Diffusion tensor imaging of vertebral bone marrow in children with Gaucher's disease type I and III: Pre- and post-therapy.

PURPOSE: To assess diffusion tensor imaging (DTI) of the vertebral bone marrow (BM) in children with Gaucher's disease (GD) types I and III before and after therapy. METHODS: Prospective study was conducted upon 25 children with GD type I (n = 17) and III (n = 8) and 13 age and sex-matched controls underwent DTI of vertebral BM. Mean diffusivity (MD) and fractional anisotropy (FA) of vertebral BM was calculated and correlated with genotyping, chitotriosidase, hemoglobin (HB) and, platelet count. RESULTS: There was a statistically significant difference in MD and FA of BM between patients and controls (P = 0.001 and 0.02). The area under the curve (AUC) of MD and FA used to differentiate untreated patients from controls was 0.902 and 0.68 with sensitivity, specificity, and, accuracy 92%, 84.6%, and, 89.5% respectively. There was a significant difference in MD and FA of BM between untreated and treated patients (P = 0.001 and 0.02). AUC of MD and FA used to differentiate untreated from treated patients was 0.93 and 0.649 with sensitivity, specificity, and accuracy of 92%, 80%, and 86% respectively. There was a significant difference in MD and FA (P = 0.03, 0.001 respectively) of BM in GD with homozygous L444P mutation (n = 9) and other mutations (n = 14). Chiotriptase, HB and platelet count of patients was correlated with MD (r = -0.36, 0.42, -0.41) and FA (r = -0.47, -0.37, -0.46) respectively. CONCLUSION: DTI of vertebral BM can help in diagnosis and monitoring patients with GD after therapy and correlated with genotyping, and hematological biomarkers of GD.

CYP2C9 (*2&*3) and CYP2C19 (*2&*3) polymorphisms among children with nonlesional epilepsy: a single-center study.

Cytochrome (CYP) P450 enzymes are responsible for metabolism of antiepileptic drugs (AEDs), and encoded by highly polymorphic genes. A case-control study was conducted in Mansoura University Children's Hospital, Egypt including 100 children with nonlesional epilepsy (50 AEDs responders and 50 resistant cases) and 50 healthy controls. All participants were investigated for frequencies of CYP2C9 (*2&*3) and CYP2C19 (*2&*3) genotypes and alleles using polymerase chain reaction. The current study reported higher frequencies of CYP2C9*2 (CT) genotype and (T) allele among responsive and resistant groups than controls (P < 0.001). Frequency of (TT) genotype was higher in resistant than responsive group (P = 0.02, OR 12, 95% CI 1.2-122.3). No significant differences were detected between responsive and resistant groups regarding CYP2C9*2 alleles (P = 0.2). CYP2C9*3 (AC) genotype was more frequent in controls than other groups (P < 0.001). No significant differences were detected between responsive and resistant groups regarding neither CYP2C9*3 genotypes nor alleles (P = 0.11 and 0.2, respectively). CYP2C19*2&*3 (GA) genotypes and (A) alleles were more frequent in responsive and resistant groups than controls (P < 0.001). No significant differences were detected between responsive and resistant groups regarding neither CYP2C19*2&*3 genotypes nor alleles (P = 0.21 and 0.89 for CYP2C19*2; P = 1 and 0.77 for CYP2C19*3). The CYP2C9*2 (TT) genotype, earlier seizure onset and higher seizures frequency were associated with higher risks of refractory epilepsy. We concluded that heterozygous genotypes of CYP2C9*2 and CYP2C19 (*2&*3) and mutant alleles of studied variants were more frequent among children with nonlesional epilepsy. CYP2C9*2 (TT) genotype increased refractory epilepsy susceptibility.

Relationship between electroencephalography and magnetic resonance imaging findings after hypoxic-ischemic encephalopathy at term.

Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality. Electroencephalography (EEG) and brain magnetic resonance imaging (MRI) are frequently performed in these infants, but the prognostic value of the combined use of EEG and MRI needs additional exploration. The purpose of this study was to investigate, in neonates with HIE, the role of early EEG and conventional MRI in the prediction of infants at risk for persistent encephalopathy at 18 months of age. Thirty-four term infants with HIE were enrolled in this prospective study. EEG was recorded within the first 72 hours after birth and a brain MRI scan was done between 1 and 4 weeks of age. Denver Developmental Screening Test II was performed at 6, 12, and 18 months of age. Three infants (9%) had mild HIE, 21 infants (62%) had moderate HIE, and 10 infants (29%) had severe HIE. The EEG background was normal, moderately, severely, and extremely discontinuous in eight (24%), three (9%), sixteen (47%), and seven (20%) neonates, respectively. EEG background activities correlated significantly with HIE severity (p = 0.0001). MRI findings significantly correlated with EEG background (p = 0.001). Normal MRI scans and minimal basal ganglia lesions were always associated with normal EEG background. Patients with severe basal ganglia and thalamic lesions in MRI (n = 2) had extreme discontinuous EEG background. For the prediction of poor outcomes, abnormal EEG background activity had a sensitivity (Sn) = 100%, a specificity (Sp) = 100%, positive predictive value (PPV) = 100%, and negative predictive value (NPV) = 100%, whereas values of abnormal MRI scans were Sn of 100%, Sp = 43%, PPV = 82%, and NPV=100%. EEG background activity is the best element to predict abnormal outcomes. Severe basal ganglia and thalamic injuries on MRI scans are associated with poor outcomes. Otherwise, MRI does not contribute to the prediction of outcomes at 18 months of age.

IL-1beta, IL-6 and TNF-alpha and outcomes of neonatal hypoxic ischemic encephalopathy.

The role of cytokines in the pathogenesis of brain injury and their relation to neurological outcomes of asphyxiated neonates is not fully defined. We hypothesize that interleukin-1 beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in cerebrospinal fluid (CSF) correlate with the severity of brain injury and can predict neurological deficits in infants who suffered from hypoxic ischemic encephalopathy (HIE). A prospective study was conducted on 24 term infants diagnosed with HIE and 13 controls. HIE was clinically classified into mild, moderate and severe according to Sarnat and Sarnat grading. Blood and CSF samples were obtained from all infants in the first 24h of life as part of routine investigations for suspected meningitis and/or sepsis. Neurological examination and Denver Developmental Screening Test II (DDST II) were performed at 6 and 12 months of life. IL-1beta, IL-6 and TNF-alpha were all significantly increased in HIE infants when compared to control. IL-1beta in the CSF correlated with the severity of HIE (r=0.61, P=0.001) more than IL-6 (r=0.45, P=0.004) or TNF-alpha (r=0.47, P=0.003). IL-1beta exhibited the highest CSF/serum ratio among the three studied cytokines suggesting its local release in the brain after the initial hypoxic injury. Abnormal neurological findings and/or abnormal DDST II at 6 and 12 months were best predicted by IL-1beta in the CSF (sensitivity=88% and specificity=80%). This study confirms the role of IL-1beta in the ongoing neuronal injury that occurs in the latent phase following the original HIE insult.