Cognitive side-effects of antiepilpetic drugs in children

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

Subjectively Perceived Side-Effects of Anti-Epileptic Drugs in Chronic Refractory Epilepsy

Purpose: Antiepileptic drugs (AEDs) can cause side-effects. Patient-reported side-effects due to this type of medication are very common, but thus far only investigated in community based populations. We investigated the subjectively perceived side-effects of anti-epileptic drug treatment in patients with refractory epilepsy. Methods: A non-selected group, of patients visiting the outpatient department between September 2011 and November 2011 was invited to complete a questionnaire only if they had experienced side-effects of their AED treatment during last year. The questionnaire, the SIDAED, assessed four different categories; cognition, mood, cosmetics and general health. Subgroup analyses were based on their medication use: mono- or polytherapy, older and newer AEDs and AEDs with a high or a low risk for cognitive and behavioral/mood side-effects. Results: In total, 203 patients or their relatives completed the questionnaire. Mean age of the patients was 37 years (2-81). Most reported complaints (85%) were about their general health followed by cognition, mood and cosmetics. Subgroup analyses showed no differences between patients using monotherapy or polytherapy. Also, no differences were found between patients using older AEDs or newer drugs. Patients using AEDs with a high risk for side-effects did complain more about their mood but not about their cognition. Regression analysis showed that using a high risk AED for behavioral side-effects contributed significantly to the total experienced side-effects. Conclusion: In conclusion, our study illustrates that patients are a reliable respondent to indicate side-effects despite of their refractory epilepsy. Particularly, mood complaints due to antiepileptic drugs (such as levetiracetam) are correctly notice

Cognitive effects of lacosamide as adjunctive therapy in refractory epilepsy

Background: Lacosamide (LCM) is a novel antiepileptic drug (AED) with potential benefit as adjunctive treatment in patients with partial-onset seizures. As yet, limited information on cognitive effects of LCM is available, especially in real-life settings. Aims: In this open clinical prospective study, the cognitive effects of LCM were evaluated when used as adjunctive antiepileptic therapy in patients with refractory epilepsy. Methods: We included 33 patients aged between 16 and 74 years (mean: 37 years). All patients had a localization-related epilepsy. Patients were assessed at baseline before starting LCM treatment and during follow-up when the optimal clinical dose was achieved. Materials: Subjective complaints were evaluated using the SIDAED; effects on cognition were evaluated using the computerized visual searching task (CVST). Results: The CVST showed significant faster information processing reaction times at the second evaluation (P = 0.013), which was not correlated with seizure control, type of epilepsy, age, gender, drug load, number of concomitant drugs, dose or duration of LCM treatment. On the SIDAED, patients complained more about their cognitive function at the second evaluation (P = 0.005). For the SIDAED, a positive correlation at follow-up was found between the total severity score and higher age (r = 0.375, P = 0.031), but not with epilepsy factors or treatment characteristics. Discussion/Conlusion: Screening of the cognitive effects of LCM showed that LCM does not have negative effects on information processing speed. As this is the most sensitive function for cognitive side effects of AEDs, LCM does not seem to induce the common negative cognitive effects. Remarkably, patients complained more, especially about their cognitive function, which is possible the 'doing better, feeling worse phenomenon'

Metabolic and functional MR biomarkers of antiepileptic drug effectiveness: a review

As a large number of patients with epilepsy do not respond favorably to antiepileptic drugs (AEDs), a better understanding of treatment failure and the cause of adverse side effects is required. The working mechanisms of AEDs also alter neurotransmitter concentrations and brain activity, which can be measured using MR spectroscopy and functional MR imaging, respectively. This review presents an overview of clinical research of MR spectroscopy and functional MR imaging studies to the effects of AEDs on the brain. Despite the scarcity of studies associating MR findings to the effectiveness of AEDs, the current research shows clear potential regarding this matter. Several GABAergic AEDs have been shown to increase the GABA concentration, which was related to seizure reductions, while language problems due to topiramate have been associated with altered activation patterns measured with functional MR imaging. MR spectroscopy and functional MR imaging provide biomarkers that may predict individual treatment outcomes, and enable the assessment of mechanisms of treatment failure and cognitive side effects

Glutamate concentrations vary with antiepileptic drug use and mental slowing

OBJECTIVE: Although antiepileptic drugs (AEDs) are effective in suppressing epileptic seizures, they also induce (cognitive) side effects, with mental slowing as a general effect. This study aimed to assess whether concentrations of MR detectable neurotransmitters, glutamate and GABA, are associated with mental slowing in patients with epilepsy taking AEDs. METHODS: Cross-sectional data were collected from patients with localization-related epilepsy using a variety of AEDs from three risk categories, i.e., AEDs with low, intermediate, and high risks of developing cognitive problems. Patients underwent 3T MR spectroscopy, including a PRESS (n=55) and MEGA-PRESS (n=43) sequence, to estimate occipital glutamate and GABA concentrations, respectively. The association was calculated between neurotransmitter concentrations and central information processing speed, which was measured using the Computerized Visual Searching Task (CVST) and compared between the different risk categories. RESULTS: Combining all groups, patients with lower processing speeds had lower glutamate concentrations. Patients in the high-risk category had a lower glutamate concentration and lower processing speed compared with patients taking low-risk AEDs. Patients taking intermediate-risk AEDs also had a lower glutamate concentration compared with patients taking low-risk AEDs, but processing speed did not differ significantly between those groups. No associations were found between the GABA concentration and risk category or processing speed. CONCLUSIONS: For the first time, a relation is shown between glutamate concentration and both mental slowing and AED use. It is suggested that the reduced excitatory action, reflected by lowered glutamate concentrations, may have contributed to the slowing of information processing in patients using AEDs with higher risks of cognitive side effects