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.

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 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.

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.

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.