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January2013 Vol.50 Issue:      1 Table of Contents
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Cognitive Function Assessment in Epileptic Females

Laila Elmosly1, Azza Bayoumy1, Manal Hafez1, Rasha El Bialy1,

Hosam Imam1, Iman Bayoumy2

Department of Neurology, Al Azhar University1; Ain Shams University2; Egypt



ABSTRACT

Background: Epilepsy is functional disturbance of central nervous system (CNS) and induced by electrical discharges. Epilepsy and antiepileptic drugs especially the older ones can have negative effects on cognitive functions. Objective: The aim of this study is to evaluate the effect of epilepsy on cognitive functions and quality of life in females under antiepileptic drugs. Methods: This study was done on 30 epileptic females, aged from 20-40 years. They were under monotherapy either valoproic acid or carbamazepine. The duration of seizures varied between 10-20 years. All cases were subjected to full history taking, general, neurological examination, routine laboratory investigations, anti epileptic drug serum level (AED), conventional EEG and assessment of cognitive functions by mini mental state examination (MMSE), P300 and quality of life  in epilepsy 31 problem (QOLIF31). Results: There is association between epilepsy, quality of life and impairment of cognitive function. The study of event related potential revealed that there is prolonged latency and decreased amplitude of P300 in epileptic patients on valproic acid. Conclusion: Females with epilepsy have some decline in  cognitive function related either to  their condition, or  AED therapy or a combination of both, which in turn  has a detrimental effect on the ability to undertake everyday activities and areas of quality of life including education, work, family life and leisure pursuits. [Egypt J Neurol Psychiat Neurosurg.  2013; 50(1): 25-30]

Key Words: epilepsy, cognitive function, P300, MMSE, QOL

Correspondence to Manal Hafez, Neurology Departments, Al Azhar University, Egypt.Tel: +201116830815. Email: drmanalhafez@yahoo.com





INTRODUCTION

 

Epilepsy has diverse and complex effects on the overall wellbeing or subjective quality of life (QOL) of the patients. Multiple factors have been shown to affect the psychosocial status and quality of life of patients with epilepsy. These factors include underlying brain lesions and associated handicaps, seizure type and semiology, seizure frequency, duration of the disease, employment and financial background, family support, social environment, and quality of medical care.1 These factors have great impact on people's lives. Patients experience social isolation, stigmatization, lack of understanding and unemployment. There are also physical risk due to seizures like fall, drowning and burns and patients may feel insecure because seizures are unpredictable.2

Cognitive and behavioral impairments have been observed as a consequence of epilepsy. In individuals with high seizure frequency, such impairments may accumulate and have a much greater impact on daily life than suspected. Clinical studies show that cognitive impairments induced by seizures are reversible for most seizure types when seizures are controlled adequately.3

 

Many of the available antiepileptic drugs (AEDs), especially the older ones, can have a negative effect on cognitive functions, including memory, such as learning in children or driving ability in adults. Reducing the dose or switching to one of the newer AEDs may improve quality of life for susceptible individuals.4 The Mini Mental State Examination (MMSE) is one of the most popular screens of cognitive functioning due to brevity and ease of administration and scoring.5

The P300 latency time is generally accepted as a measure of speed of cognitive processing and its amplitude reflect the number of neurons allocated to the eliciting task. It reflects cognitive brain functions of the subject.6 As regards the clinical variables, seizure type and frequency; they have been found to be significant predictors of high scores quality of life in epilepsy 31 problem (HROL). Several studies have highlighted that patients with epilepsy are more likely to be underemployed or unemployed, and have lower rates of marriage7 Individuals with potentially stigmatizing illness assume that they will be devalued and discriminated. These people adopt coping strategies to address these assumptions, typically social withdrawal, which have marked negative consequences for quality of life, and hence reinforce their feeling of being stigmatized.8

 

Aim of the Work

The aim of this study is to evaluate the effect of epilepsy on cognitive functions and quality of life in females under antiepileptic drugs and how to reach to early diagnosis of cognitive impairment to prevent further deterioration.

 

SUBJECTS AND METHODS

 

This case control study was conducted at neurology department Al-Zhraa University Hospital. Thirty epileptic Egyptian females were included in this study (15 patients with focal epilepsy and 15 patients with generalized epilepsy), aged between 20-40 years with focal or generalized tonic clonic seizure, duration of epilepsy ranged from 10 to 20 years, receiving monotherapy either valproic acid or carbamazepine. Ten female age-matched apparently healthy volunteers served as control.

We excluded those suffering from head injury, congenital, structural lesions, alcohol/drug abuse, neurological, psychiatric or medical disorders.

All patients were submitted to the following; complete history taken, complete general and neurological examination, routine laboratory investigations, serum AEDS level, conventional electroencephalographs in addition to assessment of the cognitive functions by MMSE, and P-300 (auditory event related potential).

We used also the Quality of life in epilepsy 31 problems (QOLIE31) instrument; a self-administrated questionnaire survey of health related quality of life for adult (18 years or older) with epilepsy. It includes 7 subscales; overall quality of life, seizure worry, emotional well being, energy/fatigue, cognitive, medication effects and social function, their responses can yield 7 individual scores (per subtest) and a total (composite) score.9

 

Statistical Methods

The data were collected, coded and SPSS (statistical package for social science), windows version 11.5 was used for analysis. Data were expressed as number and mean±standard deviation (SD). We also used analysis of variance (ANOVA); a single test used to collectively indicate the presence of any significant deference between several groups (several arithmetic means). It is based on comparing the variance between the groups to the variance within the groups.

 

RESULTS

 

Thirty epileptic female patients, aged between 20 and 40 years were included in this study. Regarding Comparison between patients and control as regard MMSE There is significant difference between epileptic patients and control as regards MMSE (P-value 0.033); Table (1).

As regard Comparison between patients and control as regard P300 latency and amplitude There is highly significant difference between epileptic patients and control as regard P300 latency and amplitude (P-value<0.001); Table (2).

Epileptic patients were divided into two groups as regards types of antiepileptic drugs the two epileptic groups were compared together to identify the effect of valproic acid and carbamazepine on P300 latency and amplitude. There is no significant difference between types of antiepileptic drugs and P300 latency and amplitude; Table (3).

As regard quality of life There is highly significant difference between epileptic patients and control being affected in epileptic patients (P-value <0.001); Table (4).

Regarding the effect of anti epileptic drugs valproic acid and carbamazepine, there is a significant difference between types of anti epileptic drugs as regard quality of life being more impaired in valproic acid type with P-value =0.023; Table (5).

Regarding correlation between P300 latency and MMSE there is inverse correlation between P300 latency and MMSE; Table (6).

Regarding correlation between Quality of life and MMSE there is direct correlation between Quality of life and MMSE. However, there is Inverse correlation between duration of epilepsy, P300 latency and Quality of life; Table (7).


 

 

Table 1. Comparison patients and control as regard MMSE.

 

Groups

MMSE

T-test

Mean±SD

t

P-value

Patients

25.9±1.2

-4.2

0.033*

Control

27.5±0.9

* Significant   

 

Table 2. Comparison between patients and control as regard P300 latency and amplitude.

 

 

Patients

Control

T-test

Mean±SD

Mean±SD

t

P-value

P300  Latency

327.1±48.9

301.4±6.3

2.0

<0.001**

P300 Amplitude

12.4±3.5

22.4±4.9

-5.8

<0.001**

** Highly significant             

 

Table 3. Comparison between types of antiepileptic drugs and P300 latency and amplitude.

 

 

Types of AED

T-test

Valproic acid

Carbamazepine

Mean±SD

Mean±Mean

t

P-value

P300 latency

323.2±45.0

331.7±54.6

-0.5

0.561

P300 Amplitude

11.6±3.2

13.4±3.7

-1.4

0.15

 

 

Table 4. Comparison between patients and control females as regard quality of life.

 

Groups

Quality of Life

T-test

Mean±SD

t

P-value

Patients

41.3±9.8

-9.021

<0.001**

Control

70.2±3.9

** Highly significant                                          

 

Table 5. Comparison between types of antiepileptic drugs as regards Quality of life.

 

Types of AED

Quality of Life

T-test

Mean±SD

t

P-value

Valproic acid

36.9±9.8

-2.4

0.023*

Carbamazepine

45.6±10.0

* Significant   

 

Table 6. Correlation between P300 latency and MMSE.

 

 

MMSE

R

P-value

P300 (Latency)

-0.400

0.028*

* Significant   

 

Table 7. Correlation between Quality of life, MMSE, Duration of epilepsy and P300 latency Quality of life.

 

 

Quality of Life

R

P-value

MMSE

0.797

0.000

Duration Of Epilepsy

-0.461

0.040*

P300 (Latency)

-0.433

0.046*

* Significant   

 


DISCUSSION

 

Cognitive alterations are observed in epileptic subjects in variable degrees and are generated by multiple factors including, seizure type, age at onset of epilepsy, seizure frequency, duration, severity of seizures, psychosocial factors, and sequelae of AEDs.10

In this study we evaluate the cognitive dysfunction in epileptic female patients under anti-epileptic drugs by the aid of event related potential and MMSE and the effects of this cognitive dysfunction on the quality of life and compared it by control group. The performance of control was better than epileptic patients. As regards MMSE, there is no significance difference between type of epilepsy and MMSE. This is in agreement with Fell  et al.11, who obtained the same results on studying MMMS in different types of epilepsy.

Event related potential (ERP) are electrical signals from the brain detected during the performance of various cognitive tasks and response to external stimulus.12

In the present study, we investigated P300 to know the effects of epilepsy and antiepileptic drugs on deterioration of cognitive function in epileptic Egyptian females. The studied groups showed a statistically significant trend toward longer P300 latency and lower P300 amplitude in the patients group. This is in agreement with Bokura et al.13, who reported that findings of the amplitude reduction and latency increase in epileptic patients appear to be the result of reduced neural capacity for processing the oddball paradigm information, even when the patient could complete the task. The P300 amplitude reduction in these patients could indicate that a smaller number of neurons are functioning or that the intensity of neural firing is diminished.

However, this is in disagreement with Hermann et al.14, who found no correlation between epilepsy and P300 latency.

Another influence that could alter P300 and cognitive function is epilepsy duration, in our group, there is inverse relationship between duration of epilepsy and P300 latency.

Fukai  et al.15 reports suggested that there is no effect of AED on the latency or amplitude of the P300.

In the present study, valproic acid and carbamazepine as monotherapy in our epileptic patient, their P300 latencies were not significantly different between them.

This is in agreement with Triantafyllou et al.16, who stated that cognitive deterioration is worse in those receiving multiple medications. In Triantafyllou’s study, patients on monotherapy either valproic acid or carbamazepine showed significantly shorter P300 latencies when compared to those on more than one anticonvulsant. This may reflect better cognitive function of patients on monotherapy. In addition, patients with shorter duration of antiepileptic therapy showed less prolonged P300 latencies when compared to those on longer treatment.

Fell et al.11 found that P300 latency became shorter with discontinuation of Carbamazepine therapy, and P300 latency showed a significant positive correlation with the serum concentration of carbamazepine which may suspect the dose dependent effect.

Epilepsy is chronic disorder, which has complex effects on the overall wellbeing or subjective quality of life (QOL) of the patients. QOL in epilepsy is a function of the interaction of various factors, which includes; clinical variables (as seizure frequency, severity, illness duration, treatment side effects, psychiatric comorbidity), social disadvantage (as divorce, unemployment, social stigma) and family circumstances (as family caregiver characteristics, social support).17

In the present study, there is an association between epilepsy and quality of life of the patients. Our results provide evidence that epilepsy promote the development or exacerbation of worry and anxiety and/or socially avoidant behaviors.

As for the social function subscale of the QOLIE-31 which measures such tasks as social activities (as visiting with friends or relatives), leisure time (as, hobbies, going out), driving and vocational limitations, our study showed that these components of the scale appear to reflect one very important motif, independence. As such, the physical aspects of seizure severity alone can have an impact on day-to-day activities. This can have amounting effects on an individual’s interpersonal relationships, financial situations and self-efficacy.

This is in agreement with Cramer18, who found that Females with epilepsy in all his groups described seizures worries related to shame of having seizure in front of other, accidental injury, and intentional injury inflicted by another person.

The cognitive domain of QOLIE-31 consists of questions concerning memory, concentration and reasoning is impaired in this study. Although progressive cognitive impairment is associated with epilepsy, the association between perceived cognitive abilities and seizure severity in this study is not intuitive.

This is in agreement with Hermann et al.19, who founds that seizure duration, severity, frequency and perceived controllability or predictability of seizures contribute significantly to learned helplessness scale scores. This result supplement the finding of our present study, which suggest that the quality of a seizure experience can result in anxiety and socially avoidant behavior measured as seizure worry and social functioning.

The present study is also in agreement with Cramer18, who reported that QOL improvement was evident only among those patients achieving seizure freedom.

The present study is also in agreement with Tavakoli et al who reported that Cognitive impairment associated with temporal lobe epilepsy (TLE) has been recognized in multiple studies.20

 

Conclusion

Our data suggest that individuals with epilepsy have some decline in  cognitive function related either to  their condition, or  AED therapy or a combination of both, which in turn  has a detrimental effect on the ability to undertake everyday activities and areas of quality of life including education, work, family life and leisure pursuits. Results of the present study provide an important basis for future research into the effects of cognitive impairment on quality of epileptic female’s life measures and direct impact of cognitive side effects related to AED therapy, from the perspective of individuals with epilepsy.

The results of this study suggest the need for careful follow up of epileptic females on AED, in other to minimize cognitive side effects and to maximize quality of life. There is a need for simple tests of cognitive functions that can screen patients with epilepsy and determine who is in need for more sophisticated tests of cognitive functions.

We believe P300 studies may have an important role in the evaluation of subclinical cognitive dysfunction in epileptic patients treated with antiepileptic drugs.

 

Recommendations

Assessment of cognitive decline by neurophysiological tests is very important step in examination of female epileptic patients to detect early subtle impairment.

Cognitive rehabilitation is recommended for affected patients. Follow up of epileptic female patients on AED in order to minimize cognitive side effects and to maximize the quality of life. MMSE and P300 have an important role in evaluating the subclinical cognitive dysfunction in epileptic patients treated with AEDs.

 

[Disclosure: Authors report no conflict of interest]

 

REFERENCES

 

1.        Blume WT, Lüders HO, Mizrahi E, Tassinari C, van Emde Boas W, Engel J Jr. Glossary of  descriptive  terminology for ictal semiology, report of the ILAE task force on classification and terminology. Epilepsia. 2001; 42: 1212-8.

2.        Bertrand D, Picard F, Le Hellard S, Weiland S, Favre I, Phillips H, Bertrand S, et al. How mutations in the nAChRs can cause ADNFLE epilepsy.  Epilepsia. 2002; 43 (Suppl 5): 112-22.

3.        Aldenkamp AP, Alpherts WC, Blennow G, Elmqvist D, Heijbel J, Nilsson HL, et al. Withdrawal of antiepileptic medication in children--effects on cognitive function: The Multicenter Holmfrid Study. Neurology. 1993; 43: 41-50.

4.        Holmes GL. Epilepsy in the developing brain, lessons from the laboratory and clinic. Epilepsia. 1997; 38: 12-30.

5.        Devinsky O, Vickrey BG, Cramer J, Perrine K, Hermann B, Meador K, et al. Development of the quality of life in epilepsy inventory. Epilepsia. 1995; 36: 1089-104.

6.        Wickens CD, Sandry D. Task-hemispheric integrity in dual task performance. Acta Psychol (Amst). 1982; 52: 227-47.

7.        Jacoby A, Baker GA, Steen N, Potts P, Chadwick DW. The clinical course of epilepsy and its psychosocial correlates: finding from a U. K. community study. Epilepsia. 1996; 37: 148-61.

8.        Jacoby A, Snape D, Baker GA. Epilepsy and social identity, the stigma of a chronic neurological disorder. Lancet Neurol. 2005; 4:171-8.

9.        Piazzini A, Beghi E, Turner K, Ferraroni M; LICE Quality of Life Group. Health-related quality of life in epilepsy, findings obtained with a new Italian instrument. Epilepsy Behav. 2008; 13: 119-26.

10.     Loring DW, Marino S, Meador KJ. Neuropsychological and behavioral effects of antiepilepsy drugs. Neuropsychol Rev. 2007; 17: 413-25.

11.     Fell J, Dietl T, Grunwald T, Kurthen M, Klaver P, Trautner P, et al. Neural bases of cognitive ERPs: More than phase reset. J Cogn Neurosci. 2004; 16: 1595-604.

12.     Hansenne M. Le potentiel évoqué cognitif P300 (I): aspects théorique et psychobiologique [The p300 cognitive event-related potential. I. Theoretical and psychobiologic perspectives]. Neurophysiol Clin. 2000; 30: 191-210. [Article in French].

13.     Bokura H, Yamaguchi S, Kobayashi S. Event- related potentials for response inhibition in Parkinson's disease. Neurophyschologia. 2005; 43: 967-75.

14.     Hermann B, Seidenberg M, Lee EJ, Chan F, Rutecki P. Cognitive phenotypes in temporal lobe epilepsy. JINS. 2007; 13: 12-20.

15.     Fukai M, Motomura N, Kobayashi S, Asaba H, Sakai T. Event-related potential (P300) in epilepsy. Acta Neurol Scand. 1990; 82: 197-202.

16.     Triantafyllou NI, Zalonis I, Kokotis P, Anthracopoulos M, Siafacas A, Malliara S, et al. Cognition in epilepsy: a multichannel event related potential (P300) study. Acta Neurol Scand. 1992; 86: 462-5.

17.     Trevathan E, Gilliam F. Lost years: delayed referral for surgically treatable epilepsy. Neurology. 2003; 61: 432-3.

18.     Cramer JA; ILAE Subcommission on Outcome Measurement in Epilepsy (Carol Camfield, Hans Carpay, Christopher Helmstaedter, John Langfitt, Kristina Malmgren, and Samuel Wiebe). Principles of health-related quality of life, assessment in clinical trials. Epilepsia. 2002; 43: 1084-95.

19.     Hermann BP, Trenerry MR, Colligan RC. Learned helplessness, attributional style, and depression in epilepsy. Bozeman Epilepsy Surgery Consortium. Epilepsia. 1996; 37: 680-6.

20.     Tavakoli M, Barekatain M, Doust HT, Molavi H, Nouri RK, Moradi A, et al. Cognitive impairments in patients with intractable temporal lobe epilepsy. J Res Med Sci. 2011; 16: 1466-72.


 

الملخص العربى

 

تقييم الوظائف المعرفية للإناث المصابات بمرض الصرع

 

يعتبر مرض الصرع هو أكثر الأمراض العصبية شيوعا وانتشارا متمثلا في نوبات صرعية متكررة بسبب نشاط عصبي زائد ومتكرر للخلايا العصبية في المخ.

تشيع أعراض الاضطرابات المعرفية فى مرضى الصرع حيث أوضحت الدراسات أن اضطرابات الذاكرة والانتباه والوظائف التنفيذية هي أكثر الاضطرابات المعرفية فى مرضى الصرع وحدوث هذه الاضطرابات المعرفية يكون له انعكاسات سلبية مميزة على نوعية حياة المرضى وعلى أدائهم الوظيفي والاجتماعي وخاصة الإناث  منهم .

إن الاختبارات المسحية هى إجراءات إكلينيكية تهدف إلى فحص الوظائف المعرفية المختلفة وقد اختيرت بحيث تكون قصيرة وذات درجة عالية من الدقة بحيث تعطى إنذار عند وجود خلل ومن أمثلة هذه الاختبارات المسحية اختبارات الوظائف المعرفية MMSE .

يعتبر اختبار نمط الحياة QOLIE31 اختبار مسحي يهدف إلى بحث نمط الحياة فى مرضى الصرع ويعطينا صورة عن مدى تأثر نمط الحياة عند مرضى الصرع.

العينة وطرق البحث: لقد تم إجراء الدراسة على أربعين من الإناث فى الفترة وقد تم تقسيم العينة إلى مجموعتين أساسيتين

أ –   مجموعة البحث؛ وتشمل ثلاثيين من الإناث المريضات بالصرع تتراوح أعمارهن بين عشرين وأربعين عاما وقد تم اختيارهن طبقا للمعايير التشخيصية للتقسيم العالمي للنوبات الصرعية مع خلوهن من أي اعتلال بالسمع أو أى مرض عضوي أو نفسي أو عصبي غير مرض الصرع.

ب-   مجموعة ضابطة؛ وتشمل عشرة إناث من الأصحاء المتطوعات تتراوح أعمارهن بين عشريين وأربعين عاما وقد تم اختيارهن على ان يكن هناك مضاهيات للمريضات من حيث العمر والمستوى التعليمي مع خلوهن من أي اعتلال بالسمع أو أي مرض عضوي أو نفسي أو عصبي.

ولقد أبرزت الدراسة النتائج الآتية :

§         لوحظ أداء مريضات الصرع فى الاختبارات المعرفية أقل من غير المريضات. فى حين لم يوجد فارق دال إحصائيا بين الإناث المتزوجات وغير المتزوجات فى كل من الاختبارات السيكولوجية واختبارات فسيولوجيا الأعصاب.

§      لوحظ وجود فارق دال إحصائيا بين المجموعة الضابطة والمرضى فى الجهود المثارة المتعلقة بالحدث حيث وجد طول فترة الكمون (السعة)  وقلة قيمة قمة الذروة للجهود المثارة السمعية طويلة المدى 300. ووجد ان الاختبارات المعرفية تتناسب تناسبا عكسيا مع الجهود المثارة المتعلقة بالحدث.

§      أداء مريضات الصرع وجد أقل من غير المريضات في اختبار نمط الحياة QOLIE31 ومن ناحية أخرى كان أداء المريضات الغير متزوجات أفضل من أداء المريضات المتزوجات وأداء مريضات النوع الكلي أفضل من مريضات النوع الجزئي.

يتناسب الأداء الوظيفي والاجتماعي في مرضى الصرع تناسبا طرديا مع الوظائف المعرفية.


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