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Neuropsychological problems among Epileptic children in Egypt

El-Alameey, Inas R.a; Monir, Zeinab M.a; Eltahlawy, Emanb

doi: 10.1097/01.MJX.0000438375.05493.f7
PEDIATRICS
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Objective This study was designed to assess the extent of comorbidities of cognitive and psychological problems, comparing the relationship between different types of seizures and these neuropsychological problems, and to identify risk factors including the effect of antiepileptic drugs on cognition and behavior that may be associated with the probability of development of these problems among children with epilepsy in Egypt.

Methods This case–control study included 30 epileptic children aged 6–14 years, mean age 9.4±2.6 years and male to female ratio 2 : 1. They were divided into two subgroups according to electroencephalography findings; 15 patients with generalized seizures were included in group I and 15 patients with partial seizures were included in group II. Thirty apparently healthy children matched for age and sex were recruited as a control group. All children were assessed for cognitive function using the Arabic version of the Wechsler Intelligence Scale for Children – Revised, and psychological evaluation was carried out using a standard questionnaire, a parent-completed Pediatric Symptom Checklist-17.

Results Impairment in cognitive function, learning problems, and developmental delay in milestones were found to be significantly more common in patients with generalized seizures compared with those with partial seizures (P<0.05), and in the patients studied versus the control groups (P<0.001). The patients showed both significantly lower cognitive performance and verbal intelligent scores (P<0.05), with significantly lower values of the cognitive performance intelligent score among the patient subgroups and among the patients studied versus control groups (P<0.05). Children with epilepsy had significant behavioral problems compared with the control groups (P<0.05); 29.7% patients had abnormally higher total psychological scores, 23.3% patients had internalizing problems, 20% patients had externalizing problems, and 36.7% patients had attention and hyperactivity problems. Significant positive correlations were present between the total psychological, internalization, hyperactivity, attention scores, and a long duration of therapy, as well as a high seizure frequency in uncontrolled cases. The higher total psychological, hyperactivity, inattention scores, learning problems, younger age at onset of seizures, longer duration of illness, multiplicity, and longer duration of antiepileptic drugs used were found to be strong predictors for higher risk and associated significantly with poor cognitive verbal and performance (P<0.05).

Conclusion Poor cognitive function and psychological problems are common in uncontrolled epileptic patients with generalized seizures compared with controlled epileptic patients with partial seizures. Short seizure-free periods, early disease onset, longer duration of illness, multiplicity and longer duration of antiepileptic drugs, poor seizure control, and missing school are associated with educational underachievement, and cognitive and psychological dysfunction in children with epilepsy. The association of cognitive impairment with psychological problems in children with epilepsy suggests a need for a comprehensive clinical and educational support program for them and their families in the community.

Departments of aChild Health

bPublic and Environmental Health, Medical Division, National Research Center, Cairo, Egypt

Correspondence to Inas R. El-Alameey, PhD, Department of Child Health, Medical Research Division, National Research Centre, Elbohouth Street, PO Box 2311, Dokki, Giza, Egypt Tel:+20 100 185 8378; +202 3370931; e-mail: inasno@hotmail.com

Received August 28, 2013

Accepted October 31, 2013

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Introduction

Epilepsy is one of the most common chronic neurological disorders in children. It is characterized by a sudden transient disturbance of brain function, manifested by involuntary motor, sensory, autonomic, or psychic phenomena, alone or in combination, often accompanied by alternation or loss of consciousness that have a significant impact on the normal cognitive process and behavior of the affected children with epilepsy. The prevalence of epilepsy at school age is between 4 and 7 per 1000 children. Many of the neuropsychological functions including cognition, attention, and behavior can be affected significantly in children with epilepsy for multiple reasons 1. These impairments can significantly affect the learning process and behavior, with resultant academic underachievement. Several studies have linked epilepsy with missing school, dropping out of school, and poor academic performance 2. Factors that predispose children with epilepsy to poor school performance include the age of the child, age at onset of seizures, seizure frequency, type of seizure, intelligence quotient (IQ) of the child, poor memory, inattention, low self-esteem, and psychosocial and sociodemographic factors 3. Children with epilepsy have also been reported to have neuropsychological maladjustment including depression and anxiety, rejection, fear, hyperactivity, and aggression. They are more isolated, less likely to be involved in an intimate relationship, and less likely to complete postsecondary education. Their rates of unemployment are more than double the national average and they are more likely to work in unskilled jobs 4. There are a variety of reasons to expect an increased risk of behavioral problems in children with epilepsy. It has been associated with limited social interaction, recurrent hospitalization, dependency on drugs, and constant threat of death. The additional stress created for the parents and children by epilepsy and by the reactions of others is frequently manifested as emotional and behavioral problems 5. Epilepsy and its treatment can have deleterious cognitive and behavioral consequences. Antiepileptic drugs work by decreasing neuronal irritability, which may also result in the nondesired side effect of decreased neuropsychological function. In addition to cognitive side effects, antiepilepsy drugs (AEDs) may be associated with behavioral effects that may range from irritability and hyperactivity to positive psychotropic effects on mood 6. Therefore, the objectives of this study were to assess the extent of comorbidities of cognitive, attention, and psychological problems, comparing the relationship between different types of seizures and these neuropsychological problems, and to identify risk factors including the effect of antiepileptic drugs on cognition and behavior that may be associated with the probability of development of these problems among children with epilepsy in Egypt.

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Patients and methods

Patients

The present study included 30 patients out of 100 patients with epilepsy on the basis of the inclusion criteria. The inclusion criteria for selection included controlled and uncontrolled epileptic patients with current age between 6 and 14 years and with regular use of AEDs of first-generation drugs (valproate) as monotherapy or second (particularly, levetiracetam, lamotrigine, topiramate)-generation drugs as polytherapy for more than 2 years, and serum levels within the referenced therapeutic range. Exclusion criteria included children with associated mental retardation (IQ<70) on the basis of the Arabic version of the Wechsler Intelligence Scale for Children – Revised (WISC-R), cerebral palsy, and metabolic conditions other than epilepsy. The study was carried out in the outpatient Neuropsychological and Behavior modification Clinic, at the National Research Center, Egypt, during their regular follow-up over a period of 1 year (from 1st April, 2012 to 31st March, 2013). Epilepsy was defined as the separate occurrence of two or more unprovoked seizures, not diagnosed as neonatal or febrile seizures. The diagnosis of epilepsy in the children was made on the basis of history and the electroencephalographic (EEG) findings as all the children had been subjected to EEG. Seizure types and epilepsy disorders in these patients were based on the International classification of epileptic seizures of the League against Epilepsy (1993) 7. Seizures were categorized as generalized and focal localization-related. On the basis of the etiology, epilepsy was categorized into idiopathic and remote symptomatic. In idiopathic epilepsy, no nervous system (brain or spinal cord) abnormalities, other than the seizures, can be identified on either an EEG or neuroimaging studies (MRI). Remote symptomatic epilepsy shows no immediate cause for the seizure, but there is a previous brain injury (e.g. major head trauma, meningitis, and stroke) that is an established risk factor for seizures. According to the degree of control on AED(s), patients are divided into controlled if there are no seizures for at least 1 year and uncontrolled if there is a decrease in the frequency or a change in the nature of seizures from a severe to a mild presentation. In our study, epileptic patients were divided into two subgroups according to EEG findings: 15 patients in group I with generalized tonic–clonic seizures and 15 patients in group II with partial seizures. Their ages ranged between 6 and 14 years, mean age 9.4±2.6 years and male to female ratio 2 : 1. Thirty apparently healthy children with no chronic illness matched for age, sex, and social class were studied as a control group. They were selected from the outpatients clinic at the National Research Center. They were attending the clinic for follow-up. Written informed consent was obtained from the parents of the children.

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Methods

Assessments

Clinical assessment of history

All patients and controls were subjected to a detailed assessment of history including age at testing, sex, residence, parental consanguineous marriage, parental education, and chronic parental medical illness. All patients were subjected to a detailed assessment of history including the presence of prenatal, perinatal and postnatal insults, history of fever before the attacks, family history of epilepsy, developmental history, learning problems, or other medical illnesses. Information on school attendance (regularity of attendance at school) and academic performance of the patients and the controls was obtained from their parents. The potential risk factors for poor cognition and behavior were evaluated medically, including a detailed description of the epilepsy severity variables including age at onset of seizures, type of epilepsy, duration of seizures, duration, number (monotherapy vs. polytherapy), type of antiepileptic drugs, and the degree of control on treatment.

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Neurological assessment

A full neurological examination was performed to determine associated neuroimpairments. Conventional EEG, awake and sleep records, was performed for all patients, using a Nihon Kohden machine (from China), with scalp electrodes placed according to the international 10–20 system with bipolar and referential montages, and neuroimaging CT-brain or MRI-brain was performed for all patients.

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Anthropometric assessment

Height (in cm) was measured to the nearest 0.5 cm on a Holtain portable anthropometer (from India) and weight (in kg) was determined to the nearest 0.1 kg on a Seca scale balance (from India) with the patient dressed in minimum clothes and no shoes. BMI was calculated as weight (kg) divided by height (m) squared. Each measurement was taken as the mean of three consecutive readings following the recommendations of the International Biological program. BMI and growth percentiles were calculated using CDC-2000 reference values 8.

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Intellectual assessment

Cognitive abilities were assessed by the administration of the Arabic version of the WISC-R 9,10. It is the most widely used scale to assess the intelligence of children aged between 6 and 16 years, and it takes around 1.5 h. It provides scores for verbal performance and a full-scale IQ score. Its subtests include different types of tasks, allowing the observation of the child’s strengths and weaknesses. Results from IQ tests help guide diagnosis, treatment, and educational planning. The average or normal IQ for children ranges from 90 to 110. In addition to its uses in intelligence assessment, the WISC-R is used in neuropsychological evaluation, specifically with respect to brain dysfunction. Large differences in verbal and performance intelligence may indicate specific types of brain damage. The WISC-R is also used as part of the diagnostic criteria for specific learning disabilities. The test may also serve to better evaluate children with attention deficit/hyperactivity disorder and other behavior disorders. This questionnaire was administered in Arabic to assess the patient’s memory and general knowledge (information), comprehension, mental balance and recall (arithmetic), and attention/concentration (digit span). The child’s verbal IQ score is derived from scores on six of the subtests: information, digit span, vocabulary, arithmetic, comprehension, and similarities. The child’s performance IQ is derived from scores on the remaining seven subtests: picture completion, picture arrangement, block design, object assembly, coding, mazes, and symbol search.

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Psychological assessment: Pediatric Symptoms Checklist-17

Children’s behavior was evaluated using a parent-completed pediatric symptom checklist (PSC) 11. Psychological evaluation of patients was carried out using the PSC. The Pediatric Symptom Checklist-17 (PSC-17) is a psychosocial screen designed to facilitate the recognition of hyperactivity, attention, emotional, conduct, and social problems, relational difficulties with peers, anxiety/depression, and aggressive behavior so that appropriate interventions can be initiated as early as possible. The PSC-17 consists of 17 items that are rated as ‘Never’, ‘Sometimes’, or ‘Often’ present. A value of 0 is assigned to ‘Never’, 1 to ‘Sometimes’, and 2 to ‘Often’. The total score is calculated by adding together the score for each of the 17 items. Items that are left blank are simply ignored (i.e. score equals 0). If four or more items are left blank, the questionnaire is considered invalid. A PSC-17 score of 15 or higher suggests the presence of significant behavioral or emotional problems. To determine what kinds of mental health problems are present, the three-factor scores on the PSC are determined. The PSC-17 Internalization Subscale (cutoff 5 or more items) includes Feels sad and unhappy, Feels hopeless, Is down on self, Seems to be having less fun, and Worries a lot. The PSC-17 Attention Subscale (Cutoff 7 or more items) includes Fidgety, Unable to sit still, Daydreams too much, Has trouble concentrating, Acts as if driven by a motor, and Distracted easily. The PSC-17 Externalizing Subscale (Cutoff 7 or more items) includes Refuses to share, Does not understand other people’s feelings, Fights with other children, Blames others for his/her troubles, Does not listen to rules, Teases others, and Takes things that do not belong to him/her contains 17 questions. Both Wechsler’s Intelligence Scale and the PSC-17 were used for epileptic children and matched control groups.

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Statistical analysis

Data were analyzed using the statistical package for the social sciences (SPSS), version 20 computer program (SPSS, Inc., Delaware, USA). Data were presented as frequencies (%), means, and SDs. The χ2-test was used for comparison of categorical data. The independent-sample Mann–Whitney test was used for comparison of numerical data. Bivariate correlations were analyzed using Pearson’s correlation coefficients (r) to assess for associations between PSC-17 scores and some demographic, clinical, anthropometric, and seizures’ variables related to AEDs (dose, duration of treatment, and number of utilized AEDs). Univariate analysis of each covariate (item by item) was carried out to determine the factors associated with the probability of poor educational verbal and performance in children with epilepsy. The odds ratio was calculated as a measure of association between the different risk factors and epilepsy at a 95% confidence limit. A P-value of less than 0.05 was considered statistically significant in all statistical tests in this study.

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Results

Sociodemographic and clinical characteristics

Table 1 shows a comparison between some important sociodemographic and clinical characteristics among the patient and control groups studied. Of 30 patients aged 6–14 years, there were 20 males (60.7%) and 10 females (33.3%), with a male to female ratio of 2 : 1 and a significant sex distribution (P<0.05). Majority of them, 70% (21/30), were from an urban area. Positive consanguineous marriage among the parents was found in 13 patients of 30 (43.3%). A positive maternal history of chronic diseases was present in six patients (20%); diabetes and hypertension were present in four cases, breast carcinoma was present in only one case, and systemic lupus complicated by renal impairment was present in one case. There was no significant difference in place of residence, parental consanguinity, maternal medical illness, and mothers’ and fathers’ education among the patient subgroups, and the patients studied versus the control groups. A positive history of chronic medical illnesses in children with epilepsy was detected in eight patients (26.7%); six patients (20%) (five males and only one female) had generalized seizures and two female patients (6.7%) had partial seizures. Two male patients (6.7%) had hemophilia, two patients (6.7%) had bronchial asthma, neurofibromatosis was present in only one male patient, tuberous sclerosis in one male patient, rheumatic heart disease in one female patient, and one female patient had severe error of refraction. A positive history of developmental delay was present in three patients (10%). Thirteen patients of 30 (43.3%) had normal learning, whereas 17 patients (56.7%) showed profound limitation in school work; of these, four patients (13.3%) had to drop out of school on account of severe epilepsy. Learning problems and developmental delay in milestones were more common in patients with generalized seizures in group I compared with patients with partial seizures in group II, with significant differences (P<0.05) between the patient subgroups and highly statistically significant differences between patients and controls (P<0.001). The number of children with chronic medical illness associated with epilepsy who had generalized seizures was significantly higher among the patients studied compared with the control groups as well as between patient subgroups (P<0.05).

Table 1

Table 1

Table 2 shows a comparison of cognitive and psychological variables between the group of epileptic patients with other medical diseases and the group of epileptic patients with no other medical diseases. There was no statistically significant difference between the two groups.

Table 2

Table 2

Table 3 shows a comparison of epilepsy-related variables and types of seizures of the patient group studied. Highly significant differences were found between patient subgroups in age at onset of seizures, duration of therapy, number of antiepileptic drugs, seizure frequency per year, and types of epilepsy.

Table 3

Table 3

Table 4 shows anthropometric measurements of the patients studied and the control group. The patients’ age ranged between 6 and 14 years, mean 9.4±2.6 years. The mean weight for age percentile was highly significantly lower in patients compared with the control groups (41.12±31.45 and 61.23±10.24, P<0.001).The mean height for age percentile was highly significantly lower in patients compared with the control groups (29.73±24.49 and 58.69±7.89, P<0.001), whereas the mean weight for height and BMI as well as height and weight for age percentiles were insignificantly lower in patients who had generalized seizures in group I compared with those patients who had partial seizures in group II (P>0.05).

Table 4

Table 4

Table 5 shows the cognitive and psychological variables of the patients studied and the control groups. In terms of cognition, the mean cognitive verbal IQ scores were highly significantly lower in patients with generalized seizures compared with those patients with partial seizures (85.60±11.43 and 98.13±9.79, P<0.001), and highly significantly lower scores were obtained in patients versus control groups (91.87±12.24 and 98.07±6.49, P<0.001). Also, the mean cognitive performance IQ scores were highly significantly lower in patients with generalized seizures compared with patients with partial seizures (76.33±14.81 and 89.6±11.34, P<0.001), and highly statistically significantly lower scores were found in patients versus control groups (86.17±9.7 and 95.67±3.41, P<0.001). In terms of psychological illness, the mean hyperactivity/attention and total psychological scores were statistically significantly higher in patients with generalized seizures compared with patients with partial seizures (P<0.05) and there were highly significant differences between the patients studied and the control group (P<0.001). The mean internalization (depression) score was statistically significantly higher among the patients studied versus the control groups, and there were no significant differences between the patient subgroups. Figure 1 shows the cognitive and psychological variables of the patients studied.

Table 5

Table 5

Figure 1

Figure 1

Table 6 shows the correlation between psychological variables and some characteristics of the patients’ disease, growth, and demography. Significant positive correlations were present between total psychological (r=0.737, P<0.001), internalization (r=0.375, P<0.01), hyperactivity, attention disorders (r=0.501, P<0.001), and duration of therapy. Also, significant positive correlations were present between total psychological (r=0.605, P<0.001), internalization (r=0.430, P<0.01), hyperactivity, attention disorders (r=0.737, P<0.001), and seizure frequency. In terms of externalization disorder, there was a significant positive correlation between externalization disorder, weight for age, and height for age percentiles. However, there was a negative correlation between externalization and total number of family members in the household, as well as between internalization and number of children in household. No correlation was present between abnormal total psychological scores and multiplicity of antiepileptic drugs used.

Table 6

Table 6

The univariate analyses for predictors of development of poor cognitive verbal and performance in children with epilepsy are presented in Table 7. High total psychological, internalization (depression), externalization (socialization and adjustment), hyperactivity, inattention scores, learning problems, sex, younger age at onset of seizures, longer duration of illness, multiplicity, and longer duration of antiepileptic drugs were strong predictors for higher risk and associated significantly with poor cognitive verbal and performance IQ. There was no significant association of parents’ education with poor cognitive verbal and performance IQ.

Table 7

Table 7

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Discussion

This is the first study to assess the extent of comorbidities of cognitive and psychological problems among children with epilepsy in Egypt, comparing the relationship between different types of seizures and these neuropsychological problems, and identifying risk factors that may be associated with these problems. Of 30 patients aged 6–14 years, mean 9.4±2.6 years, there were 20 males (60.7%) and 10 females (33.3%), with a male to female ratio of 2 : 1 and a significant sex distribution (P<0.05). This is in agreement with the findings reported by Shinnar and Pellock 12, who found that the frequency rate was higher for males (63.6%) compared with females (36.4%), with a male to female ratio of 1.9 : 1.

In our study, ∼20% of the fathers and 80% of the mothers of the patients studied were illiterate, and at least 10% of the fathers and 6.7% of the mothers discontinued education, 46.7% of the fathers and 10% of the mothers had high school education, and 23.3% of the fathers and 3.3% of the mothers were highly educated. We found no significant association of poor cognitive verbal and performance with parental education of the patients studied (P>0.05). Singh et al.5 found a significant association with fathers’ education but not with mother’s education in patients and consider this a coincidental finding.

In our present study, a positive history of chronic medical illnesses in children with epilepsy was found in eight patients (26.7%); six patients (20%) (five males and only one female) had generalized seizures and two female patients (6.7%) had partial seizures, and no statistically significant difference was found between complicated epileptic patients with other chronic medical diseases, and uncomplicated epileptic patients (P>0.05). This means that both cognitive and psychological problems are not affected by the presence of other chronic medical diseases in epileptic patients. This is in agreement with the finding reported by Okeniyi et al.13.

In our present study, additional neurological deficits were present in two male patients who had generalized intractable seizures, associated with learning disability in maths and written expression with attention problems and low average verbal and performance IQ scores. One of them was diagnosed with tuberous sclerosis and the other was diagnosed with neurofibromatosis, and he had additional externalizing problems in the form of aggression. Payne et al.14, found that neurofibromatosis type I is a genetic neurobehavioral disorder manifesting physical, intellectual, emotional and behavioral problems. Learning disabilities are present in at least 50% of individuals with neurofibromatosis type I. Tuberous sclerosis complex is a multisystem disorder in which neurological problems cause cognitive impairment 15.

In our study, hematological problems were present in two male patients, and both had generalized uncontrolled intractable seizures and learning disability in maths and written expression, with low average verbal and performance intelligent scores and problems with attention. One of them was 7.6 years old on regular factor I therapy every month as he had hemophilia with factor one deficiency (Glanzeman disease) and hepatitis C; he also had additional externalizing problems in the form of aggression toward other children and his mother was described as being overprotective. The other child was 9 years old on regular cryotherapy every month and had evidence of internalization problems in the form of depression as his mother had breast carcinoma. Miles et al.16, reported that hemophilia can lead to neuropsychological and academic deficits in children as they cannot play or compete in sports in the same way as their peers. Parents may worry about their children and may become overprotective.

In our present study, according to weight and height for age percentiles, 23.3% of the epileptic patients were below the fifth percentile and 76.7% of the epileptic patients had normal weight and height for age percentiles. The mean weight and height for age percentile were highly significantly lower in patients compared with the control groups (P<0.001). This is in agreement with the findings reported by Guo et al.17, who found that 25% of the epileptic patients had a body weight and height for age percentiles below the fifth percentile.

Children with epilepsy are known to be susceptible to educational problems and resultant academic underachievement. Psychiatric comorbidity is a recognized additional burden associated with chronic epilepsy. Several studies indicate that childhood epilepsy is a high risk factor for poor psychological outcomes including depression, anxiety, behavioral problems, and learning difficulties 18.

Learning difficulties in this study as in other reports 19,20 may also be attributed to a combination of factors acting individually or synergistically, which include the deleterious effects of antiepileptic drugs and repeated seizures on the developing brain, and psychological problems. About 43.3% of our patients had normal learning, whereas 56.7% of patients showed profound limitation in school work; of these, four patients 13.3% had to drop out of school on account of severe epilepsy. Learning problems, irregularity in school attendance, and developmental delays in milestones were significantly more common in children with generalized seizures compared with those with partial seizures (P<0.05), as well as in patients versus control groups (P<0.001).

Children with epilepsy are more likely to have cognitive deficits than healthy children, with approximately one in four children with epilepsy showing subnormal cognitive function 21. Our study indicated impairment in school activity and learning skills in 56.7% patients, nearly half of the patients evaluated, with approximately one in two children with epilepsy showing subnormal cognitive function. Patients with epilepsy had lower cognitive performance intelligent (IQ) scores than cognitive verbal intelligent (IQ) scores. The mean cognitive verbal and performance IQ scores were statistically significantly lower in children with generalized seizures compared with those with partial seizures (P<0.05), and there were highly statistically significant differences between patients and control groups (P<0.001). A low average verbal IQ score was present in 43.3% of patients, whereas a low average performance IQ score was present in 56.7% of patients. This is in agreement with the study conducted by Vinayan et al.22, who found that 54% of children with benign epilepsy had educational problems, whereas Austin et al.23 found that 44% of children with epilepsy had educational underachievement.

In our present study, children with epilepsy had significantly more psychological problems compared with the control groups (P<0.05); 29.7% of the epileptic patients had abnormal total psychological scores, 23.3% had internalizing problems, 20% had externalizing problems, and 36.7% had attention and hyperactivity problems. The percentage of epileptic patients according to psychological illness in our study was higher as compared with the study conducted by Osborne et al.24 who reported that attention deficit and hyperactivity disorder was found in 17% of children and depression in 12% of children, whereas 10% of children had conduct disorder. The higher psychological scores in our patients could be because of disease severity and longer treatment, and family stress may be responsible for the poor psychological outcome in children with epilepsy.

In this study, comorbidities of cognitive and psychiatric disorders were present in 39% of children. This percentage is in agreement with a population-based study by Hedderick and Buchhalter 25, who found comorbid psychiatric disorders in 40% of children with epilepsy.

In our present study, age at onset of seizures ranged from 1 to 10 years, 76.7% of the epileptic patients were older than 2 years and 23.3% patients were aged 2 years or younger. About 53.3% of the epileptic patients were receiving only one antiepileptic therapy in the form of valoproate and 14 patients (46.7%) were receiving polytherapy (three to five AEDs). Twelve controlled epileptic patients (40%) had been seizure free for 1 year and 18 uncontrolled epileptic patients (60%) had 2–10 fits per year. Highly significant differences were found in children with generalized seizures compared with those with partial seizures (P<0.05) for age at onset of seizures, etiology of epilepsy, duration of therapy, number of antiepileptic drugs (monotherapy vs. polytherapy), and seizure frequency per year (P<0.001). Similar results were reported by Jayashree et al.26.

Recurrent epileptic fits play a role in school absence and will thus affect their school progress. About 56.7% of our epileptic patients missed school frequently because of their illness. Some stayed at home to avoid being mocked by schoolmates should they have a seizure at school, whereas others had frequent seizures that prevented them from going to school regularly. Similarly, Ojinnaka et al.27 reported that about 57% of the epileptic patients missed school frequently because of their illness. In addition, some of them had stopped going to school, either on the advice of their teachers or the school authority, or because of a parental decision; 18.2% of the patients had in fact been expelled from school because of recurrent seizures.

In the present study, univariate analysis was carried out for significant variables to identify significant predictors of development of poor cognitive verbal and performance in children with epilepsy. Boys with epilepsy had more educational problems as compared with girls (P<0.05). Higher total psychological, hyperactivity, inattention, externalization, and internalization (depression) scores, learning problems, younger age at onset of seizures, higher frequency of seizures, longer duration of illness, multiplicity, and longer duration of antiepileptic drugs utilized were found to be strong predictors for higher risk and significantly associated with poor cognitive verbal and performance IQ (P<0.05). However, there was no significant association of parents’ education and poor cognitive, verbal, and performance scores (P>0.05). Similar results were reported by Jayashree et al.26, and Vasconcellos et al.28, who found that the mean cognitive IQ score was significantly lower for patients with onset of epilepsy at 5 years of age (74.0±21.5) versus that in patients with onset later in life (87±18.8; P=0.005). A Nigerian study found a significant association between duration of illness and educational performance (P=0.014) 29. In another study in India, it was found that duration of illness of more than 3 years was associated with severe cognitive impairment 30. Poor seizure control is often associated with polytherapy and this may be a risk factor for poor educational performance 31.

Cognitive and psychological dysfunction-related antiepileptic drug therapy in children is a critical concern, given the potential negative side effects of treatment on school performance and learning 32. Sachdeo 33 suggests that monotherapy is associated with fewer potential problems than polytherapy. The emergence of monotherapy as a mainstay treatment resulted from studies that showed the advantages and effectiveness of a single AED in controlling seizures. Our study provides support for the notion that AEDs can impair verbal and performance in cognition, mood, and behavior. Duration of drug intake and the number of AEDs utilized are the main confounding variables as in our study. Univariate analysis showed a highly significant association between poor verbal cognitive function (P<0.05), poor performance IQ (P<0.001), and multiplicity of AEDs. A highly significant association was found between long duration of therapy of more than 2 years and poor educational verbal (P<0.001), as well as poor educational performance IQ (P<0.001).

In our study, significant positive correlations were present between total psychological (r=0.737, P<0.001), internalization (r=0.375, P<0.01), hyperactivity, attention disorders (r=0.501, P<0.001), and duration of therapy. Also, significant positive correlations were present between total psychological (r=0.605, P<0.001), internalization (r=0.430, P<0.01), hyperactivity, attention disorders (r=0.737, P<0.001), and high seizure frequency in uncontrolled cases. In terms of externalization disorder, a significant positive correlation was found between externalization disorder, weight for age, and height for age percentiles. However, significant negative correlations were present between total psychological, hyperactivity, attention disorders, and age at onset of seizures, which indicates that psychological, hyperactivity, and attention disorders are correlated with younger age at onset of seizures, and these are in agreement with the study by Holdsworth and Whitmore 34 and Oseni and Adewuya 35.

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Conclusion

Poor cognitive function and psychological problems are common in uncontrolled epileptic patients with generalized seizures compared with controlled epileptic patients with partial seizures. Short seizure-free periods, early disease onset, longer duration of illness, multiplicity and longer duration of antiepileptic drugs, poor seizure control, and missing school are associated with educational underachievement, and cognitive and psychological dysfunction in children with epilepsy. Our study serves to present an overview of our current understanding of the risks of antiepileptic drugs use for both cognitive and behavioral side effects. Therefore, periodic cognitive and psychological assessment, counseling, and comprehensive clinical and educational support programs must be provided to improve psychosocial adjustment in children with epilepsy and their families in the community.

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Recommendation

The management of epilepsy in children should focus not only on seizure control and medication evaluation, but should also involve the evaluation and treatment of possible comorbid psychopathological illness. Medical school training needs to be more focused on the psychiatric disorders that affect children with epilepsy rather than on the specific issues associated with the medical illness itself.

Table

Table

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Acknowledgements

Conflicts of interest

There are no conflicts of interest.

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