Cerebral Palsy

OBJECTIVE: We sought to ascertain the risk of reduced fetal brain growth in cases of isolated congenital heart defect (CHD) based on microcephaly at birth. STUDY DESIGN: In a case-control study, head circumference in 401 newborns with isolated CHD was compared with 401 control subjects. Microcephaly was defined as head circumference less than third percentile. The rates of microcephaly in multiple different categories of major CHD were ascertained along with logistic regression analyses to determine the specific types of cardiac defects that were significantly associated with microcephaly. RESULTS: Isolated CHD in the fetus was associated with an increased risk of microcephaly as were tetralogy of Fallot, coarctation/aortic arch hypoplasia, and hypoplastic left ventricle syndrome. Tetralogy of Fallot odds ratio, 2.6; 95% confidence interval, 1.1-6.3; P < .04 and coarctation/aortic arch hypoplasia, odds ratio, 2.8; 95% confidence interval, 1.5-5.1; P < .001 were significant independent predictors of microcephaly. CONCLUSION: The finding of microcephaly at birth in nonsyndromic CHD provides strong evidence in support of intrauterine hypoxic central nervous system damage. Potential changes in prenatal management including aggressive antepartum surveillance and earlier delivery warrant urgent consideration.

The aim of this study was to investigate any structural-functional relationship between changes in white matter microstructure seen on diffusion tensor imaging and results of an executive function test in adolescents with very low birth weight (VLBW). Thirty-four VLBW adolescents were examined at 15 years of age. Executive function was assessed by the Wisconsin Card Sorting Test. Diffusion tensor imaging scans were performed at 1.5 T for calculation of individual fractional anisotropy maps. Through a voxel-wise regression analysis, correlations were found between the results on Wisconsin Card Sorting Test and fractional anisotropy values in the left cingulum and both inferior fronto-occipital fascicles. We speculate that impairments in executive function in VLBW children may be influenced by disturbed connectivity between posterior brain regions and the prefrontal cortex.

Aneugenic compounds are able to cause chromosome missegregation during mitosis which results in aneuploidy in cells that are able to survive. Aneuploidy is considered a key early condition in the progression from a normal cell into a cancerous cell. The possible toxicity of therapeutic lithium has raised concern because lithium salts are currently widely prescribed as an efficient treatment of manic-depressive disorders and numerous undesirable side effects of long-term treatment have been reported to date. We have observed a dose-dependent cytotoxic effect of both Li2CO3 and LiCl in AA8 CHO cells, while no genotoxic damage was detected. Mitotic abnormalities such as multipolar anaphases and lagging chromosomes leading to the presence of micronuclei in the next interphase were frequently observed after treatment with lithium salts. Thus, the effectiveness of both lithium salts to induce alterations in the normal segregation of chromosomes could be ascribed to interference with proteins involved in the organization and/or function of the mitotic apparatus.

Non-alcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection are major causes of liver disease frequently described in outpatient patients with glucose abnormalities. Hyperferritinemia, which suggests that iron overload plays a decisive role in the pathophysiology of insulin resistance and hyperglycemia, is a common finding in both disorders. However, the role of the hepatic iron deposition differs from one to the other. In NAFLD, a moderate liver iron accumulation has been observed and molecular mechanisms, including the downregulation of the liver iron exporter ferroportin-1, have been described. Iron overload will enhance intrahepatic oxidative stress that promotes hepatic fibrosis, interfere with insulin signalling at various levels and may hamper hepatic insulin extraction. Therefore, liver fibrosis, hyperglycemia and hyperinsulinemia will lead to increased levels of insulin resistance and the development of glucose abnormalities. Furthermore, iron depletion by phlebotomy removes liver iron content and reduces serum glucose and insulin resistance in NAFLD patients. Therefore, it seems that iron overload participates in those glucose abnormalities associated with NAFLD. Concerning chronic HCV infection, it has been classically assumed that iron overload contributes to insulin resistance associated with virus infection. However, recent evidence argues against the presence of iron overload in these patients and points to inflammation associated with diabetes as the main contributor to the elevated ferritin levels. Therefore, glucose abnormalities, and specially type 2 diabetes, should be taken into account when evaluating serum ferritin levels in patients with HCV infection. Copyright (c) 2009 John Wiley & Sons, Ltd.

OBJECTIVES: The aim of this pilot study was to explore possible ultrasound parameters for the early detection of alcohol-mediated fetal somatic and central nervous system (CNS) maldevelopment. Maternal alcohol ingestion during pregnancy may lead to fetal alcohol spectrum disorders (FASD), which encompass a broad range of structural abnormalities including growth impairment, specific craniofacial features and CNS abnormalities. Early detection of fetuses at risk of FASD would support earlier interventions. METHODS: We performed a longitudinal prospective pilot study from 2004 to 2006 at two sites in Ukraine. A sample of pregnant women who reported consuming moderate-to-heavy amounts of alcohol participated in a comprehensive maternal interview, and received ultrasound evaluation of fetal growth and specific fetal brain measurements during the second and third trimesters. These measurements were compared with those collected from a group of pregnant women who consumed little-to-no alcohol during pregnancy, and who were recruited and followed in the same manner. RESULTS: From 6745 screened women, 84 moderate-to-heavy alcohol users and 82 comparison women were identified and ultrasound examinations performed. After controlling for maternal smoking, alcohol-exposed fetuses had shorter mean femur length, caval-calvarial distance and frontothalamic measurements in the second trimester (P < 0.05), and alcohol-exposed fetuses also had shorter frontothalamic distance measurements in the third trimester relative to comparison fetuses (P < 0.05). In addition, after controlling for maternal smoking, both mean orbital diameter and biparietal diameter measurements were significantly smaller on average in the alcohol-exposed group in the third trimester relative to comparison fetuses (P < 0.05). CONCLUSIONS: Significant differences in selected somatic and brain measurements were noted between alcohol-exposed and comparison fetuses, suggesting these markers may be further explored for clinical utility in prenatal identification of affected children. Further study correlating these findings with alcohol-related physical features of the newborn and subsequent comparisons of neuro-developmental outcomes will help define potential uses of prenatal ultrasound for intervention and prevention of FASD. Copyright (c) 2009 ISUOG. Published by John Wiley & Sons, Ltd.

Both Coxsackie infection and multiple sclerosis (MS) are rare in human immunodeficiency virus (HIV) infection. We report a 35-year-old woman with known HIV infection of 12 years’ duration and a clinical illness of 4 years’ duration consistent with MS. The latter was characterized by optic neuritis, bilateral abducens palsies, recurrent Bell’s palsy, hemiparesis, and ataxia coupled with white matter abnormalities on magnetic resonance imaging (MRI). Autopsy revealed Coxsackie B meningoencephalitis; no other infectious disease were detected and no histopathological features of MS were evident. We suggest that the relapsing-remitting neurological disease in this patient was the consequence of Coxsackie B meningoencephalitis. This is the first case report, to the best of our knowledge, of an enteroviral meningoencephalitis complicating human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).

Acute intestinal bleeding is a severe condition, with a mortality rate of up to 40% in case of associated hemodynamic instability. The diagnosis of acute intestinal bleeding is often challenging and to date, there is no definite consensus upon the most appropriate technique for this specific diagnosis. This pictorial essay illustrates our preliminary use of multiplanar (MPR) and maximum intensity projection (MIP) reformations using MDCT scanner with submillimeter and isotropic voxels as an adjunct to axial images in patients with acute intestinal bleeding. MDCT examinations were routinely performed with 64-slice helical CT scanner and images were reconstructed 0.6-mm thickness at 0.5-mm intervals. Multiplanar reconstructions and MIP views were created with a commercially available workstation. Reformatted images from submillimeter isotropic voxels enhanced the depiction of subtle vascular abnormalities and served as a useful adjunct to the axial plane images to improve diagnostic capabilities. Although we are aware that reformatted images should not replace careful analysis of the axial images in patients with acute gastrointestinal bleeding, reformatted images from submillimeter isotropic voxels may clarify the cause of the bleeding, add confidence to image analysis and help interventional radiologists or surgeons improving planning approach.

To investigate whether submicroscopic chromosomal deletions or duplications can be causative of unclear syndromic nephropathies, we analyzed ten patients with congenital abnormalities of the kidney and urinary tract or glomerulopathies combined with important extrarenal anomalies by whole-genome array-based comparative genomic hybridization. In a 14-year-old girl presenting with hematuria, proteinuria, mental retardation (MR), sensorineural hearing loss, dysmorphisms, and epilepsy, we detected a microdeletion in chromosome Xq22.3-q23. This deletion was verified and characterized by fluorescence in situ hybridization and multiplex ligation-dependent probe amplification analyses, found to be de novo, uniallelic and 3.3 Mb in size. Electron microscopy of a kidney biopsy showed glomerular basement membrane thinning and segmental splitting of the lamina densa compatible with Alport syndrome. Cranial magnetic resonance and diffusion tensor imaging detected a severe neuronal migration disorder with double cortex formation and pronounced reduction of the fronto-occipital tract system. Thus, in one of ten patients with unclear syndromic nephropathies we identified a previously undescribed contiguous gene syndrome at Xq22.3-q23. The microdeletion contains the X-linked Alport syndrome gene COL4A5, the MR genes FACL4 and PAK3, and parts of the X-chromosomal lissencephaly gene DCX associated with double cortex formation in girls, MR, and epilepsy. The phenotype in our patient combines features of the Alport-MR contiguous gene syndrome with lissencephaly.

Renovascular hypertension in children is usually asymptomatic and diagnosed incidentally. Behavioral changes have not yet been well recognized as a part of the clinical spectrum of renovascular disease in children. We surveyed all children diagnosed with renovascular hypertension in our institute over a 15-year period. Eleven children were identified, of whom five (45%) had abnormal behavior, which had preceded the diagnosis of hypertension by 3-12 months. The symptoms included restlessness, sleep disturbances, temper tantrums, hyperactivity, aggressive behavior and attention deficit. In three children all behavioral symptoms disappeared following blood pressure normalization, and, in the other two a significant improvement was noted. It was concluded that behavioral symptoms may be a common and early manifestation of renovascular hypertension. Awareness of this association may bring about earlier diagnosis of the disease and prevent end-organ damage as well as unnecessary investigations for behavioral abnormalities.

OBJECTIVE: Apart from thalidomide, retinoids like isotretinoin are the strongest teratogens in humans known today. The overall risk of birth defects is estimated as up to 30% after exposure during embryogenesis. In spite of well established pregnancy prevention programs, pregnancies still occur during isotretinoin therapy in many countries including Germany. A detailed investigation of the incidence and outcome of these pregnancies would fill an important gap. METHODOLOGY: The Berlin Institute for Clinical Teratology documents prospectively the course of drug-exposed pregnancies when contacted for individual drug risk assessment. Datasets of isotretinoin exposed pregnancies recorded between 1993 and 2008 were evaluated as to the outcome of pregnancy. RESULTS: A total of 108 pregnancies exposed to systemic isotretinoin (median dosage 20 mg/day) during the contraindicated period were registered. 76% (69/91) of the pregnancies with known outcome were electively terminated-mainly for fear of medication risk. No terminations due to abnormal prenatal ultrasound findings were reported. Spontaneous abortions occurred in five pregnancies. Of 18 live births including 1 pair of twins 1 major birth defect (small ventricular septal defect) was observed. None of the infants showed symptoms of retinoid embryopathy. 70% (48/69) of the patients with data on contraception did not use any method, in 30% contraception failed. There was no evidence that poor maternal education was a major cause for the omission of contraception documented in 48 women. CONCLUSION: Inadvertent isotretinoin exposure during the first 2 weeks post conception does not necessarily require discussion of termination of pregnancy, as the risk of major birth defects appears to be much lower than it becomes beyond this period. Nevertheless, additional efforts are required to improve the effectiveness of contraception while on isotretinoin treatment considering psycho-social aspects such as improved self-confidence, unexpected new partnership and sexual activity and incorrect perception of infertility.