Cognitive and psychiatric effects of topiramate monotherapy in migraine treatment: an open study

Few data are available on cognitive and psychiatric effects of topiramate (TPM) monotherapy in migraine. Twenty patients affected by migraine were treated with TPM monotherapy. At the same time, twenty control subjects were selected. A comprehensive neuropsychological and behavioural battery of tests were performed at baseline (T0), at titration (T1) and in maintenance period (T2). Topiramate serum levels were also investigated at T1 and T2. On comparison with the control group, no cognitive and psychiatric differences were detected at baseline. A significant reduction of word fluency score ( P  < 0.05) was evident after TPM treatment, both at T1 and T2. No patient developed psychiatric adverse events. TPM induced an impairment of verbal fluency and no psychiatric adverse events, demonstrating selective negative cognitive profile in migraine therapy. Slow titration, low doses, lack of previous psychiatric disorders and/or familial history may explain our data.     

Kognitive Beeinträchtigungen unter Add-on-Therapie mit Topiramat

In an open study, 37 epilepsy patients were investigated with regard to cognitive impairments in anticonvulsant add-on therapy with topiramate (TPM). In addition to a preexisting antiepileptic medication, TPM administration was started and increased by 25 mg/week. Cognitive side effects noted by the patient or doctor were assessed by a neuropsychological test battery. In 18/37 patients (49%), cognitive deficits consisting of impaired concentration, psychomotoric slowing, memory deficits, and dysphasia were observed. The adverse effects became apparent at dosages of 50-575 mg TPM/day (average 210 mg). In four patients, they were reversible after reducing the dose of TPM by 25-150 mg/day. In eight patients, the adverse effects led to withdrawal of TPM. In spite of slow titration, the present study showed a higher frequency of cognitive side effects under TPM than was previously reported. In some patients, these side effects led to substantial impairments in daily life and at work. For early recognition of cognitive impairments, neuropsychological baseline and follow-up investigations of verbal fluency, psychomotor processing speed, and verbal memory are recommended.     

A multicenter, randomized clinical study to evaluate the effect on cognitive function of topiramate compared with valproate as add-on therapy to carbamazepine in patients with partial-onset seizures

PURPOSE: This study compares the cognitive effects of topiramate (TPM) with those of valproate (VPA) using efficacious doses of each drug when used as adjunctive therapy to carbamazepine (CBZ). A key question of the study is to what extent a more gradual introduction of TPM improves tolerability and prevents cognitive impairment. METHODS: The study is a multicenter, randomized, observer-blinded, parallel-group clinical trial with VPA or TPM given as first-line add-on therapy to steady-state treatment with CBZ. TPM is introduced at 25 mg and increased with weekly 25mg/d increments to a minimum dosage of 200 mg/d. The target dosage ranges from 200 to 400 mg/d for TPM and is 1800 mg/d for VPA. The study evaluates cognitive function changes from baseline to end point (after 20 weeks of treatment) and during titration (after 8 weeks of treatment). The primary outcome measure is the difference between the treatments (TPM versus VPA) in change from baseline to end point and change from baseline to titration, using a 95% confidence interval approach. RESULTS: For the 10 baseline-to-end point comparisons, one test measuring short-term verbal memory (Rey Auditory Verbal Learning Test) yields a statistically significant difference between the treatments (p = 0.02), showing worsening for TPM and improvement of scores for VPA. The 10 baseline-to-titration comparisons also show one statistically significant difference, again for a test measuring short-term memory (Recognition of Words; p = 0.04), showing a larger change in the negative direction for TPM. None of the mood tests or the test for subjective complaints shows statistically significant differences between the treatments, although more scores are in the negative direction for TPM during titration. CONCLUSION: Although the pattern of changes in the negative direction seems consistent with clinical information, the differences found between the treatments are small. An important finding of our study is that, when the results are compared with those of other studies, it is clear that gradual introduction of TPM can reduce the extent of cognitive impairment (with a maximum of about 0.6 SD).     

The influence of antiepileptic drugs on cognition: a comparison of levetiracetam with topiramate

Levetiracetam (LEV) and topiramate (TPM) are considered highly effective novel antiepileptic drugs (AEDs) in the treatment of focal epilepsies. To explore potential side effects, this study investigated their influence on cognitive functions comparatively by means of a standardized neuropsychological test battery assessing several cognitive domains. In this observational study, cognitive changes were explored in 30 consecutively recruited patients with focal epilepsy treated with LEV and in 21 patients treated with TPM, comparing functions assessed prior to gradual initiation and after reaching steady state of the individual target dosage. Before titration, patient groups did not differ significantly with respect to cognitive performance. Whereas the LEV group manifested no change in cognitive performance after AED titration, the TPM group worsened in the cognitive domains of cognitive speed and verbal fluency, as well as short-term memory. These findings suggest that TPM, unlike LEV, may impair frontal lobe functions. The lack of cognitive side effects related to LEV treatment may be relevant for treatment decisions.     

Cognitive effects of low-dose topiramate monotherapy in epilepsy patients: A 1-year follow-up

The present study was conducted to evaluate the long-term effects of low-dose topiramate (TPM) monotherapy on the cognitive function of epilepsy patients. Forty-seven epilepsy patients received TPM, with target doses of 50, 75, and 100 mg/day. Cognitive tests were performed twice, at baseline and 1 year after starting medication. Thirty-six patients completed the follow-up neuropsychological tests. After a year of treatment, 16 patients (44%) complained of cognitive problems. Although it improved seizure frequency and EEG abnormalities, TPM had significantly negative effects on the digit span and verbal fluency tests. These cognitive effects were dose-related and significantly improved after withdrawal from TPM and substitution with older antiepileptic drugs. In conclusion, even at a low dose, TPM has long-term, negative effects on working memory and verbal fluency.     

Comparative cognitive effects of levetiracetam and topiramate in intractable epilepsy

Aim: Anti‐epileptic drugs (AED) may cause cognitive impairment. Because intractable epilepsy (IE) represents a distinct group, the purpose of the present study was to study the comparative cognitive effects of the two efficacious AED, levetiracetam (LEV) and topiramate (TPM), on IE. Methods: This was a non‐randomized, blinded cognitive assessment and parallel design. The cognitive effects of LEV and TPM on 79 demographically comparable patients with IE were assessed at baseline (T1) and after 1 year of treatment (T2) using the Cognitive Abilities Screening Instrument. Results: Forty patients took TPM and 39 took LEV. At T1, seizure frequency, number of AED, and epilepsy duration were not significantly different. There were no significant differences in cognition between the two groups at T1 or T2. T2 orientation scores were lower than T1 scores in the TPM group (P < 0.05). In the TPM subgroup with T1 cognitive abnormalities, T2 scores for recent memory improved (P < 0.05). Conclusion: For patients with IE, LEV might preserve cognition, TPM's effects for patients with baseline cognitive abnormalities are worth observation.     

Effects of Tiagabine Monotherapy on Abilities, Adjustment, and Mood

Summary: Purpose: We evaluated the dose-related impacts of tiagabine (TGB) on cognition and mood in a monotherapy study.
Methods: Patients were 123 adults with uncontrolled partial seizures, each treated with a single currently available antiepileptic drug (AED) for management of clinical epilepsy. They completed a battery of neuropsychological tests during an 8 week prospective baseline period and once again at the end of the 12-week fixed-dose period (or earlier if they dropped out of the study). Sixty-six patients were randomized to 6 mg/day TGB and 57 were randomized to 36 mg/day TGB.
Results: Few changes in either abilities or adjustment and mood were noted when all patients were considered as a single group. However, analysis of both dose and attainment of TGB monotherapy showed that patients receiving TGB monotherapy did best, improving particularly in the areas of adjustment and mood with low-dose TGB and in the area of abilities with high-dose TGB. Patients who did not attain monotherapy showed no change except that the high-dose group did not perform as well on measures of mood and adjustment. Baseline AED and changes in seizure control did not affect the results.
Conclusions: Patients attainment of TGB monotherapy was associated with their achievement of positive changes of varying degree on psychological tests. Failure to attain TGB monotherapy was associated with no changes on the tests except in patients receiving high-dose TGB where it appeared that some alterations in mood might have been avoided if a slower titration schedule had been used.     

The longer-term cognitive effects of adjunctive antiepileptic treatment with lacosamide in comparison with lamotrigine and topiramate in a naturalistic outpatient setting

In this retrospective controlled study, the impact of adjunctive lacosamide (LCM) on cognition in patients with epilepsy was evaluated and compared with that of topiramate (TPM) and lamotrigine (LTG) in a naturalistic outpatient setting. Cognition was investigated by means of objective assessment of executive functions (EpiTrack®) and verbal memory and by subjective ratings of self-perceived side effects (cognition, mood, and vegetative). Quality of life was assessed using the QOLIE-10 questionnaire. Patients underwent assessment at baseline and after a median follow-up interval of 32 weeks. Forty-four patients were treated with LCM, 11 with LTG, and 15 with TPM. Treatment arms differed with regard to the age at onset of epilepsy (LTG > TPM) and to seizure control from baseline to follow-up, which was best in patients whose seizures were treated with LTG (55% vs. 16% in patients whose seizures were treated with LCM and 13% in patients whose seizures were treated with TPM). Groups did not differ in the type of epilepsy, daily drug load or drug load change, nor in baseline seizure frequency. Repeated measures statistics controlling for epilepsy onset and seizure outcome showed deteriorated executive functions with TPM (F = 7.5, p = 0.001). On an individual level (reliable change indices), 53% of the patients whose seizures were treated with TPM showed losses in this domain (LCM 14%, LTG 27%) and none of the patients showed improvement (LCM 23%, LTG 27%; χ² = 11.8, p = 0.019). No differences in memory, quality of life, or mood were noted among patients in the three treatment arms. Subjective cognitive complaints increased in 5 of the 9 patients whose seizures were treated with TPM (LCM 1/9, LTG 0/9; χ² = 11.9, p = 0.025). The findings of this study demonstrate for the first time that the cognitive side effect profile of LCM is comparable to that of LTG and superior to that of TPM. This is indicated by both subjective and objective measures. Given the naturalistic setting and the retrospective nature of the study, a follow-up prospective, randomized trial with larger sample sizes is required to confirm these findings.     

Cognitive profile of topiramate as compared with lamotrigine in epilepsy patients on antiepileptic drug polytherapy: relationships to blood serum levels and comedication

RATIONALE: This retrospective study was conducted to identify cognitive domains affected by topiramate (TPM), and to evaluate the role of blood serum levels of TPM and comedication in the etiology of TPM-induced cognitive impairment. METHODS: Forty-two patients on AED polytherapy containing topiramate and a random sample of 42 patients with lamotrigine as the corresponding agent underwent extensive neuropsychological testing. Current blood serum levels of TPM were correlated with test scores. RESULTS: Patients on TPM scored significantly worse in phonematic verbal fluency, memory spans, and working memory; language and memory function were not affected per se. In few cognitive domains, serum levels of TPM and performance were correlated before correction for multiple testing. Drug load of additional medication did not account for differences between or within groups. DISCUSSION: Consistent with previous reports, patients on AED polytherapy including TPM display a cognitive pattern with specific impairment in executive functions. The severity of the cognitive side effects of TPM may be related to dosing to a certain extent, but this relationship may be disclosed only with larger sample sizes. Accordingly, TPM dosage does not appear to be a good indicator of TPM-related cognitive side effects in the individual patient.     

Recovery of cognitive and emotional functioning following withdrawal of topiramate maintenance therapy

The present investigation reports cognitive improvement following withdrawal of topiramate (TPM) maintenance therapy in two patients with intractable seizures. The first patient received a neuropsychological evaluation after 10 months of adjunctive TPM treatment and was reassessed after complete withdrawal. The second patient received a first evaluation without TPM therapy. A reassessment was conducted after 13 weeks of stable TPM add-on therapy, and a third evaluation was performed after TPM withdrawal. During TPM treatment, the first patient demonstrated dysfunction on both verbal and non-verbal measures, suggesting bilateral impairment. Reassessment yielded cognitive improvement, and was consistent with a lateralized lesion as supported by seizure semiology, magnetic resonance imaging (MRI), and electroencephalogram (EEG) data. The second patient showed cognitive and emotional declines during TPM therapy. Reassessment, without TPM, demonstrated recovery on a majority of variables. These results illustrate the risk for considerable cognitive side effects after TPM habituation and support good recovery after withdrawal. Attempting to withdraw TPM and conducting a re-evaluation may be especially justified in the presence of a deflated neuropsychological profile that is inconsistent with a patient's estimated level of cognitive functioning. Reducing the influence of medical effects that could mimic bilateral dysfunction is particularly important in presurgical evaluations.     

Clobazam, Oxcarbazepine, Tiagabine, Topiramate, and Other New Antiepileptic Drugs

Summary: Clinical investigators recently have studied at least 21 new antiepileptic drugs (AEDs) in people with epilepsy. This review briefly examines 15 of these new AEDs: clobazam (CLB), dezinamide, flunarizine (FNR), loreclezole, milacemide (MLM), MK-801, nafimidone, ORG-6370, oxcarbazepine (OCBZ), progabide (PGB), ralitoline, stiripentol, tiagabine (TGB), topiramate (TPM), and zonisamide (ZNS). CLB, PGB, and TGB represent agents that act on the GABA system, and MLM acts on the glycine system. MK-801 and ZNS (in part) are excitatory amino acid antagonists, and FNR is a calcium-channel antagonist. OCBZ is a keto analogue of carbam-azepine, which is not metabolized to the epoxide and may have fewer side effects. The remaining agents are novel compounds with a variety of suspected mechanisms. TPM appears especially effective for intractable partial seizures but has a high incidence of cognitive side effects. None of these new AEDs is useful for all patients with inadequate seizure control or ongoing toxicity. The role of each will require further clinical study and experience.     

Aggravation of partial seizures by antiepileptic drugs: is there evidence from clinical trials?

OBJECTIVES: To assess clinical trials for evidence that antiepileptic drugs (AED) aggravate partial seizures. To determine if the methodology used to examine drug efficacy can also be used to examine seizure aggravation. BACKGROUND: It is widely accepted that AED aggravate epilepsy in some patients. However, there is little published objective or quantitative evidence. Most reports concern generalized epilepsies. METHODS: Pharmaceutical companies responsible for the development of five of the new AED were asked to provide data concerning seizure increases during randomized placebo-controlled, add-on clinical trials in patients with uncontrolled partial seizures. Seizure frequency in individual patients taking drug or placebo was compared with the baseline pretreatment seizure frequency. The counterpart of the 50% reduction used in efficacy analyses is a 100% increase, because both represent a twofold change. A dose-response relationship was also explored. RESULTS: More than 40% of subjects in clinical trials of tiagabine (TGB), topiramate (TPM), and levetiracetam (LEV) experienced an increase in seizures while taking a placebo. Seizure increases were no more likely to occur when taking any of the three drugs than taking placebo. A doubling or more of seizure frequency was less likely to occur with TPM or LEV than with placebo but more likely with TGB. However, for TGB, this did not reach significance. There was some evidence for a dose-response effect with TGB but a negative effect with TPM (aggravation less likely with increasing dose). Data on gabapentin and lamotrigine were not provided. CONCLUSIONS: Many patients with partial seizures experience an increase in seizures when a new AED is added to their therapy. However, it occurs no more frequently when taking drug than placebo. It probably represents the spontaneous fluctuation of seizure frequency. When a patient who has started a new AED deteriorates, this is not necessarily a drug effect.     

Neuropsychological outcomes after Gamma Knife radiosurgery for mesial temporal lobe epilepsy: a prospective multicenter study

Purpose: To assess outcomes of language, verbal memory, cognitive efficiency and mental flexibility, mood, and quality of life (QOL) in a prospective, multicenter pilot study of Gamma Knife radiosurgery (RS) for mesial temporal lobe epilepsy (MTLE). Methods: RS, randomized to 20 Gy or 24 Gy comprising 5.5–7.5 ml at the 50% isodose volume, was performed on mesial temporal structures of patients with unilateral MTLE. Neuropsychological evaluations were performed at preoperative baseline, and mean change scores were described at 12 and 24 months postoperatively. QOL data were also available at 36 months. Key Findings: Thirty patients were treated and 26 were available for the final 24‐month neuropsychological evaluation. Language (Boston Naming Test), verbal memory (California Verbal Learning Test and Logical Memory subtest of the Wechsler Memory Scale‐Revised), cognitive efficiency and mental flexibility (Trail Making Test), and mood (Beck Depression Inventory) did not differ from baseline. QOL scores improved at 24 and 36 months, with those patients attaining seizure remission by month 24s accounting for the majority of the improvement. Significance: The serial changes in cognitive outcomes, mood, and QOL are unremarkable following RS for MTLE. RS may provide an alternative to open surgery, especially in those patients at risk of cognitive impairment or who desire a noninvasive alternative to open surgery.     

Comparison of the cognitive effects of tiagabine and carbamazepine as monotherapy in newly diagnosed adult patients with partial epilepsy: pooled analysis of two long-term, randomized, follow-up studies

PURPOSE: Patients with epilepsy are at greater risk for cognitive impairment than are age- and education-matched controls. Cognitive decline is a significant adverse event associated with many first-generation anticonvulsant drugs (AEDs); however, the past decade has seen the introduction of several new AEDs with more-favorable cognitive profiles. Tiagabine (TGB) is indicated as adjunctive therapy for the treatment of partial seizures. The cognitive effects of TGB and carbamazepine (CBZ) monotherapy were evaluated in adult epilepsy patients with partial seizures. METHODS: This analysis pooled data from two randomized studies with similar populations, dosing, and cognitive assessments. TGB was titrated to 20-30 mg/day and CBZ to 400-800 mg/day over a 6-week period. A control or no-drug group of untreated patients with a single epileptic seizure was included for comparison. Cognitive function was assessed at baseline and 52 weeks. RESULTS: Of the 105 epilepsy patients enrolled, 79 completed the 52 weeks of monotherapy (TGB, 74%; CBZ, 77%). Altogether, 19 untreated patients composed the no-drug group. During the 52-week follow-up, only one statistically significant difference was found between the treatment groups and the no-drug group [verbal fluency task: F(2, 92) = 3.16; p = 0.047]. On further analysis, it was determined that this statistical difference was solely based on the patients receiving CBZ performing worse than the control group (p = 0.048). Statistically significant improvements (p < 0.05) were found on six (26%) of 23 variables with TGB and CBZ, as well as the no-drug group, although the variables differed between the groups. Significant worsening in the test scores was not seen in any of the study groups. CONCLUSIONS: The results of this 52-week, follow-up study show that successful TGB monotherapy with 20-30 mg/day has a cognitive profile similar to that of successful long-term CBZ monotherapy with 400-800 mg/day in newly diagnosed patients with epilepsy and to that of untreated patients with a single seizure. We observed no significant decline in cognitive scores associated with TGB monotherapy.     

Tiagabine versus phenytoin and carbamazepine as add-on therapies: effects on abilities, adjustment, and mood

The effects of tiagabine (TGB) on abilities and on adjustment and mood are as yet incompletely understood. These effects were compared with those of phenytoin (PHT) and carbamazepine (CBZ) in an add-on study. Patients included in the analysis were adults with uncontrolled partial seizures who at study entry were on CBZ alone (n=153) or on PHT alone (n=124). Of the patients receiving CBZ, 82 were randomized to add-on TGB and 71 were randomized to add-on PHT during the double-blind period. Of the patients receiving PHT, 58 were randomized to add-on TGB and 66 were randomized to add-on CBZ. Eight tests of mental abilities and three of mood and adjustment were given prior to assignment of add-on treatment and after up to 16 weeks of add-on treatment. For the baseline CBZ group, analyses were done to search for differential changes from baseline in the test scores of the add-on TGB and add-on PHT groups, and for the baseline PHT group in the add-on TGB and add-on CBZ groups. In the baseline CBZ group, no differences in test scores were found between PHT and TGB. In the baseline PHT group for the area of abilities, patients treated with TGB had improved verbal fluency, as well as quicker responses on a test of perceptual/motor speed compared with patients treated with CBZ. For the baseline PHT group in the area of adjustment and mood, patients treated with TGB reported less positive mood and more financial concerns compared to patients treated with CBZ. Overall, add-on TGB showed few or no differences in comparison with add-on CBZ and add-on PHT.     

Cognitive adverse events of topiramate in patients with epilepsy and intellectual disability

Topiramate (TPM) is an effective antiepileptic drug (AED). A high proportion of patients, however, experiences cognitive adverse events (CAEs), especially in verbal fluency, memory spans, and working memory. To our knowledge, CAEs of TPM have not been studied systematically in patients with intellectual disability (ID). This may be due to the fact that many of those patients are not able to follow test instructions properly and that neuropsychological instruments are not validated for that group. Cognitive deterioration in patients with ID may thus easily be overlooked. Topiramate is in frequent use in persons with ID. We included 26 consecutive patients with epilepsy and ID in this observational study who had undergone neuropsychological examinations as part of clinical routine before and after the introduction of TPM into the therapeutic regimen (n = 4) or before and after the withdrawal of TPM (n = 22). Examinations under TPM showed reduced cognitive speed, reduced verbal memory, reduced verbal fluency, and reduced flexibility compared to examinations without TPM. Despite some limitations (especially small sample size, high interindividual variation of the results dependent on the degree of ID, effects of other – limited – changes in the therapeutic regimen), our study indicates that TPM in persons with epilepsy and ID may lead to CAEs comparable to those in persons with normal intelligence. Neuropsychological testing is mandatory in order not to miss CAEs that might severely impair quality of life.     

Long-term cognitive and mood effects of zonisamide monotherapy in epilepsy patients

This study was a prospective, randomized, open-label investigation of the long-term effects of zonisamide (ZNS) monotherapy on cognition and mood of patients with epilepsy. Forty-three patients with epilepsy received ZNS, with final dose groups of 100, 200, 300, and 400mg/day. Cognitive and mood tests were done twice, at baseline and 1 year after starting medication. Nine patients were withdrawn prior to their follow-up tests. Three patients (33%) dropped out during the titration period because of cognitive and mood problems. Thirty-four patients completed follow-up neuropsychological tests. After 1 year of treatment, 16 patients (47%) complained of cognitive deficits. Only 5 patients (15%) experienced mood changes. Although ZNS decreased seizure frequency and EEG abnormalities and did not elicit significant mood changes, it had negative effects on several cognitive tests. Worse performance on delayed word recall, Trail Making Test Part B, and verbal fluency was related to dose. In conclusion, ZNS has adverse effects on cognition even after 1 year of treatment.     

Determining empirically based self-reported cognitive change: development of reliable change indices and standardized regression-based change norms for the multiple abilities self-report questionnaire in an epilepsy sample

PURPOSE: Reliable change indices (RCIs) and standardized regression-based (SRB) change score norms were calculated for a measure of self-reported cognitive function, the Multiple Abilities Self-Report Questionnaire (MASQ), in patients with complex partial seizures. Establishment of such standardized change scores could be useful in determining the magnitude and direction of self-appraised cognitive change after epilepsy surgery or other treatment interventions. The primary study objective was to calculate RCI and SRB values for the MASQ. A secondary objective was to report SRB change scores in patients who had undergone anterior temporal lobectomy (ATL) and to assess relationships between self-reported cognitive change, seizure outcome, objective memory test performance, and mood. METHODS: The MASQ was administered to 36 patients with complex partial seizures on two occasions (mean test-retest interval, 6 months). This group did not have major psychopathology and were on stable antiepileptic drugs. RCI and SRB change scores were calculated. Adjustments for baseline ratings, age, education, gender, age at seizure onset, and seizure duration were made with the SRB method. A confidence interval cutoff score (90% level) was calculated for the five MASQ cognitive domains (Language, Visual Perception, Verbal Memory, Visual-Spatial Memory, Attention/Concentration). MASQ SRB scores were computed for a second sample of 50 patients who had undergone ATL. RESULTS: Test-retest reliabilities for the MASQ domains ranged from a low of 0.63 (Attention/Concentration) to a high of 0.87 (total score). Baseline MASQ score was the single largest contributor to the regression equations. Left and right ATL groups demonstrated similar magnitudes of self-reported cognitive change across all five MASQ domains. Individual base rate change distributions were similar across four of the five domains. with a higher proportion of right ATL patients reporting worsening attention function. Both postoperative mood and SRB-based verbal memory outcome were significantly correlated to self-reported cognitive change in the patients who had undergone ATL. CONCLUSIONS: SRB methodology provides a standardized technique with which to establish patient perception of cognitive change and may be of use when examining change across individual- and group-level ratings of cognitive functioning in clinical and research settings. These techniques also provide a common metric for direct comparison between subjective self-report ratings of cognitive function and objective cognitive test instruments.     

Epilepsy in low-grade gliomas: the impact on cognitive function and quality of life

Low-grade gliomas frequently are associated with epilepsy. The purpose of this study is to determine the impact of epilepsy and antiepileptic drug (AED) treatment on cognitive functioning and health-related quality of life (HRQOL) in these patients. One hundred fifty-six patients without clinical or radiological signs of tumor recurrence for at least 1 year after histological diagnosis and with an epilepsy burden (based on seizure frequency and AED use) ranging from none to severe were compared with healthy controls. The association between epilepsy burden and cognition/HRQOL was also investigated. Eighty-six percent of the patients had epilepsy and 50% of those using AEDs actually were seizure-free. Compared with healthy controls, glioma patients had significant reductions in information processing speed, psychomotor function, attentional functioning, verbal and working memory, executive functioning, and HRQOL. The increase in epilepsy burden that was associated with significant reductions in all cognitive domains except for attentional and memory functioning could primarily be attributed to the use of AEDs, whereas the decline in HRQOL could be ascribed to the lack of complete seizure control. In conclusion, low-grade glioma patients suffer from a number of neuropsychological and psychological problems that are aggravated by the severity of epilepsy and by the intensity of the treatment.