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July2007 Vol.44 Issue:      2 Table of Contents
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Determents of Some Cognitive Functions in Adult Males with Generalized Tonic Clonic Idiopathic Epilepsy

Ghaydaa A. Shehata1, Abd El-Aziz M. Bateh2

Departments of Neurology, Assuit University1, Psychology, Faculty of Arts, Banha University2



Purpose: This study was designed to assess some cognitive functions among adult male patients with generalized tonic-clonic seizures of idiopathic epilepsy. Subjects and Methods: Forty-nine right-handed male patients with generalized (tonic – clonic) idiopathic epilepsy were recruited from outpatient epileptic clinic, Assuit University hospitals. Another 42 subjects of the same age and sex-matched adults were chosen as a control group. Each participating subject was subjected to assessment of cognitive function using Stanford-Binet (4th edition), complete medical history, clinical examination (with special emphasis on epilepsy-related factors and drug - related factors) and EEG records (for epileptic patients only). Results: Epileptic patients reported highly significant impairment across all measured cognitive functions compared with the healthy group. Polytherapy epileptic group was the worst one followed by carbamazepine monotherapy epileptic group and the least was valporate monotherapy epileptic group. Early age of onset, increased severity of seizure, and prolonged duration of treatment (years) showed significant negative correlation in some studied cognitive functions subscales. Conclusions: Adult males with generalized tonic-clonic idiopathic epilepsy experience cognitive function deterioration. Polytherapy, early age at onset, increase severity of seizure and prolonged duration of treatment increase the risk for negative cognitive dysfunction.

(Egypt J. Neurol. Psychiat. Neurosurg., 2007, 44(2): 597-606)




Epilepsy is a biomedical disturbance that results in abnormal episodic bursts of electrical activity in certain neurons, which may spread to the entire brain1. Such abnormal neuronal activity may have significant impact on the normal cognitive processes and behavior of the affected individuals2. Cognitive profiles in epilepsy are as heterogeneous as the epileptic syndromes themselves3.


Factors influencing cognitive dysfunction

A wide range of variables may underlie cognitive impairment in epilepsy including biologic, psychosocial, and treatment-induced factors4.

1.      Biologic factors: Different factors different effects on cognition as Seizure type, etiology of epilepsy, Neuropathology, Age at seizure onset, Seizure frequency, Seizure duration, Seizure severity, Intra- and interictal dysfunction and Structural cerebral damage.4-9.

2.      Non-seizures related variables: These variables include A variety of psychosocial problems associated with epilepsy can give rise to or exacerbate, cognitive and behavioral dysfunction10-13 and Socio-economic factors14.

3.      Treatment-related factors: Anti Epileptic Drugs (AEDs) may have both negative and positive effects on cognition and behavior15. Seizure reduction may improve cognition and behavior, although it may be somewhat counteracted by inducing changes in the underlying neurochemical systems that control thinking and mood 16.

So this study was designed to assess the effect of epilepsy itself, epilepsy related - factors, AEDs and treatment related factors on cognition in adult males with generalized tonic – clonic (GTC) epilepsy.




Forty-nine right-handed male patients with generalized (tonic – clonic) idiopathic epilepsy were recruited from outpatient epileptic clinic, Assuit University hospital, Assuit, Egypt. Those patients were selected out from 403 male epileptic patients   according to inclusion Criteria: Male, with age ranged from 18-45 years, Idiopathic type of epilepsy, generalized tonic- clinic type {defined according to Commission on Classification and Terminology of the International League Against Epilepsy17, clinical evaluation and EEG finding}. Intelligence Quotient {I.Q} > 70 to exclude cases of mental subnormality {according to standardized Assuit University intelligence scale 18}, Right handedness {according to standardized handed questionnaire prepared by Dr Bateh19}, Participants with epilepsy had to have at least one seizure within the last 12 months before assessment and was actively under the medical care of neurologist with one monotherapy carbamazepine (CBZ; n = 21) and valporate (VPA; n = 11) while 17 patients were taking the previous two drugs together as polytherapy with serum level of the drugs within standard therapeutic range. Participants were excluded from participation if they had another type of epilepsy, or receiving other than previous described drugs as treatment of epilepsy, had a history of alcohol/substance abuse; metabolic disorders; had a life threatening medical condition within last year; or had personality or psychiatric disorders or receiving antipsychotic treatment. Forty-two subjects who were cognitively and neurologically intact healthy right-handed male volunteers matched with the studied group regarding age, sex, right handed and educational level as in table (1a).


Table 1a. Demographic information of epileptic patients and control groups.


Demographic Data

Epileptic patients

N (49)


N (42)



Age (Mean±SD)




Numbers of educated years (Mean±SD)





The regional Ethical committee of Assuit University Hospital accepted this study and written consent was given to all patients and control groups.

For each patient, clinical diagnosis was established based on a combination of physical / medical examination, clinical history, and EEG findings. The following information’s were obtained: complete medical history and clinical examination with special emphasis on age, number of educated years, frequency of seizures, duration of illness, occurrence of status epileptics {defined according to Hoffmann8} and its numbers, history of febrile seizures, family history of epilepsy, detailed history of receiving drug include (duration of administration of drug by years and compliance in taking the drugs allover the duration of illness).



All participants were administered standardized measures of cognitive functions assessing areas of memory, attention, language and concentration

*       Standardized Scales {prepared by Assistant Professor Bateh} for measured some cognitive functions which taken from Stanford Binet (4th) edition scales20,21

We also measured the following measures according to Melika20:

*       Total Verbal Resonaning test = Vocabulary + Comprehension + Absurdities + Verbal Relations test

*       Total Non verbal Short Term Memory score = Memory for Objects   score + Bead Memory score

*       Total Verbal Short Term Memory score = Memory for Digits {forward and backwards} scores  + Memory for Sentences score


The method-used in this study is quasi – experimental 

It is based on using natural manipulation of independent variables (cognitive function in normal and generalized tonic clonic idiopathic epilepsy in adult males) with no interference on the part of the researchers, subjects in both the clinical and controlling groups have been subjected to the same tests.

The procedure is conducted individually by having a researcher and a subject sitting facing each others, each group is divided in two smaller groups the first sub-group undertakes the tests as. Vocabulary .comprehension . absurdities. Verbal relations. Memory for objects. Bead Memory. Memory for sentences .Memory for Digits forward. Memory for digits backward. The second sub –group undertakes the same tests in a reversed order. This counter balance procedure aims at controlling the training variable22.


Psychometric efficiency of the tests:

1-            Validity of the tests:

The testes used to assessment functions using Stanford-Binet (4th edition) are valid by using factorial validity, criterion validity and also some studies operate in the culture of  Egypt that sub testes of Stanford-Binet (4th edition ) are valid 20. 

The validity of intelligence test in this study used by criterion validity . The criterion is Picture Arrangement and Picture Completion from Wechsler – Beluve intelligence scale. The coefficient validity of both sub tests are (0.4), (0.5)  and their are significant p =0.001. Also this test is valid by using the technique of factorial validity. This test can discriminate between extremes groups (conflict groups) mental retardation  group and normal group ; their are different p =0.001 18 . We trust this test is suitable fore samples of our study . 

2-            Reliability of the tests:

Tests-retests after stalling terms and circumstances of both experiments with an intervening 28 days time span the replication had been applied to normal subjects to validate the reliability factor for each test 22 as in table (1b)


Table 1b. Test reliability factor.



























Verbal relations




Memory for objects




Bead Memory




Memory for sentences




Memory for Digits forward




Memory for Digits backward



Statistical analysis

Data obtained from this study were fed into an IBM compatible computer. Descriptive statistics i.e. mean, standard deviation and percentages were calculated using a computer software package (SPSS for windows, version 12). Statistical comparison using independent samples T test, One-way analysis of variance (ANOVA) followed by Post Hoc test (LSD) used to compare between the studied groups. A series of Pearson Correlation Coefficients was used to examine the impact of epilepsy – related factors and AED- related factors on cognitive function.




This study included forty-nine GTC idiopathic, male epileptic patients with mean age 20.08±7.43 years; Table (2) represented the demographic and clinical data of epileptic patients.


Cognitive functions tests results

Results of the cognitive measures are presented in table 2. Male adults with generalized idiopathic epilepsy performed significantly lower than the healthy control group in all tests of cognitive functions as presented in table (3). 


Impact of epilepsy – related factors on cognitive function:

To examine the impact of epilepsy – related factors on cognitive test performance, a series of Pearson correlation coefficients were performed. None of the cognitive variables was significantly (all P values > 0.05) related to either history of febrile convulsion and prolonged duration of seizures (years). While Age at onset was correlated with Comprehension (r = 0.286*; P = 0.047), Verbal relation (r = 0.323*; P = 0.023) and Total Verbal Resonaning (r = 0.313*; P = 0.029). There was negative correlation between frequency of seizure and vocabulary(r=- 0.399*; P=0.005), Total Verbal Resonaning (r=-0.310*; P=0.030),  Memory for Objects (r=-0.290*; P = 0.044), Memory for Digit Backwards (r=-0.341*; P=0.016) and Total Verbal Short Term Memory (r=-0.291*; P=0.043). There was correlation between history of occurrence of status epileptics and Memory for Digit Forwards (r = 0.284*; P= 0.048) and also between family history of epilepsy and Memory for Objects (r = 0.384*; P=0.006).


Impact of AED treatment on cognitive function:

To investigate the impact of AEDs on cognitive functions, series of one – way ANOVAs with using LSD post hoc test comparisons was used. There were significant impairment in all studied cognitive functions in polytherapy epileptic group followed by CBZ monotherapy epileptic group and at least VPA monotherapy epileptic group compared with control group. While there were no significant difference between CBZ and VPA, VPA and polytherapy and CBZ and polytherapy, although the polytherapy group performed worse than monotherapy groups allover all studied cognitive functions.


Impact of AED - related factors treatment on cognitive function:

To investigate the impact of AED - related factors on cognitive functions a series of Pearson correlation coefficient were performed. None of the cognitive variables was significantly (all P values > 0.05) correlated to compliance on treatment during all period of illness. Also there was negative correlations recorded with duration of treatment (years) and Memory for Objects score (r = - 0.316*; P = 0.027 (graph 1). There were significant negative correlations recorded with number of taking drugs and all studied cognitive functions as presented in table (5).



Table 2. Represents demographic and clinical data for epileptic patients.


Demographic and clinical data

Generalized epilepsy

N (49)

Age (mean±SD)


Age of onset (mean±SD)


Frequency of fits (%)

· Yearly

· Monthly

· Weekly


22  (44.9%)

13 (26.5%)

14  (28.6%)

Duration of illness (years) (mean±SD)


Occurrence of Status epilepticus (%)

23 (46.9 %)

History of febrile convulsion (%)

4  (8.2 %)

Family history of epilepsy (%)

10 (20.4 %)

Duration of treatment (years) (mean±SD)


Compliance in taking the drug (%)

17 (34.7%)




Table 3. Comparison between the studied groups and control group in cognitive functions.


Cognitive functions

Control group

N (42)

Generalized epileptic group

N (49)

P value


28.59 ± 8.49




30.76 ± 7.23



Absurdities test

21.26 ± 5.88



Verbal relations test

7.90 ± 6.33



Total Verbal Resonaning

88.52 ± 24.93



Memory for Sentences

17.81 ± 5.94



 Bead Memory

22.38 ± 8.13



Memory for Objects

8.31 ± 3.68



Total non verbal Short Term Memory




Memory for Digits forward

6.64 ± 2.49



Memory for Digits backward

3.57 ± 2.74



Total Verbal Short Term Memory

28.02 ± 10.37



* Means significant P<0.05 Significant


Table 4. Comparison between the studied groups {categorized according to type of AED treatment} and control group in cognitive functions.



Control group

N (42)

Epilepsy monotherapy (valporate) group

N (11)

Epilepsy monotherapy (CBZ) group

N (21)

Epilepsy polytherapy group

N (17)











Absurdities test





Verbal relation





Total Verbal Resonaning





Memory for Sentences





 Bead Memory





Memory for Objects





Total Non Verbal Short Term Memory





Memory for Digits forward





Memory for Digits backward





Total Verbal Short Term Memory





* Significant difference between control group and each studied group




Graph (1): Relation between the number of taking drugs and memory for object.


Table 5. The correlations coefficient between the number of taking drugs and cognitive functions.


Cognitive functions




- 0.285*



- 0.314*


Absurdities test

- 0.285*


Verbal relations test

- 0.314*


Total Verbal Resonaning

- 0.314*


Memory for Sentences

- 0.348*


Bead Memory

- 0.379*


Memory for Objects

- 0.414*


Total non verbal Short Term Memory

- 0.435*


Memory for Digits forward

- 0.393*


Memory for Digits backward

- 0.476*


Total Verbal Short Term Memory

- 0.427*


Correlation is significant at P<0.05 (two-tailed).





Most studies carried out on cognition and epileptic patients do not distinguish between subgroups of epilepsy patients, although these patients cannot be considered a homogeneous group3. Other epilepsy-related factors such as early age at seizure onset, duration of epilepsy, frequency of seizures, and the effect of anti-epileptic drugs (AEDs) also affect neuro-psychological functioning23. These differences in epilepsy related factors make firm conclusions about cognition in epilepsy patients in general impossible and thus distinct epilepsy groups should be studied separately to distinguish the effects of epilepsy itself, medication, and other factors3. In our study we tried to specify the selected patients as possible as we can. So we carefully chose our patients according to chosen inclusion and exclusion criteria that make our patient group unique in the current literature on objective neuropsychological functioning and in epilepsy.  In which we chose male patient to exclude the effect of female hormones on cognition24,25. We also chose right-handed patients to exclude the effect of dominant lobe on cognition26. Also we chose one type of epilepsy to exclude the effect of different types on cognition4 and also we specified the type of treatment (carbamazepine, valporate or combination of both) to exclude the effect of different drugs and multiple polytherapy drugs on cognition15. To minimize variations in AEDs related factors on cognitive functions27, we chose our patients on regular treatment for at least the last 6 months and we performed the serum levels of AEDs to choose patients with there serum levels within standard therapeutic range to exclude the effect of drug toxicity.

The present study demonstrates that male, right handed, adult male with generalized tonic- clonic idiopathic epilepsy on regular treatment for at least 6 months exhibited poorer performance across all studied standardized measures assessing a range of cognitive functions compared with a group of demographically and educationally matched healthy adults. This matches with many previous studies as27,4,1,5,28,2.

Additional analyses suggest that epileptic- related factors exacerbate the impairment of cognitive functions in which there is significant correlations between early age at onset and some studied cognitive functions as Comprehension, Verbal relation, and Total Verbal Resonaning. This can be explained as poor cognitive outcome is generally associated with an early onset in which seizures can induce structural damage that may in turn cause cognitive deficits3, also there is evidence that cognitive functions are already impaired at the onset of the disease, and that the maturation of cognitive functions in early age at onset is susceptible to the adverse influence of epilepsy3, while in older age at onset the cognitive decline progresses very slowly over decades with an age regression similar to that of people without epilepsy3.

There is correlation between increased frequency of seizure and vocabulary, Total Verbal Resonaning, Memory for Objects, Memory for Digit Backwards and Total Verbal Short Term Memory. The increased frequency of seizures means poor seizure control which leads to poor cognitive outcome3,29 and generalized cognitive impairment with global decline in attention, memory, and general intelligence7. The occurrence of status epileptics leads to impairment of Memory for Digit Forwards in which status epilepticus and prolonged or repetitive seizures may induce permanent neuronal injury and result in neurocognitive damage 4,8,30,31. Also family history of epilepsy is associated with decline in Memory for Objects.

The study of the relation between history of Febrile convulsions and cognitive functions shows only weak negative (non significant) correlations, this does not mean this is not important risk factors but its relations to temporal lobe epilepsy is more apparent in affection the cognitive functions 32 than in our studied group of patients who were GTC epilepsy.

This study revealed that epileptic patients receiving polytherapy AEDs have the worst cognitive functions followed by patients on carbamazepine monotherapy epileptic group and the best group is epileptic patients on valporate monotherapy. These results support the hypotheses, which state that the cognitive functions are generally modest with most of the older AEDs when the medications are used as monotherapy and blood levels are maintained within standard therapeutic ranges4. Also matches with previous study, which reported that polytherapy, AEDs leads to cognitive decline than monotherapy AEDs and valporate is better than carbamazepine in cognitive functions affection33,34,35.

As regard the effect of drug – related factors on cognitive functions, this study demonstrates the prolonged duration of antiepileptic dug (years) associated with more impairment in Memory for Objects that matches with previous studies which reported that prolonged duration of usage of AEDs lead to poor cognitive outcome27,36,33,15 .  

In summary, the present study supports the negative effects of epilepsy and AEDs on cognitive function in adult male with generalized (tonic-clonic) idiopathic epilepsy. Polytherapy, early age at onset, increase frequency of seizures, history of status epilepticus, family history of epilepsy and prolonged duration of treatment increase the risk for negative cognitive dysfunction.




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الملخـص العربى


دراسة بعض الوظائف المعرفية فى الذكور البالغين الذين يعانون من تشنجات صرعية عظمى


الغرض من الدراسة : دراسة بعض الوظائف المعرفية فى الذكور البالغين المصابين بمرض الصرع (تشنجات صرعية عظمة).

العينة : اشتملت هذه الدراسة على تسعة وأربعين ذكراً يستخدمون اليد اليمنى ويعانون من تشنجات صرعية عظمى وتمت مقارنتها باثنين وأربعين ذكراً كعينة ضابطة لهم نفس الخصائص العمرية والثقافية وقد تم تطبيق اختبار ستانفورد بينية فى صورته الرابعة على هذه العينة كما تم أخذ تاريخ مرضى كامل من هذه العينة بالإضافة إلى عمل تخطيط كهربائى للمخ لهؤلاء المرضى.

نتائج البحث : أثبتت هذه الدراسة أن هناك فروق إحصائية فى معظم الوظائف المعرفية المدروسة فى هؤلاء المرضى مقارنة بالعينة الضابطة. كما أن استخدام أكثر من عقار فى علاج مرض الصرع وحدوث النوبات مبكراً فى العمر بالإضافة إلى زيادة حدوث النوبات الصرعية وطول مدة العلاج يؤدى إلى زيادة تدهور الوظائف المعرفية.

خلاصة البحث : أن الوظائف المعرفية فى الذكور البالغين الذين يعانون من مرض الصرع (تشنجات صرعية عظمى) يتأثرون بمرض الصرع كما أنهم يتأثرون بتعدد العلاج المستخدم فى الصرع وحدوث النوبات الصرعية مبكراً بالإضافة إلى شدة حدوث النوبات الصرعية وطول فترة العلاج.

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