Fetal brain disruption sequence versus fetal brain arrest: A distinct autosomal recessive developmental brain malformation phenotype.

The term fetal brain disruption sequence (FBDS) was coined to describe a number of sporadic conditions caused by numerous external disruptive events presenting with variable imaging findings. However, rare familial occurrences have been reported. We describe five patients (two sib pairs and one sporadic) with congenital severe microcephaly, seizures, and profound intellectual disability. Brain magnetic resonance imaging (MRI) revealed unique and uniform picture of underdeveloped cerebral hemispheres with increased extraxial CSF, abnormal gyral pattern (polymicrogyria-like lesions in two sibs and lissencephaly in the others), loss of white matter, dysplastic ventricles, hypogenesis of corpus callosum, and hypoplasia of the brainstem, but hypoplastic cerebellum in one. Fetal magnetic resonance imaging (FMRI) of two patients showed the same developmental brain malformations in utero. These imaging findings are in accordance with arrested brain development rather than disruption. Molecular analysis excluded mutations in potentially related genes such as NDE1, MKL2, OCLN, and JAM3. These unique clinical and imaging findings were described before among familial reports with FBDS. However, our patients represent a recognizable phenotype of developmental brain malformations, that is, apparently distinguishable from either familial microhydranencephaly or microlissencephaly that were collectively termed FBDS. Thus, the use of the umbrella term FBDS is no longer helpful. Accordingly, we propose the term fetal brain arrest to distinguish them from other familial patients diagnosed as FBDS. The presence of five affected patients from three unrelated consanguineous families suggests an autosomal-recessive mode of inheritance. The spectrum of fetal brain disruption sequence is reviewed.

Growth hormone levels in children and adolescents with epilepsy.

BACKGROUND: Patients with epilepsy often complain of symptoms that may be caused by disturbances in their hormonal balance. Disturbances in physical growth has been previously described. The aim of this study was to evaluate the effect of epilepsy and/or anti-epileptic drugs on the physical growth of patients with idiopathic epilepsy, as well as on the growth hormone (GH) and insulin growth factor-1 (IGF-1) status in those patients. METHODS: The study comprised 40 children and adolescents with idiopathic epilepsy on either valproate or carbamazepine. Anthropometric measurements [occipitofrontal circumference, weight, height, body mass index, span, and midarm circumference] were taken. Serum levels of GH before and after provocation with L-dopa and of IGF-1 were assessed. Results were compared to a matched control group. RESULTS: The height measurements were reduced in patients with epilepsy compared to the controls group. Though weight values were not significantly different, the body mass indices of the patients were significantly higher than controls, especially in patients on valproate therapy. Basal GH levels showed no significantly variation between patients and controls. However, post provocation GH and IGF-1 levels were significantly lower in patients. The type of epilepsy, disease duration, and the degree of seizure control had no significant effect on the studied parameters. In conclusion, physical growth seems to be affected in patients with epilepsy. This may be due to hormonal imbalance as evident by reduced post provocation GH levels and IGF-1 levels in the included group of patients.

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.

Rectal bleeding in Egyptian children.

AIM: In a prospective study to outline the aetiology of bleeding per rectum (BPR) in Egyptian infants and children, a subsidiary aim was to define some of the clinical characteristics of the different aetiologies. SUBJECTS AND METHODS: 194 children with BPR are described. The diagnostic work-up included laboratory investigations, radiological and endoscopic assessment, radio-isotope scanning, angiography and histopathological examination of mucosal biopsies, as appropriate. RESULTS: Ages ranged from 3 to 192 months with a mean (SD) of 49.8 (43.5). Infectious enterocolitis was the most common cause (37.1%). Others included colorectal polyps (21.1%), chronic colitis (16%) including inflammatory bowel diseases (5.2%), allergic colitis (2.6%), solitary rectal ulcer syndrome (1.5%) and non-specific colitis (6.7%). Intussusception and Meckel's diverticulae were the cause in 7.3% and 2.6%, respectively, while other aetiologies included vascular (6.2%), systemic (3.6%), local anal (3.1%) and upper gastro-intestinal causes (1.5%). In 1.5% of cases, the cause remained 'obscure'. CONCLUSION: In Egyptian children, infectious enterocolitis followed by colorectal polyps and chronic colitis are major causes of BPR.

Physical growth and endocrinal disorders during pubertal maturation in girls with epilepsy.

PURPOSE: This study investigated the effect of epilepsy and/or antiepileptic drugs (AEDs) on the physical growth, pubertal development, and androgenic status of girls with epilepsy between ages 8 and 18 years. METHODS: Sixty-six female patients with epilepsy, their mean ages 13.47 +/- 3.5 years, were included. Anthropometric measurements, staging of pubertal maturation, and clinical manifestations of hyperandrogenism were assessed, as well as measurement of serum levels of testosterone, dehydroepiandrosterone sulfate (DHEAS), sex hormone-binding globulin (SHBG), and free androgen index (FAI). Of the included patients, 44 had transabdominal ultrasonic examination of the ovaries and fasting serum insulin levels were measured. Forty healthy age-matched females served as a control group. RESULTS: Patients showed reduced mean height percentile compared with controls (z = 2.07; p = 0.04), which was negatively correlated with the duration of their epilepsy. Patients showed increased frequency of obesity, especially postpubertal girls taking valproate (VPA; 67%), who also showed higher insulin levels (t = 8.01; p = 0.0003). Patients showed increased frequency of clinical hyperandrogenemia in the different stages of puberty. High levels of testosterone and DHEAS were found in female patients with epilepsy, especially pubertal and postpubertal girls. Hyperandrogenism (clinical and/or laboratory) was most affected by the types of AEDs, with higher incidence in patients taking VPA compared with those taking enzyme-inducing AEDs (chi2= 9.16; p = 0.01). Eighteen percent of the patients were diagnosed as having polycystic ovary syndrome (PCOS). No difference was found in the types of seizures, degree of seizure control, type of AEDs, or insulin levels between patients with and those without PCOS. CONCLUSIONS: Longer duration of the disease has a negative impact on the stature of female patients with epilepsy. Postpubertal girls taking VPA are more liable to obesity, which is associated with increased incidence of hyperinsulinemia. Clinical and/or laboratory evidence of hyperandrogenism is seen at a high frequency in patients, especially with the use of VPA. Furthermore, female patients with epilepsy especially in the postpubertal stage of sexual maturation, have a high prevalence of PCOS, independent of the type of AED or the characteristics of the epilepsy disorder.

Physical and hormonal profile of male sexual development in epilepsy.

PURPOSE: This study was designed to investigate the effect of epilepsy and antiepileptic drugs (AEDs) on both the physical and hormonal aspects of the sexual development of male patients with epilepsy. METHODS: One hundred thirty male subjects with epilepsy, their age ranging between 8 and 18 years (mean, 14 +/- 2.9 years), entered the study; all were taking AEDs. Anthropometric measurements [height, weight, and body mass index (BMI)], testicular volume, penile length, and pubarche were assessed in the studied groups, as well as measurement of the levels of testosterone (T), free testosterone (FT), estradiol (E2), lutenizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL), and the results were compared with those of a control group. RESULTS: In this study, male patients older than 16 years were significantly shorter than their matched controls. The mean values of testicular volume and penile length were significantly lower in the patients in the different age subgroups, and the pubic hair staging (pubarche) was delayed in the patients older than 16 years. The mean values of total testosterone, estradiol, LH, and FSH serum levels were significantly higher, whereas the mean values of free testosterone, total-T/E2, total. T/LH, and FT/E2 ratios were lower in the patient subgroups compared with their age-matched controls. There were no significant changes in the mean basal PRL serum levels in the patients compared with the controls. The present study demonstrated a reduction in the testicular volume and penile length, significantly lower mean values of free testosterone and total-T/E2, and a higher mean value of E2 in the patients receiving polytherapy in the age subgroup older than 16 years compared with those on monotherapy; however, there was no demonstrable effect of seizure control or the duration of illness in any of the studied parameters. CONCLUSIONS: There is a delay in the sexual development of male patients with epilepsy in the different age subgroups, with endocrine changes in the form of increase in the total testosterone, but the free testosterone is lower, and an increase in estradiol, with lower T/LH levels. Patients receiving polytherapy, especially those older than 16 years, were more likely to have delayed gonadarch and disturbances in their hormonal profile.