Brain-derived neurotrophic factor and neuroimaging in pediatric patients with sickle cell disease.

BACKGROUND: The risk of neurological complications is increased in children with sickle cell disease (SCD), such as silent cerebral infarction (SCI) and stroke. Brain-Derived Neurotrophic Factor (BDNF) is a nerve growth factor associated with elevated transcranial Doppler (TCD) velocities and increased risk of stroke in SCD patients. So, we assessed the BDNF level in children with SCD and its relation to neurological complication as silent stroke. METHODS: A comparative cross-sectional study was conducted on 40 patients with SCD, recruited from the Hematology Unit, Pediatric Department, Menoufia University Hospital, and 40 healthy children as controls. Laboratory investigations including BDNF were done. TCD was done for all patients and Magnetic Resonance Imaging (MRI) was done on high-risk patients. RESULTS: BDNF levels were significantly higher in children with SCD than in controls with a significant relation to TCD findings. There was a statistically significant diagnostic ability of BDNF in the prediction of SCD complications as its sensitivity was 89.5%, specificity (95% CI) was 80% with a cut-off point >0.69, AUC = 0.702, and p = 0.004). CONCLUSION: Serum BDNF levels were higher in sickle disease patients who had abnormal transcranial Doppler. BDNF had a significant diagnostic ability in the detection of SCD complications. IMPACT: Silent stroke is a very serious complication in children with sickle cell disease, so regular follow up should be every six months. BDNF is considered a potential biomarker for stroke risk prediction in patients unable to receive TCD.

Assessment of asymmetric dimethylarginine and homocysteine in epileptic children receiving antiepileptic drugs.

BACKGROUND: Epilepsy is a neurological disease that requires long-term antiepileptic drugs (AEDs). The old generation of AEDs may affect serum homocysteine and asymmetric dimethylarginine (ADMA) and disturb lipid levels. The aim of the study was to evaluate serum ADMA, homocysteine, lipid profile, and carotid intima-media thickness (CIMT) in epileptic children. METHODS: This study was implemented on 159 epileptic children who were subdivided into 3 subgroups, with 53 receiving sodium valproate, 53 receiving levetiracetam, and 53 receiving polytherapy, for over 6 months and 53 healthy children. RESULTS: Low-density lipoprotein, triglycerides, and cholesterol levels were increased in epileptic children (p < 0.001), which were higher in those receiving multidrug followed by a valproate receiver. While high-density lipoprotein was lower in those receiving multidrug more than those receiving valproate. ADMA and homocysteine levels increased in epileptic patients than in controls (p < 0.001). Higher ADMA was also observed in the multidrug receiver (5.78 ± 0.62), followed by the levetiracetam group (5.56 ± 0.61). Homocysteine levels were significantly higher in multidrug and valproate-treated children than those treated with levetiracetam. CIMT was significantly higher in multidrug and valproate-treated patients (p < 0.001). CONCLUSIONS: Long-term use of AEDs, especially old-generation polytherapy, can elevate lipid profiles, homocysteine, ADMA levels, and carotid intima-media thickness compared to the minimal effect of new AEDs. IMPACT: The long-term use of antiepileptic drugs, especially old-generation polytherapy, can increase lipid profiles, homocysteine levels, ADMA, and carotid intima thickness compared to the minimal effect of new antiepileptic generation. A routine follow-up of these markers and a lifestyle modification are recommended to avoid cerebrovascular events as much as possible.

MTHFR C677T Polymorphism, Plasma Homocysteine, and PDGF-AA Levels and Transcranial Doppler Velocity in Children With Sickle Cell Disease.

OBJECTIVE: To evaluate the effect of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on plasma homocysteine (tHcy) and platelet-derived growth factor (PDGF-AA) levels in children with sickle cell disease (SCD), and ascertain their role in predicting high transcranial doppler velocity (TCD). METHODS: We estimated MTHFRC677T gene poly-morphism, plasma tHyc and PDGF-AA in 44 SCD patients and 44 healthy children. RESULTS: The prevalence of mutant homozygous MTHFR (C677TT) in SCD was 13.6%. Significantly higher plasma tHcy was observed in mutant homozygous MTHFRC677TT patients. Significantly higher plasma tHcy and PDGF-AA levels were observed in SCD patients than in controls. Median (IQR) PDGF-AA levels were significantly higher in conditional and high-risk TCD patients as compared to low-riskTCD patients [325 (93.1-368) and 368 (111-480) vs 111 (56-201) pg/mL, respectively; P<0.001]. Mean (SD) tHcy levels were significantly higher in high-risk TCD children than low-risk TCD children (12.9 (2.7) vs 9.9 (2.5) µmol/L; P=0.006). The receiver operating characteristic revealed that the area under the curve (AUC) of PDGF-AA for high TCD velocity was 0.934 (95% CI 0.845-1.00; P<0.001) and tHcy had an AUC of 0.675 (95% CI 0.517-0.833; P=0.04). CONCLUSION: PDGF-AA and tHcy levels could be used as predictive markers for stroke in SCD children. MTHFR Polymorphism contributes to elevated tHcy levels.