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April2015 Vol.52 Issue:      2 Table of Contents
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Effect of Antiepileptic Medications on the Quantitative Electroencephalogram of Epileptic Patients

Ann A. Abdel Kader1, Amani M. Nawito1, Amira A. Labib1,

Mye A. Basheer1, Rania S. Ismail2, Nermeen A. Kishk2

Departments of Clinical Neurophysiology Unit1, Neurology2, Cairo University; Egypt


Background: Antiepileptic drugs (AEDs) remain the primary treatment option for epilepsy. Analysis of background EEG frequencies can be a simple and objective method of evaluating the effect of AEDs, due to the established hypothesis that the background EEG activity represents the functional state of the brain. Objective: To assess the effect of AEDs on the background activity of the inter ictal EEG recordings, using quantitative measures of some epileptic patients, known to have whether focal or generalized epilepsy. Methods: Retrospective analysis of the medical and quantitative EEG records of 61 known epileptic patients. The EEG relative powers of various frequency bands were subjected for statistical comparisons between patients, who were classified to clinical groups and subgroups. Results: Significant increase of the relative powers of the slow waves (delta and theta waves) in the non-medicated, compared to the medicated group mainly seen in the midline leads as well as the parietal ones. These findings were almost replicated in non-medicated patients having generalized epilepsies. In addition, the wave (delta, theta, alpha and beta) powers increase was expressed in a more diffuse pattern in non-medicated males. Conclusion: We support the hypothesis of drug-induced decreased cortical EEG sources synchronization as an explanation of our positive results. The males are assumed to express such drug-induced changes more prominently than females, due to lack of changes of the blood antiepileptic drug levels. However, these changes occur in females in relation to their hormonal cycles, as mentioned in otherprevious studies. [Egypt J Neurol Psychiat Neurosurg.  2015 ; 52(2) : 95-99]


Key Words: Antiepileptic medications, Digital EEG, Relative band power, Epilepsy.

Correspondence to Prof. Ann Ali Abdelkader, Clinical Neurophysiology Unit, Cairo University, Egypt

Tel: +201006063114.   Email: 



Antiepileptic drugs (AEDs) are always the primary treatment option for epilepsy. Inspite of being effective for seizure control, AEDs can also cause neurotoxicity leading to undesirable effects on normal functions of the central nervous system (CNS)1.

The use of electroencephalographic (EEG) measures can provide deep insight in studying the effect of pharmacological intervention on cognition2,3 .

Since background EEG activity reflects the functional state of the brain, its analysis can be a simple and objective method of assessment of AEDs effects4. Although some studies have shown better diagnostic yield with quantitative EEG (QEEG) measures5, however, others have reported the same findings in both QEEG and routine recordings in epileptic patients6. Some studies carried out on background EEG activity with QEEG have been conducted in IGE and focal epileptic patients, and revealed background changes despite normal visual analysis of their  background activity7-15.

The objective of this study is to assess the effect of AEDs on the background activity of the inter ictal EEG recordings, using quantitative measures of some epileptic patients, known to have whether partial or generalized epilepsy.




This study is a retrospective study. It was carried out by exploring the medical records of epileptic patients attending the epilepsy outpatient clinic of Kasr Alainy hospital, during the period from 15/1/2012 and to 9/9/2012. The EEG recordings and filing were in the Clinical Neurophysiology Unit, Kasr Alainy hospital, Cairo University. The EEG records were visually assessed by only two electroencephalographers to minimize inter reader subjective variability. The patients, by clinical history, were either on AEDs or not. The AEDs included: Carbamazepine, Clonazepam, Levetiracetam, Phenytoin, Topiramate and Valproate (or Valproic acid).

Digital EEG was recorded using Schwarzer  BrainLaB 4 GmbH.   The investigation was carried out while the patient was recumbent in dorsal position in semi-luminated room. The electrodes were placed according to the international 10-20 system, with electrode impedance below 10 Kohm, and ear lobe electrodes served as reference. Recording was carried out for about 20 minutes with 3 minutes hyperventilation as well as intermittent photic stimulation.

Five artifacts’ free epochs, each of 10 seconds duration were selected for QEEG. The relative powers of 19 electrodes (Fp1, Fp2, F7, F8, F3, F4, C3,C4, T3, T4, T5, T6, P3, P4, O1, O2, Fz, Cz and Pz) were studied in the following frequency bands: delta (1-3Hz), theta (4-7 Hz), alpha (8-12 Hz), Beta 1 (12.5–16 Hz) Beta2(16.5–20 Hz) and Beta3(20.5–28 Hz). The sum of quantitative EEG readings was 114 different readings for each patient.

Relative power is represented by the percentage of the power of a given frequency band compared to the sum of the power of all frequency bands. Relative delta power, for example, is equal to (absolute delta power/absolute delta power + absolute theta power + absolute alpha power + absolute beta power) * 100.

Data were statistically described in terms of mean ± standard deviation (± SD), median and range, or frequencies (number of cases) and percentages when appropriate. Comparison of numerical variables between the study groups was done using Student t test for independent samples when the data were normally distributed and/or the groups were large enough, while Mann Whitney U test for independent samples was used when data were not normally distributed. For comparing gender, Chi square (c2) test was performed. Correlation between various variables was done using Pearson moment correlation equation for linear relation in normally distributed variables and Spearman rank correlation equation for non-normal variables/non-linear monotonic relation. p values less than 0.05 was considered statistically significant. All statistical calculations were done using computer program SPSS (Statistical Package for the Social Science; SPSS Inc., Chicago, IL, USA) release 15 for Microsoft Windows (2006).




A)           Descriptive Data:

The study included 61 patients, 24 of them were females. Their age ranged from 11 to 57 years with a mean of 25.4 (SD=11.52). The duration of the illness ranged from “just diagnosed disease” and reached 30 years of epileptic history, with mean illness duration of 8.383 years (SD=7.986). The frequency of ictal events ranged from 1-7 fits per month, with a mean frequency of 3.262 fits/month (SD=1.569). The visual EEG analysis showed dominant background rhythm of range 8.5-11.5 Hz and a mean of 9.491Hz (SD=0.679).

There were 20 patients diagnosed as having focal epilepsy, while 41 patients were diagnosed as having generalized epilepsy. There were 30patients on AEDs, while 31 patients were not (medicated group and non-medicated group). Patients on AEDs were prescribed 1-4medication types, with an average of 1.3 AEDs. Patients taking old generation AEDs were 30, while those on new generation AEDs were 8, and patients taking both generations were 7 patients.


B)           Comparative Data:

1.      Quantitative EEG of medicated versus non-medicated group:

Both medicated and non-medicated groups are age and gender matched. The medicated males: females ratio was 17:13. While the non-medicated males: females ratio was 20:11. The age in medicated group showed a mean of 26.88 years (SD=10.72), while the non-medicated group showed a mean age of 24.16 years (SD=12.19).

Out of all the QEEG readings (114 Q-EEG readings), there was significant increase in powers among non-medicated, compared to the medicated group patients in 12 readings. They were slow (delta and theta) waves in the midline and bilateral parietal region (in addition to T4 and F4 theta waves). This is shown in Table (1).

2.      Quantitative EEG of medicated versus non-medicated patients with generalized epilepsy:

There were 20 medicated and 21 non-medicated patients with generalized epilepsy. Out of all the QEEG readings (114 Q-EEG readings), there was significant increased powers among non-medicated, compared to the medicated male patients in five readings They are midline and bilateral parietal slow waves (P3, P4, Fz, Cz theta and Pz delta).

3.      Quantitative EEG of medicated versus non-medicated males:

There were 17 medicated, and 20 non-medicated males. Out of all the QEEG readings (114 Q-EEG readings), there was consistently significant increased powers among non-medicated, compared to the medicated male patients in 56 readings. This is shown in Figure (1).


C)           Correlative Tests:

1.      Quantitative EEG readings correlation to disease duration:

Out of all the QEEG readings (114 Q-EEG readings), there were three positive correlations (two of them are non-parametric) to the disease duration (F4, O1 and Fz delta).

2.      Quantitative EEG readings correlation to epileptic fits frequency:

Out of all the QEEG readings (114 Q-EEG readings), there was a single positive correlation to the fits frequency (Cz delta).



Table 1. Significantly different QEEG readings in medicated, versus non-medicated group.



Non Medicated group (N=31)

Medicated group (N=30)









T4 theta








F4 theta








P3 theta








P3 delta








P4 theta








P4 delta








Fz theta








Fz delta








Cz theta








Cz delta








Pz theta








Pz delta












Figure 1. The widespread increased power of slow waves in non-medicated versus medicated males****= significant.





In the present study we investigated the effect of antiepileptic medications on the background EEG power spectra, using the relative power calculation. We conducted a comparison between a group of medicated and non-medicated epileptic patients, with focal and generalized seizures. The patients were age and gender matched. For all the patients, the visual background activity was normal.

The study showed a statistically significant increase in the power of slow activities of midline and parasagittal regions in the non-medicated compared to the medicated epileptic patients. This was more also noted between the medicated and non-medicated patients with generalized seizures. These findings are similar to previous works of Clemens and coworkers14,15 who found a reduced absolute power in low-frequency bands (1.5–12.5 Hz) in epileptic patients after treatment with valproate and lamotrigine. As regards our patients, 48% of the medicated group were on valproate, and in patients with generalized seizures, they were 50%.

The absolute power reflects the degree of synchronization of the cortical EEG sources at a given frequency (or in a frequency band), and is proportional to the number of the synchronously activated generators that contribute to the signal16.

According to findings of Clemens, the valproate-related decrease of synchronization was significantly greater in the medial (midline + parasagittal) leads than in the lateral derivations14, which was also seen in the present study. The medial electrodes mainly explore the frontal and parietal cortex where the majority of the so-called non-specific thalamo-cortical fibers terminate, mediating the synchronized recruiting cortical response and the spike-wave paroxysms.14, 17.

These findings are in contrast to other studies who found an increase in the absolute delta and a decrease in mean frequency of delta, which were detected in fronto-temporal and occipital leads in both medicated and non-medicated groups in patients with juvenile myoclonic epilepsy12. Another study showed a general tendency for diffuse (absolute and relative) delta, theta and alpha power excess and relative beta power deficit in patients with idiopathic generalized epilepsy to controls7.

Another study showed Carbamazepine and lamotrigine, both sodium-channel modulators, altered brain topography in the gamma range in the same frequency bands (50–60 Hz). Valproate, which has multiple actions on sodium and calcium channels as well as GABA turnover, modified brain topography in the low gamma range (30–40 Hz). They did not report any change in the other frequency bands13. Our study did not test the gamma band. Modification of gamma-power reflects changes within local cortical regions18,19 and may relate to seizure initiation20,21 unlike changes in lower frequency bands, which reflect interregional communication and might relate to seizure propagation22.

We found a decreasing power of the slow activities that was significant and widespread between medicated compared to non-medicated males, whereas similar results were not seen in females. This may be explained by the changing of the blood levels of antiepileptic drugs, as many of them are broken down by the same enzymes that metabolize estrogen and progesterone23,24.

Some studies confirmed a decrease in blood levels of antiepileptic drugs around the time of menstruation, whereas other studies were not conclusive25.

The present study showed also a significant correlation, however not widespread in locations, between the power of slow wave and duration of illness as well as with frequency of seizures in all patients. This may be related to the relationship between cognitive decline and the frequency of seizures26and the increased power of slow waves are associated with cognitive decline27.

We conclude that, inspite of normal visual analysis of background EEG in epileptic patients, there was an increase in the relative power of slow frequency bands in non-medicated compared to medicated groups, especially in the central and parasagittal regions, evident in patients with generalized seizures and in males. In order to confirm these results, future studies with larger samples of patients are recommended.


[Disclosure: Authors report no conflict of interest]




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الملخص العربي


تأثير الأدوية المضادة للصرع على رسم المخ الكمي في مرضى الصرع


تظل الأدوية المضادة للصرع هي العلاج المبدأي في مرض الصرع، وحيث أنه ثبتت الفرضية بأن نشاط خلفية رسم المخ يمثل الحالة الوظيفية للمخ، فإن تحليل ترددات خلفية رسم المخ قد تكون وسيلة بسيطة وموضوعية في تقييم تأثير الأدوية المضادة للصرع.

لذا فقد هدفت الدراسة إلى تقييم تأثير الأدوية المضادة للصرع على نشاط خلفية رسم المخ ما بين النوبات باستخدام قياسات كمية لبعض مرضى الصرع البؤري أو العام مما حدا إلى التحليل الاستعادي لملفات رسم المخ الكمي والملفات الإكلينيكية ل 61 مريض صرع والمقارنة الإحصائية بين قوى رسم المخ النسبية للترددات المتعددة بين مجموعات المرضى المختلفة.

وقد أظهرت النتائج للمرضى الذين لا يتناولون الأدوية المضادة للصرع بالمقارنة بالمرضى الذين يتناولونها: زيادة معتد بها في القوى النسبية للموجات البطيئة (دلتا وثيتا) وخاصة في منتصف الرأس والمناطق الجدارية وتم ملاحظة نتائج مشابهة في مرضى الصرع الكلي, هذا بالإضافة إلى زيادة معتد بها القوى النسبية للموجات (دلتا, ثيتا, الفا, بيتا) وبنمط أكثر شيوعا في المرضى الذكور, مما جعلنا ندعم افتراضية تسبب الأدوية المضادة للصرع في انخفاض تزامن مصادر رسم القشرة المخية وأيضا - وكما ذكر في دراسات أخرى سابقة- اعتقاد ارتبط التأثر الدوائي عند الذكور - دون الإناث - إلي عدم وجود تغيرات, في مستوى الدواء ضد الصرع في الدم, مرتبطة

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