Effects of gabapentin and carbamazepine on the EEG and cognition in healthy volunteers

PURPOSE: Antiepileptic drug (AED) therapy can be associated with neurotoxic side effects including cognitive dysfunction. Objective methods for detection of neurotoxicity in individual patients would be useful. We studied the effects of gabapentin (GBP) and carbamazepine (CBZ) on neurophysiologic and cognitive/behavioral measures in healthy volunteers. METHODS: In a 12-week, randomized, double-blind, parallel-group study of CBZ and GBP in healthy volunteers, 23 subjects completed the protocol. All achieved the target dose of 1,200 mg CBZ or 3,600 mg GBP. A structured EEG for quantitative analysis and a cognitive test battery were administered before AED therapy and again after 12 weeks of therapy. Test-retest differences were compared with those of 72 untreated control subjects. RESULTS: Both CBZ and GBP significantly decreased the peak frequency of the posterior (alpha) rhythm, with CBZ exerting a greater effect. Ten CBZ and six GBP subjects exceeded the 95% confidence interval (CI) for an individual. Cognitive tests revealed AED vs. control group effects for two of seven measures (Digit Symbol, Stroop) and all subjective measures. However, few subjects exceeded the 95% CI for any objective test. Differences between CBZ and GBP were not significant. Greater EEG slowing was associated with greater subjective neurotoxicity and poorer test-retest performance on a cognitive test summary measure. CONCLUSIONS: Prolonged CBZ and GBP therapy induced EEG slowing that correlated with cognitive complaints and often exceeded the confidence interval for individual subjects. Quantitative EEG measures may be useful in the objective determination of AED-related neurotoxicity.     

Topiramate effects on the EEG and alertness in healthy volunteers: a different profile of antiepileptic drug neurotoxicity

OBJECTIVE: Previous quantitative EEG (QEEG) studies of carbamazepine (CBZ), oxcarbazepine (OXC), and phenytoin (PHT) revealed a pattern of EEG slowing and an increase in drowsiness on the awake maintenance task (AMT). EEG slowing has been shown to correlate with negative effects on cognitive tests. Topiramate (TPM) is a novel AED with relatively large negative effects on cognitive function. We tested the hypothesis that TPM would induce significant slowing of EEG background rhythms and an increase in AMT drowsiness. METHODS: Forty healthy volunteers were randomized to TPM, gabapentin (GBP), or placebo. Doses were escalated as tolerated to a maximum of 400mg/day for TPM or 3600 mg/day for GBP, over a 10-week period, followed by a minimum 2-week plateau period. Volunteers underwent an EEG, cognitive tests, and the AMT prior to starting an AED and again 12 weeks later. The EEG was captured using a structured recording protocol and quantified using the fast Fourier transform. Four target measures were derived from the averaged occipital electrodes (peak frequency of the dominant posterior rhythm, median frequency, percentage theta, and percentage delta). Test-retest changes for all measures were scored against similar test-retest distributions previously obtained from untreated healthy volunteers. RESULTS: TPM produced no significant change in any of the four target EEG measures or on the AMT, even though several target cognitive tests revealed moderate or greater negative effects. There were also no significant changes in the placebo group. GBP slowed the peak and median frequency EEG measures and increased the percentage of theta and delta activity. Neither TPM, GBP, nor placebo caused a significant increase in drowsiness on the AMT. CONCLUSIONS: TPM has a unique neurotoxicity profile. It has no effect on EEG background measures or on the AMT, but induces moderate to large negative changes in many cognitive test scores. This profile differs from those of CBZ, OXC, PHT, and GBP.     

Assessment of Drowsiness in Epilepsy Patients Receiving Chronic Antiepileptic Drug Therapy

Drowsiness is a common complaint among patients with epilepsy taking antiepileptic drugs (AEDs) and may be of particular importance because of the potential effects on cognitive abilities. We used a novel EEG-based measure (the Awake Maintenance Task, AMT) to determine objectively whether patients on chronic, stable AED therapy had impaired ability to maintain wakefulness. Thirty patients receiving AEDs [carbamazepine (CBZ), phenytoin (PHT), phenobarbital (PB), valproate (VPA)] were compared to 35 healthy controls, 12 seizure patients not taking AEDs, and 16 patients with multiple sclerosis. A structured EEG recording was conducted under controlled conditions, and subjects were tested to determine their ability to maintain wakefulness during a 6-min unstimulated trial. Testing also included Digit Symbol, auditory reaction time, and subjective measures of fatigue or sleepiness [Profile of Mood States (POMS), Stanford Sleepiness Scale (SSS)]. Patients receiving AEDs had a mean total drowsiness score of 101 s compared with ≤ 12 s for each of the three control groups (p < 0.001). One third of the AED-treated patients had >120 s of drowsiness, in contrast to only 1 of 63 controls (p < 0.001). Among patients receiving AEDs, objective EEG drowsiness did not correlate with AED levels or performance measures. Untreated seizure patients had significantly greater complaints of lack of vigor despite a near absence of objective drowsiness on the AMT. These results suggest that epilepsy patients receiving chronic AED therapy have impaired ability to maintain wakefulness. Patient self-reports of AED-related sleepiness may not accurately represent this problem.     

Effects of oxcarbazepine and phenytoin on the EEG and cognition in healthy volunteers

We studied the EEG and cognitive effects of oxcarbazepine (OXC) and phenytoin (PHT) using a double-blind, randomized, parallel-group design. Thirty-two healthy volunteers received a maximum of 1200 mg of OXC or 360 mg of PHT. EEG and cognitive testing were performed at baseline and after 12 weeks of treatment. For each subject and measure, test-retest Z scores were calculated from regression equations derived from 73 healthy controls. Twenty-six subjects completed the study. Both the OXC and PHT groups had significant slowing of the EEG peak frequency and increased relative theta and delta power. Differences between AEDs (antiepileptic drugs) were not significant. Significant cognitive effects were seen on 5 of 20 measures, primarily measures of motor speed and reaction time. Again, there were no significant differences between AEDs. The only significant difference between AEDs was for the POMS-Vigor scale, favoring OXC. The small sample size may have contributed to the lack of significant differences between AEDs.     

Impact of levetiracetam add-on therapy on different EEG occipital frequencies in epileptic patients

SummaryThe EEG background activity reflects the functional state of the brain. The established sensitivity of EEG to drug intoxication and in particular to antiepileptic drugs (AEDs) made that EEG has become useful as an objective measure for monitoring chronic AED therapy and in investigation of cognitive functions. Therapy with classical AEDs has become associated with slowing of EEG background rhythm and the EEG changes correlated to changes on cognitive measures. So far, it has not been tested whether the relatively new AED, levetiracetam (LEV) has a detrimental effect on the EEG background frequencies, too.MethodsDuring the time of 6 months 28 patients underwent EEG-recording and neuropsychological testing at the three timepoints: before initiating LEV therapy, after 2 months and again after 4 months after achieving plateau dosing of LEV. EEG background frequency was analysed by using the fast Fourier Transform (FFT).ResultsThe titration and the following treatment with LEV add-on showed no negative effect on any of the measures analysed. In particular it did not lead to the lower peak frequency within the alpha band, it neither decreased the percentage of alpha band nor increase the percentage of theta and delta band. In addition there could be noticed an increase of the percentage of beta band.ConclusionsOur findings demonstrate, that a LEV add-on therapy is not associated with a slowing of the EEG background frequency. This is in accordance with neuropsychological reports of our own lab and others showing that LEV add-on therapy has no negative effects on cognitive functions, either.     

Intraindividual analysis of antiepileptic drug effects on EEG background rhythms

Antiepileptic drug (AED) therapy with either phenytoin or carbamazepine has been associated with generalized slowing of EEG background rhythms. These effects have been seen in groups of patients undergoing D manipulation, although the background slowing has been highly variable from patient to patient. Background slowing may represent an objective physiologic measure of drug impact on cerebral function and could be useful in monitoring for AED neurotoxicity in individual patients. This would require an intraindividual analysis of AED effects on EEG background rhythms. The present study was designed to develop a methodology for intraindividual analysis of EEG background changes and to apply this methodology to patients beginning or ending chronic AED therapy.EEG recordings were obtained under controlled conditions in 31 healthy subjects and were repeated after an interval of 12–16 weeks. EEG background rhythms from each record were analyzed using the fast Fourier transform, and test-retest differences for several quantitative measures were calculated from each subject's paired recordings. EEG recordings were also obtained in 6 patients beginning or ending chronic AED therapy. Test-retest differences for each patient's quantitative EEG measures were statistically compared with the distributions of test-retest measures obtained from the healthy controls.AED therapy was associated with an increase in absolute delta and/or theta power and a slowing of the dominant posterior rhythm; however, these EEG background changes varied widely in degree from patient to patient. Intraindividual analysis revealed that 5 patients had statistically significant slowing relative to the control group on at least 1 of the 9 target quantitative EEG measures, as well as a composite measure. Statistically significant slowing was also seen as a group effect. The results suggest that among patients undergoing chronic therapy with phenytoin or carbamazepine there are widely different degrees of EEG background slowing, often significantly beyond that expected on the basis of test-retest variability. Intraindividual analysis of the EEG background may be a practical objective measure of a patients unique response to chronic AED therapy.     

Spectral EEG During Short-Term Discontinuation of Antiepileptic Medication in Partial Epilepsy

Summary: The effect of short-term discontinuation of antiepileptic drugs (AEDs) on spectral analysis of EEG background activity (spectral EEG) was studied in patients undergoing preoperative evaluation for epilepsy surgery. We also wished to clarify whether AED discontinuation would provide lateralizing evidence in spectral EEGs of patients with temporal lobe epilepsy (TLE). Spectral EEGs were performed in 15 patients receiving their regular medication regimen and again after a 1-week period during AED withdrawal. A subgroup of 9 patients who had previously undergone temporal lobectomies (TLE group) was studied separately. In this group, we evaluated the effect of preceding seizures on spectral EEG derived from temporal neocortical areas. In all patients, spectral EEG changes were detected even after a short-term AED withdrawal. The total amount of absolute delta activity was reduced and occipital peak frequency and relative alpha activity were increased as compared with baseline values. In TLE patients with habitual seizures occurring <20 h before the spectral EEG recording, lateralization was correctly identified by the greater amount of absolute delta activity ipsilateral to the epileptogenic focus. Epileptic seizures are accompanied by subtle focal slowing in spectral EEG for a much longer period than has been assumed. In addition, postictal spectral EEG over the temporal lobes may have lateralizing value. Further studies in larger numbers of patients are needed to evaluate the role of spectral EEG in the preoperative evaluation of patients for temporal lobe surgery.     

Global dynamical analysis of the EEG in Alzheimer's disease: frequency-specific changes of functional interactions.

OBJECTIVE: EEG coherence is decreased in Alzheimer's disease (AD), suggesting decreased interaction between brain areas. Nonlinear EEG analysis in AD points to decreased complexity of brain dynamics, implicating increased interaction. To clarify these apparently paradoxical findings from linear and nonlinear analysis, we calculated global coherence and global correlation dimension (D2), a nonlinear measure, in the EEG of patients with probable AD and controls. Our hypothesis is that these measures are related to each other when calculated in a comparable way. METHODS: From 15 patients with probable AD (mean age 63.1 years; SD 6.3) and 21 age-matched controls with subjective memory complaints (mean age 62.8; SD 12.0), band filtered EEG data were analysed in six frequency bands. For each frequency band average coherence and multichannel D2 were determined. RESULTS: ANOVA for repeated measures showed for D2 an interaction between band and group, but not for coherence. In the beta band and upper alpha band, D2 was higher in patients with probable AD compared to controls, while global coherence tended to be lower in these frequency bands in patients with probable AD. In the frequency range from theta to beta, coherence and D2 were inversely correlated without group differences. CONCLUSIONS: When calculated in comparable ways, global correlation dimension and coherence are related measures. In AD, these measures change especially in the higher frequency ranges, both pointing to decreased functional cortical connectivity. SIGNIFICANCE: Both global coherence and global correlation dimension seem to measure global connectivity, but nonlinear measures may be more sensitive. In AD, connectivity measures are not equally impaired in all frequency ranges, possibly reflecting differentiated affection of the dynamical processes responsible for the different frequency bands.     

A longitudinal EEG study of mild senile dementia of Alzheimer type: changes at 1 year and at 2.5 years

This longitudinal study of resting EEGs compared patients with senile dementia of Alzheimer type (SDAT) and healthy controls at 3 times of testing over a 2.5 year period. Measures included the mean EEG frequency as well as the percentage of power in alpha, beta, theta, and delta frequency bands obtained from power spectral analysis. The values from occipital to vertex derivations were averaged for the left and right hemispheres. In healthy older adults delta increased, and both beta and mean frequency decreased over the study period; there was no significant change in theta or alpha. In the SDAT group, all 5 EEG measures changed significantly; there were increases in delta and theta, and decreases in beta, alpha and mean frequency. Theta percentage power distinguished between all 4 stages of dementia (control, mild, moderate and severe). Other EEG measures discriminated only at certain stages. In the mild stage of SDAT theta, beta and mean frequency were already different from control values. In the moderate stage, these differences persisted, and alpha became different. Delta was the last to change, and in the present small sample of those with severe SDAT the difference had not yet reached significance.     

Quantitative analysis of occipital EEG in different stages of Alzheimer's disease

EEG frequency analysis by Fast Fourier Transform (FFT) was studied in different stages of Alzheimer's disease (AD), defined according to the neuropsychological test score. It was observed that in mild AD the percentage power of the theta band, the ratio of powers in the alpha and theta bands and the mean frequency (range 1.46-20.02 c/sec) differed significantly from the old healthy controls. The percentage power of the alpha band, the occipital peak frequency and the ratio of powers in the alpha and delta bands decreased linearly in different stages of AD. These variables did not differ significantly in mild AD from the control values. Distinct slowing of the occipital peak frequency and distinct accentuation of the percentage power of the delta band occurred in advanced AD. Slowing of the dominant occipital rhythm and accentuation of the diffuse irregular slow waves, which are usually regarded as the main EEG criteria for AD, do not describe mild but advanced disease.     

Evening vs. morning wake EEG activity in adolescents with anxiety disorders

Adolescents with anxiety disorders often report sleep disturbance. To dissociate the effects of both sets of symptoms (anxiety vs. sleep disturbances) on clinical markers we recorded evening and morning wake EEG activity in 13 anxious adolescents without sleep complaints and compared results to 15 matched healthy controls. Evening EEG activity did not differ between the two groups; in the morning, patients showed a significantly higher activity than controls at central (0.75-10 Hz and 13-20 Hz) and occipital (2.5-7.75 Hz) electrodes. Trait anxiety scores of anxious participants correlated with central electrodes delta activity and occipital electrodes delta and theta activity. State anxiety correlated with delta activity on central electrodes, particularly in the low frequency range. CONCLUSION: The evening EEG results are not consistent with presence of central nervous system (CNS) hyperarousal in adolescents with anxiety disorders not complaining of sleep disorders. The morning EEG results could point toward a marker of CNS malfunctioning in pediatric anxiety disorders.     

EEG markers for cognitive decline in elderly subjects with subjective memory complaints

New treatments for Alzheimer's disease require early detection of cognitive decline. Most studies seeking to identify markers of early cognitive decline have focused on a limited number of measures. We sought to establish the profile of brain function measures which best define early neuropsychological decline. We compared subjects with subjective memory complaints to normative controls on a wide range of EEG derived measures, including a new measure of event-related spatio-temporal waves and biophysical modeling, which derives anatomical and physiological parameters based on subject's EEG measurements. Measures that distinguished the groups were then related to cognitive performance on a variety of learning and executive function tasks. The EEG measures include standard power measures, peak alpha frequency, EEG desynchronization to eyes-opening, and global phase synchrony. The most prominent differences in subjective memory complaint subjects were elevated alpha power and an increased number of spatio-temporal wave events. Higher alpha power and changes in wave activity related most strongly to a decline in verbal memory performance in subjects with subjective memory complaints, and also declines in maze performance and working memory reaction time. Interestingly, higher alpha power and wave activity were correlated with improved performance in reverse digit span in the subjective memory complaint group. The modeling results suggest that differences in the subjective memory complaint subjects were due to a decrease in cortical and thalamic inhibitory gains and slowed dendritic time-constants. The complementary profile that emerges from the variety of measures and analyses points to a nonlinear progression in electrophysiological changes from early neuropsychological decline to late-stage dementia, and electrophysiological changes in subjective memory complaint that vary in their relationships to a range of memory-related tasks.     

Computerized Analysis of EEG Background Activity in Epileptic Patients

Background activity was studied in 128 idiopathic epilepsy patients and 30 normal controls using EEG topography and t-statistic significance probability mapping (t-SPM). In epileptic patients, EEG background activity showed a marked increase in delta, theta, alpha 1, and beta 1, and a decrease in alpha 2 activity as compared with controls. Untreated epileptic patients had a significant increase in delta, theta, and alpha 1 as compared with controls. For epileptic patients treated with antiepileptic drugs (AEDs), the most marked slowing was observed in the polytherapy group, followed by the monotherapy group and then the untreated group. Among seizure types, patients with partial seizures (PS) tended to exhibit more slowing than patients with only generalized tonic-clonic seizures (GTC). Moreover, PS had a right-left asymmetry in alpha 2 and beta 1 activities. In a comparison of AEDs, patients receiving carbamazepine (CBZ) and phenobarbital (PB) showed no significant difference as compared with the untreated group. In contrast, patients receiving valproate (VPA) showed a decrease in slow and fast activities. EEG changes associated with each AED were different in GTC and PS. Patients receiving VPA for GTC showed a decrease in theta and beta 1 activities, but those with PS showed a decrease only in delta activity.     

Gabapentin as add-on therapy in focal epilepsy: a computerized EEG study.

OBJECTIVES: Gabapentin (GBP) possesses a well documented clinical efficacy in those types of focal epilepsy otherwise resistant to conventional antiepileptic drugs (AEDs); on the basis of this, it appears important to investigate the drug effects on the EEG epileptiform and background activity. METHODS: Twenty-five patients with cryptogenic or symptomatic partial epilepsy resistant to conventional AED treatment were included in the study. All patients underwent long-term video-EEG recordings before and after GBP addition (900-1200 mg/day). RESULTS: Quantitative analysis of the interictal EEG paroxysms revealed that GBP had no effect on the rate of occurrence of interictal and ictal EEG abnormalities. GBP was active in delimiting the spatial extent of the interictal spiking activity in those patients who displayed a significant reduction (> or =50%) in seizure occurrence (32% of the patients). EEG background activity recorded under rest condition from 18 out of 25 epileptic patients, before GBP therapy, was characterised by a higher content of the slow spectral components (delta and theta) with respect to control subjects. After GBP addition, the increase of theta relative power was also evident during task performance. CONCLUSIONS: These findings suggest that GBP does not interfere with the generation of interictal EEG spiking while it appears to reduce the susceptibility to seizures concomitantly with a limiting effect on the spiking activity spatial extent. The utilization of GBP in controlling focal seizures is reinforced by the absence of negative influence on cognitive functioning.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Quantitative EEG findings in different stages of Alzheimer's disease.

Although quantitative EEG (q-EEG) has been used in Alzheimer's disease (AD), q-EEG changes in AD are complex because of the progressive nature of this disease. The topographical spectral power and occipital peak frequency (OPF) were compared among elderly controls, patients with mild cognitive impairment (MCI), and patients with four stages of AD. In AD patients, except those with a Clinical Dementia Rating Scale (CDR) score of 0.5, OPF was lower than that of elderly controls. Compared with elderly controls, the left anterior alpha spectral power was reduced in CDR 0.5; both posterior theta spectral powers were increased and all alpha spectral powers were reduced in CDR 1; all alpha and beta spectral powers were reduced and theta spectral power was increased in CDR 2; and all alpha and beta spectral powers were reduced and all delta and theta spectral powers were increased in CDR 3. Patients with MCI exhibited a reduction in both centrotemporal, posterior delta and left anterior, centrotemporal theta fields. The Mini-Mental State Examination (MMSE) score was related to left OPF, right posterior delta and left anterior theta spectral power, in that order. This study suggests that q-EEG in MCI shows nonoverlapping features between controls and AD patients, and AD patients show dynamic changes as the disease progresses. Finally, the left OPF is the parameter most significantly correlated with MMSE score.     

Complaints associated with the use of antiepileptic drugs: results from a community-based study.

BACKGROUND: Few data exist with respect to the occurrence of chronic side effects due to antiepileptic drugs (AED) in routine clinical practice. OBJECTIVE: To evaluate the prevalence of subjective complaints which patients with epilepsy regard as side effects of their AED treatment in a community-based population. METHODS: Cross-sectional study. Subjects were identified through the database of AED-use in the pharmacies in a suburban area in The Netherlands. Respondents completed a brief questionnaire about their epilepsy, including a checklist with 30 complaints, which are common in AED users. RESULTS: We present data of 346 responding adults with treated epilepsy from a population of 107,000 adult inhabitants. Eighty percent was using monotherapy, with few patients taking new AEDs. Almost 60% of the patients reported complaints probably due to side effects in at least three domains. General CNS-related side effects were reported most often; memory problems (21.4% of the patients) and fatigue (20.3%) were dominant. Polytherapy was associated with more side effects than monotherapy. We identified differences in profiles of complaints between valproate, carbamazepine and phenytoin monotherapy. Complaints were not substantially associated with ongoing seizures or other treatment factors. CONCLUSIONS: The majority of patients taking AEDs for epilepsy think they have side effects form their drugs, even when seizures were in remission and when monotherapy was used. Our findings suggest a need to improve monitoring of complaints of side effects of AEDs and to explore the feasibility of interventions aimed at reduction of such complaints in everyday clinical practice.     

Does Short-Term Antiepileptic Drug Treatment in Children Result in Cognitive or Behavioral Changes?

Summary: Purpose: To determine possible cognitive and behavioral effects of antiepileptic drug (AED) therapy by assessing children with newly diagnosed epilepsy before and after initiation of treatment. A comparison group of children with diabetes mellitus (DM) was included to control for the effects of practice, maturation, and chronic illness.
Methods: Baseline neuropsychological assessments were completed for children with epilepsy (n = 37) and children with DM (n = 26) recruited through outpatient clinics at a regional children's hospital. Children were reevaluated 6 months from baseline testing. At follow-up, children with epilepsy had therapeutic AED levels and controlled seizures. Statistical analysis included a between-group repeated measures ANCOVA with pretest scores serving as the covariate.
Results: Significant differences between groups were not found for any cognitive or behavioral factors, including attention (p < 0.24), immediate memory (p < 0.24), delayed memory (p < 0.10), complex motor speed (p < 0.19), or behavior problems (p < 0.89).
Conclusions: Changes in performance on cognitive and behavioral measures were not different for children treated with AEDs and controls. Although adverse effects may be associated with prolonged treatment, results would not suggest adverse effects from AED monotherapy during the first 6 months of therapy.     

Effect of levetiracetam monotherapy on background EEG activity and cognition in drug-naïve epilepsy patients

ObjectiveTo investigate the cognitive effect of levetiracetam (LEV) monotherapy with quantitative electroencephalogram (EEG) analysis and neuropsychological (NP) tests.MethodsTwenty-two drug-naïve epilepsy patients were enrolled. EEG recordings were performed before and after LEV therapy. Relative power of discrete frequency bands was computed, as well as alpha peak frequency (APF) at occipital electrodes. Eighteen patients performed a battery of NP tests twice across LEV treatment.ResultsLEV therapy decreased the power of delta (1–3 Hz, p < 0.01) and theta (3–7 Hz, p < 0.05) bands and increased that of alpha-2 (10–13 Hz, p < 0.05) and beta-2 (19–24 Hz, p < 0.05) bands. Region-specific spectral change was observed: delta power change was significant in fronto-polar region, theta in anterior region, alpha-2 in broad region, and beta-2 in left fronto-central region. APF change was not significant. Improvement in diverse NP tests requiring attention, working memory, language and executive function was observed. Change in theta, alpha-2, and beta-2 power was correlated with improvement in several NP tests.ConclusionsOur data suggest LEV is associated with acceleration of background EEG frequencies and improved cognitive function. Change in frequency band power could predict improvement in several cognitive domains across LEV therapy.SignificanceCombined study of quantitative EEG analysis and NP tests can be useful in identifying cognitive effect of antiepileptic drugs.     

Epilepsy and antiepileptic drug therapy in juvenile neuronal ceroid lipofuscinosis

PURPOSE: To survey the characteristics of epilepsy in patients with juvenile neuronal ceroid lipofuscinosis (JNCL) and determine the antiepileptic drug (AED) treatment most suitable for these patients. METHODS: The study included 60 patients with JNCL; their mean age was 16.5 years (range 5-33). The age at onset of epilepsy, type of seizures, effect of the first AED on seizures, and the current seizure frequency and AED therapy were studied. The side effects of the AEDs were also clarified. RESULTS: Fifty of the 60 patients had epilepsy. Patients' first epileptic seizure occurred at a mean age of 10.0 years (range 5-16), the most common type being generalized seizures. As the first AED tried, valproate (VPA) and lamotrigine (LTG) appeared equally effective, with 80% of the patients responding to these AEDs. During the study year, the median seizure frequency was four seizures a year (range 0-120), and 72% of the patients had good or satisfactory seizure control (0-6 seizures a year). In the different AED therapy groups, the proportion of patients with good or satisfactory seizure control ranged from 25% to 100%. LTG in monotherapy or in combination with clonazepam (CZP) was superior to other AEDs or combinations, but VPA also seemed effective. Adverse effects leading to the discontinuation of an AED were observed in 25% of the patients, most frequently in patients receiving phenobarbital (PB). No patient receiving LTG had to discontinue the drug due to adverse effects. CONCLUSION: Epilepsy in JNCL can usually be successfully treated with the current AEDs. In Finnish patients with JNCL, treatment is based on LTG, or, secondarily, VPA. In combination therapy, CZP seems a valuable add-on AED.