Gephyrin and CYP2C9 Genetic Polymorphisms in Patients with Pharmacoresistant Epilepsy.

PURPOSE: Gephyrin (GPHN) is an essential protein in the regulation of inhibitory postsynaptic density and polymorphism in the corresponding gene may have a role in the development of pharmacoresistant epilepsy (PRE). For the first time, we aimed to evaluate the association of rs928553T/C variants with PRE susceptibility. Moreover, we have analyzed the genetic polymorphism affecting CYP2C9 "rs12782374G/A" in the same population to detect the effect of SNP on the drug-metabolizing ability of patients with PRE. PATIENTS AND METHODS: This case-control study enrolled 100 patients (group A) and 100 healthy, age and sex-matched controls, unrelated to patients (group B). TaqMan™ assays using real-time PCR were run for genotyping of rs928553T/C and rs12782374G/A in all participants. RESULTS: GPHN T>C polymorphism revealed significant risk association with occurrence of PRE using dominant, recessive and codominant models as follows: TT vs (TC+CC): OR 0.23, 95%CI: 0.13-0.43, P<0.001. In addition, (TT+TC vs CC): OR 0.38, 95%CI: 0.18-0.77, P<0.001. Also, T vs C (OR 0.34, 95%CI: 0.22-0.51, P=<0.001). Similarly, CYP2C9 G>A polymorphism showed a significant increased risk of PRE (GG vs (GA+AA): OR 0.11, 95%CI: 0.05-0.23, P<0.001). Furthermore, (GG+GA vs AA): OR 0.18, 95%CI: 0.084-0.39, P<0.001. Also, G vs A (OR 0.24, 95%CI: 0.15-0.366, P=<0.001). CONCLUSION: Mutation of both GPHN (rs928553) and CYP2C9 (rs1278237) genes may be implicated as a genetic mediators of resistance in patients with PRE.

Construction and Standardization of Dementia Arabic Scale.

PURPOSE: Validated diagnostic scales for dementia in Arabic are still scarce. The aim of this study is to construct a standardized dementia scale for dementia diagnosis among the Arabic-speaking population. PATIENTS AND METHODS: Construction of the Dementia Arabic Scale (DAS) was done, followed by evaluation of content validity. A pilot study was done to ascertain feasibility and language clarity used in the scale. Patients diagnosed to have major neurocognitive disorder according to DSM-V criteria and control group were subjected to DAS, mini-mental state examination (MMSE) and Cognitive Abilities Screening Instrument (CASI). Finally, standardization of the scale and estimation of cutoff point, sensitivity, specificity, positive predictive value and negative predictive value of the newly constructed scale (DAS) were done. RESULTS: There is significant correlation between DAS and both MMSE and CASI on Pearson's correlation study. The internal consistency of the DAS scale was good, with Cronbach's alpha correlation coefficient of 0.88. At cut-off ≤95 for literate, and ≤68 for illiterate, the sensitivity of the DAS scale was 100%, 87% for literate and illiterate, respectively, while specificity was 84%, 96% respectively, with an area under the receiver operating characteristic curve of (AUC) 0.96. CONCLUSION: The DAS scale is an acceptable, reliable and valid scale for the diagnosis of dementia in Arabic-speaking countries.

Prevalence of childhood and adolescence epilepsy in Upper Egypt (desert areas).

BACKGROUND: A high prevalence of epilepsy in children is frequently found in developing countries. OBJECTIVE: This study aimed to determine the prevalence and clinical pattern of childhood and adolescence epilepsy in Upper Egypt. METHODS: This is a door-to-door study conducted on all inhabitants < 18 years in Al Kharga district and Al Qusier city (36,195 subjects). The study was conducted through two stages; every stage consisted of two phases (screening and diagnostic). RESULTS: Lifetime prevalence of childhood and adolescence epilepsy (children < 18 years) in Upper Egypt was 9.7/1000, with higher prevalence among children < 12 years (10.8/1000) than adolescents (7.2/1000). The age-specific prevalence was highest in early childhood (12.01/1000) and least at adolescence (7.2/1000). More than half of the patients (59.4%) had idiopathic epilepsy. The most frequent etiology for structural/metabolic epilepsy was perinatal complications, particularly in infancy, followed by central nervous system (CNS) infections, in childhood, and post-traumatic epilepsy in adolescence. Partial seizures were more frequent in infancy, while generalized seizures were more frequent in late childhood and adolescence. Generalized tonic-clonic seizures (GTCS) were the most frequent type of seizures. CONCLUSION: Prevalence of childhood and adolescence epilepsy in Upper Egypt was not so much different from other developing countries. Idiopathic epilepsy was more prevalent than structural/metabolic cases. Perinatal complications, CNS infections, and head injury were the most frequent etiologies, and generalized tonic-clonic seizures were the most frequent seizure type.

Spectrum of epilepsy - prevalence, impact, and treatment gap: an epidemiological study from Al-Quseir, Egypt.

BACKGROUND: Epidemiology continues to be an important research tool in the study of epilepsy and related disorders, providing a better understanding of the frequency, causes, and natural history of the disorder. OBJECTIVE: To estimate the prevalence of epilepsy in Al-Quseir, Red Sea Governorate, Egypt, and its magnitude of treatment gap. METHODS: The study was part of a door-to-door study, including every door, to screen all inhabitants in Al-Quseir (33,818 inhabitants) by three specialists of neurology and 15 female social workers (for demographic data collection) using a standardized screening questionnaire. All suspected cases were subjected to detailed history, clinical examination, and electroencephalogram. Neuroimaging studies and estimation of serum drug level were done in select cases if needed. RESULTS: The study revealed that the lifetime prevalence rate of epilepsy in Al-Quseir is 5.5/1,000, with the highest peak during early childhood, while that of active epilepsy is 3.3/1,000 population. The annual incidence rate is 48/100,000, and the age-specific incidence rate has a U-shaped pattern with two peaks of incidence in early infancy and elderly life. Localization-related epilepsy is the most frequently encountered type (58.8%). The treatment gap of epilepsy in Al-Quseir is 83.8%. CONCLUSION: The lifetime prevalence of epilepsy in Al-Quseir city, Red Sea Governorate, was 5.5/1000.

Prevalence of multiple sclerosis in Al Quseir city, Red Sea Governorate, Egypt.

BACKGROUND: Multiple sclerosis (MS) is a chronic and disabling disorder with considerable social effects and economic sequelae. It is one of the major causes of disability in young adults. OBJECTIVES: This study aimed at detecting the prevalence of MS among the population of Al Quseir city. METHODS: This study is a part of door-to-door survey of major neurological disorders that was conducted in Al Quseir city, Red Sea Governorate, Egypt. The sample size was 33,285 persons. The youngest patient was 17 years old. The number of people at and above 17 years of age was 21,827. They were screened by three neurologists. Then, the positive cases were subjected to meticulous clinical evaluation by three staff members of Department of Neurology, Assiut University Hospital, Egypt. Essential investigations were done. RESULTS: A total of three cases of MS were diagnosed with an age-specific prevalence ≥17 years of 13.7/100,000.

Epidemiology and clinical presentation of stroke in Upper Egypt (desert area).

BACKGROUND: Stroke is a common cause of morbidity and mortality worldwide. Four out of five strokes occur in the low- and middle-income countries. This study aims to find lifetime prevalence of stroke in Upper Egypt and to identify clinical presentations and possible risk factors of stroke in this population. METHODS: This is a door-to-door (every door) study conducted on all inhabitants in Al Kharga district (representative of western desert) and Al Quseir city (representative of eastern desert). The study was conducted in two stages, and every stage consisted of three phases (screening, diagnostic, and investigatory). RESULTS: The total lifetime prevalence of stroke was 8.5/1,000 in the population aged 20 years and more. It increased with advancing age and was higher among males than females among all age groups except in the childbearing period (20 years to <40 years of age). Lifetime prevalence of ischemic stroke (7.2/1,000) was higher than hemorrhagic stroke (1.1/1,000). Hemiparesis and hemiplegia were the commonest presentation of stroke. Headache, vomiting, and vertigo were found to be significantly more common accompaniments of hemorrhagic stroke. The most common risk factor was hypertension, followed by hyperlipidemia and diabetes mellitus. CONCLUSION: The total lifetime prevalence of stroke in the population aged 20 years and more in Upper Egypt (desert area) lies within the range that is recorded in developing countries. Clinical presentation and risk factors are similar to those recorded from developing and developed countries.

Epidemiology of non-fatal cerebrovascular stroke and transient ischemic attacks in Al Quseir, Egypt.

BACKGROUND AND PURPOSE: Stroke is a medical emergency that can cause permanent neurological damage, complications, and disability. We aim to determine the epidemiology of non-fatal cerebrovascular stroke (CVS) and transient ischemic attacks (TIAs) in Al Quseir City, Red Sea, Egypt. METHODS: The total population (n=33,285) was screened through a door to door study by three specialists of neurology and 15 female social workers (for demographic data collection). All suspected stroke patients were subjected to a full clinical examination, computerized tomography (CT) and/or magnetic resonance imaging (MRI) of their brain, blood sugar, lipogram, serum uric acid, complete blood cells, blood urea, and serum creatinine, as well as evaluated by Barthel Index and Scandinavian Stroke Scale. Carotid doppler, echocardiography, and thyroid functions were done for selected cases. RESULTS: CVS was recorded among 130 patients out of 19,848 subjects aged 20 years and more, yielding a total prevalence of 6.55/1,000 population. From June 1, 2010 to May 31, 2011, 36 patients were recorded to have stroke within 1-year, yielding an incidence rate of 1.81/1,000. Prevalence and incidence rates were higher among males than females, and both indices increased steadily with advancing age to reach the highest prevalence (37.02/1,000) and incidence rate (9.5/1,000) among aged persons 60 years and more. CONCLUSION: The prevalence of non-fatal stroke in Al Quseir city (6.55/1,000) was at the lower range of that recorded in developing countries (5-10/1,000) and slightly higher than that recorded in industrialized countries (5/1,000 population). Ischemic stroke is the most common type of stroke. The prevalence of TIAs was 0.15/1,000.

Prevalence of trigeminal neuralgia in Al-Quseir city (Red sea Governorate), Egypt.

BACKGROUND: Trigeminal neuralgia or tic douloureux is sometimes described as the most excruciating pain known to humanity. OBJECTIVES: To estimate the prevalence of trigeminal neuralgia among the population of Al-Quseir city. METHODS: This study forms a part of door to door survey of major neurological disorders in Al-Quseir city, Red sea governorate, Egypt. The total population (33,285 persons) were screened through door to door (every door) by three specialists of Neurology and fifteen female social workers. Then, positive cases were subjected to clinical and neurological examination by other three staff members of neurology. Cases were identified as suffering from trigeminal neuralgia according to the diagnostic criteria of the International headache society (IHS). RESULTS: We identified 4 female patients out of 13,541 persons (aged 30 years and more) suffering from trigeminal neuralgia with age specific prevalence rate of 29.5/100,000. Co-morbid depression and hypertension were observed among the affected persons.

Epidemiology of uncontrolled epilepsy in the Al-Kharga District, New Valley, Egypt.

BACKGROUND: Despite advances in treating epilepsy, uncontrolled epilepsy continues to be a major clinical problem. Therefore, this work aimed to study the epidemiology of uncontrolled epilepsy in Al-Kharga District, New Valley. METHODS: This study was carried out in 3 stages via door-to-door screening of the total population (62,583 persons). All suspected cases of epilepsy were subjected to case ascertainment, conventional ElectroEncephaloGraphy (EEG), and the Stanford-Binet Intelligence Scale. Patients who had been receiving suitable anti-epileptic drugs (AEDs) over the previous 6 months and were having active seizures were considered uncontrolled, according to Ohtsuka et al.(23) The patients underwent serum AED level estimation, video EEG monitoring, and brain MRIs. Fifty age- and gender-matched patients with controlled epilepsy were chosen for statistical analysis and compared with true intractable patients. RESULTS: A total of 437 patients with epilepsy were identified, 30.7% of whom (n=134/437) were uncontrolled, with a prevalence of 2.1/1000. A total of 52.2% of uncontrolled patients (n=70/134) were inappropriately treated, while 47.8% (n=64/134) were compliant with appropriate treatments. Video monitoring EEG of compliant uncontrolled patients demonstrated that 78.1% patients (n=50/64) had definite epilepsy, while 21.9% (n=14/64) had psychogenic non-epileptic seizures (PNES). A logistic regression analysis revealed that status epilepticus, focal seizures, and mixed seizure types were risk factors for intractability.

Impact of nocturnal sleep deprivation on declarative memory retrieval in students at an orphanage: a psychoneuroradiological study.

BACKGROUND AND METHODS: This study investigated the effects of sleep deprivation on total and partial (early and late) declarative memory and activation in the areas of the brain involved in these activities. The study included two experiments. Experiment 1 included 40 male residents of an orphanage aged 16-19 years, who were divided into four groups (n = 10 each) and subjected to total sleep deprivation, normal sleep, early-night sleep deprivation, or late-night sleep deprivation. Experiment 2 included eight students from the same institution who were divided into the same four groups (n = 2) as in experiment 1. Declarative memory was tested using lists of associated word pairs in both experiments, and activation of the relevant brain regions was measured before and after retrieval by single-photon emission computed tomography for subjects in experiment 2 only. RESULTS: Students subjected to normal sleep had significantly higher scores for declarative memory retrieval than those subjected to total sleep deprivation (P = 0.002), early-night sleep deprivation (P = 0.005), or late-night sleep deprivation (P = 0.02). The left temporal lobe showed the highest rate of activity during memory retrieval after normal sleep, whereas the frontal, parietal, and right temporal lobes were more active after sleep deprivation. CONCLUSION: Both slow wave sleep and rapid eye movement sleep play an active role in consolidation of declarative memory, which in turn allows memory traces to be actively reprocessed and strengthened during sleep, leading to improved performance in memory recall.

Prevalence of Parkinson's disease and other types of Parkinsonism in Al Kharga district, Egypt.

Parkinson's disease (PD) is a common neurodegenerative disorder in older people. The prevalence of PD varies among ethnic and geographic groups around the world. In this study, we aimed to estimate the prevalence of PD and other types of Parkinsonism in persons aged ≥40 years in the Al Kharga district of Egypt. The study was conducted on the total population of Al Kharga district (62,583 persons) between 2005 and 2009 and involved three neurology specialists and 15 female social workers undertaking a door-to-door survey. Suspected cases of Parkinsonism were subjected to meticulous clinical and neurological examination by three neurology staff members from Assiut University hospital who carried out their examinations separately. Of the total population surveyed, 15,482 persons were aged ≥40 years and 49 of these were identified as having Parkinsonism (prevalence: 316.50 per 100,000 people [95% confidence interval {CI} 240.21-404.98]). Of the 49, 33 fulfilled the diagnostic criteria for PD, giving a prevalence rate of 213.15/100,000 (95% CI 150.51-285.80) while 14 fulfilled those for vascular Parkinsonism, with a prevalence rate of 90.43/100,000 (95% CI 49.60-137.78). Postencephalitic and unspecified Parkinsonism each had a prevalence rate of 6.46/100,000. The prevalence of Parkinsonism was found to increase steadily with age, and the prevalence of all types of Parkinsonism was statistically higher in rural compared with urban communities, with no significant difference between men and women.

Epidemiology of epilepsy in New Valley Governorate, Al Kharga District, Egypt.

UNLABELLED: Epilepsy is one of the serious neurological disorders which results in profound morbidity and mortality. Although epilepsy has no geographical boundaries, understanding cultural, social, and economic backgrounds is a very important step for interpretation of its epidemiological characteristics. This work aims to study the epidemiological profile of epilepsy in New Valley Governorate and to estimate its magnitude of treatment gap. It was conducted in a door to door survey, including all inhabitants (62,583 subjects), by 3 neurologists to detect any suspected case of focal or generalized epilepsy. All suspected cases were subjected to detailed history, clinical examination, EEG, neuroimaging studies, and estimation of serum drug level if needed. The study revealed that life time prevalence of epilepsy in Al Kharga district is 6.76/1000, with highest peak during early child hood, while that of active epilepsy is 4.99/1000 population. The annual incidence rate is 43.14/100,000, and age specific incidence rate has a U-shaped pattern with two peaks of incidence at early infancy and elderly. Localization-related epilepsy is the most frequently encountered type (53.7%). However the treatment gap of epilepsy in New Valley is similar to that in developing countries (61.5%). CONCLUSION: Prevalence and Incidence Rate of epilepsy in New Valley are similar to that in industrialized countries.

Epidemiology of cerebral palsy in El-Kharga District-New Valley (Egypt).

Cerebral palsy (CP) is the most frequent cause of motor handicap among children. The present door to door (every door) study was conducted in El-Kharga District-New Valley to estimate the epidemiology of CP among children. Each child was subjected to complete medical and neurological examination to detect cases with CP. These diseased children were subjected to meticulous neurological and medical assessment, brain MRI, EEG and Stanford Binet (4th edition). It was found that 52 out of 25,540 children had CP yielding prevalence rate of 2.04/1000 (95% CI: 1.48-2.59) of living births. Mean age of children with CP, was 7.17±4.38years. The order of frequency of different subtypes of CP was as follows, 65.4% had spastic type, 26.9% mixed type and 3.8% for each ataxic and dyskinetic types of CP. The frequency of risk factors of CP in our study is prenatal complications (cyanosis, preterm, jaundice, birth weight and obstructed labor of mothers), first baby, similar condition and recurrent abortions.

Epidemiology of major neurological disorders project in Al Kharga district, New Valley, Egypt.

BACKGROUND/METHODS: A door-to-door ('every door') study was carried out to assess the incidence and prevalence rates of epilepsy, stroke, Bell's palsy and cerebral palsy, as well as the prevalence of dementia, extrapyramidal syndromes, muscle and neuromuscular disorders, cerebellar ataxia and primary nocturnal enuresis among the urban and rural populations of Al Kharga district, New Valley, Egypt. The study was carried out in 3 stages from June 1, 2005 to May 31, 2009. A door-to-door screening including every door was carried out using a standardized questionnaire, which was administered by 3 neurologists to all inhabitants (62,583) of Al Kharga district. The study was designed to assess the prevalence, incidence and risk factors of major neurological disorders in Al Kharga district and aimed to reduce the burden of these neurological disorders in the entire region. RESULTS/CONCLUSIONS: This study clarified that dementia, primary nocturnal enuresis, epilepsy, stroke and cerebral palsy are the most common neurological disorders. On the other hand, Bell's palsy, extrapyramidal syndromes, cerebellar ataxia, muscle dystrophies and myasthenia gravis are less common neurological disorders in Al Kharga district.

Door-to-door survey of major neurological disorders in Al Kharga District, New Valley, Egypt: methodological aspects.

Epidemiology of neurological disorders is still lacking in Egypt. The door-to-door method is the most suitable one to screen neurological disorders in our country. Over a 4-year period (June 1, 2005 to May 31, 2009), screening and examination had been carried out to ascertain the incidence and prevalence rate of epilepsy, stroke, cerebral palsy and Bell's palsy, as well as the prevalence of dementia, extrapyramidal syndromes, muscle and neuromuscular disorders, cerebellar ataxia and primary nocturnal enuresis among the urban and rural population of Al Kharga District, New Valley, Egypt. A total of 62,583 people were screened by 3 neurologists in a door-to-door manner, including every door, using a standardized Arabic questionnaire to detect any patient with a neurological disorder. This was a project study of neurological disorders including 3 stages: first stage (June 1, 2005 to May 31, 2006) for data collection, designing a standardized questionnaire and screening; second stage (June 1, 2006 to May 31, 2008) for case ascertainment, classification of neurological disorders and investigations, and third stage (June 1, 2007 to May 31, 2009) for data entry and statistical analysis. The results of this study revealed that the total prevalence rate of neurological disorders in Al Kharga District, New Valley was 2.4/100 with no significant difference among both sexes. The highest prevalence rate was recorded among elderly people (60+ years; 9.25%) and among children (≤18 years; 2.9%).

Study of urinary 6 beta-hydroxycortisol/cortisol ratio in spot urine sample as a biomarker of 3A4 enzyme activity in healthy and epileptic subjects of Egyptian population.

The ratio of urinary 6 beta-hydroxycortisol/cortisol (6 beta-OHC/FC) in morning spot urine samples collected from 8:00 a.m. to 12:00 p.m. was studied using ELIZA kits (Stabiligen) in a group of healthy adult Egyptians (control group) of both sex (n=65, age range: 16-48 years). The frequency distribution of urinary 6 beta-OHC/FC ratio was widely distributed among subjects with higher values in males in comparison to females. No bimodality in either sex was observed. Another group of adult epileptic patients (n=16) was studied for the influence of chronic carbamazepine antiepileptic drug administration on urinary 6 beta-OHC/FC ratio in spot urine samples. The induction property of carbamazepine on CYP3A4 was observed through significant increase (p=0.01) in 6 beta-OHC/FC ratio among epileptic patients in comparison with control subjects. In conclusion, the frequency distribution of urinary 6 beta-OHC/FC ratio among Egyptians shows sexual dimorphism. Also, measurement of urinary 6 beta-OHC/FC ratio provides a simple non-invasive method to monitor CYP3A4 enzyme induction during administration of carbamazepine antiepileptic drug.

Construction of an Arabic reading test for assessment of dyslexic children.

OBJECTIVE: Dyslexia is a specific language-based disorder of constitutional origin, characterized by difficulties in phonological processing. The Arabic language differs in many aspects from foreign languages and the few previously designed Arabic tests for assessment of dyslexia did not pay attention to phonological awareness problems. This necessitates the design of an Arabic test which could properly assign specific difficulties among Arabic reading dyslexic children, including phonological awareness as a major contributing factor for dyslexia. METHODS: The study was carried out in Assiut City, Egypt, during the period from September 1999 to the end of January 2001. The newly designed Arabic Reading Test (ART) in this work passed through many stages. Firstly, test construction by 11 Arabic teachers (specific judges). Secondly it was applied, in a pilot study, to 50 normal students (9-10 years old) to ascertain clarity of the test. Then test standardization was proven through application on a second sample (n=252 students), and third sample (n=58 dyslexics). RESULTS: The reliability of the ART was proven by the test-retest method (r=0.913, p<0.01). Validity was proven by judgment validity, internal consistency validity (ranged from 0.238 for auditory perception to 0.940 for phonological awareness and spelling), contrasted group validity, and criterion related validity (in relation to Schonell r=0.859, Awaad reading r=0.817, Awaad comprehension r=671, mid-term Arabic scores r=0.686). CONCLUSION: The ART was thus proven to be highly reliable, and valid for assessment of dyslexia among Arabic reading children. It has great value in predicting dyslexia even among preschool age Arabic speaking children, through assessment of their phonological awareness skills, and thus, remediation programs can be properly and early directed.