الفهرس 
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Abstract
Epilepsy is a common neurological disorder characterized by unprovoked seizures. It can be caused by genetic or environmental factors, with genetic abnormalities playing a significant role in the majority of cases. Imbalances in excitatory and inhibitory signals in the brain are thought to contribute to the development of epilepsy.
The brain-derived neurotrophic factor (BDNF) is a protein that promotes neuronal survival, growth, and synaptic plasticity. Dysregulation of BDNF signaling has been linked to various neurological disorders, including epilepsy. BDNF is abundant in the central nervous system, particularly in the cerebral cortex and hippocampi, and its disruption can negatively impact neuronal function.
A specific genetic variation in the BDNF gene, known as rs6265 or val66met, affects the production and release of BDNF. This polymorphism can influence the development and severity of epilepsy by altering the packaging and secretion of BDNF in the brain.
Understanding the role of genetic factors, such as the BDNF rs6265 polymorphism, in epilepsy can provide insights into its underlying mechanisms and potential therapeutic targets.
The aim of the current study was to investigate the association between the BDNF rs6265 polymorphism and susceptibility to epilepsy in Egyptian patients. Additionally, the study also aimed to compare serum BDNF and NOS concentration in children with epileptic seizures during interictal periods to healthy controls, in order to evaluate its potential as a diagnostic tool and assess its relationship with disease severity.
The study was conducted at the departments of Pediatrics and Medical Biochemistry, Sohag Faculty of Medicine. It was a case-control study involving 60 patients with epilepsy and 30 control subjects who were apparently healthy children of matched age and sex. The study period lasted from September 2021 until the completion of the study.
For the patients, inclusion criteria included being less than 15 years old and having experienced seizures within the past year. Exclusion criteria were set to exclude patients who were older than 15 years, those whose epilepsy was caused by head injuries, brain tumors, birth-related oxygen deprivation, or infections such as meningitis or encephalitis. Patients with insufficient medical records, unreliable seizure frequency, or developmental disorders such as Autism and Neurofibromatosis were also excluded from the study.
During the study, each patient underwent a comprehensive medical history review and clinical examination. Demographic data, including age, sex, weight, and height, were recorded for both the patients and the control group.
In the study, a blood sample of 5 mL was collected from each participant through venipuncture using an EDTA tube. After centrifugation, DNA extraction was performed on the collected blood samples. The extracted DNA was used for genotyping the BDNF gene using the Real-time polymerase chain reaction (PCR) method.
To analyze the BDNF and Nitric Oxide levels in the serum, a Sandwich enzyme-linked immunosorbent assay (ELISA) kits were used. This assay allowed for the quantification of BDNF and NOS concentration in the serum samples.
The study found several important findings. Firstly, there was no significant association between the BDNF rs6265 polymorphism and epilepsy susceptibility in the Egyptian patient population. This suggests that genetic variations in the BDNF gene may not contribute to the development of epilepsy.
Secondly, the study compared serum BDNF and NOS concentration between children with epileptic seizures during interictal periods and healthy controls. The results showed that serum BDNF concentration was altered in children with epilepsy, while serum NOS concentration was higher in epileptic children, indicating a potential role of BDNF and NOS in the pathophysiology of the disease. Furthermore, the study evaluated the utility of serum BDNF and NOS concentration as a diagnostic tool for epilepsy and found promising results, suggesting its potential as a biomarker for the disease.
Lastly, the study examined the relationship between serum BDNF and NOS concentration and disease severity in children with epilepsy. The findings indicated a significant association between serum BDNF and NOS concentration and disease severity, suggesting that BDNF and NOS may be involved in the progression and severity of epilepsy.
In summary, this study provides there is no significant evidence for an association between the BDNF rs6265 polymorphism and epilepsy susceptibility in Egyptian patients. It also highlights the potential of serum BDNF and NOS concentration as a diagnostic tool and its relationship with disease severity in children with epilepsy. These findings contribute to the understanding of the molecular mechanisms underlying epilepsy and may have implications for the development of targeted therapies and personalized treatment approaches.
CONCLUSION
In conclusion, the current study examined the relationship between serum BDNF and serum nitric oxide synthase levels in epileptic cases and control groups. The findings revealed that serum BDNF levels were significantly lower in the epileptic cases compared to the controls, while serum nitric oxide synthase levels were significantly higher in the epileptic cases. Additionally, there was a significant negative correlation observed between serum BDNF and serum nitric oxide synthase levels in the studied sample.
Furthermore, the study analyzed the genotyping distribution of the BDNF gene and found no significant difference between epileptic cases and controls. However, the homozygous group showed a significantly better response to medication compared to the heterozygous group.
The study also explored the predictors of treatment response and resistance in epileptic cases. The results indicated that both serum BDNF and serum nitric oxide synthase levels were significant predictors of response to treatment. Moreover, serum BDNF concentration was identified as a significant predictor of resistance to epileptic treatment, with a specific cutoff point and high sensitivity, specificity, and accuracy rates.
In comparison to other studies, the current findings align with some previous research that highlighted the role of BDNF in epilepsy and its association with treatment response. However, discrepancies exist in the literature regarding the impact of BDNF polymorphisms and its relationship with epilepsy severity and clinical outcomes.
Overall, this study is the first study to assess both NOS and BDNF in epilepsy, it provides valuable insights into the potential involvement of serum BDNF and serum nitric oxide synthase levels and their relevance as predictors of treatment response. Further research is warranted to elucidate the underlying mechanisms and validate these findings in larger cohorts.
Despite the significant findings and contributions of the current study, there are some limitations that should be acknowledged:
1. Sample size: The study may have had a relatively small sample size, which could limit the generalizability of the findings. A larger sample size would provide more robust results and improve the reliability of the conclusions.
2. Selection bias: The study’s participants were recruited from a specific population or healthcare setting, which might introduce selection bias. This could affect the representativeness of the sample and limit the generalizability of the results to a broader population.
3. Measurement variability: The measurement of serum BDNF and nitric oxide synthase levels may have inherent variability due to assay methods or laboratory procedures. Variations in sample handling, storage, and analysis could introduce measurement errors that might affect the accuracy and reliability of the results.
4. Generalizability: The findings of this study might be specific to the studied population or setting and may not be directly applicable to other populations or geographic regions. Further studies with diverse populations are needed to validate the results across different contexts.
5. Confounding factors: Case-control studies may be prone to confounding, where the observed association between the exposure (serum BDNF and nitric oxide synthase levels) and outcome (response to treatment) may be influenced by other variables that were not accounted for in the study design or analysis. Failure to control for confounding variables can lead to inaccurate or biased estimates of the true association.
6. Temporality: Case-control studies are retrospective in nature, meaning that the exposure and outcome are assessed simultaneously or after the occurrence of the outcome. This makes it challenging to establish a clear temporal relationship between the exposure and outcome, limiting the ability to determine causality.
It is important to consider these limitations when interpreting the findings of a case-control study and to recognize the need for further research, such as prospective cohort studies, to confirm the observed association and address these limitations.