEG discharges themselves, and the central nervous system effects of antiepileptic drugs (AEDs). All commonly used AEDs have some effect on cognitive function, and the effect may be substantial when crucial functions are involved, such as learning in children. With phenobarbital, there is a high risk for serious cognitive effects impacting attention and memory. Phenytoin may affect mental speed, mainly in higher dosing and polytherapy. Moderate monotherapy doses do not seem to induce much effect. Valproate does not seem to impair cognition if sufficiently controlled for hyperammonemia. For carbamazepine, there are conflicting reports, which may be due to selection bias or dosing. For oxcarbazepine, there is no evidence for any detrimental change compared to valproate but mild improvements on attentional tests. For topiramate, there is clear evidence for topiramate-induced cognitive impairment (attention, memory, and language function) in adults and children. Although data is sketchy, levetiracetam does not seem to have a negative impact on cognition. For lamotrigine, there is evidence of a cognitive-enhancing effect on attention. No evidence for cognitive side-effects has been found for vigabatrin. Ethosuximide is not associated with cognitive impairment although the evidence is sketchy. For gabapentin, tiagabine, zonisamide, and rufinamide no studies in children are available.

Impaired Executive Function by Interictal Epileptiform Discharges in Patients with Idiopathic Generalized Epilepsy

“…A recent study demonstrated that the cognitive side effect profile of lacosamide is comparable to that of LTG and superior to that of topiramate, which was indicated by both subjective and objective measures [43]. VPA does not appear to impair cognition if sufficiently controlled for hyperammonemia [42]; however, studies have shown VPA can reduce spatial working memory and cell proliferation in the hippocampus [44]. These results support the idea that VPA may cause cognitive impairment by reducing neurogenesis within the hippocampus [44].…”

“…For example, phenytoin may affect mental speed and phenobarbital may affect attention and memory. Evidence has shown that LTG has a cognitive-enhancing effect on attention [42]. A recent study demonstrated that the cognitive side effect profile of lacosamide is comparable to that of LTG and superior to that of topiramate, which was indicated by both subjective and objective measures [43].…”

“…All commonly used AEDs have some effect on cognitive function, which may be substantial when crucial functions are involved [42]. For example, phenytoin may affect mental speed and phenobarbital may affect attention and memory.…”

Outcomes in Postoperative Pediatric Cardiac Surgical Patients Who Received an Antiepileptic Drug

“…2 The evidence is fairly strong with regard to phenobarbital and its association with cognitive deficits in pediatric patients, 6 some data showing phenytoin has an effect on mental speed, while levetiracetam does not seem to have a negative impact on cognition. 7 This is the first study to report the outcomes of post-cardiac surgical pediatric patients who received AED therapy as a result of postoperative seizures. Overall, the use of these agents at our institution is very low, considering that approximately 900 cardiac surgical procedures are performed each year.…”

Children With Epilepsy: Specific Learning Difficulties

“…Among the main factors there are: 1) the pre-disease condition (e.g., the child's skills and abilities), 2) factors connected with the disease (e.g., the etiology and type of the epilepsy syndrome) (Aldenkamp et al, 2005), 3) the moment when the disease occurred in the context of the child's developmental processes, 4) the duration of the disease, 5) the immediate effect of epileptic activity (e.g., partial seizures vs. generalized, the occur- Table 3. Illustration of the problem on the case of a 12-year-old boy rence of status epilepticus or transient cognitive impairment) (Aldenkamp, 2004), 6) factors associated with the treatment: surgical and/or pharmacological (Ijff andAldenkamp, 2013; Sherman et al, 2003), 7) the absence from school connected with the occurrence of seizures (Aguiar et al, 2007), 8) the profile of cognitive deficits that appear in the course of the disease (Aldenkamp et al, 2005), 9) factors associated with the patient's socio-economical conditions (Fastenau et al, 2004). Of significant meaning for the appearance of school difficulties can also be psychiatric disorders that co-occur with epilepsy (depression, anxiety, or intensified symptoms of attention deficit hyperactivity disorder, commonly known as ADHD) (Reilly, Agnew and Neville, 2011).…”