Evaluation of neural damage in Duchenne muscular dystrophy patients.

The presence of non-progressive cognitive impairment is recognized as a common feature in a substantial proportion of patients with Duchenne muscular dystrophy (DMD). Concurrently, the amyloid beta peptide (Aß42) protein has been associated with changes in memory and cognitive functions. Also, it has been shown that different subtypes of neural stem/progenitor cells (CD 34, CD 45, nestin) are involved in the innate repair of plasticity mechanisms by the injured brain, in which Nerve Growth Factor (NGF) acts as chemotactic agents to recruit such cells. Accordingly, the present study investigated levels of CD 34, CD 45, nestin and NGF in an attempt to investigate makers of neural regeneration in DMD. Neural damage was assayed in terms of Aß42. Results showed that Aß42 (21.9 ± 6.7 vs. 12.13 ± 4.5) was significantly increased among DMD patients compared to controls. NGF (165.8 ± 72 vs. 89.8 ± 35.9) and mononuclear cells expressing nestin (18.9 ± 6 vs. 9 ± 4), CD 45 (64 ± 5.4 vs. 53.3 ± 5.2) and CD34 (75 ± 6.2 vs. 60 ± 4.8) were significantly increased among DMD patients compared to controls. In conclusion cognitive function decline in DMD patients is associated with increased levels of Aß42, which is suggested to be the cause of brain damage in such patients. The significant increase plasma NFG and in the number of mononuclear cells bearing CD34, CD45 and nestin indicates that regeneration is an ongoing process in these patients. However, this regeneration cannot counterbalance the damage induced by dystrophine mutation and increased Aß42.

The clinical outcome of adjuvant therapy with black seed oil on intractable paediatric seizures: a pilot study.

AIM: To evaluate the effect of black seed oil, as add-on treatment to antiepileptic drugs (AEDs), on seizure frequency and severity as well as oxidative stress in intractable epilepsy patients. METHODS: A prospective, randomised, single-blinded, controlled, crossover pilot study. Five healthy children were included as controls. Thirty intractable epileptic children were randomly assigned to either Group I or II. Group I received placebo for four weeks, followed by a two-week washout period, and subsequently black seed oil for four weeks. Group II received the same intervention but in the reverse order. All patients received AEDs throughout the study period. Prior to allocation, all patients underwent a neurological assessment and evaluation of oxidative stress markers; total antioxidant capacity (TAC) and malondialehyde (MDA). Patients were assessed at Weeks 4 and 10 for oxidative stress markers and seizure frequency and severity. RESULTS: At baseline, both groups (I, II) had significantly lower serum TAC levels relative to healthy controls (p=0.007), while MDA levels were unchanged. After the 4-week period of black seed oil administration, there was no significant difference between the two groups with regards to seizure frequency, severity, or oxidative stress markers (TAC and MDA; p>0.05). Eight patients had >50% reduction in seizure frequency/severity after black seed oil versus placebo. CONCLUSION: Children with intractable epilepsy show evidence of oxidative stress. Administration of 40-80 mg/kg/day of black seed oil as add-on therapy did not alter either oxidative stress markers or seizure frequency or severity in intractable epileptic patients.

Pediatric vs. adult stroke: comparative study in a tertiary referral hospital, Cairo, Egypt.

Background: Even though stroke is rare in children, it is associated with serious or life-threatening consequences. Despite its rarity, the occurrence of stroke in children has age-related differences in risk factors, etiopathogenesis, and clinical presentations. Unlike adults, who have arteriosclerosis as the major cause of stroke, risk factors for pediatric strokes are multiple, including cardiac disorders, infection, prothrombotic disorders, moyamoya disease, moyamoya syndrome, and others. The goal of the current study was to compare the characteristics, clinical features, etiology, subtypes, and workup of pediatric and adult strokes. Methods: This was a hospital-based observational study conducted on 222 participants. All patients underwent a full clinical and neurological examination, full laboratory study, cardiac evaluation, and neuroimaging; CT scan, MRI, MRA, MRV, carotid duplex, and transcranial Doppler (TCD). Ischemic stroke (IS) etiology was classified according to the Trial of Org 10172 in Acute Stroke Treatment (TOAST) criteria, the "proposed classification for subtypes of arterial ischemic stroke in children," and the Oxfordshire Community Stroke Project (OCSP). Stroke severity was determined by the National Institutes of Health Stroke Scale (NIHSS) and PedNIHSS on admission. Results: The proportion of pediatric ischemic strokes in the current study was 63.4 percent, while hemorrhagic strokes were 36.5%. The majority of the adult patients had ischemic strokes (84.1%), while hemorrhagic strokes were noted in 15.8% of the patients. According to the original TOAST classification, in the current study, the etiology of pediatric IS was other determined causes in 63.6%, undetermined etiology in 27.2%, and cardioembolic in 9.0%. For the adult group, the major stroke subtypes were large artery disease, small vessel disease, cardioembolic, other determined causes, and undetermined etiology at 49.6%, 28.6%, 6.9%, 0.6%, and 12.5%, respectively. Conclusions: There is a greater etiological role for non-atherosclerotic arteriopathies, coagulopathies, and hematological disorders in pediatric stroke, while adults have more atherothrombotic causes. The co-existence of multiple risk factors in pediatric ischemic stroke is noticed. Thrombophilia evaluation is helpful in every case of childhood stroke. Children who have had a stroke should undergo vascular imaging as soon as possible. Imaging modalities include TCD and Doppler ultrasound, CT, MRI, MRA, and MRV, and cerebral angiography.

Reproductive hormonal changes and catamenial pattern in adolescent females with epilepsy.

PURPOSE: We aimed to evaluate the effect of epilepsy on the reproductive hormones levels among female patients, and to investigate the frequency of catamenial pattern of seizures. METHODS: A total of 42 female patients with epilepsy and 21 healthy females (control group) were included. Subjects were at least 2 years postmenarche with regular cycles. Symptoms of premenstrual syndrome (PMS) were assessed using calendar of premenstrual experience scoring. Patients were evaluated for catamenial pattern of seizures. Levels of FSH, LH, estradiol (E), and progesterone (P) were assessed for all subjects in the three phases of the cycles. Pelvi-abdominal ultrasound was performed near time of ovulation, to follow up size of mature follicle. RESULTS: Symptoms of PMS were not different in patients and controls, or in patients with and those without catamenial tendency. In both perimenstrual (M) and midluteal phases, FSH and P levels were lower and E/P ratio higher in patients group. There was a catamenial pattern of seizures in 31% of patients (53.8% M C(1); 46.15% inadequate luteal phase C(3)pattern). Patients with C(3)pattern showed lower P levels in the midluteal phase compared to patients with noncatamenial pattern, to those with C(1)pattern or to controls. Patients with C(1)pattern had lower P levels than controls in the M phase. CONCLUSION: There was evident disruption in the reproductive hormones in female patients with epilepsy with lower FSH and P levels and higher E/P ratio. A total of 31% of patients showed catamenial pattern of seizures (C(1)and C(3)patterns) that was significantly related to P withdrawal.

Frequency of inborn errors of metabolism screening for children with unexplained acute encephalopathy at an emergency department.

OBJECTIVE: Our study aimed to estimate the frequency of inborn errors of metabolism (IEMs) in patients presenting with acute encephalopathy-like picture at an emergency department (ED). SUBJECTS AND METHODS: Our study was a prospective observational study conducted on 30 patients admitted to the pediatric ED with unexplained acute encephalopathy. The study included 30 children with an age ranging from 1 month to 5 years. All patients were subjected to full history taking, thorough clinical examination, and laboratory investigations including serum ammonia, serum lactate, arterial blood gases, tandem mass spectroscopy, organic acid of urine, cerebrospinal fluid examination to exclude central nervous system infection plus the routine laboratory tests (kidney functions, liver functions, random blood glucose, complete blood picture), and brain imaging computed tomography and/or magnetic resonance imaging brain. RESULTS: Thirty children presented with acute encephalopathy at the ED. All were screened for suspected IEMs. Ten (33.3%) of them was positive in the initial screening test. There were four (13.3%) patients with possible mitochondrial diseases, four (13.3%) patients with possible organic acidemia, one (3.3%) patient with possible urea cycle defect, and one (3.3%) patient with possible nonketotic hyperglycinemia. CONCLUSION: Any case of unexplained acute encephalopathy presenting to the ED should be investigated for suspected IEM, especially in high-risk families, as early interventions will lead to improved outcome.

Cardiac autonomic balance in children with epilepsy: value of antiepileptic drugs.

BACKGROUND: Dysfunction of the autonomous nervous system causes arrhythmias and, although previous studies have investigated the effects of epilepsy on the autonomic control of the heart, there is still uncertainty about whether imbalance of sympathetic, vagal, or both systems occurs in epilepsy as well as the effect of anticonvulsants on the autonomic system. AIM: To evaluate cardiac autonomic status in children with epilepsy on antiepileptic drugs. PATIENTS AND METHODS: Sixty patients with epilepsy were recruited from the Outpatient Neurology Clinic at Ain Shams University and were divided into the following groups: group I, drug naive; and group II, patients with epilepsy on regular antiepileptic drugs. The second group was further subdivided into the following groups: group IIa, received monotherapy; and group IIb, received polytherapy. Forty age- and sex-matched healthy children served as controls. Included patients underwent videorecorded electroencephalograph, Holter electrocardiogram (EKG) for time and frequency domains of heart rate variability, and standard EKG recording for QTc, QTd. RESULTS: Mean values of all time domain, total power, and high-frequency power were significantly lower, whereas low-frequency and low-frequency/high-frequency power, QTc. and QTd were significantly higher in group I compared with group II and in patients compared with controls. No significant difference was found between patients on different antiepileptic drug regimens regarding heart rate variability values. A significant negative correlation was found between Chalfont severity score and 50% of difference between adjacent, normal RR intervals in patient groups. CONCLUSIONS: Children with epilepsy have cardiac autonomic dysfunction evident in their heart rate variability assessment. Patients on antiepileptic drugs had better autonomic balance than those not on antiepileptic drugs. Holter and EKG follow-up should be considered for early detection in those at high-risk cardiac complications.

Role of plasma amino acids and urinary organic acids in diagnosis of mitochondrial diseases in children.

BACKGROUND: Diagnostic difficulty in mitochondrial diseases (MD) results not only from the wide spectrum of symptoms and signs but also from the absence of a reliable screening or diagnostic biomarker. AIM: To investigate the likelihood of MD in patients with symptoms and signs impressive of MD through quantitative measurement of plasma amino acids, and urinary organic acids. METHODS: Twenty patients with symptoms and signs suggestive of MD were further evaluated by quantitative plasma amino acids and urinary organic acids assay and neuroimaging. RESULTS: Plasma amino acid results revealed elevation of alanine in 11, glycine in five, and proline in two patients. Abnormal urinary organic acid analysis was present in six patients; increased urinary lactate (20%), dicarboxylicaciduria (15%), and urinary ketone bodies (10%). Upon enrollment our patients scored as possible MD according to the MD scoring system. At the end of the study, five patients still scored as possible MD, eight patients as probable MD, and seven patients as definite MD. All patients with definite MD had elevated serum lactate. In three patients, elevated urinary lactate was the only abnormality. Alanine was elevated in all patients with definite MD, whereas proline was elevated in only one. Magnetic resonance imaging of the brain showed atrophic changes in one patient and bilateral basal ganglia hyperintensity in another. CONCLUSION: Urinary organic acids and quantitative plasma amino acids can help in the diagnosis of MD, especially when the economic burden and absence of specialized centers limits the diagnosis.

Metabolic effects of honey in type 1 diabetes mellitus: a randomized crossover pilot study.

The aim of this study was to evaluate the metabolic effects of 12-week honey consumption on patients suffering from type 1 diabetes mellitus (DM). This was a randomized crossover clinical trial done in the National Institute for Diabetes and Endocrinology, Cairo, Egypt. Twenty patients of both sexes aged 4-18 years with type 1 DM and HbA1C<10% participated in the study. They were randomized into two equal groups (intervention to control and control to intervention). The dietary intervention was 12-week honey consumption in a dose of 0.5 mL/kg body weight per day. The main outcome measures were serum glucose, lipids, and C-peptide, and anthropometric measurements. None of participants were lost in follow-up. The intervention resulted in significant decreases in subscapular skin fold thickness (SSFT; P=.002), fasting serum glucose (FSG; P=.001), total cholesterol (P=.0001), serum triglycerides (TG; P=.0001), and low-density lipoprotein (P=.0009), and significant increases in fasting C-peptide (FCP; P=.0004) and 2-h postprandial C-peptide (PCP; P=.002). As possible long-term effects of honey after its withdrawal, statistically significant reductions in midarm circumference (P=.000), triceps skin fold thickness (P=.006), SSFT (P=.003), FSG (P=.005), 2-h postprandial serum glucose (P=.000), TG (P=.003), and HbA1C (P=.043), and significant increases in FCP (P=.002) and PCP (P=.003) were observed. This small clinical trial suggests that long-term consumption of honey might have positive effects on the metabolic derangements of type 1 DM.

Inherited thrombophilia in pediatric ischemic stroke: an Egyptian study.

Pediatric stroke is relatively uncommon, with often subtle clinical presentations. Numerous predisposing risk factors can be both inherited and acquired, including cardiac disease, vascular abnormalities, infectious diseases, collagen tissue diseases, inborn errors of metabolism, anticardiolipin antibody, lupus anticoagulant, deficiencies of protein C, protein S, antithrombin, or plasminogen, and prothrombotic mutations. We explored risk factors, clinical features, and neuroimaging among Egyptian children with ischemic stroke, and estimated the prevalence of inherited thrombophilia. We included 20 children with ischemic stroke, recruited from the Pediatric Neurology Outpatient Clinic (Ain Shams University). Basic clinical evaluations for stroke and genotyping for factor V 1691 G-A (factor V Leiden), prothrombin 20210 G-A mutations, and methylenetetrahydrofolate reductase 677 C-T polymorphisms were performed using real-time polymerase chain reaction, with fluorescent melting curve detection analysis. Ten patients (50%) manifested methylenetetrahydrofolate reductase polymorphisms (six homozygotes and four heterozygotes). Heterozygous factor V Leiden was present in five (25%), whereas prothrombin mutation was present in only one (5%). Five patients (25%) manifested combined prothrombotic abnormalities. Thirteen demonstrated evidence of inherited thrombophilic disorder; 25% manifested more than one mutation. For appropriate risk assessment, even in the presence of overt acquired thrombotic risk factors, physicians should request complete thrombophilia screening for patients with stroke.

Correlates of parental stress and psychopathology in pediatric epilepsy.

BACKGROUND: Chronic conditions like epilepsy in a child can affect his/her entire family. The failure of the family members to adapt adequately to the unique demands of this childhood chronic illness can be considered as an important risk factor for development of psychopathology. OBJECTIVES: The objectives of this study were to study the profile of parenting stress in parents of children with epilepsy and its correlates; and, to examine the correlates of psychopathology in these children. MATERIAL AND METHODS: Twenty three epileptic children and their families were subjected to Parenting Stress Index (PSI), Scores for indices such as The Children's Depression Inventory (CDI), Benton Visual Retention test, Spence anxiety scale for children, The Child Behavior Checklist (CBCL) and Wechsler Intelligence Scale for Children were calculated. RESULTS: Mean verbal and performance IQ score was 94, while the mean total IQ score was 95. Mean scores for all Wechsler IQ Scores as well as Benton Visual retention test were within the average range. Means for total internalizing CBCL t scores (M, Mean=70; Standard Deviation, SD=4.4), total externalizing CBCL t scores (M=60, SD=9.6), and total behavior problems CBCL t scores (M=67, SD=5.2) were above the standard cut off levels of 65 for clinical behavioral problems. Mean score on CDI was 42 ± 2. Scores of the PSI equal to or higher than 85(th) percentile were considered pathologically high. CONCLUSION: The results of our study indicated that pediatric patients with epilepsy, specifically with intractable cases, are correlated with high levels of parental stress.