Corpus Callosum Abnormalities Research Articles

White matter abnormalities of corpus callosum in patients with bipolar disorder and suicidal ideation

ObjectiveAlthough many studies have shown that the corpus callosum (CC) may play an important role in bipolar disorder (BD) and suicide, the pathophysiological mechanism of BD underlying suicidal behavior is still unclear. This study aimed to explore the relationship between the CC, and BD and suicidal ideation using diffusion tensor imaging (DTI).MethodA total of 203 participants (47 BD patients with suicidal ideation, 59 with BD without suicidal ideation, and 97 healthy controls [HC]) underwent DTI scanning at a single site. We examined the white matter integrity of the CC in the three groups.ResultsA comparison among groups showed that BD patients with suicidal ideation had significant lower fractional anisotropy (FA) values than those of BD without suicidal ideation and HCs in the body and genu of the CC, and FA values of BD without suicidal ideation were significantly lower than those of HCs. However, in the splenium of corpus callosum, no difference was found between BD without suicidal ideation and HCs.ConclusionsOur findings add to the evidence suggesting that the CC plays a key role in BD with suicidal ideation, especially with respect to the role of the genu and body of the CC subserving emotion regulation.

Striking phenotypic overlap between Nicolaides-Baraitser and Coffin-Siris syndromes in monozygotic twins with ARID1B intragenic deletion

The chromatin remodeling AT-Rich interaction domain containing 1B protein (ARID1B) also known as BAF-associated factor, 250-KD, B (BAF250B) codified by the ARID1B gene (MIM#614556), is a small subunit of the mammalian SWI/SNF or BAF complex, an ATP-dependent protein machinery which is able to activate or repress gene transcription, allowing protein access to histones through DNA relaxed conformation.ARID1B gene mutations have been associated with two hereditary syndromic conditions, namely Coffin-Siris (CSS, MIM#135900) and Nicolaides-Baraitser syndromes (NCBRS, MIM#601358), characterized by neurodevelopment delay, craniofacial dysmorphisms and skeletal anomalies. Furthermore, intellectual impairment and central nervous system (CNS) alterations, comprising abnormal corpus callosum, have been associated with mutations in this gene. Moreover, ARID1B anomalies resulted to be involved in neoplastic events and Hirschprung disease.Here we report on two monozygotic male twins, displaying clinical appearance strikingly resembling NCBRS and CSS phenotype, who resulted carriers of a novel 6q25.3 microdeletion, encompassing only part of the ARID1B gene. The deleted segment was not inherited from the only parent tested and afflicted the first exons of the gene, coding for protein disordered region. We also provide, for the first time, a review of previously published ARID1B mutated patients with NCBRS and CSS phenotype and a computer-assisted dysmorphology analysis of NCBRS and ARID1B related CSS individuals, through the Face2Gene suite, confirming the existence of highly overlapping facial gestalt of both conditions.The present findings indicate that ARID1B could be considered a contributing gene not only in CSS but also in NCBRS phenotype, although the main gene related to this latter condition is the SMARCA2 gene (MIM#600014), another component of the BAF complex. So, ARID1B study should be considered in such individuals.

Association Between Neonatal Neuroimaging and Clinical Outcomes in Zika-Exposed Infants From Rio de Janeiro, Brazil

Congenital Zika virus (ZIKV) infection may present with a spectrum of clinical and neuroradiographic findings. To determine whether neuroimaging findings for infants with a history of ZIKV exposure are associated with infant clinical outcomes and gestational age at antenatal ZIKV infection. This cohort study retrospectively reviewed neuroimaging results (computed tomography and/or magnetic resonance imaging scans) of 110 ZIKV-exposed infants from a maternity and children's hospital in Rio de Janeiro, Brazil, following the 2015 to 2016 ZIKV epidemic. Neuroimaging from March 1, 2016, to June 30, 2017, was evaluated to determine whether findings were associated with clinical outcomes and the timing of maternal ZIKV infection. Data were analyzed from July 1, 2017, to August 30, 2018. Neuroimaging (computed tomography and/or magnetic resonance imaging) was performed on ZIKV-exposed infants after birth. Blood and/or urine specimens from mothers and infants were tested for ZIKV by polymerase chain reaction assay. Neuroimaging studies were evaluated for structural abnormalities and other forms of brain injury. A total of 110 infants with a mean (SD) gestational age of 38.4 (2.1) weeks had neuroimaging and clinical outcome data reviewed. Of these, 71 (65%) had abnormal neuroimaging findings, with the majority (96%) classified as having severe ZIKV infection at birth. The most common neuroimaging abnormalities were structural abnormalities including brain calcifications, especially at the cortico-subcortical white matter junction, cortex malformations, ventriculomegaly, and reduced brain volumes, followed by brainstem hypoplasia, cerebellar hypoplasia, and corpus callosum abnormalities. Frequency of abnormal imaging was higher in infants with specific clinical findings as opposed to those without them; these findings included fetal brain disruption sequence (100% vs 35%), microcephaly (100% vs 30%), congenital contractures (100% vs 58%), ophthalmologic abnormalities (95% vs 44%), hearing abnormalities (100% vs 58%), and neurologic symptoms (94% vs 10%). Four of 39 infants (10%) without initial evidence of severe ZIKV infection and normal findings on neurologic evaluation at birth had abnormal neuroimaging findings. Neuroimaging abnormalities differed by trimester of maternal ZIKV infection, with 63% of infants born to mothers infected in the first trimester, 13% of infants born to mothers infected in the second trimester, and 1% of infants born to mothers infected in the third trimester exhibiting neuroimaging abnormalities. The odds of abnormal neuroimaging were 7.9 times greater for infants with first trimester ZIKV exposure compared with other trimesters combined (odds ratio, 7.9; 95% CI, 3.0-20.4; P < .001). Neuroimaging abnormalities of computed tomography and/or magnetic resonance imaging scans were common in ZIKV-exposed infants. While neuroimaging abnormalities were seen in 10% of infants without clinically severe ZIKV, most occurred almost exclusively among those with clinically severe ZIKV, especially among those with a history of ZIKV exposure in the first trimester.

The neuroanatomy of Eml1 knockout mice, a model of subcortical heterotopia.

The cerebral cortex is a highly organized structure responsible for advanced cognitive functions. Its development relies on a series of steps including neural progenitor cell proliferation, neuronal migration, axonal outgrowth and brain wiring. Disruption of these steps leads to cortical malformations, often associated with intellectual disability and epilepsy. We have generated a new resource to shed further light on subcortical heterotopia, a malformation characterized by abnormal neuronal position. We describe here the generation and characterization of a knockout (KO) mouse model for Eml1, a microtubule-associated protein showing mutations in human ribbon-like subcortical heterotopia. As previously reported for a spontaneous mouse mutant showing a mutation in Eml1, we observe severe cortical heterotopia in the KO. We also observe abnormal progenitor cells in early corticogenesis, likely to be the origin of the defects. EML1 KO mice on the C57BL/6N genetic background also appear to present a wider phenotype than the original mouse mutant, showing additional brain anomalies, such as corpus callosum abnormalities. We compare the anatomy of male and female mice and also study heterozygote animals. This new resource will help unravel roles for Eml1 in brain development and tissue architecture, as well as the mechanisms leading to severe subcortical heterotopia.

Abnormal Structural and Functional Connectivity of the Corpus Callosum in Autism Spectrum Disorders: a Review

Autism spectrum disorder (ASD) is characterised by difficulties with social communication, interaction, and repetitive and stereotypical patterns of behaviour. Recent studies suggest that abnormalities in the corpus callosum (CC) can produce autistic symptoms, so this cerebral structure is a target for autism research. It is the largest area of white matter fibre that connects the cerebral hemispheres and has been considered an index of interhemispheric connectivity. The poor connectivity that is a characteristic of autism could be due to CC abnormalities. In this review, we describe empirical studies that have used functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) to investigate the role of the CC in functional and structural brain connectivity in individuals with ASD. Establishing the anatomical correlates of abnormal connectivity in ASD is a major objective of structural and functional connectivity studies. Reduced CC volume is one of the most consistent findings in studies of autistic brains. Structural connectivity studies have shown that the CC is generally altered in ASD. In addition, functional connectivity studies show atypical activity in individuals with ASD during social cognition tasks, working memory tasks, and tests of executive function. Research on functional and structural connectivity has contributed to understanding the role of the CC in the clinical symptoms and social and cognitive deficits associated with ASD.

Characteristics of neurological Wilson\u2019s disease with corpus callosum abnormalities

BackgroundWilson’s disease (WD) is an autosomal recessive disease of impaired copper metabolism. Previous study demonstrated that WD with corpus callosum abnormalities (WD-CCA) was limited to the posterior part (splenium). This study aimed to compare clinical features between WD-CCA and WD without corpus callosum abnormalities (WD-no-CCA).MethodsForty-one WD patients who had markedly neurological dysfunctions were included in this study. We retrospectively reviewed clinical, biochemical characteristics and MRI findings in the 41 WD patients. All patients were assessed using the Unified Wilson’s Disease Rating Scale.ResultsNine patients had corpus callosum abnormalities, 4 of 9 patients had abnormal signal in the genu and splenium, 5 of 9 patients had abnormal signal only in the splenium. WD-CCA had longer course (9.9 ± 4.0 years vs. 3.4 ± 3.6 years, p<0.01), more severe neurological dysfunctions (37.6 vs. 65.9, p<0.01) and higher psychiatric symptoms scores (11.2 vs. 22.5, p<0.01) than WD-no-CCA. The MRI findings indicated that WD-CCA had higher ratio than WD-no-CCA in globus pallidus (88.9% vs. 43.8%, p = 0.024) and thalamus (100% vs. 59.4%, p = 0.038). The index of liver function and copper metabolism had no significant in WD-CCA and WD-no-CCA patients.ConclusionOur findings indicate Wilson’s disease can involve the posterior as well as the anterior part of CC and patients with CC involvement had more extensive brain lesions, more severe neurological dysfunctions and psychiatric symptoms.

Accuracy of prenatal ultrasound in the diagnosis of corpus callosum anomalies

Objectives: The main objective of this study was to evaluate the accuracy of prenatal ultrasound to diagnose corpus callosum alterations, compared to prenatal magnetic resonance imaging (MRI), postnatal image techniques (ultrasound and/or MRI), and post-mortem examination in terminated pregnancies.Methods: Retrospective review of 86 cases of prenatal ultrasound diagnosis of corpus callosum anomalies between January 2007 and December 2015 at a third level Maternal Fetal Medicine center. The study reviewed the findings of prenatal ultrasound and MRI, post-mortem examination in cases of termination of pregnancy (TOP) or stillbirths and postnatal ultrasound, and MRI in neonates. The anomalies of corpus callosum (CC) were classified as complete agenesis of the corpus callosum (ACC), partial ACC, or dysgenesis of CC.Results: Fifty-eight (67.4%) cases resulted in TOP, 26 (30.2%) cases opted to continue with the pregnancy and two (2.3%) cases were lost to follow up. Among the 26 cases that continued with the pregnancy, 24 (92.3%) were live births and two (7.7%) were stillborn. All cases in which a third trimester MRI was performed (n = 46) confirmed the prenatal ultrasound diagnosis of CC anomaly. In seven (15.2%) of them, the MRI found additional intracranial findings and in three cases (6.5%) the type of CC anomaly (complete, partial, or dysgenesis) was reclassified (Kappa index: 0.86, 95% CI: 0.71–1.00). CC anomalies were confirmed in 46 (95.8%) of the 48 cases in which a post-mortem examination was available, the type of anomaly being reclassified in three cases (6.3%) (Kappa index: 0.88, 95% CI: 0.75–1.00). Among the 10 cases in which a postnatal ultrasound was performed, the CC anomaly was confirmed in all and the type of anomaly was reclassified in 1 (10%) of them (Kappa index: 0.75, 95% CI: 0.32–1.00).Conclusion: Corpus callosum agenesis can be detected on the routine mid-trimester ultrasound scan. Prenatal ultrasound and MRI can accurately classify the type of CC abnormality. Moreover, third trimester MRI can detect additional intracranial anomalies in 15% of cases.

Neurodevelopmental outcome following prenatal diagnosis of a short corpus callosum.

Data regarding the neurodevelopmental outcome of fetal short corpus callosum (CC) diagnosed according to standard reference charts is scarce. The purpose of this study was to assess whether the finding is related to neurodevelopmental delay, and to examine reclassification to normal fetal CC length using CC length/EFW ratio. Historical prospective cohort study including pregnant women who were referred for fetal neurosonogram due to abnormal CC. Short CC was defined below the 5th percentile according to reference charts. Twenty cases were included in the study group and compared with a control group of 59 normal cases. The patients in the study group were divided into two groups according to CC length/EFW ratio. Children's neurodevelopment was assessed using the Vineland Adaptive Behavior Scale (VABS). VABS scores were within normal range in 90% of the cases. There was no significant statistical difference between the study group and the control group. In addition, there was no statistically significant difference between fetuses reclassified as normal callosal length according to CC length/EFW ratio in comparison to the control group. The neurodevelopmental outcome of fetuses with diagnosed short CC did not differ from the neurodevelopment of normal fetuses in the control group.

Selective micro-structural integrity impairment of the isthmus subregion of the corpus callosum in alcohol-dependent males

BackgroundPrevious studies have provided evidence that alcohol-dependent patients have abnormality in corpus callosum (CC); however, it is unclear whether micro-structural integrity of the CC subregions is differentially affected in this disorder.MethodsIn this study, a total of 39 male individuals, including 19 alcohol-dependent patients and 20 age-matched healthy controls, underwent diffusion tensor imaging (DTI). CC was reconstructed by DTI tractography and was divided into seven subregions. Multiple diffusion metrics of each subregion were compared between two groups.ResultsCompared to healthy controls, patients exhibited increased axial diffusivity (P = 0.007), radial diffusivity (P = 0.009) and mean diffusivity (P = 0.005) in the isthmus. In addition, we observed that daily alcohol intake was correlated positively with radial diffusivity and mean diffusivity and negatively with fractional anisotropy, while abstinence time of hospitalization was negatively correlated with mean diffusivity in the patients.ConclusionThese findings suggest a selective micro-structural integrity impairment of the corpus callosum subregions in alcohol dependence, characterized by axon and myelin alterations in the isthmus.

Myelin Damage in Diffuse Axonal Injury.

Diffuse axonal injury (DAI) is characterized by delayed axonal disconnection. Although the effect of DAI on axonal pathology has been well documented, there is limited information regarding the role of myelin in the pathogenesis of DAI. We used a modified Marmarou method to create a moderate DAI model in adult rat and examined the corpus callosum and brain stem for myelin pathology and dynamic glial responses to DAI. During the first week following DAI, Luxol Fast Blue staining and western blot analysis for MBP showed significant loss of myelin in the corpus callosum and the brain stem. Increased apoptosis of mature oligodendrocyte, as depicted by its marker CC-1, was observed. Conversely, there was an increased number of Olig2-positive cells accompanied by hypertrophic microglia/macrophage and mild reactive astrocytes. Electron microscopy revealed degenerating axons in the corpus callosum and marked myelin abnormalities in the brain stem in the early stage of DAI. Brain stem regions exhibited myelin intrusions or external protrusions with widespread delamination and myelin collapse, leading to degeneration of accompanying axons. Our results show distinct pathologic processes involving axon and myelin between the corpus callosum and the brain stem in DAI. Oligodendrocyte selective vulnerability and subsequent demyelination may contribute to axonal degeneration in the brain stem. Defining the cause of ongoing oligodendrocyte death and promoting myelin regeneration may provide important targets for therapeutic interventions of DAI.

Updated Imaging Findings in Congenital Zika Syndrome: A Disease Story That is Still Being Written.

In congenital Zika virus syndrome (CZS), the most frequent radiological findings are calcifications in the cortical-white matter junction and malformations of cortical development (pachygyria or polymicrogyria, which occur predominantly in the frontal lobes, or a simplified gyral pattern), ventriculomegaly, enlargement of the cisterna magna and the extra-axial subarachnoid space, corpus callosum abnormalities, and reduced brain volume. This syndrome can also result in a decrease in the brainstem and cerebellum volumes and delayed myelination. Infants with CZS may show venous thrombosis and lenticulostriate vasculopathies. Over a 3-year follow-up period, many infants with CZS showed hydrocephalus, reduction in brain calcifications, and greater reduction in brain thickness.

Cytogenomic characterization of 1q43q44 deletion associated with 4q32.1q35.2 duplication and phenotype correlation

BackgroundMicrodeletion of 1q43q44 causes a syndrome characterized by intellectual disability (ID), speech delay, seizures, microcephaly (MIC), corpus callosum abnormalities (CCA) and characteristic facial features. Duplication of 4q is presented with minor to severe ID, MIC and facial dysmorphism. We aimed to verify the correlation between genotype/phenotype in a patient with 1q43q44 deletion associated with 4q32.1q35.2 duplication.Case presentationWe report on a 3 year-old female patient with delayed motor and mental milestones, MIC and facial dysmorphism. She is a child of non-consanguineous parents and no similarly affected family members. CT brain showed abnormal gyral patterns, hypogenesis of corpus callosum and bilateral deep Sylvian fissure. Electroencephalogram showed frontotemporal epileptogenic focus. Her karyotype was revealed as 46,XX,add(1)(q44). Fluorescence in situ hybridization (FISH) using whole chromosome paint (WCP1) and subtelomere 1q revealed that the add segment was not derived from chromosome 1 and there was the deletion of subtelomere 1q. Multiple ligation probe amplification (MLPA) subtelomere kit revealed the deletion of 1q and duplication of 4q. Array CGH demonstrated the 6.5 Mb deletion of 1q and 31 Mb duplication of chromosome 4q.ConclusionThe phenotype of our patient mainly reflects the effects of haploinsufficiency of AKT3, HNRNPU, ZBTB18 genes associated with duplication of GLRA3, GMP6A, HAND2 genes. Patients presented with ID, seizures, MIC together with CCA are candidates for prediction of 1q43q44 microdeletion and cytogenomic analysis.

Deformation-based Statistical Shape Analysis of the Corpus Callosum in Mild Cognitive Impairment and Alzheimer's Disease.

In this study, we investigated the influence that the pathology of Alzheimer's disease (AD) exerts upon the corpus callosum (CC) using a total of 325 mild cognitive impairment (MCI) subjects, 155 AD subjects, and 185 healthy control (HC) subjects. Regionally-specific morphological CC abnormalities, as induced by AD, were quantified using a large deformation diffeomorphic metric curve mapping based statistical shape analysis pipeline. We also quantified the association between the CC shape phenotype and two cognitive measures; the Mini Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-Cognitive Behavior Section (ADAS-cog). To identify AD-relevant areas, CC was sub-divided into three subregions; the genu, body, and splenium (gCC, bCC, and sCC). We observed significant shape compressions in AD relative to that in HC, mainly concentrated on the superior part of CC, across all three sub-regions. The HC-vs-MCI shape abnormalities were also concentrated on the superior part, but mainly occurred on bCC and sCC. The significant MCI-vs-AD shape differences, however, were only detected in part of sCC. In the shape-cognition association, significant negative correlations to ADAS-cog were detected for shape deformations at regions belonging to gCC and sCC and significant positive correlations to MMSE at regions mainly belonging to sCC. Our results suggest that the callosal shape deformation patterns, especially those of sCC, linked tightly to the cognitive decline in AD, and are potentially a powerful biomarker for monitoring the progression of AD.

Abnormal corpus callosum induced by diabetes impairs sensorimotor connectivity in patients after acute stroke.

To test the hypothesis that abnormal corpus callosum (CC) induced by diabetes may impair inter-hemispheric sensorimotor functional connectivity (FC) that is associated with poor clinical outcome after stroke. Forty-five patients with acute ischaemic stroke in the middle cerebral artery territory and 14 normal controls participated in the study. CC was divided into five subregions on three-dimensional T1-weighted image. The microstructural integrity of each subregion of CC was analysed by DTI and the inter-hemispheric FCs in primary motor cortex (M1-M1 FC) and primary sensory cortex (S1-S1 FC) were examined by resting-state functional magnetic resonance imaging. Diabetic patients (n = 26) had significantly lower fractional anisotropy (FA) in the isthmus of CC (CCisthmus) when compared with non-diabetic patients (n = 19) and normal controls (p < 0.0001). In addition, diabetic patients had the lowest M1-M1 FC (p = 0.015) and S1-S1 FC (p = 0.001). In diabetic patients, reduced FA of CCisthmus correlated with decreased M1-M1 FC (r = 0.549, p = 0.004) and S1-S1 FC (r = 0.507, p = 0.008). Decreased M1-M1 FC was independently associated with poor outcome after stroke in patients with diabetes (odds ratio = 0.448, p = 0.017). CC degeneration induced by diabetes impairs sensorimotor connectivity and dysfunction of motor connectivity can contribute to poor recovery after stroke in patients with diabetes. • Abnormal isthmus of corpus callosum in stroke patients with diabetes. • Abnormal isthmus of corpus callosum correlated with decreased inter-hemispheric sensorimotor connectivity. • Decreased motor connectivity correlated with poor stroke outcome in diabetic patients.

Neurodevelopmental outcomes in children with prenatally diagnosed corpus callosal abnormalities

ObjectiveAlthough corpus callosal abnormalities are among the most common brain malformations detected prenatally, few previous studies have described the neurodevelopmental outcomes of children with this condition. The aim of our study was to evaluate the neurodevelopmental outcomes and associated clinical features of children with corpus callosal abnormalities diagnosed by prenatal ultrasonography. MethodsBetween July 2011 and July 2016, forty-nine children with corpus callosal abnormalities were born in Asan Medical Center Children’s Hospital. Neurodevelopmental assessments were conducted in 40 patients at a median age of 24.8 months using the Bayley Scales of Infant Development II or the Korean Infant and Child Development Test. Patients were categorized according to their postnatal magnetic resonance imaging (MRI) findings and accompanying anomalies. Baseline characteristics and developmental outcomes of each group were compared. ResultsIsolated agenesis or hypoplasia of the corpus callosum was found in 16 (32.7%) patients, other associated central nervous system (CNS) abnormalities were found in 28 (57.1%) patients, and non-CNS abnormalities were found in 11 (22.4%) patients. Among the 40 patients who underwent developmental assessment, 18 (45.0%) showed normal development and 10 (25.0%) showed moderate-to-severe global developmental delay. Seven of the twelve (58.3%) patients with isolated corpus callosal abnormalities showed normal development. The combination of corpus callosal abnormalities with non-CNS anomalies was significantly associated with developmental delay (odds ratio 2.5, 95% confidence interval 1.6–3.9, p = 0.001). Conversely, children with isolated corpus callosal abnormalities showed relatively favorable neurodevelopmental outcomes. ConclusionAppropriate evaluation and comprehensive therapeutic approaches are strongly recommended for neonates who present with corpus callosal abnormalities combined with additional anomalies.

Corpus callosum shape and morphology in youth across the psychosis Spectrum

The corpus callosum is the largest white matter tract in the human brain connecting and coordinating homologous regions of the right and left hemispheres and has been strongly implicated in the pathogenesis of psychosis. We investigated corpus callosum morphology in a large community cohort of 917 individuals (aged 8–21), including 267 endorsing subsyndromal or threshold psychotic symptoms (207 on the psychosis spectrum and 60 with limited psychosis based on previously published criteria) and 650 non-psychotic volunteers. We used a highly reliable and previously published algorithm to automatically identify the midsagittal plane and to align the corpus callosum along the anterior and posterior commissures for segmentation, thereby eliminating these sources of error variance in dependent measures, which included perimeter, length, mean thickness and shape (circularity). The parcellation scheme divided the corpus callosum into 7 subregions that consisted of the rostrum, genu, rostral body, anterior midbody, posterior midbody, isthmus, and splenium. Both individuals endorsing psychotic symptoms and those with limited psychosis had significantly (p<.05) smaller area and lower thickness measures compared to healthy volunteers, but did not differ significantly from each other. Findings were relatively widespread indicating a relatively global effect not circumscribed to any particular corpus callosum subregion. These data are consistent with the hypothesis that corpus callosum abnormalities may be evident early in the course of illness and predate the onset of frank psychosis. Given that these measures can be easily obtained and are highly reliable they may assist in the identification of individuals at future risk for psychosis.

Congenital Aqueductal Stenosis: Findings at Fetal MRI That Accurately Predict a Postnatal Diagnosis.

Congenital aqueductal stenosis is a common cause of prenatal ventriculomegaly. An accurate diagnosis provides prognostic information and may guide obstetric management. The purpose of this study was to identify specific anatomic findings on prenatal MR imaging that can be used as predictors of congenital aqueductal stenosis. Prenatal and postnatal MRIs of fetuses referred to our institution for ventriculomegaly between June 2008 and August 2015 were reviewed. Imaging findings in postnatally confirmed congenital aqueductal stenosis (disease group) were compared with those of ventriculomegaly cases from other causes (control group). Univariate analysis was performed using the Fisher exact test and the Wilcoxon rank test, and multivariate analysis, via the random forest method. Forty-three cases of ventriculomegaly had a confirmed postnatal diagnosis of congenital aqueductal stenosis. Thirty-two ventriculomegaly cases negative for congenital aqueductal stenosis were included in the control group. Dominant findings associated with an accurate prenatal diagnosis of congenital aqueductal stenosis on multivariate analysis included the following: enlarged inferior third ventricular recesses, enlargement of the lateral ventricles and third ventricle, and an abnormal corpus callosum. Findings that significantly increase the probability of congenital aqueductal stenosis (high positive predictive value) included the following: enlarged third ventricular recesses, aqueduct funneling, hemorrhage in the cerebral aqueduct, ventricular diverticulum, rhombencephalosynapsis, and dystroglycanopathy-related cerebellar dysplasia. Our study identified specific characteristics on fetal MR imaging that can be used as predictors of the diagnosis of congenital aqueductal stenosis. Most of these findings are secondary to the obstructive nature of the resulting hydrocephalus. Common associated malformations such as rhombencephalosynapsis and dystroglycanopathies should also increase the suspicion of congenital aqueductal stenosis when present with ventriculomegaly.

E-Cigarettes: Effects on the Fetus

1. Nan Jiang, PhD* 2. Lily Lee†,§ 3. Judith T. Zelikoff, PhD‡ 4. Michael Weitzman, MD†,‡,¶,** 1. *Department of Population Health, 2. †Department of Pediatrics, 3. ‡Department of Environmental Medicine, School of Medicine, New York University, New York, NY 4. ¶College of Global Public Health, New York University, New York, NY 5. §Brooklyn College, Brooklyn, NY 6. **NYU Abu Dhabi Public Health Research Center, Abu Dhabi, United Arab Emirates 1. 1. Lauterstein D, 2. Hoshino R, 3. Gordon T, 4. Watkins BX, 5. Weitzman M, 6. Zelikoff J The Changing Face of Tobacco Use Among United States Youth. Lauterstein D, Hoshino R, Gordon T, Watkins BX, Weitzman M, Zelikoff J. Curr Drug Abuse Rev. 2014;7(1):29–43 [OpenUrl][1][CrossRef][2][PubMed][3] 2. 1. Nguyen KH, 2. Tong VT, 3. Marynak KL, 4. King BA US Adults' Perceptions of the Harmful Effects during Pregnancy of Using Electronic Vapor Products Versus Smoking Cigarettes, Styles Survey, 2015. Nguyen KH, Tong VT, Marynak KL, King BA. Prev Chronic Dis. 2016;13:E175 [OpenUrl][4] 3. 1. McGrath-Morrow SA, 2. Hayashi M, 3. Aherrera A, 4. et al. The Effects of Electronic Cigarette Emissions on Systemic Cotinine Levels, Weight and Postnatal Lung Growth in Neonatal Mice. McGrath-Morrow SA, Hayashi M, Aherrera A, et al. PLoS One. 2015;10(2):e0118344 [OpenUrl][5][CrossRef][6][PubMed][7] The emergence of electronic cigarettes (e-cigarettes) as devices touted to be helpful in the cessation or reduction of smoking has prompted many concerns about the prevalence and consequences of their use during pregnancy. Both pregnant women and health-care providers are poorly informed or misinformed about the potential health risks associated with e-cigarettes, which has profound consequences on clinical conversations about the product. Unfortunately, the scientific literature has not yet caught up with the rise in e-cigarette use. The safety of e-cigarettes to the mother and fetus is largely unknown, with a handful of human studies finding minimal health effects. In large part, concerns about e-cigarettes have been the result of the adverse health effects associated with nicotine during pregnancy, which include low birthweight, abnormal corpus callosum, and alterations in appetite, attention, and cognition. Although the health consequences of e-cigarette use during pregnancy remain poorly understood, it is imperative that health-care providers are well equipped to initiate conversations about e-cigarette use with pregnant women and women of childbearing age to discourage use during pregnancy as an aid to quitting smoking. E-cigarettes are the most commonly used, newly developed electronic nicotine delivery systems. They are battery-powered vaporizers that heat a liquid solution (typically containing nicotine, glycerol, propylene glycol, flavorings, and other additives) to deliver an aerosol for user inhalation with the intention of imitating conventional cigarettes. Since their introduction to the US market in 2007, e-cigarette use has increased rapidly among youths and adults. E-cigarettes are widely advertised and often are promoted as less harmful alternatives to cigarettes and also as effective smoking cessation tools, which has considerable … [1]: {openurl}?query=rft.jtitle%253DCurr%2BDrug%2BAbuse%2BRev%26rft.volume%253D7%26rft.spage%253D29%26rft_id%253Dinfo%253Adoi%252F10.2174%252F1874473707666141015220110%26rft_id%253Dinfo%253Apmid%252F25323124%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.2174/1874473707666141015220110&link_type=DOI [3]: /lookup/external-ref?access_num=25323124&link_type=MED&atom=%2Fpedsinreview%2F39%2F3%2F156.atom [4]: {openurl}?query=rft.jtitle%253DPrev%2BChronic%2BDis%26rft.volume%253D13%26rft.spage%253DE175%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [5]: {openurl}?query=rft.jtitle%253DPLoS%2BOne%26rft.volume%253D10%26rft.spage%253De0118344%26rft_id%253Dinfo%253Adoi%252F10.1371%252Fjournal.pone.0118344%26rft_id%253Dinfo%253Apmid%252F25706869%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [6]: /lookup/external-ref?access_num=10.1371/journal.pone.0118344&link_type=DOI [7]: /lookup/external-ref?access_num=25706869&link_type=MED&atom=%2Fpedsinreview%2F39%2F3%2F156.atom

Further delineation of Temtamy syndrome of corpus callosum and ocular abnormalities.

Temtamy syndrome is a syndromic form of intellectual disability characterized by ocular involvement, epilepsy and dysgenesis of the corpus callosum. After we initially mapped the disease to C12orf57, we noted a high carrier frequency of an ancient startloss founder mutation [c.1A>G; p.M1?] in our population, and variable phenotypic expressivity in newly identified cases. This study aims to combine 33 previously published patients with 23 who are described here for the first time to further delineate the phenotype of this syndrome. In addition to the known p.M1? founder, we describe four novel homozygous variants, thus increasing the number of Temtamy syndrome-related C12orf57 variants to seven, all but one predicted to be loss of function. While all patients presented with intellectual disability/developmental delay, the frequency of other phenotypic features was variable: 73.2% (41/56) had epilepsy, 63% (34/54) had corpus callosal abnormalities, 14.5% (8/55) had coloboma, and 16.4% (9/55) had microphthalmia. Our analysis also revealed a high frequency of less recognized features such as congenital heart disease (51.4%), and brain white matter abnormalities (38%, 19/50). We conclude that C12orf57 variants should be considered in the etiology of developmental delay/intellectual disability, even when typical syndromic features are lacking, especially in those who trace their ancestry to Saudi Arabia where a founder C12orf57 mutation is among the most common recessive causes of intellectual disability.

Corpus callosum abnormalities in 64 Egyptian patients: Neuropsychological and genetic studies

Introduction Corpus callosum (CC) connects the left and right cerebral hemispheres. It is the largest white matter structure in the brain connecting mainly homotopic, as well as heterotopic, brain areas of both hemispheres. It has a major role in everyday behavior. Agenesis of CC can occur as isolated finding on MRI, or more commonly, it is associated with large number of brain anomalies. Patients and methods Neuropsychological and genetic assessment was done for 64 cases with corpus callosum abnormalities, whose age ranged from 6 months to 11 years and 9 months, with a mean age of 3 years and 6 months. This study was done from January 2012 till December 2014. Results Overall, 12.5% of the cases had chromosomal aberrations, 14% of the cases had identified genetic syndrome, and 73% of the cases were nonsyndromic/unclassified. Variable degrees of mental subnormality were encountered among 58 (92.2%) of 64 studied patients. Conclusion Abnormalities of the CC are often associated with cognitive deficits, autism, and epilepsy.