Surgical management of brain-stem cavernous malformations: report of 137 cases.

PubMed

Wang, Chung-cheng; Liu, Ali; Zhang, Jun-ting; Sun, Bo; Zhao, Yuan-li

2003-06-01

With the improvement in neuroimaging and microsurgical techniques, brain stem cavernous malformations are no longer considered inoperable. Surgical indications for brainstem cavernoma are evolving, with better understanding of its natural history and decreasing surgical complications. During 1986 through 1998, a series of 137 patients (4 patients each with two brain stem lesions, total number of lesions, 141) with brain stem cavernous malformations were treated microsurgically at Beijing Neurosurgery Institute. The age distribution, lesion location, and clinical presentations were analyzed. The bleeding rate, surgical indications and microsurgical techniques were also discussed. In our series, 92 of 137 cases (67.2%) suffered more than one hemorrhage. Female patients had a higher risk of recurrent hemorrhage than that of male patients. Unlike cavernomas malformations from other locations, repeated hemorrhages from brain stem malformations are much more common and usually lead to new neurologic deficits. Among all 137 surgically treated patients, there was no operative mortality. Ninety-nine patients (72.3%) either improved or remained clinically stable postoperatively. The size of the cavernoma/hematoma does not necessarily correlate with the surgical result. While the acute hematoma can facilitate the surgical dissection, longer clinical history with multiple hemorrhages often makes total surgical resection difficult, partially because of the firmer capsule that may not shrink or collapse after hematoma is released. Pathologically those capsules were associated with more hyaline degeneration, fibrous proliferation and even calcifications. During the follow-up period between 0.5 to 11 years in 129 cases, 115 patients (89.2%) have been working, studying, or doing house work. Three patients (2.3%) suffered recurrent hemorrhages. Surgical indications of brain stem cavernoma include (1) progressive neurologic deficits; (2) overt acute or subacute hemorrhage on MRI either inside or outside cavernous malformations with mass effect; (3) cavernoma/hematoma reaching brainstem surface (<2 mm brain tissue between cavernoma /hematoma and pial surface). Grave clinical presentations like coma, respiratory, or cardiac instability are not surgical contraindications. Emergent surgical evacuation may lead to satisfactory outcome. Repeated hemorrhages will worsen the pre-existing neurologic deficits and possibly make the surgical dissections more difficult. Patients with minimum, stable neurologic deficits and lesion/hematoma that has not reached the brain stem surface should be followed conservatively.

Management of children with holoprosencephaly.

PubMed

Levey, Eric B; Stashinko, Elaine; Clegg, Nancy J; Delgado, Mauricio R

2010-02-15

Holoprosencephaly (HPE) is the most common malformation of the embryonic forebrain in humans. Although HPE occurs along a continuous spectrum, it has been categorized into four types from most severe to least severe: alobar, semilobar, lobar, and middle interhemispheric (MIH) variant. Facial malformations are often associated with HPE and usually correlate with the severity of brain malformation. With the most severely affected newborns, there is a high mortality rate in the first month of life, however, with milder forms of HPE, the majority survive beyond infancy. The Carter Centers for Brain Research in Holoprosencephaly and Related Malformations have enrolled 182 living children in a prospective research study. Based on previously published reports using this database, reports from other investigators, as well as our experience and personal observations, the range of developmental, neurological, and medical problems found in children with HPE is described in this article. Virtually all children with HPE have some developmental disability and the severity correlates with the severity of the brain malformation on neuroimaging. Common medical problems include hydrocephalus, seizures, motor impairment, oromotor dysfunction with risk of poor nutrition and aspiration, chronic lung disease, gastroesophageal reflux, constipation, hypothalamic dysfunction with disturbed sleep-wake cycles and temperature dysregulation, as well as endocrine dysfunction. Diabetes insipidus in particular is found in about 70% of children with classic HPE. Recommendations for management of these problems are given based on experiences of the authors and familiarity with the literature. 2010 Wiley-Liss, Inc.

Sutures - separated

MedlinePlus

The problem may be caused by: Arnold-Chiari malformation Battered child syndrome Bleeding inside the brain (intraventricular hemorrhage) Brain tumor Certain vitamin deficiencies Dandy-Walker malformation Down syndrome Hydrocephalus Infections that are ...

Unruptured Brain Arteriovenous Malformations: Primary ONYX Embolization in ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations)-Eligible Patients.

PubMed

Singfer, Uri; Hemelsoet, Dimitri; Vanlangenhove, Peter; Martens, Frederic; Verbeke, Luc; Van Roost, Dirk; Defreyne, Luc

2017-12-01

In light of evidence from ARUBA (A Randomized Trial of Unruptured Brain Arteriovenous Malformations), neurovascular specialists had to reconsider deliberate treatment of unruptured brain arteriovenous malformations (uBAVMs). Our objective was to determine the outcomes of uBAVM treated with primary embolization using ethylene vinyl alcohol (ONYX). Patients with uBAVM who met the inclusion criteria of ARUBA and were treated with primary Onyx embolization were assigned to this retrospective study. The primary outcome was the modified Rankin Scale score. Secondary outcomes were stroke or death because of uBAVM or intervention and uBAVM obliteration. Sixty-one patients (mean age, 38 years) were included. The median observation period was 60 months. Patients were treated by embolization alone (41.0%), embolization and radiosurgery (57.4%), or embolization and excision (1.6%). Occlusion was achieved in 44 of 57 patients with completed treatment (77.2%). Forty-seven patients (77.1%) had no clinical impairment at the end of observation (modified Rankin Scale score of <2). Twelve patients (19.7%) reached the outcome of stroke or death because of uBAVM or intervention. Treatment-related mortality was 6.6% (4 patients). In uBAVM, Onyx embolization alone or combined with stereotactic radiosurgery achieves a high occlusion rate. Morbidity remains a challenge, even if it seems lower than in the ARUBA trial. © 2017 American Heart Association, Inc.

Dandy-Walker syndrome and chromosomal abnormalities.

PubMed

Imataka, George; Yamanouchi, Hideo; Arisaka, Osamu

2007-12-01

Dandy-Walker syndrome (DWS) is a brain malformation of unknown etiology, but several reports have been published indicating that there is a causal relationship to various types of chromosomal abnormalities and malformation syndromes. In the present article, we present a bibliographical survey of several previously issued reports on chromosomal abnormalities associated with DWS, including our case of DWS found in trisomy 18. There are various types of chromosomal abnormalities associated with DWS; most of them are reported in chromosome 3, 9, 13 and 18. We also summarize some other chromosomal abnormalities and various congenital malformation syndromes.

Diencephalic-Mesencephalic Junction Dysplasia: A Novel Recessive Brain Malformation

ERIC Educational Resources Information Center

Zaki, Maha S.; Saleem, Sahar N.; Dobyns, William B.; Barkovich, A. James; Bartsch, Hauke; Dale, Anders M.; Ashtari, Manzar; Akizu, Naiara; Gleeson, Joseph G.; Grijalvo-Perez, Ana Maria

2012-01-01

We describe six cases from three unrelated consanguineous Egyptian families with a novel characteristic brain malformation at the level of the diencephalic-mesencephalic junction. Brain magnetic resonance imaging demonstrated a dysplasia of the diencephalic-mesencephalic junction with a characteristic "butterfly"-like contour of the…

RBPJ and EphrinB2 as Molecular Targets to Treat Brain Arteriovenous Malformation in Notch4 Induced Mouse Model

DTIC Science & Technology

2017-10-01

mouse genetic breeding, provided genotyping, immunostaining, histological analysis, and molecular expertise. Funding Support NIH/NHLBI Name: Bert...AWARD NUMBER: W81XWH-16-1-0665 TITLE: RBPJ and EphrinB2 as Molecular Targets to Treat Brain Arteriovenous Malformation in Notch4-Induced Mouse...2016 - 29 Sep 2017 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER RBPJ and EphrinB2 as Molecular Targets to Treat Brain Arteriovenous Malformation in

Hereditary hemorrhagic telangiectasia patient presenting with brain abscess due to silent pulmonary arteriovenous malformation.

PubMed

Themistocleous, Marios; Giakoumettis, Dimitrios; Mitsios, Andreas; Anagnostopoulos, Christos; Kalyvas, Aristoteles; Koutsarnakis, Christos

2016-01-01

Hereditary hemorrhagic telangiectasia is a rare autosomal dominant inherited disease that is usually complicated by visceral vascular malformations. Patients harboring such malformations are at increased risk of brain abscess formation, which despite advances in diagnostic and surgical methods remains a life threatening medical emergency with high mortality and morbidity rates. In the present report we describe a case of cerebral abscess due to silent pulmonary arteriovenous malformation (AVM) in a young patient previously undiagnosed for hereditary hemorrhagic telangiectasia syndrome (HHT).

Absence of the Septum Pellucidum

MedlinePlus

... accompanies various malformations of the brain that affect intelligence, behavior, and the neurodevelopmental process, and seizures may ... accompanies various malformations of the brain that affect intelligence, behavior, and the neurodevelopmental process, and seizures may ...

Computed tomography of congenital brain malformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarwar, M.

1984-01-01

This book is illustrated showing each condition. This book is designed to correlate the pathology of CNS malformations with their CT scan appearance, mainly on the axial images. The author has drawn upon his personal experience and the information gleaned from the literature dealing with the description of the CT scan findings of these malformations. The emphasis is on simplicity of description. Since a large degree of morphological variation exists in each entity, numerous illustrations (wherever applicable) are shown to depict those variations. When appropriate, deficiency of the CT scan in the evaluation of these CNS malformations also is indicated.more » A description of CNS embryology is included as well.« less

Pediatric Central Diabetes Insipidus: Brain Malformations Are Common and Few Patients Have Idiopathic Disease.

PubMed

Werny, David; Elfers, Clinton; Perez, Francisco A; Pihoker, Catherine; Roth, Christian L

2015-08-01

Pediatric cohorts of central diabetes insipidus (CDI) have shown varying prevalences for the different causes of CDI, including idiopathic. The objective of the study was to determine the causes of CDI at a pediatric tertiary care center and to characterize their clinical outcomes. All patients with CDI at Seattle Children's Hospital were identified and retrospectively analyzed. From 2000 to 2013, 147 patients with CDI were encountered (mean age 7 y at diagnosis, mean follow-up 6.2 y). The different causes of CDI were grouped, and age of diagnosis, anterior pituitary hormone deficiencies (APHDs), and presence of the posterior pituitary bright spot (PPBS) were analyzed. Patients with idiopathic CDI had infundibular thickening measured using a systematic method. Brain malformations caused 24% of CDI cases, and 12.2% were idiopathic. Four of 22 patients with initially idiopathic CDI were diagnosed with an underlying condition, none occurring later than 2.5 years from diagnosis. APHDs were as common in the brain malformation group as they were in the tumor/infiltrative group (72% vs 85%; P = .09). The PPBS was present in at least 13% of patients and in 19% of those with brain malformations. Patients with idiopathic CDI and stalk thickening on the initial magnetic resonance imaging were more likely to have an underlying diagnosis (40% vs 0%; P = .03). Brain malformations were a more common cause of pediatric CDI than previously reported. These patients have a high rate of APHDs, and many have persistence of the PPBS. Idiopathic CDI is an uncommon diagnosis, and none of our patients were diagnosed with Langerhans cell histiocytosis or germinoma for more than 3 years from CDI diagnosis. Providers can consider less frequent magnetic resonance imaging after this time point. A systematic method of infundibular measurement on the initial magnetic resonance imaging may predict an underlying germinoma or Langerhans cell histiocytosis.

Selenium teratogenesis in natural populations of aquatic birds in central California

USGS Publications Warehouse

Hoffman, D.J.; Ohlendorf, H.M.; Aldrich, T.W.

1988-01-01

The frequency and types of malformations are described that were encountered during the spring of 1983 in a natural population of aquatic birds exposed to agricultural drainwater ponds and food items containing high concentrations of selenium in central California. A total of 347 nests of aquatic birds containing 1,681 eggs was selected for study at Kesterson Reservoir located in the Kesterson National Wildlife Refuge (NWR), Merced County, California. Embryos collected during incubation or from eggs that failed to hatch were examined to determine the age at death and presence of malformations. Embryonic death was generally high; approximately 17?60% of the nests of different species contained at least one dead embryo. The incidence of malformed embryos was also high; approximately 22?65% of the nests where at least two embryos were examined contained abnormal embryos. American coots (Fulica americana) and black-necked stilts (Himantopus mexicanus) experienced the highest incidence of malformed embryos. For all species, the average percentage of eggs containing dead or live abnormal embryos was 16.1 whereas the average percentage containing live abnormal embryos was 10.7. Multiple gross malformations of the eyes, brain, and feet were often present. Brain defects included hydrocephaly and exencephaly. Eye defects included both unilateral and bilateral anophthalmia and microphthalmia. Eye and foot defects with ectrodactyly and swollen joints were the most common in coots. Beak defects also occurred frequently and most often included incomplete development of the lower beak of ducks (Anas spp.) and stilts. Wing and leg defects were most prevalent in stilts and ducks, with ectromelia and amelia most prevalent in stilts. Other malformations occurring at lower frequencies included enlarged hearts with thin ventricular walls, liver hypopiasia, and gastroschisis. Based upon simultaneous examination of a control population of aquatic birds of the same species and published studies, the incidences of embryonic mortality and deformities were 9?30 times greater than expected. The role of the form of selenium responsible for teratogenesis in laboratory studies is discussed.

A novel non-contrast-enhanced MRA using silent scan for evaluation of brain arteriovenous malformation: A case report and review of literature.

PubMed

Moon, Jin Il; Baek, Hye Jin; Ryu, Kyeong Hwa; Park, Hyun

2017-11-01

Brain arteriovenous malformations (AVMs) are congenital vascular abnormalities involving abnormal connections between arteries and veins. In clinical practice, imaging studies help evaluate feeding arteries, niduses, draining venous systems, and coexisting complications in patients with brain AVM. They also have an impact on decision-making regarding clinical management. We applied a novel non-contrast-enhanced MR angiography (MRA) technique, termed "silent MRA," for evaluating an incidental brain AVM. Here, we describe the clinical case with radiological review and highlight the technical background and clinical usefulness of silent MRA. A 60-year-old woman underwent neuroimaging study including MRA to evaluate intracranial cause of headache. The brain AVM, including its nidus and draining veins, was conspicuously delineated on silent MRA images; these findings correlated well with conventional angiographic findings. The patient did not receive interventional or surgical treatment. The patient is being followed up regularly at the outpatient department. The silent MRA can be a suitable imaging modality for repeated follow-up evaluation for not only brain AVMs but also various intracranial vascular diseases without the use of contrast materials.

Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations

PubMed Central

Cid, Elena; Gomez-Dominguez, Daniel; Martin-Lopez, David; Gal, Beatriz; Laurent, François; Ibarz, Jose M.; Francis, Fiona; Menendez de la Prida, Liset

2014-01-01

Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders. PMID:24782720

Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations.

PubMed

Cid, Elena; Gomez-Dominguez, Daniel; Martin-Lopez, David; Gal, Beatriz; Laurent, François; Ibarz, Jose M; Francis, Fiona; Menendez de la Prida, Liset

2014-01-01

Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders.

Genetics Home Reference: megalencephaly-capillary malformation syndrome

MedlinePlus

... the prognosis of a genetic condition? Genetic and Rare Diseases Information Center Frequency The prevalence of MCAP is ... Brain Malformations Health Topic: Vascular Diseases Genetic and Rare Diseases Information Center (1 link) Megalencephaly-capillary malformation syndrome ...

Comparison between magnetic resonance imaging and fetopathology in the evaluation of fetal posterior fossa non-cystic abnormalities.

PubMed

Tilea, B; Delezoide, A L; Khung-Savatovski, S; Guimiot, F; Vuillard, E; Oury, J F; Garel, C

2007-06-01

To compare magnetic resonance imaging (MRI) and fetopathological findings in the evaluation of non-cystic fetal posterior fossa anomalies and to describe associated abnormalities. This was a prospective study from 2000 to 2005 of fetuses identified on ultrasound as having sonographic suspicion of posterior fossa malformation. All underwent a thorough MRI examination of the fetal brain, after which we classified each fetus as presenting one of the following pathologies: vermian hypoplasia or agenesis, cerebellar and/or brain stem hypoplasia, destructive or dysplastic lesions. All of the pregnancies were then terminated, after which the whole fetus underwent fetopathological examination. We compared the findings from MRI and fetopathological examinations and recorded the associated cerebral and extracerebral abnormalities. Twenty-five fetuses were included. MRI was performed at a mean gestational age of 31 weeks, and fetopathological examination at 33 weeks. In 12 cases we observed vermian hypoplasia, six had partial vermian agenesis, 11 had cerebellar hemisphere hypoplasia, seven had brain stem hypoplasia, four had destructive lesions and six had dysplastic lesions. The two techniques were similar in their performance with respect to the detection of vermian agenesis, brain stem hypoplasia and destructive lesions. There were four false-positive results of MRI for vermian hypoplasia and a poor agreement regarding cerebellar hemisphere hypoplasia. No dysplastic lesions were diagnosed by MRI. None of the posterior fossa malformations was isolated and many cerebral and extracerebral abnormalities were found. A systematic analysis of the posterior fossa in fetal MRI makes it possible to diagnose accurately most posterior fossa malformations. These malformations never occurred in isolation in our study.

Unusual Association: Cerebral Arteriovenous Malformation and Chiari Type I Malformation.

PubMed

Ogul, Hayri; Kantarci, Mecit

2017-06-01

Cerebral arteriovenous malformation (AVM) is a common type of cerebral vascular malformation. The imaging findings are enlarged vessels, thrombosed sinuses, and hemorrhage or gliosis on adjacent brain parenchyma. Magnetic resonance (MR) imaging can be used safely for diagnosis. Chiari type I malformation is characterized by a caudal descent of the cerebellar tonsil. Coincidence of cerebral AVM and Chiari type I malformation is very rare. In this paper, the authors report MR imaging findings of a patient with coincidence of cerebral AVM and Chiari type I malformation.

Midline cystic malformations of the brain: imaging diagnosis and classification based on embryologic analysis.

PubMed

Utsunomiya, Hidetsuna; Yamashita, Shinichi; Takano, Koichi; Ueda, Yukiyo; Fujii, Akira

2006-07-01

This article describes a classification and imaging diagnosis of intracranial midline cystic malformations based on neuroembryologic analysis. Midline cystic malformations are classified into two categories from an embryologic point of view. In one category, the cyst represents expansion of the roof plate of the brain vesicle, and in the other the cyst consists of extraaxial structures such as an arachnoid membrane or migrating ependymal cells. Infratentorial cysts, such as the Dandy-Walker cyst or Blake's pouch cyst, and supratentorial cysts, such as a communicating interhemispheric cyst with callosal agenesis or a dorsal cyst with holoprosencephaly, are included in the first category. Infratentorial arachnoid cavities, such as the arachnoid cyst, arachnoid pouch, and mega cisterna magna, are in the second category. Noncommunicating interhemispheric cysts, such as interhemispheric arachnoid cyst or ependymal cyst, with callosal agenesis are also in the second category. A careful review of embryologic development is essential for understanding these midline cysts and for making a more accurate radiologic diagnosis.

Cochlear Implant Outcomes and Genetic Mutations in Children with Ear and Brain Anomalies

PubMed Central

Busi, Micol; Rosignoli, Monica; Minazzi, Federica; Trevisi, Patrizia; Aimoni, Claudia; Calzolari, Ferdinando; Martini, Alessandro

2015-01-01

Background. Specific clinical conditions could compromise cochlear implantation outcomes and drastically reduce the chance of an acceptable development of perceptual and linguistic capabilities. These conditions should certainly include the presence of inner ear malformations or brain abnormalities. The aims of this work were to study the diagnostic value of high resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) in children with sensorineural hearing loss who were candidates for cochlear implants and to analyse the anatomic abnormalities of the ear and brain in patients who underwent cochlear implantation. We also analysed the effects of ear malformations and brain anomalies on the CI outcomes, speculating on their potential role in the management of language developmental disorders. Methods. The present study is a retrospective observational review of cochlear implant outcomes among hearing-impaired children who presented ear and/or brain anomalies at neuroimaging investigations with MRI and HRCT. Furthermore, genetic results from molecular genetic investigations (GJB2/GJB6 and, additionally, in selected cases, SLC26A4 or mitochondrial-DNA mutations) on this study group were herein described. Longitudinal and cross-sectional analysis was conducted using statistical tests. Results. Between January 1, 1996 and April 1, 2012, at the ENT-Audiology Department of the University Hospital of Ferrara, 620 cochlear implantations were performed. There were 426 implanted children at the time of the present study (who were <18 years). Among these, 143 patients (64 females and 79 males) presented ear and/or brain anomalies/lesions/malformations at neuroimaging investigations with MRI and HRCT. The age of the main study group (143 implanted children) ranged from 9 months and 16 years (average = 4.4; median = 3.0). Conclusions. Good outcomes with cochlear implants are possible in patients who present with inner ear or brain abnormalities, even if central nervous system anomalies represent a negative prognostic factor that is made worse by the concomitant presence of cochlear malformations. Common cavity and stenosis of the internal auditory canal (less than 2 mm) are negative prognostic factors even if brain lesions are absent. PMID:26236732

Cochlear Implant Outcomes and Genetic Mutations in Children with Ear and Brain Anomalies.

PubMed

Busi, Micol; Rosignoli, Monica; Castiglione, Alessandro; Minazzi, Federica; Trevisi, Patrizia; Aimoni, Claudia; Calzolari, Ferdinando; Granieri, Enrico; Martini, Alessandro

2015-01-01

Specific clinical conditions could compromise cochlear implantation outcomes and drastically reduce the chance of an acceptable development of perceptual and linguistic capabilities. These conditions should certainly include the presence of inner ear malformations or brain abnormalities. The aims of this work were to study the diagnostic value of high resolution computed tomography (HRCT) and magnetic resonance imaging (MRI) in children with sensorineural hearing loss who were candidates for cochlear implants and to analyse the anatomic abnormalities of the ear and brain in patients who underwent cochlear implantation. We also analysed the effects of ear malformations and brain anomalies on the CI outcomes, speculating on their potential role in the management of language developmental disorders. The present study is a retrospective observational review of cochlear implant outcomes among hearing-impaired children who presented ear and/or brain anomalies at neuroimaging investigations with MRI and HRCT. Furthermore, genetic results from molecular genetic investigations (GJB2/GJB6 and, additionally, in selected cases, SLC26A4 or mitochondrial-DNA mutations) on this study group were herein described. Longitudinal and cross-sectional analysis was conducted using statistical tests. Between January 1, 1996 and April 1, 2012, at the ENT-Audiology Department of the University Hospital of Ferrara, 620 cochlear implantations were performed. There were 426 implanted children at the time of the present study (who were <18 years). Among these, 143 patients (64 females and 79 males) presented ear and/or brain anomalies/lesions/malformations at neuroimaging investigations with MRI and HRCT. The age of the main study group (143 implanted children) ranged from 9 months and 16 years (average = 4.4; median = 3.0). Good outcomes with cochlear implants are possible in patients who present with inner ear or brain abnormalities, even if central nervous system anomalies represent a negative prognostic factor that is made worse by the concomitant presence of cochlear malformations. Common cavity and stenosis of the internal auditory canal (less than 2 mm) are negative prognostic factors even if brain lesions are absent.

Editorial brain malformation surveillance in the Zika era

PubMed Central

Trevathan, Edwin

2016-01-01

The current surveillance systems for congenital microcephaly are necessary to monitor the impact of Zika virus (ZIKV) on the developing human brain, as well as the ZIKV prevention efforts. However, these congenital microcephaly surveillance systems are insufficient. Abnormalities of neuronal differentiation, development and migration may occur among infants with normal head circumference who have intrauterine exposure to ZIKV. Therefore, surveillance for congenital microcephaly does not ascertain many of the infants seriously impacted by congenital ZIKV infection. Furthermore, many infants with normal head circumference and with malformations of the brain cortex do not have clinical manifestations of their congenital malformations until several months to many years after birth, when they present with clinical manifestations such as seizures/epilepsy, developmental delays with or without developmental regression, and/or motor impairment. In response to the ZIKV threat, public health surveillance systems must be enhanced to ascertain a wide variety of congenital brain malformations, as well as their clinical manifestations that lead to diagnostic brain imaging. Birth Defects Research (Part A) 106:869–874, 2016. © 2016 The Authors Birth Defects Research Part A: Clinical and Molecular Teratology Published by Wiley Periodicals, Inc. PMID:27891785

Quantitative Analysis of Chiari-Like Malformation and Syringomyelia in the Griffon Bruxellois Dog

PubMed Central

Knowler, Susan P.; McFadyen, Angus K.; Freeman, Courtenay; Kent, Marc; Platt, Simon R.; Kibar, Zoha; Rusbridge, Clare

2014-01-01

This study aimed to develop a system of quantitative analysis of canine Chiari-like malformation and syringomyelia on variable quality MRI. We made a series of measurements from magnetic resonance DICOM images from Griffon Bruxellois dogs with and without Chiari-like malformation and syringomyelia and identified several significant variables. We found that in the Griffon Bruxellois dog, Chiari-like malformation is characterized by an apparent shortening of the entire cranial base and possibly by increased proximity of the atlas to the occiput. As a compensatory change, there appears to be an increased height of the rostral cranial cavity with lengthening of the dorsal cranial vault and considerable reorganization of the brain parenchyma including ventral deviation of the olfactory bulbs and rostral invagination of the cerebellum under the occipital lobes. PMID:24533070

Holoprosencephaly: from Homer to Hedgehog.

PubMed

Ming, J E; Muenke, M

1998-03-01

Holoprosencephaly (HPE), a common developmental defect affecting the forebrain and face, is etiologically heterogeneous and exhibits wide phenotypic variation. Graded degrees of severity of the brain malformation are also reflected in the highly variable craniofacial malformations associated with HPE. In addition, individuals with microforms of HPE, who usually have normal cognition and normal brain imaging, are at risk for having children with HPE. Some obligate carriers for HPE may not have any phenotypic abnormalities. Recurrent chromosomal rearrangements in individuals with HPE suggest loci containing genes important for brain development, and abnormalities in these genes may result in HPE. Recently, Sonic Hedgehog (SHH) was the first gene identified as causing HPE in humans. Proper function of SHH depends on cholesterol modification. Other candidate genes that may be involved in HPE include components of the SHH pathway, elements involved in cholesterol metabolism, and genes expressed in the developing forebrain.

Cerebro-fronto-facial syndrome type 3 with polymicrogyria: a clinical presentation of Baraitser-Winter syndrome.

PubMed

Eker, Hatice Koçak; Derinkuyu, Betül Emine; Ünal, Sevim; Masliah-Planchon, Julien; Drunat, Séverine; Verloes, Alain

2014-01-01

Baraitser-Winter syndrome (BRWS) is a rare condition affecting the development of the brain and the face. The most common characteristics are unusual facial appearance including hypertelorism and ptosis, ocular colobomas, hearing loss, impaired neuronal migration and intellectual disability. BRWS is caused by mutations in the ACTB and ACTG1 genes. Cerebro-fronto-facial syndrome (CFFS) is a clinically heterogeneous condition with distinct facial dysmorphism, and brain abnormalities. Three subtypes are identified. We report a female infant with striking facial features and brain anomalies (included polymicrogyria) that fit into the spectrum of the CFFS type 3 (CFFS3). She also had minor anomalies on her hands and feet, heart and kidney malformations, and recurrent infections. DNA investigations revealed c.586C>T mutation (p.Arg196Cys) in ACTB. This mutation places this patient in the spectrum of BRWS. The same mutation has been detected in a polymicrogyric patient reported previously in literature. We expand the malformation spectrum of BRWS/CFFS3, and present preliminary findings for phenotype-genotype correlation in this spectrum. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Embolization of Brain Aneurysms and Fistulas

MedlinePlus

... Resources Professions Site Index A-Z Embolization of Brain Aneurysms and Arteriovenous Malformations/Fistulas Embolization of brain ... Brain Aneurysms and Fistulas? What is Embolization of Brain Aneurysms and Fistulas? Embolization of brain aneurysms and ...

Neuroimaging of Dandy-Walker malformation: new concepts.

PubMed

Correa, Gustavo Gumz; Amaral, Lázaro Faria; Vedolin, Leonardo Modesti

2011-12-01

Dandy-Walker malformation (DWM) is the most common human cerebellar malformation, characterized by hypoplasia of the cerebellar vermis, cystic dilation of the fourth ventricle, and an enlarged posterior fossa with upward displacement of the lateral sinuses, tentorium, and torcular. Although its pathogenesis is not completely understood, there are several genetic loci related to DWM as well as syndromic malformations and congenital infections. Dandy-Walker malformation is associated with other central nervous system abnormalities, including dysgenesis of corpus callosum, ectopic brain tissue, holoprosencephaly, and neural tube defects. Hydrocephalus plays an important role in the development of symptoms and neurological outcome in patients with DWM, and the aim of surgical treatment is usually the control of hydrocephalus and the posterior fossa cyst. Imaging modalities, especially magnetic resonance imaging, are crucial for the diagnosis of DWM and distinguishing this disorder from other cystic posterior fossa lesions. Persistent Blake's cyst is seen as a retrocerebellar fluid collection with cerebrospinal fluid signal intensity and a median line communication with the fourth ventricle, commonly associated with hydrocephalus. Mega cisterna magna presents as an extraaxial fluid collection posteroinferior to an intact cerebellum. Retrocerebellar arachnoid cysts frequently compress the cerebellar hemispheres and the fourth ventricle. Patients with DWM show an enlarged posterior fossa filled with a cystic structure that communicates freely with the fourth ventricle and hypoplastic vermis. Comprehension of hindbrain embryology is of utmost importance for understanding the cerebellar malformations, including DWM, and other related entities.

Brain and bone abnormalities of thanatophoric dwarfism.

PubMed

Miller, Elka; Blaser, Susan; Shannon, Patrick; Widjaja, Elysa

2009-01-01

The purpose of this article is to present the imaging findings of skeletal and brain abnormalities in thanatophoric dwarfism, a lethal form of dysplastic dwarfism. The bony abnormalities associated with thanatophoric dwarfism include marked shortening of the tubular bones and ribs. Abnormal temporal lobe development is a common associated feature and can be visualized as early as the second trimester. It is important to assess the brains of fetuses with suspected thanatophoric dwarfism because the presence of associated brain malformations can assist in the antenatal diagnosis of thanatophoric dwarfism.

Malformations of cortical development: 3T magnetic resonance imaging features

PubMed Central

Battal, Bilal; Ince, Selami; Akgun, Veysel; Kocaoglu, Murat; Ozcan, Emrah; Tasar, Mustafa

2015-01-01

Malformation of cortical development (MCD) is a term representing an inhomogeneous group of central nervous system abnormalities, referring particularly to embriyological aspect as a consequence of any of the three developmental stages, i.e., cell proliferation, cell migration and cortical organization. These include cotical dysgenesis, microcephaly, polymicrogyria, schizencephaly, lissencephaly, hemimegalencephaly, heterotopia and focal cortical dysplasia. Since magnetic resonance imaging is the modality of choice that best identifies the structural anomalies of the brain cortex, we aimed to provide a mini review of MCD by using 3T magnetic resonance scanner images. PMID:26516429

PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia

PubMed Central

Mirzaa, Ghayda M.; Ishak, Gisele E.; O'Roak, Brian J.; Hiatt, Joseph B.; Roden, William H.; Gunter, Sonya A.; Christian, Susan L.; Collins, Sarah; Adams, Carissa; Rivière, Jean-Baptiste; St-Onge, Judith; Ojemann, Jeffrey G.; Shendure, Jay; Hevner, Robert F.; Dobyns, William B.

2015-01-01

Malformations of cortical development containing dysplastic neuronal and glial elements, including hemimegalencephaly and focal cortical dysplasia, are common causes of intractable paediatric epilepsy. In this study we performed multiplex targeted sequencing of 10 genes in the PI3K/AKT pathway on brain tissue from 33 children who underwent surgical resection of dysplastic cortex for the treatment of intractable epilepsy. Sequencing results were correlated with clinical, imaging, pathological and immunohistological phenotypes. We identified mosaic activating mutations in PIK3CA and AKT3 in this cohort, including cancer-associated hotspot PIK3CA mutations in dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia type IIa. In addition, a germline PTEN mutation was identified in a male with hemimegalencephaly but no peripheral manifestations of the PTEN hamartoma tumour syndrome. A spectrum of clinical, imaging and pathological abnormalities was found in this cohort. While patients with more severe brain imaging abnormalities and systemic manifestations were more likely to have detected mutations, routine histopathological studies did not predict mutation status. In addition, elevated levels of phosphorylated S6 ribosomal protein were identified in both neurons and astrocytes of all hemimegalencephaly and focal cortical dysplasia type II specimens, regardless of the presence or absence of detected PI3K/AKT pathway mutations. In contrast, expression patterns of the T308 and S473 phosphorylated forms of AKT and in vitro AKT kinase activities discriminated between mutation-positive dysplasia cortex, mutation-negative dysplasia cortex, and non-dysplasia epilepsy cortex. Our findings identify PI3K/AKT pathway mutations as an important cause of epileptogenic brain malformations and establish megalencephaly, hemimegalencephaly, and focal cortical dysplasia as part of a single pathogenic spectrum. PMID:25722288

Brain Arteriovenous Malformation Pathogenesis: A Response-to-Injury Paradigm

PubMed Central

Kim, Helen; Su, Hua; Weinsheimer, Shantel; Pawlikowska, Ludmila; Young, William L.

2011-01-01

Brain arteriovenous malformations (AVMs) are a rare but important cause of intracranial hemorrhage (ICH) in young adults. In this paper, we review both human and animal studies of brain AVM, focusing on the: (1) natural history of AVM hemorrhage; (2) genetic and expression studies of AVM susceptibility and hemorrhage; and (3) strategies for development of a brain AVM model in adult mice. These data target various mechanisms which must act in concert to regulate normal angiogenic response to injury. Based on the various lines of evidence reviewed in this paper, we propose a “response-to-injury” model of brain AVM pathogenesis. PMID:21725736

Brain vascular lesions: a clinicopathologic, immunohistochemistry, and ultrastructural approach.

PubMed

Navarrete, Marisol Galván; Hernández, Alma Dalia; Collado-Ortiz, Miguel Angel; Salinas-Lara, Citlaltepetl; Tena-Suck, Martha Lilia

2014-08-01

Brain vascular malformations are relatively common lesions that cause serious neurologic disability or death in a significant proportion of individuals bearing them. The purpose of this study was to analyze the clinicopathologic and immunohistochemistry these lesions, looking for common antibodies expressed such as CD31, CD34, CD15, factor VIII, nestin, vimentin, vascular endothelial grow factor (VEGF), vascular endothelial grow factor receptor-2 (VEGF-R2), glial fibrillar acidic protien (GFAP), and fibroblastic grow factor β (β-FGF) and ultrastructure in endothelial cells as well as in vessel walls. Fifty cases of vascular lesions were included in this study: 29 (58%) of them were arteriovenous malformations and 21 (52%) were brain cavernomas. Twenty-six (52%) patients were women and 24 (48%) men. The age range was from 13 to 68 years (mean age, 35.86 ± 15.19 years). The size of the lesions ranged between 1 and 8 cm (3 ± 1.65 cm), and parieto-occipital lesions had a bigger size. Evolution time varied from 1 month to 1 year (mean, 7.5 months). There was a significant statistical correlation between age and sex (P = -035), rupture of lesion (P = .015), brain hemorrhage (P = .033), necrosis (P = .011), hemosiderin deposit (P = .042), VEGF (P = .015), and VEGFR (P = .037), as well as localization of rupture (P = .017), loss of consciousness (P = .000), visual deficit (P = .026), hyaline vessels (P = .000), and CD31 (.009). Interactions between endothelial cells and mural cells (pericytes and vascular smooth muscle cells) in blood vessel walls have recently come into focus as central processes in the regulation of vascular formation, stabilization, remodeling, and function in brain vascular lesions. However, the molecular mechanisms that underlie the formation and growth of brain arteriovenous malformations are still poorly understood. Copyright © 2014 Elsevier Inc. All rights reserved.

Familial Dandy-Walker malformation associated with macrocephaly, facial anomalies, developmental delay, and brain stem dysgenesis: prenatal diagnosis and postnatal outcome in brothers. A new syndrome?

PubMed

Chitayat, D; Moore, L; Del Bigio, M R; MacGregor, D; Ben-Zeev, B; Hodgkinson, K; Deck, J; Stothers, T; Ritchie, S; Toi, A

1994-10-01

Brothers are reported with an apparently new constellation of manifestations including Dandy-Walker complex (DWC), migrational brain disorder, macrocephaly, and facial anomalies. The first brother presented at birth, the second was detected prenatally with DWC and the pregnancy terminated. Fetal brain histopathology showed DWC associated with brainstem dysgenesis. Inheritance is likely autosomal or X-linked recessive. An extensive review of the differential diagnosis of DWC is provided.

Fetal Magnetic Resonance Imaging Findings in Prenatal Zika Virus Infection.

PubMed

Sanín-Blair, José Enrique; Gutiérrez-Márquez, Carolina; Herrera, Diego A; Vossough, Arastoo

2017-01-01

Brain lesions and malformations have been described on ultrasonography of prenatal Zika infection; however, there are scarce reports about fetal magnetic resonance (MR) findings. We report 3 cases of fetuses with confirmed intrauterine Zika virus infection evaluated by ultrasound and fetal MR. Various morphometric measurements were assessed and brain maturation was calculated with the fetal total maturation score. Fetuses with prenatal Zika virus infection showed retardation in brain maturation indexes evaluated by fetal MR. Brain calcifications were demonstrated by neurosonography in all cases, while fetal MR characterized the specific type of cortical development malformation. © 2017 S. Karger AG, Basel.

Mild Malformation of Cortical Development with Oligodendroglial Hyperplasia in Frontal Lobe Epilepsy: A New Clinico-Pathological Entity.

PubMed

Schurr, Johannes; Coras, Roland; Rössler, Karl; Pieper, Tom; Kudernatsch, Manfred; Holthausen, Hans; Winkler, Peter; Woermann, Friedrich; Bien, Christian G; Polster, Tilman; Schulz, Reinhard; Kalbhenn, Thilo; Urbach, Horst; Becker, Albert; Grunwald, Thomas; Huppertz, Hans-Juergen; Gil-Nagel, Antonio; Toledano, Rafael; Feucht, Martha; Mühlebner, Angelika; Czech, Thomas; Blümcke, Ingmar

2017-01-01

The histopathological spectrum of human epileptogenic brain lesions is widespread including common and rare variants of cortical malformations. However, 2-26% of epilepsy surgery specimens are histopathologically classified as nonlesional. We hypothesized that these specimens include also new diagnostic entities, in particular when presurgical magnetic resonance imaging (MRI) can identify abnormal signal intensities within the anatomical region of seizure onset. In our series of 1381 en bloc resected epilepsy surgery brain specimens, 52 cases could not be histopathologically classified and were considered nonlesional (3.7%). An increase of Olig2-, and PDGFR-alpha-immunoreactive oligodendroglia was observed in white matter and deep cortical layers in 22 of these patients (42%). Increased proliferation activity as well as heterotopic neurons in white matter were additional histopathological hallmarks. All patients suffered from frontal lobe epilepsy (FLE) with a median age of epilepsy onset at 4 years and 16 years at epilepsy surgery. Presurgical MRI suggested focal cortical dysplasia (FCD) in all patients. We suggest to classify this characteristic histopathology pattern as "mild malformation of cortical development with oligodendroglial hyperplasia (MOGHE)." Further insights into pathomechanisms of MOGHE may help to bridge the diagnostic gap in children and young adults with difficult-to-treat FLE. © 2016 International Society of Neuropathology.

Contribution of Rare Copy Number Variants to Isolated Human Malformations

PubMed Central

Serra-Juhé, Clara; Rodríguez-Santiago, Benjamín; Cuscó, Ivon; Vendrell, Teresa; Camats, Núria; Torán, Núria; Pérez-Jurado, Luis A.

2012-01-01

Background Congenital malformations are present in approximately 2–3% of liveborn babies and 20% of stillborn fetuses. The mechanisms underlying the majority of sporadic and isolated congenital malformations are poorly understood, although it is hypothesized that the accumulation of rare genetic, genomic and epigenetic variants converge to deregulate developmental networks. Methodology/Principal Findings We selected samples from 95 fetuses with congenital malformations not ascribed to a specific syndrome (68 with isolated malformations, 27 with multiple malformations). Karyotyping and Multiplex Ligation-dependent Probe Amplification (MLPA) discarded recurrent genomic and cytogenetic rearrangements. DNA extracted from the affected tissue (46%) or from lung or liver (54%) was analyzed by molecular karyotyping. Validations and inheritance were obtained by MLPA. We identified 22 rare copy number variants (CNV) [>100 kb, either absent (n = 7) or very uncommon (n = 15, <1/2,000) in the control population] in 20/95 fetuses with congenital malformations (21%), including 11 deletions and 11 duplications. One of the 9 tested rearrangements was de novo while the remaining were inherited from a healthy parent. The highest frequency was observed in fetuses with heart hypoplasia (8/17, 62.5%), with two events previously related with the phenotype. Double events hitting candidate genes were detected in two samples with brain malformations. Globally, the burden of deletions was significantly higher in fetuses with malformations compared to controls. Conclusions/Significance Our data reveal a significant contribution of rare deletion-type CNV, mostly inherited but also de novo, to human congenital malformations, especially heart hypoplasia, and reinforce the hypothesis of a multifactorial etiology in most cases. PMID:23056206

PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia.

PubMed

Jansen, Laura A; Mirzaa, Ghayda M; Ishak, Gisele E; O'Roak, Brian J; Hiatt, Joseph B; Roden, William H; Gunter, Sonya A; Christian, Susan L; Collins, Sarah; Adams, Carissa; Rivière, Jean-Baptiste; St-Onge, Judith; Ojemann, Jeffrey G; Shendure, Jay; Hevner, Robert F; Dobyns, William B

2015-06-01

Malformations of cortical development containing dysplastic neuronal and glial elements, including hemimegalencephaly and focal cortical dysplasia, are common causes of intractable paediatric epilepsy. In this study we performed multiplex targeted sequencing of 10 genes in the PI3K/AKT pathway on brain tissue from 33 children who underwent surgical resection of dysplastic cortex for the treatment of intractable epilepsy. Sequencing results were correlated with clinical, imaging, pathological and immunohistological phenotypes. We identified mosaic activating mutations in PIK3CA and AKT3 in this cohort, including cancer-associated hotspot PIK3CA mutations in dysplastic megalencephaly, hemimegalencephaly, and focal cortical dysplasia type IIa. In addition, a germline PTEN mutation was identified in a male with hemimegalencephaly but no peripheral manifestations of the PTEN hamartoma tumour syndrome. A spectrum of clinical, imaging and pathological abnormalities was found in this cohort. While patients with more severe brain imaging abnormalities and systemic manifestations were more likely to have detected mutations, routine histopathological studies did not predict mutation status. In addition, elevated levels of phosphorylated S6 ribosomal protein were identified in both neurons and astrocytes of all hemimegalencephaly and focal cortical dysplasia type II specimens, regardless of the presence or absence of detected PI3K/AKT pathway mutations. In contrast, expression patterns of the T308 and S473 phosphorylated forms of AKT and in vitro AKT kinase activities discriminated between mutation-positive dysplasia cortex, mutation-negative dysplasia cortex, and non-dysplasia epilepsy cortex. Our findings identify PI3K/AKT pathway mutations as an important cause of epileptogenic brain malformations and establish megalencephaly, hemimegalencephaly, and focal cortical dysplasia as part of a single pathogenic spectrum. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Management of small arteriovenous malformations of the brain.

PubMed

Morgan, M K; Davidson, J; Sorby, W; Grinnell, V

1995-10-01

A consecutive series of arteriovenous malformations of the brain, no greater than 3 cm in diameter, referred to the author between January 1989 and October 1994 is reviewed. Of these 42 cases 39 underwent surgical excision of the lesion. The surgical group had mortality, 2.5% morbidity and 100% angiographic cure. Surgery in non-eloquent brain (n=21) resulted in no neurological morbidity and surgery in eloquent brain (n=18) resulted in a 5.5% neurological morbidity. The reason for not operating in three cases was elderly age in one, poor neurological condition in one, and involvement of the posterior limb of the internal capsule in one. Arteriovenous malformations with diameters no greater than 3 cm are considered by some to be suitable for treatment by focussed irradiation. However, surgery is likely to remain the more effective and safer mode of treatment for the majority of cases when factoring in the expected complications of focussed irradiation during the latency period. These risks are discussed.

Molecular genetics in fetal neurology.

PubMed

Huang, Jin; Wah, Isabella Y M; Pooh, Ritsuko K; Choy, Kwong Wai

2012-12-01

Brain malformations, particularly related to early brain development, are a clinically and genetically heterogeneous group of fetal neurological disorders. Fetal cerebral malformation, predominantly of impaired prosencephalic development namely agenesis of the corpus callosum and septo-optic dysplasia, is the main pathological feature in fetus, and causes prominent neurodevelopmental retardation, and associated with congenital facial anomalies and visual disorders. Differential diagnosis of brain malformations can be extremely difficult even through magnetic resonance imaging. Advances in genomic and molecular genetics technologies have led to the identification of the sonic hedgehog pathways and genes critical to the normal brain development. Molecular cytogenetic and genetic studies have identified numeric and structural chromosomal abnormalities as well as mutations in genes important for the etiology of fetal neurological disorders. In this review, we update the molecular genetics findings of three common fetal neurological abnormalities, holoprosencephaly, lissencephaly and agenesis of the corpus callosum, in an attempt to assist in perinatal and prenatal diagnosis. Copyright © 2012 Elsevier Ltd. All rights reserved.

Genetics Home Reference: spondylocostal dysostosis

MedlinePlus

... spina bifida and a brain abnormality called a Chiari malformation. Although breathing problems can be fatal early in ... Resources MedlinePlus (6 links) Encyclopedia: Scoliosis Health Topic: Chiari Malformation Health Topic: Neural Tube Defects Health Topic: Scoliosis ...

Profound microcephaly, primordial dwarfism with developmental brain malformations: a new syndrome.

PubMed

Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Saleem, Sahar N; Ahmed, Mahmoud K H; Issa, Mahmoud; Effat, Laila K; Kayed, Hisham F; Zaki, Maha S; Gaber, Khaled R

2012-08-01

We describe two sibs with a lethal form of profound congenital microcephaly, intrauterine and postnatal growth retardation, subtle skeletal changes, and poorly developed brain. The sibs had striking absent cranial vault with sloping of the forehead, large beaked nose, relatively large ears, and mandibular micro-retrognathia. Brain magnetic resonance imaging (MRI) revealed extremely simplified gyral pattern, large interhemispheric cyst and agenesis of corpus callosum, abnormally shaped hippocampus, and proportionately affected cerebellum and brainstem. In addition, fundus examination showed foveal hypoplasia with optic nerve atrophy. No abnormalities of the internal organs were found. This profound form of microcephaly was identified at 17 weeks gestation by ultrasound and fetal brain MRI helped in characterizing the developmental brain malformations in the second sib. Molecular analysis excluded mutations in potentially related genes such as RNU4ATAC, SLC25A19, and ASPM. These clinical and imaging findings are unlike that of any recognized severe forms of microcephaly which is believed to be a new microcephalic primordial dwarfism (MPD) with developmental brain malformations with most probably autosomal recessive inheritance based on consanguinity and similarly affected male and female sibs. Copyright © 2012 Wiley Periodicals, Inc.

A newborn with neurocutaneous melanocytosis and Dandy-Walker malformation.

PubMed

De Cock, Jens; Snauwaert, Julie; Van Rompaey, Walter; Morren, Marie-Anne; Demaerel, Philippe

2014-03-01

Neurocutaneous melanocytosis is a rare congenital dysplasia of the neuroectodermal melanocyte precursor cells that leads to proliferation of melanin-producing cells in the skin and leptomeninges. We describe a newborn with a giant congenital melanocytic nevus on his back, buttocks, and thighs. His brain magnetic resonance imaging study revealed bilateral T1 hyperintense lesions in the cerebellum and in the amygdala, hydrocephalus, and a Blake's pouch cyst, consistent with neurocutaneous melanocytosis and Dandy-Walker malformation. Neurocutaneous melanocytosis has a wide clinical spectrum that includes hydrocephalus, epilepsy, cranial nerve palsy, increased intracranial pressure, and sensorimotor deficits. Copyright © 2014. Published by Elsevier Inc.

Transverse sinus stenosis in adult patients with Chiari malformation type I.

PubMed

Saindane, Amit M; Bruce, Beau B; Desai, Nilesh K; Roller, Lauren A; Newman, Nancy J; Biousse, Valérie

2014-10-01

Transverse sinus stenosis is an imaging finding very highly associated with elevated intracranial pressure (ICP). Patients with the Chiari I malformation may potentially have elevated ICP due to impairment of CSF flow at the foramen magnum. This study evaluated whether patients with Chiari I malformation have transverse sinus stenosis and other imaging findings indicative of elevated ICP. Thirty patients with Chiari I malformation treated surgically and 76 control subjects were identified retrospectively. All control subjects and all patients with Chiari I malformation (preoperatively) underwent standardized contrast-enhanced brain MRI including a contrast-enhanced 3D T1-weighted sequence from which curved reformats of the transverse sinuses were generated. Two different readers blinded to the diagnosis then independently evaluated these curved reformats for severity of transverse sinus stenosis. Orbital and skull-base findings previously described in association with elevated ICP were also evaluated. Frequency of MRI findings between the two groups was compared. Patients with Chiari I malformation had significantly greater frequency of unilateral or bilateral transverse sinus stenosis than did control subjects (p < 0.001). There was complete interreader agreement on presence or absence of transverse sinus stenosis by patient (κ = 1.0 [95% CI, 0.89-1.0]). Logistic regression analysis controlling for age, sex, and body mass index found that transverse sinus stenosis significantly predicted Chiari I malformation versus control status (odds ratio, 11.2 [95% CI, 2.1-59.0]; p = 0.004) but that no other features were significantly associated with the Chiari I malformation. Patients with Chiari I malformation who had transverse sinus stenosis had significantly greater pituitary flattening than did those without transverse sinus stenosis (p = 0.02). Patients with Chiari I malformation have higher likelihood of transverse sinus stenosis, which may reflect associated elevated ICP.

First-trimester sonographic findings associated with a Dandy-Walker malformation and inferior vermian hypoplasia.

PubMed

Bornstein, Eran; Goncalves Rodríguez, José Luis; Álvarez Pavón, Erika Carolina; Quiroga, Héctor; Or, Drorit; Divon, Michael Y

2013-10-01

We report 2 cases in which first-trimester measurements of the intracranial translucency and the brain stem-to-occipital bone diameter were markedly enlarged. This finding was thought to represent an abnormal fourth ventricle-cisterna magna complex. Subsequently, the diagnoses of a Dandy-Walker malformation with partial vermian agenesis in 1 case and inferior vermian hypoplasia in the other were established and confirmed by either postmortem autopsy or postnatal magnetic resonance imaging. These cases suggest that evaluation of the fourth ventricle-cisterna magna complex, by measuring the intracranial translucency or brain stem-to-occipital bone diameter may identify some cases with structural malformations of the cerebellum as early as the first trimester.

Using Ferumoxytol-Enhanced MRI to Measure Inflammation in Patients With Brain Tumors or Other Conditions of the CNS

ClinicalTrials.gov

2017-08-30

Brain Injury; Central Nervous System Degenerative Disorder; Central Nervous System Infectious Disorder; Central Nervous System Vascular Malformation; Hemorrhagic Cerebrovascular Accident; Ischemic Cerebrovascular Accident; Primary Brain Neoplasm; Brain Cancer; Brain Tumors

Mixed vascular nevus syndrome: a report of four new cases and a literature review.

PubMed

Ruggieri, Martino; Polizzi, Agata; Strano, Serena; Schepis, Carmelo; Morano, Massimiliano; Belfiore, Giuseppe; Palmucci, Stefano; Foti, Pietro Valerio; Pirrone, Concetta; Sofia, Vito; David, Emanuele; Salpietro, Vincenzo; Mankad, Kshitij; Milone, Pietro

2016-10-01

Mixed vascular nevus (or nevus vascularis mixtus) represents an admixture of cutaneous vascular malformations of the telangiectatic type and angiospastic spots of nevus anemicus. It can occur as an purely cutaneous trait or as a hallmark of a neurocutaneous phenotype (mixed vascular nevus syndrome) characterised by the combination of: (I) paired vascular (telangiectatic and anemic) twin nevi and brain abnormalities of the Dyke-Davidoff-Masson type (i.e., crossed cerebral/cerebellar hemiatrophy with hypoplasia of the ipsilateral cerebral vessels and homolateral hypertrophy of the skull and sinuses (hyperpneumatisation) with contralateral hemispheric hypertrophy); or (II) paired vascular twin nevi and brain malformations of the Dyke-Davidoff-Masson type in association with systemic abnormalities consisting in facial asymmetry, skeletal anomalies (i.e., Legg-Calvé-Perthes-like disease) and disorders of autoimmunity (i.e., diabetes, thyroiditis). In 2014, Happle proposed to name the syndrome with the eponym Ruggieri-Leech syndrome. Review of the existing literature on nevus vascularis mixtus and information on our personal experience on new cases and follow-up of previously reported cases by some of us. The existing literature revealed 4 previous studies including 33 cases with an inferred purely cutaneous trait and 3 cases with a combination of paired vascular twin nevi and brain malformation of the Dyke-Davidoff-Masson type. Our personal experience includes 4 unpublished patients (1 female and 3 males; currently aged 2 to 34 years) seen and followed-up at our Institutions in Italy who had: paired vascular nevi involving either the face (n=2) or the face and parts of the body (n=2); facial asymmetry (n=4); mild to moderate facial dysmorphic features (n=2); developmental delay (n=3); seizures/stroke-like episodes and associated hemiplegia (n=4); muscular hypotrophy (n=2); mild to moderate hemispheric atrophy (n=4); skull osseous hypertrophy (n=4); hyperpneumatisation of the sinuses (n=2); hypoplastic brain vessels (n=4); colpocephaly and malformation of cortical development (n=2). Follow-up data on our previous 2 cases revealed that the vascular abnormalities in the skin and nervous system were stable over years without neurological progression or deterioration. Pathogenically, this complex phenotype suggests that embryonic pairing and somatic recombination of recessive (didymotic) alleles controlling the balance between constriction (i.e., nevus anemicus) and dilatation (i.e., nevus telangiectaticus) of blood vessels could be the primary event causing the phenomena of cutaneous and brain vascular twin spotting and the paired phenomena of skull hyperpneumatisation vs . hypertrophy and brain megalencephaly/colpocephaly vs . cortical dysplasia. This association is likely more frequent than previously thought and should be investigated by means of: (I) brain and spinal cord imaging (combination of CT and MRI studies); (II) skeletal X-ray studies (when dictated by clinical findings); (III) systemic ultrasound studies; (IV) neurophysiologic studies (EEG); (V) psychomotor testing; (VI) and laboratory investigation (including immune-mediated dysfunction).

Mixed vascular nevus syndrome: a report of four new cases and a literature review

PubMed Central

Polizzi, Agata; Strano, Serena; Schepis, Carmelo; Morano, Massimiliano; Belfiore, Giuseppe; Palmucci, Stefano; Foti, Pietro Valerio; Pirrone, Concetta; Sofia, Vito; David, Emanuele; Salpietro, Vincenzo; Mankad, Kshitij; Milone, Pietro

2016-01-01

Background Mixed vascular nevus (or nevus vascularis mixtus) represents an admixture of cutaneous vascular malformations of the telangiectatic type and angiospastic spots of nevus anemicus. It can occur as an purely cutaneous trait or as a hallmark of a neurocutaneous phenotype (mixed vascular nevus syndrome) characterised by the combination of: (I) paired vascular (telangiectatic and anemic) twin nevi and brain abnormalities of the Dyke-Davidoff-Masson type (i.e., crossed cerebral/cerebellar hemiatrophy with hypoplasia of the ipsilateral cerebral vessels and homolateral hypertrophy of the skull and sinuses (hyperpneumatisation) with contralateral hemispheric hypertrophy); or (II) paired vascular twin nevi and brain malformations of the Dyke-Davidoff-Masson type in association with systemic abnormalities consisting in facial asymmetry, skeletal anomalies (i.e., Legg-Calvé-Perthes-like disease) and disorders of autoimmunity (i.e., diabetes, thyroiditis). In 2014, Happle proposed to name the syndrome with the eponym Ruggieri-Leech syndrome. Methods Review of the existing literature on nevus vascularis mixtus and information on our personal experience on new cases and follow-up of previously reported cases by some of us. Results The existing literature revealed 4 previous studies including 33 cases with an inferred purely cutaneous trait and 3 cases with a combination of paired vascular twin nevi and brain malformation of the Dyke-Davidoff-Masson type. Our personal experience includes 4 unpublished patients (1 female and 3 males; currently aged 2 to 34 years) seen and followed-up at our Institutions in Italy who had: paired vascular nevi involving either the face (n=2) or the face and parts of the body (n=2); facial asymmetry (n=4); mild to moderate facial dysmorphic features (n=2); developmental delay (n=3); seizures/stroke-like episodes and associated hemiplegia (n=4); muscular hypotrophy (n=2); mild to moderate hemispheric atrophy (n=4); skull osseous hypertrophy (n=4); hyperpneumatisation of the sinuses (n=2); hypoplastic brain vessels (n=4); colpocephaly and malformation of cortical development (n=2). Follow-up data on our previous 2 cases revealed that the vascular abnormalities in the skin and nervous system were stable over years without neurological progression or deterioration. Conclusions Pathogenically, this complex phenotype suggests that embryonic pairing and somatic recombination of recessive (didymotic) alleles controlling the balance between constriction (i.e., nevus anemicus) and dilatation (i.e., nevus telangiectaticus) of blood vessels could be the primary event causing the phenomena of cutaneous and brain vascular twin spotting and the paired phenomena of skull hyperpneumatisation vs. hypertrophy and brain megalencephaly/colpocephaly vs. cortical dysplasia. This association is likely more frequent than previously thought and should be investigated by means of: (I) brain and spinal cord imaging (combination of CT and MRI studies); (II) skeletal X-ray studies (when dictated by clinical findings); (III) systemic ultrasound studies; (IV) neurophysiologic studies (EEG); (V) psychomotor testing; (VI) and laboratory investigation (including immune-mediated dysfunction). PMID:27942471

The Dandy-Walker malformation. A review of 40 cases.

PubMed

Hirsch, J F; Pierre-Kahn, A; Renier, D; Sainte-Rose, C; Hoppe-Hirsch, E

1984-09-01

Forty cases of Dandy-Walker malformation referred to the Hôpital Necker Enfants-Malades between 1969 and 1982 have been reviewed. The incidence of the malformation in hydrocephalus was 2.4%. There was a slight, statistically insignificant, female prevalence. Hydrocephalus should not be included in the definition of the syndrome. In 80% of the cases, it was actually a post-natal complication of the malformation and most often developed within 3 months after birth. In 80% of the cases, a communication, although insufficient, was found between the dilated 4th ventricle and the subarachnoid space. Since this communication is probably established through the foramina of Luschka, the definition of the Dandy-Walker malformation should only include atresia of the foramen of Magendie. Associated brain and systemic malformations were numerous. Among facial anomalies, facial angiomas were found in 10% of our cases. The association of facial and cardiovascular anomalies favors the hypothesis that the onset of the malformation occurs between the formation and the migration of the cells of the neural crest (that is, between the 3rd and the 4th post-ovulatory week, earlier than previously thought). Except in selected patients, membrane excision has a high rate of failure and should be abandoned. Cyst-peritoneal shunting avoids the risk of an entrapped fourth ventricle and is presently the best surgical procedure. The overall mortality in this series was 12.5%. Intelligence quotients were over 80 in 60% of the patients. Other studies will be necessary to understand why the communication between the fourth ventricle and the subarachnoid spaces, sufficient in utero, usually becomes insufficient for a normal cerebrospinal fluid (CSF) circulation in the first months following birth. Two hypotheses are discussed: a change in CSF circulation, or bleeding in the dilated fourth ventricle during delivery.

Pathophysiology of increased cerebrospinal fluid pressure associated to brain arteriovenous malformations: The hydraulic hypothesis.

PubMed

Rossitti, Sandro

2013-01-01

Brain arteriovenous malformations (AVMs) produce circulatory and functional disturbances in adjacent as well as in remote areas of the brain, but their physiological effect on the cerebrospinal fluid (CSF) pressure is not well known. The hypothesis of an intrinsic disease mechanism leading to increased CSF pressure in all patients with brain AVM is outlined, based on a theory of hemodynamic control of intracranial pressure that asserts that CSF pressure is a fraction of the systemic arterial pressure as predicted by a two-resistor series circuit hydraulic model. The resistors are the arteriolar resistance (that is regulated by vasomotor tonus), and the venous resistance (which is mechanically passive as a Starling resistor). This theory is discussed and compared with the knowledge accumulated by now on intravasal pressures and CSF pressure measured in patients with brain AVM. The theory provides a basis for understanding the occurrence of pseudotumor cerebri syndrome in patients with nonhemorrhagic brain AVMs, for the occurrence of local mass effect and brain edema bordering unruptured AVMs, and for the development of hydrocephalus in patients with unruptured AVMs. The theory also contributes to a better appreciation of the pathophysiology of dural arteriovenous fistulas, of vein of Galen aneurismal malformation, and of autoregulation-related disorders in AVM patients. The hydraulic hypothesis provides a comprehensive frame to understand brain AVM hemodynamics and its effect on the CSF dynamics.

Pathophysiology of increased cerebrospinal fluid pressure associated to brain arteriovenous malformations: The hydraulic hypothesis

PubMed Central

Rossitti, Sandro

2013-01-01

Background: Brain arteriovenous malformations (AVMs) produce circulatory and functional disturbances in adjacent as well as in remote areas of the brain, but their physiological effect on the cerebrospinal fluid (CSF) pressure is not well known. Methods: The hypothesis of an intrinsic disease mechanism leading to increased CSF pressure in all patients with brain AVM is outlined, based on a theory of hemodynamic control of intracranial pressure that asserts that CSF pressure is a fraction of the systemic arterial pressure as predicted by a two-resistor series circuit hydraulic model. The resistors are the arteriolar resistance (that is regulated by vasomotor tonus), and the venous resistance (which is mechanically passive as a Starling resistor). This theory is discussed and compared with the knowledge accumulated by now on intravasal pressures and CSF pressure measured in patients with brain AVM. Results: The theory provides a basis for understanding the occurrence of pseudotumor cerebri syndrome in patients with nonhemorrhagic brain AVMs, for the occurrence of local mass effect and brain edema bordering unruptured AVMs, and for the development of hydrocephalus in patients with unruptured AVMs. The theory also contributes to a better appreciation of the pathophysiology of dural arteriovenous fistulas, of vein of Galen aneurismal malformation, and of autoregulation-related disorders in AVM patients. Conclusions: The hydraulic hypothesis provides a comprehensive frame to understand brain AVM hemodynamics and its effect on the CSF dynamics. PMID:23607064

Modern radiosurgical and endovascular classification schemes for brain arteriovenous malformations.

PubMed

Tayebi Meybodi, Ali; Lawton, Michael T

2018-05-04

Stereotactic radiosurgery (SRS) and endovascular techniques are commonly used for treating brain arteriovenous malformations (bAVMs). They are usually used as ancillary techniques to microsurgery but may also be used as solitary treatment options. Careful patient selection requires a clear estimate of the treatment efficacy and complication rates for the individual patient. As such, classification schemes are an essential part of patient selection paradigm for each treatment modality. While the Spetzler-Martin grading system and its subsequent modifications are commonly used for microsurgical outcome prediction for bAVMs, the same system(s) may not be easily applicable to SRS and endovascular therapy. Several radiosurgical- and endovascular-based grading scales have been proposed for bAVMs. However, a comprehensive review of these systems including a discussion on their relative advantages and disadvantages is missing. This paper is dedicated to modern classification schemes designed for SRS and endovascular techniques.

Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation.

PubMed

Ravindran, Ethiraj; Hu, Hao; Yuzwa, Scott A; Hernandez-Miranda, Luis R; Kraemer, Nadine; Ninnemann, Olaf; Musante, Luciana; Boltshauser, Eugen; Schindler, Detlev; Hübner, Angela; Reinecker, Hans-Christian; Ropers, Hans-Hilger; Birchmeier, Carmen; Miller, Freda D; Wienker, Thomas F; Hübner, Christoph; Kaindl, Angela M

2017-04-01

Mid-hindbrain malformations can occur during embryogenesis through a disturbance of transient and localized gene expression patterns within these distinct brain structures. Rho guanine nucleotide exchange factor (ARHGEF) family members are key for controlling the spatiotemporal activation of Rho GTPase, to modulate cytoskeleton dynamics, cell division, and cell migration. We identified, by means of whole exome sequencing, a homozygous frameshift mutation in the ARHGEF2 as a cause of intellectual disability, a midbrain-hindbrain malformation, and mild microcephaly in a consanguineous pedigree of Kurdish-Turkish descent. We show that loss of ARHGEF2 perturbs progenitor cell differentiation and that this is associated with a shift of mitotic spindle plane orientation, putatively favoring more symmetric divisions. The ARHGEF2 mutation leads to reduction in the activation of the RhoA/ROCK/MLC pathway crucial for cell migration. We demonstrate that the human brain malformation is recapitulated in Arhgef2 mutant mice and identify an aberrant migration of distinct components of the precerebellar system as a pathomechanism underlying the midbrain-hindbrain phenotype. Our results highlight the crucial function of ARHGEF2 in human brain development and identify a mutation in ARHGEF2 as novel cause of a neurodevelopmental disorder.

Homozygous ARHGEF2 mutation causes intellectual disability and midbrain-hindbrain malformation

PubMed Central

Yuzwa, Scott A.; Hernandez-Miranda, Luis R.; Musante, Luciana; Boltshauser, Eugen; Schindler, Detlev; Hübner, Angela; Reinecker, Hans-Christian; Ropers, Hans-Hilger; Miller, Freda D.; Hübner, Christoph; Kaindl, Angela M.

2017-01-01

Mid-hindbrain malformations can occur during embryogenesis through a disturbance of transient and localized gene expression patterns within these distinct brain structures. Rho guanine nucleotide exchange factor (ARHGEF) family members are key for controlling the spatiotemporal activation of Rho GTPase, to modulate cytoskeleton dynamics, cell division, and cell migration. We identified, by means of whole exome sequencing, a homozygous frameshift mutation in the ARHGEF2 as a cause of intellectual disability, a midbrain-hindbrain malformation, and mild microcephaly in a consanguineous pedigree of Kurdish-Turkish descent. We show that loss of ARHGEF2 perturbs progenitor cell differentiation and that this is associated with a shift of mitotic spindle plane orientation, putatively favoring more symmetric divisions. The ARHGEF2 mutation leads to reduction in the activation of the RhoA/ROCK/MLC pathway crucial for cell migration. We demonstrate that the human brain malformation is recapitulated in Arhgef2 mutant mice and identify an aberrant migration of distinct components of the precerebellar system as a pathomechanism underlying the midbrain-hindbrain phenotype. Our results highlight the crucial function of ARHGEF2 in human brain development and identify a mutation in ARHGEF2 as novel cause of a neurodevelopmental disorder. PMID:28453519

White matter reorganization after surgical resection of brain tumors and vascular malformations.

PubMed

Lazar, M; Alexander, A L; Thottakara, P J; Badie, B; Field, A S

2006-01-01

Diffusion tensor imaging (DTI) and white matter tractography (WMT) are promising techniques for estimating the course, extent, and connectivity patterns of the white matter (WM) structures in the human brain. In this study, DTI and WMT were used to evaluate WM tract reorganization after the surgical resection of brain tumors and vascular malformations. Pre- and postoperative DTI data were obtained in 6 patients undergoing surgical resection of brain lesions. WMT using a tensor deflection algorithm was used to reconstruct WM tracts adjacent to the lesions. Reconstructed tracts included corticospinal tracts, the corona radiata, superior longitudinal and inferior fronto-occipital fasciculi, cingulum bundles, and the corpus callosum. WMT revealed a series of tract alteration patterns including deviation, deformation, infiltration, and apparent tract interruption. In general, the organization of WM tracts appeared more similar to normal anatomy after resection, with either disappearance or reduction of the deviation, deformation, or infiltration present preoperatively. In patients whose lesions were associated with corticospinal tract involvement, the WMT reconstructions showed that the tract was preserved during surgery and improved in position and appearance, and this finding correlated with improvement or preservation of motor function as determined by clinical assessment. WMT is useful for appreciating the complex relationships between specific WM structures and the anatomic distortions created by brain lesions. Further studies with intraoperative correlation are necessary to confirm these initial findings and to determine WMT utility for presurgical planning and evaluation of surgical treatments.

Evaluation of the Embryotoxicity of Hydrazine in Rats

DTIC Science & Technology

1982-08-01

HYDRONEPHROSIS, MODERATE DILATION OF BRAIN VENTRICLES AND OTHER SIMILAR BUT LESS FREQUENTLY OCCURRING ABNORMALITIES E MAJOR MALFORMATION WAS ANOPHTHALMIA F...THREE FETUSES WITH ANOPHTHALMIA WERE FOUND IN ONE LITTER G MAJOR MALFORMATIONS WERE ANOPHTHALMIA (2) RIGHT SIDE AORTA (1) AND MONORCHID (1) 5 60 - 0 o...MALFORMATIONS CONSISTED OF ANOPHTHALMIA AND ADRENAL AGENESIS F ANOMALIES DETECTED IN THE 7-9 DAY TREATMENT GROUP WERE SUPERNUMERARY RIBS (2) MODERATE

Somatic GNAQ Mutation is Enriched in Brain Endothelial Cells in Sturge-Weber Syndrome.

PubMed

Huang, Lan; Couto, Javier A; Pinto, Anna; Alexandrescu, Sanda; Madsen, Joseph R; Greene, Arin K; Sahin, Mustafa; Bischoff, Joyce

2017-02-01

Sturge-Weber syndrome (SWS) is a rare congenital neurocutaneous disorder characterized by facial and extracraniofacial capillary malformations and capillary-venule malformations in the leptomeninges. A somatic mosaic mutation in GNAQ (c.548G>A; p.R183Q) was found in SWS brain and skin capillary malformations. Our laboratory showed endothelial cells in skin capillary malformations are enriched for the GNAQ mutation. The purpose of this study is to determine whether the GNAQ mutation is also enriched in endothelial cells in affected SWS brain. Two human SWS brain specimens were fractionated by fluorescence-activated cell sorting into hematopoietic (CD45), endothelial (CD31, VE-Cadherin, and vascular endothelial growth factor receptor 2), and perivascular (platelet-derived growth factor receptor beta) cells and cells negative for all markers. The sorted cell populations were analyzed for GNAQ p.R183Q mutation by droplet digital polymerase chain reaction. SWS patient-derived brain endothelial cells were selected by anti-CD31-coated magnetic beads and cultured in endothelial growth medium in vitro. The GNAQ p.R183Q mutation was present in brain endothelial cells in two SWS specimens, with mutant allelic frequencies of 34.7% and 24.0%. Cells negative for all markers also harbored the GNAQ mutation. The mutant allelic frequencies in these unidentified cells were 9.2% and 8.4%. SWS patient-derived brain endothelial cells with mutant allelic frequencies of 14.7% and 21% survived and proliferated in vitro. Our study provides evidence that GNAQ p.R183Q mutation is enriched in endothelial cells in SWS brain lesions and thereby reveals endothelial cells as a source of aberrant Gαq signaling. This will help to understand the pathophysiology of SWS, to discover biomarkers for predicting cerebral involvement, and to develop therapeutic targets to prevent neurological impairments in SWS. Copyright © 2016 Elsevier Inc. All rights reserved.

Blood-brain barrier-on-a-chip: Microphysiological systems that capture the complexity of the blood-central nervous system interface.

PubMed

Phan, Duc Tt; Bender, R Hugh F; Andrejecsk, Jillian W; Sobrino, Agua; Hachey, Stephanie J; George, Steven C; Hughes, Christopher Cw

2017-11-01

The blood-brain barrier is a dynamic and highly organized structure that strictly regulates the molecules allowed to cross the brain vasculature into the central nervous system. The blood-brain barrier pathology has been associated with a number of central nervous system diseases, including vascular malformations, stroke/vascular dementia, Alzheimer's disease, multiple sclerosis, and various neurological tumors including glioblastoma multiforme. There is a compelling need for representative models of this critical interface. Current research relies heavily on animal models (mostly mice) or on two-dimensional (2D) in vitro models, neither of which fully capture the complexities of the human blood-brain barrier. Physiological differences between humans and mice make translation to the clinic problematic, while monolayer cultures cannot capture the inherently three-dimensional (3D) nature of the blood-brain barrier, which includes close association of the abluminal side of the endothelium with astrocyte foot-processes and pericytes. Here we discuss the central nervous system diseases associated with blood-brain barrier pathology, recent advances in the development of novel 3D blood-brain barrier -on-a-chip systems that better mimic the physiological complexity and structure of human blood-brain barrier, and provide an outlook on how these blood-brain barrier-on-a-chip systems can be used for central nervous system disease modeling. Impact statement The field of microphysiological systems is rapidly evolving as new technologies are introduced and our understanding of organ physiology develops. In this review, we focus on Blood-Brain Barrier (BBB) models, with a particular emphasis on how they relate to neurological disorders such as Alzheimer's disease, multiple sclerosis, stroke, cancer, and vascular malformations. We emphasize the importance of capturing the three-dimensional nature of the brain and the unique architecture of the BBB - something that until recently had not been well modeled by in vitro systems. Our hope is that this review will provide a launch pad for new ideas and methodologies that can provide us with truly physiological BBB models capable of yielding new insights into the function of this critical interface.

Dandy Walker Syndrome with Tessier 7 Cleft-a Rare Case Report and a Surgical Note on the Use of Vermilion Flap and Lazy W-Plasty.

PubMed

Dhupar, Vikas; Kumar, Praveen; Akkara, Francis; Kumar, Ananth

2012-09-01

The Dandy-Walker syndrome is a malformation of the brain that involves the mal-development of the cerebellum, associated with a cystic enlargement of this area, and frequently hydrocephalus. This malformation occurs in ~1 in 30,000 babies. It is seen mostly in females. Developmental anomalies like cleft lip, cleft palate, and cardiac malformation, orthopaedic and urinary structural abnormalities may also occur in 30% of the individuals. We report a case of Dandy Walker syndrome with Tessier 7 facial cleft with paramedian cleft palate in a 6 month old child. Surgical methods used to correct this anomaly include commissuroplasty, myoplasty of the orbicularis oris, and closure of the cleft cheek. Authors report a vermilion square flap technique that combines a lower lip mucocutaneous vermilion border flap with a lazy W-plasty to ensure a natural commissure and skin closure.

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

PubMed

Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; El-Khayat, Hamed A; Eid, Ola M; Saba, Soliman; Farag, Mona K; Saleem, Sahar N; Gaber, Khaled R

2015-05-01

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. © 2015 Wiley Periodicals, Inc.

22.5 MB DELETION OF 13q31.1-q34 ASSOCIATED WITH HPE, DWM, AND HSCR: A CASE REPORT AND REDEFINING THE SMALLEST DELETED REGIONS.

PubMed

Alp, M Y; Çebi, A H; Seyhan, S; Cansu, A; Aydin, H; Ikbal, M

2016-01-01

Partial deletion of the long arm of the chromosome 13, 13q deletion syndrome is a rare chromosomal disorder characterized by severe growth and mental retardation, microcephaly, facial dysmorphism, brain malformations (holoprosencephaly, Dandy-Walker malformation), distal limb defects, eye anomalies, genitourinary and gastrointestinal tract malformations (Hirschsprung's disease). Approximately 1.2 Mb region in 13q32 was suggested as minimal critical region which is responsible for severe mental and growth retardation and brain anomalies. Here we described a male patient with de novo interstitial deletion of 13q31.1-q34 associated with short stature, microcephaly, facial dysmorphism, clinodactyly, cryptorchidism, micropenis, epilepsy, HPE, DWM, and HSCR. According to the literature review, present case indicated that smallest deleted region associated with DWM and HPE might be located at the 13q32.3, limb defects 13q34, anogenital malformations 13q33.3-34, and HSCR 13q31.1-32.1.

Subcortical heterotopia appearing as huge midline mass in the newborn brain.

PubMed

Fukumura, Shinobu; Watanabe, Toshihide; Kimura, Sachiko; Ochi, Satoko; Yoshifuji, Kazuhisa; Tsutsumi, Hiroyuki

2016-02-01

We report the case of a 2-year-old boy who showed a huge midline mass in the brain at prenatal assessment. After birth, magnetic resonance imaging (MRI) revealed a conglomerate mass with an infolded microgyrus at the midline, which was suspected as a midline brain-in-brain malformation. MRI also showed incomplete cleavage of his frontal cortex and thalamus, consistent with lobar holoprosencephaly. The patient underwent an incisional biopsy of the mass on the second day of life. The mass consisted of normal central nervous tissue with gray and white matter, representing a heterotopic brain. The malformation was considered to be a subcortical heterotopia. With maturity, focal signal changes and decreased cerebral perfusion became clear on brain imaging, suggesting secondary glial degeneration. Coincident with these MRI abnormalities, the child developed psychomotor retardation and severe epilepsy focused on the side of the intracranial mass.

RADIATION MALFORMATIONS BELONGING TO THE CYCLOPIA-ARRHINENCEPHALIA- OTECEPHALIA GROUP IN THE MOUSE FETUS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Marakami, U.; Kameyana, Y.; Majima, A.

1962-03-01

Pregnant mice on the 8.5th day of gestation were subjected to 200-r whole-body irradiation and the fetuses were examined on the l3th to l9th day of gestation. Incidence of fetal death (23.0%) was much higher than in the controls (8.2%1, and malformations of the nose, eyes, and ears cecurred in 32%. These malformations included alterations leading to a beaklike snout (19%), a univentricular telencephalon with cyclopia (6%), and forms transitional between these two (6%). These malformations were specific for irradiation on the 8.5th day of gestation; in previous studies they were not prominent when irradiation was carried out on themore » 8th, lOth, or llth day. During this most sensitive developmental stsge at 8.5 days, 3 to 5 brain vesicles are formed and the anterior neuropore is closed, which may account for the greater effect of teratogenic agents on the central nervous system at this time. Other abnormalities included exencephalia 12%), hydrocephalus (4%), microcephalia 10.7%), abnormally shaped head (5%), spinal cord anomalies (6%), eye anomalies (29%1, harelip and cleft palate (12%), tail abnormalities (6%), and thoraco- abdominal hernia (5%). (H.H.D.)« less

RADIATION MALFORMATIONS BELONGING TO THE CYCLOPIA-ARRHINECEPHALIA- OCTOCEPHALIA GROUP IN THE MOUSE FETUS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Murakami, U.; Kameyama, Y.; Majima, A.

1962-03-01

Pregnant mice on the 8 1/2th day of gestation were subjected to 200 r whole-body irradiation and the fetuses were examined on the l3th to l9th day of gestation. Incidence of fetal death (23.0%) was much higher than in the controls (8.2%), and malformations of the nose, eyes, and ears occurred in 32%. These malformations included alterations leading to a beaklike snout (19%), a univentricular telencephalon with cyclopia (6%), and fomas transitional between these two (6%). These malformations were specific for irradiation on the 8 1/2th day of gestation. In previous studies they were not prominent when irradiation was carriedmore » out on the 8th, l0th, or llth day. During this most sensitive developmental stage at 8 1/2 days, 3 to 5 brain vesicles are formed and the anterior neuropore is closed, which may account for the greater effect of teratogenic agents on the central nervous system at this time. Other abnormalities included exencephalia (2%), hydrocephalus (4%), microcephalia (0.7%), abnormally shaped head (5%), spinal cord anomalies (6%), eye anomalies (29%), harelip and cleft palate (l2%), tail abnormalities (6%), and thoraco- abdominal hennia (5%). (H.H.D.)« less

The human brain and face: mechanisms of cranial, neurological and facial development revealed through malformations of holoprosencephaly, cyclopia and aberrations in chromosome 18

PubMed Central

Gondré-Lewis, Marjorie C; Gboluaje, Temitayo; Reid, Shaina N; Lin, Stephen; Wang, Paul; Green, William; Diogo, Rui; Fidélia-Lambert, Marie N; Herman, Mary M

2015-01-01

The study of inborn genetic errors can lend insight into mechanisms of normal human development and congenital malformations. Here, we present the first detailed comparison of cranial and neuro pathology in two exceedingly rare human individuals with cyclopia and alobar holoprosencephaly (HPE) in the presence and absence of aberrant chromosome 18 (aCh18). The aCh18 fetus contained one normal Ch18 and one with a pseudo-isodicentric duplication of chromosome 18q and partial deletion of 18p from 18p11.31 where the HPE gene, TGIF, resides, to the p terminus. In addition to synophthalmia, the aCh18 cyclopic malformations included a failure of induction of most of the telencephalon – closely approximating anencephaly, unchecked development of brain stem structures, near absence of the sphenoid bone and a malformed neurocranium and viscerocranium that constitute the median face. Although there was complete erasure of the olfactory and superior nasal structures, rudiments of nasal structures derived from the maxillary bone were evident, but with absent pharyngeal structures. The second non-aCh18 cyclopic fetus was initially classified as a true Cyclops, as it appeared to have a proboscis and one median eye with a single iris, but further analysis revealed two eye globes as expected for synophthalmic cyclopia. Furthermore, the proboscis was associated with the medial ethmoid ridge, consistent with an incomplete induction of these nasal structures, even as the nasal septum and paranasal sinuses were apparently developed. An important conclusion of this study is that it is the brain that predicts the overall configuration of the face, due to its influence on the development of surrounding skeletal structures. The present data using a combination of macroscopic, computed tomography (CT) and magnetic resonance imaging (MRI) techniques provide an unparalleled analysis on the extent of the effects of median defects, and insight into normal development and patterning of the brain, face and their skeletal support. PMID:26278930

The human brain and face: mechanisms of cranial, neurological and facial development revealed through malformations of holoprosencephaly, cyclopia and aberrations in chromosome 18.

PubMed

Gondré-Lewis, Marjorie C; Gboluaje, Temitayo; Reid, Shaina N; Lin, Stephen; Wang, Paul; Green, William; Diogo, Rui; Fidélia-Lambert, Marie N; Herman, Mary M

2015-09-01

The study of inborn genetic errors can lend insight into mechanisms of normal human development and congenital malformations. Here, we present the first detailed comparison of cranial and neuro pathology in two exceedingly rare human individuals with cyclopia and alobar holoprosencephaly (HPE) in the presence and absence of aberrant chromosome 18 (aCh18). The aCh18 fetus contained one normal Ch18 and one with a pseudo-isodicentric duplication of chromosome 18q and partial deletion of 18p from 18p11.31 where the HPE gene, TGIF, resides, to the p terminus. In addition to synophthalmia, the aCh18 cyclopic malformations included a failure of induction of most of the telencephalon - closely approximating anencephaly, unchecked development of brain stem structures, near absence of the sphenoid bone and a malformed neurocranium and viscerocranium that constitute the median face. Although there was complete erasure of the olfactory and superior nasal structures, rudiments of nasal structures derived from the maxillary bone were evident, but with absent pharyngeal structures. The second non-aCh18 cyclopic fetus was initially classified as a true Cyclops, as it appeared to have a proboscis and one median eye with a single iris, but further analysis revealed two eye globes as expected for synophthalmic cyclopia. Furthermore, the proboscis was associated with the medial ethmoid ridge, consistent with an incomplete induction of these nasal structures, even as the nasal septum and paranasal sinuses were apparently developed. An important conclusion of this study is that it is the brain that predicts the overall configuration of the face, due to its influence on the development of surrounding skeletal structures. The present data using a combination of macroscopic, computed tomography (CT) and magnetic resonance imaging (MRI) techniques provide an unparalleled analysis on the extent of the effects of median defects, and insight into normal development and patterning of the brain, face and their skeletal support. © 2015 Anatomical Society.

Transverse Sinus Stenosis in Adult Patients With Chiari Malformation Type I

PubMed Central

Saindane, Amit M.; Bruce, Beau B.; Desai, Nilesh K.; Roller, Lauren A.; Newman, Nancy J.; Biousse, Valérie

2014-01-01

OBJECTIVE Transverse sinus stenosis is an imaging finding very highly associated with elevated intracranial pressure (ICP). Patients with the Chiari I malformation may potentially have elevated ICP due to impairment of CSF flow at the foramen magnum. This study evaluated whether patients with Chiari I malformation have transverse sinus stenosis and other imaging findings indicative of elevated ICP. MATERIALS AND METHODS Thirty patients with Chiari I malformation treated surgically and 76 control subjects were identified retrospectively. All control subjects and all patients with Chiari I malformation (preoperatively) underwent standardized contrast-enhanced brain MRI including a contrast-enhanced 3D T1-weighted sequence from which curved reformats of the transverse sinuses were generated. Two different readers blinded to the diagnosis then independently evaluated these curved reformats for severity of transverse sinus stenosis. Orbital and skull-base findings previously described in association with elevated ICP were also evaluated. Frequency of MRI findings between the two groups was compared. RESULTS Patients with Chiari I malformation had significantly greater frequency of unilateral or bilateral transverse sinus stenosis than did control subjects (p < 0.001). There was complete interreader agreement on presence or absence of transverse sinus stenosis by patient (κ = 1.0 [95% CI, 0.89–1.0]). Logistic regression analysis controlling for age, sex, and body mass index found that transverse sinus stenosis significantly predicted Chiari I malformation versus control status (odds ratio, 11.2 [95% CI, 2.1–59.0]; p = 0.004) but that no other features were significantly associated with the Chiari I malformation. Patients with Chiari I malformation who had transverse sinus stenosis had significantly greater pituitary flattening than did those without transverse sinus stenosis (p = 0.02). CONCLUSION Patients with Chiari I malformation have higher likelihood of trans-verse sinus stenosis, which may reflect associated elevated ICP. PMID:25247957

Sella turcica morphology and the pituitary gland-a new contribution to craniofacial diagnostics based on histology and neuroradiology.

PubMed

Kjær, Inger

2015-02-01

The present review summarizes two decades of published and unpublished studies on normal and pathological development of sella turcica and pituitary gland in humans. The pathological conditions are studied in known genotype deviations, syndromes, and other malformations. The studies include histological analyses of human prenatal material and profile radiographic analyses of human postnatal material, supplemented in a few cases with neuroradiology. Prenatal and postnatal results are compared. Similarities between prenatal and postnatal deviations in sella turcica morphology were demonstrated. Malformations in the pituitary gland were observed in several cases. For diagnostic purposes, the review distinguishes between deviations in the anterior wall and in the posterior wall of the sella turcica. Deviations in the anterior wall seem to be associated with deviations specifically in the frontonasal developmental field, while deviations in the posterior wall are often connected with malformations in the posterior structures, e.g. the cerebellum. In normal cases, minor variations in morphology are observed. In each pathological case, a specific malformation pattern was observed in sella turcica morphology, varying from mild to severe phenotype. The malformation in the sella turcica/pituitary gland can be associated with a malformation within a developmental field that forms the craniofacial region (frontonasal, maxillary, palatal, and mandibular fields), sometimes also involving the brain stem, thymus, thyroid, and heart (velocardiofacial syndrome). Pathological sella turcica morphology can also be associated with malformations in the cerebellum and larynx (Cri-du-Chat syndrome). This review demonstrates the value of combining profile radiographic diagnostics with neuroradiological diagnostics in cases with malformed sella turcicae. © The Author 2012. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Salient lesions in domestic ruminants infected with the emerging so-called Schmallenberg virus in Germany.

PubMed

Herder, V; Wohlsein, P; Peters, M; Hansmann, F; Baumgärtner, W

2012-07-01

The so-called Schmallenberg virus (SBV), first detected in a German town of the same name in October 2011, is a novel emerging orthobunyavirus in Europe causing malformations and severe economic loss in ruminants. This report describes lesions in 40 sheep, 2 goats, and 16 cattle naturally infected with SBV as determined by real-time quantitative reverse transcription polymerase chain reaction. The most common macroscopic changes were arthrogryposis, vertebral malformations, brachygnathia inferior, and malformations of the central nervous system, including hydranencephaly, porencephaly, hydrocephalus, cerebellar hypoplasia, and micromyelia. Histologic lesions included lymphohistiocytic meningoencephalomyelitis in some cases, glial nodules mainly in the mesencephalon and hippocampus of lambs and goats, and neuronal degeneration and necrosis mainly in the brain stem of calves. Micromyelia was characterized by a loss of gray and white matter, with few neurons remaining in the ventral horn in calves. The skeletal muscles had myofibrillar hypoplasia in lambs and calves. The lesions of SBV-associated abortion and perinatal death are similar to those attributed to Akabane virus and other viruses in the Simbu group of bunyaviruses.

The neurologic findings in Taybi-Linder syndrome (MOPD I/III): case report and review of the literature.

PubMed

Pierce, Melinda J; Morse, Richard P

2012-03-01

Taybi-Linder syndrome, also known as microcephalic osteodysplastic primordial dwarfism types I and III, is a rare disorder with presumed autosomal recessive inheritance. It is characterized by intrauterine growth retardation, distinctive bone dysplasia, and central nervous system malformations. We present two siblings with Taybi-Linder syndrome, with an emphasis on the neurological profile in this disease, which includes brain malformations, intractable epilepsy, sensory deficits, profound cognitive deficits, and neuroendocrine dysfunction. We also present distinctive correlative neuroimaging (MRI) and electroencephalographic (EEG) findings. Increased knowledge of the neurological profile of Taybi-Linder syndrome may be helpful for clinicians and genetic counselors managing these patients. Copyright © 2012 Wiley Periodicals, Inc.

Word Finding in Children and Adolescents with a History of Brain Injury.

ERIC Educational Resources Information Center

Dennis, Maureen

1992-01-01

Word finding in relation to brain injury is discussed for children and adolescents with unilateral congenital malformations of the brain, early hydrocephalus, childhood-acquired left hemisphere stroke, and acquired traumatic head injury. Studies examining the recovery of word-finding deficits after brain injury are discussed, along with…

Autism Traits in Individuals with Agenesis of the Corpus Callosum

ERIC Educational Resources Information Center

Lau, Yolanda C.; Hinkley, Leighton B. N.; Bukshpun, Polina; Strominger, Zoe A.; Wakahiro, Mari L. J.; Baron-Cohen, Simon; Allison, Carrie; Auyeung, Bonnie; Jeremy, Rita J.; Nagarajan, Srikantan S.; Sherr, Elliott H.; Marco, Elysa J.

2013-01-01

Autism spectrum disorders (ASD) have numerous etiologies, including structural brain malformations such as agenesis of the corpus callosum (AgCC). We sought to directly measure the occurrence of autism traits in a cohort of individuals with AgCC and to investigate the neural underpinnings of this association. We screened a large AgCC cohort (n =…

Factors Associated With Proximal Intracranial Aneurysms to Brain Arteriovenous Malformations: A Prospective Cohort Study.

PubMed

Morgan, Michael Kerin; Alsahli, Khalid; Wiedmann, Markus; Assaad, Nazih N; Heller, Gillian Z

2016-06-01

The risk of hemorrhage from a brain arteriovenous malformation (bAVM) is increased when an associated proximal intracranial aneurysm (APIA) is present. Identifying factors that are associated with APIA may influence the prediction of hemorrhage in patients with bAVM. To identify patient- and bAVM-specific factors associated with APIA. We analyzed a prospective database of bAVMs for factors associated with the presence of APIA. Factors analyzed included age, sex, bAVM size, aneurysm size, circulation contributing to the bAVM, location of the aneurysm, deep venous drainage, and Spetzler-Ponce categories. Multiple logistic regression was performed to identify an association with APIA. Of 753 cases of bAVM with complete angiographic surveillance, 67 (9%) were found to have APIA. Older age (continuous variable; odds ratio, 1.04; 95% confidence interval, 1.02-1.05) and posterior circulation supply to the bAVM (odds ratio, 2.29; 95% confidence interval, 1.32-3.99) were factors associated with increased detection of APIA. The association of posterior circulation-supplied bAVM was not due to infratentorial bAVM location because 72% of posterior circulation APIAs were supplying supratentorial bAVM. APIAs appear to develop with time, as evident from the increased age for those with APIAs. Furthermore, they were more likely present in bAVMs supplied by the posterior circulation. This may be due to a difference in hemodynamic stress. APIA, associated proximal intracranial aneurysmbAVM, brain arteriovenous malformationDSA, digital subtraction angiographySMG, Spetzler-Martin gradeSPC, Spetzler-Ponce category.

[Cerebrovenous orthostatic reactivity in pathology of the craniovertebral junction (Chiari malformation)].

PubMed

Shakhnovich, V A; Mitrofanova, E V; Shimanskiy, V N; Konovalov, N A; Shkarubo, A N

2015-01-01

Chiari malformation is characterized by herniation of the cerebellar tonsils into the foramen magnum, which leads to disturbance of CSF circulation through the craniovertebral junction. Orthostatic stress, which leads to the movement of SCF through the craniovertebral junction, is an adequate method to detect these disorders. It is accompanied by changes in the intracranial pressure, affecting the cerebrovenous orthostatic reactivity (CVOR), which is noninvasively assessed in patients with Chiari malformation. The study involved 35 patients with Chiari malformation (26 patients with Chiari I and 9 patients with Chiari II) aged 4 to 58 years (of them 12 males). Hydrocephalus was diagnosed in 4 examined patients and myelosyringosis was diagnosed in 6 patients. Transcranial Doppler sonography was used to record the venous blood flow in the tentorial sinus of the brain while changing body position on the fracture table from +90° to -30°. There is significant CVOR abnormality in most patients with Chiari malformation (more than 90%), which is characterized by either increased CVOR (sometimes 5-6-fold compared to the upper normal level (considerable hyperreactivity) or complete absence of any changes during the orthostatic load (areactivity). Before surgical treatment, CVOR of patients with Chiari malformation is often characterized by areactivity, as well as a moderate or significant hyperreactivity. After surgical treatment (decompression of the foramen magnum), patients with Chiari malformation demonstrate significant normalization of the craniovertebral volumetric ratios and CVOR if often characterized by normoreactivity (in 63%) or, more rarely, moderate hyperreactivity. The rate of venous blood flow in the tentorial sinus of the brain in patients with Chiari malformation can be increased before the surgery and normalizes after surgery. The high incidence of disturbance of CVOR (over 90%) in patients with Chiari malformation was revealed. After surgical treatment, complete normalization of CVOR was observed in more than half of these patients (63%).

Intracranial Hypertension in a Patient with a Chiari Malformation Accompanied by Hyperthyroidism.

PubMed

Pang, Chang Hwan; Lee, Soo Eon; Kim, Chi Heon; Chung, Chun Kee

2015-09-01

The Chiari malformation is an infrequently detected congenital anomaly characterized by the downward displacement of the cerebellum with a tonsillar herniation below the foramen magnum that may be accompanied by either syringomyelia or hydrocephalus. Surgery, such as foramen magnum decompression, is indicated for a symptomatic Chiari malformation, although an incidental lesion may be followed-up without further treatment. Infrequently, increased intracranial pressure emerges due to hyperthyroidism. A nineteen-year-old girl visited our outpatient clinic presented with a headache, nausea and vomiting. A brain and spinal magnetic resonance image study (MRI) indicated that the patient had a Chiari I malformation without syringomyelia or hydrocephalus. An enlarged thyroid gland was detected on a physical examination, and serum markers indicated Graves' disease. The patient started anti-hyperthyroid medical treatment. Subsequently, the headache disappeared after the medical treatment of hyperthyroidism without surgical intervention for the Chiari malformation. A symptomatic Chiari malformation is indicated for surgery, but a surgeon should investigate other potential causes of the symptoms of the Chiari malformation to avoid unnecessary surgery.

The Arnold-Chiari Malformation and Its Implications for Individuals with Spina Bifida and Hydrocephalus.

ERIC Educational Resources Information Center

Mittler, Joel E.

1986-01-01

The Arnold-Chiari malformation is present in most infants born with myelomeningocele (a form of spina bifida) and hydrocephalus. The syndrome is responsible for structural abnormalities in the brain, and peripheral nervous system. Etiology, symptoms, impact on central nervous system structures, surgical treatment, and implications for education…

Computational modelling for the embolization of brain arteriovenous malformations.

PubMed

Orlowski, Piotr; Summers, Paul; Noble, J Alison; Byrne, James; Ventikos, Yiannis

2012-09-01

Treatment of arteriovenous malformations (AVMs) of the brain often requires the injection of a liquid embolic material to reduce blood flow through the malformation. The type of the liquid and the location of injection have to be carefully planned in a pre-operative manner. We introduce a new model of the interaction of liquid embolic materials with blood for the simulation of their propagation and solidification in the AVM. Solidification is mimicked by an increase of the material's viscosity. Propagation is modelled by using the concept of two-fluids modelling and that of scalar transport. The method is tested on digital phantoms and on one anatomically derived patient AVM case. Simulations showed that intuitive behaviour of the two-fluid system can be confirmed and that two types of glue propagation through the malformation can be reproduced. Distinction between the two types of propagation could be used to identify fistulous and plexiform compartments composing the AVM and to characterize the solidification of the embolic material in them. Copyright © 2011 IPEM. Published by Elsevier Ltd. All rights reserved.

Magnetic resonance imaging features of complex Chiari malformation variant of Chiari 1 malformation.

PubMed

Moore, Hannah E; Moore, Kevin R

2014-11-01

Complex Chiari malformation is a subgroup of Chiari 1 malformation with distinct imaging features. Children with complex Chiari malformation are reported to have a more severe clinical phenotype and sometimes require more extensive surgical treatment than those with uncomplicated Chiari 1 malformation. We describe reported MR imaging features of complex Chiari malformation and evaluate the utility of craniometric parameters and qualitative anatomical observations for distinguishing complex Chiari malformation from uncomplicated Chiari 1 malformation. We conducted a retrospective search of the institutional imaging database using the keywords "Chiari" and "Chiari 1" to identify children imaged during the 2006-2011 time period. Children with Chiari 2 malformation were excluded after imaging review. We used the first available diagnostic brain or cervical spine MR study for data measurement. Standard measurements and observations were made of obex level (mm), cerebellar tonsillar descent (mm), perpendicular distance to basion-C2 line (pB-C2, mm), craniocervical angle (degrees), clivus length, and presence or absence of syringohydromyelia, basilar invagination and congenital craniovertebral junction osseous anomalies. After imaging review, we accessed the institutional health care clinical database to determine whether each subject clinically met criteria for Chiari 1 malformation or complex Chiari malformation. Obex level and craniocervical angle measurements showed statistically significant differences between the populations with complex Chiari malformation and uncomplicated Chiari 1 malformation. Cerebellar tonsillar descent and perpendicular distance to basion-C2 line measurements trended toward but did not meet statistical significance. Odontoid retroflexion, craniovertebral junction osseous anomalies, and syringohydromyelia were all observed proportionally more often in children with complex Chiari malformation than in those with Chiari 1 malformation. Characteristic imaging features of complex Chiari malformation, especially obex level, permit its distinction from the more common uncomplicated Chiari 1 malformation.

Multiple cavernous malformations presenting in a patient with Poland syndrome: A case report

PubMed Central

2011-01-01

Introduction Poland syndrome is a congenital disorder related to chest and hand anomalies on one side of the body. Its etiology remains unclear, with an ipsilateral vascular alteration (of unknown origin) to the subclavian artery in early embryogenesis being the currently accepted theory. Cavernous malformations are vascular hamartomas, which have been linked to a genetic etiology, particularly in familial cases, which commonly present with multiple lesions. Our case report is the first to describe multiple cavernous malformations associated with Poland syndrome, further supporting the vascular etiology theory, but pointing to a genetic rather than a mechanistic factor disrupting blood flow in the corresponding vessels. Case presentation A 41-year-old Caucasian man with Poland syndrome on the right side of his body presented to our hospital with a secondary generalized seizure and was found to have multiple cavernous malformations distributed in his brain, cerebellum, and brain stem, with a predominance of lesions in the left hemisphere. Conclusion The distribution of cavernous malformations in the left hemisphere and the right-sided Poland syndrome in our patient could not be explained by a mechanistic disruption of one of the subclavian arteries. A genetic alteration, as in familial cavernous malformations, would be a more appropriate etiologic diagnosis of Poland syndrome in our patient. Further genetic and pathological studies of the involved blood vessels in patients with Poland syndrome could lead to a better understanding of the disease. PMID:21933407

Automatic localization of cerebral cortical malformations using fractal analysis.

PubMed

De Luca, A; Arrigoni, F; Romaniello, R; Triulzi, F M; Peruzzo, D; Bertoldo, A

2016-08-21

Malformations of cortical development (MCDs) encompass a variety of brain disorders affecting the normal development and organization of the brain cortex. The relatively low incidence and the extreme heterogeneity of these disorders hamper the application of classical group level approaches for the detection of lesions. Here, we present a geometrical descriptor for a voxel level analysis based on fractal geometry, then define two similarity measures to detect the lesions at single subject level. The pipeline was applied to 15 normal children and nine pediatric patients affected by MCDs following two criteria, maximum accuracy (WACC) and minimization of false positives (FPR), and proved that our lesion detection algorithm is able to detect and locate abnormalities of the brain cortex with high specificity (WACC  =  85%, FPR  =  96%), sensitivity (WACC  =  83%, FPR  =  63%) and accuracy (WACC  =  85%, FPR  =  90%). The combination of global and local features proves to be effective, making the algorithm suitable for the detection of both focal and diffused malformations. Compared to other existing algorithms, this method shows higher accuracy and sensitivity.

Automatic localization of cerebral cortical malformations using fractal analysis

NASA Astrophysics Data System (ADS)

De Luca, A.; Arrigoni, F.; Romaniello, R.; Triulzi, F. M.; Peruzzo, D.; Bertoldo, A.

2016-08-01

Malformations of cortical development (MCDs) encompass a variety of brain disorders affecting the normal development and organization of the brain cortex. The relatively low incidence and the extreme heterogeneity of these disorders hamper the application of classical group level approaches for the detection of lesions. Here, we present a geometrical descriptor for a voxel level analysis based on fractal geometry, then define two similarity measures to detect the lesions at single subject level. The pipeline was applied to 15 normal children and nine pediatric patients affected by MCDs following two criteria, maximum accuracy (WACC) and minimization of false positives (FPR), and proved that our lesion detection algorithm is able to detect and locate abnormalities of the brain cortex with high specificity (WACC  =  85%, FPR  =  96%), sensitivity (WACC  =  83%, FPR  =  63%) and accuracy (WACC  =  85%, FPR  =  90%). The combination of global and local features proves to be effective, making the algorithm suitable for the detection of both focal and diffused malformations. Compared to other existing algorithms, this method shows higher accuracy and sensitivity.

FOXC1 is required for normal cerebellar development and is a major contributor to chromosome 6p25.3 Dandy-Walker malformation

PubMed Central

Aldinger, Kimberly A; Lehmann, Ordan J; Hudgins, Louanne; Chizhikov, Victor V; Bassuk, Alexander G; Ades, Lesley C; Krantz, Ian D; Dobyns, William B; Millen, Kathleen J

2010-01-01

Dandy-Walker malformation (DWM), the most common human cerebellar malformation, has only one characterized associated locus1,2. Here we characterize a second DWM-linked locus on 6p25.3, showing that deletions or duplications encompassing FOXC1 are associated with cerebellar and posterior fossa malformations including cerebellar vermis hypoplasia (CVH), mega-cisterna magna (MCM) and DWM. Foxc1-null mice have embryonic abnormalities of the rhombic lip due to loss of mesenchyme-secreted signaling molecules with subsequent loss of Atoh1 expression in vermis. Foxc1 homozygous hypomorphs have CVH with medial fusion and foliation defects. Human FOXC1 heterozygous mutations are known to affect eye development, causing a spectrum of glaucoma-associated anomalies (Axenfeld-Rieger syndrome, ARS; MIM no. 601631). We report the first brain imaging data from humans with FOXC1 mutations and show that these individuals also have CVH. We conclude that alteration of FOXC1 function alone causes CVH and contributes to MCM and DWM. Our results highlight a previously unrecognized role for mesenchyme-neuroepithelium interactions in the mid-hindbrain during early embryogenesis. PMID:19668217

Mandibulofacial Dysostosis with Microcephaly: Mutation and Database Update

PubMed Central

Huang, Lijia; Vanstone, Megan R.; Hartley, Taila; Osmond, Matthew; Barrowman, Nick; Allanson, Judith; Baker, Laura; Dabir, Tabib A.; Dipple, Katrina M.; Dobyns, William B.; Estrella, Jane; Faghfoury, Hanna; Favaro, Francine P.; Goel, Himanshu; Gregersen, Pernille A.; Gripp, Karen W.; Grix, Art; Guion-Almeida, Maria-Leine; Harr, Margaret H.; Hudson, Cindy; Hunter, Alasdair G.W.; Johnson, John; Joss, Shelagh K.; Kimball, Amy; Kini, Usha; Kline, Antonie D.; Lauzon, Julie; Lildballe, Dorte L.; López-González, Vanesa; Martinezmoles, Johanna; Meldrum, Cliff; Mirzaa, Ghayda M.; Morel, Chantal F.; Morton, Jenny E.V.; Pyle, Louise C.; Quintero-Rivera, Fabiola; Richer, Julie; Scheuerle, Angela E.; Schönewolf-Greulich, Bitten; Shears, Deborah J.; Silver, Josh; Smith, Amanda C.; Temple, I. Karen; van de Kamp, Jiddeke M.; van Dijk, Fleur S.; Vandersteen, Anthony M.; White, Sue M.; Zackai, Elaine H.; Zou, Ruobing; Bulman, Dennis E.; Boycott, Kym M.; Lines, Matthew A.

2017-01-01

Mandibulofacial dysostosis with microcephaly (MFDM) is a multiple malformation syndrome comprising microcephaly, craniofacial anomalies, hearing loss, dysmorphic features, and, in some cases, esophageal atresia. Haploinsufficiency of a spliceosomal GTPase, U5–116 kDa/EFTUD2, is responsible. Here, we review the molecular basis of MFDM in the 69 individuals described to date, and report mutations in 38 new individuals, bringing the total number of reported individuals to 107 individuals from 94 kindreds. Pathogenic EFTUD2 variants comprise 76 distinct mutations and seven microdeletions. Among point mutations, missense substitutions are infrequent (14 out of 76; 18%) relative to stop-gain (29 out of 76; 38%), and splicing (33 out of 76; 43%) mutations. Where known, mutation origin was de novo in 48 out of 64 individuals (75%), dominantly inherited in 12 out of 64 (19%), and due to proven germline mosaicism in four out of 64 (6%). Highly penetrant clinical features include, microcephaly, first and second arch craniofacial malformations, and hearing loss; esophageal atresia is present in an estimated ~27%. Microcephaly is virtually universal in childhood, with some adults exhibiting late “catch-up” growth and normocephaly at maturity. Occasionally reported anomalies, include vestibular and ossicular malformations, reduced mouth opening, atrophy of cerebral white matter, structural brain malformations, and epibulbar dermoid. All reported EFTUD2 mutations can be found in the EFTUD2 mutation database (http://databases.lovd.nl/shared/genes/EFTUD2). PMID:26507355

Mandibulofacial Dysostosis with Microcephaly: Mutation and Database Update.

PubMed

Huang, Lijia; Vanstone, Megan R; Hartley, Taila; Osmond, Matthew; Barrowman, Nick; Allanson, Judith; Baker, Laura; Dabir, Tabib A; Dipple, Katrina M; Dobyns, William B; Estrella, Jane; Faghfoury, Hanna; Favaro, Francine P; Goel, Himanshu; Gregersen, Pernille A; Gripp, Karen W; Grix, Art; Guion-Almeida, Maria-Leine; Harr, Margaret H; Hudson, Cindy; Hunter, Alasdair G W; Johnson, John; Joss, Shelagh K; Kimball, Amy; Kini, Usha; Kline, Antonie D; Lauzon, Julie; Lildballe, Dorte L; López-González, Vanesa; Martinezmoles, Johanna; Meldrum, Cliff; Mirzaa, Ghayda M; Morel, Chantal F; Morton, Jenny E V; Pyle, Louise C; Quintero-Rivera, Fabiola; Richer, Julie; Scheuerle, Angela E; Schönewolf-Greulich, Bitten; Shears, Deborah J; Silver, Josh; Smith, Amanda C; Temple, I Karen; van de Kamp, Jiddeke M; van Dijk, Fleur S; Vandersteen, Anthony M; White, Sue M; Zackai, Elaine H; Zou, Ruobing; Bulman, Dennis E; Boycott, Kym M; Lines, Matthew A

2016-02-01

Mandibulofacial dysostosis with microcephaly (MFDM) is a multiple malformation syndrome comprising microcephaly, craniofacial anomalies, hearing loss, dysmorphic features, and, in some cases, esophageal atresia. Haploinsufficiency of a spliceosomal GTPase, U5-116 kDa/EFTUD2, is responsible. Here, we review the molecular basis of MFDM in the 69 individuals described to date, and report mutations in 38 new individuals, bringing the total number of reported individuals to 107 individuals from 94 kindreds. Pathogenic EFTUD2 variants comprise 76 distinct mutations and seven microdeletions. Among point mutations, missense substitutions are infrequent (14 out of 76; 18%) relative to stop-gain (29 out of 76; 38%), and splicing (33 out of 76; 43%) mutations. Where known, mutation origin was de novo in 48 out of 64 individuals (75%), dominantly inherited in 12 out of 64 (19%), and due to proven germline mosaicism in four out of 64 (6%). Highly penetrant clinical features include, microcephaly, first and second arch craniofacial malformations, and hearing loss; esophageal atresia is present in an estimated ∼27%. Microcephaly is virtually universal in childhood, with some adults exhibiting late "catch-up" growth and normocephaly at maturity. Occasionally reported anomalies, include vestibular and ossicular malformations, reduced mouth opening, atrophy of cerebral white matter, structural brain malformations, and epibulbar dermoid. All reported EFTUD2 mutations can be found in the EFTUD2 mutation database (http://databases.lovd.nl/shared/genes/EFTUD2). © 2015 WILEY PERIODICALS, INC.

Inclusion bodies in cerebral cortical astrocytes: a new change of astrocytes.

PubMed

Minagawa, M; Shioda, K; Shimizu, Y; Isshiki, T

1992-01-01

A unique pathological finding of astrocytes was observed in the brain of a 20-year-old man who had severe physical and mental retardation. The brain was malformed showing micropolygyria in several cortical areas. A large number of hypertrophic astrocytes with eosinophilic granular substances in their cytoplasm were found throughout the cerebral cortex. Several staining procedures and electron microscopical examinations were carried out on these intracytoplasmic inclusion. It was found that the appearance and staining character of these inclusions were different from other astrocytic changes, especially the Rosenthal fiber, described so far. The authors consider that these inclusion bodies in cerebral cortical astrocytes represent new pathological changes of astrocytes that appear to be associated with malformation of the brain.

A late presentation of Dandy-Walker malformation and aortic coarctation.

PubMed

Venturini, Elio; Magni, Lucia; Pucci, Giovanna; Mazzinghi, Fabio

2017-05-01

The Dandy-Walker malformation is a rare anomaly of the posterior cranial fossa. Concomitant brain or systemic malformations are frequent and can influence the outcome. Associated cardiac congenital defects usually induce a poor prognosis. We report a case of a 58-yearold man with hydrocephalus, in whom Dandy-Walker malformation was diagnosed, for the first time, after the demonstration of aortic coarctation. This association is very rare and only a few cases have been described; moreover, to our knowledge, this is the first description of this incidence in a middle-aged patient. The characteristic of diseases and physiopathologic features are discussed, focusing attention on the rare and late clinical manifestations.

Diagnosis of Schmallenberg virus infection in malformed lambs and calves and first indications for virus clearance in the fetus.

PubMed

De Regge, Nick; van den Berg, Thierry; Georges, Laura; Cay, Brigitte

2013-03-23

Since mid-December 2011, samples from malformed lambs and calves are sent to CODA-CERVA in Belgium for diagnosis of Schmallenberg virus (SBV), a novel Orthobunyavirus that was first detected by researchers of the Friedrich-Loeffler-Institut (FLI, Germany) in German cattle in autumn 2011 and was later shown to be involved in congenital malformations in lambs, goat kids and calves. Surprisingly, by making use of real time RT-PCR (rRT-PCR) assays developed by the FLI, presence of SBV RNA could only be confirmed in part of the SBV suspected newborns examined. To investigate possible causes for non-confirmation by rRT-PCR, a comparative analysis between different organs and tissues (cerebrum, cerebellum, brain stem, spinal cord, thymus, spleen, lymph nodes, meconium) originating from respectively 90 and 81 malformed lambs and calves was undertaken. Furthermore, thoracic fluids of respectively 55 malformed lambs and calves were examined by a virus neutralization test (VNT) to evaluate the presence of neutralizing anti-SBV antibodies in these animals. Our results show that among the different organs tested by rRT-PCR, brain stem material is the most appropriate tissue for SBV detection while it could also be detected in all other tissues but to a more variable degree. The VNT test showed that 95% of the malformed lambs were positive for anti-SBV neutralizing antibodies while this was only the case for 44% of malformed calves. These immunological data suggest that a humoral immune response could assist in the clearance of SBV from the fetus during gestation and that SBV specific antibody testing should be considered together with rRT-PCR analysis for confirmation of SBV infection. Copyright © 2012 Elsevier B.V. All rights reserved.

[Orbito-palpebral vascular pathology].

PubMed

Heran Dreyfus, F; Galatoire, O; Koskas, P; Lafitte, F; Nau, E; Bergès, O

2016-11-01

Orbito-palpebral vascular pathology represents 10% of all the diseases of this area. The lesion may be discovered during a brain CT scan or MRI, or because it causes clinical symptoms such as orbital mass, visual or oculomotor alteration, pain, proptosis, or acute bleeding due to a complication of the lesion (hemorrhage, thrombosis). We present these lesions using an anatomical, clinical, imaging and therapeutic approach. We distinguish four different entities. Vascular tumors have common imaging characteristics (hypersignal on T2 sequence, contrast enhancement, abnormal vascularization well depicted with ultrasound and Doppler, and possible bleeding). The main lesions are cavernous hemangiomas, the most frequent lesion of that type during adulthood; infantile hemangiomas, the most frequent vascular tumor in children; and more seldomly, hemangioperitcytomas. True vascular malformations are divided according to their flow. Low flow lesions are venous (orbital varix), capillarovenous or lymphatic (lymphangioma). High flow malformations, more rare, are either arteriovenous or arterial malformations (aneurisms). Complex malformations include both low and high flow elements. Lesions leading to modifications of the orbito-palpebral blood flow are mainly due to cavernous sinus abnormalities, either direct carotid-cavernous fistula affecting young adults after severe head trauma, or dural fistula, more insidious, found in older adults. The last section is devoted to congenital syndromic vascular malformations (Sturge-Weber, Rendu-Olser…). This classification allows for a better understanding of these pathologies and their specific imaging features. Copyright © 2016. Published by Elsevier Masson SAS.

Baraitser and Winter syndrome with growth hormone deficiency.

PubMed

Chentli, Farida; Zellagui, Hadjer

2014-01-01

Baraitser-Winter syndrome (BWS), first reported in 1988, is apparently due to genetic abnormalities that are still not well-defined, although many gene abnormalities are already discovered and de novo missense changes in the cytoplasmic actin-encoding genes (called ACTB and ACTG1) have been recently discovered. The syndrome combines facial and cerebral malformations. Facial malformations totally or partially present in the same patient are: Iris coloboma, bilateral ptosis, hypertelorism, broad nasal bridge, and prominent epicanthic folds. The various brain malformations are probably responsible for growth and mental retardation. To the best of our knowledge, the syndrome is very rare as few cases have been reported so far. Our aim was to describe a child with a phenotype that looks like BWS with proved partial growth hormone (GH) deficiency which was not reported before. A girl aged 7-year-old of consanguineous parents was referred for short stature and mental retardation. Clinical examination showed dwarfism and a delay in her mental development. Other clinical features included: Strabismus, epicanthic folds, broad nasal bridge, and brain anomalies such as lissencephaly, bilateral hygroma, and cerebral atrophy. Hormonal assessment showed partial GH deficiency without other endocrine disorders. Our case looks exactly like BWS. However, apart from facial and cerebral abnormalities, there is a partial GH deficiency which can explain the harmonious short stature. This case seems worth to be reported as it adds GH deficiency to the very rare syndrome.

Adult onset of the Dandy-Walker syndrome.

PubMed

Lipton, H L; Preziosi, T J; Moses, H

1978-10-01

Two patients with the Dandy-Walker malformation first developed neurologic symptoms in adult life. In both patients there was normal motor and intellectual development during childhood, but as adults they had gradual evolution of brain stem and cerebellar signs and obstructive hydrocephalus. Following resection of the fourth ventricular cyst, both patients recovered. A review of the literature disclosed seven additional patients in whom the Dandy-Walker syndrome was first diagnosed in adult life. These cases illustrate that this congenital brain malformation may not only first become symptomatic later in life, but that it is possible for patients to remain asymptomatic.

Spontaneous thrombosis of the main draining vein revealing an unruptured brain arteriovenous malformation

PubMed Central

Cao, Catherine; Sourour, Nader; Reina, Vincent; Nouet, Aurélien; Di Maria, Federico; Chiras, Jacques; Cornu, Philippe

2015-01-01

Haemorrhage is the most frequent revealing condition of brain arteriovenous malformations (bAVMs). We report a rare case of unruptured parietal bAVM revealed by spontaneous thrombosis of the main draining vein, responsible for a focal neurological deficit. The bAVM was embolized in emergency conditions; complete regression of the neurological symptoms was observed within five days after the embolization. Potential mechanisms of such spontaneous thrombosis of the bAVM’s main drainage pathway as well as an exhaustive review of the literature concerning this rare revealing condition are presented and discussed. PMID:25964440

Developmental Thyroid Hormone Insufficiency Induces Cortical Brain Malformation and Learning Impairments: A Cross-Fostering Study

EPA Science Inventory

Thyroid hormones (TH) are essential for brain development, but animal models of well-defined and sensitive downstream apical neurotoxic outcomes associated with developmental TH disruption are lacking. A structural anomaly, a cortical heterotopia, in the brains of hypothyroid rat...

Evaluation of the central sleep apnea in asymptomatic children with Chiari 1 malformation: an open question.

PubMed

Zaffanello, Marco; Sala, Francesco; Sacchetto, Luca; Gasperi, Emma; Piacentini, Giorgio

2017-05-01

Type I is the most common Chiari malformation in children. In this condition, the lower part of the cerebellum, but not the brain stem, extends into the foramen magnum at the base of the skull leading to intermittent brain hypertension. In symptomatic children, central sleep apneas are shown in polysomnography evaluation. A central apnea index of 1/h or more is considered abnormal, but >5/h is clearly considered pathological. Therefore, central sleep apnea evaluation in pediatric age may show great age-related variability. We present three patients who were assessed by polysomnography with two different scores for central sleep apneas published in the literature: the method by Scholle (2011) and the American Academy of Sleep Medicine scoring system (2012). We speculated that the Scholle scoring system can be more helpful in assessing children with asymptomatic Chiari 1 malformation for a closer follow-up. More studies are needed.

Exposure to benzidine caused apoptosis and malformation of telencephalon region in zebrafish.

PubMed

Chen, Mark Hung-Chih; Hsu, Li-Chi; Wu, Jia-Lun; Yeh, Chi-Wei; Tsai, Jen-Ning; Hseu, You-Cheng; Hsu, Li-Sung

2014-12-01

Exposure to benzidine has been known to induce human cancers, particularly bladder carcinomas. In this study, the zebrafish model was used to investigate the developmental toxicity of benzidine. Embryos at 6 h postfertilization (hpf) that were exposed to benzidine exhibited embryonic death in a dose- and time-dependent manner. Benzidine induced malformations in zebrafish, such as small brain development, shorter axes, and a slight pericardial edema. High concentrations (50, 100, and 200 µM) of benzidine triggered widespread apoptosis in the brain and dorsal neurons, as evidenced by acridine orange and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assays. Real-time polymerase chain reaction analysis also showed that benzidine treatment affected p53, bax, and noxa expression. Decreases in specific brain markers, such as emx1 in the telencephalon, ngn1 in differentiated neurons, and otx2 in the midbrain, were observed in benzidine-treated embryos at 24 hpf. Conversely, no overt changes to pax2.1 expression in the midbrain-hindbrain boundary were found. Moreover, the use of Tg(HuC:GFP) zebrafish showed that benzidine caused a malformation of the telencephalon region. Our findings show that benzidine exposure triggers widespread apoptosis in the zebrafish brain and dorsal neurons, resulting in the development of an abnormal telencephalon. © 2013 Wiley Periodicals, Inc.

De novo interstitial deletion of 3q22.3-q25.2 encompassing FOXL2, ATR, ZIC1, and ZIC4 in a patient with blepharophimosis/ptosis/epicanthus inversus syndrome, Dandy-Walker malformation, and global developmental delay.

PubMed

Lim, Byung Chan; Park, Woong Yang; Seo, Eul-Ju; Kim, Ki Joong; Hwang, Yong Seung; Chae, Jong Hee

2011-05-01

We report a case carrying a de novo interstitial deletion of chromosome 3q22-q25. The clinical phenotype of this case included blepharophimosis/ptosis/epicanthus inversus syndrome, Dandy-Walker malformation, and global developmental delay. Contiguous heterozygous deletion of FOXL2, ATR, ZIC1, and ZIC4 was postulated as the causative mechanism of the clinical phenotype. The association of blepharophimosis, ptosis, and epicanthus inversus syndrome with developmental delay or mental retardation may be an indication for the use of brain imaging and chromosomal analysis capable of detecting chromosomal rearrangements encompassing several candidate genes.

Intracranial Hypertension in a Patient with a Chiari Malformation Accompanied by Hyperthyroidism

PubMed Central

Pang, Chang Hwan; Kim, Chi Heon; Chung, Chun Kee

2015-01-01

The Chiari malformation is an infrequently detected congenital anomaly characterized by the downward displacement of the cerebellum with a tonsillar herniation below the foramen magnum that may be accompanied by either syringomyelia or hydrocephalus. Surgery, such as foramen magnum decompression, is indicated for a symptomatic Chiari malformation, although an incidental lesion may be followed-up without further treatment. Infrequently, increased intracranial pressure emerges due to hyperthyroidism. A nineteen-year-old girl visited our outpatient clinic presented with a headache, nausea and vomiting. A brain and spinal magnetic resonance image study (MRI) indicated that the patient had a Chiari I malformation without syringomyelia or hydrocephalus. An enlarged thyroid gland was detected on a physical examination, and serum markers indicated Graves' disease. The patient started anti-hyperthyroid medical treatment. Subsequently, the headache disappeared after the medical treatment of hyperthyroidism without surgical intervention for the Chiari malformation. A symptomatic Chiari malformation is indicated for surgery, but a surgeon should investigate other potential causes of the symptoms of the Chiari malformation to avoid unnecessary surgery. PMID:26512271

Arteriovenous Malformations and Other Vascular Lesions of the Central Nervous System

MedlinePlus

... Neurological Disorders and Stroke (NINDS) is to seek fundamental knowledge about the brain and spinal cord and ... NINDS-funded research hopes to determine molecular pathways fundamental to the formation of brain AVMs, which may ...

A caprine chimera produced by injection of embryonic germ cells into a blastocyst.

PubMed

Jia, W; Yang, W; Lei, A; Gao, Z; Yang, C; Hua, J; Huang, W; Ma, X; Wang, H; Dou, Z

2008-02-01

This report details a chimeric goat derived by injecting caprine embryonic germ (EG) cells into a host blastocyst. The EG cells, isolated from the primordial genital ridge of white Guanzhong goat fetuses (28-42 days of pregnancy), had alkaline phosphatase activity and several stem cell markers, including SSEA-1, c-kit, and Nanog. Ten to 20EG cells were microinjected into the blastocoelic cavity of a host blastocyst collected from a black goat following natural service. Twenty-nine injected blastocysts were transferred into nine white surrogate goats. One of the recipients maintained pregnancy to term and gave birth to three kids: one male, one female, and a dead, malformed fetus of undetermined gender; all three fetuses were black, but the female and the malformed fetus each had a large white spot on their head. Based on PCR and microsatellite DNA assay, the female and the malformed fetus were monozygotic twins and chimeras. Microsatellite assay on various tissues from the dead fetus (including skin, blood, liver, placenta, lung, heart, spleen, muscle, and brain), revealed that these tissues and organs were chimeric and contained cells derived from EG cells. In conclusion, caprine EG cells differentiated into all three germ layers in vivo.

Development of three-dimensional brain arteriovenous malformation model for patient communication and young neurosurgeon education.

PubMed

Dong, Mengqi; Chen, Guangzhong; Qin, Kun; Ding, Xiaowen; Zhou, Dong; Peng, Chao; Zeng, Shaojian; Deng, Xianming

2018-01-15

Rapid prototyping technology is used to fabricate three-dimensional (3D) brain arteriovenous malformation (AVM) models and facilitate presurgical patient communication and medical education for young surgeons. Two intracranial AVM cases were selected for this study. Using 3D CT angiography or 3D rotational angiography images, the brain AVM models were reconstructed on personal computer and the rapid prototyping process was completed using a 3D printer. The size and morphology of the models were compared to brain digital subtraction arteriography of the same patients. 3D brain AVM models were used for preoperative patient communication and young neurosurgeon education. Two brain AVM models were successfully produced. By neurosurgeons' evaluation, the printed models have high fidelity with the actual brain AVM structures of the patients. The patient responded positively toward the brain AVM model specific to himself. Twenty surgical residents from residency programs tested the brain AVM models and provided positive feedback on their usefulness as educational tool and resemblance to real brain AVM structures. Patient-specific 3D printed models of brain AVM can be constructed with high fidelity. 3D printed brain AVM models are proved to be helpful in preoperative patient consultation, surgical planning and resident training.

Appearance of fetal posterior fossa at 11-14 weeks in fetuses with Dandy-Walker malformation or chromosomal anomalies.

PubMed

Volpe, P; Contro, E; Fanelli, T; Muto, B; Pilu, G; Gentile, M

2016-06-01

To describe the sonographic appearance of fetal posterior fossa anatomy at 11-14 weeks of pregnancy and to assess the outcome of fetuses with increased intracranial translucency (IT) and/or brainstem-to-occipital bone (BSOB) diameter. Reference ranges for brainstem (BS), IT and cisterna magna (CM) measurements, BSOB diameter and the BS : BSOB ratio were obtained from the first-trimester ultrasound examination of 233 fetuses with normal postnatal outcome (control group). The intraobserver and interobserver variability of measurements were investigated using 73 stored ultrasound images. In addition, a study group of 17 fetuses with increased IT and/or BSOB diameter was selected to assess outcome. No significant intraobserver or interobserver variability was found for any measurement in the control group. In the study group, IT was increased in all cases and BSOB diameter was above the 95(th) centile of the calculated normal range in all but two (88%) cases. In 13/17 study cases, only two of the three posterior brain spaces were recognized on ultrasound. These 13 fetuses had a larger BSOB diameter than did the four cases that showed all three posterior brain spaces, and had severe associated anomalies including Dandy-Walker malformation (DWM) and/or chromosomal anomalies. Visualization of the fetal posterior fossa anatomy at 11-14 weeks' gestation is feasible. Increased fluid in the posterior brain at 11-14 weeks, particularly in the case of non-visibility of the septation that divides the future fourth ventricle from the CM, is an important risk factor for cystic posterior fossa malformations, in particular DWM, and/or chromosomal aberrations. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Malformations of Cortical Development and Epilepsy

PubMed Central

Barkovich, A. James; Dobyns, William B.; Guerrini, Renzo

2015-01-01

Malformations of cortical development (MCDs) are an important cause of epilepsy and an extremely interesting group of disorders from the perspective of brain development and its perturbations. Many new MCDs have been described in recent years as a result of improvements in imaging, genetic testing, and understanding of the effects of mutations on the ability of their protein products to correctly function within the molecular pathways by which the brain functions. In this review, most of the major MCDs are reviewed from a clinical, embryological, and genetic perspective. The most recent literature regarding clinical diagnosis, mechanisms of development, and future paths of research are discussed. PMID:25934463

Spontaneous thrombosis of the main draining vein revealing an unruptured brain arteriovenous malformation.

PubMed

Cao, Catherine; Sourour, Nader; Reina, Vincent; Nouet, Aurélien; Di Maria, Federico; Chiras, Jacques; Cornu, Philippe; Clarençon, Frédéric

2015-04-01

Haemorrhage is the most frequent revealing condition of brain arteriovenous malformations (bAVMs). We report a rare case of unruptured parietal bAVM revealed by spontaneous thrombosis of the main draining vein, responsible for a focal neurological deficit. The bAVM was embolized in emergency conditions; complete regression of the neurological symptoms was observed within five days after the embolization. Potential mechanisms of such spontaneous thrombosis of the bAVM's main drainage pathway as well as an exhaustive review of the literature concerning this rare revealing condition are presented and discussed. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Missense-depleted regions in population exomes implicate ras superfamily nucleotide-binding protein alteration in patients with brain malformation

PubMed Central

Ge, Xiaoyan; Gong, Henry; Dumas, Kevin; Litwin, Jessica; Phillips, Joanna J; Waisfisz, Quinten; Weiss, Marjan M; Hendriks, Yvonne; Stuurman, Kyra E; Nelson, Stanley F; Grody, Wayne W; Lee, Hane; Kwok, Pui-Yan; Shieh, Joseph T C

2016-01-01

Genomic sequence interpretation can miss clinically relevant missense variants for several reasons. Rare missense variants are numerous in the exome and difficult to prioritise. Affected genes may also not have existing disease association. To improve variant prioritisation, we leverage population exome data to identify intragenic missense-depleted regions (MDRs) genome-wide that may be important in disease. We then use missense depletion analyses to help prioritise undiagnosed disease exome variants. We demonstrate application of this strategy to identify a novel gene association for human brain malformation. We identified de novo missense variants that affect the GDP/GTP-binding site of ARF1 in three unrelated patients. Corresponding functional analysis suggests ARF1 GDP/GTP-activation is affected by the specific missense mutations associated with heterotopia. These findings expand the genetic pathway underpinning neurologic disease that classically includes FLNA. ARF1 along with ARFGEF2 add further evidence implicating ARF/GEFs in the brain. Using functional ontology, top MDR-containing genes were highly enriched for nucleotide-binding function, suggesting these may be candidates for human disease. Routine consideration of MDR in the interpretation of exome data for rare diseases may help identify strong genetic factors for many severe conditions, infertility/reduction in reproductive capability, and embryonic conditions contributing to preterm loss. PMID:28868155

Microsurgical management of a high-grade brain arteriovenous malformation in the central lobe after unsuccessful radiosurgery.

PubMed

de Oliveira, Jean G; Massella, Carlos R; de Holanda, Carlos Vanderlei M; Giudicissi-Filho, Miguel; Borba, Luis A B

2017-07-01

The recommendation for the great majority of high-grade brain arteriovenous malformations (bAVMs) is observation, except for those patients with recurrent hemorrhages, progressive neurological deficits, steal-related symptoms, or AVM-related aneurysms, for whom intervention should be considered. These are general recommendations, and the decision should be made on an individual basis. Surgical resection of an AVM in the central lobe may cause postoperative sensorimotor deficits since this anatomical region includes the pre- and postcentral gyri on the lateral surface and the paracentral lobule on the medial surface. The authors present a patient with a ruptured high-grade bAVM in the central lobe who underwent previous surgery for hematoma evacuation and previous radiosurgery, and whose indication for reoperation was proposed based on progressive hemiparesis. Microsurgical resection was possible after a wide frontoparietal craniotomy, which made all the nidus borders accessible. This case illustrates the anatomy and surgical technique for large nidus AVMs in eloquent areas, showing that complete microsurgical resection is possible with good clinical outcome. The video can be found here: https://youtu.be/Cpd1PK6BLIM .

Treatment of Brain Arteriovenous Malformations with Hemodynamic Aneurysms: A Series of 131 Consecutive Cases.

PubMed

Eliava, Shalva; Dmitriev, Alexey; Shekhtman, Oleg; Yakovlev, Sergey; Kheireddin, Ali; Pilipenko, Yuriy

2018-02-01

The natural history of hemodynamic aneurysms (HAs) associated with brain arteriovenous malformations (AVMs) remains controversial, with no single approach to treatment. The purpose of this study was to justify preventive treatment tactics for HAs that pose an increased risk of rupture based on hemodynamic studies demonstrating hypertension in the afferent bed after AVM exclusion. This retrospective analysis included 131 of 1740 patients (8%) with brain AVMs and at least 1 aneurysm treated at Burdenko Neurosurgical Institute between 2000 and 2016. Treatment consisted of microsurgery, endovascular interventions, or a combination of modalities. Patients were evaluated with the modified Rankin Scale before and after treatment. A total of 205 aneurysms were discovered. Multiple HAs were found in 46 patients (35%), and were significantly more often associated with posterior fossa AVMs; in addition, most were distally located. There was no difference in the incidence of hemorrhage between proximal and distal HAs. Microsurgical treatment was marked by high radicalism; 85% of HAs and 94% of AVMs were totally excluded based on control studies. In 10 cases, aneurysms were found after AVM removal, including 4 de novo aneurysms. In 1 case, the aneurysm regressed after AVM treatment. The mortality rate was 2.3%. Preoperative imaging should be carefully examined for associated aneurysms before and after surgical treatment. Our data suggests that HA exclusion, either as the first step or simultaneously with AVM treatment, is most beneficial to patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Fiber-probe optical spectroscopy discriminates normal brain from focal cortical dysplasia in pediatric subjects

NASA Astrophysics Data System (ADS)

Anand, Suresh; Cicchi, Riccardo; Giordano, Flavio; Conti, Valerio; Buccoliero, Anna Maria; Guerrini, Renzo; Pavone, Francesco S.

2017-02-01

Focal cortical dysplasia (FCD) is an abnormality in the cerebral cortex that is caused by malformations during cortical development. Currently, magnetic resonance imaging (MRI) and electro-corticography (ECoG) are used for detecting FCD. On the downside, MRI is very much insensitive to small malformations in the brain, while ECoG is an invasive and time consuming procedure. Recently, optical techniques were widely exploited as a minimally invasive and quantitative approaches for disease diagnosis. These techniques include fluorescence and Raman spectroscopy. The aim of this investigation is to study the diagnostic performances of optical spectroscopy incorporating fluorescence (at 378 nm and 445 nm excitation wavelengths) and Raman spectroscopy (at 785 nm excitation) for the discrimination of FCD from normal brain in pediatric subjects. The study included 10 normal and 17 FCD tissue sites from 3 normal and 7 FCD samples. The emission spectra of FCD at 378 nm excitation wavelength presented a blue-shifted peak with respect to normal tissue. Prominent spectral differences between normal and FCD tissue were observed at 1298 cm-1, 1302 cm-1, 1445 cm-1 and 1660 cm-1 using Raman spectroscopy. Tissue classification models were developed using a multivariate statistical method, principal component analysis. This study demonstrates that a combined spectroscopic approach can provide a better diagnostic capability for classifying normal and FCD tissues. Further, the implementation of the technology within a fiber probe could open the way for in vivo diagnostics and intra-operative surgical guidance.

Role of stereotactic radiosurgery with a linear accelerator in treatment of intracranial arteriovenous malformations and tumors in children.

PubMed

Loeffler, J S; Rossitch, E; Siddon, R; Moore, M R; Rockoff, M A; Alexander, E

1990-05-01

Between 1986 and 1988, 16 children were treated for 10 arteriovenous malformations and 6 recurrent intracranial tumors with stereotactic radiation therapy using a modified Clinac 6/100 linear accelerator. The median age of our patients was 10.5 years. For the group with arteriovenous malformation, follow-up ranged from 6 months to 37 months (median was 20 months). No patient bled during the follow-up period. Five of eight patients with follow-up longer than 12 months have achieved complete obliteration of their arteriovenous malformation by angiogram. The four remaining patients who have not achieved a complete obliteration are awaiting their 2-year posttreatment angiogram. The other patient has been treated within the year and have not yet been studied. Five of the six recurrent tumor patients are alive with a median follow-up of 8 months. The remaining patient was controlled locally, but he died of recurrent disease outside the area treated with radiosurgery. The radiographic responses of these patients have included three complete responses, two substantial reductions in tumor volume (greater than 50%) and one stabilization. Despite previous radiotherapy, there have been no significant complications in these patients. We conclude that stereotactic radiation therapy using a standard linear accelerator is an effective and safe technique in the treatment of selected intracranial arteriovenous malformations and tumors in children. In addition, stereotactic radiosurgery may have unique applications in the treatment of localized primary and recurrent pediatric brain tumors.

Conventional digital subtractional vs non-invasive MR angiography in the assessment of brain arteriovenous malformation.

PubMed

Cuong, Nguyen Ngoc; Luu, Vu Dang; Tuan, Tran Anh; Linh, Le Tuan; Hung, Kieu Dinh; Ngoc, Vo Truong Nhu; Sharma, Kulbhushan; Pham, Van Huy; Chu, Dinh-Toi

2018-06-01

Digital subtractional angiography (DSA) is the standard method for diagnosis, assessment and management of arteriovenous malformation in the brain. Conventional DSA (cDSA) is an invasive imaging modality that is often indicated before interventional treatments (embolization, open surgery, gamma knife). Here, we aimed to compare this technique with a non-invasive MR angiography (MRI DSA) for brain arteriovenous malformation (bAVM). Fourteen patients with ruptured brain AVM underwent embolization treatment pre-operation. Imaging was performed for all patients using MRI (1.5 T). After injecting contrast Gadolinium, dynamic MRI was performed with 40 phases, each phase of a duration of 1.2 s and having 70 images. The MRI results were independently assessed by experienced radiologist blinded to the cDSA. The AVM nidus was depicted in all patients using cDSA and MRI DSA; there was an excellent correlation between these techniques in terms of the maximum diameter and Spetzler Martin grading. Of the fourteen patients, the drainage vein was depicted in 13 by both cDSA and MRI DSA showing excellent correlation between the techniques used. MRI DSA is a non-invasive imaging modality that can give the images in dynamic view. It can be considered as an adjunctive method with cDSA to plan the strategy treatment for bAVM. Copyright © 2018 Elsevier B.V. All rights reserved.

Genome-wide association study of sporadic brain arteriovenous malformations.

PubMed

Weinsheimer, Shantel; Bendjilali, Nasrine; Nelson, Jeffrey; Guo, Diana E; Zaroff, Jonathan G; Sidney, Stephen; McCulloch, Charles E; Al-Shahi Salman, Rustam; Berg, Jonathan N; Koeleman, Bobby P C; Simon, Matthias; Bostroem, Azize; Fontanella, Marco; Sturiale, Carmelo L; Pola, Roberto; Puca, Alfredo; Lawton, Michael T; Young, William L; Pawlikowska, Ludmila; Klijn, Catharina J M; Kim, Helen

2016-09-01

The pathogenesis of sporadic brain arteriovenous malformations (BAVMs) remains unknown, but studies suggest a genetic component. We estimated the heritability of sporadic BAVM and performed a genome-wide association study (GWAS) to investigate association of common single nucleotide polymorphisms (SNPs) with risk of sporadic BAVM in the international, multicentre Genetics of Arteriovenous Malformation (GEN-AVM) consortium. The Caucasian discovery cohort included 515 BAVM cases and 1191 controls genotyped using Affymetrix genome-wide SNP arrays. Genotype data were imputed to 1000 Genomes Project data, and well-imputed SNPs (>0.01 minor allele frequency) were analysed for association with BAVM. 57 top BAVM-associated SNPs (51 SNPs with p<10(-05) or p<10(-04) in candidate pathway genes, and 6 candidate BAVM SNPs) were tested in a replication cohort including 608 BAVM cases and 744 controls. The estimated heritability of BAVM was 17.6% (SE 8.9%, age and sex-adjusted p=0.015). None of the SNPs were significantly associated with BAVM in the replication cohort after correction for multiple testing. 6 SNPs had a nominal p<0.1 in the replication cohort and map to introns in EGFEM1P, SP4 and CDKAL1 or near JAG1 and BNC2. Of the 6 candidate SNPs, 2 in ACVRL1 and MMP3 had a nominal p<0.05 in the replication cohort. We performed the first GWAS of sporadic BAVM in the largest BAVM cohort assembled to date. No GWAS SNPs were replicated, suggesting that common SNPs do not contribute strongly to BAVM susceptibility. However, heritability estimates suggest a modest but significant genetic contribution. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Appreciating the broad clinical features of SMAD4 mutation carriers: a multicenter chart review.

PubMed

Wain, Karen E; Ellingson, Marissa S; McDonald, Jamie; Gammon, Amanda; Roberts, Maegan; Pichurin, Pavel; Winship, Ingrid; Riegert-Johnson, Douglas L; Weitzel, Jeffrey N; Lindor, Noralane M

2014-08-01

Heterozygous loss-of-function SMAD4 mutations are associated with juvenile polyposis syndrome and hereditary hemorrhagic telangiectasia. Some carriers exhibit symptoms of both conditions, leading to juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome. Three families have been reported with connective tissue abnormalities. To better understand the spectrum and extent of clinical findings in SMAD4 carriers, medical records of 34 patients (20 families) from five clinical practices were reviewed. Twenty-one percent of the patients (7/34) had features suggesting a connective tissue defect: enlarged aortic root (n = 3), aortic and mitral insufficiency (n = 2), aortic dissection (n = 1), retinal detachment (n = 1), brain aneurysms (n = 1), and lax skin and joints (n = 1). Juvenile polyposis-specific findings were almost uniformly present but variable. Ninety-seven percent of the patients had colon polyps that were generally pan-colonic and of variable histology and number. Forty-eight percent of the patients (15/31) had extensive gastric polyposis. Hereditary hemorrhagic telangiectasia features, including epistaxis (19/31, 61%), mucocutaneous telangiectases (15/31, 48%), liver arteriovenous malformation (6/16, 38%), brain arteriovenous malformation (1/26, 4%), pulmonary arteriovenous malformation (9/17, 53%), and intrapulmonary shunting (14/23, 61%), were documented in 76% of the patients. SMAD4 carriers should be managed for juvenile polyposis and hereditary hemorrhagic telangiectasia because symptoms of both conditions are likely yet unpredictable. Connective tissue abnormalities are an emerging component of juvenile polyposis-hereditary hemorrhagic telangiectasia syndrome, and larger studies are needed to understand these manifestations.

Acquired Chiari I Malformation with Syringomyelia Secondary to Colloid Cyst with Hydrocephalus-Case Report and Review of Literature.

PubMed

Thotakura, Amit Kumar; Marabathina, Nageswara R

2017-12-01

Acquired Chiari malformation and associated syringomyelia have been previously described following lumbar puncture/drainage, lumboperitoneal shunts, and spontaneous cerebrospinal fluid leakage. In addition to these etiologies, space-occupying lesions such as meningiomas, epidermoid cysts, medulloblastomas, and arachnoid cysts are rare causes of acquired Chiari malformation and syringomyelia. We report a rare case of colloid cyst with hydrocephalus causing secondary Chiari malformation with syringomyelia. A 58-year-old lady presented with neck pain and difficulty in walking and numbness of all 4 limbs of 1-year duration. Diagnostics with magnetic resonance imaging of the head and the cervical spine were done in the referring hospital. The patients was then referred with the diagnosis of colloid cyst with hydrocephalus and Chiari malformation 1 with cervicodorsal syringomyelia. She underwent colloid cyst excision through the transcallosal approach. Postoperatively the patient showed improvement in her symptomatology. Magnetic resonance imaging of the brain and cervical spine at 6 months' follow-up showed resolved Chiari malformation and resolving syrinx. Colloid cyst with hydrocephalus is a rare cause of secondary Chiari malformation with syringomyelia. Surgical management of the underlying lesion improves acquired Chiari malformation and associated syringomyelia. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical results of stereotactic heavy-charged-particle radiosurgery for intracranial angiographically occult vascular malformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Levy, R.P.; Fabrikant, J.I.; Phillips, M.H.

1989-12-01

Angiographically occult vascular malformations (AOVMs) of the brain have been recognized for many years to cause neurologic morbidity and mortality. They generally become symptomatic due to intracranial hemorrhage, focal mass effect, seizures or headaches. The true incidence of AOVMs is unknown, but autopsy studies suggest that they are more common than high-flow angiographically demonstrable arteriovenous malformations (AVMs). We have developed stereotactic heavy-charged-particle Bragg peak radiosurgery for the treatment of inoperable intracranial vascular malformations, using the helium ion beams at the Lawrence Berkeley Laboratory 184-inch Synchrocyclotron and Bevatron. This report describes the protocol for patient selection, radiosurgical treatment planning method, clinicalmore » and neuroradiologic results and complications encountered, and discusses the strengths and limitations of the method. 10 refs., 1 fig.« less

Brainstem conundrum: the Chiari I malformation.

PubMed

Mueller, D

2001-04-01

To describe the Chairi I Malformation in relation to the anatomy of the brain and spinal cord, the common manifestations of the condition, diagnostic considerations, and management for the primary care provider. Extensive review of the world-wide scientific literature on the condition, supplemented with actual case studies. The adult Chairi I Malformation is an insidious congenital brainstem anomaly that consists of caudal displacement of the cerebellar tonsils, brainstem and fourth ventricle into the upper cervical space, resulting in overcrowding of the posterior fossa. Due to the vague, and often ambiguous presenting symptoms of Chiari I Malformation, many patients are misdiagnosed with conditions such as multiple sclerosis, fibromyalgia, chronic fatigue syndrome, or psychiatric disorders. Patients frequently experience symptoms months to years prior to accurate diagnosis and often incur irreversible neurologic deficits.

Antiepileptic drugs and brain maturation: fetal exposure to lamotrigine generates cortical malformations in rats.

PubMed

Manent, Jean-Bernard; Jorquera, Isabel; Franco, Valentina; Ben-Ari, Yehezkel; Perucca, Emilio; Represa, Alfonso

2008-02-01

Intake of antiepileptic drugs (AEDs) during pregnancy can provoke severe and subtle fetal malformations associated with deleterious sequelae, reflecting the need for experimental investigations on the comparative teratogenic potential of these agents. We recently reported that prenatal exposure to vigabatrin and valproate, two AEDs which act through GABAergic mechanisms, induces hippocampal and cortical dysplasias in rodents. We have now investigated the effects of phenobarbital (PB, 30 mg/kg day) i.p.), a drug also endowed with GABAergic effects, and the new generation AEDs lamotrigine (LTG, 5-20mg/kg/day i.p.), topiramate (TPM, 10mg/kg/day i.p.), and levetiracetam (LEV, 50mg/kg/day i.p.) on brain development. Prenatal exposure to LTG induced hippocampal and cortical malformations in a dose-dependent manner, at maternal plasma concentrations within the clinically occurring range. These abnormalities were not observed after exposure to PB, TP and LEV. These observations raise concerns about potential clinical correlates and call for detailed comparative investigations on the consequences of AED use during pregnancy.

Are Major Dementias Triggered by Poor Blood Flow to the Brain? Theoretical Considerations.

PubMed

de la Torre, Jack C

2017-01-01

There is growing evidence that chronic brain hypoperfusion plays a central role in the development of Alzheimer's disease (AD) long before dyscognitive symptoms or amyloid-β accumulation in the brain appear. This commentary proposes that dementia with Lewy bodies (DLB), frontotemporal dementia (FTD), and Creutzfeldt-Jakob disease (CJD) may also develop from chronic brain hypoperfusion following a similar but not identical neurometabolic breakdown as AD. The argument to support this conclusion is that chronic brain hypoperfusion, which is found at the early stages of the three dementias reviewed here, will reduce oxygen delivery and lower oxidative phosphorylation promoting a steady decline in the synthesis of the cell energy fuel adenosine triphosphate (ATP). This process is known to lead to oxidative stress. Virtually all neurodegenerative diseases, including FTD, DLB, and CJD, are characterized by oxidative stress that promotes inclusion bodies which differ in structure, location, and origin, as well as which neurological disorder they typify. Inclusion bodies have one thing in common; they are known to diminish autophagic activity, the protective intracellular degradative process that removes malformed proteins, protein aggregates, and damaged subcellular organelles that can disrupt neuronal homeostasis. Neurons are dependent on autophagy for their normal function and survival. When autophagic activity is diminished or impaired in neurons, high levels of unfolded or misfolded proteins overwhelm and downregulate the neuroprotective activity of unfolded protein response which is unable to get rid of dysfunctional organelles such as damaged mitochondria and malformed proteins at the synapse. The endpoint of this neuropathologic process results in damaged synapses, impaired neurotransmission, cognitive decline, and dementia.

Brain magnetic resonance imaging findings in Smith-Lemli-Opitz syndrome.

PubMed

Lee, Ryan W Y; Conley, Sandra K; Gropman, Andrea; Porter, Forbes D; Baker, Eva H

2013-10-01

Smith-Lemli-Opitz syndrome (SLOS) is a neurodevelopmental disorder caused by inborn errors of cholesterol metabolism resulting from mutations in 7-dehydrocholesterol reductase (DHCR7). There are only a few studies describing the brain imaging findings in SLOS. This study examines the prevalence of magnetic resonance imaging (MRI) abnormalities in the largest cohort of patients with SLOS to date. Fifty-five individuals with SLOS (27 M, 28 F) between age 0.17 years and 25.4 years (mean = 6.2, SD = 5.8) received a total of 173 brain MRI scans (mean = 3.1 per subject) on a 1.5T GE scanner between September 1998 and December 2003, or on a 3T Philips scanner between October 2010 and September 2012; all exams were performed at the Clinical Center of the National Institutes of Health. We performed a retrospective review of these imaging studies for both major and minor brain anomalies. Aberrant MRI findings were observed in 53 of 55 (96%) SLOS patients, with abnormalities of the septum pellucidum the most frequent (42/55, 76%) finding. Abnormalities of the corpus callosum were found in 38 of 55 (69%) patients. Other findings included cerebral atrophy, cerebellar atrophy, colpocephaly, white matter lesions, arachnoid cysts, Dandy-Walker variant, and type I Chiari malformation. Significant correlations were observed when comparing MRI findings with sterol levels and somatic malformations. Individuals with SLOS commonly have anomalies involving the midline and para-midline structures of the brain. Further studies are required to examine the relationship between structural brain abnormalities and neurodevelopmental disability in SLOS. © 2013 The Authors. American Journal of Medical Genetics Part A Published by U.S. Government Work.

Syndrome of microcephaly, Dandy-Walker malformation, and Wilms tumor caused by mosaic variegated aneuploidy with premature centromere division (PCD): report of a new case and review of the literature.

PubMed

Kawame, H; Sugio, Y; Fuyama, Y; Hayashi, Y; Suzuki, H; Kurosawa, K; Maekawa, K

1999-01-01

We report a male infant with multiple congenital anomalies and mosaic variegated aneuploidy; a rare cytogenetic abnormality characterized by mosaicism for several different aneuploidies involving many different chromosomes. He had prenatal-onset growth retardation, microcephaly, dysmorphic face, seizures, hypotonia, feeding difficulty, and developmental delay. In addition, he developed bilateral Wilms tumors. Neuroradiological examination revealed Dandy-Walker malformation and hypoplasia of the cerebral hemisphere and pons. Cytogenetic analysis revealed various multiple numerical aneuploidies in blood lymphocytes, fibroblasts, and bone marrow cells, together with premature centromere division (PCD). Peripheral blood chromosome analysis from his parents also showed PCD, but no aneuploid cells. The clinical phenotype and multiple aneuploidies of the patient may be a consequence of the homozygous PCD trait inherited from his parents. Comparison with previously reported cases of multiple aneuploidy suggests that mosaic variegated aneuploidy with PCD may be a clinically recognizable syndrome with major phenotypes being mental retardation, microcephaly, structural brain anomalies (including Dandy-Walker malformation), and possible cancer predisposition.

Enhanced Burst-Suppression and Disruption of Local Field Potential Synchrony in a Mouse Model of Focal Cortical Dysplasia Exhibiting Spike-Wave Seizures.

PubMed

Williams, Anthony J; Zhou, Chen; Sun, Qian-Quan

2016-01-01

Focal cortical dysplasias (FCDs) are a common cause of brain seizures and are often associated with intractable epilepsy. Here we evaluated aberrant brain neurophysiology in an in vivo mouse model of FCD induced by neonatal freeze lesions (FLs) to the right cortical hemisphere (near S1). Linear multi-electrode arrays were used to record extracellular potentials from cortical and subcortical brain regions near the FL in anesthetized mice (5-13 months old) followed by 24 h cortical electroencephalogram (EEG) recordings. Results indicated that FL animals exhibit a high prevalence of spontaneous spike-wave discharges (SWDs), predominately during sleep (EEG), and an increase in the incidence of hyper-excitable burst/suppression activity under general anesthesia (extracellular recordings, 0.5%-3.0% isoflurane). Brief periods of burst activity in the local field potential (LFP) typically presented as an arrhythmic pattern of increased theta-alpha spectral peaks (4-12 Hz) on a background of low-amplitude delta activity (1-4 Hz), were associated with an increase in spontaneous spiking of cortical neurons, and were highly synchronized in control animals across recording sites in both cortical and subcortical layers (average cross-correlation values ranging from +0.73 to +1.0) with minimal phase shift between electrodes. However, in FL animals, cortical vs. subcortical burst activity was strongly out of phase with significantly lower cross-correlation values compared to controls (average values of -0.1 to +0.5, P < 0.05 between groups). In particular, a marked reduction in the level of synchronous burst activity was observed, the closer the recording electrodes were to the malformation (Pearson's Correlation = 0.525, P < 0.05). In a subset of FL animals (3/9), burst activity also included a spike or spike-wave pattern similar to the SWDs observed in unanesthetized animals. In summary, neonatal FLs increased the hyperexcitable pattern of burst activity induced by anesthesia and disrupted field potential synchrony between cortical and subcortical brain regions near the site of the cortical malformation. Monitoring the altered electrophysiology of burst activity under general anesthesia with multi-dimensional micro-electrode arrays may serve to define distinct neurophysiological biomarkers of epileptogenesis in human brain and improve techniques for surgical resection of epileptogenic malformed brain tissue.

Cyclopia and cebocephaly in two newborn infants with unbalanced segregation of a familial translocation rcp (1;7)(q32;q34).

PubMed

Schinzel, A

1984-05-01

This is a report of a family with a balanced reciprocal translocation, rcp (1;7)(q32;q34). Among pregnancies from translocation carriers, there were several miscarriages, and two unbalanced offspring with dup(1q32----qter) and del (7q34----qter) who died perinatally. One was a male cyclops with additional brain malformations and hydronephrosis, the other was a cebocephalic female with multiple additional malformations of heart, kidneys, and skeleton. In both pregnancies, the brain and renal anomalies were detected prenatally by ultrasound, in the cyclops during the 32nd and in the cebocephalic fetus during the 28th week of gestation.

Report of a trisomy 8p infant with carrier father.

PubMed

Funderburk, S J; Barrett, C T; Klisak, I

1978-12-01

This report describes an infant with fatal congenital heart disease, cleft palate, brain malformations, and trisomy 8p resultant from the paternal balanced reciprocal translocation, rcp(8;15) (p11;p11). Review of six previously reported trisomy 8p patients (resultant from parental balanced translocation in each instance) revealed severe mental retardation in five, short stature in all, and a variety of brain, skeletal, and cardiac defects. The features of the seven trisomy 8p patients reviewed here are not sufficiently similar to suggest a distinct dysmorphic syndrome. In addition the features differ from those in the trisomy 8 mosaicism syndrome, in which the mental retardation and malformations are generally less severe.

DMRTA2 (DMRT5) is mutated in a novel cortical brain malformation.

PubMed

Urquhart, J E; Beaman, G; Byers, H; Roberts, N A; Chervinsky, E; O'Sullivan, J; Pilz, D; Fry, A; Williams, S G; Bhaskar, S S; Khayat, M; Simanovsky, N; Shachar, I B; Shalev, S A; Newman, W G

2016-06-01

Lissencephaly is a phenotypically and genetically heterogeneous group of cortical brain malformations due to abnormal neuronal migration. The identification of many causative genes has increased the understanding of normal brain development. A consanguineous family was ascertained with three siblings affected by a severe prenatal neurodevelopmental disorder characterised by fronto-parietal pachygyria, agenesis of the corpus callosum and progressive severe microcephaly. Autozygosity mapping and exome sequencing identified a homozygous novel single base pair deletion, c.1197delT in DMRTA2, predicted to result in a frameshift variant p.(Pro400Leufs*33). DMRTA2 encodes doublesex and mab-3-related transcription factor a2, a transcription factor key to the development of the dorsal telencephalon. Data from murine and zebrafish knockout models are consistent with the variant of DMTRA2 (DMRT5) as responsible for the cortical brain phenotype. Our study suggests that loss of function of DMRTA2 leads to a novel disorder of cortical development. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Limb/pelvis hypoplasia/aplasia with skull defect (Schinzel phocomelia): distinctive features and prenatal detection.

PubMed

Olney, R S; Hoyme, H E; Roche, F; Ferguson, K; Hintz, S; Madan, A

2001-11-01

Schinzel phocomelia syndrome is characterized by limb/pelvis hypoplasia/aplasia: specifically, intercalary limb deficiencies and absent or hypoplastic pelvic bones. The phenotype is similar to that described in a related multiple malformation syndrome known as Al-Awadi/Raas-Rothschild syndrome. The additional important feature of large parietooccipital skull defects without meningocele, encephalocele, or other brain malformation has thus far been reported only in children with Schinzel phocomelia syndrome. We recently evaluated a boy affected with Schinzel phocomelia born to nonconsanguineous healthy parents of Mexican origin. A third-trimester fetal ultrasound scan showed severe limb deficiencies and an absent pelvis. The infant died shortly after birth. Dysmorphology examination, radiographs, and autopsy revealed quadrilateral intercalary limb deficiencies with preaxial toe polydactyly; an absent pelvis and a 7 x 3-cm skull defect; and extraskeletal anomalies including microtia, telecanthus, micropenis with cryptorchidism, renal cysts, stenosis of the colon, and a cleft alveolar ridge. A normal 46,XY karyotype was demonstrated, and autosomal recessive inheritance was presumed on the basis of previously reported families. This case report emphasizes the importance of recognizing severe pelvic and skull deficiencies (either post- or prenatally) in differentiating infants with Schinzel phocomelia from other multiple malformation syndromes that feature intercalary limb defects, including thalidomide embryopathy and Roberts-SC phocomelia. Copyright 2001 Wiley-Liss, Inc.

Interdisciplinary approach to neurocritical care in the intensive care nursery.

PubMed

Glass, Hannah C; Rogers, Elizabeth E; Peloquin, Susan; Bonifacio, Sonia L

2014-12-01

Neurocritical care is a multidisciplinary subspecialty that combines expertise in critical care medicine, neurology, and neurosurgery, and has led to improved outcomes in adults who have critical illnesses. Advances in resuscitation and critical care have led to high rates of survival among neonates with life-threatening conditions such as perinatal asphyxia, extreme prematurity, and congenital malformations. The sequelae of neurologic conditions arising in the neonatal period include lifelong disabilities such as cerebral palsy and epilepsy, as well as intellectual and behavioral disabilities. Centers of excellence have adapted the principles of neurocritical care to reflect the needs of the developing newborn brain, including early involvement of a neurologist for recognition and treatment of neurologic conditions, attention to physiology to help prevent secondary brain injury, a protocol-driven approach for common conditions like seizures and hypoxic-ischemic encephalopathy, and education of specialized teams that use brain monitoring and imaging to evaluate the effect of critical illness on brain function and development. Copyright © 2014. Published by Elsevier Inc.

Spinning, hurting, still, afraid: Living life spaces with Type I Chiari Malformation.

PubMed

Andrews, Gavin J

2018-01-31

Human geography's varied engagement with the brain has involved considerations of the way people know and respond to their environments, and their place-based experiences with emotions, mental illnesses and disorders, intellectual disabilities and particular neurological conditions. This paper argues however that this scholarship could be augmented by, and existing expertise be directed towards, considering physical brain abnormalities and injuries. As a case in point it considers the spatial experience of living with Type 1 Chiari Malformation. Through interviews with four sufferers, the research articulates three domains that they have had to re-negotiate - home space, social space and medical space - emphasizing supportive and challenging aspects of each, as well as meaningful and affective qualities to encounters. The paper concludes with some pointers towards the future study of physical brain abnormalities and injuries and the kinds of knowledge it might create to increase awareness and inform care. Copyright © 2018 Elsevier Ltd. All rights reserved.

Congenital malformations induced by mescaline, lysergic acid diethylamide, and bromolysergic acid in the hamster.

PubMed

Geber, W F

1967-10-13

Malformations of the brain, spinal cord, liver, and other viscera; body edema; and localized hemorrhages were found in fetal hamsters from mothers injected subcutaneously with a single dose of mescaline, lysergic acid diethylamide, or 2-bromo-D lysergic acid diethylamide on the 8th day of pregnancy. In addition, all three drugs produced an increase in the percentages of small fetuses per litter, of resorptions, and of fetal mortality.

Three-dimensional magnetic resonance imaging based on time-of-flight magnetic resonance angiography for superficial cerebral arteriovenous malformation--technical note.

PubMed

Murata, Takahiro; Horiuchi, Tetsuyoshi; Rahmah, Nunung Nur; Sakai, Keiichi; Hongo, Kazuhiro

2011-01-01

Direct surgery remains important for the treatment of superficial cerebral arteriovenous malformation (AVM). Surgical planning on the basis of careful analysis from various neuroimaging modalities can aid in resection of superficial AVM with favorable outcome. Three-dimensional (3D) magnetic resonance (MR) imaging reconstructed from time-of-flight (TOF) MR angiography was developed as an adjunctive tool for surgical planning of superficial AVM. 3-T TOF MR imaging without contrast medium was performed preoperatively in patients with superficial AVM. The images were imported into OsiriX imaging software and the 3D reconstructed MR image was produced using the volume rendering method. This 3D MR image could clearly visualize the surface angioarchitecture of the AVM with the surrounding brain on a single image, and clarified feeding arteries including draining veins and the relationship with sulci or fissures surrounding the nidus. 3D MR image of the whole AVM angioarchitecture was also displayed by skeletonization of the surrounding brain. Preoperative 3D MR image corresponded to the intraoperative view. Feeders on the brain surface were easily confirmed and obliterated during surgery, with the aid of the 3D MR images. 3D MR imaging for surgical planning of superficial AVM is simple and noninvasive to perform, enhances intraoperative orientation, and is helpful for successful resection.

Thalidomide Reduces Hemorrhage of Brain Arteriovenous Malformations in a Mouse Model.

PubMed

Zhu, Wan; Chen, Wanqiu; Zou, Dingquan; Wang, Liang; Bao, Chen; Zhan, Lei; Saw, Daniel; Wang, Sen; Winkler, Ethan; Li, Zhengxi; Zhang, Meng; Shen, Fanxia; Shaligram, Sonali; Lawton, Michael; Su, Hua

2018-05-01

Brain arteriovenous malformation (bAVM) is an important risk factor for intracranial hemorrhage. Current treatments for bAVM are all associated with considerable risks. There is no safe method to prevent bAVM hemorrhage. Thalidomide reduces nose bleeding in patients with hereditary hemorrhagic telangiectasia, an inherited disorder characterized by vascular malformations. In this study, we tested whether thalidomide and its less toxic analog, lenalidomide, reduce bAVM hemorrhage using a mouse model. bAVMs were induced through induction of brain focal activin-like kinase 1 ( Alk1 , an AVM causative gene) gene deletion and angiogenesis in adult Alk1 -floxed mice. Thalidomide was injected intraperitoneally twice per week for 6 weeks, starting either 2 or 8 weeks after AVM induction. Lenalidomide was injected intraperitoneally daily starting 8 weeks after AVM induction for 6 weeks. Brain samples were collected at the end of the treatments for morphology, mRNA, and protein analyses. The influence of Alk1 downregulation on PDGFB (platelet-derived growth factor B) expression was also studied on cultured human brain microvascular endothelial cells. The effect of PDGFB in mural cell recruitment in bAVM was explored by injection of a PDGFB overexpressing lentiviral vector to the mouse brain. Thalidomide or lenalidomide treatment reduced the number of dysplastic vessels and hemorrhage and increased mural cell (vascular smooth muscle cells and pericytes) coverage in the bAVM lesion. Thalidomide reduced the burden of CD68 + cells and the expression of inflammatory cytokines in the bAVM lesions. PDGFB expression was reduced in ALK1-knockdown human brain microvascular endothelial cells and in mouse bAVM lesion. Thalidomide increased Pdgfb expression in bAVM lesion. Overexpression of PDGFB mimicked the effect of thalidomide. Thalidomide and lenalidomide improve mural cell coverage of bAVM vessels and reduce bAVM hemorrhage, which is likely through upregulation of Pdgfb expression. © 2018 American Heart Association, Inc.

Cortical Brain Malformation and Learning Impairments Induced by Developmental Thyroid Hormone Insufficiency: A Cross-Fostering Study

EPA Science Inventory

Although it is clear that severe reductions in thyroid hormones (TH) during development alter brain structure and function, the impact of low level, timing, and duration of TH insufficiency is less well understood. We have previously reported the presence of a cortical heterotopi...

Malformation syndromes caused by disorders of cholesterol synthesis

PubMed Central

Porter, Forbes D.; Herman, Gail E.

2011-01-01

Cholesterol homeostasis is critical for normal growth and development. In addition to being a major membrane lipid, cholesterol has multiple biological functions. These roles include being a precursor molecule for the synthesis of steroid hormones, neuroactive steroids, oxysterols, and bile acids. Cholesterol is also essential for the proper maturation and signaling of hedgehog proteins, and thus cholesterol is critical for embryonic development. After birth, most tissues can obtain cholesterol from either endogenous synthesis or exogenous dietary sources, but prior to birth, the human fetal tissues are dependent on endogenous synthesis. Due to the blood-brain barrier, brain tissue cannot utilize dietary or peripherally produced cholesterol. Generally, inborn errors of cholesterol synthesis lead to both a deficiency of cholesterol and increased levels of potentially bioactive or toxic precursor sterols. Over the past couple of decades, a number of human malformation syndromes have been shown to be due to inborn errors of cholesterol synthesis. Herein, we will review clinical and basic science aspects of Smith-Lemli-Opitz syndrome, desmosterolosis, lathosterolosis, HEM dysplasia, X-linked dominant chondrodysplasia punctata, Congenital Hemidysplasia with Ichthyosiform erythroderma and Limb Defects Syndrome, sterol-C-4 methyloxidase-like deficiency, and Antley-Bixler syndrome. PMID:20929975

Early outcomes and periprocedural complications of transarterial embolization of brain arteriovenous malformations with Onyx®.

PubMed

Poncyljusz, Wojciech; Sawicki, Marcin; Lubkowska, Katarzyna; Rać, Monika

Brain arteriovenous malformation (BAVM) is a rare pathology diagnosed mostly in young adults. However, due to its hemorrhagic complications, it constitutes an important clinical problem. Treatment modalities available include endovascular, surgery and radiosurgery. The aim of the study was to assess the efficacy and safety of endovascular treatment of BAVM with Onyx ® by reporting one-center experience. Between 2006 and 2013, 54 patients with BAVM were embolized with Onyx. The group consisted of 24 males and 30 females, aged 10 to 65 years (mean 42.6±15.4). Clinical manifestations of BAVMs were: hemorrhage in 27 (50.0%), headaches in 12 (22.2%), seizures in 7 (13.0%) and focal neurologic deficits in 2 (3.7%) patients. Six (11.1%) patients were asymptomatic. A majority of BAVMs were of II and III grade in Spetzler-Martin scale (19 and 22 cases respectively). A total number of 108 endovascular procedures were performed (mean 2.00±0.98 sessions/patient). Complete obliteration of malformation was achieved in 25 (46.3%) patients, mostly with grade II and III BAVMs. In 29 (53.7%) patients, embolization led to a decrease in size of BAVM that made it feasible for other treatment modality. Morbidity and mortality rates were 5.6% and 1.8% respectively. The rate of hemorrhagic complications was 9.3%. Embolization of BAVM with Onyx ® is an effective and safe method of treatment. However, regarding type and consequences of complications, the technique needs further improvement. Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

Modern classification and outcome predictors of surgery in patients with brain arteriovenous malformations.

PubMed

Tayebi Meybodi, Ali; Lawton, Michael T

2018-02-23

Brain arteriovenous malformations (bAVM) are challenging lesions. Part of this challenge stems from the infinite diversity of these lesions regarding shape, location, anatomy, and physiology. This diversity has called on a variety of treatment modalities for these lesions, of which microsurgical resection prevails as the mainstay of treatment. As such, outcome prediction and managing strategy mainly rely on unraveling the nature of these complex tangles and ways each lesion responds to various therapeutic modalities. This strategy needs the ability to decipher each lesion through accurate and efficient categorization. Therefore, classification schemes are essential parts of treatment planning and outcome prediction. This article summarizes different surgical classification schemes and outcome predictors proposed for bAVMs.

Anterior Mesencephalic Cap Dysplasia: Novel Brain Stem Malformative Features Associated with Joubert Syndrome.

PubMed

Arrigoni, F; Romaniello, R; Peruzzo, D; De Luca, A; Parazzini, C; Valente, E M; Borgatti, R; Triulzi, F

2017-12-01

In Joubert syndrome, the "molar tooth" sign can be associated with several additional supra- and infratentorial malformations. Here we report on 3 subjects (2 siblings, 8-14 years of age) with Joubert syndrome, showing an abnormal thick bulging of the anterior profile of the mesencephalon causing a complete obliteration of the interpeduncular fossa. DTI revealed that the abnormal tissue consisted of an ectopic white matter tract with a laterolateral transverse orientation. Tractographic reconstructions support the hypothesis of impaired axonal guidance mechanisms responsible for the malformation. The 2 siblings were compound heterozygous for 2 missense variants in the TMEM67 gene, while no mutations in a panel of 120 ciliary genes were detected in the third patient. The name "anterior mesencephalic cap dysplasia," referring to the peculiar aspect of the mesencephalon on sagittal MR imaging, is proposed for this new malformative feature. © 2017 by American Journal of Neuroradiology.

Dandy-Walker malformation: analysis of 19 cases.

PubMed

Alexiou, George A; Sfakianos, George; Prodromou, Neofytos

2010-02-01

Dandy-Walker malformation is a congenital disorder that involves the cerebellum and fourth ventricle. Regarding treatment, there is still controversy over the optimum surgical management. In the current study, we present 19 consecutive cases of Dandy-Walker malformation diagnosed between January 1992 and January 2008 that were treated in our institute. All patients presented with hydrocephalus at the time of diagnosis and were treated surgically. Combined drainage of the ventricular system and posterior fossa cyst, using a 3-way connector was performed in 5 patients. Posterior fossa cyst drainage alone was performed in 10 patients and the remaining 4 patients were treated by ventricular drainage alone. All patients improved after treatment. Dandy-Walker malformation is a developmental abnormality of the central nervous system associated with various brain and extracranial abnormalities. Surgical treatment remains controversial, whereas prognosis varies greatly according to the severity of syndrome and associated comorbidities.

Dyke-Davidoff-Masson Syndrome. An unusual cause of status epilepticus.

PubMed

Zawar, Ifrah; Khan, Ashfa A; Sultan, Tipu; Rathore, Ahsan W

2015-10-01

The Dyke-Davidoff-Masson Syndrome (DDMS) results from an insult to the growing brain in utero or early infancy, which lead to loss of neurons compromising the growth of the brain. Clinical presentation includes seizures, hemiparesis, facial asymmetry, and learning disability. Radiological findings include cerebral atrophy on one side. Here, we present a case with status epilepticus who had underlying DDMS. It is a rare syndrome and uncommon cause for status epilepticus. Infections of CNS, hypoxic ischemic encephalopathy, intracranial bleed, trauma, congenital vascular malformations are the common causes of this syndrome. Diagnosis is established after clinical history, examination, and MRI. Intractable seizures can be controlled with appropriate anticonvulsants. Subsequently, these children may require physiotherapy, speech therapy, and occupational therapy in addition to the anticonvulsant medication. Outcome is better if the seizures are controlled.

Intraoperative monitoring of brain tissue oxygenation during arteriovenous malformation resection.

PubMed

Arikan, Fuat; Vilalta, Jordi; Noguer, Montserrat; Olive, Montserrat; Vidal-Jorge, Marian; Sahuquillo, Juan

2014-10-01

In normal perfusion pressure breakthrough (NPPB) it is assumed that following arteriovenous malformation (AVM) resection, vasoparalysis persists in the margins of the lesion and that a sudden increase in cerebral blood flow (CBF) after AVM exclusion leads to brain swelling and postsurgical complications. However, the pathophysiology NPPB remains controversial.The aim of our study was to investigate the oxygenation status in tissue surrounding AVMs and in the distant brain using intraoperative monitoring of cerebral partial pressure of oxygen (PtiO(2)) to achieve a better understanding of NPPB pathophysiology. Patients with supratentorial AVMs were monitored intraoperatively using 2 polarographic Clark-type electrodes. To establish reference values, we also studied PtiO(2) in a group of patients who underwent surgery to treat incidental aneurysms. Twenty-two patients with supratentorial AVMs and 16 patients with incidentally found aneurysms were included. Hypoxic pattern was defined as PtiO(2)≤15 mm Hg and/or PtiO(2)/PaO(2) ratio ≤0.10. Tissue hypoxia was detected in 63.6% of the catheters placed in the perinidal area and in 43.8% of catheters placed in a distant area. AVM excision significantly improved oxygenation both around the AVM and in the distant area. The PtiO(2)/PaO(2) ratio is a better indicator than absolute PtiO(2) in detecting tissue hypoxia in mechanically ventilated patients. Intraoperative monitoring showed tissue hypoxia in the margins of AVMs and in the distant ipsilateral brain as the most common finding. Surgical removal of AVMs induces a significant improvement in the oxygenation status in both areas.

Brain AVM (Arteriovenous Malformation)

MedlinePlus

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Molecular and cellular biology of cerebral arteriovenous malformations: a review of current concepts and future trends in treatment.

PubMed

Rangel-Castilla, Leonardo; Russin, Jonathan J; Martinez-Del-Campo, Eduardo; Soriano-Baron, Hector; Spetzler, Robert F; Nakaji, Peter

2014-09-01

Arteriovenous malformations (AVMs) are classically described as congenital static lesions. However, in addition to rupturing, AVMs can undergo growth, remodeling, and regression. These phenomena are directly related to cellular, molecular, and physiological processes. Understanding these relationships is essential to direct future diagnostic and therapeutic strategies. The authors performed a search of the contemporary literature to review current information regarding the molecular and cellular biology of AVMs and how this biology will impact their potential future management. A PubMed search was performed using the key words "genetic," "molecular," "brain," "cerebral," "arteriovenous," "malformation," "rupture," "management," "embolization," and "radiosurgery." Only English-language papers were considered. The reference lists of all papers selected for full-text assessment were reviewed. Current concepts in genetic polymorphisms, growth factors, angiopoietins, apoptosis, endothelial cells, pathophysiology, clinical syndromes, medical treatment (including tetracycline and microRNA-18a), radiation therapy, endovascular embolization, and surgical treatment as they apply to AVMs are discussed. Understanding the complex cellular biology, physiology, hemodynamics, and flow-related phenomena of AVMs is critical for defining and predicting their behavior, developing novel drug treatments, and improving endovascular and surgical therapies.

Ten-year detection rate of brain arteriovenous malformations in a large, multiethnic, defined population.

PubMed

Gabriel, Rodney A; Kim, Helen; Sidney, Stephen; McCulloch, Charles E; Singh, Vineeta; Johnston, S Claiborne; Ko, Nerissa U; Achrol, Achal S; Zaroff, Jonathan G; Young, William L

2010-01-01

To evaluate whether increased neuroimaging use is associated with increased brain arteriovenous malformation (BAVM) detection, we examined detection rates in the Kaiser Permanente Medical Care Program of northern California between 1995 and 2004. We reviewed medical records, radiology reports, and administrative databases to identify BAVMs, intracranial aneurysms (IAs: subarachnoid hemorrhage [SAH] and unruptured aneurysms), and other vascular malformations (OVMs: dural fistulas, cavernous malformations, Vein of Galen malformations, and venous malformations). Poisson regression (with robust standard errors) was used to test for trend. Random-effects meta-analysis generated a pooled measure of BAVM detection rate from 6 studies. We identified 401 BAVMs (197 ruptured, 204 unruptured), 570 OVMs, and 2892 IAs (2079 SAHs and 813 unruptured IAs). Detection rates per 100 000 person-years were 1.4 (95% CI, 1.3 to 1.6) for BAVMs, 2.0 (95% CI, 1.8 to 2.3) for OVMs, and 10.3 (95% CI, 9.9 to 10.7) for IAs. Neuroimaging utilization increased 12% per year during the time period (P<0.001). Overall, rates increased for IAs (P<0.001), remained stable for OVMs (P=0.858), and decreased for BAVMs (P=0.001). Detection rates increased 15% per year for unruptured IAs (P<0.001), with no change in SAHs (P=0.903). However, rates decreased 7% per year for unruptured BAVMs (P=0.016) and 3% per year for ruptured BAVMs (P=0.005). Meta-analysis yielded a pooled BAVM detection rate of 1.3 (95% CI, 1.2 to 1.4) per 100 000 person-years, without heterogeneity between studies (P=0.25). Rates for BAVMs, OVMs, and IAs in this large, multiethnic population were similar to those in other series. During 1995 to 2004, a period of increasing neuroimaging utilization, we did not observe an increased rate of detection of unruptured BAVMs, despite increased detection of unruptured IAs.

Updates and Future Horizons on the Understanding, Diagnosis, and Treatment of Sturge-Weber Syndrome Brain Involvement

ERIC Educational Resources Information Center

Lo, Warren; Marchuk, Douglas A.; Ball, Karen L.; Juhasz, Csaba; Jordan, Lori C.; Ewen, Joshua B.; Comi, Anne

2012-01-01

Aim: To review recent developments in the understanding, diagnosis, and treatment of Sturge-Weber syndrome (SWS). Method: Members of the Brain Vascular Malformation Consortium Sturge-Weber Syndrome National Workgroup contributed their expertise to review the literature and present promising directions for research. Results: The increasing number…

MODEST THYROID HORMONE INSUFFICIENCY DURING DEVELOPMENT INDUCES A CELLULAR MALFORMATION IN THE CORPUS CALLOSUM: A MODEL OF CORTICAL DYSPLASIA.

EPA Science Inventory

There is a growing body of evidence that subtle decreases in maternal thyroid hormone during gestation can impact fetal brain development. The present study examined the impact of graded levels of thyroid hormone insufficiency on brain development in rodents. Maternal thyroid ho...

[Clinical-neuropsychological study of patients with hematomas, cavernomas and arteriovenous malformations of the brain stem].

PubMed

Buklina, S B; Gavriushin, A V; Okishev, D N

2009-01-01

A clinical-neuropsychological study of 25 patients with hematomas, cavernomas and arteriovenous malformations of different brain stem regions has been performed. Patients with hydrocephalic-hypertensive and dislocation syndromes as well as a history of neurological diseases were excluded from the study. All patients had hemorrhages in different brain stem regions, most of which had occurred several weeks ago. Hematomas were located in different regions of the pons (14 patients) and midbrain (7 patients) and spread to both regions in 4 patients. All patients underwent MRI study of the brain and complex neuropsychological investigation using the A.R. Luria's method. Neuropsychological symptoms before the surgery were found in 20 patients. Cognitive disturbances similar by the lesion of frontal lobes, in particular the promoter zone, that manifested themselves in disturbances of dynamic praxis, writing, verbal memory, were observed most often. Cognitive disturbances similar by the lesion of occipital hemisphere regions, i.e. disturbances of visual gnosis and spatial defects, were found less often. The most severe symptoms were observed in the lesion of the midbrain and upper regions of the pons.

Prenatal neurologic anomalies: sonographic diagnosis and treatment.

PubMed

De Catte, Luc; De Keersmaeker, Bart; Claus, Filip

2012-06-01

The low prevalence of fetal CNS anomalies results in a restricted level of exposure to, and limited experience for most obstetricians involved in, prenatal ultrasound. Sonographic guidelines for screening the fetal brain in a systematic way may increase the detection rate of fetal CNS anomalies, thus promoting correct referral to tertiary care centers offering patients a multidisciplinary approach to the condition. The aim of this review is to elaborate on the prenatal sonographic diagnosis and outcome of various CNS malformations. Detailed neurosonographic investigation has become available through high-resolution vaginal ultrasound probes and the development of a variety of 3-dimensional (3D) ultrasound modalities, such as ultrasound tomographic imaging. In addition, fetal magnetic resonance imaging is particularly helpful in the detection of gyration and neurulation anomalies, and disorders of the gray and white matter. Isolated mild ventriculomegaly is a rather common finding with good overall outcome. With an increasing diameter of the atria, however, and especially with the presence of associated malformations, long-term neurodevelopmental and behavioral outcome is disturbed in about 15% or more of cases. In view of recent developments in fetal therapy for neural tube defects, there is a clear need for a high level of ultrasound screening, work-up and counseling in tertiary care centers to identify those cases that might benefit from in utero intervention. The failure of prosencephalic midline induction and development results in midline defects ranging from alobar holoprosencephaly to isolated corpus callosum defects. The detection of callosal abnormaties is enhanced by 3D ultrasound, but counseling on neurodevelopmental outcome remains challenging. The Dandy-Walker spectrum includes isolated megacisterna magna, Blake's pouch cyst, hypoplasia of the vermis and Dandy-Walker malformation. Except for complete agenesis of the vermis associated with fourth ventricle cyst formation, data on long-term outcomes for the various conditions is largely lacking. Congenital cytomegalovirus (CMV) results in the highest incidence of children born with, or developing, long-term neurologic conditions. If proof of fetal infection has been delivered, microcephaly, cortical malformations, and intraparenchymal cysts show a strong correlation with poor outcome. Fetuses with CMV-related ultrasound abnormalities might benefit from maternal transplacental treatment. The aneurysm of the vein of Galen, a vascular malformation of the brain, often results in high cardiac output failure. After neonatal arterial embolization, survival is about 50% with normal neurologic development in 36% of cases. Over 50% of intracranial tumors are teratomata, presenting as fast-growing heterogeneous solid-cystic masses with calcifications. Most intracranial hemorrhages are related to the ventricular system, and prognosis is often poor, particularly in cases involving parenchymal and subdural bleeding. Proliferation disorders of the brain are often characterized by microcephaly. Their etiology is heterogeneous and prenatal diagnosis is often made late in gestation.

Brain abscesses associated with right-to-left shunts in adults.

PubMed

Memon, Kashif A; Cleveland, Kerry O; Gelfand, Michael S

2012-04-01

Although brain abscesses are frequently cryptogenic in origin, bacteria must reach the brain either by direct or hematogenous spread. Right-to-left shunts, caused either by intrapulmonary vascular malformations or congenital heart defects, may allow microorganisms to evade the normal host defenses in the lungs and lead to development of brain abscesses. Two patients recently presented with brain abscesses and were found to have conditions associated with right-to-left shunts. The diagnosis of brain abscess should prompt the clinician to consider right-to-left shunts as a possible predisposing condition for brain abscess.

40 CFR 158.500 - Toxicology data requirements table.

Code of Federal Regulations, 2013 CFR

2013-07-01

..., following pre- and postnatal exposure (i.e., nervous system malformations or neuropathy, brain weight... the nervous system (e.g., SAR relationship to known neurotoxicants, altered neuroreceptor or...

Cerebral arteriovenous malformation

MedlinePlus

AVM - cerebral; Arteriovenous hemangioma; Stroke - AVM; Hemorrhagic stroke - AVM ... The cause of cerebral AVM is unknown. An AVM occurs when arteries in the brain connect directly to nearby veins without having the ...

Bilateral Acute Subdural Hematoma from Ruptured Posterior Communicating Artery Aneurysm

PubMed Central

Boujemâa, H.; Góngora-Rivera, F.; Barragán-Campos, H.; Karachi, K.; Chiras, J.; Sourour, N.

2006-01-01

Summary Brain tumors, hematological diseases and vascular malformations like fistulas or arteriovenous malformations are the most well known causes of non-traumatic subdural hematoma (SDH) 1. Although spontaneous subdural hematoma from ruptured intracranial aneurysm has been reported 2, SDH with non radiographic evidence of subarachnoid hemorrhage is very rare 3,4. Moreover, a patient with acute and bilateral spontaneous subdural hematoma secondary to ruptured left posterior communicating artery aneurysm has not been reported to date. The clinical findings and etiologic mechanisms are discussed. PMID:20569549

Sylvian fissure lipoma with angiomatous component and associated brain malformation: A case report.

PubMed

Thakur, Shruti; Sood, Ram Gopal; Jhobta, Anupam; Makhaik, Sushma; Thakur, Charusmita

2013-01-01

Intracranial lipomas are congenital malformations. These uncommon lesions have an incidence of 0.1 to 1.7% of all intracranial tumors. Most cases are located at midline and 5% are along the sylvian fissures. If symptomatic, seizures are the most common symptom. These tumors are slow growing and have favorable outcome. We report a case of a 25-year-old man whose CT and MRI revealed a lesion in right sylvian fissure suggesting a lipoma with abnormal vasculature and overlying cortical dysplasia.

Clinical presentation and treatment paradigms of brain arteriovenous malformations in patients with hereditary hemorrhagic telangiectasia.

PubMed

Gamboa, Nicholas T; Joyce, Evan J; Eli, Ilyas; Park, Min S; Taussky, Philipp; Schmidt, Richard H; McDonald, Jamie; Whitehead, Kevin J; Kalani, M Yashar S

2018-05-01

Hereditary hemorrhagic telangiectasia (HHT) is characterized by recurrent spontaneous epistaxis, mucocutaneous telangiectases, and multisystem arteriovenous malformations (AVMs). Brain AVMs typically present at birth and are identified in approximately 10-20% of patients with HHT. A retrospective review was undertaken of all HHT patients with known single or multiple brain AVMs treated at our institution. Thirty-nine patients with brain AVM(s) were diagnosed with HHT. Most patients presented with at least one Curaçao criterion. A total of 78 brain AVMs were identified in 39 patients. Two-thirds of patients had solitary brain AVMs, whereas 33% of patients harbored at least two lesions (range: 2-16). Brain AVMs of the supratentorial cerebral hemispheres comprised 83% of all lesions, whereas infratentorial lesions accounted for only 17%. Of the 55 brain AVMs assigned Spetzler-Martin grading, the majority of patients were Grade 1 (73%), and 23% and 4% were Grades 2 and 3, respectively. Patients were treated with surgery alone (51%), embolization alone (6%), embolization followed by surgery (9%), stereotactic radiosurgery (11%), stereotactic radiosurgery followed by surgery (3%), or observation (20%). Of patients who underwent genetic analysis, 62% possessed mutations in ENG (HHT type 1), whereas 38% had mutations in ACVRL1 (HHT type 2). This robust patient cohort of brain AVMs in 39 patients with HHT advances the collective understanding of this disease's varied presentation, diagnostic workup, genetic underpinnings, and available treatment options. Copyright © 2018. Published by Elsevier Ltd.

Use of the TriSpan Coil to Facilitate the Transcatheter Occlusion of Pulmonary Arteriovenous Malformation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cil, Barbaros E., E-mail: barbaroscil@hotmail.com, E-mail: barbaros@hacettepe.edu.tr; Erdogan, Cueneyt; Akmangit, Ilkay

Pulmonary arteriovenous malformation (PAVM) is a rare vascular malformation of the lung which may occur as an isolated entity or in association with hereditary hemorrhagic telangiectasia (HHT). Because of considerable risk of serious complications such as cerebral embolism, brain abscess and pulmonary hemorrhage, definitive treatment should be considered in most patients. Embolization with coils or detachable balloons is currently the preferred treatment. Paradoxical embolization of coils and balloons may happen, especially in patients with PAVMs with large feeding arteries. In this report we present our initial experience with the use of the TriSpan coil to lower the risk of coilmore » migration during the transcatheter occlusion of PAVMs.« less

Demographic confounders in volumetric MRI analysis: is the posterior fossa really small in the adult Chiari 1 malformation?

PubMed

Roller, Lauren A; Bruce, Beau B; Saindane, Amit M

2015-04-01

Measurement of posterior fossa volume has been proposed to have diagnostic utility and physiologic significance in the Chiari malformation type 1. This study evaluated the effects of demographics on posterior fossa volume and total intracranial volume in adult control subjects, adult patients with Chiari malformation type 1, and adult patients with idiopathic intracranial hypertension, who may share some imaging features of patients with Chiari malformation type 1. Twenty-eight patients with Chiari malformation type 1, 21 patients with idiopathic intracranial hypertension, and 113 control subjects underwent brain MRI including contrast-enhanced 3D gradient-recalled echo (GRE) T1-weighted imaging. Linear measurements of the posterior fossa and intracranial space were obtained. Manual segmentation of the posterior fossa and intracranial space was performed to yield posterior fossa volume and total intracranial volume. Age, sex, race, and body mass index (weight in kilograms divided by the square of height in meters; BMI) were controlled for when comparing cohorts. Three of the 12 linear measurements significantly predicted total intracranial volume (accounting for 74% of variance), and four predicted posterior fossa volume (54% of variance). Age, race, sex, and BMI each statistically significantly influenced posterior fossa volume and total intracranial volume. No statistically significant differences in posterior fossa volume, total intracranial volume, or ratio of posterior fossa volume to total intracranial volume were seen between the Chiari malformation type 1 group and control group after controlling for demographics. Patients with idiopathic intracranial hypertension were more likely than control subjects to have smaller posterior fossa volumes (odds ratio [OR]=1.81; p=0.01) and larger total intracranial volumes (OR=1.24; p=0.06). Linear measurements of the posterior fossa are not strong predictors of posterior fossa volume. Age, race, sex, and BMI have statistically significant effects on intracranial measurements that must be considered, particularly with respect to posterior fossa volume in Chiari malformation type 1. Even when these demographic variables are appropriately accounted for, other similarly presenting diseases may show small posterior fossa volumes.

Malformations of the craniocervical junction (chiari type I and syringomyelia: classification, diagnosis and treatment)

PubMed Central

2009-01-01

Chiari disease (or malformation) is in general a congenital condition characterized by an anatomic defect of the base of the skull, in which the cerebellum and brain stem herniate through the foramen magnum into the cervical spinal canal. The onset of Chiari syndrome symptoms usually occurs in the second or third decade (age 25 to 45 years). Symptoms may vary between periods of exacerbation and remission. The diagnosis of Chiari type I malformation in patients with or without symptoms is established with neuroimaging techniques. The most effective therapy for patients with Chiari type I malformation/syringomyelia is surgical decompression of the foramen magnum, however there are non-surgical therapy to relieve neurophatic pain: either pharmacological and non-pharmacological. Pharmacological therapy use drugs that act on different components of pain. Non-pharmacological therapies are primarly based on spinal or peripheral electrical stimulation. It is important to determine the needs of the patients in terms of health-care, social, educational, occupational, and relationship issues, in addition to those derived from information aspects, particularly at onset of symptoms. Currently, there is no consensus among the specialists regarding the etiology of the disease or how to approach, monitor, follow-up, and treat the condition. It is necessary that the physicians involved in the care of people with this condition comprehensively approach the management and follow-up of the patients, and that they organize interdisciplinary teams including all the professionals that can help to increase the quality of life of patients. PMID:20018097

Onyx in Brain Arteriovenous Malformation Embolisation.

PubMed

Hashim, Hilwati; Muda, A Sobri; Abdul Aziz, Aida; Abdul Hamid, Zuhanis

2016-07-01

Embolisation has long been used as an adjunct to surgical resection in the treatment of brain arteriovenous malformation (bAVM). The most commonly used embolic material, n-butylcyanoacrylate glue, requires experience and skill to handle its quick and unpredictable flow and polymerisation. A new liquid embolic agent, ethylene vinyl alcohol copolymer (Onyx), is less adhesive and polymerises slowly, which provides better control for radiologists performing embolisation. To report our experience in embolisation using Onyx alone or in combination with histoacryl for bAVM embolisation in our tertiary referral centre. We retrospectively reviewed the anatomy, technical conditions, complications and clinical outcome of all bAVM patients embolised at our centre using Onyx alone or in combination with n-butylcyanoacrylate glue. Between 2010 and 2013, 13 patients [6 (46.2%) male; 7 (53.8%) female; aged, 14-57 years] were included, and a total of 31 embolisations were performed. Clinical presentation included hemorrhage [9 (69.2%)], seizures [2 (15.4%)], and headache [2 (15.4%)]. Most AVMs were located in the brain hemispheres [12 (92.3%)] and measured <3 cm [7 (53.8%]. Complete occlusion of the AVM was obtained in 2 (15.4%) patients; 11 (84.6%) patients had partial occlusion [6 (54.5%) had <50% nidus occlusion]. Complications occurred in four procedures involving 3 patients (morbidity, 23.1%). This resulted in the death of 1 patient (mortality, 7.7%) and complete recovery with no disability in 2 patients. The total nidal occlusion achieved herein is comparable to other similar studies. Our morbidity and mortality were higher compared to other studies which may be attributed to the small number of patients. More data is being collected which may better reflect on our experience.

21 CFR 878.4010 - Tissue adhesive.

Code of Federal Regulations, 2012 CFR

2012-04-01

... DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4010 Tissue adhesive. (a) Tissue... intended for use in the embolization of brain arteriovenous malformation or for use in ophthalmic surgery...

21 CFR 878.4010 - Tissue adhesive.

Code of Federal Regulations, 2014 CFR

2014-04-01

... DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4010 Tissue adhesive. (a) Tissue... intended for use in the embolization of brain arteriovenous malformation or for use in ophthalmic surgery...

21 CFR 878.4010 - Tissue adhesive.

Code of Federal Regulations, 2013 CFR

2013-04-01

... DEVICES GENERAL AND PLASTIC SURGERY DEVICES Surgical Devices § 878.4010 Tissue adhesive. (a) Tissue... intended for use in the embolization of brain arteriovenous malformation or for use in ophthalmic surgery...

Cyclopia: from Greek antiquity to medical genetics.

PubMed

Kalantzis, George C; Tsiamis, Costas B; Poulakou-Rebelakou, Effie L

2013-01-01

Cyclops are among the best-known monsters of Greek mythology, also mentioned in art and literature. According to the most recent scientific knowledge, the malformations caused by defective development of the anterior brain and midline mesodermal structures include cyclopia (synophthalmos), ethmocephaly, cebocephaly and arrhinencephaly. These severe forebrain lesions often are accompanied by severe systemic malformations, and affected infants rarely survive. Neither true cyclopia nor synophthalmos are compatible with life because an anomalous development of the brain is involved. Thus, it is difficult to assume that ancient Greeks drew their inspiration from an adult patient suffering from cyclopia. Cyclops appear for the first time in literature in Homer's Odyssey (8th-7th century BC) and one of them, Polyphemus, is blinded by the hero of the epic poem. The description of the creature is identical with patients suffering from cyclopia; eyes are fused and above the median eye there is a proboscis, which is the result of an abnormal development of the surface ectodermal structures covering the brain. The next literature appearance of Cyclops is at the end of 7th century BC in "Theogonia", written by Hesiodus. Another interesting description is made by Euripides in his satyr play entitled 'Cyclops' (5th century BC). In conclusion, though it is not certain whether Homer's description of Cyclops was based on his personal experience or the narration of his ancestors, there is no doubt that the ophthalmological disease, cyclopia, was named after this mythical creature.

Physical biology of human brain development.

PubMed

Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

2015-01-01

Neurodevelopment is a complex, dynamic process that involves a precisely orchestrated sequence of genetic, environmental, biochemical, and physical events. Developmental biology and genetics have shaped our understanding of the molecular and cellular mechanisms during neurodevelopment. Recent studies suggest that physical forces play a central role in translating these cellular mechanisms into the complex surface morphology of the human brain. However, the precise impact of neuronal differentiation, migration, and connection on the physical forces during cortical folding remains unknown. Here we review the cellular mechanisms of neurodevelopment with a view toward surface morphogenesis, pattern selection, and evolution of shape. We revisit cortical folding as the instability problem of constrained differential growth in a multi-layered system. To identify the contributing factors of differential growth, we map out the timeline of neurodevelopment in humans and highlight the cellular events associated with extreme radial and tangential expansion. We demonstrate how computational modeling of differential growth can bridge the scales-from phenomena on the cellular level toward form and function on the organ level-to make quantitative, personalized predictions. Physics-based models can quantify cortical stresses, identify critical folding conditions, rationalize pattern selection, and predict gyral wavelengths and gyrification indices. We illustrate that physical forces can explain cortical malformations as emergent properties of developmental disorders. Combining biology and physics holds promise to advance our understanding of human brain development and enable early diagnostics of cortical malformations with the ultimate goal to improve treatment of neurodevelopmental disorders including epilepsy, autism spectrum disorders, and schizophrenia.

RASA1 analysis guides management in a family with capillary malformation-arteriovenous malformation

PubMed Central

Flore, Leigh Anne; Leon, Eyby; Maher, Tom A.; Milunsky, Jeff M.

2012-01-01

Capillary malformation-arteriovenous malformation (CM-AVM; MIM 60354) is an autosomal dominant disorder characterized by multifocal cutaneous capillary malformations, often in association with fast-flow vascular lesions, which may be cutaneous, subcutaneous, intramuscular, intraosseus, or cerebral arteriovenous malformations or arteriovenous fistulas. CM-AVM results from heterozygous mutations in the RASA1 gene. Capillary malformations of the skin are common, and clinical examination alone may not be able to definitively diagnose-or exclude- CM-AVM. We report a family in which the proband was initially referred for a genetic evaluation in the neonatal period because of the presence of a cardiac murmur and minor dysmorphic features. Both he and his mother were noted to have multiple capillary malformations on the face, head, and extremities. Echocardiography revealed dilated head and neck vessels and magnetic resonance imaging and angiography of the brain revealed a large infratentorial arteriovenous fistula, for which he has had two embolization procedures. RASA1 sequence analysis revealed a heterozygous mutation, confirming his diagnosis of CM-AVM. We established targeted mutation analysis for the proband's mother and sister, the latter of whom is a healthy 3-year-old whose only cutaneous finding is a facial capillary malformation. This revealed that the proband's mother is also heterozygous for the RASA1 mutation, but his sister is negative. Consequently, his mother will undergo magnetic resonance imaging and angiography screening for intracranial and spinal fast-flow lesions, while his sister will require no imaging or serial evaluations. Targeted mutation analysis has been offered to additional maternal family members. This case illustrates the benefit of molecular testing in diagnosis and making screening recommendations for families with CM-AVM. PMID:27625812

RASA1 analysis guides management in a family with capillary malformation-arteriovenous malformation.

PubMed

Flore, Leigh Anne; Leon, Eyby; Maher, Tom A; Milunsky, Jeff M

2012-06-01

Capillary malformation-arteriovenous malformation (CM-AVM; MIM 60354) is an autosomal dominant disorder characterized by multifocal cutaneous capillary malformations, often in association with fast-flow vascular lesions, which may be cutaneous, subcutaneous, intramuscular, intraosseus, or cerebral arteriovenous malformations or arteriovenous fistulas. CM-AVM results from heterozygous mutations in the RASA1 gene. Capillary malformations of the skin are common, and clinical examination alone may not be able to definitively diagnose-or exclude- CM-AVM. We report a family in which the proband was initially referred for a genetic evaluation in the neonatal period because of the presence of a cardiac murmur and minor dysmorphic features. Both he and his mother were noted to have multiple capillary malformations on the face, head, and extremities. Echocardiography revealed dilated head and neck vessels and magnetic resonance imaging and angiography of the brain revealed a large infratentorial arteriovenous fistula, for which he has had two embolization procedures. RASA1 sequence analysis revealed a heterozygous mutation, confirming his diagnosis of CM-AVM. We established targeted mutation analysis for the proband's mother and sister, the latter of whom is a healthy 3-year-old whose only cutaneous finding is a facial capillary malformation. This revealed that the proband's mother is also heterozygous for the RASA1 mutation, but his sister is negative. Consequently, his mother will undergo magnetic resonance imaging and angiography screening for intracranial and spinal fast-flow lesions, while his sister will require no imaging or serial evaluations. Targeted mutation analysis has been offered to additional maternal family members. This case illustrates the benefit of molecular testing in diagnosis and making screening recommendations for families with CM-AVM.

A mouse model of DEPDC5-related epilepsy: Neuronal loss of Depdc5 causes dysplastic and ectopic neurons, increased mTOR signaling, and seizure susceptibility.

PubMed

Yuskaitis, Christopher J; Jones, Brandon M; Wolfson, Rachel L; Super, Chloe E; Dhamne, Sameer C; Rotenberg, Alexander; Sabatini, David M; Sahin, Mustafa; Poduri, Annapurna

2018-03-01

DEPDC5 is a newly identified epilepsy-related gene implicated in focal epilepsy, brain malformations, and Sudden Unexplained Death in Epilepsy (SUDEP). In vitro, DEPDC5 negatively regulates amino acid sensing by the mTOR complex 1 (mTORC1) pathway, but the role of DEPDC5 in neurodevelopment and epilepsy has not been described. No animal model of DEPDC5-related epilepsy has recapitulated the neurological phenotypes seen in patients, and germline knockout rodent models are embryonic lethal. Here, we establish a neuron-specific Depdc5 conditional knockout mouse by cre-recombination under the Synapsin1 promotor. Depdc5 flox/flox -Syn1 Cre (Depdc5cc+) mice survive to adulthood with a progressive neurologic phenotype that includes motor abnormalities (i.e., hind limb clasping) and reduced survival compared to littermate control mice. Depdc5cc+ mice have larger brains with increased cortical neuron size and dysplastic neurons throughout the cortex, comparable to the abnormal neurons seen in human focal cortical dysplasia specimens. Depdc5 results in constitutive mTORC1 hyperactivation exclusively in neurons as measured by the increased phosphorylation of the downstream ribosomal protein S6. Despite a lack of increased mTORC1 signaling within astrocytes, Depdc5cc+ brains show reactive astrogliosis. We observed two Depdc5cc+ mice to have spontaneous seizures, including a terminal seizure. We demonstrate that as a group Depdc5cc+ mice have lowered seizure thresholds, as evidenced by decreased latency to seizures after chemoconvulsant injection and increased mortality from pentylenetetrazole-induced seizures. In summary, our neuron-specific Depdc5 knockout mouse model recapitulates clinical, pathological, and biochemical features of human DEPDC5-related epilepsy and brain malformations. We thereby present an important model in which to study targeted therapeutic strategies for DEPDC5-related conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Korean Database of Cerebral Palsy: A Report on Characteristics of Cerebral Palsy in South Korea

PubMed Central

2017-01-01

Objective To introduce the Korean Database of Cerebral Palsy (KDCP) and to provide the first report on characteristics of subjects with cerebral palsy (CP). Methods The KDCP is a nationwide database of subjects with CP, which includes a total of 773 subjects. Characteristics such as demography, birth history, onset and type of CP, brain magnetic resonance imaging (MRI) findings, functional ability and accompanying impairments, were extracted and analyzed. Results Preterm delivery and low birth weight were found in 59.51% and 60.28% of subjects, respectively. Postnatally acquired CP was 15.3%. The distribution of CP was 87.32%, 5.17%, and 1.81% for spastic, dyskinetic, and ataxic types, respectively. Functional ability was the worst in dyskinetic CP, as compared to other types of CP. Speech-language disorder (43.9%), ophthalmologic impairment (32.9%), and intellectual disability (30.3%) were the three most common accompanying impairments. The number of accompanying impairments was elevated in subjects with preterm birth and low birth weight. Brain MRI showed normal findings, malformations, and non-malformations in 10.62%, 9.56%, and 77.35% of subjects, respectively. Subjects with normal MRI findings had better functional ability than subjects with other MRI findings. MRI findings of a non-malformation origin, such as periventricular leukomalacia, were more common in subjects with preterm birth and low birth weight. Conclusion The KDCP and its first report are introduced in this report, wherein the KDCP established agreement on terminologies of CP. This study added information on the characteristics of subjects with CP in South Korea, which can now be compared to those of other countries and ethnicities. PMID:28971049

The Usefulness of Diffusion Tensor Imaging and Tractography in Surgery of Brainstem Cavernous Malformations.

PubMed

Januszewski, Jacob; Albert, Lauren; Black, Karen; Dehdashti, Amir R

2016-09-01

Diffusion tensor imaging (DTI) estimates the course and connectivity patterns of white matter tracts. The objective of this study is to evaluate whether findings in the brain stem modify the preoperative surgical trajectory planning or postoperative outcome in patients with brain stem cavernous malformations. Ten patients with symptomatic brainstem cavernous malformation underwent surgical resection. Five patients received preoperative DTI evaluation and the remaining 5 did not. Reconstructed DTI tracts consisted of corticospinal, medial lemnisci, and cerebellar peduncles. The surgical planning and postoperative outcome were evaluated. In 5 patients with no preoperative DTI evaluation, surgical planning was based on anatomic landmark and the 2-point technique. The other 5 patients underwent preoperative DTI, and findings were factored into the selection of the surgical approach. In 3 of the 5 cases with DTI evaluation, the 2-point technique suggested a similar trajectory. In the other 2, the DTI findings suggested a different approach to avoid damage to the white matter tract. Two patients in the group with no DTI had immediate postoperative new or worsened deficit, which improved at long-term follow-up. No patient in the DTI group had a new neurologic deficit. Compared with the standard magnetic resonance imaging, DTI provided improved visualization of cavernous malformation involvement in eloquent fiber tracts of the brainstem. This additional information might help in selecting a more appropriate surgical trajectory in selected lesions. Larger patient cohorts are needed to assess the effect of this modality in patients' outcome. Published by Elsevier Inc.

Stereotactic radiosurgery of angiographically occult vascular malformations: Indications and preliminary experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kondziolka, D.; Lunsford, L.D.; Coffey, R.J.

1990-12-01

Stereotactic radiosurgery has been shown to treat successfully angiographically demonstrated arteriovenous malformations of the brain. Angiographic obliteration has represented cure and eliminated the risk of future hemorrhage. The role of radiosurgery in the treatment of angiographically occult vascular malformations (AOVMs) has been less well defined. In the initial 32 months of operation of the 201-source cobalt-60 gamma knife at the University of Pittsburgh, 24 patients meeting strict criteria for high-risk AOVMs were treated. Radiosurgery was used conservatively; each patient had sustained two or more hemorrhages and had a magnetic resonance imaging-defined AOVM located in a region of the brain wheremore » microsurgical removal was judged to pose an excessive risk. Venous angiomas were excluded by performance of high-resolution subtraction angiography in each patient. Fifteen malformations were in the medulla, pons, and/or mesencephalon, and 5 were located in the thalamus or basal ganglia. Follow-up ranged from 4 to 24 months. Nineteen patients either improved or remained clinically stable and did not hemorrhage again during the follow-up interval. One patient suffered another hemorrhage 7 months after radiosurgery. Five patients experienced temporary worsening of pre-existing neurological deficits that suggested delayed radiation injury. Magnetic resonance imaging demonstrated signal changes and edema surrounding the radiosurgical target. Dose-volume guidelines for avoiding complications were constructed. Our initial experience indicates that stereotactic radiosurgery can be performed safely in patients with small, well-circumscribed AOVMs located in deep, critical, or relatively inaccessible cerebral locations.« less

Pathophysiological analyses of cortical malformation using gyrencephalic mammals

PubMed Central

Masuda, Kosuke; Toda, Tomohisa; Shinmyo, Yohei; Ebisu, Haruka; Hoshiba, Yoshio; Wakimoto, Mayu; Ichikawa, Yoshie; Kawasaki, Hiroshi

2015-01-01

One of the most prominent features of the cerebral cortex of higher mammals is the presence of gyri. Because malformations of the cortical gyri are associated with severe disability in brain function, the mechanisms underlying malformations of the cortical gyri have been of great interest. Combining gyrencephalic carnivore ferrets and genetic manipulations using in utero electroporation, here we successfully recapitulated the cortical phenotypes of thanatophoric dysplasia (TD) by expressing fibroblast growth factor 8 in the ferret cerebral cortex. Strikingly, in contrast to TD mice, our TD ferret model showed not only megalencephaly but also polymicrogyria. We further uncovered that outer radial glial cells (oRGs) and intermediate progenitor cells (IPs) were markedly increased. Because it has been proposed that increased oRGs and/or IPs resulted in the appearance of cortical gyri during evolution, it seemed possible that increased oRGs and IPs underlie the pathogenesis of polymicrogyria. Our findings should help shed light on the molecular mechanisms underlying the formation and malformation of cortical gyri in higher mammals. PMID:26482531

A prospective, multicenter, randomized trial of the Onyx liquid embolic system and N-butyl cyanoacrylate embolization of cerebral arteriovenous malformations. Clinical article.

PubMed

Loh, Yince; Duckwiler, Gary R

2010-10-01

The Onyx liquid embolic system (Onyx) was approved in the European Union in 1999 for embolization of lesions in the intracranial and peripheral vasculature, including brain arteriovenous malformations (AVMs) and hypervascular tumors. In 2001 a prospective, equivalence, multicenter, randomized controlled trial was initiated to support a submission for FDA approval. The objective of this study was to verify the safety and efficacy of Onyx compared with N-butyl cyanoacrylate (NBCA) for the presurgical treatment of brain AVMs. One hundred seventeen patients with brain AVMs were treated with either Onyx (54 patients) or NBCA (63 patients) for presurgical endovascular embolization between May 2001 and April 2003. The primary end point was technical success in achieving ≥ 50% reduction in AVM volume. Secondary end points were operative blood loss and resection time. All adverse events (AEs) were reported and assigned a relationship to the Onyx or NBCA system, treatment, disease, surgery, or other/unknown. The Data Safety Monitoring Board adjudicated AEs, and a blinded, independent core lab assessed volume measurements. Patients were monitored through discharge after the final surgery or through a 3- and/or 12-month follow-up if resection had not been performed or was incomplete. The use of Onyx led to ≥ 50% AVM volume reduction in 96% of cases versus 85% for NBCA (p = not significant). The secondary end points of resection time and blood loss were similar. Serious AEs were also similar between the 2 treatment groups. Onyx is equivalent to NBCA in safety and efficacy as a preoperative embolic agent in reducing brain AVM volume by at least 50%.

mTOR: A pathogenic signaling pathway in developmental brain malformations.

PubMed

Crino, Peter B

2011-12-01

The mTOR signaling network functions as a pivotal regulatory cascade during the development of the cerebral cortex. Aberrant hyperactivation of mTOR as a consequence of loss-of-function gene mutations encoding mTOR inhibitor proteins such as TSC1, TSC2, PTEN and STRADα has been recently linked to developmental cortical malformations associated with epilepsy and neurobehavioral disabilities. Investigation of mTOR signaling in these disorders provides for the first time exciting future avenues for assessment of biomarkers, patient stratification and prognostic measures as well as the opportunity for targeted therapy to regulate mTOR activity across all age groups. As we learn more about mTOR and its activity in the developing brain, many challenges will arise that must be overcome before widespread clinical therapeutics can be implemented. Copyright © 2011. Published by Elsevier Ltd.

Radiological evolution of peri-odontoid pannus in a patient with Chiari I malformation: a case-based review.

PubMed

Sanders, Felipe Hada; Wang, Joy M H; Oskouian, Rod J; Tubbs, R Shane; Oakes, W Jerry

2017-08-01

The Chiari I malformation (CIM) is commonly encountered by neurosurgeons and can have different etiologies and clinical presentations. We report a CIM patient who presented with symptoms of ventral brain stem compression and was found to have a large peri-odontoid pannus. Posterior fossa decompression was performed with a planned second-stage odontoidectomy. However, at the 6-month follow-up, postoperative images demonstrated a mostly resolved pannus and improvement of the brain stem compression symptoms, and the patient progressed uneventfully without the need for odontoidectomy. This case illustrates the resolution of a significant and symptomatic peri-odontoid pannus in a patient with CIM without craniocervical fusion or odontoidectomy. Such a case indicates that not all peri-odontoid pannus formations in CIM patients are due to hypermobility at the craniocervical junction.

Computer-aided diagnosis of cavernous malformations in brain MR images.

PubMed

Wang, Huiquan; Ahmed, S Nizam; Mandal, Mrinal

2018-06-01

Cavernous malformation or cavernoma is one of the most common epileptogenic lesions. It is a type of brain vessel abnormality that can cause serious symptoms such as seizures, intracerebral hemorrhage, and various neurological disorders. Manual detection of cavernomas by physicians in a large set of brain MRI slices is a time-consuming and labor-intensive task and often delays diagnosis. In this paper, we propose a computer-aided diagnosis (CAD) system for cavernomas based on T2-weighted axial plane MRI image analysis. The proposed technique first extracts the brain area based on atlas registration and active contour model, and then performs template matching to obtain candidate cavernoma regions. Texture, the histogram of oriented gradients and local binary pattern features of each candidate region are calculated, and principal component analysis is applied to reduce the feature dimensionality. Support vector machines (SVMs) are finally used to classify each region into cavernoma or non-cavernoma so that most of the false positives (obtained by template matching) are eliminated. The performance of the proposed CAD system is evaluated and experimental results show that it provides superior performance in cavernoma detection compared to existing techniques. Copyright © 2018 Elsevier Ltd. All rights reserved.

Atypical psychotic symptoms and Dandy-Walker variant.

PubMed

Williams, Aislinn J; Wang, Zhenni; Taylor, Stephan F

2016-10-01

New-onset psychotic symptoms often respond well to antipsychotic treatment; however, symptoms may be difficult to treat when an underlying brain malformation is present. Here, we present a case of atypical psychotic symptoms in the context of a congenital cerebellar malformation (Dandy-Walker variant). The patient ultimately improved with paliperidone palmitate after multiple antipsychotic medication trials (both oral and one long-acting injectable) were ineffective. Neuroimaging may provide valuable diagnostic and prognostic information in cases of new-onset psychosis with atypical features and treatment resistance, even in the absence of neurologic signs and symptoms.

[Computer tomography of the brain in children. I. 1. Perinatal encephalopathy of vascular origin. 2. Congenital brain malformations].

PubMed

Cernoch, Z; Sercl, M; Parízek, J; Lichý, J

1990-01-01

CT findings are evaluated in 103 children with vascular lesions (aged up to 15 years), and in 59 children with congenital cerebral and cerebellar malformations. Their maximum has been stated to occur perinatally due to hypoxic and ischemic brain affections. Therefore most of diagnostical problems were related to the differentiation of hypodense immature brain from ischemic changes. Mentioned findings were always correlated with clinical course. Similar confrontations along with earlier CT control examination may be helpful in distinguishing milder transitory postischemic oedema from serious necrotic and malatic changes. In more aged children, vascular lesions are of rare occurrence being different in etiology. More unambiguous CT patterns are obtained in vascular changes with hemorrhagies. Of special importance in their onset is a hypoxic attack with subsequent venous bleeding mainly into the germinative matrix. While well tolerated in premature newborns, the extensive hemorrhagies in on-term ones have worser prognosis, resulting in significant changes on control examination, predominantly hydrocephalus and porencephalia. Atrophies of various extent were the most common consequence of all encephalopathies of vascular origine. In almost a half of congenital brain and cerebellar anomalies, unsignificant findings of smaller middle line cavities were obtained predominantly in pellucide septum. From the serious findings, most frequent were different varieties of dysgenesis, hypogenesis up to agenesis of corpus callosum combined sometimes with either the lipomas or cysts. Another findings consisted in Dandy-Walker's cerebellar malformation, holoprosencephalia and only two patients manifested hydrencephalia and basal meningoencephalocele. Most of diagnostical effort has been made in mainly anomalies associated with ventriculomegalia and/or cystic formations in order to elucidate the eventual communication between the structures mentioned. In addition, CT ventriculo-cysto-orcisternography has also been performed using smaller amount of nonionic contrast. At present, an important portion of CT examinations may be replaced with sonography which is more simple as used in both newborns and toddlers.

Pathological Evaluation of Radiation-Induced Vascular Lesions of the Brain: Distinct from De Novo Cavernous Hemangioma

PubMed Central

Cha, Yoon Jin; Nahm, Ji Hae; Ko, Ji Eun; Shin, Hyun Joo; Chang, Jong-Hee; Cho, Nam Hoon

2015-01-01

Purpose We aimed to evaluate the histologic and radiologic findings of vascular lesions after stereotactic radiosurgery (SRS) categorized as radiation-induced cavernous hemangioma (RICH). Materials and Methods Among 89 patients who underwent neurosurgery for cavernous hemangioma, eight RICHs from 7 patients and 10 de novo CHs from 10 patients were selected for histopathological and radiological comparison. Results Histologically, RICHs showed hematoma-like gross appearance. Microscopically, RICH exhibited a hematoma-like area accompanied by proliferation of thin-walled vasculature with fibrin deposits and infiltrating foamy macrophages. In contrast, CHs demonstrated localized malformed vasculature containing fresh and old clotted blood on gross examination. Typically, CHs consisted of thick, ectatic hyalinized vessels lined by endothelium under a light microscope. Magnetic resonance imaging of RICHs revealed some overlapping but distinct features with CHs, including enhancing cystic and solid components with absence or incomplete popcorn-like appearance and partial hemosiderin rims. Conclusion Together with histologic and radiologic findings, RICH may result from blood-filled space after tissue destruction by SRS, accompanied with radiation-induced reactive changes rather than vascular malformation. Thus, the term "RICH" would be inappropriate, because it is more likely to be an inactive organizing hematoma rather than proliferation of malformed vasculature. PMID:26446658

Experimental and clinical standards, and evolution of lasers in neurosurgery.

PubMed

Devaux, B C; Roux, F X

1996-01-01

From initial experiments of ruby, argon and CO2 lasers on the nervous system so far, dramatic progress was made in delivery systems technology as well as in knowledge of laser-tissue interaction effects and hazards through various animal experiments and clinical experience. Most surgical effects of laser light on neural tissue and the central nervous system (CNS) are thermal lesions. Haemostasis, cutting and vaporization depend on laser emission parameters--wavelength, fluence and mode--and on the exposed tissues optical and thermal properties--water and haemoglobin content, thermal conductivity and specific heat. CO2 and Nd-YAG lasers have today a large place in the neurosurgical armamentarium, while new laser sources such as high power diode lasers will have one in the near future. Current applications of these lasers derive from their respective characteristics, and include CNS tumour and vascular malformation surgery, and stereotactic neurosurgery. Intracranial, spinal cord and intra-orbital meningiomas are the best lesions for laser use for haemostasis, dissection and tissue vaporization. Resection of acoustic neuromas, pituitary tumours, spinal cord neuromas, intracerebral gliomas and metastases may also benefit from lasers as accurate, haemostatic, non-contact instruments which reduce surgical trauma to the brain and eloquent structures such as brain stem and cranial nerves. Coagulative lasers (1.06 microns and 1.32 microns Nd-YAG, argon, or diode laser) will find an application for arteriovenous malformations and cavernomas. Any fiberoptic-guided laser will find a use during stereotactic neurosurgical procedures, including image-guided resection of tumours and vascular malformations and endoscopic tumour resection and cysts or entry into a ventricle. Besides these routine applications of lasers, laser interstitial thermotherapy (LITT) and photodynamic therapy (PDT) of brain tumours are still in the experimental stage. The choice of a laser in a neurosurgical operating room implies an evaluation of the laser use (applications, frequency), of the available budget and costs--including purchase, maintenance and staff training--, and material that will be necessary: unit, peripherals, safety devices and measures, training programme. Future applications of lasers in neurosurgery will come from technological advances and refined experimental applications. The availability of new wavelength, tunable, small sized and "smart" laser units, will enlarge the thermal and non-thermal interactions between laser energy and neural tissue leading to new surgical applications. Tissue photo-ablation, photohynamic therapy using second generation of photosensitizers, updated thermotherapy protocols, are current trends for further use of lasers in neurosurgery.

Use of Morphometric Mapping to Characterise Symptomatic Chiari-Like Malformation, Secondary Syringomyelia and Associated Brachycephaly in the Cavalier King Charles Spaniel

PubMed Central

Cross, Chloe; Griffiths, Sandra; McFadyen, Angus K.; Jovanovik, Jelena; Tauro, Anna; Kibar, Zoha; Driver, Colin J.; La Ragione, Roberto M.; Rusbridge, Clare

2017-01-01

Objectives To characterise the symptomatic phenotype of Chiari-like malformation (CM), secondary syringomyelia (SM) and brachycephaly in the Cavalier King Charles Spaniel using morphometric measurements on mid-sagittal Magnetic Resonance images (MRI) of the brain and craniocervical junction. Methods This retrospective study, based on a previous quantitative analysis in the Griffon Bruxellois (GB), used 24 measurements taken on 130 T1-weighted MRI of hindbrain and cervical region. Associated brachycephaly was estimated using 26 measurements, including rostral forebrain flattening and olfactory lobe rotation, on 72 T2-weighted MRI of the whole brain. Both study cohorts were divided into three groups; Control, CM pain and SM and their morphometries compared with each other. Results Fourteen significant traits were identified in the hindbrain study and nine traits in the whole brain study, six of which were similar to the GB and suggest a common aetiology. The Control cohort had the most elliptical brain (p = 0.010), least olfactory bulb rotation (p = 0.003) and a protective angle (p = 0.004) compared to the other groups. The CM pain cohort had the greatest rostral forebrain flattening (p = 0.007), shortest basioccipital (p = 0.019), but a greater distance between the atlas and basioccipital (p = 0.002) which was protective for SM. The SM cohort had two conformation anomalies depending on the severity of craniocervical junction incongruities; i) the proximity of the dens (p <0.001) ii) increased airorhynchy with a smaller, more ventrally rotated olfactory bulb (p <0.001). Both generated ‘concertina’ flexures of the brain and craniocervical junction. Conclusion Morphometric mapping provides a diagnostic tool for quantifying symptomatic CM, secondary SM and their relationship with brachycephaly. It is hypothesized that CM pain is associated with increased brachycephaly and SM can result from different combinations of abnormalities of the forebrain, caudal fossa and craniocervical junction which compromise the neural parenchyma and impede cerebrospinal fluid flow. PMID:28122014

Superficial middle cerebral vein connection to the cavernous sinus is not infrequent in brain arteriovenous malformations: an argument against their congenital origin?

PubMed

Shotar, Eimad; Guédon, Alexis; Sourour, Nader; Di Maria, Federico; Gabrieli, Joseph; Nouet, Aurélien; Chiras, Jacques; Clarençon, Frédéric

2016-07-01

The aim of this study was to test the hypothesis that the superficial middle cerebral vein (SMCV) is frequently absent or fails to connect with the cavernous sinus (CS) in the presence of brain arteriovenous malformations (AVMs), a frequently reported argument for the congenital origin of brain AVMs. The SMCV was retrospectively compared between patients with a brain AVM and a control group. The presence or absence of the SMCV, its direct or indirect connection to the CS and its termination in a laterocavernous sinus (LCS), paracavernous sinus (PCS), or directly in the CS was studied on digital subtraction angiography. One hundred twenty-five left or right side carotid angiograms from 70 patients with a brain AVM were compared to 125 angiograms from 74 controls. The SMCV was present in 88 (70.4 %) cases in the brain AVM group and 96 (76.8 %) cases in controls (p = 0.25). The SMCV was connected directly or indirectly to the CS in 65 (52 %) cases in the brain AVM group and 65 (52 %) cases in controls (p = 1). When comparing the subgroup of carotid angiograms ipsilateral to a supratentorial AVM, no statistically significant difference was found with controls. In three of six cases in which a SMCV drained an AVM, the vein terminated directly or indirectly in the CS. No difference of SMCV presence and direct or indirect connection to the CS was found between patients with AVM and a control group. SMCV anatomy does not support the congenital origin of brain AVMs.

Psychosis in a Case of Dandy-Walker Syndrome: A Case Report.

PubMed

Dawra, Ripu Daman; Karia, Sagar; Shah, Nilesh; Desousa, Avinash

2017-05-01

Dandy Walker Syndrome (DWS) is a congenital malformation with brain abnormalities, intellectual disabilities, epilepsy and visible structural changes in particular brain structures. We present here a case of psychosis in an 18-year-old male with DWS, epilepsy and intellectual disability. The purpose of this paper is to discuss the clinically relevant issues, psychopharmacological issues, neuropsychiatric manifestations and consultation liaison issues involved.

Psychosis in a Case of Dandy-Walker Syndrome: A Case Report

PubMed Central

Dawra, Ripu Daman; Karia, Sagar; Shah, Nilesh

2017-01-01

Dandy Walker Syndrome (DWS) is a congenital malformation with brain abnormalities, intellectual disabilities, epilepsy and visible structural changes in particular brain structures. We present here a case of psychosis in an 18-year-old male with DWS, epilepsy and intellectual disability. The purpose of this paper is to discuss the clinically relevant issues, psychopharmacological issues, neuropsychiatric manifestations and consultation liaison issues involved. PMID:28658885

[Paradoxical brain embolism mediated through a pulmonary arteriovenous malformation with hereditary hemorrhagic telangiectasia in a Japanese patient].

PubMed

Takeda, June; Todo, Kenichi; Yamamoto, Shiro; Yamagami, Hiroshi; Kawamoto, Michi; Kohara, Nobuo

2012-01-01

We report a case of paradoxical brain embolism mediated through a pulmonary arteriovenous malformation (PAVM) with hereditary hemorrhagic telangiectasia (HHT). A 25-year-old right handed man was admitted to our hospital after sudden headache and visual field abnormality. In neurologic examinations, he had left superior-quadrantanopsia. Laboratory findings showed iron deficiency anemia. Diffusion weighted images disclosed a high-signal-intensity area in the right occipito-temporal lobe, and intraarterial digital subtraction cerebral angiography revealed occlusion of the right posterior cerebral artery. Transesophageal echocardiography revealed continuous right-to-left shunt. We confirmed his history of spontaneous recurrent epistaxis and the first-degree relatives with epistaxis or PAVM. A contrast enhanced CT scan of the chest revealed a PAVM. The diagnosis of paradoxical brain embolism mediated through the PAVM with HHT was, thus, established. The PAVM was occluded by using embolization coils successfully. In Asian countries, the prevalence of PAVM with HHT is thought to be lower than in European countries. We should carefully take medical and family histories, especially epistaxis, in a young stroke patient.

Brain stem and inner ear abnormalities in children with auditory neuropathy spectrum disorder and cochlear nerve deficiency.

PubMed

Huang, B Y; Roche, J P; Buchman, C A; Castillo, M

2010-11-01

Cranial abnormalities, including CND, are common in children with ANSD. The purpose of this study was to assess whether CND is associated with brain or inner ear abnormalities in a cohort of children with ANSD. Two neuroradiologists retrospectively reviewed cranial MR imaging examinations in 103 children with ANSD. Brain, cochlear nerve, and temporal bone abnormalities were described and tabulated. Findings were stratified on the basis of the presence and laterality of CND, and differences in the presence of associated inner ear or intracranial abnormalities were assessed by using 2-tailed Fisher exact tests. CND was identified in 33.0% of children and 26.9% of ears with ANSD. Significantly more patients with bilateral CND had intracranial abnormalities than those with unilateral CND (60.0% versus 15.8%; P = .012). Forty percent of patients with bilateral CND, 0% of patients with unilateral CND, and 10.1% of those without CND demonstrated hindbrain malformations. Patients with bilateral CND were more likely to demonstrate hindbrain malformations than patients with normal nerves (P = .01) or unilateral CND (P = .004). Labyrinthine abnormalities were significantly more common in patients with bilateral CND than in those without CND (P ≤ .001). Cochlear anomalies were more common in patients with bilateral versus unilateral CND (P = .01). IAC and cochlear aperture stenosis were more common in those with unilateral and bilateral CND than those without CND (both P < .001). Cochlear and hindbrain abnormalities are significantly more common among patients with ANSD with bilateral CND compared with those with at least 1 intact cochlear nerve.

Delayed diagnosis of Gorlin syndrome: Learning from mistakes!

PubMed

Ramanathan, Subramaniyan; Kumar, Devendra; Al Heidous, Mahmoud; Palaniappan, Yegu

2015-01-01

Gorlin syndrome (GS) is a rare inherited multisystem disorder with predisposition to basal cell carcinomas and various other neoplasms. Characteristic features include falx calcification, multiple odontogenic keratocysts (OKCs), early onset medulloblastoma, craniofacial and skeletal malformations, cardiac and ovarian fibroma. We present a case of GS in a 9-year-old girl with recurrent dental infections which was overlooked for 8 years. Diagnosis was finally suggested by the incidental detection of multiple OKCs and ovarian fibromas on follow-up magnetic resonance imaging performed for surveillance of previous operated brain tumor.

Dramatic response to levetiracetam in post-ischaemic Holmes’ tremor

PubMed Central

Striano, P; Elefante, Andrea; Coppola, Antonietta; Tortora, Fabio; Zara, Federico; Minetti, Carlo

2009-01-01

Holmes’ tremor refers to an unusual combination of rest, postural and kinetic tremor of extremities. Common causes of Holmes’ tremor include stroke, trauma, vascular malformations and multiple sclerosis, with lesions involving the thalamus, brain stem or cerebellum. Although some drugs (eg, levodopa and dopaminergic drugs, clonazepam and propranolol) have been occasionally reported to give some benefit, medical treatment of Holmes’ tremor is unsatisfactory, and many patients require thalamic surgery to achieve satisfactory control. We report a patient in whom post-ischaemic Holmes’ tremor dramatically responded to levetiracetam treatment. PMID:21686707

North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2

ClinicalTrials.gov

2018-06-06

Epilepsy; Seizure; Neuromuscular Diseases; Brain Malformation; Intellectual Disability; Autism Spectrum Disorder; Hypotonia; Inborn Errors of Metabolism; Movement Disorders; Genetic Disease; Development Delay; Chromosome Abnormality; Hearing Loss; Dysmorphic Features; Skeletal Dysplasia; Congenital Abnormality; Microcephaly; Macrocephaly

Genetics Home Reference: familial focal epilepsy with variable foci

MedlinePlus

... SF, Dibbens LM. Mutations in mammalian target of rapamycin regulator DEPDC5 cause focal epilepsy with brain malformations. ... caused by mutation in the mammalian target of rapamycin regulator NPRL3. Ann Neurol. 2016 Jan;79(1): ...

Dandy-Walker malformation and neurocutaneous melanosis in a three-month-old infant

PubMed Central

Mahgoub, Shaza Mohamed; Yassin, Rehab Omer; Osman, Atika Mohamed

2013-01-01

Dandy-Walker Malformation (DWM) is a rare congenital malformation of the brain. It is characterized by cystic enlargement of the fourth ventricle which is communicating with an enlarged posterior fossa, cerebellar dysgenesis, high tentorial insertion and hydrocephalus. Neurocutaneous Melanosis (NCM) is a congenital neurocutaneous syndrome characterized by large or multiple melanocytic nevi and benign or malignant melanocytic tumors of the leptomeninges. We report three months old boy who presented with projectile vomiting associated with a noticeable increase in head size. Several congenital nevi were seen all over his body with evident signs of hydrocephalus. The association of DWM and NCM is a rare complex, and to our knowledge, this is the eleventh case to be reported in the literature. In this article, we discuss the proposed pathogenesis, classification and management of the condition. PMID:27493376

The Return of an Old Worm: Cerebral Paragonimiasis Presenting with Intracerebral Hemorrhage

PubMed Central

Koh, Eun Jung; Kim, Seung-Ki; Wang, Kyu-Chang; Chai, Jong-Yil; Chong, Sangjoon; Park, Sung-Hye; Cheon, Jung-Eun

2012-01-01

Paragonimiasis is caused by ingesting crustaceans, which are the intermediate hosts of Paragonimus. The involvement of the brain was a common presentation in Korea decades ago, but it becomes much less frequent in domestic medical practices. We observed a rare case of cerebral paragonimiasis manifesting with intracerebral hemorrhage. A 10-yr-old girl presented with sudden-onset dysarthria, right facial palsy and clumsiness of the right hand. Brain imaging showed acute intracerebral hemorrhage in the left frontal area. An occult vascular malformation or small arteriovenous malformation compressed by the hematoma was initially suspected. The lesion progressed for over 2 months until a delayed surgery was undertaken. Pathologic examination was consistent with cerebral paragonimiasis. After chemotherapy with praziquantel, the patient was monitored without neurological deficits or seizure attacks for 6 months. This case alerts practicing clinicians to the domestic transmission of a forgotten parasitic disease due to environmental changes. PMID:23166429

Dandy-Walker variant associated with bipolar affective disorder

PubMed Central

Lingeswaran, Anand; Barathi, Deepak; Sharma, Gyaneswahr

2009-01-01

The Dandy-Walker malformation is a congenital brain malformation, typically involving the fourth ventricle and the cerebellum. To date, the Dandy-Walker syndrome has not been described in association with bipolar disorder type I mania, and therefore we briefly report the case of a Dandy-Walker variant associated with acute mania. A 10-year-old boy was brought by his mother to the outpatient clinic of the Department of Psychiatry of a tertiary care hospital, with symptoms of mania. The MRI brain of the patient showed a posterior fossa cystic lesion, a giant cisterna magna communicating with the fourth ventricle and mild hypoplasia of the cerebellar vermis, with the rest of the structures being normal and no signs of hydrocephalus. These findings showed that the patient had a Dandy-Walker variant. He responded partially to valproate and olanzepine, which controlled the acute manic symptoms in the ward. PMID:21887198

Double trisomy 48,XXX,+18 with multiple dysmorphic features.

PubMed

Jiang, Zi-Yan; Wu, Xiao-Hui; Zou, Chao-Chun

2015-02-01

Chromosomal abnormality is a common cause of congenital anomalies, psychiatric disorders, and mental retardation. However, the double trisomy 48,XXX,+18 is a rare chromosome abnormality. Case report and literature review. A 7-hour-old girl presented to our unit because of poor response after birth. She presented with multiple dysmorphic features, including small for gestational age infant, flat nasal bridge, widely-spaced eyes, the left thumb deformities, flat facial profile, raised sternum, ventricular septal defect, the third lateral brain ventricle enlargement, and small liver. This case expands the spectrum of malformations reported in association with the double trisomy 48,XXX,+18. The literature on 16 fetuses or infants with the 48,XXX,+18 were also reviewed. These data suggested that in patients with clinical features similar to trisomy 18, especially with anomalies of the ears and/or reproductive malformations, double trisomy (48,XXX,+18) should be considered and karyotyping should be performed although it is a rare disease.

Teratogenic effects of external egg applications of methyl mercury in the mallard, Anas platyrhynchos

USGS Publications Warehouse

Hoffman, D.J.; Moore, Johnnie N.

1979-01-01

The embryotoxic potential of external applications of methyl mercury on mallard eggs was investigated to assess the possible impact of mercury transferred from the plumage of effluent-contaminated aquatic birds to their eggs. Eggs were treated on day 3 of development with microliter applications of methyl mercury that was dissolved with ethyl acetate into an aliphatic hydrocarbon vehicle. Mercury analysis by atomic absorption indicated that almost half of the mercury applied entered the eggs past the shell membranes within several days of treatment. Most mortality occurred within this period at doses of 9 microgram of mercury per egg or higher. Decreased embryonic growth resulted with similar doses. A significant incidence of malformations occurred at a dose of 1 microgram per egg. These malformations were mainly minor skeletal aberrations and incomplete ossification. With higher doses of mercury, defects included gross external ones such as micromella, gastroschisis, and eye and brain defects. Application of the aliphatic hydrocarbon vehicle did not result in any of these defects.

The cephaloceles: A clinical, epidemiological and therapeutic study of 50 cases.

PubMed

Kabré, A; Zabsonre, D S; Sanou, A; Bako, Y

2015-08-01

Cephaloceles are congenital malformations characterized by externalization of the meninges and/or brain tissue through a congenital skull bone defect. In developed countries, this malformation is rare but in our developing countries, this pathology remains one of our concerns. To describe the epidemiological, clinical and therapeutic aspects of the cephaloceles. A retrospective study was conducted from 2007 to 2013 on all cases of cephalocele supported in the department of neurosurgery of the Yalgado Ouédraogo University Teaching Hospital of Ouagadougou. The malformations were supplemented by CT scan. All patients were operated. The surgical procedure in cephaloceles of the convexity consisted of a direct approach. Sincipital cephaloceles were operated by transcranial approach or combined approach associating transcranial and transnasal approaches. Fifty patients were gathered during the 7-year period. There were 18 boys and 32 girls. The ages ranged from 1 day to 11 years. The cephaloceles were located on the vault of the skull in 78%; the lesion was sincipital in 22%. The malformation was covered with normal skin in 92%; it was pediculated in 78%. CT scan allowed the classification of cases as meningo-encephaloceles in 31 cases (62%) and meningoceles in 18 cases (36%) and one pure encephalocele. The immediate postoperative course was uneventful in 42 cases (84%); 8 postoperative deaths were recorded. At medium and long term, 4 patients (8%) developed complications of psychomotor deficiency in 3 cases and hydrocephalus in 1 case. The main reasons for the poor prognosis were superinfection, hydrocephalus and/or other brain malformations. Cephaloceles remain relatively frequent in our practice. After surgery, mental failure and hydrocephalus can occur impairing the prognosis. The most suitable solution is a policy of prevention with folic acid treatment before and during pregnancy and following up adequate pregnancies. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

De Novo Mutations in SON Disrupt RNA Splicing of Genes Essential for Brain Development and Metabolism, Causing an Intellectual-Disability Syndrome.

PubMed

Kim, Jung-Hyun; Shinde, Deepali N; Reijnders, Margot R F; Hauser, Natalie S; Belmonte, Rebecca L; Wilson, Gregory R; Bosch, Daniëlle G M; Bubulya, Paula A; Shashi, Vandana; Petrovski, Slavé; Stone, Joshua K; Park, Eun Young; Veltman, Joris A; Sinnema, Margje; Stumpel, Connie T R M; Draaisma, Jos M; Nicolai, Joost; Yntema, Helger G; Lindstrom, Kristin; de Vries, Bert B A; Jewett, Tamison; Santoro, Stephanie L; Vogt, Julie; Bachman, Kristine K; Seeley, Andrea H; Krokosky, Alyson; Turner, Clesson; Rohena, Luis; Hempel, Maja; Kortüm, Fanny; Lessel, Davor; Neu, Axel; Strom, Tim M; Wieczorek, Dagmar; Bramswig, Nuria; Laccone, Franco A; Behunova, Jana; Rehder, Helga; Gordon, Christopher T; Rio, Marlène; Romana, Serge; Tang, Sha; El-Khechen, Dima; Cho, Megan T; McWalter, Kirsty; Douglas, Ganka; Baskin, Berivan; Begtrup, Amber; Funari, Tara; Schoch, Kelly; Stegmann, Alexander P A; Stevens, Servi J C; Zhang, Dong-Er; Traver, David; Yao, Xu; MacArthur, Daniel G; Brunner, Han G; Mancini, Grazia M; Myers, Richard M; Owen, Laurie B; Lim, Ssang-Taek; Stachura, David L; Vissers, Lisenka E L M; Ahn, Eun-Young Erin

2016-09-01

The overall understanding of the molecular etiologies of intellectual disability (ID) and developmental delay (DD) is increasing as next-generation sequencing technologies identify genetic variants in individuals with such disorders. However, detailed analyses conclusively confirming these variants, as well as the underlying molecular mechanisms explaining the diseases, are often lacking. Here, we report on an ID syndrome caused by de novo heterozygous loss-of-function (LoF) mutations in SON. The syndrome is characterized by ID and/or DD, malformations of the cerebral cortex, epilepsy, vision problems, musculoskeletal abnormalities, and congenital malformations. Knockdown of son in zebrafish resulted in severe malformation of the spine, brain, and eyes. Importantly, analyses of RNA from affected individuals revealed that genes critical for neuronal migration and cortex organization (TUBG1, FLNA, PNKP, WDR62, PSMD3, and HDAC6) and metabolism (PCK2, PFKL, IDH2, ACY1, and ADA) are significantly downregulated because of the accumulation of mis-spliced transcripts resulting from erroneous SON-mediated RNA splicing. Our data highlight SON as a master regulator governing neurodevelopment and demonstrate the importance of SON-mediated RNA splicing in human development. Copyright © 2016 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

Standard dose valproic acid does not cause additional cognitive impact in a rodent model of intractable epilepsy.

PubMed

Jellett, Adam P; Jenks, Kyle; Lucas, Marcella; Scott, Rod C

2015-02-01

Children with epilepsy face significant cognitive and behavioral impairments. These impairments are due to a poorly characterized interaction between the underlying etiology, the effect of seizures and the effect of medication. The large variation in these factors make understanding the main drivers of cognitive impairment in humans extremely difficult. Therefore, we investigated the cognitive effect of seizures and the antiepileptic drug valproic acid in a rodent model of cortical dysplasia. Rats were divided into seizure-receiving and non-receiving groups. Rats experienced frequent early life seizures using the flurothyl inhalation method: 50 seizures between postnatal day 5 and 15 and then one seizure a day following that. Rats were further divided into drug-treated and vehicle treated groups. Valproic acid treated animals were treated from 5 days preceding behavioral testing in the Morris water maze at a clinically relevant concentration. We show here that the main driver of cognitive impairments are the brain malformations, and that persistent seizures in animals with brain malformations and valproic acid caused no additional impact. These findings suggest that neither an appropriate dose of a standard antiepileptic drug or intractable seizures worsen cognition associated with a malformation of cortical development and that alternative treatment strategies to improve cognition are required. Copyright © 2014 Elsevier B.V. All rights reserved.

Atretic cephalocele: the tip of the iceberg.

PubMed

Martinez-Lage, J F; Sola, J; Casas, C; Poza, M; Almagro, M J; Girona, D G

1992-08-01

Atretic cephalocele appears as an unimportant and benign lesion. This malformation consists of meningeal and vestigial tissues (arachnoid, glial, or central nervous system rests). The authors report the findings in 16 cases (seven parietal and nine occipital) of rudimentary cephaloceles. Twelve patients presented with associated brain abnormalities detected by either computerized tomography (CT) or magnetic resonance imaging (MR). Nine lesions also exhibited an anomalous vascular component demonstrated by CT or MR imaging or at surgery. The existence of this tiny malformation in five cases was the main diagnostic clue to a severe complex of cerebral anomalies, namely cerebro-oculomuscular (Walker-Warburg) syndrome. An occipital location of the atretic cephalocele was associated with the worst prognosis, with only two children developing normally. However, a parietal location carried a better prognosis, which is contrary to the outcome reported in the current literature. The authors classify atretic cephaloceles into two types based on histological examination of the surgical specimens, and suggest that these types represent different stages in the development of this malformation. It is concluded that, in the evaluation of the atretic cephalocele, the neurosurgeon is obliged to proceed to a detailed neuroradiological study of the patient and that the prognosis does not depend on the existence of the cephalocele itself, but rather on associated "occult" brain anomalies.

Sleep disturbance: a forgotten syndrome in patients with Chiari I malformation.

PubMed

Ferré Masó, A; Poca, M A; de la Calzada, M D; Solana, E; Romero Tomás, O; Sahuquillo, J

2014-06-01

Chiari type I malformation (CM-I) is characterised by caudal ectopia of the cerebellar tonsils through the foramen magnum. This is associated with brain stem, high spinal cord, and cranial nerve compression phenomena. The most frequent symptoms are occipital headaches and dizziness. Less well-known symptoms are sleep disorders and nocturnal respiratory abnormalities. MEDLINE and information from patients evaluated at the Neurosurgery and Clinical Neurophysiology Departments at Hospital Universitario Vall d'Hebron. Review article based on data obtained from MEDLINE articles since 1966, using combinations of the following keywords: «Chiari malformation» or «Arnold-Chiari malformation» and «sleep apnea» or «sleep disorders». CM-I patients show a higher prevalence of sleep disorders than that observed in the general population. Some studies report a 50% prevalence of sleep apnea-hypopnea syndrome (SAHS), probably associated with sudden death in some cases. These results support analysing sleep respiratory parameters in theses patients. Identifying SAHS symptoms may help optimise treatment, thereby improving quality of life and prognosis. Copyright © 2010 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

[Etiologies of cerebral palsy and classical treatment possibilities].

PubMed

Maurer, Ute

2002-01-01

Cerebral palsy is a non-progressive disorder of the developing brain with different etiologies in the pre-, peri- or postnatal period. The most important of these diseases is cystic periventricular leukomalacia (PVL), followed by intra- and periventricular hemorrhage, hypoxic-ischemic encephalopathy, vascular disorders, infections or brain malformations. The underlying cause is always a damage of the first motor neuron. Prevalence of cerebral palsy in Europe is 2-3 per 1000 live births with a broad spectrum in different birth weight groups. Our own data concerning only pre-term infants in the NICU with birth weight below 1500 g (VLBW) are between 10%-20%. Established classical treatment methods include physiotherapy (Bobath, Vojta, Hippotherapy), methods of speech and occupational therapists (Castillo-Morales, Sensory Integration) and other therapeutical concepts (Petö, Affolter, Frostig).

Brainstem arteriovenous malformation presenting with dyspraxic handwriting in a young girl.

PubMed

Coppola, Giangennaro; D'Amico, Alessandra; Pironti, Erica; Martino, Federica; Santoro, Elena; Di Paolo, Nilde; Isone, Claudia; Catone, Gennaro

2014-06-01

We report the case of a 11-year-old girl who developed an isolated hand-writing disorder with dysgraphia at the beginning of the school year in the sixth grade. A brain magnetic resonance angiography showed a round arteriovenous malformation sited in the left side of the midbrain extending to the ipsilateral medio-basal thalamus. Child neurologists should never neglect a thorough neurological evaluation in case of isolated worsening of handwriting, to rule out possible underlying organic causes. Copyright © 2013 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Trans-venous embolization of a basal ganglia ruptured arteriovenous malformation with open surgical arterial control: A hybrid technique.

PubMed

Kulcsár, Zsolt; Machi, Paolo; Schaller, Karl; Lovblad, Karl Olof; Bijlenga, Philippe

2018-05-01

Treatment of ruptured deep-seated arteriovenous malformations is challenging and associated with elevated risks. This is due to the proximity or involvement of critical brain structures and the specifically fine and delicate angioarchitecture of these lesions, making both endovascular and surgical access technically complicated. We present the advantages of a true combined, open surgical and endovascular transvenous approach in a hybrid operating room. The technique may overcome in part the difficulties and may improve safety and risk related concerns. Copyright © 2018. Published by Elsevier Masson SAS.

Effect of Gastrointestinal Malformations on the Outcomes of Patients With Congenital Heart Disease.

PubMed

Mery, Carlos M; De León, Luis E; Rodriguez, J Rubén; Nieto, R Michael; Zhang, Wei; Adachi, Iki; Heinle, Jeffrey S; Kane, Lauren C; McKenzie, E Dean; Fraser, Charles D

2017-11-01

The goal of this study was to assess the effect of associated gastrointestinal malformations (GI) on the outcomes of patients undergoing congenital heart operations. Neonates and infants with thoracic (esophageal atresia, tracheoesophageal fistula) and abdominal (duodenal stenosis/atresia, imperforate anus, Hirschsprung disease) GI malformations undergoing congenital heart operations between 1995 and 2015 were included. Two control groups were created, one for each group. Patients were matched by diagnosis, procedure, history of prematurity, presence of genetic syndrome, and a propensity score including weight and year of operation. The cohort included 383 patients: 52 (14%) with thoracic GI malformations and 98 (25%) thoracic GI controls, 80 (21%) with abdominal GI malformations and 153 (40%) abdominal GI controls. Median follow-up was 6 years (range, 16 days to 20 years). Patients with thoracic GI malformations had longer length of stay (p < 0.001), longer intubation times (p = 0.002), and higher perioperative death (p = 0.015) than controls. There was a tendency for worse overall survival than controls, mainly explained by the higher risk of early death (p = 0.06). No difference was found in outcomes between patients with abdominal GI malformations and controls. Patients with thoracic GI malformations have worse perioperative outcomes than controls, but their long-term survival does not seem to be significantly different. Abdominal GI malformations do not have a significant effect on outcomes. The presence of GI malformations should likely not preclude patients from undergoing congenital heart operations, but careful family counseling is necessary, especially for thoracic GI malformations. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

[Lymphatic malformations in the head and neck area].

PubMed

Wiegand, S; Werner, J A

2016-02-01

Lymphatic malformations are congenital malformations of the lymphatic system. They are mainly located in the head and neck area, and grow proportional to the patients' body growth. Depending on the morphology, it can be distinguished between macrocystic, microcystic and mixed lymphatic malformations. Due to their infiltrative growth, microcystic lymphatic malformations are particularly difficult to treat. Therapeutic approaches include conventional surgical resection, laser therapy, sclerotherapy and systemic drug therapies.

The Treatment of Brain Arteriovenous Malformation Study (TOBAS): A preliminary inter- and intra-rater agreement study on patient management.

PubMed

Fahed, Robert; Batista, André L; Darsaut, Tim E; Gentric, Jean-Christophe; Ducroux, Célina; Chaalala, Chiraz; Roberge, David; Bojanowski, Michel W; Weill, Alain; Roy, Daniel; Magro, Elsa; Raymond, Jean

2017-07-01

The best management of brain arteriovenous malformation (bAVM) patients remains unknown. Randomized allocation may be more readily accepted when there is uncertainty and disagreement regarding the management of potential participants. In planning for a trial, we aimed to assess variability and agreement among physicians managing bAVM patients. A portfolio composed of 35 patients was sent to 47 clinicians of various specialties managing bAVM patients. For each patient, physicians were asked their best management decision (surgery/embolization/radiosurgery/conservative), their confidence level, and whether they would include the patient in a randomized trial comparing conservative and curative management. Seven physicians, who had access to all images of each patient, independently responded twice, to assess inter and intra-rater agreement using kappa statistics. The inter-rater agreement (30 raters, including 16 neuroradiologists) for best management decision was only "fair" (κ [95%CI]=0.210[0.157; 0.295]). Agreement remained below 'substantial' (κ<.6) between physicians of the same specialty, and when no distinctions were made between various treatments (when responses were dichotomized as conservative versus curative). With access to all images the inter-rater agreement remained fair. The intra-rater agreement reached "substantial" only for the dichotomized decisions. Responding clinicians were willing to include 54.4% of patients (mainly unruptured bAVMs) in a randomized trial. There is a lack of agreement among clinicians involved in the management of bAVM patients. In this study a substantial proportion of clinicians were willing to offer randomized allocation of management options to a substantial number of patients. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Management of Low-Flow Vascular Malformations: Clinical Presentation, Classification, Patient Selection, Imaging and Treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

McCafferty, Ian, E-mail: ian.mccafferty@uhb.nhs.uk

This review article aims to give an overview of the current state of imaging, patient selection, agents and techniques used in the management of low-flow vascular malformations. The review includes the current classifications for low-flow vascular malformations including the 2014 updates. Clinical presentation and assessment is covered with a detailed section on the common sclerosant agents used to treat low-flow vascular malformations, including dosing and common complications. Imaging is described with a guide to a simple stratification of the use of imaging for diagnosis and interventional techniques.

Incidental occlusion of anterior spinal artery due to Onyx reflux in embolization of spinal type II arteriovenous malformation.

PubMed

Kim, Joohyun; Lee, Jang-Bo; Cho, Tai-Hyoung; Hur, Junseok W

2017-05-01

Onyx embolization is one of the standard treatments for brain arteriovenous malformations (AVMs) and is a promising method for spinal AVMs as well. Its advantages have been emphasized, and few complications have been reported with Onyx embolization in spinal AVMs. Here, we report an incidental anterior spinal artery (ASA) occlusion due to Onyx reflux during embolization of a spinal type II AVM. A 15-year-old boy presented with weakness in both upper and lower extremities. Magnetic resonance imaging and spinal angiogram revealed a spinal type II AVM with two feeders including the right vertebral artery (VA) and the right deep cervical artery. Onyx embolization was performed gradually from the VA to the deep cervical artery and an unexpected Onyx reflux to the ASA was observed during the latter stage deep cervical artery embolization. Post-operative quadriplegia and low cranial nerves (CN) dysfunction were observed. Rehabilitation treatment was performed and the patient showed marked improvement of neurologic deterioration at 1-year follow-up. Onyx is an effective treatment choice for spinal AVMs. However, due to the small vasculature of the spine compared to the brain, the nidus is rapidly packed with a small amount of Onyx, which allows Onyx reflux to unexpected vessels. Extreme caution is required and dual-lumen balloon catheter could be considered for Onyx embolization in spinal AVMs treatment.

Early Rebleeding after Brain Arteriovenous Malformation Rupture, Clinical Impact and Predictive Factors: A Monocentric Retrospective Cohort Study.

PubMed

Shotar, Eimad; Pistocchi, Silvia; Haffaf, Idriss; Bartolini, Bruno; Jacquens, Alice; Nouet, Aurélien; Chiras, Jacques; Degos, Vincent; Sourour, Nader-Antoine; Clarençon, Frédéric

2017-01-01

Brain arteriovenous malformations (BAVMs) are a leading cause of intracranial hemorrhage in young adults. This study aimed to identify individual predictive factors of early rebleeding after BAVM rupture and determine its impact on prognosis. Early rebleeding was defined as a spontaneous intracranial hemorrhage within 30 days of BAVM rupture in patients with nonobliterated BAVMs. One hundred fifty one patients with 158 BAVM hemorrhagic events admitted to a tertiary care center during 14 years were included. Univariate followed by multivariate logistic regression was performed to assess the impact of early rebleeding on in-hospital mortality and modified Rankin Scale (mRS) score beyond 3 months and to identify independent predictors of early rebleeding. Eight early rebleeding events were observed, 6 of which occurred during the first 7 days. Early rebleeding was independently and significantly associated with poor outcome (mRS ≥3 beyond 3 months, p = 0.004) but not with in-hospital mortality (p = 0.9). Distal flow-related aneurysms (p = 0.009) and altered consciousness with a Glasgow coma scale score of 3 (p = 0.01) were independently associated with early rebleeding. Early rebleeding is a severe complication that can occur after BAVM-related hemorrhage. Distal flow-related aneurysms and initial altered consciousness are associated with early rebleeding. © 2017 S. Karger AG, Basel.

Onyx extravasation during embolization of a brain arteriovenous malformation.

PubMed

Ikeda, Hiroyuki; Imamura, Hirotoshi; Agawa, Yuji; Imai, Yukihiro; Tani, Shoichi; Adachi, Hidemitsu; Ishikawa, Tatsuya; Mineharu, Yohei; Sakai, Nobuyuki

2017-04-01

During Onyx embolization to treat brain arteriovenous malformation (AVM), carefully observing the penetration of Onyx to the nidus is important in order to avoid complications such as hemorrhage, ischemia, and difficulty with microcatheter removal. We encountered a case of Onyx extravasation during embolization of a cerebellar AVM confirmed by surgical resection and pathological analysis. The patient was a 44-year-old man with Spetzler-Martin grade I cerebellar AVM who underwent Onyx embolization prior to resection of the brain AVM. While injecting Onyx into the nidus using the "plug-and-push" technique, Onyx extravasation was observed. Onyx injection was paused and subsequently restarted, thereby allowing continuation of embolization. An oblate Onyx cast that was entirely covered in cerebellar tissue was removed during total resection of the AVM, performed the same day. The surgically removed oblate Onyx cast did not contain brain tissue or vessel wall, and immunohistochemical staining against glial fibrillary acidic protein (GFAP) showed Onyx penetration into GFAP-positive cerebellar tissue. Onyx extravasation was confirmed based on intraoperative findings during resection as well as pathological findings. The patient has been followed for four years postoperatively, and adverse events caused by Onyx extravasation have not been observed. Unexpected cast of Onyx, remote from the vascular architecture of the AVM, may represent an intra-parenchymal extravasation.

Onyx extravasation during embolization of a brain arteriovenous malformation

PubMed Central

Imamura, Hirotoshi; Agawa, Yuji; Imai, Yukihiro; Tani, Shoichi; Adachi, Hidemitsu; Ishikawa, Tatsuya; Mineharu, Yohei; Sakai, Nobuyuki

2016-01-01

During Onyx embolization to treat brain arteriovenous malformation (AVM), carefully observing the penetration of Onyx to the nidus is important in order to avoid complications such as hemorrhage, ischemia, and difficulty with microcatheter removal. We encountered a case of Onyx extravasation during embolization of a cerebellar AVM confirmed by surgical resection and pathological analysis. The patient was a 44-year-old man with Spetzler-Martin grade I cerebellar AVM who underwent Onyx embolization prior to resection of the brain AVM. While injecting Onyx into the nidus using the “plug-and-push” technique, Onyx extravasation was observed. Onyx injection was paused and subsequently restarted, thereby allowing continuation of embolization. An oblate Onyx cast that was entirely covered in cerebellar tissue was removed during total resection of the AVM, performed the same day. The surgically removed oblate Onyx cast did not contain brain tissue or vessel wall, and immunohistochemical staining against glial fibrillary acidic protein (GFAP) showed Onyx penetration into GFAP-positive cerebellar tissue. Onyx extravasation was confirmed based on intraoperative findings during resection as well as pathological findings. The patient has been followed for four years postoperatively, and adverse events caused by Onyx extravasation have not been observed. Unexpected cast of Onyx, remote from the vascular architecture of the AVM, may represent an intra-parenchymal extravasation. PMID:27903925

Diagnosis of Vein of Galen aneurysmal malformation using fetal MRI.

PubMed

Zhou, Li-Xia; Dong, Su-Zhen; Zhang, Ming-Feng

2017-11-01

To present three fetal vein of Galen aneurysmal malformations (VGAMs), which were diagnosed through magnetic resonance imaging (MRI), and highlight these cardiovascular findings. We retrospectively reviewed three fetuses with VGAM at 31, 32, and 33 weeks of gestation. Feeding arteries and draining veins were observed by MRI. Secondary changes in the brain and high-output heart failure caused by high blood flow in the lesion were evaluated. Two fetuses were born, and neonatal MRI was performed. One fetus was terminated. A characteristic dilated structure in the midline of the brain presented in each fetus. The arteriovenous fistula led to anatomical brain changes such as in the hydrocephalus, dilated feeding vessels (one or more), jugular vein, and/or superior vena cava. Substantial brachiocephalic vessel dilation was observed in two fetuses. Following parturition, one baby had neonatal asphyxia and sinus thrombosis, and MRI revealed hypoxic-ischemic encephalopathy. Cardiomegaly was detected in all three cases. With a large field of view, fetal MRI can observe brain VGAM, as well as the heart and affected large vessels. It can determine hydrocephalus, ischemia, intracranial hemorrhage, and sinus thrombosis. Providing such information on the infant's entire body can aid clinicians in determining the most appropriate treatment. 4 J. Magn. Reson. Imaging 2017;46:1535-1539. © 2016 International Society for Magnetic Resonance in Medicine.

Klippel-Feil syndrome and Dandy-Walker malformation.

PubMed

Karaman, A; Kahveci, H

2011-01-01

The Klippel-Feil deformity is a complex of osseous and visceral anomalies, which include low hairline, platybasia, fused cervical vertebrae with a short neck, and deafness. Associated central nervous system abnormalities include occipital cephalocele, Chiari I malformation, syrinx, microcephaly, and hydrocephalus. Herein, we report a case with Klippel-Feil syndrome and Dandy-Walker malformation.

The need for improved brain lesion segmentation techniques for children with cerebral palsy: A review.

PubMed

Pagnozzi, Alex M; Gal, Yaniv; Boyd, Roslyn N; Fiori, Simona; Fripp, Jurgen; Rose, Stephen; Dowson, Nicholas

2015-12-01

Cerebral palsy (CP) describes a group of permanent disorders of posture and movement caused by disturbances in the developing brain. Accurate diagnosis and prognosis, in terms of motor type and severity, is difficult to obtain due to the heterogeneous appearance of brain injury and large anatomical distortions commonly observed in children with CP. There is a need to optimise treatment strategies for individual patients in order to lead to lifelong improvements in function and capabilities. Magnetic resonance imaging (MRI) is critical to non-invasively visualizing brain lesions, and is currently used to assist the diagnosis and qualitative classification in CP patients. Although such qualitative approaches under-utilise available data, the quantification of MRIs is not automated and therefore not widely performed in clinical assessment. Automated brain lesion segmentation techniques are necessary to provide valid and reproducible quantifications of injury. Such techniques have been used to study other neurological disorders, however the technical challenges unique to CP mean that existing algorithms require modification to be sufficiently reliable, and therefore have not been widely applied to MRIs of children with CP. In this paper, we present a review of a subset of available brain injury segmentation approaches that could be applied to CP, including the detection of cortical malformations, white and grey matter lesions and ventricular enlargement. Following a discussion of strengths and weaknesses, we suggest areas of future research in applying segmentation techniques to the MRI of children with CP. Specifically, we identify atlas-based priors to be ineffective in regions of substantial malformations, instead propose relying on adaptive, spatially consistent algorithms, with fast initialisation mechanisms to provide additional robustness to injury. We also identify several cortical shape parameters that could be used to identify cortical injury, and shape modelling approaches to identify anatomical injury. The benefits of automatic segmentation in CP is important as it has the potential to elucidate the underlying relationship between image derived features and patient outcome, enabling better tailoring of therapy to individual patients. Copyright © 2015 Elsevier Ltd. All rights reserved.

Entire syringomyelia associated with Chiari II malformation and severe scoliosis and hydrocephalus.

PubMed

Liang, Jie; Wu, Weifei; Ru, Neng; Chen, Jianfeng

2017-01-01

The syrinx can occur in any region of the spinal cord and is common in cervical and/or thoracic region, and distributing along spinal cord is unusual, especially association with Chiari II malformation and scoliosis. To report a first case of entire syringomyelia associated with Chiari II malformation and severe scoliosis and hydrocephalus. The patient began to experience symptoms of bilateral hand weakness in adulthood. In this patient, MR imaging of the brain and spine showed syrinx along entire spine and hydrocephalus, cerebellar tonsillar herniation, and expansion of the fourth ventricle and posterior cranial fossa. The patient underwent operative treatment to prevent the progression of her neurological deficit. At 12 months' follow-up, the patient's neurological deficit remains stable with the scoliosis left untreated. Foramen magnum decompression, duraplasty and syrinx-shunting are effective methods even to CM II and entire syrinx.

Radiological Characterization of Cerebral Phenotype in Newborn Microcephaly Cases from 2015 Outbreak in Brazil

PubMed Central

Ramalho Rocha, Yuri Raoni; Cavalcanti Costa, José Ricardo; Almeida Costa, Pericles; Maia, Gessica; Vasconcelos, Rafael de Medeiros; Ramos Tejo, Cynthia; Martins Batista, Rafaella; Lima Neto, Manoel; Martins de Lima, Gustavo Graco; Negromonte, Francisco; Borba, Marcelle; Bezerra Jeronimo, Selma Maria; Sequerra, Eduardo Bouth; Moreira Neto, Manuel

2016-01-01

Introduction: Brazil is facing, since October of 2015, an outbreak of microcephalic fetuses. This outbreak is correlated with the beginning of circulation of Zika virus (ZIKV) in the country. Although it is clear that the size of the head is diminished in these fetuses, the brain phenotype associated with these malformations is unknown. Methods: We collected computed tomography images of the microcephaly cases from the region of Natal, Rio Grande do Norte, from September 2015 to February 2016. Findings: The microcephalies derived from the current outbreak are associated with intracerebral calcifications, malformation of the ventricular system, migratory disorders in the telencephalon and, in a lower frequency, malformation of the cerebellum and brainstem. Discussion: The characteristics described herein are not usually found in other types of microcephaly. We suggest that this work can be used as a guideline to identify microcephaly cases associated to the current outbreak. PMID:27617166

Cartilaginous metaplasia and overgrowth of neurocranium skull after X-irradiation in utero.

PubMed

Schmahl, W; Meyer, I; Kriegel, H; Tempel, K H

1979-01-01

Prenatal X-irradiation of mice in the late organogenesis stage either with a fractionated or a single exposure dose (3 X 160 R or 200 R) leads to remarkable, previously undescribed malformations of the skull. These malformations range from mild hyperostotic nodule formation in about 90% of the offspring to excessive formation of desmal bony tissues, which extend deep into the forebrain and are thus only detectable in histological sections. Metaplastic and hyperplastic formation of cartilage in all the neurocranial regions is observed in about 10% of the offspring. The pathogenesis of these overgrowth phenomena is presumably related to a growth disturbance of both the mesenchymal skull primordium and the brain. While malformation of the latter leads to a decrease of intracranial pressure and consequently to altered growth activity of the skull sutures, the reparative and proliferative capacities of the mesenchyme are also stimulated, in a hyperplastic direction, by X-irradiation.

Complete Reversibility of the Chiari Type II Malformation After Postnatal Repair of Myelomeningocele.

PubMed

Beuriat, Pierre-Aurélien; Szathmari, Alexandru; Rousselle, Christophe; Sabatier, Isabelle; Di Rocco, Federico; Mottolese, Carmine

2017-12-01

It was believed that Chiari type II malformation (CM-II) was always present in a myelomeningocele (MMC). In fact, it is associated in about 80% of cases. Improvement of the hindbrain herniation after prenatal closure of MMC has challenged the idea that this condition was irreversible. Only 2 studies report ascent of the cerebellar tonsil after postnatal closure. This work aimed to study a large group of patients with MMC who benefited from a postnatal repair to evaluate the rate of long-term total reversibility of CM-II. Sixty-one patients were included. Mean time of follow-up was 8.1 years. The presence of CM-II after closure of the MMC was assessed on the most recent brain scan available for each patient. Forty-seven patients (77%) had a CM-II at birth (confirmed before the MMC repair). There was a significant correlation between the level of the malformation and the presence of a CM-II at birth (P = 0.003). After MMC closure, only 28 (45.9%) patients had a remaining CM-II. The reversibility rate was 40.4%. The reversibility was higher in lower level malformations (P = 0.004). The number of patients treated for hydrocephalus was significantly higher in the group of patients with remaining CM-II (P = 0.004). Only 11.5% of the children needed surgery for a symptomatic CM-II. MMC is not always associated with CM-II. The outcome of CM-II has improved. Postnatal closure can reverse the CM-II. This must be kept in mind when analyzing the result of prenatal series. Copyright © 2017 Elsevier Inc. All rights reserved.

Familial Cerebral Cavernous Malformations Are Associated with Adrenal Calcifications on CT Scans: An Imaging Biomarker for a Hereditary Cerebrovascular Condition.

PubMed

Strickland, Corinne D; Eberhardt, Steven C; Bartlett, Mary R; Nelson, Jeffrey; Kim, Helen; Morrison, Leslie A; Hart, Blaine L

2017-08-01

Purpose To determine if adrenal calcifications seen at computed tomography (CT) are associated with familial cerebral cavernous malformations (fCCMs) in carriers of the CCM1 Common Hispanic Mutation. Materials and Methods This study was approved by the institutional review board. The authors retrospectively reviewed abdominal CT scans in 38 patients with fCCM, 38 unaffected age- and sex-matched control subjects, and 13 patients with sporadic, nonfamilial cerebral cavernous malformation (CCM). The size, number, and laterality of calcifications and the morphologic characteristics of the adrenal gland were recorded. Brain lesion count was recorded from brain magnetic resonance (MR) imaging in patients with fCCM. The prevalence of adrenal calcifications in patients with fCCM was compared with that in unaffected control subjects and those with sporadic CCM by using the Fisher exact test. Additional analyses were performed to determine whether age and brain lesion count were associated with adrenal findings in patients with fCCM. Results Small focal calcifications (SFCs) (≤5 mm) were seen in one or both adrenal glands in 19 of the 38 patients with fCCM (50%), compared with 0 of the 38 unaffected control subjects (P < .001) and 0 of the 13 subjects with sporadic CCM (P = .001). Adrenal calcifications in patients with fCCM were more frequently left sided, with 17 of 19 patients having more SFCs in the left adrenal gland than the right adrenal gland and 50 of the 61 observed SFCs (82%) found in the left adrenal gland. No subjects had SFCs on the right side only. In patients with fCCM, the presence of SFCs showed a positive correlation with age (P < .001) and number of brain lesions (P < .001). Conclusion Adrenal calcifications identified on CT scans are common in patients with fCCM and may be a clinically silent manifestation of disease. © RSNA, 2017.

History of functional neurosurgery.

PubMed

Iskandar, B J; Nashold, B S

1995-01-01

Whereas in the early days of evil spirits, electric catfish, and phrenology, functional neurosurgery was based on crude observations and dogma, the progress made in neurophysiology at the turn of the century gave the field a strong scientific foundation. Subsequently, the advent of stereotaxis allowed access to deep brain regions and contributed an element of precision. Future directions include the development of frameless stereotaxy; the use of MRI-generated anatomic data, which would circumvent the serious problem of individual variations seen with standard brain atlases; the introduction of various chemicals into brain structures, in an attempt to influence neurochemically mediated disease processes; and finally, the use of the promising techniques of neural transplantation. On hearing of Penfield's intraoperative brain stimulations, Sherrington commented: "It must be great fun to have the physiological preparation speak to you." The idea of therapeutic neurophysiologic interventions is appealing, especially because many disorders show no obvious treatable pathologic cause (e.g., tumor, vascular malformation). As stereotactic technology becomes less cumbersome and more precise, more sophisticated in vivo neurophysiologic preparations become possible. In turn, as our understanding of nervous system physiology grows, our ability to understand pathophysiology and treat disease processes increases.

Utility of brain MRI in children with sleep-disordered breathing.

PubMed

Selvadurai, Sarah; Al-Saleh, Suhail; Amin, Reshma; Zweerink, Allison; Drake, James; Propst, Evan J; Narang, Indra

2017-02-01

To investigate the utility of a brain magnetic resonance imaging (MRI) in children with sleep-disordered breathing (SDB), classified as isolated obstructive sleep apnea (OSA) in the absence of adenotonsillar hypertrophy, persistent OSA following adenotonsillectomy, isolated central sleep apnea (CSA) of unclear etiology, OSA with coexisting CSA of unclear etiology, or unexplained nocturnal hypoventilation (NH). Retrospective chart review of polysomnography (PSG) and brain MRI data. Children with PSG evidence of SDB, as described above, and who subsequently had their first brain MRI, were included. PSG, MRI data, and subsequent interventions were recorded. A total of 59 of 6,087 (1%) children met inclusion criteria. Of those, 28 of 59 (47%) were nonsyndromic children and 31 of 59 (53%) were syndromic children with an underlying medical disorder. Abnormal brain MRI findings were observed in 19 of 59 (32%) children, where eight of 19 (42%) were nonsyndromic and 11 of 19 (58%) were syndromic. Abnormal brain MRI findings were most common in syndromic children with combined OSA and CSA without adenotonsillar hypertrophy. Isolated OSA was also a common PSG finding associated with an abnormal brain MRI. Of the nonsyndromic children with an abnormal brain MRI, the most common abnormal brain MRI finding was Chiari malformation (CM), observed in 88% of the group. A brainstem tumor was identified in one nonsyndromic child. Interventions following brain MRI included neurosurgery, chemotherapy, and noninvasive positive pressure ventilation (NiPPV). A brain MRI is an important diagnostic tool in syndromic and nonsyndromic children, especially in children with either isolated OSA or combined OSA and CSA without a clear etiology. 4. Laryngoscope, 2016 127:513-519, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Compliance of systematic reviews articles in brain arteriovenous malformation with PRISMA statement guidelines: Review of literature.

PubMed

Akhigbe, T; Zolnourian, A; Bulters, D

2017-05-01

The knowledge of reporting compliance of systematic reviews with PRISMA guidelines may assist in improving the quality of secondary research in brain AVM management and subsequently application to patient population and clinical practice. This may allow researchers and clinicians to be equipped to appraise existing literatures based on known deficit to look for or expect. The objective of this study was to assess the compliance of systematic reviews and meta-analysis in the management of brain AVM. Systematic reviews and meta-analyses articles published in medical journals between 1st of May 2011 and 30th April 2016 (five-year period) were examined. Exclusion criteria were articles that were not systematic reviews and not meta-analyses, narrative literature reviews, historical literature reviews, animal studies, unpublished articles, commentaries and letter to the editor. Electronic database search performed through Medline PubMed on 20th September 2016. This systematic review examined seven systematic review articles on intracranial arteriovenous malformation compliance with PRISMA statement guidelines. The mean percentage of applicable PRISMA items across all studies was 74% (range 67-93%). Protocol registration and declaration, risk of bias and funding sources were the most poorly reported of the PRISMA items (14% each). A significant variance in the total percentages was evident between studies (67-93%). Systematic review reporting in medical literature is excessively variable and overall poor. As these papers are being published with increasing frequency, need to fully adhere to PRISMA statement guide for systematic review to ensure high-quality publications. Complete reporting of PRISMA items within systematic reviews in cerebral arteriovenous malformation enhance quality assessment, robust critical appraisal, better judgement and ultimately sound application to practice thereby improving research standards and patients care. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Alternatively Activated Macrophages Play an Important Role in Vascular Remodeling and Hemorrhaging in Patients with Brain Arteriovenous Malformation.

PubMed

Nakamura, Yukihiko; Sugita, Yasuo; Nakashima, Shinji; Okada, Yousuke; Yoshitomi, Munetake; Kimura, Yoshizou; Miyoshi, Hiroaki; Morioka, Motohiro; Ohshima, Koichi

2016-03-01

Angiogenic and immunoactive lesions in brain arteriovenous malformation (BAVM) contribute to hemorrhagic events and the growth of BAVMs. However, the detailed mechanism is unclear. Our objective is to clarify the relationship between hemorrhagic events of BAVM and alternatively activated macrophages in the perinidal dilated capillary network (PDCN). We examined microsurgical specimens of BVMs (n = 29) and focused on the PDCN area. Ten autopsied brains without intracranial disease were the controls. We performed immunostaining of the inflammatory and endothelial cell markers, macrophage markers (CD163 and CD68), and vascular endothelial growth factor A (VEGF-A). We evaluated each cell's density and the vessel density in the PDCN and analyzed the relationship to hemorrhagic events of BAVM. The PDCN was involved in all the resected arteriovenous malformations, and these vessels showed a high rate of CD105 expression (72.0 ± 10.64%), indicating newly proliferating vessels. Alternatively activated macrophages were found, with a high rate (85.6%) for all macrophages (controls, 56.6%). In the hemorrhagic cases, the cell density was significantly higher than that in the nonhemorrhagic cases and controls (hemorrhagic group, 290 ± 44 cells/mm(2); nonhemorrhagic group, 180 ± 59 cells/mm(2); and control, 19 ± 8 cells/mm(2)). The cell density of alternatively activated macrophages showed a positive correlation with the vessel density of the PDCN. Double immunostaining showed that VEGF-A was secreted by alternatively activated macrophages. Our data suggest that alternatively activated macrophages may have some relationships with angiogenesis of PDCN and hemorrhagic event of BAVM. Copyright © 2016 National Stroke Association. Published by Elsevier Inc. All rights reserved.

Developmental abnormalities of the occipital bone in human chondrodystrophies (achondroplasia and thanatophoric dwarfism).

PubMed

Marin-Padilla, M; Marin-Padilla, T M

1977-01-01

Specific developmental malformations have been demonstrated in the occipital bone of two chondrodysplastic disorders (achondroplasia and thanatophoric dwarfism). Analysis of these malformations indicates that the occipital bone is primary affected in these disorders. In both cases, the endochondral-derived components of the occipital bone (the basioccipital, the two lateral parts, and the planum nuchale of the squama occipitalis) have failed to grow properly and are smaller and shorter than normal. On the other hand, the planum occipitalis of the squama, which derives from intramembranous ossification, is unaffected. In addition, the nature of these abnormalities indicates that the occipital synchondroses, together with the epiphyseal plates of other bones, are primarily affected in these two chondrodysplasias. The components of the occipital bone formed between the affected synchondroses failed to grow normally. The resulting malformation of the occipital bone is undoubtedly the cause of the shortening of the posterior cerebral fossa and of the considerable narrowing of the foramen magnum often described in these chondrodysplasias. It is postulated that growth disturbances between the affected occipital bone and the unaffected central nervous system results in the inadequacy of the posterior cerebral fossa and the foramen magnum to accommodate the growing brain. Consequently, compression of the brain at the posterior cerebral fossa or the foramen magnum levels could occur and thus lead to neurologic complications such as hydrocephalus and compression of the brain stem. It is suggested that the surgical removal of the fused posterior border of the lateral parts of the occipital bone (partial nuchalectomy) for the purpose of enlarging the narrow foramen magnum may be indicated in those chondrodysplastic children who develop these types of neurologic complications.

[New developments in spastic unilateral cerebral palsy].

PubMed

Chabrier, S; Roubertie, A; Allard, D; Bonhomme, C; Gautheron, V

2010-01-01

Hemiplegic (or spastic unilateral) cerebral palsy accounts for about 30% of all cases of cerebral palsy. With a population prevalence of 0.6 per 1000 live births, it is the most common type of cerebral palsy among term-born children and the second most common type after diplegia among preterm infants. Many types of prenatal and perinatal brain injury can lead to congenital hemiplegia and brain MRI is the most useful tool to classify them with accuracy and to provide early prognostic information. Perinatal arterial ischemic stroke thus appears as the leading cause in term infants, whereas encephalopathy of prematurity is the most common cause in premature babies. Other causes include brain malformations, neonatal sinovenous thrombosis, parenchymal hemorrhage (for example due to coagulopathy or alloimmune thrombocytopenia) and the more recently described familial forms of porencephaly associated with mutations in the COL4A1 gene. In adjunction with pharmacologic treatment (botulinium neurotoxin injection), new evidence-based rehabilitational interventions, such as constraint-induced movement therapy and mirror therapy, are increasingly being used.

[The clinico-neuropsychological aspects of arteriovenous malformations of the hippocampus].

PubMed

Buklina, S B; Filatov, Iu M; Eliava, Sh Sh

1998-01-01

A comprehensive examination was made in 39 patients with arteriovenous malformations (AVM) of hippocampus. Prior to and following surgery, all the patients underwent neuropsychological study after A. R. Luriia (1962). Mnestic disorder was found to be the most common abnormality in patients with AVM at this site. Before surgery, they were detected in 34 of 39 patients, 11 of them having severe memory disorders with the traits of the Korsakoff's syndrome. These patients were found to have mixed posthemorrhagic lesion of the hippocampus, other portions of the temporal lobe and periventricular structures. Twenty nine patients were operated on, 14 of them had progressive mnestic disorder of the modally nonspecific type irrespective the side operated on. There were no postoperative Korsakoff's syndromes. There was no progression in memory defects in patients after surgery on the brain drastically changed after hemorrhage or removal of minor malformations. Before hemorrhage, epileptic paroxysms were observed in 2 of the 39 patients only in the presence of massive AVM obligatorily involving the temporal cortex. Following surgery, there were no new epileptic paroxysms and changes in the emotional status and motivations in the patients. Thus, the hippocampal formation is involved in the primary mechanisms of fixation, retention, reproduction of a memory trace. The participation of many structures of the brain is required to form an emotional status, motivation, and clinical manifestations of epileptic activity.

Comparison of brain MRI findings with language and motor function in the dystroglycanopathies.

PubMed

Brun, Brianna N; Mockler, Shelley R H; Laubscher, Katie M; Stephan, Carrie M; Wallace, Anne M; Collison, Julia A; Zimmerman, M Bridget; Dobyns, William B; Mathews, Katherine D

2017-02-14

To describe the spectrum of brain MRI findings in a cohort of individuals with dystroglycanopathies (DGs) and relate MRI results to function. All available brain MRIs done for clinical indications on individuals enrolled in a DG natural history study (NCT00313677) were reviewed. Reports were reviewed when MRI was not available. MRIs were categorized as follows: (1) cortical, brainstem, and cerebellar malformations; (2) cortical and cerebellar malformations; or (3) normal. Language development was assigned to 1 of 3 categories by a speech pathologist. Maximal motor function and presence of epilepsy were determined by history or examination. Twenty-five MRIs and 9 reports were reviewed. The most common MRI abnormalities were cobblestone cortex or dysgyria with an anterior-posterior gradient and cerebellar hypoplasia. Seven individuals had MRIs in group 1, 8 in group 2, and 19 in group 3. Language was impaired in 100% of those in MRI groups 1 and 2, and degree of language impairment correlated with severity of imaging. Eighty-five percent of the whole group achieved independent walking, but only 33% did in group 1. Epilepsy was present in 8% of the cohort and rose to 37% of those with an abnormal MRI. Developmental abnormalities of the brain such as cobblestone lissencephaly, cerebellar cysts, pontine hypoplasia, and brainstem bowing are hallmarks of DG and should prompt consideration of these diagnoses. Brain imaging in individuals with DG helps to predict outcomes, especially language development, aiding clinicians in prognostic counseling. © 2017 American Academy of Neurology.

Micro-computed tomography in murine models of cerebral cavernous malformations as a paradigm for brain disease.

PubMed

Girard, Romuald; Zeineddine, Hussein A; Orsbon, Courtney; Tan, Huan; Moore, Thomas; Hobson, Nick; Shenkar, Robert; Lightle, Rhonda; Shi, Changbin; Fam, Maged D; Cao, Ying; Shen, Le; Neander, April I; Rorrer, Autumn; Gallione, Carol; Tang, Alan T; Kahn, Mark L; Marchuk, Douglas A; Luo, Zhe-Xi; Awad, Issam A

2016-09-15

Cerebral cavernous malformations (CCMs) are hemorrhagic brain lesions, where murine models allow major mechanistic discoveries, ushering genetic manipulations and preclinical assessment of therapies. Histology for lesion counting and morphometry is essential yet tedious and time consuming. We herein describe the application and validations of X-ray micro-computed tomography (micro-CT), a non-destructive technique allowing three-dimensional CCM lesion count and volumetric measurements, in transgenic murine brains. We hereby describe a new contrast soaking technique not previously applied to murine models of CCM disease. Volumetric segmentation and image processing paradigm allowed for histologic correlations and quantitative validations not previously reported with the micro-CT technique in brain vascular disease. Twenty-two hyper-dense areas on micro-CT images, identified as CCM lesions, were matched by histology. The inter-rater reliability analysis showed strong consistency in the CCM lesion identification and staging (K=0.89, p<0.0001) between the two techniques. Micro-CT revealed a 29% greater CCM lesion detection efficiency, and 80% improved time efficiency. Serial integrated lesional area by histology showed a strong positive correlation with micro-CT estimated volume (r(2)=0.84, p<0.0001). Micro-CT allows high throughput assessment of lesion count and volume in pre-clinical murine models of CCM. This approach complements histology with improved accuracy and efficiency, and can be applied for lesion burden assessment in other brain diseases. Copyright © 2016 Elsevier B.V. All rights reserved.

Progressive brain damage, synaptic reorganization and NMDA activation in a model of epileptogenic cortical dysplasia.

PubMed

Colciaghi, Francesca; Finardi, Adele; Nobili, Paola; Locatelli, Denise; Spigolon, Giada; Battaglia, Giorgio Stefano

2014-01-01

Whether severe epilepsy could be a progressive disorder remains as yet unresolved. We previously demonstrated in a rat model of acquired focal cortical dysplasia, the methylazoxymethanol/pilocarpine - MAM/pilocarpine - rats, that the occurrence of status epilepticus (SE) and subsequent seizures fostered a pathologic process capable of modifying the morphology of cortical pyramidal neurons and NMDA receptor expression/localization. We have here extended our analysis by evaluating neocortical and hippocampal changes in MAM/pilocarpine rats at different epilepsy stages, from few days after onset up to six months of chronic epilepsy. Our findings indicate that the process triggered by SE and subsequent seizures in the malformed brain i) is steadily progressive, deeply altering neocortical and hippocampal morphology, with atrophy of neocortex and CA regions and progressive increase of granule cell layer dispersion; ii) changes dramatically the fine morphology of neurons in neocortex and hippocampus, by increasing cell size and decreasing both dendrite arborization and spine density; iii) induces reorganization of glutamatergic and GABAergic networks in both neocortex and hippocampus, favoring excitatory vs inhibitory input; iv) activates NMDA regulatory subunits. Taken together, our data indicate that, at least in experimental models of brain malformations, severe seizure activity, i.e., SE plus recurrent seizures, may lead to a widespread, steadily progressive architectural, neuronal and synaptic reorganization in the brain. They also suggest the mechanistic relevance of glutamate/NMDA hyper-activation in the seizure-related brain pathologic plasticity.

Diagnosis and surgical treatment of a Chiari I-like malformation in an African lion (Panthera leo).

PubMed

McCain, Stephanie; Souza, Marcy; Ramsay, Ed; Schumacher, Juergen; Hecht, Silke; Thomas, William

2008-09-01

A 13-mo-old intact male African lion (Panthera leo) presented with a 3-mo history of lethargy, ventral flexion of the neck, abnormal vocalization, and ataxia. Hemogram and serum biochemistries were within normal limits except for the presence of hypokalemia (2.7 mEq/L) and hypochloridemia (108 mEq/L). When no improvement was noted with oral potassium gluconate supplementation, a computed tomography scan of the brain and skull was performed, and no abnormalities were noted. However, magnetic resonance imaging detected occipital bone thickening, crowding of the caudal cranial fossa with cerebellar compression and herniation, and cervical syringohydromyelia, which was consistent with a Chiari I-like malformation. Foramen magnum decompression was performed to relieve the compression of the cerebellum. The animal recovered well with subsequent resolution of clinical signs. Hypovitaminosis A has been proposed previously as the underlying etiology for this malformation in lions with similar clinical presentations. This lion's serum and liver vitamin A concentrations were low (100 ng/ml and 25.31 microg/g, respectively) compared to concentrations reported for domestic carnivores and support hypovitaminosis A as the underlying cause of this animal's Chiari I-like malformation.

21 CFR 882.5175 - Carotid artery clamp.

Code of Federal Regulations, 2014 CFR

2014-04-01

... carotid artery to treat intracranial aneurysms (balloonlike sacs formed on blood vessels) or other intracranial vascular malformations that are difficult to attach directly by reducing the blood pressure and... (the principal artery in the neck that supplies blood to the brain) and has a removable adjusting...

21 CFR 882.5175 - Carotid artery clamp.

Code of Federal Regulations, 2013 CFR

2013-04-01

... carotid artery to treat intracranial aneurysms (balloonlike sacs formed on blood vessels) or other intracranial vascular malformations that are difficult to attach directly by reducing the blood pressure and... (the principal artery in the neck that supplies blood to the brain) and has a removable adjusting...

21 CFR 882.5175 - Carotid artery clamp.

Code of Federal Regulations, 2010 CFR

2010-04-01

... carotid artery to treat intracranial aneurysms (balloonlike sacs formed on blood vessels) or other intracranial vascular malformations that are difficult to attach directly by reducing the blood pressure and... (the principal artery in the neck that supplies blood to the brain) and has a removable adjusting...

21 CFR 882.5175 - Carotid artery clamp.

Code of Federal Regulations, 2012 CFR

2012-04-01

... carotid artery to treat intracranial aneurysms (balloonlike sacs formed on blood vessels) or other intracranial vascular malformations that are difficult to attach directly by reducing the blood pressure and... (the principal artery in the neck that supplies blood to the brain) and has a removable adjusting...

21 CFR 882.5175 - Carotid artery clamp.

Code of Federal Regulations, 2011 CFR

2011-04-01

... carotid artery to treat intracranial aneurysms (balloonlike sacs formed on blood vessels) or other intracranial vascular malformations that are difficult to attach directly by reducing the blood pressure and... (the principal artery in the neck that supplies blood to the brain) and has a removable adjusting...

Onyx (Ethylene-vinyl Alcohol Copolymer) in Peripheral Applications

PubMed Central

Guimaraes, Marcelo; Wooster, Mathew

2011-01-01

Onyx is a nonadhesive liquid embolic agent approved for the treatment of brain arteriovenous malformations. Here, the use of Onyx is discussed in different peripheral procedures. The Onyx's features, its manipulation, technical details, tips, and tricks are presented followed by illustrative cases. PMID:22942553

Identification of a rare BMP pathway mutation in a non-syndromic human brain arteriovenous malformation via exome sequencing.

PubMed

Walcott, Brian P; Winkler, Ethan A; Zhou, Sirui; Birk, Harjus; Guo, Diana; Koch, Matthew J; Stapleton, Christopher J; Spiegelman, Dan; Dionne-Laporte, Alexandre; Dion, Patrick A; Kahle, Kristopher T; Rouleau, Guy A; Lawton, Michael T

2018-01-01

Brain arteriovenous malformations (AVMs) are abnormal connections between arteries and veins that can result in hemorrhagic stroke. A genetic basis for AVMs is suspected, and we investigated potential mutations in a 14-year-old girl who developed a recurrent brain AVM. Whole-exome sequencing (WES) of AVM lesion tissue and blood was performed accompanied by in silico modeling, protein expression observation in lesion tissue and zebrafish modeling. A stop-gain mutation (c.C739T:p.R247X) in the gene SMAD family member 9 ( SMAD9 ) was discovered. In the human brain tissue, immunofluorescent staining demonstrated a vascular predominance of SMAD9 at the protein level. Vascular SMAD9 was markedly reduced in AVM peri-nidal blood vessels, which was accompanied by a decrease in phosphorylated SMAD4, a downstream effector protein of the bone morphogenic protein signaling pathway. Zebrafish modeling ( Tg kdrl:eGFP ) of the morpholino splice site and translation-blocking knockdown of SMAD9 resulted in abnormal cerebral artery-to-vein connections with morphologic similarities to human AVMs. Orthogonal trajectories of evidence established a relationship between the candidate mutation discovered in SMAD9 via WES and the clinical phenotype. Replication in similar rare cases of recurrent AVM, or even more broadly sporadic AVM, may be informative in building a more comprehensive understanding of AVM pathogenesis.

Cerebellar hematoma in a patient with Marfan syndrome.

PubMed

Passalacqua, Marcello; Grasso, Giovanni; Alafaci, Concetta; Collufio, Domenicantonio; Morabito, Antonio; Salpietro, Francesco M; Tomasello, Francesco

2003-08-01

Marfan syndrome is a connective tissue disorder affecting many structures, including the skeleton, lungs, eyes, heart and blood vessels. It is an autosomal dominant inherited disorder due to a mutation of a gene encoding fibrillin-1, which affects connective tissue. Few case reports have associated Marfan syndrome with vascular malformations of the brain and spinal cord. In this regard, association with intracranial aneurysm has been vaguely proposed. We report here a patient with Marfan syndrome who was admitted because of a sudden loss of consciousness. The patient underwent computed tomography (CT) examination, which disclosed a right intracerebellar hematoma. Cerebral angiogram did not demonstrate aneurysm or arteriovenous malformation (AVM), or evidence of any other vascular lesions or neoplasms in the posterior fossa. Conservative treatment was undertaken. The clinical course was uneventful and after 6 weeks the patient was discharged free of symptoms. Although patients with Marfan syndrome are at high risk of vascular abnormalities, a clear association with cerebral aneurysm has not yet been established. Our experience and the contrasting reports available in the medical literature strongly warrant further studies in order to better clarify this controversial association.

Characterization of subtle brain abnormalities in a mouse model of Hedgehog pathway antagonist-induced cleft lip and palate.

PubMed

Lipinski, Robert J; Holloway, Hunter T; O'Leary-Moore, Shonagh K; Ament, Jacob J; Pecevich, Stephen J; Cofer, Gary P; Budin, Francois; Everson, Joshua L; Johnson, G Allan; Sulik, Kathleen K

2014-01-01

Subtle behavioral and cognitive deficits have been documented in patient cohorts with orofacial clefts (OFCs). Recent neuroimaging studies argue that these traits are associated with structural brain abnormalities but have been limited to adolescent and adult populations where brain plasticity during infancy and childhood may be a confounding factor. Here, we employed high resolution magnetic resonance microscopy to examine primary brain morphology in a mouse model of OFCs. Transient in utero exposure to the Hedgehog (Hh) signaling pathway antagonist cyclopamine resulted in a spectrum of facial dysmorphology, including unilateral and bilateral cleft lip and palate, cleft of the secondary palate only, and a non-cleft phenotype marked by midfacial hypoplasia. Relative to controls, cyclopamine-exposed fetuses exhibited volumetric differences in several brain regions, including hypoplasia of the pituitary gland and olfactory bulbs, hyperplasia of the forebrain septal region, and expansion of the third ventricle. However, in affected fetuses the corpus callosum was intact and normal division of the forebrain was observed. This argues that temporally-specific Hh signaling perturbation can result in typical appearing OFCs in the absence of holoprosencephaly--a condition classically associated with Hh pathway inhibition and frequently co-occurring with OFCs. Supporting the premise that some forms of OFCs co-occur with subtle brain malformations, these results provide a possible ontological basis for traits identified in clinical populations. They also argue in favor of future investigations into genetic and/or environmental modulation of the Hh pathway in the etiopathogenesis of orofacial clefting.

The role of mechanics during brain development

NASA Astrophysics Data System (ADS)

Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

2014-12-01

Convolutions are a classical hallmark of most mammalian brains. Brain surface morphology is often associated with intelligence and closely correlated with neurological dysfunction. Yet, we know surprisingly little about the underlying mechanisms of cortical folding. Here we identify the role of the key anatomic players during the folding process: cortical thickness, stiffness, and growth. To establish estimates for the critical time, pressure, and the wavelength at the onset of folding, we derive an analytical model using the Föppl-von Kármán theory. Analytical modeling provides a quick first insight into the critical conditions at the onset of folding, yet it fails to predict the evolution of complex instability patterns in the post-critical regime. To predict realistic surface morphologies, we establish a computational model using the continuum theory of finite growth. Computational modeling not only confirms our analytical estimates, but is also capable of predicting the formation of complex surface morphologies with asymmetric patterns and secondary folds. Taken together, our analytical and computational models explain why larger mammalian brains tend to be more convoluted than smaller brains. Both models provide mechanistic interpretations of the classical malformations of lissencephaly and polymicrogyria. Understanding the process of cortical folding in the mammalian brain has direct implications on the diagnostics of neurological disorders including severe retardation, epilepsy, schizophrenia, and autism.

The role of mechanics during brain development

PubMed Central

Budday, Silvia; Steinmann, Paul; Kuhl, Ellen

2014-01-01

Convolutions are a classical hallmark of most mammalian brains. Brain surface morphology is often associated with intelligence and closely correlated to neurological dysfunction. Yet, we know surprisingly little about the underlying mechanisms of cortical folding. Here we identify the role of the key anatomic players during the folding process: cortical thickness, stiffness, and growth. To establish estimates for the critical time, pressure, and the wavelength at the onset of folding, we derive an analytical model using the Föppl-von-Kármán theory. Analytical modeling provides a quick first insight into the critical conditions at the onset of folding, yet it fails to predict the evolution of complex instability patterns in the post-critical regime. To predict realistic surface morphologies, we establish a computational model using the continuum theory of finite growth. Computational modeling not only confirms our analytical estimates, but is also capable of predicting the formation of complex surface morphologies with asymmetric patterns and secondary folds. Taken together, our analytical and computational models explain why larger mammalian brains tend to be more convoluted than smaller brains. Both models provide mechanistic interpretations of the classical malformations of lissencephaly and polymicrogyria. Understanding the process of cortical folding in the mammalian brain has direct implications on the diagnostics of neurological disorders including severe retardation, epilepsy, schizophrenia, and autism. PMID:25202162

Trends over time in congenital malformations in live-born children conceived after assisted reproductive technology.

PubMed

Henningsen, Anna-Karina A; Bergh, Christina; Skjaerven, Rolv; Tiitinen, Aila; Wennerholm, Ulla-Britt; Romundstad, Liv B; Gissler, Mika; Opdahl, Signe; Nyboe Andersen, Anders; Lidegaard, Øjvind; Forman, Julie L; Pinborg, Anja

2018-07-01

Children born after assisted reproductive technology, particularly singletons, have been shown to have an increased risk of congenital malformations compared with children born after spontaneous conception. We wished to study whether there has been a change in the past 20 years in the risk of major congenital malformations in children conceived after assisted reproductive technology compared with children spontaneously conceived. Population-based cohort study including 90 201 assisted reproductive technology children and 482 552 children spontaneously conceived, born in Denmark, Finland, Norway and Sweden. Both singletons and twins born after in vitro fertilization, intracytoplasmatic sperm injection and frozen embryo transfer were included. Data on children were taken from when the national Nordic assisted reproductive technology registries were established until 2007. Multiple logistic regression analyses were used to estimate the risks and adjusted odds ratios for congenital malformations in four time periods: 1988-1992, 1993-1997, 1998-2002 and 2003-2007. Only major malformations were included. The absolute risk for singletons of being born with a major malformation was 3.4% among assisted reproductive technology children vs. 2.9% among children spontaneously conceived during the study period. The relative risk of being born with a major congenital malformation between all assisted reproductive technology children and children spontaneously conceived remained similar through all four time periods (p = 0.39). However, we found that over time the number of children diagnosed with a major malformation increased in both groups across all four time periods. When comparing children conceived after assisted reproductive technology and spontaneously conceived, the relative risk of being born with a major congenital malformation did not change during the study period. © 2018 Nordic Federation of Societies of Obstetrics and Gynecology.

Fetal magnetic resonance imaging (MRI): a tool for a better understanding of normal and abnormal brain development.

PubMed

Saleem, Sahar N

2013-07-01

Knowledge of the anatomy of the developing fetal brain is essential to detect abnormalities and understand their pathogenesis. Capability of magnetic resonance imaging (MRI) to visualize the brain in utero and to differentiate between its various tissues makes fetal MRI a potential diagnostic and research tool for the developing brain. This article provides an approach to understand the normal and abnormal brain development through schematic interpretation of fetal brain MR images. MRI is a potential screening tool in the second trimester of pregnancies in fetuses at risk for brain anomalies and helps in describing new brain syndromes with in utero presentation. Accurate interpretation of fetal MRI can provide valuable information that helps genetic counseling, facilitates management decisions, and guides therapy. Fetal MRI can help in better understanding the pathogenesis of fetal brain malformations and can support research that could lead to disease-specific interventions.

Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study.

PubMed

de Fatima Vasco Aragao, Maria; van der Linden, Vanessa; Brainer-Lima, Alessandra Mertens; Coeli, Regina Ramos; Rocha, Maria Angela; Sobral da Silva, Paula; Durce Costa Gomes de Carvalho, Maria; van der Linden, Ana; Cesario de Holanda, Arthur; Valenca, Marcelo Moraes

2016-04-13

To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. Retrospective study with a case series. Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil. 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus--the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases. Severe cerebral damage was found on imaging in most of the children in this case series with congenital infection presumably associated with the Zika virus. The features most commonly found were brain calcifications in the junction between cortical and subcortical white matter associated with malformations of cortical development, often with a simplified gyral pattern and predominance of pachygyria or polymicrogyria in the frontal lobes. Additional findings were enlarged cisterna magna, abnormalities of corpus callosum (hypoplasia or hypogenesis), ventriculomegaly, delayed myelination, and hypoplasia of the cerebellum and the brainstem. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study

PubMed Central

van der Linden, Vanessa; Brainer-Lima, Alessandra Mertens; Coeli, Regina Ramos; Rocha, Maria Angela; Sobral da Silva, Paula; Durce Costa Gomes de Carvalho, Maria; van der Linden, Ana; Cesario de Holanda, Arthur; Valenca, Marcelo Moraes

2016-01-01

Objective To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic. Design Retrospective study with a case series. Setting Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil. Participants 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic. Main outcome measures Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans. Results Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus—the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases. Conclusion Severe cerebral damage was found on imaging in most of the children in this case series with congenital infection presumably associated with the Zika virus. The features most commonly found were brain calcifications in the junction between cortical and subcortical white matter associated with malformations of cortical development, often with a simplified gyral pattern and predominance of pachygyria or polymicrogyria in the frontal lobes. Additional findings were enlarged cisterna magna, abnormalities of corpus callosum (hypoplasia or hypogenesis), ventriculomegaly, delayed myelination, and hypoplasia of the cerebellum and the brainstem. PMID:27075009

The presentation and management of complex female genital malformations.

PubMed

Acién, Pedro; Acién, Maribel

2016-01-01

Common uterine anomalies are important owing to their impact on fertility, and complex mesonephric anomalies and certain Müllerian malformations are particularly important because they cause serious clinical symptoms and affect woman's quality of life, in addition to creating fertility problems. In these cases of complex female genital tract malformations, a correct diagnosis is essential to avoid inappropriate and/or unnecessary surgery. Therefore, acquiring and applying the appropriate embryological knowledge, management and therapy is a challenge for gynaecologists. Here, we considered complex malformations to be obstructive anomalies and/or those associated with cloacal and urogenital sinus anomalies, urinary and/or extragenital anomalies, or other clinical implications or symptoms creating a difficult differential diagnosis. A diligent and comprehensive search of PubMed and Scopus was performed for all studies published from 1 January 2011 to 15 April 2015 (then updated up to September 2015) using the following search terms: 'management' in combination with either 'female genital malformations' or 'female genital tract anomalies' or 'Müllerian anomalies'. The MeSH terms 'renal agenesis', 'hydrocolpos', 'obstructed hemivagina' 'cervicovaginal agenesis or atresia', 'vaginal agenesis or atresia', 'Herlyn-Werner-Wunderlich syndrome', 'uterine duplication' and 'cloacal anomalies' were also used to compile a list of all publications containing these terms since 2011. The basic embryological considerations for understanding female genitourinary malformations were also revealed. Based on our experience and the updated literature review, we studied the definition and classification of the complex malformations, and we analysed the clinical presentation and different therapeutic strategies for each anomaly, including the embryological and clinical classification of female genitourinary malformations. From 755 search retrieved references, 230 articles were analysed and 120 studied in detail. They were added to those included in a previous systematic review. Here, we report the clinical presentation and management of: agenesis or hypoplasia of one urogenital ridge; unilateral renal agenesis and ipsilateral blind or obstructed hemivagina or unilateral cervicovaginal agenesis; cavitated and non-communicating uterine horns and Müllerian atresias or agenesis, including Rokitansky syndrome; anomalies of the cloaca and urogenital sinus, including congenital vagino-vesical fistulas and cloacal anomalies; malformative combinations and other complex malformations. The clinical symptoms and therapeutic strategies for each complex genitourinary malformation are discussed. In general, surgical techniques to correct genital malformations depend on the type of anomaly, its complexity, the patient's symptoms and the correct embryological interpretation of the anomaly. Most anomalies can typically be resolved vaginally or by hysteroscopy, but laparoscopy or laparotomy is often required as well. We also include additional discussion of the catalogue and classification systems for female genital malformations, the systematic association between renal agenesis and ipsilateral genital malformation, and accessory and cavitated uterine masses. Knowledge of the correct genitourinary embryology is essential for the understanding, study, diagnosis and subsequent treatment of genital malformations, especially complex ones and those that lead to gynaecological and reproductive problems, particularly in young patients. Some anomalies may require complex surgery involving multiple specialties, and patients should therefore be referred to centres that have experience in treating complex genital malformations. © The Author 2015. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Study of placenta of children born with congenital malformations.

PubMed

Stoll, Claude; Alembik, Yves; Dott, Béatrice; Roth, Marie-Paule

2003-01-01

The malformations in this study were observed in a series of 279,642 consecutive births of known outcome registered in our Registry of congenital anomalies. For each case, more than 50 factors included in the registration forms were studied. One of the factors studied was the placenta. For each malformed child, a control was chosen. Cases with maternal known factors impairing placenta function, i.e. vasculopathy and diabetes, were excluded. In each category of malformations studied, the malformed children were divided into isolated and non-isolated (multiple malformed) cases. The weight of placenta of isolated cases was not lower than the weight of placenta of the controls. In contrast, the weight of placenta of the cases with non-isolated malformations was lower than the weight of placenta of the controls and of the isolated cases, for all categories of malformations but gastroschisis and omphalocele. The mean weights at birth of the cases with multiple malformations were also lower than those of the controls. The human placenta discounts a principal functional part, the maternal blood in the intervillous space. Congenital malformations may interact with this function.

Impact on cognitive functions following gamma knife radiosurgery for cerebral arteriovenous malformations.

PubMed

Raghunath, A; Bennett, Niranjana; Arimappamagan, Arivazhagan; Bhat, Dhananjaya I; Srinivas, Dwarakanath; Thennarasu, K; Jamuna, R; Somanna, Sampath

2016-01-01

Radiosurgery is an alternative to surgical resection of arteriovenous malformation (AVM). Very few studies have addressed the concern of radiation injury to the brain and its attendant adverse effects on cognitive function. This prospective study included all patients who underwent gamma knife radiosurgery (GKRS) at our institute for cerebral AVM between 2006 and December 2008 (n = 34). All patients underwent neuropsychological evaluation before the procedure. Neuropsychological evaluation was repeated in eighteen patients 2 years following GKRS. Clinical outcome, AVM obliteration, and factors influencing outcome were analyzed in these eighteen patients. Before GKRS, more than 50% had significant impairment of neuropsychological functions compared to normal population norms. 66.6% achieved the excellent radiosurgical outcome. At 2 years follow-up, patients showed varied improvement in neuropsychological function in various categories. Pretherapeutic median value for percentage perseverative responses was 26.5 and at follow-up, it reduced to 18.2 (P = 0.039). Set shifting improved in 11 patients (61.1%), remained same in 5 patients (27.7%), and deteriorated in two patients (11.1%). Patients with a higher Spetzler-Martin grade AVM demonstrated a significantly more favorable shift in follow-up test values for set shifting function (P = 0.021). Patients with postradiation imaging changes had lesser tendency to improve in neuropsychological performance at follow-up. GKRS has no clinically harmful effect on cognitive and neuropsychological functioning in patients with brain AVM. On the contrary, there is an improvement in majority of patients at 2 years following radiosurgery when nidus is obliterated.

The syndrome of perisylvian polymicrogyria with congenital arthrogryposis.

PubMed

Poduri, Annapurna; Chitsazzadeh, Vida; D'Arrigo, Stefano; Fedrizzi, Ermellina; Pantaleoni, Chiara; Riva, Daria; Busse, Claudia; Küster, Helmut; Duplessis, Adre; Gaitanis, John; Sahin, Mustafa; Garganta, Cheryl; Topcu, Meral; Dies, Kira A; Barry, Brenda J; Partlow, Jennifer; Barkovich, A James; Walsh, Christopher A; Chang, Bernard S

2010-08-01

Bilateral perisylvian polymicrogyria (BPP) is a well-recognized malformation of cortical development commonly associated with epilepsy, cognitive impairment, and oromotor apraxia. Reports have suggested the association of BPP with arthrogryposis multiplex congenita. We sought to investigate the clinical, electrophysiological, and neuroradiological features of this combined syndrome to determine if there are unique features that distinguish BPP with arthrogryposis from BPP alone. Cases of BPP with congenital arthrogryposis were identified from a large research database of individuals with polymicrogyria. Clinical features (including oromotor function, seizures, and joint contractures), MR brain imaging, and results of neuromuscular testing were reviewed. Ten cases of BPP with congenital arthrogryposis were identified. Most cases had some degree of oromotor apraxia. Only a few had seizures, but a majority of cases were still young children. Electrophysiological studies provided evidence for lower motor neuron or peripheral nervous system involvement. On brain imaging, bilateral polymicrogyria (PMG) centered along the Sylvian fissures was seen, with variable extension frontally or parietally; no other cortical malformations were present. We did not identify obvious neuroimaging features that distinguish this syndrome from that of BPP without arthrogryposis. The clinical and neuroimaging features of the syndrome of BPP with congenital arthrogryposis appear similar to those seen in cases of isolated BPP without joint contractures, but electrophysiological studies often demonstrate coexistent lower motor neuron or peripheral nervous system pathology. These findings suggest that BPP with arthrogryposis may have a genetic etiology with effects at two levels of the neuraxis. Copyright 2009 Elsevier B.V. All rights reserved.

[The causes of symptomatic epilepsy in children aged 3-18 years hospitalized in the year 2006-2007].

PubMed

Gergont, Aleksandra; Kroczka, Sławomir; Kaciński, Marek

2008-01-01

Epilepsy can be one of symptoms of the damage to CNS in children with neurodevelopmental deficits, it is more difficult however to diagnose seizures if they are the first symptom of severe brain damage. This retrospective research was conducted to study causes of symptomatic epilepsy in children aged 3-18 year hospitalized between 2006 and 2007 year in the Department of Pediatric Neurology. 156 children with symptomatic epilepsy occurred after 2 years of life were included. The diagnosis of symptomatic epilepsy was established including clinical picture, neuro-radiological tests and EEG. The information from parents was helpful to analyze the type of seizures. The clinical state of children was analyzed, especially psychomotor development, focal deficits, as well as results of CT and/or MRI, in some children psychological testing was performed, molecular or serological. 156 children with epilepsy were hospitalized, within encephalopathy was diagnosed in 61 children. In 42 children static encephalopathy was associated with birth trauma, in 7 progressive encephalopathy was diagnosed, in 1 child CO intoxication caused encephalopathy, and in 11 cases the cause was not identified. Malformations of nervous system were associated with epilepsy in 37 children, geneticaly determined syndromes in 6, and the head trauma in other 6 children. Disorders of vascular origin caused epilepsy in 16 children, and neuroinfections in 9 children. In 2 children epilepsy was associated with ADEM, and in 11 children nonspecific de/dysmyelination was detected. The brain tumor was detected in 6 children with symptomatic epilepsy. The most common disorder leading to epilepsy in children aged 3-18 years was encephalopathy, within hypoxic-ischemic encephalopathy. The other in sequence were malformations of nervous system and vascular diseases.

An open-label study to evaluate sildenafil for the treatment of lymphatic malformations.

PubMed

Danial, Christina; Tichy, Andrea L; Tariq, Umar; Swetman, Glenda L; Khuu, Phuong; Leung, Thomas H; Benjamin, Latanya; Teng, Joyce; Vasanawala, Shreyas S; Lane, Alfred T

2014-06-01

Lymphatic malformations can be challenging to treat. Mainstay interventions including surgery and sclerotherapy are invasive and can result in local recurrence and complications. We sought to assess the effect of 20 weeks of oral sildenafil on reducing lymphatic malformation volume and symptoms in children. Seven children (4 boys, 3 girls; ages 13-85 months) with lymphatic malformations were given oral sildenafil for 20 weeks in this open-label study. The volume of the lymphatic malformation was calculated blindly using magnetic resonance imaging performed before and after 20 weeks of sildenafil. Lymphatic malformations were assessed clinically on weeks 4, 12, 20, and 32. Both the physician and parents evaluated the lymphatic malformation in comparison with baseline. Four subjects had a lymphatic malformation volume decrease (1.0%-31.7%). In 2 subjects, despite a lymphatic malformation volume increase (1.1%-3.7%), clinical improvement was noted while on sildenafil. One subject had a 29.6% increase in lymphatic malformation volume and no therapeutic response. Lymphatic malformations of all 6 subjects who experienced a therapeutic response on sildenafil softened and became easily compressible. Adverse events were minimal. A randomized controlled trial will be necessary to verify the effects of sildenafil on lymphatic malformations. Sildenafil can reduce lymphatic malformation volume and symptoms in some children. Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

Management of lymphatic malformations in children.

PubMed

Bagrodia, Naina; Defnet, Ann M; Kandel, Jessica J

2015-06-01

To review the literature on lymphatic malformations and to provide current opinion about the management of these lesions. Current treatment options include nonoperative management, surgery, sclerotherapy, radiofrequency ablation, and laser therapy. New therapies are emerging, including sildenafil, propranolol, sirolimus, and vascularized lymph node transfer. The primary focus of management centers on the patient's quality of life. Multimodal treatment of lymphatic malformations continues to expand as new information about the biology and genetics of these lesions is discovered, in addition to knowledge gained from clinical practice. A patient-centered approach should guide timing and modality of treatment. Continued study of lymphatic malformations will increase and solidify a treatment algorithm for these complicated lesions.

Post-mortem cytogenomic investigations in patients with congenital malformations.

PubMed

Dias, Alexandre Torchio; Zanardo, Évelin Aline; Dutra, Roberta Lelis; Piazzon, Flavia Balbo; Novo-Filho, Gil Monteiro; Montenegro, Marilia Moreira; Nascimento, Amom Mendes; Rocha, Mariana; Madia, Fabricia Andreia Rosa; Costa, Thais Virgínia Moura Machado; Milani, Cintia; Schultz, Regina; Gonçalves, Fernanda Toledo; Fridman, Cintia; Yamamoto, Guilherme Lopes; Bertola, Débora Romeo; Kim, Chong Ae; Kulikowski, Leslie Domenici

2016-08-01

Congenital anomalies are the second highest cause of infant deaths, and, in most cases, diagnosis is a challenge. In this study, we characterize patterns of DNA copy number aberrations in different samples of post-mortem tissues from patients with congenital malformations. Twenty-eight patients undergoing autopsy were cytogenomically evaluated using several methods, specifically, Multiplex Ligation-dependent Probe Amplification (MLPA), microsatellite marker analysis with a MiniFiler kit, FISH, a cytogenomic array technique and bidirectional Sanger sequencing, which were performed on samples of different tissues (brain, heart, liver, skin and diaphragm) preserved in RNAlater, in formaldehyde or by paraffin-embedding. The results identified 13 patients with pathogenic copy number variations (CNVs). Of these, eight presented aneuploidies involving chromosomes 13, 18, 21, X and Y (two presented inter- and intra-tissue mosaicism). In addition, other abnormalities were found, including duplication of the TYMS gene (18p11.32); deletion of the CHL1 gene (3p26.3); deletion of the HIC1 gene (17p13.3); and deletion of the TOM1L2 gene (17p11.2). One patient had a pathogenic missense mutation of g.8535C>G (c.746C>G) in exon 7 of the FGFR3 gene consistent with Thanatophoric Dysplasia type I. Cytogenomic techniques were reliable for the analysis of autopsy material and allowed the identification of inter- and intra-tissue mosaicism and a better understanding of the pathogenesis of congenital malformations. Copyright © 2016 Elsevier Inc. All rights reserved.

Posterior reversible encephalopathy syndrome in a patient with a Chiari I malformation

PubMed Central

Hansberry, David R.; Agarwal, Nitin; Tomei, Krystal L.; Goldstein, Ira M.

2013-01-01

Background: The authors describe a unique case of a patient who developed posterior reversible encephalopathy syndrome (PRES) following postoperative treatment of a Chiari I malformation. Case Decsription: A 25-year-old female presented with complaints of left upper and lower extremity paresthesias and gait disturbances. A magnetic resonance imaging (MRI) of the brain and cervical spine showed a Chiari I malformation with tonsillar descent beyond the level of the C1 lamina. She underwent a suboccipital craniectomy and C1 laminectomy with cerebellar tonsillar cauterization and duraplasty. Postoperatively, an MRI showed bilateral acute infarcts of the cerebellar vermis. She was initially treated for cerebellar ischemia with hypertensive therapy with a subsequent decline in her neurologic status and generalized tonic–clonic seizure. Further workup showed evidence of PRES. After weaning pressors, the patient had a significant progressive improvement in her mental status. Conclusion: Although the mechanism of PRES remains controversial given its diverse clinical presentation, several theories implicate hypertension and steroid use as causative agents. PMID:24232171

MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations

PubMed Central

Le Meur, Nathalie; Holder-Espinasse, Muriel; Jaillard, Sylvie; Goldenberg, Alice; Joriot, Sylvie; Amati-Bonneau, Patrizia; Guichet, Agnès; Barth, Magalie; Charollais, Aude; Journel, Hubert; Auvin, Stéphane; Boucher, Cécile; Kerckaert, Jean-Pierre; David, Véronique; Manouvrier-Hanu, Sylvie; Saugier-Veber, Pascale; Frébourg, Thierry; Dubourg, Christèle; Andrieux, Joris; Bonneau, Dominique

2010-01-01

Over the last few years, array-CGH has remarkably improved the ability to detect cryptic unbalanced rearrangements in patients presenting with syndromic mental retardation. Using whole genome oligonucleotide array-CGH, we detected 5q14.3 microdeletions ranging from 216 kb to 8.8 Mb in 5 unrelated patients showing phenotypic similarities, namely severe mental retardation with absent speech, hypotonia and stereotypic movements. Most of the patients presented also with facial dysmorphic features, epilepsy and/or cerebral malformations. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, known to act in brain as a neurogenesis effector which regulates excitatory synapse number. In a patient presenting a similar phenotype, we subsequently identified a MEF2C nonsense mutation. Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations. PMID:19592390

Testing for Zika virus infection in pregnancy: key concepts to deal with an emerging epidemic.

PubMed

Eppes, Catherine; Rac, Martha; Dunn, James; Versalovic, James; Murray, Kristy O; Suter, Melissa A; Sanz Cortes, Magda; Espinoza, Jimmy; Seferovic, Maxim D; Lee, Wesley; Hotez, Peter; Mastrobattista, Joan; Clark, Steven L; Belfort, Michael A; Aagaard, Kjersti M

2017-03-01

Zika virus is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Following epidemics in Micronesia and French Polynesia during the past decade, more recent Zika virus infection outbreaks were first reported in South America as early as May 2013 and spread to now 50 countries throughout the Americas. Although no other flavivirus has previously been known to cause major fetal malformations following perinatal infection, reports of a causal link between Zika virus and microcephaly, brain and ocular malformations, and fetal loss emerged from hard-hit regions of Brazil by October 2015. Among the minority of infected women with symptoms, clinical manifestations of Zika virus infection may include fever, headache, arthralgia, myalgia, and maculopapular rash; however, only 1 of every 4-5 people who are infected have any symptoms. Thus, clinical symptom reporting is an ineffective screening tool for the relative risk assessment of Zika virus infection in the majority of patients. As previously occurred with other largely asymptomatic viral infections posing perinatal transmission risk (such as HIV or cytomegalovirus), we must develop and implement rapid, sensitive, and specific screening and diagnostic testing for both viral detection and estimation of timing of exposure. Unfortunately, despite an unprecedented surge in attempts to rapidly advance perinatal clinical testing for a previously obscure arbovirus, there are several ongoing hindrances to molecular- and sonographic-based screening and diagnosis of congenital Zika virus infection. These include the following: (1) difficulty in estimating the timing of exposure for women living in endemic areas and thus limited interpretability of immunoglobulin M serologies; (2) cross-reaction of immunoglobulin serologies with other endemic flaviruses, such as dengue; (3) persistent viremia and viruria in pregnancy weeks to months after primary exposure; and (4) fetal brain malformations and anomalies preceding the sonographic detection of microcephaly. In this commentary, we discuss screening and diagnostic considerations that are grounded not only in the realities of current obstetrical practice in a largely global population but also in basic immunology and virology. We review recent epidemiological data pertaining to the risk of congenital Zika virus malformations based on trimester of exposure and consider side by side with emerging data demonstrating replication of Zika virus in placental and fetal tissue throughout gestation. We discuss limitations to ultrasound based strategies that rely largely or solely on the detection of microcephaly and provide alternative neurosonographic approaches for the detection of malformations that may precede or occur independent of a small head circumference. This expert review provides information that is of value for the following: (1) obstetrician, maternal-fetal medicine specialist, midwife, patient, and family in cases of suspected Zika virus infection; (2) review of the methodology for laboratory testing to explore the presence of the virus and the immune response; (3) ultrasound-based assessment of the fetus suspected to be exposed to Zika virus with particular emphasis on the central nervous system; and (4) identification of areas ready for development. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Augmentative Communication with Computer Assist.

ERIC Educational Resources Information Center

Kinzer, Gay

To provide a communication method for children who are non-verbal due to hearing impairments, brain damage, or malformed oral structures, sign language and language boards have been utilized. However, these methods have limitations, and alternate means of communication have been explored. An Apple 2E computer with an echo speech synthesizer was…

Developmental outcomes of Down syndrome and Dandy-Walker malformation

PubMed Central

Love, Kaitlin; Huddleston, Lillie; Olney, Pat; Wrubel, David; Visootsak, Jeannie

2012-01-01

Dandy-Walker syndrome (DWS), or Dandy-Walker complex, is a congenital brain malformation of the posterior fossa, typically resulting in developmental delay and cognitive disability. The co-occurrence of Down syndrome (DS) and DWS is relatively uncommon; thus, its impact on developmental outcomes has not been fully elucidated. Herein, we report a case of a 37-month-old child with DS and DWS, who is functioning at the following age-equivalent: gross motor at a 9-mo level, fine motor 6 mo, expressive language 14 mo, receptive language 9 mo. As such, it is important to determine how the DWS influences developmental outcomes, and appreciate the importance of early interventional therapy. PMID:22866020

Familial Aggregation of Chiari Malformation: Presentation, Pedigree, and Review of the Literature.

PubMed

Nagy, Laszlo; Mobley, James; Ray, Coby

2016-01-01

This article reports the largest familial aggregation of Chiari malformation in a single family to date as reported in the literature. This study is a retrospective case series of a family of whom five individuals have a confirmed case of Chiari malformation and three additional individuals have Chiari signs and symptoms. This contribution further supports the implication of genetics in the transmission of Chiari malformation. The family reported in this study also has a significant incidence of Ehlers-Danlos. Three sisters, including a set of twins, presented with confirmed cases of Chiari malformation and four of the five children of the twin sisters presented with confirmed or suspected Chiari malformation. Of note, the non-twin sister has three children who are unaffected. This report provides further evidence for a shared loci between the Chiari malformation and Ehlers-Danlos.

Agenesis of the corpus callosum and gray matter heterotopia in three patients with constitutional mismatch repair deficiency syndrome

PubMed Central

Baas, Annette F; Gabbett, Michael; Rimac, Milan; Kansikas, Minttu; Raphael, Martine; Nievelstein, Rutger AJ; Nicholls, Wayne; Offerhaus, Johan; Bodmer, Danielle; Wernstedt, Annekatrin; Krabichler, Birgit; Strasser, Ulrich; Nyström, Minna; Zschocke, Johannes; Robertson, Stephen P; van Haelst, Mieke M; Wimmer, Katharina

2013-01-01

Constitutional mismatch repair deficiency (CMMR-D) syndrome is a rare inherited childhood cancer predisposition caused by biallelic germline mutations in one of the four mismatch repair (MMR)-genes, MLH1, MSH2, MSH6 or PMS2. Owing to a wide tumor spectrum, the lack of specific clinical features and the overlap with other cancer predisposing syndromes, diagnosis of CMMR-D is often delayed in pediatric cancer patients. Here, we report of three new CMMR-D patients all of whom developed more than one malignancy. The common finding in these three patients is agenesis of the corpus callosum (ACC). Gray matter heterotopia is present in two patients. One of the 57 previously reported CMMR-D patients with brain tumors (therefore all likely had cerebral imaging) also had ACC. With the present report the prevalence of cerebral malformations is at least 4/60 (6.6%). This number is well above the population birth prevalence of 0.09–0.36 live births with these cerebral malformations, suggesting that ACC and heterotopia are features of CMMR-D. Therefore, the presence of cerebral malformations in pediatric cancer patients should alert to the possible diagnosis of CMMR-D. ACC and gray matter heterotopia are the first congenital malformations described to occur at higher frequency in CMMR-D patients than in the general population. Further systematic evaluations of CMMR-D patients are needed to identify possible other malformations associated with this syndrome. PMID:22692065

Agenesis of the corpus callosum and gray matter heterotopia in three patients with constitutional mismatch repair deficiency syndrome.

PubMed

Baas, Annette F; Gabbett, Michael; Rimac, Milan; Kansikas, Minttu; Raphael, Martine; Nievelstein, Rutger Aj; Nicholls, Wayne; Offerhaus, Johan; Bodmer, Danielle; Wernstedt, Annekatrin; Krabichler, Birgit; Strasser, Ulrich; Nyström, Minna; Zschocke, Johannes; Robertson, Stephen P; van Haelst, Mieke M; Wimmer, Katharina

2013-01-01

Constitutional mismatch repair deficiency (CMMR-D) syndrome is a rare inherited childhood cancer predisposition caused by biallelic germline mutations in one of the four mismatch repair (MMR)-genes, MLH1, MSH2, MSH6 or PMS2. Owing to a wide tumor spectrum, the lack of specific clinical features and the overlap with other cancer predisposing syndromes, diagnosis of CMMR-D is often delayed in pediatric cancer patients. Here, we report of three new CMMR-D patients all of whom developed more than one malignancy. The common finding in these three patients is agenesis of the corpus callosum (ACC). Gray matter heterotopia is present in two patients. One of the 57 previously reported CMMR-D patients with brain tumors (therefore all likely had cerebral imaging) also had ACC. With the present report the prevalence of cerebral malformations is at least 4/60 (6.6%). This number is well above the population birth prevalence of 0.09-0.36 live births with these cerebral malformations, suggesting that ACC and heterotopia are features of CMMR-D. Therefore, the presence of cerebral malformations in pediatric cancer patients should alert to the possible diagnosis of CMMR-D. ACC and gray matter heterotopia are the first congenital malformations described to occur at higher frequency in CMMR-D patients than in the general population. Further systematic evaluations of CMMR-D patients are needed to identify possible other malformations associated with this syndrome.

Functional Connectivity and Genetic Profile of a “Double-Cortex”-Like Malformation

PubMed Central

Sprugnoli, Giulia; Vatti, Giampaolo; Rossi, Simone; Cerase, Alfonso; Renieri, Alessandra; Mencarelli, Maria A.; Zara, Federico; Rossi, Alessandro; Santarnecchi, Emiliano

2018-01-01

Laminar heterotopia is a rare condition consisting in an extra layer of gray matter under properly migrated cortex; it configures an atypical presentation of periventricular nodular heterotopia (PNH) or a double cortex (DC) syndrome. We conducted an original functional MRI (fMRI) analysis in a drug-resistant epilepsy patient with “double-cortex”-like malformation to reveal her functional connectivity (FC) as well as a wide genetic analysis to identify possible genetic substrates. Heterotopias were segmented into region of interests (ROIs), whose voxel-wise FC was compared to that of (i) its normally migrated counterpart, (ii) its contralateral homologous, and (iii) those of 30 age-matched healthy controls. Extensive genetic analysis was conducted to screen cortical malformations-associated genes. Compared to healthy controls, both laminar heterotopias and the overlying cortex showed significant reduction of FC with the contralateral hemisphere. Two heterozygous variants of uncertain clinical significance were found, involving autosomal recessive disease-causing genes, FAT4 and COL18A1. This first FC analysis of a unique case of “double-cortex”-like malformation revealed a hemispheric connectivity segregation both in the laminar cortex as in the correctly migrated one, with a new pattern of genes’ mutations. Our study suggests the altered FC could have an electrophysiological and functional impact on large-scale brain networks, and the involvement of not yet identified genes in “double-cortex”-like malformation with a possible role of rare variants in recessive genes as pathogenic cofactors. PMID:29946244

Structural MRI biomarkers of shared pathogenesis in autism spectrum disorder and epilepsy.

PubMed

Blackmon, Karen

2015-06-01

Etiological factors that contribute to a high comorbidity between autism spectrum disorder (ASD) and epilepsy are the subject of much debate. Does epilepsy cause ASD or are there common underlying brain abnormalities that increase the risk of developing both disorders? This review summarizes evidence from quantitative MRI studies to suggest that abnormalities of brain structure are not necessarily the consequence of ASD and epilepsy but are antecedent to disease expression. Abnormal gray and white matter volumes are present prior to onset of ASD and evident at the time of onset in pediatric epilepsy. Aberrant brain growth trajectories are also common in both disorders, as evidenced by blunted gray matter maturation and white matter maturation. Although the etiological factors that explain these abnormalities are unclear, high heritability estimates for gray matter volume and white matter microstructure demonstrate that genetic factors assert a strong influence on brain structure. In addition, histopathological studies of ASD and epilepsy brain tissue reveal elevated rates of malformations of cortical development (MCDs), such as focal cortical dysplasia and heterotopias, which supports disruption of neuronal migration as a contributing factor. Although MCDs are not always visible on MRI with conventional radiological analysis, quantitative MRI detection methods show high sensitivity to subtle malformations in epilepsy and can be potentially applied to MCD detection in ASD. Such an approach is critical for establishing quantitative neuroanatomic endophenotypes that can be used in genetic research. In the context of emerging drug treatments for seizures and autism symptoms, such as rapamycin and rapalogs, in vivo neuroimaging markers of subtle structural brain abnormalities could improve sample stratification in human clinical trials and potentially extend the range of patients that might benefit from treatment. This article is part of a Special Issue entitled "Autism and Epilepsy". Copyright © 2015 Elsevier Inc. All rights reserved.

PHACES syndrome associated with carcinoid endobronchial tumor.

PubMed

Mama, Nadia; H'mida, Dorra; Lahmar, Imen; Yacoubi, Mohamed Tahar; Tlili-Graiess, Kalthoum

2014-05-01

PHACES syndrome consists of the constellation of manifestations including posterior fossa anomalies of the brain (most commonly Dandy-Walker malformations), hemangiomas of the face and scalp, arterial abnormalities, cardiac defects, eye anomalies and sternal defects. We present a case with a possible PHACES syndrome including sternal cleft and supraumbilical raphé, precordial skin tag, persistent left superior vena cava and subtle narrowing of the aorta with an endobronchial carcinoid tumor. All these anomalies were discovered on chest multi-detector CT. This is a unique case of PHACES syndrome associated with carcinoid tumor. Review of the literature revealed 3 cases of PHACES syndrome with glial tumor. The authors tried to find the relationship between PHACES syndrome and carcinoid tumors or gliomas, which all derive from the neural crest cells.

Schmallenberg virus, a novel orthobunyavirus infection in ruminants in Europe: potential global impact and preventive measures.

PubMed

Conraths, F J; Peters, M; Beer, M

2013-03-01

In autumn 2011, Schmallenberg virus was the first orthobunyavirus detected in Europe. The virus belongs to the Simbu serogroup. Like other orthobunyaviruses, it is apparently transmitted by arthropod vectors, primarily by biting midges (Culicoides spp.). Ruminants and new-world camelids (alpacas) are susceptible to infection. Adult animals may develop mild disease, if any. However, transplacental infection can lead to severe congenital malformations such asarthrogryposis, malformation of the vertebral column (kyphosis, lordosis, scoliosis, torticollis) and of the skull (macrocephaly, brachygnathia inferior) as well as variable malformations of the brain (hydranencephaly, porencephaly, cerebellar hypoplasia, hypoplasia of the brain stem) and of the spinal cord in lambs, goat kids and calves. The infection spread rapidly over large parts of North-Western Europe. Belgium, Denmark, Germany, France, Italy, Luxembourg, the Netherlands, Spain and the United Kingdom were affected in the transmission season 2011/2012. The disease has re-emerged, at least in France, Germany and the United Kingdom during the vector-active season in 2012 and recently spread to Austria, Finland, Poland, Switzerland and Sweden. It remains to be seen whether the infection will establish permanently in the affected area. Measures have been proposed by the World Organisation for Animal Health (OIE) to help countries free from Schmallenberg virus to avoid the introduction of the infection without imposing inappropriate trade barriers. The aim of this article is to provide a state-of-the-art review on Schmallenberg virus 1 year after its first detection.

Impaired cerebral development in fetuses with congenital cardiovascular malformations: Is it the result of inadequate glucose supply?

PubMed

Rudolph, Abraham M

2016-08-01

Cerebral development may be impaired in fetuses with congenital cardiovascular malformations, particularly hypoplastic left heart syndrome (HLHS) and aortopulmonary transposition (APT). The decreased cerebral arterial pusatility index observed in some of these fetuses led to the belief that cerebral vascular resistance was reduced as a result of arterial hypoxemia and cerebral hypoxia is thought to be responsible for impaired cerebral growth. However, other hemodynamic factors could affect pulsatility index. I propose that cerebral blood flow is reduced in fetuses with HLHS and that reduced glucose, rather than oxygen, delivery interferes with cerebral development. This is based on the fact that most of these fetuses do not have lactate accumulation in the brain.In fetuses with APT, umbilical venous blood, containing oxygen and glucose derived across the placenta, is distributed to the lungs and lower body; venous blood, with low oxygen and glucose content, is delivered to the ascending aorta and brain. Oxygen and glucose delivery may further be reduced by decreased cerebral blood flow resulting from run-off of aortic blood through the ductus arteriosus to the pulmonary circulation during diastole. In APT fetuses, lack of lactate in the brain also supports my proposal that glucose deficiency interferes with cerebral development.

Clinical and mutational spectrum in Korean patients with Rubinstein-Taybi syndrome: the spectrum of brain MRI abnormalities.

PubMed

Lee, Jin Sook; Byun, Christine K; Kim, Hunmin; Lim, Byung Chan; Hwang, Hee; Choi, Ji Eun; Hwang, Yong Seung; Seong, Moon-Woo; Park, Sung Sup; Kim, Ki Joong; Chae, Jong-Hee

2015-04-01

Rubinstein-Taybi syndrome (RSTS) is one of the neurodevelopmental disorders caused by mutations of epigenetic genes. The CREBBP gene is the most common causative gene, encoding the CREB-binding protein with histone acetyltransferase (HAT) activity, an epigenetic modulator. To date, there have been few reports on the structural abnormalities of the brain in RSTS patients. In addition, there are no reports on the analysis of CREBBP mutations in Korean RSTS patients. We performed mutational analyses on 16 unrelated patients with RSTS, with diagnosis based on the typical clinical features. Their medical records and brain MRI images were reviewed retrospectively. Ten of 16 patients (62.5%) had mutations in the CREBBP gene. The mutations included five frameshift mutations (31.2%), two nonsense mutations (12.5%), and three multiexon deletions (18.8%). There were no remarkable significant differences in the clinical features between those with and without a CREBBP mutation, although brain MRI abnormalities were more frequently observed in those with a CREBBP mutation. Seven of 10 patients in whom brain imaging was performed had structural abnormalities, including Chiari malformation type 1, thinning of the corpus callosum, and delayed myelination. There were no differences in delayed development or cognitive impairment between those with and without abnormal brain images, while epilepsy was involved in two patients who had abnormalities on brain MRI images. We investigated the spectrum of CREBBP mutations in Korean patients with RSTS for the first time. Eight novel mutations extended the genetic spectrum of CREBBP mutations in RSTS patients. This is also the first study showing the prevalence and spectrum of abnormalities on brain MRI in RSTS patients. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Cystic kidneys in fetal Walker-Warburg syndrome with POMT2 mutation: Intrafamilial phenotypic variability in four siblings and review of literature.

PubMed

Nabhan, Marwa M; ElKhateeb, Nour; Braun, Daniela A; Eun, Sungho; Saleem, Sahar N; YungGee, Heon; Hildebrandt, Friedhelm; Soliman, Neveen A

2017-10-01

Walker-Warburg syndrome (WWS) is a severe form of congenital muscular dystrophy secondary to α-dystroglycanopathy with muscle, brain, and eye abnormalities often leading to death in the first weeks of life. It is transmitted in an autosomal recessive pattern, and has been linked to at least 15 different genes; including protein O-mannosyltransferase 1 (POMT1), protein O-mannosyltransferase 2 (POMT2), protein O-mannose beta-1,2-N acetylglucosaminyltransferase (POMGNT1), fukutin (FKTN), isoprenoid synthase domain-containing protein (ISPD), and other genes. We report on a consanguineous family with four consecutive siblings affected by this condition with lethal outcome in three (still birth), and termination of the fourth pregnancy based on antenatal MRI identification of brain and kidney anomalies that heralded proper and deep clinical phenotyping. The diagnosis of WWS was suggested based on the unique collective phenotype comprising brain anomalies in the form of lissencephaly, subcortical/subependymal heterotopia, and cerebellar hypoplasia shared by all four siblings; microphthalmia in one sibling; and large cystic kidneys in the fetus and another sibling. Other unshared neurological abnormalities included hydrocephalus and Dandy-Walker malformation. Whole exome sequencing of the fetus revealed a highly conserved missense mutation in POMT2 that is known to cause WWS with brain and eye anomalies.In conclusion, the heterogeneous clinical presentation in the four affected conceptions with POMT2 mutation expands the current clinical spectrum of POMT2-associated WWS to include large cystic kidneys; and confirms intra-familial variability in terms of brain, kidney, and eye anomalies. © 2017 Wiley Periodicals, Inc.

B3GALNT2-Related Dystroglycanopathy: Expansion of the Phenotype with Novel Mutation Associated with Muscle-Eye-Brain Disease, Walker-Warburg Syndrome, Epileptic Encephalopathy-West Syndrome, and Sensorineural Hearing Loss.

PubMed

Al Dhaibani, Muna A; El-Hattab, Ayman W; Ismayl, Omar; Suleiman, Jehan

2018-05-23

Mutations in B3GALNT2 , encoding a glycosyltransferase enzyme involved in α-dystroglycan glycosylation, have been recently associated with dystroglycanopathy, a well-recognized subtype of congenital muscular dystrophy (CMD). Only a few cases have been reported with B3GALNT2 -related dystroglycanopathy with variable severity ranging from mild CMD to severe muscle-eye-brain disease. Here, we describe a child with a novel homozygous nonsense mutation in B3GALNT2 . The affected child has severe neurological disease since birth, including muscle disease manifested as hypotonia, muscle weakness, and wasting with elevated creatine kinase, eye disease including microphthalmia and blindness, brain disease with extensive brain malformations including massive hydrocephalus, diffuse cobblestone-lissencephaly, deformed craniocervical junction, and pontocerebellar hypoplasia. The clinical and radiologic findings are compatible with a diagnosis of severe muscle-eye-brain disease and more specifically Walker-Warburg syndrome. A more distinct aspect of the clinical phenotype in this child is the presence of refractory epilepsy in the form of epileptic spasms, epileptic encephalopathy, and West syndrome, as well as sensorineural hearing loss. These findings could expand the phenotype of B3GALNT2 -related dystroglycanopathy. In this report, we also provide a detailed review of previously reported cases with B3GALNT2 -related dystroglycanopathy and compare them to our reported child. In addition, we study the genotype-phenotype correlation in these cases. Georg Thieme Verlag KG Stuttgart · New York.

Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations

PubMed Central

Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Dejene, Sara Z; Fischer, Michael A; Friedman, Alexander M; Hernandez-Diaz, Sonia; Huybrechts, Krista F

2016-01-01

Objective To examine the association between first-trimester angiotensin-converting enzyme (ACE) inhibitor exposure and the risk for overall major congenital, cardiac, and central nervous system (CNS) malformations. Methods We used a cohort of completed pregnancies linked to liveborn infants derived from Medicaid claims from 2000 to 2010. We examined the risk of malformations associated with first-trimester exposure to an ACE inhibitor. Propensity score based methods were used to control for potential confounders including maternal demographics, medical conditions, exposure to other medications, and measures of health care utilization. Results The cohort included 1,333,624 pregnancies, of which 4,107 (0.31%) were exposed to ACE inhibitors during the first trimester. The prevalence of overall malformations in the ACE inhibitor–exposed was 5.9% versus 3.3% in the unexposed (unadjusted relative risk (RR), 1.82; 95% confidence interval (CI) 1.61 to 2.06), of cardiac malformations was 3.4% versus 1.2% (RR 2.95; 95% CI 2.50 to 3.47), and of CNS malformations was 0.27% versus 0.18% (RR 1.46; 95% CI 0.81 to 2.64). After restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk for any of the outcomes assessed. Relative risks associated with first-trimester ACE inhibitor exposure were 0.89 (95% CI 0.75 to 1.06) for overall malformations, 0.95 (95% CI 0.75 to 1.21) for cardiac malformations, and 0.54 (95% CI 0.26 to 1.11) for CNS malformations. Conclusions After accounting for confounders, among women with hypertension, exposure to ACE inhibitors during the first trimester was not associated with an increased risk of major congenital malformations. PMID:27926639

Slide tracheoplasty outcomes in children with congenital pulmonary malformations.

PubMed

DeMarcantonio, Michael A; Hart, Catherine K; Yang, Christina J; Tabangin, Meredith; Rutter, Michael J; Bryant, Roosevelt; Manning, Peter B; de Alarcón, Alessandro

2017-06-01

Evaluate and compare surgical outcomes of slide tracheoplasty for the treatment of congenital tracheal stenosis in children with and without pulmonary malformations. Retrospective chart review at a tertiary care pediatric medical center. We identified patients with tracheal stenosis who underwent slide tracheoplasty from 2001 to 2014, and a subset of these patients who were diagnosed with congenital pulmonary malformations. Hospital course and preoperative and postoperative complications were recorded. One hundred thirty patients (18 with pulmonary malformations, 112 with normal pulmonary anatomy) were included. Pulmonary malformations included unilateral pulmonary agenesis (61%) and hypoplasia (39%). Children with pulmonary malformations had a greater median age compared to their normal lung anatomy counterparts. Preoperatively, patients with pulmonary malformations more frequently required preoperative mechanical ventilation (55.6% vs. 21.3%, P = .007), extracorporeal membrane oxygenation (ECMO) (11% vs. 0.9%, P = .05), and tracheostomy (22.2% vs. 3.6%, P = .01). Postoperatively, patients with pulmonary malformations more frequently required mechanical ventilation >48 hours (78% vs. 37%, P =.005) and ECMO use (11% vs. 0.9%, P = .05). Pulmonary malformation patients and children with normal anatomy did not differ in terms of postoperative tracheostomy (16.7% vs. 4.4%, P > .05), dehiscence (6% vs. 0%, P > .05%), restenosis (11% vs. 6%, P > .05) or postoperative figure 8 deformity (6% vs. 3%, P > .05). Mortality, however, was significantly increased (22.2% vs. 3.6%, P = .01) in children with pulmonary malformations. Although slide tracheoplasty can be successfully performed in patients with abnormal pulmonary anatomy, surgeons and families should anticipate a more difficult postoperative course, with possible associated prolonged mechanical ventilation, ECMO use, and higher mortality than in children with tracheal stenosis alone. 4. Laryngoscope, 127:1283-1287, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

[Characteristics of pregnancy and delivery of fetuses affected by either central nervous system malformations or chromosomal abnormalities].

PubMed

Friedler, Jordana Mashiach; Mazor, Moshe; Shoham-Vardi, Ilana; Bashiri, Asher

2011-11-01

To determine whether fetuses affected by either chromosomal abnormalities or central nervous system (CNS) malformations are prone to complications during pregnancy and delivery. In this study, 320 singleton pregnancies with CNS malformations and 133 singleton pregnancies with chromosomal abnormaLities were compared with 149,112 singleton births without any known congenital anomalies. Exclusion criteria were: births with other congenital anomalies or malformations, pregnancies Lacking prenatal care and multiple pregnancies. Data was obtained using the computerized birth discharge records. The statistical analysis was performed with the SPSS package. There were no statistically significant differences in maternal age, ethnicity, uterine anomalies or parity. The ratio of general anesthesia was almost double in the study groups compared to the control group: 25% in the CNS malformation group (RR 2.617, CI 2.031-3.372) and 25.6% in the chromosomal abnormality group (RR 2.696, CI 1.825-3.982) and 11.3% in the control group (p < 0.001). There were nearly double cesarean sections (CS) rates in both study groups: 21.5% in the CNS malformation group, 20.3% in the chromosomal abnormaLity group and 12% in the control group. A logistic regression model that included previous CS, maLpresentation, non-reassuring fetal heart monitor (NRFHR) and presence of a malformation, concluded that the presence of a malformation was not an independent risk factor for CS. However, indirect causes, such as malpresentation (4.34 OR), were independently associated with the malformations. Fetuses affected by either CNS malformations or chromosomal abnormalities have a higher rate of pregnancy and delivery complications, including those which increase the risk of maternal morbidity and mortality.

Angiotensin-Converting Enzyme Inhibitors and the Risk of Congenital Malformations.

PubMed

Bateman, Brian T; Patorno, Elisabetta; Desai, Rishi J; Seely, Ellen W; Mogun, Helen; Dejene, Sara Z; Fischer, Michael A; Friedman, Alexander M; Hernandez-Diaz, Sonia; Huybrechts, Krista F

2017-01-01

To examine the association between first-trimester angiotensin-converting enzyme (ACE) inhibitor exposure and the risk of overall major congenital, cardiac, and central nervous system malformations. We used a cohort of completed pregnancies linked to liveborn neonates derived from Medicaid claims from 2000 to 2010. We examined the risk of malformations associated with first-trimester exposure to an ACE inhibitor. Propensity score-based methods were used to control for potential confounders including maternal demographics, medical conditions, exposure to other medications, and measures of health care utilization. The cohort included 1,333,624 pregnancies, of which 4,107 (0.31%) were exposed to ACE inhibitors during the first trimester. The prevalence of overall malformations in the ACE inhibitor-exposed pregnancies was 5.9% compared with 3.3% in the unexposed (unadjusted relative risk, 1.82; 95% confidence interval [CI] 1.61-2.06), of cardiac malformations was 3.4% compared with 1.2% (relative risk 2.95, 95% CI 2.50-3.47), and of central nervous system malformations was 0.27% compared with 0.18% (relative risk 1.46, 95% CI 0.81-2.64). After restricting the cohort to pregnancies complicated by chronic hypertension (both exposed and unexposed) and accounting for other confounding factors, there was no significant increase in the risk of any of the outcomes assessed. Relative risks associated with first-trimester ACE inhibitor exposure were 0.89 (95% CI 0.75-1.06) for overall malformations, 0.95 (95% CI 0.75-1.21) for cardiac malformations, and 0.54 (95% CI 0.26-1.11) for CNS malformations. After accounting for confounders, among women with hypertension, exposure to ACE inhibitors during the first trimester was not associated with an increased risk of major congenital malformations.

Description of 13 Infants Born During October 2015-January 2016 With Congenital Zika Virus Infection Without Microcephaly at Birth - Brazil.

PubMed

van der Linden, Vanessa; Pessoa, André; Dobyns, William; Barkovich, A James; Júnior, Hélio van der Linden; Filho, Epitacio Leite Rolim; Ribeiro, Erlane Marques; Leal, Mariana de Carvalho; Coimbra, Pablo Picasso de Araújo; Aragão, Maria de Fátima Viana Vasco; Verçosa, Islane; Ventura, Camila; Ramos, Regina Coeli; Cruz, Danielle Di Cavalcanti Sousa; Cordeiro, Marli Tenório; Mota, Vivian Maria Ribeiro; Dott, Mary; Hillard, Christina; Moore, Cynthia A

2016-12-02

Congenital Zika virus infection can cause microcephaly and severe brain abnormalities (1). Congenital Zika syndrome comprises a spectrum of clinical features (2); however, as is the case with most newly recognized teratogens, the earliest documented clinical presentation is expected to be the most severe. Initial descriptions of the effects of in utero Zika virus infection centered prominently on the finding of congenital microcephaly (3). To assess the possibility of clinical presentations that do not include congenital microcephaly, a retrospective assessment of 13 infants from the Brazilian states of Pernambuco and Ceará with normal head size at birth and laboratory evidence of congenital Zika virus infection was conducted. All infants had brain abnormalities on neuroimaging consistent with congenital Zika syndrome, including decreased brain volume, ventriculomegaly, subcortical calcifications, and cortical malformations. The earliest evaluation occurred on the second day of life. Among all infants, head growth was documented to have decelerated as early as 5 months of age, and 11 infants had microcephaly. These findings provide evidence that among infants with prenatal exposure to Zika virus, the absence of microcephaly at birth does not exclude congenital Zika virus infection or the presence of Zika-related brain and other abnormalities. These findings support the recommendation for comprehensive medical and developmental follow-up of infants exposed to Zika virus prenatally. Early neuroimaging might identify brain abnormalities related to congenital Zika infection even among infants with a normal head circumference (4).

European consensus conference on unruptured brain AVMs treatment (Supported by EANS, ESMINT, EGKS, and SINCH).

PubMed

Cenzato, Marco; Boccardi, Edoardo; Beghi, Ettore; Vajkoczy, Peter; Szikora, Istvan; Motti, Enrico; Regli, Luca; Raabe, Andreas; Eliava, Shalva; Gruber, Andreas; Meling, Torstein R; Niemela, Mika; Pasqualin, Alberto; Golanov, Andrey; Karlsson, Bengt; Kemeny, Andras; Liscak, Roman; Lippitz, Bodo; Radatz, Matthias; La Camera, Alessandro; Chapot, René; Islak, Civan; Spelle, Laurent; Debernardi, Alberto; Agostoni, Elio; Revay, Martina; Morgan, Michael K

2017-06-01

In December of 2016, a Consensus Conference on unruptured AVM treatment, involving 24 members of the three European societies dealing with the treatment of cerebral AVMs (EANS, ESMINT, and EGKS) was held in Milan, Italy. The panel made the following statements and general recommendations: (1) Brain arteriovenous malformation (AVM) is a complex disease associated with potentially severe natural history; (2) The results of a randomized trial (ARUBA) cannot be applied equally for all unruptured brain arteriovenous malformation (uBAVM) and for all treatment modalities; (3) Considering the multiple treatment modalities available, patients with uBAVMs should be evaluated by an interdisciplinary neurovascular team consisting of neurosurgeons, neurointerventionalists, radiosurgeons, and neurologists experienced in the diagnosis and treatment of brain AVM; (4) Balancing the risk of hemorrhage and the associated restrictions of everyday activities related to untreated unruptured AVMs against the risk of treatment, there are sufficient indications to treat unruptured AVMs grade 1 and 2 (Spetzler-Martin); (5) There may be indications for treating patients with higher grades, based on a case-to-case consensus decision of the experienced team; (6) If treatment is indicated, the primary strategy should be defined by the multidisciplinary team prior to the beginning of the treatment and should aim at complete eradication of the uBAVM; (7) After having considered the pros and cons of a randomized trial vs. a registry, the panel proposed a prospective European Multidisciplinary Registry.

The history of female genital tract malformation classifications and proposal of an updated system.

PubMed

Acién, Pedro; Acién, Maribel I

2011-01-01

A correct classification of malformations of the female genital tract is essential to prevent unnecessary and inadequate surgical operations and to compare reproductive results. An ideal classification system should be based on aetiopathogenesis and should suggest the appropriate therapeutic strategy. We conducted a systematic review of relevant articles found in PubMed, Scopus, Scirus and ISI webknowledge, and analysis of historical collections of 'female genital malformations' and 'classifications'. Of 124 full-text articles assessed for eligibility, 64 were included because they contained original general, partial or modified classifications. All the existing classifications were analysed and grouped. The unification of terms and concepts was also analysed. Traditionally, malformations of the female genital tract have been catalogued and classified as Müllerian malformations due to agenesis, lack of fusion, the absence of resorption and lack of posterior development of the Müllerian ducts. The American Fertility Society classification of the late 1980s included seven basic groups of malformations also considering the Müllerian development and the relationship of the malformations to fertility. Other classifications are based on different aspects: functional, defects in vertical fusion, embryological or anatomical (Vagina, Cervix, Uterus, Adnex and Associated Malformation: VCUAM classification). However, an embryological-clinical classification system seems to be the most appropriate. Accepting the need for a new classification system of genitourinary malformations that considers the experience gained from the application of the current classification systems, the aetiopathogenesis and that also suggests the appropriate treatment, we proposed an update of our embryological-clinical classification as a new system with six groups of female genitourinary anomalies.

[The case of completed pregnancy of the patient with Dandy-Walker malformation].

PubMed

Beliaeva, E V; Lapshina, L V; Shaposhnikova, E V; Molgachev, A A

2018-01-01

Dandy-Walker malformation is a rare disease of the central nervous system pathology (congenital malformations of the fossa cranii posterior). The key features of this syndrome are an enlargement of the fourth ventricle; complete absence of the cerebellar vermis, the posterior midline area of cerebellar cortex responsible for coordination of the axial musculature; and cyst formation near the internal base of the skull. Pregnant patients with Dandy-Walker malformation are at high risk and are managed by multidisciplinary teams including neurologists and obstetricians. We present a case report of full-term pregnancy and uncomplicated delivery in a women with Dandy-Walker malformation.

The Battle for Richard Lapointe's Life.

ERIC Educational Resources Information Center

Perske, Robert

1996-01-01

This narrative describes the case of Richard Lapointe, a man with Dandy-Walker syndrome (a congenital brain malformation resulting in a build-up of cerebrospinal fluid in the skull), who was accused of homicide. The questionable practices of the police in acquiring a confession are recounted. The narrative discusses the court appeals process and…

Stroke-Related Translational Research

PubMed Central

Caplan, Louis R.; Arenillas, Juan; Cramer, Steven C.; Joutel, Anne; Lo, Eng H.; Meschia, James; Savitz, Sean; Tournier-Lasserve, Elizabeth

2013-01-01

Stroke-related translational research is multifaceted. Herein, we highlight genome-wide association studies and genetic studies of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy, COL4A1 mutations, and cerebral cavernous malformations; advances in molecular biology and biomarkers; newer brain imaging research; and recovery from stroke emphasizing cell-based and other rehabilitative modalities. PMID:21555605

[Expansive suboccipital cranioplasty in Chiari 1 malformation (a case report and technical notes)].

PubMed

Korshunov, A E; Kushel', Yu V

In this case report, we describe the use of expansive suboccipital cranioplasty in Chiari-1 malformation. The technique improves the efficacy and safety of treatment for Chiari-1 malformation. The technique can be used as an adjunct treatment together with any variant of posterior fossa decompression, including duroplasty and extradural decompression.

Genetically induced abnormal cranial development in human trisomy 18 with holoprosencephaly: comparisons with the normal tempo of osteogenic-neural development.

PubMed

Reid, Shaina N; Ziermann, Janine M; Gondré-Lewis, Marjorie C

2015-07-01

Craniofacial malformations are common congenital defects caused by failed midline inductive signals. These midline defects are associated with exposure of the fetus to exogenous teratogens and with inborn genetic errors such as those found in Down, Patau, Edwards' and Smith-Lemli-Opitz syndromes. Yet, there are no studies that analyze contributions of synchronous neurocranial and neural development in these disorders. Here we present the first in-depth analysis of malformations of the basicranium of a holoprosencephalic (HPE) trisomy 18 (T18; Edwards' syndrome) fetus with synophthalmic cyclopia and alobar HPE. With a combination of traditional gross dissection and state-of-the-art computed tomography, we demonstrate the deleterious effects of T18 caused by a translocation at 18p11.31. Bony features included a single developmentally unseparated frontal bone, and complete dual absence of the anterior cranial fossa and ethmoid bone. From a superior view with the calvarium plates removed, there was direct visual access to the orbital foramen and hard palate. Both the eyes and the pituitary gland, normally protected by bony structures, were exposed in the cranial cavity and in direct contact with the brain. The middle cranial fossa was shifted anteriorly, and foramina were either missing or displaced to an abnormal location due to the absence or misplacement of its respective cranial nerve (CN). When CN development was conserved in its induction and placement, the respective foramen developed in its normal location albeit with abnormal gross anatomical features, as seen in the facial nerve (CNVII) and the internal acoustic meatus. More anteriorly localized CNs and their foramina were absent or heavily disrupted compared with posterior ones. The severe malformations exhibited in the cranial fossae, orbital region, pituitary gland and sella turcica highlight the crucial involvement of transcription factors such as TGIF, which is located on chromosome 18 and contributes to neural patterning, in the proper development of neural and cranial structures. Our study of a T18 specimen emphasizes the intricate interplay between bone and brain development in midline craniofacial abnormalities in general. © 2015 Anatomical Society.

Orbital exenteration after transarterial embolization in a patient with Wyburn-Mason syndrome: pathological findings.

PubMed

Matsuo, Toshihiko; Yanai, Hiroyuki; Sugiu, Kenji; Tominaga, Susumu; Kimata, Yoshihiro

2008-01-01

We present the pathological findings at orbital exenteration in a patient with Wyburn-Mason syndrome who underwent transarterial embolization. A 31-year-old man with a 10-year history of gradual exacerbation of left exophthalmos and left cheek swelling was found to have facial and orbital arteriovenous malformations on the left side. There was no vascular malformation in the brain. The feeding arteries derived from the left internal maxillary artery, facial artery, and ophthalmic artery. He underwent several courses of transarterial embolization of the feeding arteries from the left internal maxillary artery and then from the facial artery, resulting in no reduction of the arteriovenous malformation. He finally elected to undergo ophthalmic artery embolization in the expectation of a reduction and with the understanding that he would lose sight in his left eye. Two years later, he requested lid-sparing orbital exenteration and reconstruction with cutaneous flap transfer and prosthesis for cosmetic reasons. Pathologically, orbital vascular channels of varying sizes were filled with embolizing glue and had degenerating vascular wall cells surrounded by inflammatory cell infiltration. The central retinal artery in the optic nerve was also filled with the embolizing glue, and the retina lost the ganglion cell layer and inner nuclear layer but maintained the outer nuclear layer and outer segments. Marked anastomoses and hence incomplete embolization among the feeding arteries of facial and orbital vascular malformations in Wyburn-Mason syndrome do not respond well to attempts at feeding vessel embolization, which result in unsuccessful closure of the malformation.

The TRAP (twin reversed arterial perfusion) sequence - case presentation.

PubMed

Mărginean, Claudiu; Mărginean, Maria Oana; Mureşan, Daniel; Zahiu, LuminiŢa; Horváth, Emőke

2016-01-01

We present a particular case of TRAP (twin reversed arterial perfusion) syndrome, which has a very rarely association of the simultaneous existence of a rudimentary malformed heart and brain, and also other malformations like abdominal wall abnormality, absent bladder with present kidneys, and absence of the lungs, which appear only in a few cases on the receptor twin from this sequence, malformations incompatible with life. A Caucasian 26-year-old pregnant woman, at the first pregnancy, with a monochorionic-diamniotic pregnancy, 26 weeks of gestation was referred to our hospital, for polyhydramnios. The patient delivered a living female newborn, weighing 950 g, with an Apgar score of 2 at one minute - the donor fetus and a second female newborn with multiple malformations, no signs of life and who weighed 2300 g - the receptor fetus. The anatomopathological examination confirmed the TRAP sequence associated with severe facial dysmorphism, bilateral phocomelia and cardiac malformations (rudimentary hypoplastic, univentricular) and a vascular anastomosis between the two umbilical cords. Anemia and cardiac complications which can lead to cardiac failure, appear early during pregnancy and caused the death of the pumping twin. We emphasize that in our case of TRAP sequence, the ultrasound examination established the diagnosis of the syndrome with high accuracy. Therefore, we can conclude that the existence of a rudimentary heart and a vascular anastomosis between the two umbilical cords supports the apparition of TRAP sequence. The early diagnosis of this pathology, the observation of the pregnancy with the help of weekly ultrasounds and the intrauterine interventions can increase the survival chances of the donor fetus from the TRAP sequence.

Congenital heart defects and extracardiac malformations.

PubMed

Rosa, Rosana Cardoso M; Rosa, Rafael Fabiano M; Zen, Paulo Ricardo G; Paskulin, Giorgio Adriano

2013-06-01

To review the association between congenital heart defects and extracardiac malformations. Scientific articles were searched in the Medline, Lilacs, and SciELO databases, using the descriptors "congenital heart disease," "congenital heart defects," "congenital cardiac malformations," "extracardiac defects," and "extracardiac malformations." All case series that specifically explored the association between congenital heart defects and extracardiac malformations were included. Congenital heart diseases are responsible for about 40% of birth defects, being one of the most common and severe malformations. Extracardiac malformations are observed in 7 to 50% of the patients with congenital heart disease, bringing a greater risk of comorbidity and mortality and increasing the risks related to heart surgery. Different studies have attempted to assess the presence of extracardiac abnormalities in patients with congenital heart disease. Among the changes described, those of the urinary tract are more often reported. However, no study has evaluated all patients in the same way. Extracardiac abnormalities are frequent among patients with congenital heart disease, and patients with these alterations may present an increased risk of morbimortality. Therefore, some authors have been discussing the importance and cost-effectiveness of screening these children for other malformations by complementary exams.

Impact on cognitive functions following gamma knife radiosurgery for cerebral arteriovenous malformations

PubMed Central

Raghunath, A.; Bennett, Niranjana; Arimappamagan, Arivazhagan; Bhat, Dhananjaya I.; Srinivas, Dwarakanath; Thennarasu, K.; Jamuna, R.; Somanna, Sampath

2016-01-01

Background: Radiosurgery is an alternative to surgical resection of arteriovenous malformation (AVM). Very few studies have addressed the concern of radiation injury to the brain and its attendant adverse effects on cognitive function. Materials and Methods: This prospective study included all patients who underwent gamma knife radiosurgery (GKRS) at our institute for cerebral AVM between 2006 and December 2008 (n = 34). All patients underwent neuropsychological evaluation before the procedure. Neuropsychological evaluation was repeated in eighteen patients 2 years following GKRS. Clinical outcome, AVM obliteration, and factors influencing outcome were analyzed in these eighteen patients. Results: Before GKRS, more than 50% had significant impairment of neuropsychological functions compared to normal population norms. 66.6% achieved the excellent radiosurgical outcome. At 2 years follow-up, patients showed varied improvement in neuropsychological function in various categories. Pretherapeutic median value for percentage perseverative responses was 26.5 and at follow-up, it reduced to 18.2 (P = 0.039). Set shifting improved in 11 patients (61.1%), remained same in 5 patients (27.7%), and deteriorated in two patients (11.1%). Patients with a higher Spetzler-Martin grade AVM demonstrated a significantly more favorable shift in follow-up test values for set shifting function (P = 0.021). Patients with postradiation imaging changes had lesser tendency to improve in neuropsychological performance at follow-up. Conclusions: GKRS has no clinically harmful effect on cognitive and neuropsychological functioning in patients with brain AVM. On the contrary, there is an improvement in majority of patients at 2 years following radiosurgery when nidus is obliterated. PMID:26933340

Safety and efficacy of endovascular therapy and gamma knife surgery for brain arteriovenous malformations in China: Study protocol for an observational clinical trial.

PubMed

Jin, Hengwei; Huo, Xiaochuan; Jiang, Yuhua; Li, Xiaolong; Li, Youxiang

2017-09-01

Brain arteriovenous malformations (BAVMs) are associated with high morbidity and mortality. The treatment of BAVM remains controversial. Microinvasive treatment, including endovascular therapy and gamma knife surgery, has been the first choice in many conditions. However, the overall clinical outcome of microinvasive treatment remains unknown and a prospective trial is needed. This is a prospective, non-randomized, and multicenter observational registry clinical trial to evaluate the safety and efficacy of microinvasive treatment for BAVMs. The study will require up to 400 patients in approximately 12 or more centers in China, followed for 2 years. Main subjects of this study are BAVM patients underwent endovascular therapy and/or gamma knife surgery. The trial will not affect the choice of treatment modality. The primary outcomes are perioperative complications (safety), and postoperative hemorrhage incidence rate and complete occlusion rate (efficacy). Secondary outcomes are elimination of hemorrhage risk factors (coexisting aneurysms and arteriovenous fistula), volume reduction and remission of symptoms. Safety and efficacy of endovascular therapy, gamma knife surgery, and various combination modes of the two modalities will be compared. Operative complications and outcomes at pretreatment, post-treatment, at discharge and at 3 months, 6 months and 2 years follow-up intervals will be analyzed using the modified Rankin Scale (mRS). The most confusion on BAVM treatment is whether to choose interventional therapy or medical therapy, and the choice of interventional therapy modes. This study will provide evidence for evaluating the safety and efficacy of microinvasive treatment in China, to characterize the microinvasive treatment strategy for BAVMs.

Thalamic Massa Intermedia Duplication in a Dysmorphic 14 month-old Toddler.

PubMed

Whitehead, Matthew T

2015-06-01

The massa intermedia is an inconstant parenchymal band connecting the medial thalami. It may be thickened in various disease processes such as Chiari II malformation or absent in other disease states. However, the massa intermedia may also be absent in up to 30% of normal human brains. To the best of my knowledge, detailed imaging findings of massa intermedia duplication have only been described in a single case report. An additional case of thalamic massa intermedia duplication discovered on a routine brain MR performed for dysmorphic facial features is reported herein.

In utero negativization of Zika virus in a foetus with serious central nervous system abnormalities.

PubMed

Rodó, C; Suy, A; Sulleiro, E; Soriano-Arandes, A; Antón, A; García-Ruiz, I; Arévalo, S; Vázquez, É; Vázquez, A; de Ory, F; Sánchez-Seco, M P; Rodrigo, C; Pumarola, T; Carreras, E

2018-05-01

We describe a case of a pregnant woman with Zika virus (ZIKV) infection and a foetus with severe brain malformations. ZIKV tested positive in amniotic fluid at 19 weeks but was negative at delivery. The newborn did not meet the case definition of congenital ZIKV syndrome because neither ZIKV RNA nor IgM antibodies were detected; however, prenatal brain lesions were confirmed after birth (Graphical Abstract). Copyright © 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

[Coexistence of female sexual organ malformation and urinary tract anomalies].

PubMed

Rzymski, P; Szpakowska-Rzymska, I; el Yubi, R; Wilczak, M; Sajdak, S; Opala, T

2001-02-01

The aim of the study was to estimate the correlation between sexual organs and urinary tract malformation. The retrospective analysis of clinical data obtained from 50 patients with sexual organs anomalies diagnosed in the Academic Gynaecological Centre between 1992-1999 was performed. Material included 24 patients with the Meyer-Rokitansky-Küster-Hauser syndrome and 26 with other sexual organs' malformations. Frequency of urinary tract anomalies was 42%, 11 patients with Meyer-Rokitansky-Küster-Hauser syndrome and 11 with other malformations. The gravity of urinary tract anomalies showed no statistical significant difference dependent on the type and symmetry of genital malformation. Urinary tract anomalies were more frequent in cases of asymmetric genital malformation and the difference was statistically significant. Intravenous urography proofed to be more sensitive than ultrasonography in diagnosing urinary tract anomalies.

Classification of Newborn Ear Malformations and their Treatment with the EarWell Infant Ear Correction System.

PubMed

Daniali, Lily N; Rezzadeh, Kameron; Shell, Cheryl; Trovato, Matthew; Ha, Richard; Byrd, H Steve

2017-03-01

A single practice's treatment protocol and outcomes following molding therapy on newborn ear deformations and malformations with the EarWell Infant Ear Correction System were reviewed. A classification system for grading the severity of constricted ear malformations was created on the basis of anatomical findings. A retrospective chart/photograph review of a consecutive series of infants treated with the EarWell System from 2011 to 2014 was undertaken. The infants were placed in either deformation or malformation groups. Three classes of malformation were identified. Data regarding treatment induction, duration of treatment, and quality of outcome were collected for all study patients. One hundred seventy-five infant ear malformations and 303 infant ear deformities were treated with the EarWell System. The average age at initiation of treatment was 12 days; the mean duration of treatment was 37 days. An average of six office visits was required. Treated malformations included constricted ears [172 ears (98 percent)] and cryptotia [three ears (2 percent)]. Cup ear (34 ears) was considered a constricted malformation, in contrast to the prominent ear deformity. Constricted ears were assigned to one of three classes, with each subsequent class indicating increasing severity: class I, 77 ears (45 percent); class II, 81 ears (47 percent); and class III, 14 ears (8 percent). Molding therapy with the EarWell System reduced the severity by an average of 1.2 points (p < 0.01). Complications included minor superficial excoriations and abrasions. The EarWell System was shown to be effective in eliminating or reducing the need for surgery in all but the most severe malformations. Therapeutic, IV.

Deformed Skull Morphology Is Caused by the Combined Effects of the Maldevelopment of Calvarias, Cranial Base and Brain in FGFR2-P253R Mice Mimicking Human Apert Syndrome

PubMed Central

Luo, Fengtao; Xie, Yangli; Xu, Wei; Huang, Junlan; Zhou, Siru; Wang, Zuqiang; Luo, Xiaoqing; Liu, Mi; Chen, Lin; Du, Xiaolan

2017-01-01

Apert syndrome (AS) is a common genetic syndrome in humans characterized with craniosynostosis. Apert patients and mouse models showed abnormalities in sutures, cranial base and brain, that may all be involved in the pathogenesis of skull malformation of Apert syndrome. To distinguish the differential roles of these components of head in the pathogenesis of the abnormal skull morphology of AS, we generated mouse strains specifically expressing mutant FGFR2 in chondrocytes, osteoblasts, and progenitor cells of central nervous system (CNS) by crossing Fgfr2+/P253R-Neo mice with Col2a1-Cre, Osteocalcin-Cre (OC-Cre), and Nestin-Cre mice, respectively. We then quantitatively analyzed the skull and brain morphology of these mutant mice by micro-CT and micro-MRI using Euclidean distance matrix analysis (EDMA). Skulls of Col2a1-Fgfr2+/P253R mice showed Apert syndrome-like dysmorphology, such as shortened skull dimensions along the rostrocaudal axis, shortened nasal bone, and evidently advanced ossification of cranial base synchondroses. The OC-Fgfr2+/P253R mice showed malformation in face at 8-week stage. Nestin-Fgfr2+/P253R mice exhibited increased dorsoventral height and rostrocaudal length on the caudal skull and brain at 8 weeks. Our study indicates that the abnormal skull morphology of AS is caused by the combined effects of the maldevelopment in calvarias, cranial base, and brain tissue. These findings further deepen our knowledge about the pathogenesis of the abnormal skull morphology of AS, and provide new clues for the further analyses of skull phenotypes and clinical management of AS. PMID:28123344

Deformed Skull Morphology Is Caused by the Combined Effects of the Maldevelopment of Calvarias, Cranial Base and Brain in FGFR2-P253R Mice Mimicking Human Apert Syndrome.

PubMed

Luo, Fengtao; Xie, Yangli; Xu, Wei; Huang, Junlan; Zhou, Siru; Wang, Zuqiang; Luo, Xiaoqing; Liu, Mi; Chen, Lin; Du, Xiaolan

2017-01-01

Apert syndrome (AS) is a common genetic syndrome in humans characterized with craniosynostosis. Apert patients and mouse models showed abnormalities in sutures, cranial base and brain, that may all be involved in the pathogenesis of skull malformation of Apert syndrome. To distinguish the differential roles of these components of head in the pathogenesis of the abnormal skull morphology of AS, we generated mouse strains specifically expressing mutant FGFR2 in chondrocytes, osteoblasts, and progenitor cells of central nervous system (CNS) by crossing Fgfr2 +/P253R-Neo mice with Col2a1-Cre, Osteocalcin-Cre (OC-Cre), and Nestin-Cre mice, respectively. We then quantitatively analyzed the skull and brain morphology of these mutant mice by micro-CT and micro-MRI using Euclidean distance matrix analysis (EDMA). Skulls of Col2a1-Fgfr2 +/P253R mice showed Apert syndrome-like dysmorphology, such as shortened skull dimensions along the rostrocaudal axis, shortened nasal bone, and evidently advanced ossification of cranial base synchondroses. The OC-Fgfr2 +/P253R mice showed malformation in face at 8-week stage. Nestin-Fgfr2 +/P253R mice exhibited increased dorsoventral height and rostrocaudal length on the caudal skull and brain at 8 weeks. Our study indicates that the abnormal skull morphology of AS is caused by the combined effects of the maldevelopment in calvarias, cranial base, and brain tissue. These findings further deepen our knowledge about the pathogenesis of the abnormal skull morphology of AS, and provide new clues for the further analyses of skull phenotypes and clinical management of AS.

Planning Evaluation of C-Arm Cone Beam CT Angiography for Target Delineation in Stereotactic Radiation Surgery of Brain Arteriovenous Malformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kang, Jun; Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland; Huang, Judy

Purpose: Stereotactic radiation surgery (SRS) is one of the therapeutic modalities currently available to treat cerebral arteriovenous malformations (AVM). Conventionally, magnetic resonance imaging (MRI) and MR angiography (MRA) and digital subtraction angiography (DSA) are used in combination to identify the target volume for SRS treatment. The purpose of this study was to evaluate the use of C-arm cone beam computed tomography (CBCT) in the treatment planning of SRS for cerebral AVMs. Methods and Materials: Sixteen consecutive patients treated for brain AVMs at our institution were included in this retrospective study. Prior to treatment, all patients underwent MRA, DSA, and C-arm CBCT.more » All images were coregistered using the GammaPlan planning system. AVM regions were delineated independently by 2 physicians using either C-arm CBCT or MRA, resulting in 2 volumes: a CBCT volume (VCBCT) and an MRA volume (V{sub MRA}). SRS plans were generated based on the delineated regions. Results: The average volume of treatment targets delineated using C-arm CBCT and MRA were similar, 6.40 cm{sup 3} and 6.98 cm{sup 3}, respectively (P=.82). However, significant regions of nonoverlap existed. On average, the overlap of the MRA with the C-arm CBCT was only 52.8% of the total volume. In most cases, radiation plans based on V{sub MRA} did not provide adequate dose to the region identified on C-arm CBCT; the mean minimum dose to V{sub CBCT} was 29.5%, whereas the intended goal was 45% (P<.001). The mean volume of normal brain receiving 12 Gy or more in C-arm CBCT-based plans was not greater than in the MRA-based plans. Conclusions: Use of C-arm CBCT images significantly alters the delineated regions of AVMs for SRS planning, compared to that of MRA/MRI images. CT-based planning can be accomplished without increasing the dose to normal brain and may represent a more accurate definition of the nidus, increasing the chances for successful obliteration.« less

Color-coded perfusion analysis of CEUS for pre-interventional diagnosis of microvascularisation in cases of vascular malformations.

PubMed

Teusch, V I; Wohlgemuth, W A; Piehler, A P; Jung, E M

2014-01-01

Aim of our pilot study was the application of a contrast-enhanced color-coded ultrasound perfusion analysis in patients with vascular malformations to quantify microcirculatory alterations. 28 patients (16 female, 12 male, mean age 24.9 years) with high flow (n = 6) or slow-flow (n = 22) malformations were analyzed before intervention. An experienced examiner performed a color-coded Doppler sonography (CCDS) and a Power Doppler as well as a contrast-enhanced ultrasound after intravenous bolus injection of 1 - 2.4 ml of a second-generation ultrasound contrast medium (SonoVue®, Bracco, Milan). The contrast-enhanced examination was documented as a cine sequence over 60 s. The quantitative analysis based on color-coded contrast-enhanced ultrasound (CEUS) images included percentage peak enhancement (%peak), time to peak (TTP), area under the curve (AUC), and mean transit time (MTT). No side effects occurred after intravenous contrast injection. The mean %peak in arteriovenous malformations was almost twice as high as in slow-flow-malformations. The area under the curve was 4 times higher in arteriovenous malformations compared to the mean value of other malformations. The mean transit time was 1.4 times higher in high-flow-malformations compared to slow-flow-malformations. There was no difference regarding the time to peak between the different malformation types. The comparison between all vascular malformation and surrounding tissue showed statistically significant differences for all analyzed data (%peak, TTP, AUC, MTT; p < 0.01). High-flow and slow-flow vascular malformations had statistically significant differences in %peak (p < 0.01), AUC analysis (p < 0.01), and MTT (p < 0.05). Color-coded perfusion analysis of CEUS seems to be a promising technique for the dynamic assessment of microvasculature in vascular malformations.

Primary Human Placental Trophoblasts are Permissive for Zika Virus (ZIKV) Replication.

PubMed

Aagaard, Kjersti M; Lahon, Anismrita; Suter, Melissa A; Arya, Ravi P; Seferovic, Maxim D; Vogt, Megan B; Hu, Min; Stossi, Fabio; Mancini, Michael A; Harris, R Alan; Kahr, Maike; Eppes, Catherine; Rac, Martha; Belfort, Michael A; Park, Chun Shik; Lacorazza, Daniel; Rico-Hesse, Rebecca

2017-01-27

Zika virus (ZIKV) is an emerging mosquito-borne (Aedes genus) arbovirus of the Flaviviridae family. Although ZIKV has been predominately associated with a mild or asymptomatic dengue-like disease, its appearance in the Americas has been accompanied by a multi-fold increase in reported incidence of fetal microcephaly and brain malformations. The source and mode of vertical transmission from mother to fetus is presumptively transplacental, although a causal link explaining the interval delay between maternal symptoms and observed fetal malformations following infection has been missing. In this study, we show that primary human placental trophoblasts from non-exposed donors (n = 20) can be infected by primary passage ZIKV-FLR isolate, and uniquely allowed for ZIKV viral RNA replication when compared to dengue virus (DENV). Consistent with their being permissive for ZIKV infection, primary trophoblasts expressed multiple putative ZIKV cell entry receptors, and cellular function and differentiation were preserved. These findings suggest that ZIKV-FLR strain can replicate in human placental trophoblasts without host cell destruction, thereby serving as a likely permissive reservoir and portal of fetal transmission with risk of latent microcephaly and malformations.

Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III.

PubMed

Juric-Sekhar, Gordana; Kapur, Raj P; Glass, Ian A; Murray, Mitzi L; Parnell, Shawn E; Hevner, Robert F

2011-04-01

Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria-lissencephaly.

Flexible omnidirectional carbon dioxide laser as an effective tool for resection of brainstem, supratentorial, and intramedullary cavernous malformations.

PubMed

Choudhri, Omar; Karamchandani, Jason; Gooderham, Peter; Steinberg, Gary K

2014-03-01

Lasers have a long history in neurosurgery, yet bulky designs and difficult ergonomics limit their use. With its ease of manipulation and multiple applications, the OmniGuide CO2 laser has reintroduced laser technology to the microsurgical resection of brain and spine lesions. This laser, delivered through a hollow-core fiber lined with a unidirectional mirror, minimizes energy loss and allows precise targeting. To analyze resections performed by the senior author from April 2009 to March 2013 of 58 cavernous malformations (CMs) in the brain and spine with the use of the OmniGuide CO2 laser, to reflect on lessons learned from laser use in eloquent areas, and to share data on comparisons of laser power calibration and histopathology. Data were collected from electronic medical records, radiology reports, operative room records, OmniGuide CO2 laser case logs, and pathology records. Of 58 CMs, approximately 50% were in the brainstem (30) and the rest were in supratentorial (26) and intramedullary spinal locations (2). Fifty-seven, ranging from 5 to 45 mm, were resected, with a subtotal resection in 1. Laser power ranged from 2 to 10 W. Pathology specimens showed minimal thermal damage compared with traditionally resected specimens with bipolar coagulation. The OmniGuide CO2 laser is safe and has excellent precision for the resection of supratentorial, brainstem, and spinal intramedullary CMs. No laser-associated complications occurred, and very low energy was used to dissect malformations from their surrounding hemosiderin-stained parenchymas. The authors recommend its use for deep-seated and critically located CMs, along with traditional tools.

Congenital Malformations of the Central Nervous System in Rural Western Honduras: A 6-Year Report on Trends.

PubMed

Estevez-Ordonez, Dagoberto; Dewan, Michael C; Feldman, Michael J; Montalvan-Sanchez, Eleazar E; Montalvan-Sanchez, Daniela M; Rodriguez-Murillo, Aida A; Urrutia-Argueta, Samuel A; Cherry, Charlotte B; Morgan, Douglas R; Alvarez-Rodriguez, Roberto; Bonfield, Christopher M

2017-11-01

Central nervous system (CNS) malformations, including neural tube defects (NTDs), are the second most common type of birth defects worldwide and are major causes of childhood disability and mortality. We report the first analysis of birth prevalence in Western Honduras of CNS malformations including NTDs over 6 consecutive years. Data from all patients with congenital CNS malformations and total live births for the period 2010-2015 were obtained through institution and regional registries from all 3 public referral hospitals in Western Honduras, representing 67 municipalities. Cases were identified using the International Classification of Diseases, Tenth Revision CNS malformation codes. Birth prevalence was calculated as cases per 10,000 live births. From 123,903 live births, 275 cases of CNS malformations were identified (54% females, 58% NTDs). Six-year birth prevalence of CNS malformations was 13.9-31.1. Spina bifida variants and anencephaly represented 80% and 19% of reported NTDs, respectively. Total 6-year prevalence of NTDs in Western Honduras was 7.0-17.4 over years studied. In 6 municipalities, average prevalence was >30 (maximum 49.0). This is the first study reporting disease burden of CNS malformations in Western Honduras. The nationwide birth prevalence of NTDs in rural Honduras may have decreased since the implementation of prenatal health policies in 2005. However, we identified regions with unexpectedly elevated prevalence, indicating high regional prevalence that could be targeted for improved preventive efforts, ultimately decreasing the burden of these conditions. Copyright © 2017 Elsevier Inc. All rights reserved.

Signal quality of endovascular electroencephalography

NASA Astrophysics Data System (ADS)

He, Bryan D.; Ebrahimi, Mosalam; Palafox, Leon; Srinivasan, Lakshminarayan

2016-02-01

Objective, Approach. A growing number of prototypes for diagnosing and treating neurological and psychiatric diseases are predicated on access to high-quality brain signals, which typically requires surgically opening the skull. Where endovascular navigation previously transformed the treatment of cerebral vascular malformations, we now show that it can provide access to brain signals with substantially higher signal quality than scalp recordings. Main results. While endovascular signals were known to be larger in amplitude than scalp signals, our analysis in rabbits borrows a standard technique from communication theory to show endovascular signals also have up to 100× better signal-to-noise ratio. Significance. With a viable minimally-invasive path to high-quality brain signals, patients with brain diseases could one day receive potent electroceuticals through the bloodstream, in the course of a brief outpatient procedure.

Real-time imaging of de novo arteriovenous malformation in a mouse model of hereditary hemorrhagic telangiectasia

PubMed Central

Park, Sung Ok; Wankhede, Mamta; Lee, Young Jae; Choi, Eun-Jung; Fliess, Naime; Choe, Se-Woon; Oh, Seh-Hoon; Walter, Glenn; Raizada, Mohan K.; Sorg, Brian S.; Oh, S. Paul

2009-01-01

Arteriovenous malformations (AVMs) are vascular anomalies where arteries and veins are directly connected through a complex, tangled web of abnormal arteries and veins instead of a normal capillary network. AVMs in the brain, lung, and visceral organs, including the liver and gastrointestinal tract, result in considerable morbidity and mortality. AVMs are the underlying cause of three major clinical symptoms of a genetic vascular dysplasia termed hereditary hemorrhagic telangiectasia (HHT), which is characterized by recurrent nosebleeds, mucocutaneous telangiectases, and visceral AVMs and caused by mutations in one of several genes, including activin receptor–like kinase 1 (ALK1). It remains unknown why and how selective blood vessels form AVMs, and there have been technical limitations to observing the initial stages of AVM formation. Here we present in vivo evidence that physiological or environmental factors such as wounds in addition to the genetic ablation are required for Alk1-deficient vessels to develop to AVMs in adult mice. Using the dorsal skinfold window chamber system, we have demonstrated for what we believe to be the first time the entire course of AVM formation in subdermal blood vessels by using intravital bright-field images, hyperspectral imaging, fluorescence recordings of direct arterial flow through the AV shunts, and vascular casting techniques. We believe our data provide novel insights into the pathogenetic mechanisms of HHT and potential therapeutic approaches. PMID:19805914

Effects of Pollutants on Eggs, Embryos and Larvae of Amphibian Species

DTIC Science & Technology

1976-04-01

of octyl-phenyl-,- naphthylamine may retard the growth rate of tadpoles . However, histological study indicated that these animals were not malformed ...all embryos become malformed if treatment 6 begins prior to completion of neurulation. Embryos exposed to trypan blue after closure of the neural...folds are not affected. The syndrome of malformations exhibited includes microcephaly, tailessness, and re- duction of mesonephros (fig. 1). Lithium

Brain Stem Cavernous Malformations: Operative Nuances of a Less-Invasive Resection Technique.

PubMed

Singh, Harminder; Elarjani, Turki; da Silva, Harley Brito; Shetty, Rakshith; Kim, Louis; Sekhar, Laligam N

2017-12-08

Different operative techniques are reported for the resection of brainstem cavernous malformations (BSCMs). The senior author has previously reported on a less-invasive technique of entering the brain stem with piecemeal removal of BSCMs, especially the deep-seated ones. To present a larger series of these lesions, emphasizing the approach to the brain stem via case selection. We discuss the nuances of the less-invasive operative technique through case illustrations and intraoperative videos. A retrospective review of 46 consecutive cases of BSCMs, with their clinical and radiographic data, was performed. Nine cases were selected to illustrate 7 different operative approaches, and discuss surgical nuances of the less-invasive technique unique to each. Postoperative morbidity, defined as an increase in modified Rankin Scale, was observed in 5 patients (10.9%). A residual BSCM was present in 2 patients (4.3%); both underwent reoperation to remove the remainder. At follow-up of 31.1 ± 27.8 mo, 3 patients experienced recurrence (6.5%). Overall, 65% of our patients improved, 20% stayed the same, and 11% worsened postsurgery. Two patients died, yielding a mortality of 4.3%. Using the less-invasive resection technique for piecemeal BSCM removal, in appropriately selected patients, has yielded comparable to improved patient outcomes over existing large series. In our experience, lateral, anterolateral, and posterolateral approaches are favorable over direct midline (dorsal or ventral) approaches. A thorough understanding of brain-stem safe-entry zones, in conjunction with appropriate approach selection, is key to a good outcome in challenging cases. Copyright © 2017 by the Congress of Neurological Surgeons

Spatiotemporal Fractionation Schemes for Irradiating Large Cerebral Arteriovenous Malformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unkelbach, Jan, E-mail: junkelbach@mgh.harvard.edu; Bussière, Marc R.; Chapman, Paul H.

2016-07-01

Purpose: To optimally exploit fractionation effects in the context of radiosurgery treatments of large cerebral arteriovenous malformations (AVMs). In current practice, fractionated treatments divide the dose evenly into several fractions, which generally leads to low obliteration rates. In this work, we investigate the potential benefit of delivering distinct dose distributions in different fractions. Methods and Materials: Five patients with large cerebral AVMs were reviewed and replanned for intensity modulated arc therapy delivered with conventional photon beams. Treatment plans allowing for different dose distributions in all fractions were obtained by performing treatment plan optimization based on the cumulative biologically effective dosemore » delivered at the end of treatment. Results: We show that distinct treatment plans can be designed for different fractions, such that high single-fraction doses are delivered to complementary parts of the AVM. All plans create a similar dose bath in the surrounding normal brain and thereby exploit the fractionation effect. This partial hypofractionation in the AVM along with fractionation in normal brain achieves a net improvement of the therapeutic ratio. We show that a biological dose reduction of approximately 10% in the healthy brain can be achieved compared with reference treatment schedules that deliver the same dose distribution in all fractions. Conclusions: Boosting complementary parts of the target volume in different fractions may provide a therapeutic advantage in fractionated radiosurgery treatments of large cerebral AVMs. The strategy allows for a mean dose reduction in normal brain that may be valuable for a patient population with an otherwise normal life expectancy.« less

Prenatal diagnosis and molecular characterization of a novel locus for Dandy-Walker malformation on chromosome 7p21.3.

PubMed

Liao, Can; Fu, Fang; Li, Ru; Yang, Xin; Xu, Qing; Li, Dong-Zhi

2012-01-01

We present three foetuses with Dandy-Walker malformation, intra-uterine growth restriction and multiple congenital abnormalities, who were studied by array-based comparative genomic hybridization and revealed a novel locus on chromosome 7p21.3. The association of pure chromosome 7p aberrations with Dandy-Walker malformation has rarely been reported. The present study suggests that the critical region associated with Dandy-Walker malformation is restricted to 7p21.3, including the cerebellar disease associated genes NDUFA4 and PHF14. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Pathophysiological Responses in Rat and Mouse Models of Radiation-Induced Brain Injury.

PubMed

Yang, Lianhong; Yang, Jianhua; Li, Guoqian; Li, Yi; Wu, Rong; Cheng, Jinping; Tang, Yamei

2017-03-01

The brain is the major dose-limiting organ in patients undergoing radiotherapy for assorted conditions. Radiation-induced brain injury is common and mainly occurs in patients receiving radiotherapy for malignant head and neck tumors, arteriovenous malformations, or lung cancer-derived brain metastases. Nevertheless, the underlying mechanisms of radiation-induced brain injury are largely unknown. Although many treatment strategies are employed for affected individuals, the effects remain suboptimal. Accordingly, animal models are extremely important for elucidating pathogenic radiation-associated mechanisms and for developing more efficacious therapies. So far, models employing various animal species with different radiation dosages and fractions have been introduced to investigate the prevention, mechanisms, early detection, and management of radiation-induced brain injury. However, these models all have limitations, and none are widely accepted. This review summarizes the animal models currently set forth for studies of radiation-induced brain injury, especially rat and mouse, as well as radiation dosages, dose fractionation, and secondary pathophysiological responses.

[The scintigraphic 99mTc-MAA imaging quantification of the right-to-left shunt in a patients with multiple pulmonary arteriovenous malformation and familial teleangiectasis].

PubMed

Dolezal, J

2008-02-01

To present a case report about 57-years-old woman with hypoxemia, multiple pulmonary arteriovenous (AV) malformations and lips teleangiectasis where the right-to-left shunt quantification was assessed by means of whole body scintigraphy with 9mTc-labelled human macro-aggregated albumin (MAA). A 57-years-old woman underwent X-ray and bolus enhanced lung CT for dyspnoea, hypoxemia and cyanosis. A multiple intrapulmonary arteriovenous malformations were detected. The whole-body 99mTc-MAA scintigraphy for the right-to-left shunt quantification was performed. The whole-body scintigraphy in anterior and posterior view was started after intravenous application of 185 MBq 99mTc-MAA. The double-head gamma camera Infinia (General Electric Medical Systems--GE MS) with infrared body countouring and the large field of view was used. The Gamma camera was fitted with low-energy, high resolution, parallel-hole collimator. Images were evaluated by processing system Xeleris (GE MS). The whole-body 99mTc-MAA scintigraphy revealed significant R-L shunt and uptake of radiotracer in extrapulmonary organs (brain, kidney, spleen). The right-to-left shunt ratio was 36%. The woman underwent successful percutaneous transcatheter microembolization treatment. After treatment the woman underwent the next 99mTc-MAA whole-body scintigraphy and the R-L shunt ratio decreased to 17%. The 99mTc-MAA whole-body scintigraphy assessed the right-to-left shunt ratio and improved the management of patients with multiple intrapulmonary A-V malformations. The next 99mTc-MAA scintigraphy after the percutaneous transcatheter microembolization of multiple intrapulmonary A-V malformations confirmed success of treatment.

De Novo 3q22.3q24 Microdeletion in a Patient With Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome, Dandy-Walker Malformation, and Wisconsin Syndrome.

PubMed

Ramineni, Anand; Coman, David

2016-01-01

Interstitial deletions affecting the long arm of chromosome 3 have been associated with a broad phenotype. This has included the features of blepharophimosis-ptosis-epicanthus inversus syndrome, Dandy-Walker malformation, and the rare Wisconsin syndrome. The authors report a young female patient presenting with features consistent with all 3 of these syndromes. This has occurred in the context of a de novo 3q22.3q24 microdeletion including FOXL2 , ZIC1 , and ZIC4 . This patient provides further evidence for the role of ZIC1 and ZIC4 in Dandy-Walker malformation and is the third reported case of Dandy-Walker malformation to have associated corpus callosum thinning. This patient is also only the seventh to be reported with the rare Wisconsin syndrome phenotype.

Oral-facial-digital syndrome type 1 with hypothalamic hamartoma and Dandy-Walker malformation.

PubMed

Azukizawa, Takayuki; Yamamoto, Masahito; Narumiya, Seirou; Takano, Tomoyuki

2013-04-01

We report a 1-year-old girl with oral-facial-digital syndrome type 1 with multiple malformations of the oral cavity, face, digits, and central nervous system, including agenesis of the corpus callosum, the presence of intracerebral cysts, and agenesis of the cerebellar vermis, which is associated with the subarachnoid space separating the medial sides of the cerebellar hemispheres. This child also had a hypothalamic hamartoma and a Dandy-Walker malformation, which have not been reported previously. The clinical features, including cerebral malformations, in several types of oral-facial-digital syndrome, overlap with each other. Further accumulation of new case reports and identification of new genetic mutations in oral-facial-digital syndrome may provide novel and important insights into the genetic mechanisms of this syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Imaging of head and neck venous malformations.

PubMed

Flis, Christine M; Connor, Stephen E

2005-10-01

Venous malformations (VMs) are non proliferative lesions that consist of dysplastic venous channels. The aim of imaging is to characterise the lesion and define its anatomic extent. We will describe the plain film, ultrasound (US) (including colour and duplex Doppler), computed tomography (CT), magnetic resonance imaging (MRI), conventional angiographic and direct phlebographic appearances of venous malformations. They will be illustrated at a number of head and neck locations, including orbit, oral cavity, superficial and deep facial space, supraglottic and intramuscular. An understanding of the classification of such vascular anomalies is required to define the correct therapeutic procedure to employ. Image-guided sclerotherapy alone or in combination with surgery is now the first line treatment option in many cases of head and neck venous malformations, so the radiologist is now an integral part of the multidisciplinary management team.

Incidence and impact of axial malformations in larval bullfrogs (Rana catesbeiana) developing in sites polluted by a coal-burning power plant

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hopkins, W.A.; Congdon, J.; Ray, J.K.

2000-04-01

Amphibian malformations have recently received much attention from the scientific community, but few studies have provided evidence linking environmental pollution to larval amphibian malformations in the field. The authors document an increased incidence of axial malformations in bullfrog larvae (Rana catesbeiana) inhabiting two sites contaminated with coal combustion wastes. In the polluted sites, 18 and 37% of larvae exhibited lateral curvatures of the spine, whereas zero and 4% of larvae from two reference sites had similar malformations. Larvae from the most heavily polluted site had significantly higher tissue concentrations of potentially toxic trace elements, including As, Cd, Se, Cu, Cr,more » and V, compared with conspecifics from the reference sites. In addition, malformed larvae from the cost contaminated site had decreased swimming speeds compared with those of normal larvae from the same site. The authors hypothesize that the complex mixture of contaminants produced by coal combustion is responsible for the high incidence of malformations and associated effects on swimming performance.« less

Neural Development in tsc2-Deficient Zebrafish

DTIC Science & Technology

2011-10-01

mTOR signaling pathway, current therapies remain ineffective with many patients suffering from intractable epilepsy as well as autism , developmental...are generally severe, with many patients suffering from intractable epilepsy, autism , behavioral problems and mental retardation (Ess, 2006). These...is an important model system for the study of brain malformations as well as the pathogenesis of epilepsy and autism . Advances in these fields require

Chronic exposure to environmental levels of tribromophenol impairs zebrafish reproduction

DOE Office of Scientific and Technical Information (OSTI.GOV)

Deng Jun; Graduate School of the Chinese Academy of Sciences, Beijing 100039; Liu Chunsheng

Tribromophenol (2,4,6-TBP) is ubiquitously found in aquatic environments and biota. In this study, we exposed zebrafish embryos (F{sub 0}; 2'''' days post-fertilization, dpf) to environmental concentration (0.3 mug/L) and a higher concentration (3.0 mug/L) of TBP and assessed the impact of chronic exposure (120 dpf) on reproduction. TBP exposure did not cause a significant increase in the malformation and reduction in the survival in the F{sub 0}-generation fish. After TBP exposure, the plasma testosterone and estradiol levels significantly increased in males and decreased in females. The transcription of steroidogenic genes (3beta-HSD, 17beta-HSD, CYP17, CYP19A, CYP19B) was significantly upregulated in themore » brain and testes in males and downregulated in the brain and ovary in females. TBP exposure significantly downregulated and upregulated the expression of VTG in the liver of female and male fish, respectively. Meanwhile, TBP exposure altered the sex ratio toward a male-dominant state. The F{sub 1}-generation larvae exhibited increased malformation, reduced survival, and retarded growth, suggesting that TBP in the aquatic environment has significant adverse effects on fish population.« less

3D brain MR angiography displayed by a multi-autostereoscopic screen

NASA Astrophysics Data System (ADS)

Magalhães, Daniel S. F.; Ribeiro, Fádua H.; Lima, Fabrício O.; Serra, Rolando L.; Moreno, Alfredo B.; Li, Li M.

2012-02-01

The magnetic resonance angiography (MRA) can be used to examine blood vessels in key areas of the body, including the brain. In the MRA, a powerful magnetic field, radio waves and a computer produce the detailed images. Physicians use the procedure in brain images mainly to detect atherosclerosis disease in the carotid artery of the neck, which may limit blood flow to the brain and cause a stroke and identify a small aneurysm or arteriovenous malformation inside the brain. Multi-autostereoscopic displays provide multiple views of the same scene, rather than just two, as in autostereoscopic systems. Each view is visible from a different range of positions in front of the display. This allows the viewer to move left-right in front of the display and see the correct view from any position. The use of 3D imaging in the medical field has proven to be a benefit to doctors when diagnosing patients. For different medical domains a stereoscopic display could be advantageous in terms of a better spatial understanding of anatomical structures, better perception of ambiguous anatomical structures, better performance of tasks that require high level of dexterity, increased learning performance, and improved communication with patients or between doctors. In this work we describe a multi-autostereoscopic system and how to produce 3D MRA images to be displayed with it. We show results of brain MR angiography images discussing, how a 3D visualization can help physicians to a better diagnosis.

Atlas of neuroanatomy with radiologic correlation and pathologic illustration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dublin, A.B.; Dublin, W.B.

1982-01-01

This atlas correlates gross neuroanatomic specimens with radiographs and computed tomographic scans. Pathologic specimens and radiographs are displayed in a similar manner. The first chapter, on embryology, shows the development of the telencephalon, diencephalon, mesencephalon, and metencephalon through a series of overlays. The anatomical section shows the surface of the brain, the ventricles and their adjacent structures, and the vascular system. CT anatomy is demonstrated by correlating CT scans with pathologic brain specimens cut in the axial plane. Pathologic changes associated with congenital malformations, injections, injuries, tumors, and other causes are demonstrated in the last six chapters.

Defining the molecular pathologies in cloaca malformation: similarities between mouse and human

PubMed Central

Runck, Laura A.; Method, Anna; Bischoff, Andrea; Levitt, Marc; Peña, Alberto; Collins, Margaret H.; Gupta, Anita; Shanmukhappa, Shiva; Wells, James M.; Guasch, Géraldine

2014-01-01

Anorectal malformations are congenital anomalies that form a spectrum of disorders, from the most benign type with excellent functional prognosis, to very complex, such as cloaca malformation in females in which the rectum, vagina and urethra fail to develop separately and instead drain via a single common channel into the perineum. The severity of this phenotype suggests that the defect occurs in the early stages of embryonic development of the organs derived from the cloaca. Owing to the inability to directly investigate human embryonic cloaca development, current research has relied on the use of mouse models of anorectal malformations. However, even studies of mouse embryos lack analysis of the earliest stages of cloaca patterning and morphogenesis. Here we compared human and mouse cloaca development and retrospectively identified that early mis-patterning of the embryonic cloaca might underlie the most severe forms of anorectal malformation in humans. In mouse, we identified that defective sonic hedgehog (Shh) signaling results in early dorsal-ventral epithelial abnormalities prior to the reported defects in septation. This is manifested by the absence of Sox2 and aberrant expression of keratins in the embryonic cloaca of Shh knockout mice. Shh knockout embryos additionally develop a hypervascular stroma, which is defective in BMP signaling. These epithelial and stromal defects persist later, creating an indeterminate epithelium with molecular alterations in the common channel. We then used these animals to perform a broad comparison with patients with mild-to-severe forms of anorectal malformations including cloaca malformation. We found striking parallels with the Shh mouse model, including nearly identical defective molecular identity of the epithelium and surrounding stroma. Our work strongly suggests that early embryonic cloacal epithelial differentiation defects might be the underlying cause of severe forms of anorectal malformations in humans. Moreover, deranged Shh and BMP signaling is correlated with severe anorectal malformations in both mouse and humans. PMID:24524909

Arteriovenous Malformations

MedlinePlus

Arteriovenous malformations (AVMs) are defects in your vascular system. The vascular system includes arteries, veins, and capillaries. Arteries carry blood away from the heart to other organs; veins carry blood back to the heart. Capillaries connect the arteries and veins. An ...

A descriptive model for a multidisciplinary unit for colorectal and pelvic malformations.

PubMed

Vilanova-Sanchez, Alejandra; Halleran, Devin R; Reck-Burneo, Carlos A; Gasior, Alessandra C; Weaver, Laura; Fisher, Meghan; Wagner, Andrea; Nash, Onnalisa; Booth, Kristina; Peters, Kaleigh; Williams, Charae; Brown, Sarah Mayer; Lu, Peter; Fuchs, Molly; Diefenbach, Karen; Leonard, Jeffrey R; Hewitt, Geri; McCracken, Kate; Di Lorenzo, Carlo; Wood, Richard J; Levitt, Marc A

2018-04-19

Patients with anorectal malformations (ARM), Hirschsprung disease (HD), and colonic motility disorders often require care from specialists across a variety of fields, including colorectal surgery, urology, gynecology, and GI motility. We sought to describe the process of creating a collaborative process for the care of these complex patients. We developed a model of a devoted center for these conditions that includes physicians, psychologists, social workers, nurses, and advanced practice nurses. Our weekly planning strategy includes a meeting with representatives of all specialties to review all patients prior to evaluation in our multidisciplinary clinic, followed by combined exams under anesthesia or surgical intervention as needed. There are 31 people working directly in the Center at present. From the Center's start in 2014 until 2017, 1258 patients were cared for from all 50 United States and 62 countries. 360 patients had an ARM (110 had a cloacal malformation, 11 had cloacal exstrophy), 223 presented with HD, 71 had a spinal malformation or injury causing neurogenic bowel, 321 had severe functional constipation or colonic dysmotility, and 162 had other diagnoses including familial polyposis, Crohn's disease, or ulcerative colitis. We have had 170 multidisciplinary meetings, 170 multispecialty outpatient, and 52 nurse practitioner clinics. In our bowel management program we have seen a total of 514 patients in 36 sessions. This is the first report describing the design of a multidisciplinary team approach for patients with colorectal and complex pelvic malformations. We found that approaching these patients in a collaborative way allows for combined medical and surgical decisions with many providers simultaneously, facilitates therapy, and can potentially improve patient outcomes. We hope that this model will help establish new-devoted centers in other locations to encourage centralized care for these rare malformations. IV. Copyright © 2018. Published by Elsevier Inc.

The archipelago of Fernando de Noronha: an intriguing malformed toad hotspot in South America.

PubMed

Toledo, Luís Felipe; Ribeiro, Ricardo S

2009-09-01

Malformed anurans raise concern among scientists, because deformities may relate to the recent global crisis among amphibian populations, although declining populations also may be associated with other causes (e.g., diseases, over-exploitation, and land use/land cover change). We examined a sample of toads (Rhinella jimi, Bufonidae) from an introduced population in the Archipelago of Fernando de Noronha, Brazil where malformations of anurans were thought to be high. Our sample of 159 specimens from the site revealed that 44.6% of all specimens had one or more malformations. Incidence of malformed toads on the mainland sites was substantially lower: 10.5% at Itamaracá, and 3.7% at Propriá. We describe the malformations observed, including six undescribed types of malformation of anurans, and we pose possible hypotheses to explain this high incidence of malformed toads. In addition to existing hypotheses, we suggest for the first time the hypothesis that lack of predation pressures contributes to numbers of malformed toads. We indicate the need of specific studies to understand the causes of malformations in the R. jimi population of Fernando de Noronha, which is thought to be extreme foci of malformed amphibians in the world. Our results may improve local conservation action plans as this is an alien population that may be affecting endemic fauna, and may affect populations in other parts of the world, because toad species of the genus Rhinella are recognized as exceptional colonizers. More importantly, unknown variables in these toads' environment are evidently affecting toads during development, which should be a concern for all species that inhabit the area, perhaps even humans.

Congenital malformations in offspring of women with a history of malignancy.

PubMed

Sabeti Rad, Zahra; Friberg, Britt; Henic, Emir; Rylander, Lars; Ståhl, Olof; Källén, Bengt; Lingman, Göran

2017-02-15

Survival after malignancy has increased and the question of risks, including risk for congenital malformations for the offspring of these women has become important. Data on congenital malformations in such offspring are limited. We compared congenital malformation in offspring, born 1994 to 2011 of women with a history of malignancy (at least 1 year before delivery) with all other offspring. Adjustment for confounders was mainly made by Mantel-Haenszel methodology. Data were obtained by linkage between Swedish national health registers. We identified 71,954 (4.1%) infants with congenital malformation, of which 47,081 (2.7%) were relatively severe (roughly corresponding to major malformation). Among 7284 infants to women with a history of malignancy 204 relatively severe malformations were found (2.8%; odds ratio [OR] = 1.04; 95% confidence interval [CI], 0.91-1.20). After in vitro fertilization, the risk of a relatively severe malformation was significantly increased in women without a history of malignancy (OR = 1.31; 95% CI, 1.24-1.38) and still more in women with such a history (risk ratio = 1.85; 95% CI, 1.08-2.97). However, there were no significant differences neither, for any malformations (OR = 1.04; 95% CI, 0.92-1.16) nor for relatively severe malformations (OR = 1.04; 95% CI, 0.91-1.20), when comparing offspring only after maternal history of malignancy. No general increase in malformation rate was found in infants born to women with a history of malignancy. A previously known increased risk after in vitro fertilization was verified and it is possible that this risk is further augmented among infants born of women with a history of malignancy. Birth Defects Research 109:224-233, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Quality of life and disability 12 months after surgery vs. conservative management for unruptured brain arteriovenous malformations: Scottish population-based and Australian hospital-based studies.

PubMed

O'Donnell, Joan Margaret; Al-Shahi Salman, Rustam; Manuguerra, Maurizio; Assaad, Nazih; Morgan, Michael Kerin

2018-03-01

Few data are available on disability and quality of life (QOL) after surgery versus conservative management for unruptured brain arteriovenous malformations (uAVMs). The aim of this study was to test the hypothesis that QOL and disability are worse after surgery ± preoperative embolisation for uAVM compared with conservative management. We included consecutive patients diagnosed with uAVM from a prospective population-based study in Scotland (1999-2003; 2006-2010) and a prospective hospital-based series in Australia (2011-2015). We assessed outcomes on the modified Rankin Scale (mRS) and the Short Form (SF)-36 at ~ 12 months after surgery or conservative treatment and compared these groups using continuous ordinal regression in the two cohorts separately. Surgery was performed for 29% of all uAVM cases diagnosed in Scotland and 84% of all uAVM referred in Australia. There was no statistically significant difference between surgery and conservative management at 12 months among 79 patients in Scotland (mean SF-36 Physical Component Score (PCS) 39 [SD 14] vs. 39 [SD 13]; mean SF-36 Mental Component Score (MCS) 38 [SD 14] vs. 39 [SD 14]; mRS > 1, 24 vs. 9%), nor among 37 patients in Australia (PCS 51 [SD 10] vs. 49 [SD 6]; MCS 48 [SD 12] vs. 49 [SD 10]; mRS > 1, 19 vs. 30%). In the Australian series, there was no statistically significant change in the MCS and PCS between baseline before surgery or conservative management and 12 months. We did not find a statistically significant difference between surgery ± preoperative embolisation and conservative management in disability or QOL at 12 months.

EPH Receptor B4 (EPHB4) Gene Polymorphisms and Risk of Intracranial Hemorrhage in Patients with Brain Arteriovenous Malformations

PubMed Central

Weinsheimer, Shantel; Kim, Helen; Pawlikowska, Ludmila; Chen, Yongmei; Lawton, Michael T.; Sidney, Stephen; Kwok, Pui-Yan; McCulloch, Charles E.; Young, William L.

2009-01-01

Background Brain arteriovenous malformations (BAVM) are a tangle of abnormal vessels directly shunting blood from the arterial to venous circulation and an important cause of intracranial hemorrhage (ICH). EphB4 is involved in arterial-venous determination during embryogenesis; altered signaling could lead to vascular instability resulting in ICH. We investigated the association of single-nucleotide polymorphisms (SNPs) and haplotypes in EPHB4 with risk of ICH at clinical presentation in BAVM patients. Methods and Results Eight haplotype-tagging SNPs spanning ∼29 kb were tested for association with ICH presentation in 146 Caucasian BAVM patients (phase I: 56 ICH, 90 non-ICH) using allelic, haplotypic, and principal components analysis. Associated SNPs were then genotyped in 102 additional cases (phase II: 37 ICH, 65 non-ICH) and data combined for multivariable logistic regression. Minor alleles of 2 SNPs were associated with reduced risk of ICH presentation (rs314313 C, P=0.005; rs314308 T, P=0.0004). Overall, haplotypes were also significantly associated with ICH presentation (χ2=17.24, 6 df, P=0.008); 2 haplotypes containing the rs314308 T allele (GCCTGGGT, P=0.003; GTCTGGGC, P=0.036) were associated with reduced risk. In principal components analysis, 2 components explained 91% of the variance, and complemented haplotype results by implicating 4 SNPs at the 5′ end, including rs314308 and rs314313. These 2 SNPs were replicated in the phase II cohort, and combined data resulted in greater significance (rs314313, P=0.0007; rs314308, P=0.00008). SNP association with ICH presentation persisted after adjusting for age, sex, BAVM size, and deep venous drainage. Conclusions EPHB4 polymorphisms are associated with risk of ICH presentation in BAVM patients, warranting further study. PMID:20031623

Outcomes and Complications After Endovascular Treatment of Brain Arteriovenous Malformations: A Prognostication Attempt Using Artificial Intelligence.

PubMed

Asadi, Hamed; Kok, Hong Kuan; Looby, Seamus; Brennan, Paul; O'Hare, Alan; Thornton, John

2016-12-01

To identify factors influencing outcome in brain arteriovenous malformations (BAVM) treated with endovascular embolization. We also assessed the feasibility of using machine learning techniques to prognosticate and predict outcome and compared this to conventional statistical analyses. A retrospective study of patients undergoing endovascular treatment of BAVM during a 22-year period in a national neuroscience center was performed. Clinical presentation, imaging, procedural details, complications, and outcome were recorded. The data was analyzed with artificial intelligence techniques to identify predictors of outcome and assess accuracy in predicting clinical outcome at final follow-up. One-hundred ninety-nine patients underwent treatment for BAVM with a mean follow-up duration of 63 months. The commonest clinical presentation was intracranial hemorrhage (56%). During the follow-up period, there were 51 further hemorrhagic events, comprising spontaneous hemorrhage (n = 27) and procedural related hemorrhage (n = 24). All spontaneous events occurred in previously embolized BAVMs remote from the procedure. Complications included ischemic stroke in 10%, symptomatic hemorrhage in 9.8%, and mortality rate of 4.7%. Standard regression analysis model had an accuracy of 43% in predicting final outcome (mortality), with the type of treatment complication identified as the most important predictor. The machine learning model showed superior accuracy of 97.5% in predicting outcome and identified the presence or absence of nidal fistulae as the most important factor. BAVMs can be treated successfully by endovascular techniques or combined with surgery and radiosurgery with an acceptable risk profile. Machine learning techniques can predict final outcome with greater accuracy and may help individualize treatment based on key predicting factors. Copyright © 2016 Elsevier Inc. All rights reserved.

Giant occipital meningocele in an 8-year-old child with Dandy-Walker malformation.

PubMed

Talamonti, Giuseppe; Picano, Marco; Debernardi, Alberto; Bolzon, Moreno; Teruzzi, Mario; D'Aliberti, Giuseppe

2011-01-01

The possibility of an association between Dandy-Walker malformation and occipital meningocele is well-known. However, just an overall number of about 40 cases have been previously reported. Giant occipital meningocele has been described only in three newborns. Incidence, pathology, clinical presentation, and proper management of this association are still poorly defined. An 8-year-old boy with Dandy-Walker malformation and giant (25 cm in diameter) occipital meningocele is presented. This boy was born without any apparent occipital mass and harbored no other significant malformations including hydrocephalus. On admission, he was neurologically intact and the giant occipital mass presented partially calcified cyst walls. Treatment consisted of the excision of the occipital malformation, cranioplasty, and cysto-peritoneal shunt. Outcome was excellent. To the best of our knowledge, among the few reported patients with Dandy-Walker malformation associated to occipital meningocele, this is the oldest one and the one with the largest occipital meningocele; he is unique with calcified walls of the occipital meningocele and the only one who survived the repair of the giant malformation. In Dandy-Walker malformation, occipital meningocele may develop and grow regardless of hydrocephalus. Giant size may be reached and the cyst may become calcified. Surgical repair may warrant favorable outcome.

Cerebellar and Brainstem Malformations.

PubMed

Poretti, Andrea; Boltshauser, Eugen; Huisman, Thierry A G M

2016-08-01

The frequency and importance of the evaluation of the posterior fossa have increased significantly over the past 20 years owing to advances in neuroimaging. Conventional and advanced neuroimaging techniques allow detailed evaluation of the complex anatomic structures within the posterior fossa. A wide spectrum of cerebellar and brainstem malformations has been shown. Familiarity with the spectrum of cerebellar and brainstem malformations and their well-defined diagnostic criteria is crucial for optimal therapy, an accurate prognosis, and correct genetic counseling. This article discusses cerebellar and brainstem malformations, with emphasis on neuroimaging findings (including diagnostic criteria), neurologic presentation, systemic involvement, prognosis, and recurrence. Copyright © 2016 Elsevier Inc. All rights reserved.

Parasitic twin--a supernumerary limb associated with spinal malformations. A case report.

PubMed

Sahlu, Abat; Mesfin, Brook; Tirsit, Abenezer; Debebe, Tequam; Wester, Knut

2016-03-01

We describe a case of rachipagus parasitic twin with spinal cord malformations (lipomyelomeningocele and tethered cord) in a 7-month-old Ethiopian infant. The parasitic mass had a well-formed foot, ankle and lower leg and a small sinus that resembled an anus. Magnetic resonance imaging scans revealed spinal malformations including a distal syringohydromyelia. The mass was successfully resected and the dural attachment was closed. Histopathological examination confirmed the diagnosis. Postoperatively, the child had unchanged, intact neurological function in both lower limbs. Almost all rachipagus parasitic twins are associated with spinal malformations. They should, therefore, be operated on by surgeons experienced in myelomeningocele surgery.

High-flow vascular malformation treatment using ultrasound-guided laser combined with polidocanol sclerotherapy.

PubMed

Zhang, Yan; Zhou, Ping; Li, Lan; Li, Jia-le

2015-07-01

The current treatment for vascular malformations includes surgery, sclerotherapy, and embolization. However, each method has its limitations, such as recurrence, complications, scarring, and radiation exposure. Therefore, identifying an effective, minimally invasive treatment that reduces lesion recurrence is particularly important. We describe in detail a patient who received treatment with ultrasound-guided laser interruption of feeding vessels combined with polidocanol sclerotherapy after the recurrence of forearm high-flow vascular malformation.

Neurodevelopmental Malformations of the Cerebellar Vermis in Genetically Engineered Rats.

PubMed

Ramos, Raddy L; Van Dine, Sarah E; Gilbert, Mary E; Leheste, Joerg R; Torres, German

2015-12-01

The cerebellar vermis is particularly vulnerable to neurodevelopmental malformations in humans and rodents. Sprague-Dawley, and Long-Evans rats exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the vermis. Malformations are almost exclusively found along the primary fissure and are indicative of deficits of neuronal migration during cerebellar development. In the present report, we test the prediction that genetically engineered rats on Sprague-Dawley or Long-Evans backgrounds will also exhibit the same cerebellar malformations. Consistent with our hypothesis, we found that three different transgenic lines on two different backgrounds had cerebellar malformations. Heterotopia in transgenic rats had identical cytoarchitecture as that observed in wild-type rats including altered morphology of Bergmann glia. In light of the possibility that heterotopia could affect results from behavioral studies, these data suggest that histological analyses be performed in studies of cerebellar function or development when using genetically engineered rats on these backgrounds in order to have more careful interpretation of experimental findings.

Damage and repair of irradiated mammalian brain

DOE Office of Scientific and Technical Information (OSTI.GOV)

Frankel, K.; Lo, E.; Phillips, M.

1989-07-01

We have demonstrated that focal charged particle irradiation of the rabbit brain can create well-defined lesions which are observable by nuclear magnetic resonance imaging (NMR) and positron emission tomography (PET) imaging techniques. These are similar, in terms of location and characteristic NMR and PET features, to those that occur in the brain of about 10% of clinical research human subjects, who have been treated for intracranial vascular malformations with stereotactic radiosurgery. These lesions have been described radiologically as vasogenic edema of the deep white matter,'' and the injury is of variable intensity and temporal duration, can recede or progress tomore » serious neurologic sequelae, and persist for a considerable period of time, frequently 18 mon to 3 yr. 8 refs., 6 figs.« less

Untreated brain arteriovenous malformation

PubMed Central

Al-Shahi Salman, Rustam; McCulloch, Charles E.; Stapf, Christian; Young, William L.

2014-01-01

Objective: To identify risk factors for intracranial hemorrhage in the natural history course of brain arteriovenous malformations (AVMs) using individual patient data meta-analysis of 4 existing cohorts. Methods: We harmonized data from Kaiser Permanente of Northern California (n = 856), University of California San Francisco (n = 787), Columbia University (n = 672), and the Scottish Intracranial Vascular Malformation Study (n = 210). We censored patients at first treatment, death, last visit, or 10-year follow-up, and performed stratified Cox regression analysis of time-to-hemorrhage after evaluating hemorrhagic presentation, sex, age at diagnosis, deep venous drainage, and AVM size as predictors. Multiple imputation was performed to assess impact of missing data. Results: A total of 141 hemorrhage events occurred during 6,074 patient-years of follow-up (annual rate of 2.3%, 95% confidence interval [CI] 2.0%–2.7%), higher for ruptured (4.8%, 3.9%–5.9%) than unruptured (1.3%, 1.0%–1.7%) AVMs at presentation. Hemorrhagic presentation (hazard ratio 3.86, 95% CI 2.42–6.14) and increasing age (1.34 per decade, 1.17–1.53) independently predicted hemorrhage and remained significant predictors in the imputed dataset. Female sex (1.49, 95% CI 0.96–2.30) and exclusively deep venous drainage (1.60, 0.95–2.68, p = 0.02 in imputed dataset) may be additional predictors. AVM size was not associated with intracerebral hemorrhage in multivariable models (p > 0.5). Conclusion: This large, individual patient data meta-analysis identified hemorrhagic presentation and increasing age as independent predictors of hemorrhage during follow-up. Additional AVM cohort data may further improve precision of estimates, identify new risk factors, and allow validation of prediction models. PMID:25015366

Management of parturients in active labor with Arnold Chiari malformation, tonsillar herniation, and syringomyelia

PubMed Central

Ghaly, Ramsis F.; Tverdohleb, Tatiana; Candido, Kenneth D.; Knezevic, Nebojsa Nick

2017-01-01

Background: Arnold-Chiari malformation Type 1 (ACM-1) in parturients is a topic of ongoing discussion between obstetricians and anesthesiologists. The primary unanswered question remains; How should the anesthesia provider proceed with labor analgesia and anesthesia for cesarean section when confronted with an advanced, asymptomatic, or minimally symptomatic case of ACM-1 during labor? Case Description: A 24-year-old, ASA II, G1P0 full-term parturient presented to Labor and Delivery for vaginal delivery. A diagnosis of ACM-1 was made 12 years ago when a brain magnetic resonance imaging (MRI) was performed for right-sided numbness following a rear-end motor vehicle collision. The patient had been asymptomatic since then and had been seen by an outside neurologist frequently for the past 10 years. During the anesthesia evaluation, it was noted that she had an exaggerated patellar reflex, and a questionable left-sided Babinski; subsequently, an MRI study was requested. Review of a brain MRI demonstrated an advanced form of ACM with a 1.7 cm transtonsillar herniation and a large syrinx extending from C1 down to C5. Following a discussion with the patient, family, and primary OB team, a plan for elective cesarean section was made per neurosurgical recommendations. This was conducted uneventfully under general anesthesia. The patient had no complaints in the post-anesthesia care unit. Conclusion: Unfamiliarity of health care providers with regards to ACM-1 parturients can be countered by increasing awareness of this condition throughout medical specialties involved in their care. The Ghaly Obstetric Guide to Arnold-Chiari malformation Type 1, along with proper training of anesthesia care providers regarding the specificities of ACM-1 parturients aids in better management and understanding of this complex condition. PMID:28217389

Management of parturients in active labor with Arnold Chiari malformation, tonsillar herniation, and syringomyelia.

PubMed

Ghaly, Ramsis F; Tverdohleb, Tatiana; Candido, Kenneth D; Knezevic, Nebojsa Nick

2017-01-01

Arnold-Chiari malformation Type 1 (ACM-1) in parturients is a topic of ongoing discussion between obstetricians and anesthesiologists. The primary unanswered question remains; How should the anesthesia provider proceed with labor analgesia and anesthesia for cesarean section when confronted with an advanced, asymptomatic, or minimally symptomatic case of ACM-1 during labor? A 24-year-old, ASA II, G1P0 full-term parturient presented to Labor and Delivery for vaginal delivery. A diagnosis of ACM-1 was made 12 years ago when a brain magnetic resonance imaging (MRI) was performed for right-sided numbness following a rear-end motor vehicle collision. The patient had been asymptomatic since then and had been seen by an outside neurologist frequently for the past 10 years. During the anesthesia evaluation, it was noted that she had an exaggerated patellar reflex, and a questionable left-sided Babinski; subsequently, an MRI study was requested. Review of a brain MRI demonstrated an advanced form of ACM with a 1.7 cm transtonsillar herniation and a large syrinx extending from C1 down to C5. Following a discussion with the patient, family, and primary OB team, a plan for elective cesarean section was made per neurosurgical recommendations. This was conducted uneventfully under general anesthesia. The patient had no complaints in the post-anesthesia care unit. Unfamiliarity of health care providers with regards to ACM-1 parturients can be countered by increasing awareness of this condition throughout medical specialties involved in their care. The Ghaly Obstetric Guide to Arnold-Chiari malformation Type 1, along with proper training of anesthesia care providers regarding the specificities of ACM-1 parturients aids in better management and understanding of this complex condition.

Language comprehension in nonspeaking children with severe cerebral palsy: Neuroanatomical substrate?

PubMed

Geytenbeek, Joke J; Oostrom, Kim J; Harlaar, Laurike; Becher, Jules G; Knol, Dirk L; Barkhof, Frederik; Pinto, Pedro S; Vermeulen, R Jeroen

2015-09-01

To identify relations between brain abnormalities and spoken language comprehension, MRI characteristics of 80 nonspeaking children with severe CP were examined. MRI scans were analysed for patterns of brain abnormalities and scored for specific MRI measures: white matter (WM) areas; size of lateral ventricles, WM abnormality/reduction, cysts, subarachnoid space, corpus callosum thinning and grey matter (GM) areas; cortical GM abnormalities, thalamus, putamen, globus pallidus and nucleus caudatus and cerebellar abnormalities. Language comprehension was assessed with a new validated instrument (C-BiLLT). MRI scans of 35 children were classified as a basal ganglia necrosis (BGN) pattern, with damage to central GM areas; in 60% of these children damage to WM areas was also found. MRI scans of 13 children were classified as periventricular leukomalacia (PVL) with little concomitant damage to central GM areas, 13 as malformations and 19 as miscellaneous. Language comprehension was best in children with BGN, followed by malformations and miscellaneous, and was poorest in PVL. Linear regression modelling per pattern group (malformations excluded), with MRI measures as independent variables, revealed that corpus callosum thinning in BGN and parieto-occipital WM reduction in PVL were the most important explanatory factors for poor language comprehension. No MRI measures explained outcomes in language comprehension in the miscellaneous group. Comprehension of spoken language differs between MRI patterns of severe CP. In children with BGN and PVL differences in language comprehension performance is attributed to damage in the WM areas. Language comprehension was most affected in children with WM lesions in the subcortical and then periventricular areas, most characteristic for children with PVL. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

[Neurobiology and neurogenetics of dyslexia].

PubMed

Benítez-Burraco, A

2010-01-01

Dyslexia is a learning disability in which reading (but not any other) impairment is the most prominent symptom. There seems to be a high comorbidity among dyslexia and other learning disabilities, such as SLI, SSD or ADHD. The nulear deficit in dyslexia appears to correspond to an impairment in phonological processing. Structural and functional studies in dyslexic readers converge to indicate the presence of malformations in the brain areas corresponding to the reading systems, but also a failure of these systems to function properly during reading. Genes linked (or associated) to dyslexia have been shown to be involved in neuronal migration and axon guidance during the formation of the cortex. In the developing cerebral neocortex of rats, local loss of function of most of these genes not only results in abnormal neuronal migration and neocortical and hippocampal malformations, but also in deficits related to auditory processing and learning. While the structural malformations resemble neuronal migration abnormalities observed in the brains of individuals with developmental dyslexia, processing/learning deficits also resemble deficits described in individuals affected by the disease. On the whole, dyslexia seems to be on a continuum with typical reading at different biological levels (genetic, biochemical, physiological, cognitive). Furthermore, certain elements belonging to some of these levels (mainly -some of the- genes linked or associated to the disease, but also -some of the- neuronal structures whose development is regulated by these genes) would simultaneously belong to those of other cognitive abilities, which give rise to diseases of a different nature (i.e. non- dyslexic impairments) when they are impaired. Copyright © 2009 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

Language Development and Brain Magnetic Resonance Imaging Characteristics in Preschool Children With Cerebral Palsy.

PubMed

Choi, Ja Young; Choi, Yoon Seong; Park, Eun Sook

2017-05-24

The purpose of this study was to investigate characteristics of language development in relation to brain magnetic resonance imaging (MRI) characteristics and the other contributing factors to language development in children with cerebral palsy (CP). The study included 172 children with CP who underwent brain MRI and language assessments between 3 and 7 years of age. The MRI characteristics were categorized as normal, malformation, periventricular white matter lesion (PVWL), deep gray matter lesion, focal infarct, cortical/subcortical lesion, and others. Neurodevelopmental outcomes such as ambulatory status, manual ability, cognitive function, and accompanying impairments were assessed. Both receptive and expressive language development quotients (DQs) were significantly related to PVWL or deep gray matter lesion severity. In multivariable analysis, only cognitive function was significantly related to receptive language development, whereas ambulatory status and cognitive function were significantly associated with expressive language development. More than one third of the children had a language developmental discrepancy between receptive and expressive DQs. Children with cortical/subcortical lesions were at high risk for this discrepancy. Cognitive function is a key factor for both receptive and expressive language development. In children with PVWL or deep gray matter lesion, lesion severity seems to be useful to predict language development.

Management of Arteriovenous Malformations Associated with Developmental Venous Anomalies: A Literature Review and Report of 2 Cases.

PubMed

Zhang, Michael; Connolly, Ian D; Teo, Mario K; Yang, George; Dodd, Robert; Marks, Michael; Zuccarello, Mario; Steinberg, Gary K

2017-10-01

Classification of cerebrovascular malformations has revealed intermediary lesions that warrant further review owing to their unusual presentation and management. We present 2 cases of arteriovenous malformation (AVM) associated with a developmental venous anomaly (DVA), and discuss the efficacy of previously published management strategies. Two cases of AVMs associated with DVA were identified, and a literature search for published cases between 1980 and 2016 was conducted. Patient demographic data and clinical features were documented. In case 1, a 29-year-old female presenting with parenchymal hemorrhage and left homonymous hemianopia was found to have a right parieto-occipital AVM fed from the anterior cerebral, middle cerebral, and posterior cerebral arteries, with major venous drainage to the superior sagittal sinus. In case 2, imaging in a 34-year-old female evaluated for night tremors and incontinence revealed a left parietal AVM with venous drainage to the superior sagittal sinus. Including our 2 cases, 22 cases of coexisting AVMs and DVAs have been reported in the literature. At presentation, 68% had radiographic evidence of hemorrhage. Stereotactic radiosurgery was performed in 7 cases, embolization in 6 cases, surgical resection in 4 cases, and multimodal therapy in 5 cases. Radiography at follow-up demonstrated successful AVM obliteration in 67% of cases (12 of 18). Patients with coexisting AVMs and DVAs tend to have a hemorrhagic presentation. Contrary to traditional AVM management, in these cases it is important to preserve the draining vein via the DVA to ensure a safe, sustained circulatory outflow of the associated brain parenchyma while achieving safe AVM obliteration. Copyright © 2017 Elsevier Inc. All rights reserved.

De Novo 3q22.3q24 Microdeletion in a Patient With Blepharophimosis–Ptosis–Epicanthus Inversus Syndrome, Dandy-Walker Malformation, and Wisconsin Syndrome

PubMed Central

Ramineni, Anand

2016-01-01

Interstitial deletions affecting the long arm of chromosome 3 have been associated with a broad phenotype. This has included the features of blepharophimosis–ptosis–epicanthus inversus syndrome, Dandy-Walker malformation, and the rare Wisconsin syndrome. The authors report a young female patient presenting with features consistent with all 3 of these syndromes. This has occurred in the context of a de novo 3q22.3q24 microdeletion including FOXL2, ZIC1, and ZIC4. This patient provides further evidence for the role of ZIC1 and ZIC4 in Dandy-Walker malformation and is the third reported case of Dandy-Walker malformation to have associated corpus callosum thinning. This patient is also only the seventh to be reported with the rare Wisconsin syndrome phenotype. PMID:28503614

Clinical importance of the anterior choroidal artery: a review of the literature.

PubMed

Yu, Jing; Xu, Ning; Zhao, Ying; Yu, Jinlu

2018-01-01

The anterior choroidal artery (AChA) is a critical artery in brain physiology and function. The AChA is involved in many diseases, including aneurysm, brain infarct, Moyamoya disease (MMD), brain tumor, arteriovenous malformation (AVM), etc. The AChA is vulnerable to damage during the treatment of these diseases and is thus a very important vessel. However, a comprehensive systematic review of the importance of the AChA is currently lacking. In this study, we used the PUBMED database to perform a literature review of the AChA to increase our understanding of its role in neurophysiology. Although the AChA is a small thin artery, it supplies an extremely important region of the brain. The AChA consists of cisternal and plexal segments, and the point of entry into the choroidal plexus is known as the plexal point. During treatment for aneurysms, tumors, AVM or AVF, the AChA cisternal segments should be preserved as a pathway to prevent the infarction of the AChA target region in the brain. In MMD, a dilated AChA provides collateral flow for posterior circulation. In brain infarcts, rapid treatment is necessary to prevent brain damage. In Parkinson disease (PD), the role of the AChA is unclear. In trauma, the AChA can tear and result in intracranial hematoma. In addition, both chronic and non-chronic branch vessel occlusions in the AChA are clinically silent and should not deter aneurysm treatment with flow diversion. Based on the data available, the AChA is a highly essential vessel.

Frontal Lobe Cavernous Malformations in Pediatric Patients: Clinical Features and Surgical Outcomes.

PubMed

Wang, Chengjun; Zhao, Meng; Wang, Jia; Wang, Shuo; Jiang, Zhongli; Zhao, Jizong

2018-01-01

The purpose of this study is to investigate the clinical manifestations, surgical treatment, and neurologic outcomes of frontal lobe cavernous malformations in children. A retrospective analysis of 23 pediatric frontal lobe cavernous malformation patients who underwent surgical treatment in Beijing Tiantan Hospital was performed. The case series included 16 boys and 7 girls. Gross total removal without surgical mortality was achieved in all patients. The mean follow-up period after surgery was 33.1 months. Two patients who left hospital with motor deficits gradually recovered after rehabilitative treatment, and other patients were considered to be in excellent clinical condition. For symptomatic frontal lobe cavernous malformations, neurosurgical management should be the treatment of choice. Conservative treatment may be warranted in asymptomatic frontal lobe cavernous malformations, especially the deep-seated or eloquently located cases.

Scleroderma en coup de sabre with recurrent episodes of brain hemorrhage.

PubMed

Takahashi, Takehiro; Asano, Yoshihide; Oka, Tomonori; Miyagaki, Tomomitsu; Tamaki, Zenshiro; Nonaka, Senshu; Sato, Shinichi

2016-02-01

We report a 39-year-old man referred to our facility with linear sclerotic lesions along the several Blaschko's lines of the scalp. A year before the referral, he had had an episode of brain hemorrhage, although there was no evidence of vascular malformation or any other risk factors of brain hemorrhage for his young age. On the diagnosis of scleroderma en coup de sabre, prednisolone intake was initiated, and the skin lesions were well controlled. However, in the course of our follow up, he had another episode of brain hemorrhage, again without any evidence of cerebral vascular abnormalities. Organic intracranial abnormalities in this disease are well-documented, but there have been few reports on comorbid recurrent brain hemorrhages. We herein discuss the possible relationship of the skin lesions with the brain hemorrhages in our case, taking notice of the implication of developmental abnormalities behind these apparently independent phenomena inside and outside the cranium. © 2015 Japanese Dermatological Association.

Mutations at the PAX6 locus are found in heterogeneous anterior segment malformations including Peters' anomaly.

PubMed

Hanson, I M; Fletcher, J M; Jordan, T; Brown, A; Taylor, D; Adams, R J; Punnett, H H; van Heyningen, V

1994-02-01

Mutation or deletion of the PAX6 gene underlies many cases of aniridia. Three lines of evidence now converge to implicate PAX6 more widely in anterior segment malformations including Peters' anomaly. First, a child with Peters' anomaly is deleted for one copy of PAX6. Second, affected members of a family with dominantly inherited anterior segment malformations, including Peters' anomaly are heterozygous for an R26G mutation in the PAX6 paired box. Third, a proportion of Sey/+ Smalleye mice, heterozygous for a nonsense mutation in murine Pax-6, have an ocular phenotype resembling Peters' anomaly. We therefore propose that a variety of anterior segment anomalies may be associated with PAX6 mutations.

An epidemiologic study of environmental and genetic factors in congenital hydrocephalus.

PubMed

Stoll, C; Alembik, Y; Dott, B; Roth, M P

1992-11-01

Risk factors were studied in 96 children with congenital hydrocephalus (CH) coming from 118,265 consecutive births of known outcome. Hydrocephalus with neural tube defects, intracranial tumors or secondary to brain atrophy were excluded. The prevalence of CH was 0.81 per thousand. Diagnosis was performed prenatally in 41 cases. Forty-three (44.8%) of the cases had hydrocephalus without other malformations (isolated hydrocephalus), 18 (18.7%) infants had recognized chromosomal or non-chromosomal syndromes and 35 children (36.4%) had multiple malformations. Each case was matched to a control. Weight and length at birth of children with hydrocephalus were less than in the controls (p < 0.001). The weight of the placenta was lower than in the controls (p < 0.05). The pregnancy with a hydrocephalic child was more often complicated by threatened abortion, polyhydramnios and oligohydramnios. The mothers of children with hydrocephalus and multiple malformations had used oral contraceptives during the first trimester of pregnancy more often than the mothers of the controls. No differences appeared between the mothers of children with CH and the controls for the other risk factors studied: parental age, parity, previous pregnancies, previous stillbirths, smoking, diabetes, epilepsy, X-rays, hypertension, fever "flu", medication and occupational exposure. There was an increase of parental consanguinity in the parents of our patients (6.2% v. 1.1%, p < 0.001) and first degree relatives had more non-cerebral malformations than the controls (7.3% v. 3.2%, p < 0.05).

Prenatal diagnosis of Chiari malformation with syringomyelia in the second trimester.

PubMed

Iruretagoyena, Jesus Igor; Trampe, Barbara; Shah, Dinesh

2010-02-01

Routine anatomic ultrasound performed in the second trimester has a detection rate of approximately 70-90% for fetal congenital abnormalities (Nyberg and Souter, J Ultrasound Med 2001;6:655-674). The central nervous system abnormalities are one of the most common ones detected. Chiari malformation is among the CNS abnormalities diagnosed in the fetal period (Bianchi et al., Fetology - diagnosis and management of the fetal patient, McGraw-Hill, 2000). The Arnold-Chiari malformation was first described in 1883 by Cleland (Romero et al., Prenatal diagnosis of congenital anomalies, Appleton and Lange, 1988). It is characterised by the prolapse of the hindbrain structures below the level of the foramen magnum. It can be associated with skeletal abnormalities and neurological dysfunction. In type I, a lip of cerebellum is downwardly displaced with the tonsils, but the fourth ventricle remains in the posterior fossa. This condition may coexist with syringomyelia, which is a cyst formation on the cervical portion of the spinal cord (Creasy et al., Maternal fetal medicine principles and practice, 2004). We present a case where Chiari type 1 and syringomyelia detected at 18 weeks of gestation. The reason for referral to our center was an abnormal inward posturing of both upper and lower extremities (minimal gross movement and almost inexistent range of motion on fetal joints). On further fetal evaluation, an abnormal brain ultrasound was identified. Prenatal diagnosis of Chiari type 1 malformation and syringomyelia is almost nonexistent when reviewing the literature is the reason why this case is presented.

MEF2C haploinsufficiency caused by either microdeletion of the 5q14.3 region or mutation is responsible for severe mental retardation with stereotypic movements, epilepsy and/or cerebral malformations.

PubMed

Le Meur, N; Holder-Espinasse, M; Jaillard, S; Goldenberg, A; Joriot, S; Amati-Bonneau, P; Guichet, A; Barth, M; Charollais, A; Journel, H; Auvin, S; Boucher, C; Kerckaert, J-P; David, V; Manouvrier-Hanu, S; Saugier-Veber, P; Frébourg, T; Dubourg, C; Andrieux, J; Bonneau, D

2010-01-01

Over the last few years, array-comparative genomic hybridisation (CGH) has considerably improved our ability to detect cryptic unbalanced rearrangements in patients with syndromic mental retardation. Molecular karyotyping of six patients with syndromic mental retardation was carried out using whole-genome oligonucleotide array-CGH. 5q14.3 microdeletions ranging from 216 kb to 8.8 Mb were detected in five unrelated patients with the following phenotypic similarities: severe mental retardation with absent speech, hypotonia and stereotypic movements. Facial dysmorphic features, epilepsy and/or cerebral malformations were also present in most of these patients. The minimal common deleted region of these 5q14 microdeletions encompassed only MEF2C, the gene for a protein known to act in brain as a neurogenesis effector, which regulates excitatory synapse number. In a patient with a similar phenotype, an MEF2C nonsense mutation was subsequently identified. Taken together, these results strongly suggest that haploinsufficiency of MEF2C is responsible for severe mental retardation with stereotypic movements, seizures and/or cerebral malformations.

Neuronal migration disorders in microcephalic osteodysplastic primordial dwarfism type I/III

PubMed Central

Juric-Sekhar, Gordana; Kapur, Raj P.; Glass, Ian A.; Murray, Mitzi L.; Parnell, Shawn E.

2011-01-01

Microcephalic osteodysplastic primordial dwarfism (MOPD) is a rare microlissencephaly syndrome, with at least two distinct phenotypic and genetic types. MOPD type II is caused by pericentrin mutations, while types I and III appear to represent a distinct entity (MOPD I/III) with variably penetrant phenotypes and unknown genetic basis. The neuropathology of MOPD I/III is little understood, especially in comparison to other forms of lissencephaly. Here, we report postmortem brain findings in an 11-month-old female infant with MOPD I/III. The cerebral cortex was diffusely pachygyric, with a right parietal porencephalic lesion. Histologically, the cortex was abnormally thick and disorganized. Distinct malformations were observed in different cerebral lobes, as characterized using layer-specific neuronal markers. Frontal cortex was severely disorganized and coated with extensive leptomeningeal glioneuronal heterotopia. Temporal cortex had a relatively normal 6-layered pattern, despite cortical thickening. Occipital cortex was variably affected. The corpus callosum was extremely hypoplastic. Brainstem and cerebellar malformations were also present, as well as old necrotic foci. Findings in this case suggest that the cortical malformation in MOPD I/III is distinct from other forms of pachygyria–lissencephaly. PMID:20857301

Congenital extrahepatic portosystemic shunts (Abernethy malformation): a histopathologic evaluation.

PubMed

Lisovsky, Mikhail; Konstas, Angelos A; Misdraji, Joseph

2011-09-01

Congenital extrahepatic portosystemic shunt, also known as Abernethy malformation, is a rare malformation in which intestinal and splenic venous blood bypasses the liver and drains into systemic veins. Aside from the complete or near-complete absence of portal veins, other histologic features of Abernethy malformation have not been evaluated in the literature. The goal of this study was to detail the hepatic histopathology in 5 patients with Abernethy malformation diagnosed at our institution. Paraffin-embedded tissue sections from 1 explant, 2 liver tumor resections, and 2 liver biopsies were evaluated using hematoxylin and eosin stains, reticulin, elastic, and trichrome stains, and immunohistochemistry for D2-40. Histologic findings included absence of portal veins in small portal tracts, absent or hypoplastic portal veins in medium-sized and large-sized portal tracts, isolated capillaries and arterioles in the lobules, hypertrophy of hepatic artery branches, remodeling of the liver architecture, and nodular regenerative hyperplasia in 1 case. Two patients had hepatocellular carcinoma without cirrhosis, and 2 had focal nodular hyperplasia. In addition to loss of portal veins, Abernethy malformation is characterized by multiple abnormalities due to remodeling of the hepatic vasculature. Abernethy malformation may also be associated with hepatocellular carcinoma and focal nodular hyperplasia in some patients.

Leaping lopsided: a review of the current hypotheses regarding etiologies of limb malformations in frogs.

PubMed

Loeffler, I K; Stocum, D L; Fallon, J F; Meteyer, C U

2001-10-15

Recent progress in the investigation of limb malformations in free-living frogs has underlined the wide range in the types of limb malformations and the apparent spatiotemporal clustering of their occurrence. Here, we review the current understanding of normal and abnormal vertebrate limb development and regeneration and discuss some of the molecular events that may bring about limb malformation. Consideration of the differences between limb development and regeneration in amphibians has led us to the hypothesis that some of the observed limb malformations come about through misdirected regeneration. We report the results of a pilot study that supports this hypothesis. In this study, the distal aspect of the right hindlimb buds of X. laevis tadpoles was amputated at the pre-foot paddle stage. The tadpoles were raised in water from a pond in Minnesota at which 7% of surveyed newly metamorphosed feral frogs had malformations. Six percent (6 of 100) of the right limbs of the tadpoles raised in pond water developed abnormally. One truncated right limb was the only malformation in the control group, which was raised in dechlorinated municipal water. All unamputated limbs developed normally in both groups. Three major factors under consideration for effecting the limb malformations are discussed. These factors include environmental chemicals (primarily agrichemicals), encysted larvae (metacercariae) of trematode parasites, and increased levels of ultraviolet light. Emphasis is placed on the necessary intersection of environmental stressors and developmental events to bring about the specific malformations that are observed in free-living frog populations.

Leaping lopsided: a review of the current hypotheses regarding etiologies of limb malformations in frogs

USGS Publications Warehouse

Loeffler, I.K.; Stocum, D.L.; Fallon, J.F.; Meteyer, C.U.

2001-01-01

Recent progress in the investigation of limb malformations in free-living frogs has underlined the wide range in the types of limb malformations and the apparent spatiotemporal clustering of their occurrence. Here, we review the current understanding of normal and abnormal vertebrate limb development and regeneration and discuss some of the molecular events that may bring about limb malformation. Consideration of the differences between limb development and regeneration in amphibians has led us to the hypothesis that some of the observed limb malformations come about through misdirected regeneration. We report the results of a pilot study that supports this hypothesis. In this study, the distal aspect of the right hindlimb buds of X. laevis tadpoles was amputated at the pre-foot paddle stage. The tadpoles were raised in water from a pond in Minnesota at which 7% of surveyed newly metamorphosed feral frogs had malformations. Six percent (6 of 100) of the right limbs of the tadpoles raised in pond water developed abnormally. One truncated right limb was the only malformation in the control group, which was raised in dechlorinated municipal water. All unamputated limbs developed normally in both groups. Three major factors under consideration for effecting the limb malformations are discussed. These factors include environmental chemicals (primarily agrichemicals), encysted larvae (metacercariae) of trematode parasites, and increased levels of ultraviolet light. Emphasis is placed on the necessary intersection of environmental stressors and developmental events to bring about the specific malformations that are observed in free-living frog populations.

Identification of a novel synaptic protein, TMTC3, involved in periventricular nodular heterotopia with intellectual disability and epilepsy

PubMed Central

Farhan, Sali M K; Nixon, Kevin C J; Everest, Michelle; Edwards, Tara N; Long, Shirley; Segal, Dmitri; Knip, Maria J; Arts, Heleen H; Chakrabarti, Rana; Wang, Jian; Robinson, John F; Lee, Donald; Mirsattari, Seyed M; Rupar, C Anthony; Siu, Victoria M; Poulter, Michael O; Hegele, Robert A; Kramer, Jamie M

2017-01-01

Abstract Defects in neuronal migration cause brain malformations, which are associated with intellectual disability (ID) and epilepsy. Using exome sequencing, we identified compound heterozygous variants (p.Arg71His and p. Leu729ThrfsTer6) in TMTC3, encoding transmembrane and tetratricopeptide repeat containing 3, in four siblings with nocturnal seizures and ID. Three of the four siblings have periventricular nodular heterotopia (PVNH), a common brain malformation caused by failure of neurons to migrate from the ventricular zone to the cortex. Expression analysis using patient-derived cells confirmed reduced TMTC3 transcript levels and loss of the TMTC3 protein compared to parental and control cells. As TMTC3 function is currently unexplored in the brain, we gathered support for a neurobiological role for TMTC3 by generating flies with post-mitotic neuron-specific knockdown of the highly conserved Drosophila melanogaster TMTC3 ortholog, CG4050/tmtc3. Neuron-specific knockdown of tmtc3 in flies resulted in increased susceptibility to induced seizures. Importantly, this phenotype was rescued by neuron-specific expression of human TMTC3, suggesting a role for TMTC3 in seizure biology. In addition, we observed co-localization of TMTC3 in the rat brain with vesicular GABA transporter (VGAT), a presynaptic marker for inhibitory synapses. TMTC3 is localized at VGAT positive pre-synaptic terminals and boutons in the rat hypothalamus and piriform cortex, suggesting a role for TMTC3 in the regulation of GABAergic inhibitory synapses. TMTC3 did not co-localize with Vglut2, a presynaptic marker for excitatory neurons. Our data identified TMTC3 as a synaptic protein that is involved in PVNH with ID and epilepsy, in addition to its previously described association with cobblestone lissencephaly. PMID:28973161

Onyx Embolization Before the Surgical Treatment of Grade III Spetzler-Martin Brain Arteriovenous Malformations: Single-Center Experience and Technical Nuances.

PubMed

Luzzi, Sabino; Del Maestro, Mattia; Bongetta, Daniele; Zoia, Cesare; Giordano, Aldo V; Trovarelli, Donatella; Raysi Dehcordi, Sohelia; Galzio, Renato J

2018-05-09

Grade III Spetzler-Martin brain arteriovenous malformations (AVMs) are a specific set of AVMs with high variability in terms of site, size, angioarchitecture, flow dynamics, and involvement of eloquent areas. Surgery preceded by preoperative embolization has been reported as a useful treatment option for these lesions. The aim of this study is to report outcomes and personal experience of combined preoperative Onyx embolization and surgical resection on a consecutive series of grade III brain AVMs. Between 2005 and 2017, 27 grade III AVMs were treated by means of a staged Onyx embolization and subsequent surgical treatment. Site and size of the AVMs, embolization, and surgical specifics as well as complications and outcomes were retrospectively reviewed. All AVMs were supratentorial, 13 of which were hemorrhagic. Mean nidal volume was 19.5 mL. Average embolization sessions were 1.6. Mean embolization-related obliteration rate and morbidity were 28.8% and 3.7%, respectively. Surgery was performed within 3.7 days on average. In our experience, Onyx embolization made the nidus excision easier, facilitated the hemostasis, and contributed to the early identification of the lesion in cases of small or racemose nidus. The surgical obliteration rate was 92.6%. A good overall outcome (modified Rankin Scale score 0-2) was achieved in 70.4% of patients. In our experience, preoperative Onyx embolization helped the surgical management of grade III Spetzler-Martin brain AVMs. Careful evaluation of the angioarchitecture, a tailored strategy in the embolization process, and full cooperation within the neurosurgical-neuroendovascular team are mandatory. Copyright © 2018 Elsevier Inc. All rights reserved.

Gamma Knife surgery for arteriovenous malformations in the brain: integration of time-resolved contrast-enhanced magnetic resonance angiography into dosimetry planning. Technical note.

PubMed

Taschner, Christian A; Le Thuc, Vianney; Reyns, Nicolas; Gieseke, Juergen; Gauvrit, Jean-Yves; Pruvo, Jean-Pierre; Leclerc, Xavier

2007-10-01

The aim of this study was to develop an algorithm for the integration of time-resolved contrast-enhanced magnetic resonance (MR) angiography into dosimetry planning for Gamma Knife surgery (GKS) of arteriovenous malformations (AVMs) in the brain. Twelve patients harboring brain AVMs referred for GKS underwent intraarterial digital subtraction (DS) angiography and time-resolved MR angiography while wearing an externally applied cranial stereotactic frame. Time-resolved MR angiography was performed on a 1.5-tesla MR unit (Achieva, Philips Medical Systems) using contrast-enhanced 3D fast field echo sequencing with stochastic central k-space ordering. Postprocessing with interactive data language (Research Systems, Inc.) produced hybrid data sets containing dynamic angiographic information and the MR markers necessary for stereotactic transformation. Image files were sent to the Leksell GammaPlan system (Elekta) for dosimetry planning. Stereotactic transformation of the hybrid data sets containing the time-resolved MR angiography information with automatic detection of the MR markers was possible in all 12 cases. The stereotactic coordinates of vascular structures predefined from time-resolved MR angiography matched with DS angiography data in all cases. In 10 patients dosimetry planning could be performed based on time-resolved MR angiography data. In two patients, time-resolved MR angiography data alone were considered insufficient. The target volumes showed a notable shift of centers between modalities. Integration of time-resolved MR angiography data into the Leksell GammaPlan system for patients with brain AVMs is feasible. The proposed algorithm seems concise and sufficiently robust for clinical application. The quality of the time-resolved MR angiography sequencing needs further improvement.

Identification of a novel synaptic protein, TMTC3, involved in periventricular nodular heterotopia with intellectual disability and epilepsy.

PubMed

Farhan, Sali M K; Nixon, Kevin C J; Everest, Michelle; Edwards, Tara N; Long, Shirley; Segal, Dmitri; Knip, Maria J; Arts, Heleen H; Chakrabarti, Rana; Wang, Jian; Robinson, John F; Lee, Donald; Mirsattari, Seyed M; Rupar, C Anthony; Siu, Victoria M; Poulter, Michael O; Hegele, Robert A; Kramer, Jamie M

2017-11-01

Defects in neuronal migration cause brain malformations, which are associated with intellectual disability (ID) and epilepsy. Using exome sequencing, we identified compound heterozygous variants (p.Arg71His and p. Leu729ThrfsTer6) in TMTC3, encoding transmembrane and tetratricopeptide repeat containing 3, in four siblings with nocturnal seizures and ID. Three of the four siblings have periventricular nodular heterotopia (PVNH), a common brain malformation caused by failure of neurons to migrate from the ventricular zone to the cortex. Expression analysis using patient-derived cells confirmed reduced TMTC3 transcript levels and loss of the TMTC3 protein compared to parental and control cells. As TMTC3 function is currently unexplored in the brain, we gathered support for a neurobiological role for TMTC3 by generating flies with post-mitotic neuron-specific knockdown of the highly conserved Drosophila melanogaster TMTC3 ortholog, CG4050/tmtc3. Neuron-specific knockdown of tmtc3 in flies resulted in increased susceptibility to induced seizures. Importantly, this phenotype was rescued by neuron-specific expression of human TMTC3, suggesting a role for TMTC3 in seizure biology. In addition, we observed co-localization of TMTC3 in the rat brain with vesicular GABA transporter (VGAT), a presynaptic marker for inhibitory synapses. TMTC3 is localized at VGAT positive pre-synaptic terminals and boutons in the rat hypothalamus and piriform cortex, suggesting a role for TMTC3 in the regulation of GABAergic inhibitory synapses. TMTC3 did not co-localize with Vglut2, a presynaptic marker for excitatory neurons. Our data identified TMTC3 as a synaptic protein that is involved in PVNH with ID and epilepsy, in addition to its previously described association with cobblestone lissencephaly. © The Author 2017. Published by Oxford University Press.

MICROCOMPUTED TOMOGRAPHIC, MORPHOMETRIC, AND HISTOPATHOLOGIC ASSESSMENT OF CONGENITAL BONE MALFORMATIONS IN TWO NEOTROPICAL VIPERIDS.

PubMed

de Carvalho, Marcelo Pires Nogueira; Sant'Anna, Sávio Stefanini; Grego, Kathleen Fernandes; de Campos Fonseca-Pinto, Ana Carolina Brandão; Lorigados, Carla Aparecida Batista; Queiroz-Hazarbassanov, Nicolle Gilda Teixeira; Catão-Dias, José Luiz

2017-10-01

Congenital malformations have been reported in all classes of vertebrates and may be a determinant of life span and survival. In reptiles, the incidence of congenital malformations can be associated with genetic and environmental causes, including pollution. The characterization of pathological processes involved in the development of congenital malformations of bone in snakes is rare in the literature, but is of great relevance in the field of reptile conservation and environmental health. We describe congenital bone lesions in 50 newborn jararaca (Bothrops jararaca) and 26 South American rattlesnakes (Crotalus durissus terrificus) born from wild-caught pregnant females in Southeastern Brazil. Lesions were evaluated by morphometric quantitative analysis, x-ray microtomography, and histopathologic descriptive analysis. Morphometric analysis showed that jararaca presented more severe axial lesions (kyphosis, scoliosis, and kyphoscoliosis) than rattlesnakes. Female rattlesnakes presented more severe axial lesions than did males. In rattlesnakes, spinal deformities were more frequently diagnosed in the caudal segment of the body. We present x-ray microtomographic assessments and images of malformed snakes (n=9) and characterized novel malformations, such as the agenesis of frontal, parietal, and supraoccipital bones in a jararaca specimen. Histopathologic findings included vertebral body fusion, myositis, coagulation necrosis, and disorganization of periaxial muscle fibers. The new methods and results presented in this study will be useful and informative for future research in pathology, teratology, embryology, and ecotoxicology in snakes.

Beckwith-Wiedemann syndrome and Chiari I malformation--a case-based review of central nervous system involvement in hemihypertrophy syndromes.

PubMed

Udayakumaran, Suhas; Onyia, Chiazor U

2015-05-01

Beckwith-Wiedemann syndrome (BWS) is an unusual complex of abnormalities that includes mainly omphalocele, macroglossia, gigantism, visceromegaly, and neonatal hypoglycemia. Type I Chiari malformation, on the other hand, is defined as ectopia of the cerebellar tonsils below the plane of the foramen magnum. Only one case of association of BWS with Chiari I malformation has been previously reported in the literature. Several conditions involving congenital hemihypertrophy have been previously reported in association with Type I Chiari malformation. The pathophysiological mechanism for most of these associations is thought to be quite complex and still remains unclear. However, the presence of tonsillar herniation in BWS has been explained by Tubbs and Oakes in the only one existing case report of BWS with Type I Chiari malformation in the literature, to be due to associated hemihypertrophy of the skull base. We additionally suggest that cerebellar hypertrophy may also contribute to the tonsillar herniation and fourth ventricular outlet obstruction. We now report our recent experience on this association following a review of the literature on association of other hemihypertrophy syndromes with the central nervous system anomalies. We believe that a common pathogenesis of Type I Chiari malformation occurs in conditions of hemihypertrophy including BWS, probably secondary to dysmorphology involving the posterior cranial fossa, and is not just an associated finding.

[The Role of Physician In Enhancement of Rehabilitation of Disabled Children].

PubMed

Nizova, L M; Kislisyna, I G

2017-09-01

The national and international experience of rehabilitation of disabled children was investigated. On the basis of monitoring data problem of increasing of number of children with diagnosis of infantile cerebral paralysis, including necessity of development of new methods of their rehabilitation was established. The comparative dynamics of nosology of disabled children permitted to detect diseases of nervous system and congenital abnormalities (malformations), deformations and chromosomal disorders, psychological disorders and behavioral disorders mostly specific for urban and rural area. The model of institutional environment of rehabilitation of disabled children was developed including system of formal (state, legislative acts, health institutions, organizations of social support of population)and non-formal (public, non-commercial and social psychological organizations) institutions impacted by economic, social,legal and demographic factors. The role of physician is substantiated concerning increasing of quality of rehabilitation services: diagnostic of disordered functions, detection of optimal volume of medical, psychological and pedagogue activities in patients with severe speech disorders, motoric and and neuro-censorial disorders developed as a result of early organic damage of brain, neuro-infections, strokes, and other affection of brain. The adequate curative rehabilitative complex programs were developed of social everyday and social labor rehabilitation.

36th Annual David W. Smith Workshop on Malformations and Morphogenesis: Abstracts of the 2015 annual meeting.

PubMed

Gripp, Karen W; Adam, Margaret P; Hudgins, Louanne; Carey, John C

2016-07-01

The 36th Annual David W Smith Workshop on Malformations and Morphogenesis was held on August 14-19, 2015 at the Harbourtowne Conference Center in St. Michaels Maryland. The Workshop, which honors the legacy of David W Smith, brought together over 120 clinicians and researchers interested in congenital malformations and their underlying mechanisms of morphogenesis. As is the tradition of the meeting, the Workshop highlighted five themes besides mechanisms of morphogenesis: Rasopathies, Eye Malformations, Therapeutics, Prenatal Diagnosis, and Disorders of Sex Development. This Conference Report includes the abstracts presented at the 2015 Workshop. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Prospective long-term follow up of children with anorectal malformation: growth and development until 5years of age.

PubMed

van den Hondel, Desiree; Sloots, Cornelius E J; Gischler, Saskia J; Meeussen, Conny J H M; Wijnen, Rene M H; IJsselstijn, Hanneke

2013-04-01

To evaluate growth and development in children with anorectal malformations and to analyze effects of type of malformation and comorbidities. Non-syndromal children with anorectal malformations were prospectively evaluated at 0.5, 1, 2, and 5 years. Biometrics were obtained at all visits. Mental and psychomotor function development was determined. 108 children (59% male) were included. 49% had a high malformation, and 46% had ≥ 1 additional major comorbidity. All growth parameters were below the norm at all ages (p<0.01), irrespective of type of malformation. Children with ≥ 1 additional major anomaly had lower height at all ages; at 5 years, mean (95% CI) height was -1.83 (-2.7 to -1.1) and -0.70 (-1.3 to -0.1) in children with and without comorbidities, respectively (p=0.019). Mental development was normal, irrespective of the type of malformation or comorbidities. Motor development was delayed at all ages. At 5 years, motor development (n=30) was normal in 70%, borderline in 23%, and 7% had definitive motor problems (p=0.043). Non-syndromal children with anorectal malformations are at risk for growth impairment, especially those with additional major comorbidity. Mental development is normal. Motor development is slightly impaired. Supportive care should focus on growth, dietary management, and motor development besides defecation problems. Copyright © 2013 Elsevier Inc. All rights reserved.

The association between sleep-disordered breathing and magnetic resonance imaging findings in a pediatric cohort with Chiari 1 malformation

PubMed Central

Amin, Reshma; Sayal, Priya; Sayal, Aarti; Massicote, Colin; Pham, Robin; Al-Saleh, Suhail; Drake, James; Narang, Indra

2015-01-01

BACKGROUND: The prevalence of sleep-disordered breathing (SDB) reported in the literature for Chiari malformation type 1 (CM1) is uniformly high (24% to 70%). In Canada, there is limited access to pediatric polysomnography (PSG). Therefore, the identification of clinical features would be invaluable for triaging these children. OBJECTIVE: To identify demographic features, clinical symptoms/signs and radiological findings associated with SDB in a large pediatric cohort with CM1. METHODS: A retrospective review was conducted on children with CM1 who underwent baseline PSG. Data were collected on patient demographics (age, sex, weight, height, body mass index), clinical symptoms (chart review and clinical questionnaires), diagnostic imaging of the brain and cervicothoracic spine, and medical history at the time of referral. RESULTS: A total of 68 children were included in the review. The mean (± SD) age of the children at the time of PSG was 7.33±4.01 years; 56% (n=38) were male. There was a 49% prevalence of SDB in this cohort based on the overall apnea-hypopnea index. Obstructive sleep apnea was the predominant type of SDB. Tonsillar herniation was significantly correlated with obstructive apnea-hypopnea index (r=0.24; P=0.036). CONCLUSIONS: A direct relationship between the degree of cerebellar tonsillar herniation and obstructive sleep apnea was demonstrated. However, further prospective studies that include neurophysiological assessment are needed to further translate the central nervous system imaging findings to predict the presence of SDB. PMID:25379655

Neurosurgical Issues in Pregnancy.

PubMed

Can, Anil; Du, Rose

2017-12-01

Although rare, intracranial hemorrhage due to rupture of cerebral vascular malformations or intracranial aneurysms during pregnancy is a potentially devastating and life-threatening disorder, posing a diagnostic and therapeutic challenge to a multidisciplinary team of neurosurgeons, neurologists, obstetricians, and anesthesiologists. Despite the significant risk of morbidity and mortality affecting both the mother and the unborn child, knowledge of the natural history, epidemiology, and appropriate management of cerebral vascular malformations and intracranial aneurysms in pregnant women is limited. Although emergent neurosurgical concerns usually outweigh obstetric considerations, and treatment of these disorders is generally similar in pregnant and nonpregnant women, any necessary and feasible modifications to protect the unborn child should be made. This article reviews the management of ruptured intracranial aneurysms and cerebral vascular malformations, including arteriovenous malformations, cavernous malformations, and moyamoya disease, in women during pregnancy, partus, and puerperium. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inner ear abnormalities in patients with Goldenhar syndrome.

PubMed

Bisdas, Sotirios; Lenarz, Minoo; Lenarz, Thomas; Becker, Hartmut

2005-05-01

The objective of this study is to investigate the inner ear malformations in patients with Goldenhar syndrome and to hypothesize the potential embryopathogenesis of these malformations. Retrospective case review. Tertiary referral center. Fourteen patients with Goldenhar syndrome. Each patient underwent hearing tests and high-resolution computed tomography (CT) of the temporal bone. In six patients, magnetic resonance imaging of the temporal bone also was performed. Among the 14 patients with Goldenhar syndrome, 13 had outer and middle ear anomalies and 5 (36%) had inner ear malformations, including one case of common cavity. Our observations regarding inner ear anomalies in Goldenhar syndrome correlate with the reported cases in the literature and may help to hypothesize the embryological origin of these malformations, which can caused by an early developmental arrest in the fourth gestational week. Specialists evaluating patients with Goldenhar syndrome should be aware of the possibility of inner ear malformations, which could be diagnosed earlier with appropriate imaging studies.

[Report of a case with Joubert syndrome and literature review].

PubMed

Yi, Ya-hui; Li, Gang; Lu, Zhong-lie; Zhou, Jian-sheng; Yao, Zhen-wei; Wang, Peng-fei; Yao, Jin-xiang

2011-12-01

To explore the clinical feature, imaging and their diagnostic value for Joubert syndrome (JS). The clinical data, imaging feature, and 31 references from China Biomedical literature database (CBMdise) were reviewed and analyzed. The age of onset of 32 patients including male 20 and female 12 ranged from 3 days to 6 years (mean 2.2 years). All the 32 patients with Joubert syndrome showed "slow growth" and "reduced muscle tension", 26 cases (81.3%) showed "gasp for breath", 26 cases (81.3%) showed "unusual motion of eyeball", 2 cases (6.3%) showed additional fingers (toes), 6 cases (18.8%) showed stretching tongue with agape. The typical imaging features of Joubert syndrome included "molar tooth sign", "midline cleavage" between cerebellar hemispheres and "bat-wing" like fourth ventricle, all the 32 patients with Joubert syndrome showed "midline cleavage", "molar tooth sign" was present in 29 cases (90.1%), and "bat-wing" like fourth ventricle in 30 cases (93.8%). Joubert syndrome is a rare congenital brain malformation. The typical clinical manifestations included "gasp for breath", "reduced tension of muscle", "slow growth" and "unusual motion of eyeball", and at the same time the patients had the following typical imaging features of brain: "molar tooth sign", "midline cleavage" and "bat-wing" like fourth ventricle.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buis, Dennis R.; Lagerwaard, Frank J.; Dirven, Clemens M.F.

Purpose: To assess the dosimetric consequences of brain arteriovenous malformation (bAVM) delineation on magnetic resonance angiography (MRA) for the purpose of stereotactic radiosurgery. Methods and Materials: Three observers contoured a bAVM in 20 patients, using digital subtraction angiography (V{sub DSA}) and three-dimensional time-of-flight MRA (V{sub MRA}). Displacement between contours was calculated. Agreement and differences between observers and imaging modalities were assessed. A standardized treatment plan with dynamic conformal arcs was generated and dosimetric coverage of all contours and the volume of normal brain tissue within the high dose region was determined. Results: The generalized reliability coefficient was 'fair' for targetmore » volume (0.79), but 'poor' for displacement (0.35). V{sub MRA} was larger than V{sub DSA} (5.0 vs. 4.0 mL, p = 0.001). No difference in displacement was found (2.8 vs. 2.5 mm, p = 0.156). Dosimetric coverage of V{sub MRA} was 62.9% (95% CI, 56.9-68.8) when V{sub DSA} was used as planning target volume, and coverage of V{sub DSA} was 83.5% (95% CI, 78.1-88.8) when V{sub MRA} was used for planning (p < 0.001). The mean volume of normal brain within the 80% isodose was larger when the bAVM was delineated on MRA (0.7 vs. 1.0 mL (p = 0.02) for targets {<=}3 mL and 3.7 vs. 7.0 mL (p = 0.01) for targets >3 mL). Conclusions: Brain arteriovenous malformations delineated on MRA are larger and more randomly displaced. However, for bAVMs {<=}3 mL, the difference in volume of normal brain tissue within the high-dose region does not seem to be clinically relevant. Therefore, MRA-images might be used as the sole imaging modality for the radiosurgical treatment of bAVMs {<=}3 mL when the bAVM is located in a noneloquent position.« less

Visualization of migration of human cortical neurons generated from induced pluripotent stem cells.

PubMed

Bamba, Yohei; Kanemura, Yonehiro; Okano, Hideyuki; Yamasaki, Mami

2017-09-01

Neuronal migration is considered a key process in human brain development. However, direct observation of migrating human cortical neurons in the fetal brain is accompanied by ethical concerns and is a major obstacle in investigating human cortical neuronal migration. We established a novel system that enables direct visualization of migrating cortical neurons generated from human induced pluripotent stem cells (hiPSCs). We observed the migration of cortical neurons generated from hiPSCs derived from a control and from a patient with lissencephaly. Our system needs no viable brain tissue, which is usually used in slice culture. Migratory behavior of human cortical neuron can be observed more easily and more vividly by its fluorescence and glial scaffold than that by earlier methods. Our in vitro experimental system provides a new platform for investigating development of the human central nervous system and brain malformation. Copyright © 2017 Elsevier B.V. All rights reserved.

Foetal asphyxia as a strong stimulator of the sympathetic nervous system in the brain. Case Report.

PubMed

Brucknerová, Ingrid; Ujházy, Eduard

2016-12-18

The aim of the study was to analyse case report of prenatally unknown asphyxia of the foetus (a preterm newborn from the second pregnancy delivered by urgent caesarean section in 31st gestational week; birth weight 850 grams, birth length 41 cm, value of Apgar score 7/8) with signs of respiratory insufficiency immediately after birth with hypotonicity. The authors present the case of postnatal at the 1st day of life assessed cystic malformation in the brain of premature newborn. They emphasize the importance of detailed prenatal investigation as most important in preventing prenatal asphyxia and consequent complications. Central nervous system and especially white matter of the brain of the newborn is most vulnerable area of the brain. Together with oxidative stress after exceeding of antioxidant capacity belong among main factors that play an important role in the pathogenesis of hypoxic-ischemic encephalopathy.

Inclusion of attentional networks in the pre-surgical neuroimaging assessment of a large deep hemispheric cavernous malformation: an FMRI case report.

PubMed

Mickleborough, Marla J S; Kelly, Michael E; Gould, Layla; Ekstrand, Chelsea; Lorentz, Eric; Ellchuk, Tasha; Babyn, Paul; Borowsky, Ron

2015-01-01

Functional magnetic resonance imaging (fMRI) is a noninvasive and reliable tool for mapping eloquent cortex in patients prior to brain surgery. Ensuring intact perceptual and cognitive processing is a key goal for neurosurgeons, and recent research has indicated the value of including attentional network processing in pre-surgical fMRI in order to help preserve such abilities, including reading, after surgery. We report a 42-year-old patient with a large cavernous malformation, near the left basal ganglia. The lesion measured 3.8 × 1.7 × 1.8 cm. In consultation with the patient and the multidisciplinary cerebrovascular team, the decision was made to offer the patient surgical resection. The surgical resection involved planned access via the left superior parietal lobule using stereotactic location. The patient declined an awake craniotomy; therefore, direct electrocortical stimulation (ECS) could not be used for intraoperative language localization in this case. Pre-surgical planning included fMRI localization of language, motor, sensory, and attentional processing. The key finding was that both reading and attention-processing tasks revealed consistent activation of the left superior parietal lobule, part of the attentional control network, and the site of the planned surgical access. Given this information, surgical access was adjusted to avoid interference with the attentional control network. The lesion was removed via the left inferior parietal lobule. The patient had no new neurologic deficits postoperatively but did develop mild neuropathic pain in the left hand. This case report supports recent research that indicates the value of including fMRI maps of attentional tasks along with traditional language-processing tasks in preoperative planning in patients undergoing neurosurgery procedures. © 2015 S. Karger AG, Basel.

[Macro- and microscopic systematization of cerebral cortex malformations in children].

PubMed

Milovanov, A P; Milovanova, O A

2011-01-01

For the first time in pediatric pathologicoanatomic practice the complete systematization of cerebral cortex malformations is represented. Organ, macroscopic forms: microencephaly, macroencephaly, micropolygyria, pachygyria, schizencephaly, porencephaly, lissencephaly. Histic microdysgenesis of cortex: type I includes isolated abnormalities such as radial (IA) and tangential (I B) subtypes of cortical dislamination; type II includes sublocal cortical dislamination with immature dysmorphic neurons (II A) and balloon cells (II B); type III are the combination focal cortical dysplasia with tuberous sclerosis of the hippocampus (III A), tumors (III B) and malformations of vessels, traumatic and hypoxic disorders (III C). Band heterotopias. Subependimal nodular heterotopias. Tuberous sclerosis. Cellular typification of cortical dysplasia: immature neurons and balloon cells.

Stratified active screening: where neurotechnology meets public health.

PubMed

Valdés, Pedro; Obrador-Fragoso, Adianez

2007-10-01

Nearly one quarter of the global burden of disease stems from neurological, psychiatric and neurodevelopmental disorders due to malformations or dysfunctions of the central nervous system.[1] Such neuropsychiatric conditions influence quality of life worldwide, causing one third of years lost due to disability (YDL).[2] Ranging from congenital conditions to dementias of the elderly, these disorders appear throughout the life cycle and also account for a substantial proportion of mortality. Recent advances in neuroimaging and neuroinformatics have opened the way for early identification of dysfunctional brain networks, providing essential information for the early detection, proper diagnosis, treatment selection, and follow-up of people with disabilities due to brain disorders.

Stratified active screening: where neurotechnology meets public health.

PubMed

Valdés, Pedro; Obrador-Fragoso, Adianez

2008-10-01

Nearly one quarter of the global burden of disease stems from neurological, psychiatric and neurodevelopmental disorders due to malformations or dysfunctions of the central nervous system.[1] Such neuropsychiatric conditions influence quality of life worldwide, causing one third of years lost due to disability (YDL).[2] Ranging from congenital conditions to dementias of the elderly, these disorders appear throughout the life cycle and also account for a substantial proportion of mortality. Recent advances in neuroimaging and neuroinformatics have opened the way for early identification of dysfunctional brain networks, providing essential information for the early detection, proper diagnosis, treatment selection, and follow-up of people with disabilities due to brain disorders.

Stratified active screening: where neurotechnology meets public health.

PubMed

Valdés, Pedro; Obrador-Fragoso, Adianez

2009-01-01

Nearly one quarter of the global burden of disease stems from neurological, psychiatric and neurodevelopmental disorders due to malformations or dysfunctions of the central nervous system.[1] Such neuropsychiatric conditions influence quality of life worldwide, causing one third of years lost due to disability (YDL).[2] Ranging from congenital conditions to dementias of the elderly, these disorders appear throughout the life cycle and also account for a substantial proportion of mortality. Recent advances in neuroimaging and neuroinformatics have opened the way for early identification of dysfunctional brain networks, providing essential information for the early detection, proper diagnosis, treatment selection, and follow-up of people with disabilities due to brain disorders.

Unique cerebrovascular anomalies in Noonan syndrome with RAF1 mutation.

PubMed

Zarate, Yuri A; Lichty, Angie W; Champion, Kristen J; Clarkson, L Kate; Holden, Kenton R; Matheus, M Gisele

2014-08-01

Noonan syndrome is a common autosomal dominant neurodevelopmental disorder caused by gain-of-function germline mutations affecting components of the Ras-MAPK pathway. The authors present the case of a 6-year-old male with Noonan syndrome, Chiari malformation type I, shunted benign external hydrocephalus in infancy, and unique cerebrovascular changes. A de novo heterozygous change in the RAF1 gene was identified. The patient underwent brain magnetic resonance imaging, computed tomography angiography, and magnetic resonance angiography to further clarify the nature of his abnormal brain vasculature. The authors compared his findings to the few cases of Noonan syndrome reported with cerebrovascular pathology. © The Author(s) 2013.

Dandy-Walker Malformation Presenting with Affective Symptoms.

PubMed

Batmaz, Mert; Balçik, Zeynep Ezgi; Özer, Ürün; Hamurişçi Yalçin, Burcu; Özen, Şakir

2017-09-01

Dandy-Walker malformation is defined by enlarged posterior fossa, cystic dilatation of the fourth ventricle, and cerebellar hypoplasia. Although developmental delay and mental retardation are common in Dandy-Walker malformation cases, other comorbid psychiatric conditions have been rarely reported. There are limited numbers of case reports about comorbidity of bipolar disorder with Dandy-Walker malformation in the literature. Herein, a Dandy-Walker malformation case presenting affective symptoms is reported, and psychiatric symptoms which might be seen in this rare malformation are discussed along with diagnosis, treatment, and follow-up processes. A 27-year-old male patient, hospitalized for compulsory treatment, had been diagnosed with Dandy-Walker malformation in childhood. First complaints were attention deficiency, behavioral problems, learning difficulties; and manic and depressive episodes have occurred during follow-ups. He recently complained of decreased need for sleep, irritability, and increased speed of thought, and psychiatric examination was consistent with manic episode. Cranial computed tomography (CT) revealed bilateral ventriculomegaly, enlarged third and fourth ventricles with posterior fossa cyst, and cerebellar hypoplasia. His treatment included 30 mg/day aripiprazole, 1000 mg/day valproic acid, 200 mg/day quetiapine, 4 mg/day biperiden, and 100 mg/month paliperidone palmitate. Beside its traditional role in the regulation of coordination and motor functions, cerebellum is increasingly emphasized for its involvement in the mood regulation. Thus, as seen in Dandy-Walker malformation, cerebellar anomalies are suggested to play a role in the pathophysiology of mood disorders. Further studies are needed to better understand the relationship between mood disorders and cerebellum. Moreover, treatment options should be considered carefully in terms of resistance to treatment and potential side effects, for psychiatric disorders occurring in these cases; and detailed examinations, including cranial imaging, would be beneficial in bipolar cases with early onset, unresponsiveness to treatment, presenting atypical symptoms, mental retardation, and developmental delay as well as neurological symptoms and signs.

Dandy-Walker Malformation Presenting with Affective Symptoms

PubMed Central

BATMAZ, Mert; BALÇIK, Zeynep Ezgi; ÖZER, Ürün; HAMURİŞÇİ YALÇIN, Burcu; ÖZEN, Şakir

2017-01-01

Dandy-Walker malformation is defined by enlarged posterior fossa, cystic dilatation of the fourth ventricle, and cerebellar hypoplasia. Although developmental delay and mental retardation are common in Dandy-Walker malformation cases, other comorbid psychiatric conditions have been rarely reported. There are limited numbers of case reports about comorbidity of bipolar disorder with Dandy-Walker malformation in the literature. Herein, a Dandy-Walker malformation case presenting affective symptoms is reported, and psychiatric symptoms which might be seen in this rare malformation are discussed along with diagnosis, treatment, and follow-up processes. A 27-year-old male patient, hospitalized for compulsory treatment, had been diagnosed with Dandy-Walker malformation in childhood. First complaints were attention deficiency, behavioral problems, learning difficulties; and manic and depressive episodes have occurred during follow-ups. He recently complained of decreased need for sleep, irritability, and increased speed of thought, and psychiatric examination was consistent with manic episode. Cranial computed tomography (CT) revealed bilateral ventriculomegaly, enlarged third and fourth ventricles with posterior fossa cyst, and cerebellar hypoplasia. His treatment included 30 mg/day aripiprazole, 1000 mg/day valproic acid, 200 mg/day quetiapine, 4 mg/day biperiden, and 100 mg/month paliperidone palmitate. Beside its traditional role in the regulation of coordination and motor functions, cerebellum is increasingly emphasized for its involvement in the mood regulation. Thus, as seen in Dandy-Walker malformation, cerebellar anomalies are suggested to play a role in the pathophysiology of mood disorders. Further studies are needed to better understand the relationship between mood disorders and cerebellum. Moreover, treatment options should be considered carefully in terms of resistance to treatment and potential side effects, for psychiatric disorders occurring in these cases; and detailed examinations, including cranial imaging, would be beneficial in bipolar cases with early onset, unresponsiveness to treatment, presenting atypical symptoms, mental retardation, and developmental delay as well as neurological symptoms and signs. PMID:29033643

Vulnerability of children and the developing brain to neurotoxic hazards.

PubMed

Weiss, B

2000-06-01

For much of the history of toxicology, the sensitivity of the developing organism to chemical perturbation attracted limited attention. Several tragic episodes and new insights finally taught us that the course of early brain development incurs unique risks. Although the process is exquisitely controlled, its lability renders it highly susceptible to damage from environmental chemicals. Such disturbances, as recognized by current testing protocols and legislation such as the Food Quality Protection Act, can result in outcomes ranging from death to malformations to functional impairment. The latter are the most difficult to determine. First, they require a variety of measures to assay their extent. Second, adult responses may prove an inadequate guide to the response of the developing brain, which is part of the reason for proposing additional safety factors for children. Third, neuropsychological tests are deployed in complex circumstances in which many factors, including economic status, combine to produce a particular effect such as lowered intelligence quotient score. Fourth, the magnitude of the effect, for most environmental exposure levels, may be relatively small but extremely significant for public health. Fifth, changes in brain function occur throughout life, and some consequences of early damage may not even emerge until advanced age. Such factors need to be addressed in estimating the influence of a particular agent or group of agents on brain development and its functional expression. It is especially important to consider ways of dealing with multiple risks and their combinations in addition to the prevailing practice of estimating risks in isolation.

The possible association between exposure to air pollution and the risk for congenital malformations.

PubMed

Farhi, Adel; Boyko, Valentina; Almagor, Jonatan; Benenson, Itzhak; Segre, Enrico; Rudich, Yinon; Stern, Eli; Lerner-Geva, Liat

2014-11-01

Over the last decade, there is growing evidence that exposure to air pollution may be associated with increased risk for congenital malformations. To evaluate the possible association between exposures to air pollution during pregnancy and congenital malformations among infants born following spontaneously conceived (SC) pregnancies and assisted reproductive technology (ART) pregnancies. This is an historical cohort study comprising 216,730 infants: 207,825 SC infants and 8905 ART conceived infants, during the periods 1997-2004. Air pollution data including sulfur dioxide (SO2), particulate matter <10 µm (PM10), nitrogen oxides (NOx) and ozone (O3) were obtained from air monitoring stations database for the study period. Using a geographic information system (GIS) and the Kriging procedure, exposure to air pollution during the first trimester and the entire pregnancy was assessed for each woman according to her residential location. Logistic regression models with generalized estimating equation (GEE) approach were used to evaluate the adjusted risk for congenital malformations. In the study cohort increased concentrations of PM10 and NOx pollutants in the entire pregnancy were associated with slightly increased risk for congenital malformations: OR 1.06(95% CI, 1.01-1.11) for 10 µg/m(3) increase in PM10 and OR 1.03(95% CI, 1.01-1.04) for 10 ppb increase in NOx. Specific malformations were evident in the circulatory system (for PM10 and NOx exposure) and genital organs (for NOx exposure). SO2 and O3 pollutants were not significantly associated with increased risk for congenital malformations. In the ART group higher concentrations of SO2 and O3 in entire pregnancy were associated (although not significantly) with an increased risk for congenital malformations: OR 1.06(95% CI, 0.96-1.17) for 1 ppb increase in SO2 and OR 1.15(95% CI, 0.69-1.91) for 10 ppb increase in O3. Exposure to higher levels of PM10 and NOx during pregnancy was associated with an increased risk for congenital malformations. Specific malformations were evident in the circulatory system and genital organs. Among ART pregnancies possible adverse association of SO2 and O3 exposure was also observed. Further studies are warranted, including more accurate exposure assessment and a larger sample size for ART pregnancies, in order to confirm these findings. Copyright © 2014 Elsevier Inc. All rights reserved.

Assessment of environmental stressors potentially responsible for malformations in North American anuran amphibians.

PubMed

Ankley, Gerald T; Degitz, S J; Diamond, S A; Tietge, J E

2004-05-01

Several species of anuran amphibians from different regions across North America have recently exhibited an increased occurrence of malformations, predominantly of the hindlimb. Research concerning the potential causes of these malformations has focused extensively on three stressors: chemical contaminants, ultraviolet (UV) radiation, and parasitic trematodes. In this overview of recent work with each of these stressors, we assess their plausibility as contributors to the malformations observed in field-collected amphibians. There is as yet little evidence that chemical contaminants are responsible for the limb malformations. This includes chemicals, such as the pesticide methoprene, that could affect retinoid-signaling pathways that are critical to limb development. Exposure to UV radiation also seems to be an unlikely explanation for hindlimb malformations in amphibians. Although solar UV can cause hindlimb deficiencies in amphibians, a probabilistic assessment based on empirical dose-response and exposure data indicates that UV exposures sufficient to induce limb defects would be uncommon in most wetlands. Results of controlled studies conducted with some affected species and field-monitoring work suggest infection by digenetic trematodes as a promising explanation for the malformations observed in anurans collected from many field sites. Controlled experimentation with additional species and monitoring across a broader range of affected sites are required to assess fully the role of trematodes in relation to other stressors in causing limb malformations. If trematode infestations are indeed related to the recent increases in malformed amphibians, then the question remains as to what alterations in the environment might be causing changes in the distribution and abundance of the parasites.

[Management of occult malformations at the lateral skull base].

PubMed

Bryson, E; Draf, W; Hofmann, E; Bockmühl, U

2005-12-01

Occult malformations of the lateral skull base are rare anomalies, but can cause severe complications such as recurrent meningitis. Therefore, they need to be precisely delineated and sufficient surgical closure is mandatory. Between 1986 and 2004 twenty patients (10 children and 10 adults) with occult malformations at the lateral skull base were treated surgically at the ENT-Department of the Hospital Fulda gAG. Of these 3 Mondini-malformations, 11 defects of the tegmen tympani or the mastoidal roof, 2 dural lesions to the posterior fossa and 4 malformations within the pyramidal apex have been found. Four patients have had multiple anomalies. Routing symptom was in all cases at least one previous meningitis. Radiological diagnostics included high-resolution computed tomography (CT) and magnetic resonance imaging (MRI) as well as CT- or MR-cisternography. Depending on type and localisation of the defect the following surgical algorithm was carried out: The trans-mastoidal approach was used in all cases of Mondini-malformation (including obliteration of the ear), in case of lesions to the posterior fossa as well as partly in anomalies at the tegmen tympani and mastoidal roof, respectively. Defects of the pyramidal apex should be explored via the trans-mastoidal way if the lesion is located caudally to the inner auditory canal (IAC), whereas the trans-temporal approach should be used if the lesion is situated ventral to the IAC and dorso-medially to the internal carotid artery (ICA). The trans-temporal approach was also performed in large defects of the tegmen tympani and mastoidal roof as well as in recurrences. In all cases of recurrent meningitis caused by agents of the upper airway tract the basic principle should be to search for occult skull base malformations radiologically as well as by sodium fluorescein endoscopy as long as the anomaly is detected.

Arteriovenous malformation of the external ear: a clinical assessment with a scoping review of the literature.

PubMed

Kim, Shin Hye; Han, Seung Hoon; Song, Yoonjae; Park, Chang Sik; Song, Jae-Jin

Auricular Arteriovenous Malformation of the external ear is a rarely encountered disease; in particular, arteriovenous malformation arising from the auricle, with spontaneous bleeding, has seldom been reported. In the current study, we report an unusual case of late-onset auricular arteriovenous malformation originating from the posterior auricular artery that was confirmed by computed tomographic angiography. The case was successfully managed by pre-surgical intravascular embolization followed by total lesion excision. Prompted by this case, we also present a scoping review of the literature. A case of a 60 year-old man with right auricular arteriovenous malformation treated in our tertiary care center, and 52 patients with auricular arteriovenous malformation described in 10 case reports and a retrospective review are presented. Auricular arteriovenous malformation can manifest as swelling of the ear, pulsatile tinnitus, pain, and/or bleeding. On physical examination, a pulsatile swelling and/or a tender mass is evident. When arteriovenous malformation is suspected, the lesions should be visualized using imaging modalities that optimally detect vascular lesions, and managed via embolization, mass excision, or auricular resection. Effectiveness of the various diagnostic methods used and the treatment outcomes were analyzed. Various imaging modalities including Doppler sonography, computed tomographic angiography, magnetic resonance angiography, and/or transfemoral cerebral angiography were used to diagnose 38 cases reported in the literature. In another 15 cases, no imaging was performed; treatment was determined solely by physical examination and auscultation. Of the total of 53 cases, 12 were not treated (their symptoms were merely observed) whereas 20 underwent therapeutic embolization. In total, 32 patients, including 1 patient who was not treated and 10 with persistent or aggravated arteriovenous malformation after previous embolization, underwent mass excision or auricular resection depending on the extent of the lesion. No major postoperative complication was recorded. The postoperative follow-up duration varied from 1 month to 19 years, and only one case of unresectable, residual cervicofacial arteriovenous malformation was recorded. Auricular arteriovenous malformation is a rarely encountered disease, but should be suspected if a patient presents with a swollen ear and pulsatile tinnitus. Appropriate imaging is essential for diagnosis and evaluation of the extent of disease. As embolization affords only relatively poor control, total surgical removal of the vascular mass is recommended. Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.

Real-Time Ultrasound-Guided Catheter Navigation for Approaching Deep-Seated Brain Lesions: Role of Intraoperative Neurosonography with and without Fusion with Magnetic Resonance Imaging.

PubMed

Manjila, Sunil; Karhade, Aditya; Phi, Ji Hoon; Scott, R Michael; Smith, Edward R

2017-01-01

Brain shift during the exposure of cranial lesions may reduce the accuracy of frameless stereotaxy. We describe a rapid, safe, and effective method to approach deep-seated brain lesions using real-time intraoperative ultrasound placement of a catheter to mark the dissection trajectory to the lesion. With Institutional Review Board approval, we retrospectively reviewed the radiographic, pathologic, and intraoperative data of 11 pediatric patients who underwent excision of 12 lesions by means of this technique. Full data sets were available for 12 lesions in 11 patients. Ten lesions were tumors and 2 were cavernous malformations. Lesion locations included the thalamus (n = 4), trigone (n = 3), mesial temporal lobe (n = 3), and deep white matter (n = 2). Catheter placement was successful in all patients, and the median time required for the procedure was 3 min (range 2-5 min). There were no complications related to catheter placement. The median diameter of surgical corridors on postresection magnetic resonance imaging was 6.6 mm (range 3.0-12.1 mm). Use of real-time ultrasound guidance to place a catheter to aid in the dissection to reach a deep-seated brain lesion provides advantages complementary to existing techniques, such as frameless stereotaxy. The catheter insertion technique described here provides a quick, accurate, and safe method for reaching deep-seated lesions. © 2017 S. Karger AG, Basel.

Benomyl induction of brain aromatase and toxic effects in the zebrafish embryo.

PubMed

Kim, Dong-Jae; Seok, Seung-Hyeok; Baek, Min-Won; Lee, Hui-Young; Na, Yi-Rang; Park, Sung-Hoon; Lee, Hyun-Kyoung; Dutta, Noton Kumar; Kawakami, Koichi; Park, Jae-Hak

2009-05-01

Benomyl is a benzimidazole fungicide that has been widely used on a variety of food crops and ornamental plants. It is known to cause adverse effects on reproductive systems, including decreased testicular and epididymal weights and reduced epididymal sperm counts and fertility. The brain aromatase gene is up-regulated by estrogens and estrogen mimics and considered a target gene to screen estrogen mimics. This study was designed to test the estrogenic potential and toxic effects of benomyl in the zebrafish system, and validated this system as a model that may correspond to the effect of benomyl in rodents. Concentrations of 20 x 10(-6), 40 x 10(-6) and 80 x 10(-6) M of benomyl-treated embryos showed decreased survival, hatching and heart rates, and increased incidence of malformations, such as pericardial edema, spinal lordosis, elongated heart, head edema, eye lens protrusion and caudal fin disappearance. Benomyl induced enhanced green fluorescent protein (EGFP) expression in the mediobasal hypothalamus (MBH) in transient zebrafish embryos with a brain aromatase-based reporter gene. In this study, we determined that benomyl has estrogenic potential based on zebrafish brain aromatase gene induction, and that benomyl is toxic at 20 x 10(-6) M concentration and higher. These results demonstrate the usefulness of zebrafish embryos as an in vivo system to examine the estrogenic and developmental toxic potential of unknown compounds.

Transarterial Coil-Augmented Onyx Embolization for Brain Arteriovenous Malformation

PubMed Central

Gao, Xu; Liang, Guobiao; Li, Zhiqing; Wang, Xiaogang; Yu, Chunyong; Cao, Peng; Chen, Jun; Li, Jingyuan

2014-01-01

Summary Onyx has been widely adopted for the treatment of arteriovenous malformations (AVMs). However, its control demands operators accumulate a considerable learning curve. We describe our initial experience using a novel injection method for the embolization of AVMs. We retrospectively reviewed the data of all 22 patients with brain AVMs (12 men, 10 women; age range, 12-68 years; mean age, 43.2 years) treated by the transarterial coil-augmented Onyx injection technique. The size of the AVMs ranged from 25 mm to 70 mm (average 35.6 mm). The technical feasibility of the procedure, procedure-related complications, angiographic results, and clinical outcome were evaluated. In every case, endovascular treatment (EVT) was completed. A total of 31 sessions were performed, with a mean injection volume of 6.1 mL (range, 1.5-16.0 mL). An average of 96.7% (range 85%-100%) estimated size reduction was achieved, and 18 AVMs could be completely excluded by EVT alone. The results remained stable on follow-up angiograms. A procedural complication occurred in one patient, with permanent mild neurologic deficit. Our preliminary series demonstrated that the coil-augmented Onyx injection technique is a valuable adjunct achieving excellent nidal penetration and improving the safety of the procedure. PMID:24556304

Retrieving microcatheters from Onyx casts in a series of brain arteriovenous malformations: a technical report.

PubMed

Alamri, A; Hyodo, A; Suzuki, K; Tanaka, Y; Uchida, T; Takano, I; Kowata, K; Iwatate, K; Suzuki, R

2012-11-01

To date, the "monorail snare technique" for the retrieval of entombed microcatheter tips during Onyx(TM) (ev3, Irvine, CA) embolisation of brain arteriovenous malformations (BAVM) has not been described. We report our experiences and some technical aspects in using this technique for the retrieval of entombed Marathon(TM) microcatheter (ev3, Plymouth, MN) tips during Onyx embolisation of BAVM treatment. Onyx was used in the embolisation of 11 patients using 25 feeders over 14 sessions. The 'monorail snare technique' was employed for 14 feeders. Each time, an Amplatz 4 mm Gooseneck Microsnare(TM) (ev3, Plymouth, MN) was loaded into an Excelsior 1018(TM) microcatheter (Boston Scientific, Natick, MA). The Marathon microcatheter was cut just distal to the hub, and the Amplatz/Excelsior combination was introduced along the length of the Marathon microcatheter towards its distal end, as far as possible. The embedded catheter was ensnared and both catheters were pulled free. Microcatheter tip removal was successful in all cases, except for one microcatheter tip becoming detached and needing no further intervention. There were no complications as a direct result of the snare technique. The monorail snare technique is a safe and easy technique for retrieving Onyx-encased microcatheter tips in the treatment of BAVM.

Molecular analysis of holoprosencephaly in South America

PubMed Central

Savastano, Clarice Pagani; El-Jaick, Kênia Balbi; Costa-Lima, Marcelo Aguiar; Abath, Cristina Maria Batista; Bianca, Sebastiano; Cavalcanti, Denise Pontes; Félix, Têmis Maria; Scarano, Gioacchino; Llerena, Juan Clinton; Vargas, Fernando Regla; Moreira, Miguel Ângelo Martins; Seuánez, Hector N.; Castilla, Eduardo Enrique; Orioli, Iêda Maria

2014-01-01

Holoprosencephaly (HPE) is a spectrum of brain and facial malformations primarily reflecting genetic factors, such as chromosomal abnormalities and gene mutations. Here, we present a clinical and molecular analysis of 195 probands with HPE or microforms; approximately 72% of the patients were derived from the Latin American Collaborative Study of Congenital Malformations (ECLAMC), and 82% of the patients were newborns. Alobar HPE was the predominant brain defect in almost all facial defect categories, except for patients without oral cleft and median or lateral oral clefts. Ethmocephaly, cebocephaly, and premaxillary agenesis were primarily observed among female patients. Premaxillary agenesis occurred in six of the nine diabetic mothers. Recurrence of HPE or microform was approximately 19%. The frequency of microdeletions, detected using Multiplex Ligation-dependant Probe Amplification (MLPA) was 17% in patients with a normal karyotype. Cytogenetics or QF-PCR analyses revealed chromosomal anomalies in 27% of the probands. Mutational analyses in genes SHH, ZIC2, SIX3 and TGIF were performed in 119 patients, revealing eight mutations in SHH, two mutations in SIX3 and two mutations in ZIC2. Thus, a detailed clinical description of new HPE cases with identified genetic anomalies might establish genotypic and phenotypic correlations and contribute to the development of additional strategies for the analysis of new cases. PMID:24764759

Clinico-radiological and molecular characterization of a child with ring chromosome 2 presenting growth failure, microcephaly, kidney and brain malformations.

PubMed

Severino, Mariasavina; Accogli, Andrea; Gimelli, Giorgio; Rossi, Andrea; Kotzeva, Svetlana; Di Rocco, Maja; Ronchetto, Patrizia; Cuoco, Cristina; Tassano, Elisa

2015-01-01

Ring chromosome 2 is a rare constitutional abnormality that generally occurs de novo. About 14 cases have been described to date, but the vast majority of papers report exclusively conventional cytogenetic investigations and only two have been characterized by array-CGH. Here we describe the clinical, neuroradiological, and molecular features of a 5-year-old boy harbouring a ring chromosome 2 presenting with severe growth failure, facial and bone dysmorphisms, microcephaly, and renal malformation. Brain MR with diffusion tensor imaging revealed simplified cortical gyration, pontine hypoplasia, and abnormally thick posterior corpus callosum, suggesting an underlying axonal guidance defect. Cytogenetic investigations showed a karyotype with a ring chromosome 2 and FISH analysis with subtelomeric probes revealed the absence of signals on both arms. These results were confirmed by array-CGH showing terminal deletions on 2p25.3 (~439 kb) and 2q37.3 (~3.4 Mb). Our report describes a new patient with a ring chromosome 2 completely characterised by array-CGH providing additional information useful not only to study genotype-phenotype correlation but also to validate the role of already reported candidate genes and to suggest novel ones which could improve our understanding of the clinical features associated with ring chromosome 2.

Perioperative management of a patient with Dandy Walker malformation with tetralogy of Fallot undergoing total correction and fresh homologous pericardial pulmonary valve conduit implantation: Report of a rare case

PubMed Central

Datt, Vishnu; Tempe, D. K.; Lalwani, Parin; Aggarwal, Saket; Kumar, Pradeep; Diwakar, Anitha; Tomar, A. S.

2015-01-01

Perioperative management of a patient with Dandy–Walker malformation (DWM) with tetralogy of Fallot (TOF), patent ductus arteriosus, and pulmonary artery stenosis is a great challenge to the anesthesiologist. Anesthetic management in such patients can trigger tet spells that might rapidly increase intracranial pressure (ICP), conning and even death. The increase in ICP can precipitate tet spells and further brain hypoxia. To avoid an increase in ICP during TOF corrective surgery ventriculo-peritoneal (VP) shunt should be performed before cardiac surgery. We present the first case report of a 11-month-old male baby afflicted with DWM and TOF who underwent successful TOF total corrective surgery and fresh autologous pericardial pulmonary valve conduit implantation under cardiopulmonary bypass after 1 week of VP shunt insertion. PMID:26139758

Perioperative management of a patient with Dandy Walker malformation with tetralogy of Fallot undergoing total correction and fresh homologous pericardial pulmonary valve conduit implantation: Report of a rare case.

PubMed

Datt, Vishnu; Tempe, D K; Lalwani, Parin; Aggarwal, Saket; Kumar, Pradeep; Diwakar, Anitha; Tomar, A S

2015-01-01

Perioperative management of a patient with Dandy-Walker malformation (DWM) with tetralogy of Fallot (TOF), patent ductus arteriosus, and pulmonary artery stenosis is a great challenge to the anesthesiologist. Anesthetic management in such patients can trigger tet spells that might rapidly increase intracranial pressure (ICP), conning and even death. The increase in ICP can precipitate tet spells and further brain hypoxia. To avoid an increase in ICP during TOF corrective surgery ventriculo-peritoneal (VP) shunt should be performed before cardiac surgery. We present the first case report of a 11-month-old male baby afflicted with DWM and TOF who underwent successful TOF total corrective surgery and fresh autologous pericardial pulmonary valve conduit implantation under cardiopulmonary bypass after 1 week of VP shunt insertion.

Disease-modifying anti-rheumatic drug use in pregnant women with rheumatic diseases: a systematic review of the risk of congenital malformations.

PubMed

Baldwin, Corisande; Avina-Zubieta, Antonio; Rai, Sharan K; Carruthers, Erin; De Vera, Mary A

2016-01-01

Despite the high incidence of rheumatic diseases during the reproductive years, little is known about the impact of disease-modifying anti-rheumatic drug (DMARD) use during pregnancy. Our objective was to systematically review and appraise evidence in women with rheumatic disease on the use of traditional and biologic DMARDs during pregnancy and the risk of congenital malformation outcomes. We conducted a systematic search of MEDLINE, EMBASE, and INTERNATIONAL PHARMACEUTICAL ABSTRACTS databases. Inclusion criteria were: 1) study sample including women with rheumatic disease; 2) use of traditional and/or biologic DMARDs during pregnancy; and 3) congenital malformation outcome(s) reported. We extracted information on study design, data source, number of exposed pregnancies, type of DMARD, number of live births, and number of congenital malformations. Altogether, we included 79 studies; the majority were based on designs that did not involve a comparison group, including 26 case reports, 17 case series, 20 cross-sectional studies, and 4 surveys. Studies that had a comparator group included 1 case control, 10 cohort studies, and 1 controlled trial. Hydroxychloroquine and azathioprine represent the most studied traditional DMARD exposures and, among biologics, most of the reports were on infliximab and etanercept. This is the first systematic review on the use of both traditional and biologic DMARDs during pregnancy among women with rheumatic diseases and congenital malformation outcomes, with a focus on study design and quality. Findings confirm the limited number of studies, as well as the need to improve study designs.

Comparative transcriptomic analyses of normal and malformed flowers in sugar apple (Annona squamosa L.) to identify the differential expressed genes between normal and malformed flowers.

PubMed

Liu, Kaidong; Li, Haili; Li, Weijin; Zhong, Jundi; Chen, Yan; Shen, Chenjia; Yuan, Changchun

2017-10-23

Sugar apple (Annona squamosa L.), a popular fruit with high medicinal and nutritional properties, is widely cultivated in tropical South Asia and America. The malformed flower is a major cause for a reduction in production of sugar apple. However, little information is available on the differences between normal and malformed flowers of sugar apple. To gain a comprehensive perspective on the differences between normal and malformed flowers of sugar apple, cDNA libraries from normal and malformation flowers were prepared independently for Illumina sequencing. The data generated a total of 70,189,896 reads that were integrated and assembled into 55,097 unigenes with a mean length of 783 bp. A large number of differentially expressed genes (DEGs) were identified. Among these DEGs, 701 flower development-associated transcript factor encoding genes were included. Furthermore, a large number of flowering- and hormone-related DEGs were also identified, and most of these genes were down-regulated expressed in the malformation flowers. The expression levels of 15 selected genes were validated using quantitative-PCR. The contents of several endogenous hormones were measured. The malformed flowers displayed lower endogenous hormone levels compared to the normal flowers. The expression data as well as hormone levels in our study will serve as a comprehensive resource for investigating the regulation mechanism involved in floral organ development in sugar apple.

Effects of diquat, an aquatic herbicide, on the development of mallard embryos

USGS Publications Warehouse

Sewalk, C.J.; Brewer, G.L.; Hoffman, D.J.

2001-01-01

Bipyridylium herbicides produce embryotoxic and teratogenic effects in dipteran, amphibian, avian, and mammalian organisms. Diquat dibromide, a bipyridylium compound, is commonly used as an aquatic herbicide. Mallard (Anas platyrhynchos) eggs were exposed to diquat by immersing the eggs for 10s in solutions of 0.88, 3.5, 7, 14, or 56 g/L on either the fourth or twenty-first day of incubation. Application of diquat on day 4 yielded an estimated LC50 of 19.5 g/L through 18 days of incubation, and 9.6 g/L through hatching. Body and organ weights, and bone lengths of hatchlings did not differ between control and treatment groups with the exception of a slight increase in brain weight in the 14 g/L group. Malformations in diquat-treated embryos included defects of the brain, eye, bill, limb, and pelvis; skeletal scoliosis; and incomplete ossification. Subcutaneous edema was also present. Significant manifestations of oxidative stress were apparent in hatchlings and included increased hepatic thiobarbituric acid reactive substances (TBARS) (lipid peroxidation) and decreased brain reduced glutathione (GSH). Brain protein-bound sulfhydryls (PBSH) increased. Diquat applied on day 21 of incubation yielded an estimated LC50 of 12.6 g/L through hatching. Exposure at this late stage of development did not produce deformities. Body and organ weights, and, bone lengths of hatchlings did not differ between control and treatment groups. Significant manifestations of oxidative stress in hatchlings included decreased brain GSH, increased oxidized glutathione (GSSG) and ratio of GSSG:GSH. This study suggests that concentrations of diquat commonly used for aquatic weed control, when based upon the expected dilution effect of average water depth of the application area, would probably have little impact on mallard embryos. However, concentrations applied above ground to weeds and cattails along the edge of waters and ditches could adversely affect the survival and development of mallard embryos, and presumably other avian species nesting in such habitats.

Temporal requirement of dystroglycan glycosylation during brain development and rescue of severe cortical dysplasia via gene delivery in the fetal stage.

PubMed

Sudo, Atsushi; Kanagawa, Motoi; Kondo, Mai; Ito, Chiyomi; Kobayashi, Kazuhiro; Endo, Mitsuharu; Minami, Yasuhiro; Aiba, Atsu; Toda, Tatsushi

2018-04-01

Congenital muscular dystrophies (CMDs) are characterized by progressive weakness and degeneration of skeletal muscle. In several forms of CMD, abnormal glycosylation of α-dystroglycan (α-DG) results in conditions collectively known as dystroglycanopathies, which are associated with central nervous system involvement. We recently demonstrated that fukutin, the gene responsible for Fukuyama congenital muscular dystrophy, encodes the ribitol-phosphate transferase essential for dystroglycan function. Brain pathology in patients with dystroglycanopathy typically includes cobblestone lissencephaly, mental retardation, and refractory epilepsy; however, some patients exhibit average intelligence, with few or almost no structural defects. Currently, there is no effective treatment for dystroglycanopathy, and the mechanisms underlying the generation of this broad clinical spectrum remain unknown. Here, we analysed four distinct mouse models of dystroglycanopathy: two brain-selective fukutin conditional knockout strains (neuronal stem cell-selective Nestin-fukutin-cKO and forebrain-selective Emx1-fukutin-cKO), a FukutinHp strain with the founder retrotransposal insertion in the fukutin gene, and a spontaneous Large-mutant Largemyd strain. These models exhibit variations in the severity of brain pathology, replicating the clinical heterogeneity of dystroglycanopathy. Immunofluorescence analysis of the developing cortex suggested that residual glycosylation of α-DG at embryonic day 13.5 (E13.5), when cortical dysplasia is not yet apparent, may contribute to subsequent phenotypic heterogeneity. Surprisingly, delivery of fukutin or Large into the brains of mice at E12.5 prevented severe brain malformation in Emx1-fukutin-cKO and Largemyd/myd mice, respectively. These findings indicate that spatiotemporal persistence of functionally glycosylated α-DG may be crucial for brain development and modulation of glycosylation during the fetal stage could be a potential therapeutic strategy for dystroglycanopathy.

Endovascular balloon-assisted embolization of intracranial and cervical arteriovenous malformations using dual-lumen coaxial balloon microcatheters and Onyx: initial experience.

PubMed

Jagadeesan, Bharathi D; Grigoryan, Mikayel; Hassan, Ameer E; Grande, Andrew W; Tummala, Ramachandra P

2013-12-01

Ethylene vinyl alcohol copolymer (Onyx) is widely used for the embolization of arteriovenous malformations (AVMs) of the brain, head, and neck. Balloon-assisted Onyx embolization may provide additional unique advantages in the treatment of AVMs in comparison with traditional catheter-based techniques. To report our initial experience in performing balloon-assisted AVM embolization for brain and neck AVMs with the use of the new Scepter-C and Scepter-XC coaxial dual-lumen balloon microcatheters. Balloon-assisted transarterial embolization was performed in a series of 7 patients with AVMs (4 with brain AVMs, 1 with a dural arteriovenous fistula, and 2 with neck AVMs) by using Onyx delivered through the lumen of Scepter-C or Scepter XC coaxial balloon microcatheters. Following the initial balloon-catheter navigation into a feeding artery and the subsequent inflation of the balloon, the embolization was performed by using Onyx 18, Onyx 34, or both. A total of 12 embolization sessions were performed via 17 arterial feeders in these 7 patients. In 1 patient, there was an arterial perforation from the inflation of the balloon; in all others, the embolization goals were successfully achieved with no adverse events. The balloon microcatheters showed excellent navigability, and there were no problems with retrieval or with the repeated inflation and deflation of the balloons. A proximal Onyx plug, which is crucial in many AVM embolizations, was not necessary with this technique. Additionally, fluoroscopy and procedural times seemed lower with this technique compared with conventional embolization methods.

[Septo-optic dysplasia].

PubMed

Martínez-Sánchez, L; Arce, A; Caritg-Bosch, J; Campistol, J; Pavía, C; Gean-Molins, E

Septo optic syndrome, described by De Morsier in 1956, consists in the hypoplasia of one or both optic nerves, mid line brain malformations and hypothalamohypophysial dysfunction, which is inconstant. It is an infrequent, but treatable, cause of hepatic and neurological damage, and it is important to obtain an early diagnosis and to begin hormone replacement therapy. We report the clinical case of a female baby who was diagnosed early on as suffering from septo?optic dysplasia, after discovery of the existence of cholestatic jaundice. In our case the three components of the syndrome were present: hypothalamohypophysial dysfunction, bilateral hypoplasia of the optic nerves and brain malformations with dysplasia of the transparent septum. All this gives rise to complex clinical features and the predominance of hypernatraemic dehydration secondary to insipid diabetes, nystagmus and serious psychomotor retardation. Our patient died, as in other cases reported in the literature, from an episode of sudden death. Despite the importance of an early diagnosis of this disorder, it is usually late. Most children who present hypopituitarism traits in the neonatal period are not diagnosed at that time, with the subsequent risk of death or brain damage. Some clinical findings, which appear early on and can provide clues which aid us to reach a diagnosis, are the appearance of episodes of hypoglycaemia in the neonatal period, the existence of micropenis and cryptorchidism with hypoplasic testes, jaundice or the appearance of clinical manifestations of insipid diabetes. Later on nystagmus and neurological symptoms may appear. The final diagnosis is performed through the use of neuroimaging techniques (CT or MRI) and hormonal studies.

[Treatment analyses of 143 patients with maxillofacial and cervical venous malformations involved in isthmus faucium area].

PubMed

Ge, C X; Tai, M Z; Chen, T; Li, K L; Qin, Z P

2017-12-07

Objective: To analyze the clinical data and summarize therapeutic experiences of cervicofacial venous malformations involving isthmus faucium area. Methods: Clinical records from 143 patients with venous malformations involving isthmus faucium area treated at our hospital between January 2012 and January 2016 were reviewed. There were 70 males and 73 females. Age ranged from 1 to 52 years old, with a median age of 14.5 years. There were 19 cases with lesions involving in only 1 subanatomic area above and 124 cases with lesions involving in more than 1 subanatomic areas, including 63 cases with lesions involving in more than 2 areas. There were 50 patients presenting with additional maxillofacial and cervical lesions. Clinical symptoms included snoring ( n =98), indistinct phonation ( n =49), and tonsil hypertrophy more than degree Ⅱ ( n =19). Tracheotomy was performed in 3 patients prior to hospitalization, contigency tracheotomy during hospitalization in 10 patients, and oral trachea cannula in other patients. All therapeutic procedures, including single chemical ablation with ethanol injection ( n =94), single lesion resection ( n =9) and both of them ( n =40), were performed under general anesthesia. Treatment remedies included mesh suture, macroglossia reduction and excision of maxillofacial and cervical lesions for patients presenting with extensive malformations extending to maxillofacial and cervical area. Tonsil resection were done in patients having tonsil venous malformations or tonsil hypertrophy more than degree II. Achauer's 4-grade criterion was applied to evaluate the treatment outcomes. SPSS 18.0 software was used to analyze the data. Results: Trachea cannula were not extubated untill 24 to 48 hours after treatment. Emergency tracheotomy was done in 2 cases after extubations because of dyspnea, and successful extubations were obtained in other cases. There were no advents of pulmonary vascular spasm or pulmonary embolism. There was significant difference between before and after operation (snore: χ(2)=105.431, ambiguous pronunciation: χ(2)=59.698, tonsil hypertrophy more than degree Ⅱ: χ(2)=33.530, all P <0.01). The patients were followed-up for 1-4 years, and there were 123 cases at grade Ⅳ (complete disappear of lesions in 62 cases without recurrence), 17 at grade Ⅲ , 3 at grade Ⅱ, and no case at gradeⅠ. Conclusions: Chemical ablation with ethanol injection for venous malformations involving isthmus faucium area is recommended, wheras combined remedies including injection, mesh suture, macroglossia reduction, and excision of cervicofacial lesions are suggested in treatment of extensive lesions extending to maxillofacial and cervical area. Tonsil resection should be done in patients having tonsil venous malformations or tonsil hypertrophy more than degree Ⅱ, which is safe and highly effective, with good reservation of function, in the treatment of maxillofacial and cervical venous malformations involving isthmus faucium area.

Anatomic Malformations of the Middle and Inner Ear in 22q11.2 Deletion Syndrome: Case Series and Literature Review.

PubMed

Verheij, E; Elden, L; Crowley, T B; Pameijer, F A; Zackai, E H; McDonald-McGinn, D M; Thomeer, H G X M

2018-05-01

The 22q11.2 deletion syndrome is characterized by a heterogenic phenotype, including hearing loss. The underlying cause of hearing loss, especially sensorineural hearing loss, is not yet clear. Therefore, our objective was to describe anatomic malformations in the middle and inner ear in patients with 22q11.2 deletion syndrome. A retrospective case series was conducted in 2 tertiary referral centers. All patients with 22q11.2 deletion syndrome who had undergone CT or MR imaging of the temporal bones were included. Radiologic images were evaluated on predetermined parameters, including abnormalities of the ossicular chain, cochlea, semicircular canals, and vestibule. There were 26 patients (52 ears) with a CT or MR imaging scan available. A dense stapes superstructure was found in 18 ears (36%), an incomplete partition type II was suspected in 12 cochleas (23%), the lateral semicircular canal was malformed with a small bony island in 17 ears (33%), and the lateral semicircular canal and vestibule were fused to a single cavity in 15 ears (29%). Middle and inner ear abnormalities were frequently encountered in our cohort, including malformations of the lateral semicircular canal. © 2018 by American Journal of Neuroradiology.

Anomalous optic discs in a patient with a Dandy-Walker cyst.

PubMed

Orcutt, J C; Bunt, A H

1982-03-01

A 19-month-old female infant with a Dandy-Walker cyst had anomalous optic discs, each of which appeared to divide to form an accessory optic nerve. The discs probably lie within the spectrum of anomalous discs including optic nerve aplasia and hypoplasia, megallopapillae, morning glory disc, optic disc dysplasia, and optic nerve colobomas. The association of anomalous optic discs with a Dandy-Walker cyst has not been previously recognized. The ocular and brain malformations in this patient likely occurred during the fourth to eighth week of gestation, when the retinal ganglion cell axons were penetrating the optic nerve, and the rhombic lips were enlarging in early cerebellar development. The etiology of these anomalies is not known; however, teratogens, sporadic events, and genetic disorders should be considered.

Autism traits in individuals with agenesis of the corpus callosum

PubMed Central

Lau, Yolanda C.; Hinkley, Leighton B. N.; Bukshpun, Polina; Strominger, Zoe A.; Wakahiro, Mari L. J.; Baron-Cohen, Simon; Allison, Carrie; Auyeung, Bonnie; Jeremy, Rita J.; Nagarajan, Srikantan S.; Sherr, Elliott H.; Marco, Elysa J.

2013-01-01

Autism spectrum disorders (ASD) have numerous etiologies, including structural brain malformations such as agenesis of the corpus callosum (AgCC). We sought to directly measure the occurrence of autism traits in a cohort of individuals with AgCC and to investigate the neural underpinnings of this association. We screened a large AgCC cohort (n = 106) with the Autism Spectrum Quotient (AQ) and found that 45% of children, 35% of adolescents, and 18% of adults exceeded the predetermined autism-screening cut-off. Interestingly, performance on the AQ’s imagination domain was inversely correlated with magnetoencephalography measures of resting-state functional connectivity in the right superior temporal gyrus. Individuals with AgCC should be screened for ASD and disorders of the corpus callosum should be considered in autism diagnostic evaluations as well. PMID:23054201

Structural basis for regulation of GPR56/ADGRG1 by its alternatively spliced extracellular domains

PubMed Central

Salzman, Gabriel S.; Ackerman, Sarah D.; Ding, Chen; Koide, Akiko; Leon, Katherine; Luo, Rong; Stoveken, Hannah M.; Fernandez, Celia G.; Tall, Gregory G.; Piao, Xianhua; Monk, Kelly R.; Koide, Shohei; Araç, Demet

2016-01-01

Summary Adhesion G-protein-coupled receptors (aGPCRs) play critical roles in diverse neurobiological processes including brain development, synaptogenesis, and myelination. aGPCRs have large alternatively spliced extracellular regions (ECRs) that likely mediate intercellular signaling; however, the precise roles of ECRs remain unclear. The aGPCR GPR56/ADGRG1 regulates both oligodendrocyte and cortical development. Accordingly, human GPR56 mutations cause myelination defects and brain malformations. Here, we determined the crystal structure of the GPR56 ECR, the first structure of any complete aGPCR ECR, in complex with an inverse-agonist monobody, revealing a GPCR-Autoproteolysis-Inducing domain and a previously unidentified domain that we term Pentraxin/Laminin/neurexin/sex-hormone-binding-globulin-Like (PLL). Strikingly, PLL domain deletion caused increased signaling and characterizes a GPR56 splice variant. Finally, we show that an evolutionarily conserved residue in the PLL domain is critical for oligodendrocyte development in vivo. Thus, our results suggest that the GPR56 ECR has unique and multifaceted regulatory functions, providing novel insights into aGPCR roles in neurobiology. PMID:27657451

De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes

PubMed Central

Rivière, Jean-Baptiste; Mirzaa, Ghayda M.; O’Roak, Brian J.; Beddaoui, Margaret; Alcantara, Diana; Conway, Robert L.; St-Onge, Judith; Schwartzentruber, Jeremy A.; Gripp, Karen W.; Nikkel, Sarah M.; Worthylake, Thea; Sullivan, Christopher T.; Ward, Thomas R.; Butler, Hailly E.; Kramer, Nancy A.; Albrecht, Beate; Armour, Christine M.; Armstrong, Linlea; Caluseriu, Oana; Cytrynbaum, Cheryl; Drolet, Beth A.; Innes, A. Micheil; Lauzon, Julie L.; Lin, Angela E.; Mancini, Grazia M. S.; Meschino, Wendy S.; Reggin, James D.; Saggar, Anand K.; Lerman-Sagie, Tally; Uyanik, Gökhan; Weksberg, Rosanna; Zirn, Birgit; Beaulieu, Chandree L.; Majewski, Jacek; Bulman, Dennis E.; O’Driscoll, Mark; Shendure, Jay; Graham, John M.; Boycott, Kym M.; Dobyns, William B.

2012-01-01

Megalencephaly-capillary malformation (MCAP) and megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndromes are sporadic overgrowth disorders associated with markedly enlarged brain size and other recognizable features1-5. We performed exome sequencing in three families with MCAP or MPPH and confirmed our initial observations in exomes from 7 MCAP and 174 control individuals, as well as in 40 additional megalencephaly subjects using a combination of Sanger sequencing, restriction-enzyme assays, and targeted deep sequencing. We identified de novo germline or postzygotic mutations in three core components of the phosphatidylinositol-3-kinase (PI3K)/AKT pathway. These include two mutations of AKT3, one recurrent mutation of PIK3R2 in 11 unrelated MPPH families, and 15 mostly postzygotic mutations of PIK3CA in 23 MCAP and one MPPH patients. Our data highlight the central role of PI3K/AKT signaling in vascular, limb and brain development, and emphasize the power of massively parallel sequencing in a challenging context of phenotypic and genetic heterogeneity combined with postzygotic mosaicism. PMID:22729224

Anomalous vascularization in a Wnt medulloblastoma: a case report.

PubMed

Di Giannatale, Angela; Carai, Andrea; Cacchione, Antonella; Marrazzo, Antonio; Dell'Anna, Vito Andrea; Colafati, Giovanna Stefania; Diomedi-Camassei, Francesca; Miele, Evelina; Po, Agnese; Ferretti, Elisabetta; Locatelli, Franco; Mastronuzzi, Angela

2016-07-15

Medulloblastoma is the most common malignant brain tumor in children. To date only few cases of medulloblastoma with hemorrhages have been reported in the literature. Although some studies speculate on the pathogenesis of this anomalous increased vascularization in medulloblastoma, the specific mechanism is still far from clearly understood. A correlation between molecular medulloblastoma subgroups and hemorrhagic features has not been reported, although recent preliminary studies described that WNT-subtype tumors display increased vascularization and hemorrhaging. Herein, we describe a child with a Wnt-medulloblastoma presenting as cerebellar-vermian hemorrhagic lesion. Brain magnetic resonance imaging (MRI) showed the presence of a midline posterior fossa mass with a cystic hemorrhagic component. The differential diagnosis based on imaging included cavernous hemangioma, arteriovenous malformation and traumatic lesion. At surgery, the tumor appeared richly vascularized as documented by the preoperative angiography. The case we present showed that Wnt medulloblastoma may be associated with anomalous vascularization. Further studies are needed to elucidate if there is a link between the hypervascularization and the Wnt/β-catenin signaling activation and if this abnormal vasculature might influence drug penetration contributing to good prognosis of this medulloblastoma subgroup.

De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes.

PubMed

Rivière, Jean-Baptiste; Mirzaa, Ghayda M; O'Roak, Brian J; Beddaoui, Margaret; Alcantara, Diana; Conway, Robert L; St-Onge, Judith; Schwartzentruber, Jeremy A; Gripp, Karen W; Nikkel, Sarah M; Worthylake, Thea; Sullivan, Christopher T; Ward, Thomas R; Butler, Hailly E; Kramer, Nancy A; Albrecht, Beate; Armour, Christine M; Armstrong, Linlea; Caluseriu, Oana; Cytrynbaum, Cheryl; Drolet, Beth A; Innes, A Micheil; Lauzon, Julie L; Lin, Angela E; Mancini, Grazia M S; Meschino, Wendy S; Reggin, James D; Saggar, Anand K; Lerman-Sagie, Tally; Uyanik, Gökhan; Weksberg, Rosanna; Zirn, Birgit; Beaulieu, Chandree L; Majewski, Jacek; Bulman, Dennis E; O'Driscoll, Mark; Shendure, Jay; Graham, John M; Boycott, Kym M; Dobyns, William B

2012-06-24

Megalencephaly-capillary malformation (MCAP) and megalencephaly-polymicrogyria-polydactyly-hydrocephalus (MPPH) syndromes are sporadic overgrowth disorders associated with markedly enlarged brain size and other recognizable features. We performed exome sequencing in 3 families with MCAP or MPPH, and our initial observations were confirmed in exomes from 7 individuals with MCAP and 174 control individuals, as well as in 40 additional subjects with megalencephaly, using a combination of Sanger sequencing, restriction enzyme assays and targeted deep sequencing. We identified de novo germline or postzygotic mutations in three core components of the phosphatidylinositol 3-kinase (PI3K)-AKT pathway. These include 2 mutations in AKT3, 1 recurrent mutation in PIK3R2 in 11 unrelated families with MPPH and 15 mostly postzygotic mutations in PIK3CA in 23 individuals with MCAP and 1 with MPPH. Our data highlight the central role of PI3K-AKT signaling in vascular, limb and brain development and emphasize the power of massively parallel sequencing in a challenging context of phenotypic and genetic heterogeneity combined with postzygotic mosaicism.

Hydrocephalus in Dandy-Walker malformation.

PubMed

Spennato, Pietro; Mirone, Giuseppe; Nastro, Anna; Buonocore, Maria Consiglio; Ruggiero, Claudio; Trischitta, Vincenzo; Aliberti, Ferdinando; Cinalli, Giuseppe

2011-10-01

Even if the first description of Dandy-Walker dates back 1887, difficulty in the establishment of correct diagnosis, especially concerning differential diagnosis with other types of posterior fossa CSF collection, still persists. Further confusion is added by the inclusion, in some classification, of different malformations with different prognosis and therapeutic strategy under the same label of "Dandy-Walker". An extensive literature review concerning embryologic, etiologic, pathogenetic, clinical and neuroradiological aspects has been performed. Therapeutic options, prognosis and intellectual outcome are also reviewed. The correct interpretation of the modern neuroradiologic techniques, including CSF flow MR imaging, may help in identifying a "real" Dandy-Walker malformation. Among therapeutical strategies, single shunting (ventriculo-peritoneal or cyst-peritoneal shunts) appears effective in the control of both ventricle and cyst size. Endoscopic third ventriculostomy may be considered an acceptable alternative, especially in older children, with the aim to reduce the shunt-related problems. Prognosis and intellectual outcome mostly depend on the presence of associated malformations, the degree of vermian malformation and the adequate control of hydrocephalus.

Intestinal atresia, encephalocele, and cardiac malformations in infants with 47,XXX: Expansion of the phenotypic spectrum and a review of the literature.

PubMed

Bağci, Soyhan; Müller, Andreas; Franz, Axel; Heydweiller, Andreas; Berg, Christoph; Nöthen, Markus M; Bartmann, Peter; Reutter, Heiko

2010-01-01

Identification of the 47,XXX karyotype often occurs adventitiously during prenatal fetal karyotyping in cases of advanced maternal age. Although most females with 47,XXX appear healthy at birth, various types of congenital malformations have been reported, of which urinary tract anomalies are the most frequent. We report on 2 newborns with 47,XXX and congenital cardiac defects, one of whom had duodenal atresia and the other an occipital encephalocele. This expands the spectrum of malformations reported in association with the triple-X syndrome. We also present a review of the literature on non-urinary tract malformations in females with 47,XXX. We conclude that prenatal identification of the 47,XXX karyotype is an indication for detailed fetal ultrasonography which should include examination of multiple organ systems. Such prenatal screening for possible associated congenital malformations should help to ensure optimal perinatal clinical management of 47,XXX cases. 2010 S. Karger AG, Basel.

Brain Lesions in Children with Unilateral Spastic Cerebral Palsy.

PubMed

Hadzagic-Catibusic, Feriha; Avdagic, Edin; Zubcevic, Smail; Uzicanin, Sajra

2017-02-01

Unilateral spastic cerebral palsy (US CP) is the second most common subtype of cerebral palsy. The aim of the study was to analyze neuroimaging findings in children with unilateral spastic cerebral palsy. The study was hospital based, which has included 106 patients with US CP (boys 72/girls 34, term 82/preterm 24). Neuroimaging findings were classified into 5 groups: Brain maldevelopment, predominant white matter injury, predominant gray matter injury, non specific findings and normal neuroimaging findings. Predominant white matter lesions where the most frequent (48/106,45.28%; term 35/preterm 13), without statistically significant difference between term and preterm born children (x2=0.4357; p=0.490517). Predominant gray matter lesions had 32/106 children, 30.19%; (term 25/preterm 7, without statistically significant difference between term and preterm born children (x2=0.902; p=0.9862). Brain malformations had 10/106 children, 9.43%, and all of them were term born. Other finding had 2/106 children, 1.89%, both of them were term born. Normal neuroimaging findings were present in14/106 patients (13.21%). Neuroimaging may help to understand morphological background of motor impairment in children with US CP. Periventricular white matter lesions were the most frequent, then gray matter lesions.

Description and initial evaluation of an educational and psychosocial support model for adults with congenitally malformed hearts.

PubMed

Rönning, Helén; Nielsen, Niels Erik; Swahn, Eva; Strömberg, Anna

2011-05-01

Various programmes for adults with congenitally malformed hearts have been developed, but detailed descriptions of content, rationale and goals are often missing. The aim of this study was to describe and make an initial evaluation of a follow-up model for adults with congenitally malformed hearts, focusing on education and psychosocial support by a multidisciplinary team (EPS). The model is described in steps and evaluated with regards to perceptions of knowledge, anxiety and satisfaction. The EPS model included a policlinic visit to the physician/nurse (medical consultation, computer-based and individual education face-to-face as well as psychosocial support) and a 1-month telephone follow-up. Fifty-five adults (mean age 34, 29 women) with the nine most common forms of congenitally malformed hearts participated in the EPS model as well as the 3-months follow-up. Knowledge about congenital heart malformation had increased in 40% of the participants at the 3-months follow-up. This study describes and evaluates a model that combines a multidisciplinary approach and computer-based education for follow-up of adults with congenitally malformed hearts. The EPS model was found to increase self-estimated knowledge, but further evaluations need to be conducted to prove patient-centred outcomes over time. The model is now ready to be implemented in adults with congenitally malformed hearts. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Caloric Requirements of Patients With Brain Impairment and Cerebral Palsy Who Are Dependent on Chronic Ventilation.

PubMed

Gale, Rena; Namestnic, Julia; Singer, Pierre; Kagan, Ilya

2017-11-01

Israeli law mandates chronic ventilator support for children and adolescents who are severely brain impaired and show minimal responses. Feeding protocols in these cases have been based on the caloric requirements of healthy children, deducting calories for lack of activity as well as an individual adjustment according to the cerebral palsy growth curves. However, patients are still inclined to gain excessive weight. Our objective was to determine the caloric requirements of these patients. Sixteen patients hospitalized in a dedicated unit who were ventilated through tracheostomies and fed via gastrostomies were included. Patients were aged 3-24 years; duration of ventilation was 1-7.5 years; and diagnoses included congenital genetic or brain malformations (n = 9), hypoxic accidents (n = 4), and postbacterial or postviral encephalitis (n = 3). Resting energy expenditure (REE) was determined by indirect calorimetry. REE values were compared with the caloric requirements of age-comparable healthy children and the calories actually delivered. Data were analyzed with paired t tests, Pearson correlations, and linear regression. The REE of our patients was 46% lower than the estimated caloric requirements of healthy children. In practice, patients received 32% more calories than that measured by REE. These findings were not affected by age, weight, diagnosis, or length of hospitalization. The caloric expenditure of these patients is very low. A diet guided by indirect calorimetry is proposed to aid in providing optimal nutrition support for this unique population to avoid overfeeding and obesity.

Annual trends in use of periconceptional folic acid and birth prevalence of major congenital malformations.

PubMed

Richard-Tremblay, Audrey-Ann; Sheehy, Odile; Bérard, Anick

2013-07-01

Recent evidence suggests that periconceptional folic acid use could not only prevent neural tube defects but also other malformations. The objectives of this study were to assess trends in dispensed high dose periconceptional folic acid (5 mg) and birth prevalence of major congenital malformations. The Quebec Pregnancy Registry, an administrative database with information on periconceptional prescribed medication and diagnostic codes was used to conduct this study. All pregnant women insured by the Quebec public drug plan between January 1(st) 1998 and December 31(st) 2008 were included. The exposure was defined as the use of high dose periconceptional folic acid 30 days before, and during the first 70 days of pregnancy. The outcome measured was the birth prevalence of major congenital malformations among live births. We identified 152,392 pregnancies and babies. The annual prevalence of high dose periconceptional folic acid use increased from 0.17% to 0.80% (p<0.05) during the study period; birth prevalence of congenital malformations increased by 15% (3.35% to 3.87%, p<0.05). More specifically, a 23% increase in the prevalence of cardiac malformation and 23% increase in musculoskeletal defects were observed, whereas there was no change in the prevalence of malformations of the nervous system. Although there was an increase in the use of periconceptional high dose folic acid over the past decade, there was no decrease in the prevalence of major congenital malformations. A limitation of this study is the absence of data on low dose folic acid use, available over the counter, in our administrative database.

Phenotype in girls and women with Turner syndrome: Association between dysmorphic features, karyotype and cardio-aortic malformations.

PubMed

Noordman, Iris; Duijnhouwer, Anthonie; Kapusta, Livia; Kempers, Marlies; Roeleveld, Nel; Schokking, Michiel; Smeets, Dominique; Freriks, Kim; Timmers, Henri; van Alfen-van der Velden, Janiëlle

2018-06-01

Turner syndrome (TS) is a genetic disorder characterized by the (partial) absence or a structural aberration of the second sex chromosome and is associated with a variety of phenotypes with specific physical features and cardio-aortic malformations. The objective of this study was to gain a better insight into the differences in dysmorphic features between girls and women with TS and to explore the association between these features, karyotype and cardio-aortic malformations. This prospective study investigated 14 dysmorphic features of TS girls and women using a checklist. Three major phenotypic patterns were recognized (severe phenotype, lymphatic phenotype and skeletal phenotype). Patient data including karyotype and cardio-aortic malformations (bicuspid aortic valve (BAV) and aortic coarctation (COA)) were collected. Associations between the prevalence of dysmorphic features, karyotype and cardio-aortic malformations were analysed using chi 2 -test and odds ratios. A total of 202 patients (84 girls and 118 women) were analysed prospectively. Differences in prevalence of dysmorphic features were found between girls and women. A strong association was found between monosomy 45,X and the phenotypic patterns. Furthermore, an association was found between COA and lymphatic phenotype, but no association was found between karyotype and cardio-aortic malformations. This study uncovered a difference in dysmorphic features between girls and women. Monosomy 45,X is associated with a more severe phenotype, lymphatic phenotype and skeletal phenotype. All patients with TS should be screened for cardio-aortic malformations, because in contrast to previous reports, karyotype and cardio-aortic malformations showed no significant association. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Developmental Toxicity of Drinking Water Disinfection By-Products to Embryos of the African Clawed Frog (Xenopus laevis)

DTIC Science & Technology

2005-06-10

and as representatives of byproducts of different disinfection processes . Endpoints measured included embryo mortality (LC50), embryo malformation...chemicals were selected for testing based on their potential for human harm and as representatives of byproducts of different disinfection processes ...highest frequency include notochord maldevelopment, craniofacial defects, and cardiac edema. The EC50 for BDCM malformations (62-72 mg/L) was at a much

Role of mechanical factors in cortical folding development

NASA Astrophysics Data System (ADS)

Razavi, Mir Jalil; Zhang, Tuo; Li, Xiao; Liu, Tianming; Wang, Xianqiao

2015-09-01

Deciphering mysteries of the structure-function relationship in cortical folding has emerged as the cynosure of recent research on brain. Understanding the mechanism of convolution patterns can provide useful insight into the normal and pathological brain function. However, despite decades of speculation and endeavors the underlying mechanism of the brain folding process remains poorly understood. This paper focuses on the three-dimensional morphological patterns of a developing brain under different tissue specification assumptions via theoretical analyses, computational modeling, and experiment verifications. The living human brain is modeled with a soft structure having outer cortex and inner core to investigate the brain development. Analytical interpretations of differential growth of the brain model provide preliminary insight into the critical growth ratio for instability and crease formation of the developing brain followed by computational modeling as a way to offer clues for brain's postbuckling morphology. Especially, tissue geometry, growth ratio, and material properties of the cortex are explored as the most determinant parameters to control the morphogenesis of a growing brain model. As indicated in results, compressive residual stresses caused by the sufficient growth trigger instability and the brain forms highly convoluted patterns wherein its gyrification degree is specified with the cortex thickness. Morphological patterns of the developing brain predicted from the computational modeling are consistent with our neuroimaging observations, thereby clarifying, in part, the reason of some classical malformation in a developing brain.

Gamma Knife Radiosurgery for Pediatric Arteriovenous Malformations: A Canadian Experience.

PubMed

Zeiler, Fred A; Janik, Maciej K; McDonald, Patrick J; Kaufmann, Anthony M; Fewer, Derek; Butler, Jim; Schroeder, Garry; West, Michael

2016-01-01

Gamma Knife (GK) radiosurgery for pediatric arteriovenous malformations (AVM) of the brain presents a non-invasive treatment option. We report our institutional experience with GK for pediatric AVMs. We performed a retrospective review of all pediatric patients treated with GK for cerebral AVMs at our institution from November 2003 up to and including September 2014. Patient demographics, AVM characteristics, treatment parameters and AVM responses were recorded. Nineteen patients were treated, with 4 lost to follow-up. The mean age was 14.2 years (range. 7-18 years), with 10 being males (52.6%). The mean AVM diameter and volume were 2.68 cm and 3.10 cm3 respectively. The mean Spetzler-Martin (SM) and Pollock grades of the treated AVMs were 2.4 and 0.99 respectively. The mean follow-up was 62 months. All AVMs treated demonstrated a response on follow-up imaging. Nine of 15 (60.0%) patients displayed obliteration of their AVMs. Nine of 11 patients with a minimum of 3 years follow-up (81.8%) displayed obliteration, with SM and Pollock grades correlating to the chance of obliteration in this group. Two patients developed post-GK edema requiring short course dexamethasone therapy. No other major complications occurred. No permanent complications occurred. GK radiosurgery for pediatric AVMs offers a safe and effective treatment option, with low permanent complication rates during early follow-up.

Comments on: "Perinatal toxicity of cyfluthrin in Mice: developmental and behavioral effects" by Soni et al, which is accepted in Human & Experimental Toxicology (DOl: 10.1177/0960327110391386)

EPA Science Inventory

Soni and colleagues recently reported that perinatal maternal exposure to cyfluthrin, a pyrethroid insecticide, caused fetal malformations and behavioral changes in offspring, including skeletal malformations and alterations in righting reflexes and locomotion (Soni et al., 2011)...

Results of Surgery for Low-Grade Brain Arteriovenous Malformation Resection by Early Career Neurosurgeons: An Observational Study.

PubMed

Patel, Nirav J; Bervini, David; Eftekhar, Behzad; Davidson, Andrew Stewart; Walsh, Daniel C; Assaad, Nazih N; Morgan, Michael Kerin

2018-03-28

For sustainability of arteriovenous malformation (AVM) surgery, results from early career cerebrovascular neurosurgeons (ECCNs) must be acceptably safe. To determine whether ECCNs performance of Spetzler-Ponce Class A AVM (SPC A) resection can be acceptably safe. ECCNs completing a cerebrovascular fellowship (2004-2015) with the last author were included. Inclusion of the ECCN cases occurred if they: had a prospective database of all AVM cases since commencing independent practice; were the primary surgeon on SPC A; and had made the significant management decisions. All SPC A surgical cases from the beginning of the ECCN's independent surgical practice to a maximum of 8 yr were included. An adverse outcome was considered a complication of surgery leading to a new permanent neurological deficit with a last modified Rankin Scale score >1. A cumulative summation (Cusum) plot examined the performance of each surgery. The highest acceptable level of adverse outcomes for the Cusum was 3.3%, derived from the upper 95% confidence interval of the last author's reported series. Six ECCNs contributed 110 cases for analysis. The median number of SPC A cases operated by each ECCN was 16.5 (range 4-40). Preoperative embolization was performed in 5 (4.5%). The incidence of adverse outcomes was 1.8% (95% confidence interval: <0.01%-6.8%). At no point during the accumulated series did the combined cohort become unacceptable by the Cusum plot. ECCNs with appropriate training appointed to large-volume cerebrovascular centers can achieve results for surgery for SPC A that are not appreciably worse than those published from high-volume neurosurgeons.

A de novo missense mutation of FGFR2 causes facial dysplasia syndrome in Holstein cattle.

PubMed

Agerholm, Jørgen S; McEvoy, Fintan J; Heegaard, Steffen; Charlier, Carole; Jagannathan, Vidhya; Drögemüller, Cord

2017-08-02

Surveillance for bovine genetic diseases in Denmark identified a hitherto unreported congenital syndrome occurring among progeny of a Holstein sire used for artificial breeding. A genetic aetiology due to a dominant inheritance with incomplete penetrance or a mosaic germline mutation was suspected as all recorded cases were progeny of the same sire. Detailed investigations were performed to characterize the syndrome and to reveal its cause. Seven malformed calves were submitted examination. All cases shared a common morphology with the most striking lesions being severe facial dysplasia and complete prolapse of the eyes. Consequently the syndrome was named facial dysplasia syndrome (FDS). Furthermore, extensive brain malformations, including microencephaly, hydrocephalus, lobation of the cerebral hemispheres and compression of the brain were present. Subsequent data analysis of progeny of the sire revealed that around 0.5% of his offspring suffered from FDS. High density single nucleotide polymorphism (SNP) genotyping data of the seven cases and their parents were used to map the defect in the bovine genome. Significant genetic linkage was obtained for three regions, including chromosome 26 where whole genome sequencing of a case-parent trio revealed two de novo variants perfectly associated with the disease: an intronic SNP in the DMBT1 gene and a single non-synonymous variant in the FGFR2 gene. This FGFR2 missense variant (c.927G>T) affects a gene encoding a member of the fibroblast growth factor receptor family, where amino acid sequence is highly conserved between members and across species. It is predicted to change an evolutionary conserved tryptophan into a cysteine residue (p.Trp309Cys). Both variant alleles were proven to result from de novo mutation events in the germline of the sire. FDS is a novel genetic disorder of Holstein cattle. Mutations in the human FGFR2 gene are associated with various dominant inherited craniofacial dysostosis syndromes. Given the phenotypic similarities in FDS affected calves, the genetic mapping and absence of further high impact variants in the critical genome regions, it is highly likely that the missense mutation in the FGFR2 gene caused the FDS phenotype in a dominant mode of inheritance.

Clinical Characteristics of Patients Who Underwent Surgery for Genital Tract Malformations at Peking Union Medical College Hospital across 31 Years.

PubMed

Wang, Guang-Han; Zhu, Lan; Liu, Ai-Ming; Xu, Tao; Lang, Jing-He

2016-10-20

Female genital malformations represent miscellaneous deviations from normal anatomy. This study aimed to explore the clinical characteristics of patients who underwent surgery for genital tract malformations at Peking Union Medical College Hospital (PUMCH) during a 31-year period. We retrospectively reviewed surgical cases of congenital malformation of the female genital tract at PUMCH for a 31-year period, analyzed the clinical characteristics of 1634 hospitalized patients, and investigated their general condition, diagnosis, and treatment process. The average patient age was 27.6 ± 9.9 years. The average ages of patients who underwent surgery for uterine malformation and vaginal malformation were 31.9 ± 8.8 years and 24.7 ± 9.0 years, respectively; these ages differed significantly (P < 0.01). Among patients with genital tract malformation, the percentages of vaginal malformation, uterine malformation, vulva malformation, cervical malformation, and other malformations were 43.9%, 43.5%, 7.4%, 2.3%, and 2.8%, respectively. Among patients with uterine malformation, 34.5% underwent surgery for the genital tract malformation, whereas in patients with vaginal malformation, the proportion is 70.6%; the difference between the two groups was statistically significant (P < 0.01). The percentage of complications of the urinary system in patients with vaginal malformations was 10.2%, which was statistically significantly higher than that (5.3%) in patients with uterine malformations (P < 0.01). Compared to patients with uterine malformations, patients with vaginal malformations displayed more severe clinical symptoms, a younger surgical age, and a greater need for attention, early diagnosis, and treatment. Patients with genital tract malformations, particularly vaginal malformations, tend to have more complications of the urinary system and other malformations than patients with uterine malformations.

Congenital Auricular Malformations: Description of Anomalies and Syndromes.

PubMed

Bartel-Friedrich, Sylva

2015-12-01

Half of the malformations in the ear, nose, and throat region affect the ear. Malformations of the external ear (pinna or auricle with external auditory canal [EAC]) are collectively termed microtia. Microtia is a congenital anomaly that ranges in severity from mild structural abnormalities to complete absence of the external ear (anotia). Microtia occurs more frequently in males (∼2 or 3:1), is predominantly unilateral (∼70-90%), and more often involves the right ear (∼60%). The reported prevalence varies geographically from 0.83 to 17.4 per 10,000 births. Microtia may be genetic (with family history, spontaneous mutations) or acquired. Malformations of the external ear can also involve the middle ear and/or inner ear. Microtia may be an isolated birth defect, but associated anomalies or syndromes are described in 20 to 60% of cases, depending on study design. These generally fit within the oculo-auriculo-vertebral spectrum; defects are located most frequently in the facial skeleton, facial soft tissues, heart, and vertebral column, or comprise a syndrome (e.g., Treacher Collins syndrome). Diagnostic investigation of microtia includes clinical examination, audiologic testing, genetic analysis and, especially in higher grade malformations with EAC deformities, computed tomography (CT) or cone-beam CT for the planning of surgery and rehabilitation procedures, including implantation of hearing aids. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

[Nuclear magnetic resonance of anorectal malformations and persistent postoperative fecal incontinence].

PubMed

de Agustín, J C; Alami, H; Lassaletta, L; Gámez, M; Fernández, A; Fraile, E; Alenda, J G; Rollán, V; Utrilla, J G

1992-07-01

We review our experience with Magnetic Resonance Imaging (MRI) in the evaluation of 6 patients showing anorectal malformation, and 4 more with persistent postoperative fecal incontinence. Preoperative sagittal, axial and coronal planes were studied with special consideration to the pelvic and vertebral structures. The excellent resolution of MRI allowed accurate identification of the pelvic musculature in all patients, including those with bizarre sacral abnormalities. MRI revealed structural anomalies not detected previously, such as teathering cord, intraspinal lipoma, presacral mass and renal malformation. In our institution, MRI has replaced the CT scan in the study of patients suffering of persistent fecal incontinence. In non operated on cases of anorectal malformations, MRI determines with extraordinary accuracy the location of the rectal atretic pouch, the actual pelvic muscular quality, and the detection of previously unsuspected associated anomalies.

Role of endothelial-to-mesenchymal transition in the pathogenesis of central nervous system hemangioblastomas.

PubMed

Takada, Shigeki; Hojo, Masato; Takebe, Noriyoshi; Tanigaki, Kenji; Miyamoto, Susumu

2018-06-07

Hemangioblastomas (HBs) are benign vascular tumors of the central nervous system and histologically contain abundant microvessels. Therefore, they clinically exhibit vascular malformation-like characteristics. It has been described that endothelial-to-mesenchymal transition (EndMT) contributes to the pathogenesis of cerebral cavernous malformations. However, it remains unknown whether EndMT contributes to the pathogenesis of central nervous system HBs. The aim of our study was to investigate whether EndMT occurs in central nervous system HBs. Ten central nervous system HBs were immunohistochemically investigated. CD31 (an endothelial marker) and EndMT markers, such as α-smooth muscle actin (a mesenchymal marker) and CD44 (a mesenchymal stem cell marker), were expressed in the endothelial layer of microvessels in all cases. These findings suggest that endothelial cells (ECs) of microvessels in central nervous system HBs have acquired mesenchymal and stem-cell-like characteristics and undergone EndMT. In all cases, both ephrin-B2 and EphB4, which are not detected in adult normal brain vessels, were expressed in the endothelial layer of microvessels. These data suggest that ECs of microvessels in central nervous system HBs are immature or malformed cells and have both arterial and venous characteristics. This is the first report showing the possibility that EndMT contributes to the pathogenesis of central nervous system HBs. It is likely that ECs of microvessels in central nervous system HBs are immature or malformed cells and have both arterial and venous characteristics. EndMT is expected to be a new therapeutic target in central nervous system HBs. Copyright © 2018 Elsevier Inc. All rights reserved.

A novel OTX2 mutation in a patient with combined pituitary hormone deficiency, pituitary malformation, and an underdeveloped left optic nerve.

PubMed

Gorbenko Del Blanco, Darya; Romero, Christopher J; Diaczok, Daniel; de Graaff, Laura C G; Radovick, Sally; Hokken-Koelega, Anita C S

2012-09-01

Orthodenticle homolog 2 (OTX2) is a homeobox family transcription factor required for brain and eye formation. Various genetic alterations in OTX2 have been described, mostly in patients with severe ocular malformations. In order to expand the knowledge of the spectrum of OTX2 mutation, we performed OTX2 mutation screening in 92 patients with combined pituitary hormone deficiency (CPHD). We directly sequenced the coding regions and exon-intron boundaries of OTX2 in 92 CPHD patients from the Dutch HYPOPIT study in whom mutations in the classical CPHD genes PROP1, POU1F1, HESX1, LHX3, and LHX4 had been ruled out. Among 92 CPHD patients, we identified a novel heterozygous missense mutation c.401C>G (p.Pro134Arg) in a patient with CPHD, pituitary malformation, and an underdeveloped left optic nerve. Binding of both the wild-type and mutant OTX2 proteins to bicoid binding sites was equivalent; however, the mutant OTX2 exhibited decreased transactivation. We describe a novel missense heterozygous OTX2 mutation that acts as a dominant negative inhibitor of target gene expression in a patient with CPHD, pituitary malformation, and optic nerve hypoplasia. We provide an overview of all OTX2 mutations described till date, which show that OTX2 is a promising candidate gene for genetic screening of patients with CPHD or isolated GH deficiency (IGHD). As the majority of the OTX2 mutations found in patients with CPHD, IGHD, or short stature have been found in exon 5, we recommend starting mutational screening in those patients in exon 5 of the gene.

Aesthetic treatment of pectus excavatum: a new endoscopic technique using a porous polyethylene implant.

PubMed

Grappolini, Simone; Fanzio, Paolo M; D'Addetta, Pierluca G C; Todde, Alberto; Infante, Maurizio

2008-01-01

Pectus excavatum is the most frequent malformation of the rib cage. Functional aspects associated with this malformation often are absent even in adults not involved in competitive sports activities. Overall, these patients often live with extreme psychological discomfort when the malformations are minor. Traditionally, the correction of these malformations has been geared toward interventions that modify the architecture of the rib cage. However, all these interventions, even the most recent, involve considerably invasive major surgery. In fact, optimal results are not always achieved with corrective surgery using the insertion of silicone prosthesis, and patients often experience complications. To correct intermediate and modest pectus excavatum in a stable manner and with the least amount of invasiveness, the authors developed a camouflage technique that uses porous prostheses made from high-density linear polyethylene. This material is generally used for reconstruction of the brain case. Between February 2001 and March 2006, in the I Unit of Plastic Surgery of the authors' Institute, 11 adult pectus excavatum patients with no previous cardiorespiratory symptoms underwent the authors' surgical technique. The average patient age was 29 years. Surgical repair was successful in all cases, and the average hospital stay was short. There were no complications during the follow-up period. The described approach repairs nonfunctional pectus excavatum in the adult with satisfying aesthetic and stable results, short hospital stay, and high patient popularity ratings. The best therapeutic option for pectus excavatum, especially with intermediate or moderate severity, is still controversial: thoracic surgery or camouflage surgery with implant? Trying to address those issues we propose a new technique by a multidisciplinary, not aggressive approach using a high density linear polyethylene implant and Omentus flap and the early analysis of our data.

Vascular anomalies: classification, imaging characteristics and implications for interventional radiology treatment approaches

PubMed Central

Prajapati, H J S; Martin, L G; Patel, T H

2014-01-01

The term vascular anomaly represents a broad spectrum of vascular pathology, including proliferating vascular tumours and vascular malformations. While the treatment of most vascular anomalies is multifactorial, interventional radiology procedures, including embolic therapy, sclerotherapy and laser coagulation among others, are playing an increasingly important role in vascular anomaly management. This review discusses the diagnosis and treatment of common vascular malformations, with emphasis on the technique, efficacy and complications of different interventional radiology procedures. PMID:24588666

Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations.

PubMed

Huybrechts, Krista F; Hernández-Díaz, Sonia; Patorno, Elisabetta; Desai, Rishi J; Mogun, Helen; Dejene, Sara Z; Cohen, Jacqueline M; Panchaud, Alice; Cohen, Lee; Bateman, Brian T

2016-09-01

The frequency of antipsychotic (AP) use during pregnancy has approximately doubled during the last decade. However, little is known about their safety for the developing fetus, and concerns have been raised about a potential association with congenital malformations. To examine the risk for congenital malformations overall and cardiac malformations associated with first-trimester exposure to APs. This nationwide sample of 1 360 101 pregnant women enrolled in Medicaid with a live-born infant constituted the pregnancy cohort nested in the Medicaid Analytic Extract database, which included data from January 1, 2000, to December 31, 2010. Participants were enrolled in Medicaid from 3 months before their last menstrual period through at least 1 month after delivery. Relative risks (RRs) were estimated using generalized linear models with fine stratification on the propensity score to control for the underlying psychiatric disorders and other potential confounders. Data were analyzed during 2015. Use of APs during the first trimester, the etiologically relevant period for organogenesis. Major congenital malformations overall and cardiac malformations identified during the first 90 days after delivery. Of the 1 341 715 pregnancies that met inclusion criteria (mean [SD] age of women, 24.02 [5.77] years), 9258 (0.69%) filled at least 1 prescription for an atypical AP and 733 (0.05%) filled at least 1 prescription for a typical AP during the first trimester. Overall, 32.7 (95% CI, 32.4-33.0) per 1000 births not exposed to APs were diagnosed with congenital malformations compared with 44.5 (95% CI, 40.5-48.9) per 1000 births exposed to atypical and 38.2 (95% CI, 26.6-54.7) per 1000 births exposed to typical APs. Unadjusted analyses suggested an increased risk for malformations overall for atypical APs (RR, 1.36; 95% CI, 1.24-1.50) but not for typical APs (RR, 1.17; 95% CI, 0.81-1.68). After confounding adjustment, the RR was reduced to 1.05 (95% CI, 0.96-1.16) for atypical APs and 0.90 (95% CI, 0.62-1.31) for typical APs. The findings for cardiac malformations were similar. For the individual agents examined, a small increased risk in overall malformations (RR, 1.26; 95% CI, 1.02-1.56) and cardiac malformations (RR, 1.26; 95% CI, 0.88-1.81) was found for risperidone that was independent of measured confounders. Evidence from this large study suggests that use of APs early in pregnancy generally does not meaningfully increase the risk for congenital malformations overall or cardiac malformations in particular. The small increase in the risk for malformations observed with risperidone requires additional study.

[Ocular coloboma and results of brain MRI: preliminary results].

PubMed

Denis, D; Girard, N; Levy-Mozziconacci, A; Berbis, J; Matonti, F

2013-03-01

Congenital ocular colobomas are the result of a failure in closure of the embryonal fissure. We present a prospective study (2007-2011) in which we report brain MRI findings in children with ocular coloboma. Thirty-five children (54 eyes) were included; 15 boys, 20 girls with a median age of 24.0 months (1.0-96.0) at first presentation. Within 2 to 3 months following complete ophthalmologic examination, brain MRI was performed. Colobomas were bilateral in 19 cases and unilateral in 16 cases. Eleven different types of coloboma were identified. Of 54 eyes, 74% demonstrated optic nerve coloboma, of which 28 were severe. Of 35 MRI's performed, abnormalities were present in 86%: gyration abnormalities (n=21), lateral ventricular dilatation (n=17), dilatation of the Virchow-Robin and subarachnoid spaces (n=14), signal abnormalities and brain stem malformations (n=14), white matter signal abnormalities (n=11), corpus callosum abnormalities (n=10). Most of these abnormalities were related. Gyration abnormalities were the most frequent. There was no significant association between the severity of the coloboma and the abnormalities found (P=1.0). Likewise, there was no significant association of gyration abnormalities with the severity of coloboma in children (P=1.0). This study shows, for the first time, the existence of frequent cerebral abnormalities on MRI in children with ocular coloboma. The most common abnormality being gyration abnormalities, in 60% of cases. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Ultrasound diagnosis and management of acquired uterine enhanced myometrial vascularity/arteriovenous malformations.

PubMed

Timor-Tritsch, Ilan E; Haynes, Meagan Campol; Monteagudo, Ana; Khatib, Nizar; Kovács, Sándor

2016-06-01

Arteriovenous malformation is a short circuit between an organ's arterial and venous circulation. Arteriovenous malformations are classified as congenital and acquired. In the uterus, they may appear after curettage, cesarean delivery, and myomectomy among others. Their clinical feature is usually vaginal bleeding, which may be severe, if curettage is performed in unrecognized cases. Sonographically on 2-dimensional grayscale ultrasound scanning, the pathologic evidence appears as irregular, anechoic, tortuous, tubular structures that show evidence of increased vascularity when color Doppler is applied. Most of the time they resolve spontaneously; however, if left untreated, they may require involved treatments such as uterine artery embolization or hysterectomy. In the past, uterine artery angiography was the gold standard for the diagnosis; however, ultrasound scanning has diagnosed successfully and helped in the clinical management. Recently, arteriovenous malformations have been referred to as enhanced myometrial vascularities. The purpose of this study was to evaluate the role of transvaginal ultrasound scanning in the diagnosis and treatment of acquired enhanced myometrial vascularity/arteriovenous malformations to outline the natural history of conservatively followed vs treated lesions. This was a retrospective study to assess the presentation, treatment, and clinical pictures of patients with uterine Enhanced myometrial vascularity/arteriovenous malformations that were diagnosed with transvaginal ultrasound scanning. We reviewed both (1) ultrasound data (images, measured dimensions, and Doppler blood flow that were defined by its peak systolic velocity and (2) clinical data (age, reproductive status, clinical presentation, inciting event or procedure, surgical history, clinical course, time intervals that included detection to resolution or detection to treatment, and treatment rendered). The diagnostic criteria were "subjective" with a rich vascular network in the myometrium with the use of color Doppler images and "objective" with a high peak systolic velocity of ≥20 cm/sec in the vascular web. Statistical analysis was performed and coded with statistical software where necessary. Twenty-seven patients met the diagnostic criteria of uterine enhanced myometrial vascularity/arteriovenous malformation. Mean age was 31.8 years (range, 18-42 years). Clinical diagnoses of the patients included 10 incomplete abortions, 6 missed abortions, 5 spontaneous complete abortions, 5 cesarean scar pregnancies, and 1 molar pregnancy. Eighty-nine percent of patients had bleeding (n = 24/27), although 1 patient was febrile, and 2 patients were asymptomatic. Recent surgical procedures were performed in 55.5% patients (15/27) that included curettage (n = 10), cesarean deliveries (n = 5), or both (n = 1); 4 patients had a remote history of uterine surgery that included myomectomy. Treatment was varied and included expectant treatment alone in 48% of the patients with serial ultrasound scans and serum human chorionic gonadotropin until resolution (n = 13/27 patients), uterine artery embolization (29.6%; 8/27 patients), methotrexate administration (22.2%; 6/27 patients), hysterectomy (7.4%; 2/27 patients), and curettage (3.7%; 1/27 patients). Three patients required a blood transfusion. Of the 9 patients whose condition required embolization, the conditions of 7 patients resolved after the procedure although 1 patient's condition required operative hysteroscopy and 1 patient's condition required hysterectomy for intractable bleeding. Average peak systolic velocity after embolization in the 9 patients was 85.2 cm/sec (range, 35-170 cm/sec); the average peak systolic velocity of the 16 patients with spontaneous resolution was 58.5 cm/sec (range, 23-90 cm/sec). Acquired enhanced myometrial vascularity/arteriovenous malformations occurred after unsuccessful pregnancies or treatment procedures that included uterine curettage, cesarean delivery, or cesarean scar pregnancy. Triage of patients for expectant treatment vs intervention with uterine artery embolization based on their clinical status, which was supplemented by objective measurements of blood velocity measurement in the arteriovenous malformation, appears to be a good predictor of outcome. Ultrasound evaluation of patients with early pregnancy failure and persistent bleeding should be considered for evaluation of a possible enhanced myometrial vascularity/arteriovenous malformation. Copyright © 2016 Elsevier Inc. All rights reserved.

Increase in fluoroscopic radiation dose in successive sessions of multistage Onyx embolization of brain arteriovenous malformations compared with the first session.

PubMed

Sheen, Jae Jon; Jiang, Yuan Yuan; Kim, Young Eun; Maeng, Jun Young; Kim, Tae-Il; Lee, Deok Hee

2018-03-23

Onyx embolization is a treatment for brain arteriovenous malformations (AVMs). However, multistage embolization usually involves the presence of radiodense Onyx cast from the previous sessions, which may influence the fluoroscopic radiation dose. We compared the fluoroscopic dose between the initial and final embolization sessions. From January 2014 to September 2016, 18 patients underwent multistage Onyx embolization (more than twice) for brain AVMs. The total fluoroscopic duration (minutes), dose-area product (DAP, Gy×cm 2 ), and cumulative air kerma (CAK, mGy) of both the frontal and lateral planes were obtained. We compared the frontal and lateral fluoroscopic dose rates (dose/time) of the final embolization session with those of the initial session. The relationship between the injected Onyx volume and radiation dose was tested. The initial and final procedures on the frontal plane showed significantly different fluoroscopic dose rates (DAP: initial 0.668 Gy×cm 2 /min, final 0.848 Gy×cm 2 /min, P=0.02; CAK: initial 12.7 mGy/min, final 23.1 mGy/min, P=0.007). Those on the lateral plane also showed a similar pattern (DAP: initial 0.365 Gy×cm 2 /min, final 0.519 Gy×cm 2 /min, P=0.03; CAK: initial 6.2 mGy/min, final 12.9 mGy/min, P=0.01). The correlation between the cumulative Onyx volume (vials) and radiation dose ratio of both planes showed an increasing trend (rho 0.4325-0.7053; P=0.0011-0.0730). Owing to the automatic exposure control function during fluoroscopy, successive Onyx embolization procedures increase the fluoroscopic radiation dose in multistage brain AVM embolization because of the presence of radiodense Onyx mass. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

[Isotretinoin embryopathy. Report of one case].

PubMed

Troncoso Sch, Mónica; Rojas H, Carla; Bravo C, Eduardo

2008-06-01

Retinoic acid is a widely used drug in the treatment of cystic acne. It has teratogenic effects that depend on the gestational period in which it is used. We report a seven months old female whose mother was exposed to retinoic acid in both pre-gestational and gestational periods. She had a retardation of psychomotor development and a brain MRI showed frontal atrophy and a malformation of the posterior fossa. We discuss the mechanisms of the teratogenic effects of retinoic acid.

Beta-lactam antibiotics during pregnancy: a cross-sectional comparative study Zagreb-Novi Sad.

PubMed

Erić, M; Leppée, M; Sabo, A; Culig, J

2012-01-01

During pregnancy, a number of changes occur in women's body, and some medications are safe and some are not. The aim of our study was to establish the possible correlation between use of beta-lactam antibiotics in pregnancy and occurrence of congenital malformations. The study included 893 pregnant women from Zagreb and 6099 pregnant women from Novi Sad. 527 pregnant women used beta-lactams. First part of the study (one month study) was performed at four maternity hospitals in Zagreb, Croatia. Second part were collected as a part of the study analysing the teratogenicity of drugs used in pregnancy, a longitudinal study performed in Novi Sad district. Pregnant women most frequently used antibacterial agents in the first trimester of pregnancy. They used 15 different antibacterial medications, most often beta-lactams. In Zagreb arm, out of the total number of pregnant women that used medications during pregnancy (859), 231 (26.9%) used beta-lactam antibiotics. Malformations were detected in 8 (3.5%) cases. The prevalence of malformations in newborns whose mothers did not take beta-lactam antibiotics in pregnancy (662) was 2.7% (18 newborns with malformations). In Novi Sad arm, out of the total number of pregnant women that used medications during pregnancy (2013), 296 (14.7%) used beta-lactam antibiotics. Malformations were detected in 14 (4.7%) cases. The prevalence of malformations in newborns whose mothers did not take beta-lactam antibiotics in pregnancy (5803) was 1.7% (99 newborns with malformations). The results show possible teratogenic potential even with those antibacterials which are considered safe (amoxicillin) but as those are usually minor malformations they often pass undetected. International pharmacoepidemiological studies of drug use in pregnancy could substantially contribute to the improvement of pharmacotherapy, and could be of great help in assessing the fetal risks.

An approach to the symbolic representation of brain arteriovenous malformations for management and treatment planning.

PubMed

Orlowski, Piotr; Mahmud, Imran; Kamran, Mudassar; Summers, Paul; Noble, Alison; Ventikos, Yiannis; Byrne, James V

2014-03-01

There is currently no standardised approach to arteriovenous malformation (AVM) reporting. Existing AVM classification systems focuses on angioarchitectural features and omit haemodynamic, anatomical and topological parameters intuitively used by therapists. We introduce a symbolic vocabulary to represent the state of an AVM of the brain at different stages of treatment. The vocabulary encompasses the main anatomic and haemodynamic features of interest in treatment planning and provides shorthand symbols to represent the interventions themselves in a schematic representation. The method was presented to 50 neuroradiologists from 14 countries during a workshop and graded 7.34 ± 1.92 out of ten for its usefulness as means of standardising and facilitating communication between clinicians and allowing comparisons between AVM cases. Feedback from the survey was used to revise the method and improve its completeness. For an AVM test case, participants were asked to produce a conventional written report and subsequently a diagrammatic report. The two required, on average, 6.19 ± 2.05 and 5.09 ± 3.01 min, respectively. Eighteen participants said that producing the diagram changed the way they thought about the AVM test case. Introduced into routine practice, the diagrams would represent a step towards a standardised approach to AVM reporting with consequent benefits for comparative analysis and communication as well as for identifying best treatment strategies.

Replication Study of Polymorphisms Associated With Brain Arteriovenous Malformation in a Population From South of Brazil

PubMed Central

Ludwig, Fernanda S; Matte, Ursula S; Mota, Simone; Stefani, Marco A

2016-01-01

Introduction The aim of this study was to reproducibly determine if any of the polymorphisms were associated with the susceptibility to brain arteriovenous malformations (BAVM) or the risk of intracranial hemorrhage (ICH) presentation. Methods We recruited 63 BAVM patients and 96 controls. The polymorphisms selected for evaluation were apolipoprotein E (APOE), tumor necrosis factor alpha (TNF 238G>A - rs361525), interleukin 1 beta (IL1B 511C>T - rs16944 and IL1B -31T>C - rs1143627), activin-like kinase 1 (ACVRL1 IVS3-35A>G - rs2071219), endoglin (ENG 207G>A - rs11545664), and interleukin 6 (IL6 174G>C - rs1800795). Results In the single analysis, we observed statistically significant differences in the allele distributions for IL1B -31T>C (rs1143627) between the BAVM patients and control subjects (P = 0.02). There was a trend toward significance for the association between the IL1B 511C>T (rs16944) allele and BAVM risk (P = 0.07). In further logistic regression analysis, no polymorphism was significantly associated with the risk of BAVM. No polymorphisms were associated with hemorrhage presentation according to both single and multivariable analyses. Conclusions In our sample from a south Brazil population, we found no association between the risks of BAVM and ICH presentation with any of the selected polymorphisms. PMID:27026833

Replication Study of Polymorphisms Associated With Brain Arteriovenous Malformation in a Population From South of Brazil.

PubMed

Franciscatto, André Cerutti; Ludwig, Fernanda S; Matte, Ursula S; Mota, Simone; Stefani, Marco A

2016-02-24

The aim of this study was to reproducibly determine if any of the polymorphisms were associated with the susceptibility to brain arteriovenous malformations (BAVM) or the risk of intracranial hemorrhage (ICH) presentation. We recruited 63 BAVM patients and 96 controls. The polymorphisms selected for evaluation were apolipoprotein E (APOE), tumor necrosis factor alpha (TNF 238G>A - rs361525), interleukin 1 beta (IL1B 511C>T - rs16944 and IL1B -31T>C - rs1143627), activin-like kinase 1 (ACVRL1 IVS3-35A>G - rs2071219), endoglin (ENG 207G>A - rs11545664), and interleukin 6 (IL6 174G>C - rs1800795). In the single analysis, we observed statistically significant differences in the allele distributions for IL1B -31T>C (rs1143627) between the BAVM patients and control subjects (P = 0.02). There was a trend toward significance for the association between the IL1B 511C>T (rs16944) allele and BAVM risk (P = 0.07). In further logistic regression analysis, no polymorphism was significantly associated with the risk of BAVM. No polymorphisms were associated with hemorrhage presentation according to both single and multivariable analyses. In our sample from a south Brazil population, we found no association between the risks of BAVM and ICH presentation with any of the selected polymorphisms.

PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution

PubMed Central

Timms, Andrew E.; Conti, Valerio; Girisha, Katta M.; Martin, Beth; Olds, Carissa; Collins, Sarah; Park, Kaylee; Carter, Melissa; Krägeloh-Mann, Inge; Chitayat, David; Parikh, Aditi Shah; Bradshaw, Rachael; Torti, Erin; Braddock, Stephen; Burke, Leah; Ghedia, Sondhya; Stephan, Mark; Stewart, Fiona; Prasad, Chitra; Napier, Melanie; Saitta, Sulagna; Straussberg, Rachel; Gabbett, Michael; O’Connor, Bridget C.; Yin, Lim Jiin; Lai, Angeline Hwei Meeng; Martin, Nicole; McKinnon, Margaret; Addor, Marie-Claude; Schwartz, Charles E.; Lanoel, Agustina; Conway, Robert L.; Devriendt, Koenraad; Tatton-Brown, Katrina; Pierpont, Mary Ella; Painter, Michael; Worgan, Lisa; Reggin, James; Hennekam, Raoul; Pritchard, Colin C.; Aracena, Mariana; Gripp, Karen W.; Cordisco, Maria; Van Esch, Hilde; Garavelli, Livia; Curry, Cynthia; Goriely, Anne; Kayserilli, Hulya; Shendure, Jay; Graham, John; Guerrini, Renzo; Dobyns, William B.

2016-01-01

Mosaicism is increasingly recognized as a cause of developmental disorders with the advent of next-generation sequencing (NGS). Mosaic mutations of PIK3CA have been associated with the widest spectrum of phenotypes associated with overgrowth and vascular malformations. We performed targeted NGS using 2 independent deep-coverage methods that utilize molecular inversion probes and amplicon sequencing in a cohort of 241 samples from 181 individuals with brain and/or body overgrowth. We identified PIK3CA mutations in 60 individuals. Several other individuals (n = 12) were identified separately to have mutations in PIK3CA by clinical targeted-panel testing (n = 6), whole-exome sequencing (n = 5), or Sanger sequencing (n = 1). Based on the clinical and molecular features, this cohort segregated into three distinct groups: (a) severe focal overgrowth due to low-level but highly activating (hotspot) mutations, (b) predominantly brain overgrowth and less severe somatic overgrowth due to less-activating mutations, and (c) intermediate phenotypes (capillary malformations with overgrowth) with intermediately activating mutations. Sixteen of 29 PIK3CA mutations were novel. We also identified constitutional PIK3CA mutations in 10 patients. Our molecular data, combined with review of the literature, show that PIK3CA-related overgrowth disorders comprise a discontinuous spectrum of disorders that correlate with the severity and distribution of mutations. PMID:27631024

Features predictive of brain arteriovenous malformation hemorrhage: extrapolation to a physiologic model.

PubMed

Sahlein, Daniel H; Mora, Paloma; Becske, Tibor; Huang, Paul; Jafar, Jafar J; Connolly, E Sander; Nelson, Peter K

2014-07-01

Although there is generally thought to be a 2% to 4% per annum rupture risk for brain arteriovenous malformations (bAVMs), there is no way to estimate risk for an individual patient. In this retrospective study, patients were eligible who had nidiform bAVMs and underwent detailed pretreatment diagnostic cerebral angiography at our medical center from 1996 to 2006. All patients had superselective microcatheter angiography, and films were reviewed for the purpose of this project. Patient demographics, clinical presentation, and angioarchitectural characteristics were analyzed. A univariate analysis was performed, and angioarchitectural features with potential physiological significance that showed at least a trend toward significance were added to a multivariate logistic regression model. One hundred twenty-two bAVMs met criteria for study entry. bAVMs with single venous drainage anatomy were more likely to present with hemorrhage. In addition, patients with multiple draining veins and a venous stenosis reverted to a risk similar to those with 1 draining vein, whereas those with multiple draining veins and without stenosis had diminished association with hemorrhage presentation. Those bAVMs with associated aneurysms were more likely to present with hemorrhage. These findings were robust in both univariate and multivariate models. The results of this article lead to the first physiological, internally consistent model of individual bAVM hemorrhage risk, where 1 draining vein, venous stenosis, and associated aneurysms increase risk. © 2014 American Heart Association, Inc.

Micro-CT Imaging Reveals Mekk3 Heterozygosity Prevents Cerebral Cavernous Malformations in Ccm2-Deficient Mice

PubMed Central

Choi, Jaesung P.; Foley, Matthew; Zhou, Zinan; Wong, Weng-Yew; Gokoolparsadh, Naveena; Arthur, J. Simon C.; Li, Dean Y.; Zheng, Xiangjian

2016-01-01

Mutations in CCM1 (aka KRIT1), CCM2, or CCM3 (aka PDCD10) gene cause cerebral cavernous malformation in humans. Mouse models of CCM disease have been established by deleting Ccm genes in postnatal animals. These mouse models provide invaluable tools to investigate molecular mechanism and therapeutic approaches for CCM disease. However, the full value of these animal models is limited by the lack of an accurate and quantitative method to assess lesion burden and progression. In the present study we have established a refined and detailed contrast enhanced X-ray micro-CT method to measure CCM lesion burden in mouse brains. As this study utilized a voxel dimension of 9.5μm (leading to a minimum feature size of approximately 25μm), it is therefore sufficient to measure CCM lesion volume and number globally and accurately, and provide high-resolution 3-D mapping of CCM lesions in mouse brains. Using this method, we found loss of Ccm1 or Ccm2 in neonatal endothelium confers CCM lesions in the mouse hindbrain with similar total volume and number. This quantitative approach also demonstrated a rescue of CCM lesions with simultaneous deletion of one allele of Mekk3. This method would enhance the value of the established mouse models to study the molecular basis and potential therapies for CCM and other cerebrovascular diseases. PMID:27513872

Influence of craniofacial surgery on the social attitudes toward the malformed and their handling in different cultures and at different times: a contribution to social world history.

PubMed

Sailer, H F; Kolb, E

1995-07-01

A historic overview including the European, American, Asian, and African continents is given on attitudes toward and the handling of humans with congenital malformations in ancient cultures and on pertinent customs in some prehistoric peoples. Figures of early works of art showing malformed individuals are presented testifying to this worldwide and timeless problem of humankind. In parallel, analogous patient photographs from our hospital before and after reconstructive surgery are shown. Philosophies of ancient Greece, rome, and China on the subject of malformed infants essentially did not differ from the known attitudes of the less developed tribes in Europe and pre-Columbian America, although the means of elimination of unwanted offspring were rather passive (exposure) than active (manual killing). A radical change in attitudes and practices occurred with the spread of the Christian religion and its political installment in Europe. The care for the underprivileged including the malformed ones was considered a Christian duty to be performed with compassion and love. In our century, the clocks have been and apparently are turned back again. Atheistic and Darwinian influences, political atheism, and the belief in "higher ethics" issued by "superman" have led to a relapse into barbarism, also within the medical system. We, as craniofacial surgeons, are privileged to have the means to turn the clocks forward again by rehabilitating the physically most underprivileged: those with conspicuous craniofacial malformations. The necessary techniques exist and are applied, as the figures of patients from our hospital demonstrate, but the will and the emotional strength for their consequent application require more than our hands.

Effects of oxidative stress on hyperglycaemia-induced brain malformations in a diabetes mouse model

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jin, Ya; Wang, Guang; Han, Sha-Sha

Pregestational diabetes mellitus (PGDM) enhances the risk of fetal neurodevelopmental defects. However, the mechanism of hyperglycaemia-induced neurodevelopmental defects is not fully understood. In this study, several typical neurodevelopmental defects were identified in the streptozotocin-induced diabetes mouse model. The neuron-specific class III beta-tubulin/forkhead box P1-labelled neuronal differentiation was suppressed and glial fibrillary acidic protein-labelled glial cell lineage differentiation was slightly promoted in pregestational diabetes mellitus (PGDM) mice. Various concentrations of glucose did not change the U87 cell viability, but glial cell line-derived neurotrophic factor expression was altered with varying glucose concentrations. Mouse maternal hyperglycaemia significantly increased Tunel{sup +} apoptosis but didmore » not dramatically affect PCNA{sup +} cell proliferation in the process. To determine the cause of increased apoptosis, we determined the SOD activity, the expression of Nrf2 as well as its downstream anti-oxidative factors NQO1 and HO1, and found that all of them significantly increased in PGDM fetal brains compared with controls. However, Nrf2 expression in U87 cells was not significantly changed by different glucose concentrations. In mouse telencephalon, we observed the co-localization of Tuj-1 and Nrf2 expression in neurons, and down-regulating of Nrf2 in SH-SY5Y cells altered the viability of SH-SY5Y cells exposed to high glucose concentrations. Taken together, the data suggest that Nrf2-modulated antioxidant stress plays a crucial role in maternal hyperglycaemia-induced neurodevelopmental defects. - Highlights: • Typical neurodevelopmental defects could be observed in STZ-treated mouse fetuses. • Nrf2 played a crucial role in hyperglycaemia-induced brain malformations. • The effects of hyperglycaemia on neurons and glia cells were not same.« less

Detachable-Tip Microcatheters for Liquid Embolization of Brain Arteriovenous Malformations and Fistulas: A United States Single-Center Experience.

PubMed

Herial, Nabeel A; Khan, Asif A; Sherr, Gregory T; Qureshi, Mushtaq H; Suri, M Fareed K; Qureshi, Adnan I

2015-09-01

The US Food and Drug Administration recently approved a detachable-tip microcatheter, the Apollo microcatheter (eV3, Inc, Irvine, California), to prevent catheter entrapment during embolization of brain arteriovenous malformations (AVMs) using liquid embolic systems. To report technical aspects and clinical results of cerebral embolizations with the Apollo microcatheter in 7 embolizations in 3 adult patients. A 62-year-old man presented with an AVM in the parieto-occipital region measuring 3.6 × 1.6 cm with major cortical feeders from the right middle cerebral artery (MCA) and minor contribution from the distal right anterior cerebral artery. Two pedicles originating from the MCA were embolized. A 48-year-old woman presented with a left frontal AVM measuring 3.3 × 1.8 cm with arterial feeders from the left MCA, left middle meningeal artery, and contralateral anterior cerebral artery. Three pedicles originating from the left MCA were embolized. A 76-year-old man presented with an arteriovenous fistula with multiple fistulous connections and feeders from both vertebral and occipital arteries and the left posterior cerebral artery draining into the left transverse, torcula, and left sigmoid sinus. Two major occipital artery feeders were embolized. Seven Apollo microcatheters were used with the Onyx 18 liquid embolic system. The length of the detachable tip was 15 mm in 2 and 30 mm in 5 embolizations. The mean microcatheter in-position time within the pedicle was 20 minutes. Detachment of tip occurred in 3 instances. No limitations in accessing target arterial feeders and safe tip disengagement were noted despite prolonged injection times. Our initial experience supports the feasibility, safety, and effectiveness of detachable-tip microcatheters in treating brain AVMs and arteriovenous fistulas.

New Lethal Skeletal Dysplasia with Dandy-Walker Malformation, Congenital Heart Defects, Abnormal Thumbs, Hypoplastic Genitalia, and Distinctive Facies

PubMed Central

Stevens, Cathy A.; Lachman, Ralph S.

2011-01-01

We report on two sibs with a lethal form of bone dysplasia with distinctive skeletal findings including rhizomelic and mesomelic limb shortening, hooked clavicles, dumbbell femurs, and absence of talus and calcaneus ossification. Other clinical features include Dandy-Walker malformation, congenital heart defects, joint contractures, genital hypoplasia, and distinctive facial features. These sibs appear to have a previously undescribed skeletal dysplasia, which is most likely inherited in an autosomal recessive fashion. PMID:20602491

Teratogenic effects of Mimosa tenuiflora in a rat model and possible role of N-methyl- and N,N-dimethyltryptamine.

PubMed

Gardner, Dale; Riet-Correa, Franklin; Lemos, Danilo; Welch, Kevin; Pfister, James; Panter, Kip

2014-07-30

Mimosa tenuiflora is a shrub/tree found in northeastern Brazil sometimes eaten by livestock and believed to be responsible for malformations observed in many animals from that region. The teratogenic compounds in M. tenuiflora are not known. This study used pregnant rats fed M. tenuiflora and components therefrom for bioassay and fractionation of possible teratogenic compounds. Rat pups were examined for cranial-facial defects and skeletal malformations. Experimental diets included M. tenuiflora leaf and seed material, extracts of leaf and seed, alkaloid extracts of leaf and seed, and N-methyltryptamine and N,N-dimethyltryptamine. Pups from mothers who received M. tenuiflora plant material, methanol extracts, alkaloid extracts, and purified N-methyltryptamines had a higher incidence of soft tissue cleft palate and skeletal malformations. Results are summarized as to the frequency of observed cleft palate and other noted malformations for each diet versus control.

Congenital absence of the portal vein associated with focal nodular hyperplasia of the liver and congenital heart disease (Abernethy malformation): A case report and literature review

PubMed Central

HAO, YABIN; HONG, XU; ZHAO, XINYAN

2015-01-01

Abernethy malformation is a rare congenital malformation defined by an extrahepatic portosystemic shunt. The majority of affected patients are young (<18 years of age) and experience various symptoms, including vomiting, jaundice, dyspnea and coma. The current study presents a case of Abernethy malformation in an asymptomatic adult male patient. The patient exhibited congenital absence of the portal vein, congenital heart disease (postoperative ventricular septal defect status), and multiple liver lesions, confirmed to be focal nodular hyperplasia by biopsy. Ultrasonography and magnetic resonance imaging findings revealing the liver lesions, type II congenital absence of the portal vein and the portosystemic shunt are presented. In addition, the common clinical presentations, associated anomalies, diagnostic workup and treatment options of this disorder are investigated by reviewing 101 previously reported cases. PMID:25624897

Frog decline, frog malformations, and a comparison of frog and human health.

PubMed

Cohen, M M

2001-11-22

The decline in frog populations and the increase in the frequency of frog malformations are discussed. Topics considered for analysis include chytridiomycosis, retinoids, UV-B radiation, chemical contaminants, environmental threats, introduced invasive species and predation, unsustainable use, and enigmatic decline. Care must be taken to distinguish between hypotheses, laboratory experiments, and the findings in feral frog populations. Clearly, the causes of population decline and malformations are heterogeneous. The subject of frogs and humans is addressed under three subheadings: the importance of frogs to human societies, medical implications of frog studies, and a comparison of frog and human disease factors. Copyright 2001 Wiley-Liss, Inc.

Functional Plasticity in Childhood Brain Disorders: When, What, How, and Whom to Assess

PubMed Central

Dennis, Maureen; Spiegler, Brenda J.; Simic, Nevena; Sinopoli, Katia J.; Wilkinson, Amy; Yeates, Keith Owen; Taylor, H. Gerry; Bigler, Erin D.; Fletcher, Jack M.

2014-01-01

At every point in the lifespan, the brain balances malleable processes representing neural plasticity that promote change with homeostatic processes that promote stability. Whether a child develops typically or with brain injury, his or her neural and behavioral outcome is constructed through transactions between plastic and homeostatic processes and the environment. In clinical research with children in whom the developing brain has been malformed or injured, behavioral outcomes provide an index of the result of plasticity, homeostasis, and environmental transactions. When should we assess outcome in relation to age at brain insult, time since brain insult, and age of the child at testing? What should we measure? Functions involving reacting to the past and predicting the future, as well as social-affective skills, are important. How should we assess outcome? Information from performance variability, direct measures and informants, overt and covert measures, and laboratory and ecological measures should be considered. In whom are we assessing outcome? Assessment should be cognizant of individual differences in gene, socio-economic status (SES), parenting, nutrition, and interpersonal supports, which are moderators that interact with other factors influencing functional outcome. PMID:24821533

The Use of Central Nervous System Active Drugs During Pregnancy

PubMed Central

Källén, Bengt; Borg, Natalia; Reis, Margareta

2013-01-01

CNS-active drugs are used relatively often during pregnancy. Use during early pregnancy may increase the risk of a congenital malformation; use during the later part of pregnancy may be associated with preterm birth, intrauterine growth disturbances and neonatal morbidity. There is also a possibility that drug exposure can affect brain development with long-term neuropsychological harm as a result. This paper summarizes the literature on such drugs used during pregnancy: opioids, anticonvulsants, drugs used for Parkinson’s disease, neuroleptics, sedatives and hypnotics, antidepressants, psychostimulants, and some other CNS-active drugs. In addition to an overview of the literature, data from the Swedish Medical Birth Register (1996–2011) are presented. The exposure data are either based on midwife interviews towards the end of the first trimester or on linkage with a prescribed drug register. An association between malformations and maternal use of anticonvulsants and notably valproic acid is well known from the literature and also demonstrated in the present study. Some other associations between drug exposure and outcome were found. PMID:24275849

Expression analysis of an evolutionarily conserved metallophosphodiesterase gene, Mpped1, in the normal and beta-catenin-deficient malformed dorsal telencephalon.

PubMed

Chen, Chun-Ming; Wang, Hsuan-Yao; You, Li-Ru; Shang, Rong-Li; Liu, Fu-Chin

2010-06-01

We report the expression of the mouse Mpped1 in the telencephalon through embryonic stages to adulthood. Using Northern blotting analysis and RNA in situ hybridization (ISH), our data show that Mpped1 is specifically expressed in the brain and is enriched in the cortical plate of the developing telencephalon. Postnatally, the expression of Mpped1 is reduced in the cerebral cortex relative to its levels in the embryonic dorsal telencephalon. Also, Mpped1 expression is sustained in the hippocampal CA1 region. Examination of the expression of Mpped1 and other cortical layer markers by ISH in a malformed beta-catenin null dorsal telencephalon show that the Mpped1-, Cux2-, and Rorbeta-expressing superficial cortical layers are reduced and form patchy patterns, and the Tbr-1-expressing deep-layer neurons are incorrectly located on superficial layers, indicative of a migration defect of cortical neurons in the absence of beta-catenin.

Pathophysiological analyses of leptomeningeal heterotopia using gyrencephalic mammals.

PubMed

Matsumoto, Naoyuki; Kobayashi, Naoki; Uda, Natsu; Hirota, Miwako; Kawasaki, Hiroshi

2018-03-15

Leptomeningeal glioneuronal heterotopia (LGH) is a focal malformation of the cerebral cortex and frequently found in patients with thanatophoric dysplasia (TD). The pathophysiological mechanisms underlying LGH formation are still largely unclear because of difficulties in obtaining brain samples from human TD patients. Recently, we established a new animal model for analysing cortical malformations of human TD by utilizing our genetic manipulation technique for gyrencephalic carnivore ferrets. Here we investigated the pathophysiological mechanisms underlying the formation of LGH using our TD ferrets. We found that LGH was formed during corticogenesis in TD ferrets. Interestingly, we rarely found Ki-67-positive and phospho-histone H3-positive cells in LGH, suggesting that LGH formation does not involve cell proliferation. We uncovered that vimentin-positive radial glial fibers and doublecortin-positive migrating neurons were accumulated in LGH. This result may indicate that preferential cell migration into LGH underlies LGH formation. Our findings provide novel mechanistic insights into the pathogenesis of LGH in TD.

Environmental enrichment normalizes hippocampal timing coding in a malformed hippocampus.

PubMed

Hernan, Amanda E; Mahoney, J Matthew; Curry, Willie; Richard, Greg; Lucas, Marcella M; Massey, Andrew; Holmes, Gregory L; Scott, Rod C

2018-01-01

Neurodevelopmental insults leading to malformations of cortical development (MCD) are a common cause of psychiatric disorders, learning impairments and epilepsy. In the methylazoxymethanol (MAM) model of MCDs, animals have impairments in spatial cognition that, remarkably, are improved by post-weaning environmental enrichment (EE). To establish how EE impacts network-level mechanisms of spatial cognition, hippocampal in vivo single unit recordings were performed in freely moving animals in an open arena. We took a generalized linear modeling approach to extract fine spike timing (FST) characteristics and related these to place cell fidelity used as a surrogate of spatial cognition. We find that MAM disrupts FST and place-modulated rate coding in hippocampal CA1 and that EE improves many FST parameters towards normal. Moreover, FST parameters predict spatial coherence of neurons, suggesting that mechanisms determining altered FST are responsible for impaired cognition in MCDs. This suggests that FST parameters could represent a therapeutic target to improve cognition even in the context of a brain that develops with a structural abnormality.

Further delineation of the clinical spectrum in RNU4ATAC related microcephalic osteodysplastic primordial dwarfism type I.

PubMed

Abdel-Salam, Ghada M H; Abdel-Hamid, Mohamed S; Hassan, Nihal A; Issa, Mahmoud Y; Effat, Laila; Ismail, Samira; Aglan, Mona S; Zaki, Maha S

2013-08-01

We describe five patients from three different families with microcephalic osteodysplastic primordial dwarfism type I (MOPD I), which was molecularly confirmed by homozygosity for the g.51G >A and g.55G >A mutations in RNU4ATAC, respectively. The patients showed the classical phenotype and demonstrated in addition variable degrees of gyration abnormalities and malformations of the callosal body with an interhemispheric cyst. One patient also showed underdevelopment of the cerebellar vermis. This confirms that cortical malformations should be considered cardinal manifestations of MOPD I. Oculocutaneous albinism, brain hemorrhage and chilblains have been found to be associated with MOPD I. The present study showed lack of retinal pigmentation in three patients of whom two had an unusually fair complexion of hair and skin. One patient was found to have a hematoma in the left thalamus. This may indicate that both pigmentary abnormalities and vascular anomalies may be part of the phenotype of MOPD I as well. Copyright © 2013 Wiley Periodicals, Inc.

Introduction to the supratentorial cerebral arteriovenous malformation video supplement.

PubMed

Starke, Robert M; Albuquerque, Felipe C; Lawton, Michael T

2017-07-01

It is with great pleasure that we present this Neurosurgical Focus video supplement on supratentorial cerebral arteriovenous malformations (AVMs). We were privileged to view a remarkable number of outstanding videos demonstrating current state-of-the-art management of brain AVMs using endovascular and microsurgical modalities. Careful and critical review was required to narrow down the submitted videos to a workable volume for this supplement, which reflects the excellent work being done at multiple centers with these lesions. This issue consists of videos that represent modern microsurgical and neuroendovascular techniques for the treatment of supratentorial cerebral AVMs. The videos demonstrate cutting-edge therapies as well as standard ones, which will be valuable to both novice and expert neurointerventionists and neurosurgeons. We are honored to be involved with this project and proud of its content and expert authors. We believe you will enjoy the video content of this supplement and hope that it will raise the collective expertise of our community of AVM surgeons.

Effectiveness of senna vs polyethylene glycol as laxative therapy in children with constipation related to anorectal malformation.

PubMed

Santos-Jasso, Karla Alejandra; Arredondo-García, José Luis; Maza-Vallejos, Jorge; Lezama-Del Valle, Pablo

2017-01-01

Constipation is present in 80% of children with corrected anorectal malformations, usually associated to rectal dilation and hypomotility. Osmotic laxatives are routinely used for idiopathic constipation. Senna is a stimulant laxative that produces contractions improving colonic motility without affecting the stool consistency. We designed this trial to study the effectiveness of Senna versus polyethylene glycol for the treatment of constipation in children with anorectal malformation. A randomized controlled crossover design clinical trial, including a washout period, was conducted, including children with corrected anorectal malformations with fecal continence and constipation. The sample size was calculated for proportions (n=28) according to available data for Senna. Effectiveness of laxative therapy was measured with a three variable construct: 1) daily bowel movement, 2) fecal soiling, 3) a "clean" abdominal x-ray. Data analysis included descriptive statistics and a Fisher's exact test for the outcome variable (effectiveness). The study was terminated early because the interim analysis showed a clear benefit toward Senna (p = 0.026). The sample showed a normal statistical distribution for the variables age and presence of megarectum. The maximum daily dose of Senna (sennosides A and B) was 38.7mg and 17g for polyethylene glycol. No adverse effects were identified. Therapy with Senna should be the laxative treatment of choice as part of a bowel management program in children with repaired anorectal malformations and constipation, since the stimulation of colonic propulsion waves could lead to stool evacuation without modification of its consistency which can affect fecal continence. I - randomized controlled trial with adequate statistical power. Copyright © 2017 Elsevier Inc. All rights reserved.

Nonimmune hydrops fetalis, hydramnios, microcephaly, and intracranial meningeal hemangioendothelioma.

PubMed

Drut, R; Sapia, S; Gril, D; Velasco, J C; Drut, R M

1993-01-01

Necropsy findings in a male stillborn at 31 weeks gestational age included nonimmune hydrops, hydramnios, and microcephaly secondary to a hemangioendotheliomatous malformation at the tentorium. The vascular lesion was composed by large and small tortuous endothelium-lined vessels and leiomuscular septa. The lesion is thought to be related to the more frequent arteriovenous malformation of the vein of Galen.

Chiari Type I Malformations in Young Adults: Implications for the College Health Practitioner

ERIC Educational Resources Information Center

Elam, Mary Jane; Vaughn, John A.

2011-01-01

In this article, the authors describe 2 cases of Chiari type I malformation (CM-I) in students presenting to a college health center within a 6-month period. A review of CM-I, including epidemiology, typical presentation, evaluation, and management, is followed by a discussion of the clinical and functional implications of the disorder in an…

Venous malformations of the head and neck: current concepts in management.

PubMed

Fowell, C; Verea Linares, C; Jones, R; Nishikawa, H; Monaghan, A

2017-01-01

Low-flow venous malformations are congenital lesions and they are the third most common vascular anomaly in the head and neck. In this paper, the third in a series of three educational reviews, we discuss current trends in their management, and include a summary of common sclerosant agents used in their control. Copyright © 2016. Published by Elsevier Ltd.

Effects of physiotherapy combined with sirolimus in a patient with vascular malformation: A case report.

PubMed

Akbayrak, Türkan; Orhan, Ceren; Baran, Emine; Kaya, Serap; Coskun, Gürsoy; Varan, Ali

2016-01-01

The aim of the present case report was to investigate the effects of a physiotherapy program combined with sirolimus in a child patient with upper extremity edema and joint limitation due to low-flow vascular malformation. This case report included an 11-year-old male patient (26 kg, 130 cm) diagnosed with congenital lymphovascular malformation on the left and right chest. The patient, who had edema on the upper left extremity and experienced joint limitations, was administered complete decongestive therapy (CDT) and manual therapy in combination with sirolimus. Physiotherapy included a total of 24 sessions, 3 sessions a week for 8 weeks. Following the physiotherapy, the patient was assigned to a home therapy program, and then the maintenance phase of the CDT was initiated. Evaluations were carried out at baseline, at the end of week 8, and after 12 months. Following the physiotherapy program combined with sirolimus, a decrease in extremity volume, an increase in joint movement range, and an improvement in disease-related complaints were observed. Physiotherapy methods combined with sirolimus may be an effective treatment method in patients with vascular malformations. However, further studies with larger sample size are warranted.

Abernethy malformation associated with Caroli's syndrome in a patient with a PKHD1 mutation: a case report.

PubMed

Mi, Xiao-Xiao; Li, Xiao-Guang; Wang, Zi-Rong; Lin, Ling; Xu, Chun-Hai; Shi, Jun-Ping

2017-08-16

Abernethy malformation is a rare congenital anomaly characterised by the partial or complete absence of the portal vein and the subsequent development of an extrahepatic portosystemic shunt. Caroli's disease is a rare congenital condition characterised by non-obstructive saccular intrahepatic bile duct dilation. Caroli's disease combined with congenital hepatic fibrosis and/or renal cystic disease is referred to - Caroli's syndrome. The combination of Abernethy malformation and Caroli's syndrome has not been reported previously. We present the case of a 23-year-old female who was found to have both type II Abernethy malformation and Caroli's syndrome. Radiological imaging was performed, including computed tomography with three-dimensional reconstruction and magnetic resonance imaging with (magnetic resonance cholangiopancreatography (MRCP), which revealed a side-to-side portocaval shunt, intrahepatic bile duct dilation, congenital hepatic fibrosis, and renal cysts. In addition, PKHD1 (polycystic kidney and hepatic disease 1) gene mutational analysis revealed a paternally inherited heterozygous missense mutation (c.1877A > G, p.Lys626Arg). A liver biopsy confirmed the pathological features of Caroli's syndrome. To our knowledge, this is the first reported case of a patient with both type II Abernethy malformation and Caroli's syndrome diagnosed using a comprehensive approach that included imaging, mutational analysis, and liver biopsy. Additionally, this is the second reported case to date of an Asian patient presenting with liver and renal disorders with the same paternally inherited PKHD1 missense mutation.

Assessment of the risk of solar ultraviolet radiation to amphibians. I. Dose-dependent induction of hindlimb malformations in the northern leopard frog (Rana pipiens).

PubMed

Ankley, Gerald T; Diamond, Stephen A; Tietge, Joseph E; Holcombe, Gary W; Jensen, Kathleen M; Defoe, David L; Peterson, Ryan

2002-07-01

A number of environmental stressors have been hypothesized as responsible for recent increases in limb malformations in several species of North American amphibians. The purpose of this study was to generate dose-response data suitable for assessing the potential role of solar ultraviolet (UV) radiation in causing limb malformations in a species in which this phenomenon seemingly is particularly prevalent, the northern leopard frog (Rana pipiens). Frogs were exposed from early embryonic stages through complete metamorphosis to varying natural sunlight regimes, including unaltered (100%) sunlight, sunlight subjected to neutral density filtration to achieve relative intensities of 85%, 75%, 65%, 50%, and 25% of unaltered sunlight, and sunlight filtered with glass or acrylamide to attenuate, respectively, the UVB (290-320 nm) and UVB plus UVA (290-380 nm) portions of the spectrum. The experiments were conducted in a controlled setting, with continual monitoring of UVB, UVA, and visible light to support a robust exposure assessment. Full sunlight caused approximately 50% mortality of the frogs during early larval development; no significant treatment-related mortality occurred under any of the other exposure regimes, including 100% sunlight with glass or acrylamide filtration. There was a dose-dependent (p < 0.0001) induction of hindlimb malformations in the frogs, with the percentage of affected animals ranging from about 97% under unaltered sunlight to 0% in the 25% neutral density treatment. Malformations were comprised mostly of missing or truncated digits, and generally were bilateral as well as symmetrical. Filtration of sunlight with either glass or acrylamide both significantly reduced the incidence of malformed limbs. The estimated sunlight dose resulting in a 50% limb malformation rate (ED50) was 63.5%. The limb ED50 values based on measured sunlight intensities corresponded to average daily doses of 4.5 and 100 Wh x m(-2) for UVB and UVA, respectively. Exposure to sunlight also resulted in increased eye malformations in R. pipiens, however, the dose-response relationship for this endpoint was not monotonic. The results of this study, in conjunction with measured or predicted exposure data from natural settings, provide a basis for quantitative prediction of the risk of solar UV radiation to amphibians.

Hypertrophic olivary degeneration following surgical resection or gamma knife radiosurgery of brainstem cavernous malformations: an 11-case series and a review of literature.

PubMed

Yun, Jung-Ho; Ahn, Jae Sung; Park, Jung Cheol; Kwon, Do Hoon; Kwun, Byung Duk; Kim, Chang Jin

2013-03-01

We describe 11 patients with hypertrophic olivary degeneration (HOD) after surgical resection or gamma knife radiosurgery for brainstem cavernous malformations. In addition, we statistically analyzed the predicting factors associated with the development of HOD. From January 2001 to May 2011, a total of 73 patients (30 in the surgical group and 43 in the radiosurgery group) with brainstem cavernous malformations were treated in our institute. Of them, 11 patients (incidence: 15 %) developed HOD with high signal intensity on T2-weighted MRI during follow-up. The predicting factors (location, size, age, and treatment method) associated with the development of HOD were statistically analyzed. Among the 11 HOD patients, seven patients received surgical resection and four patients received gamma knife radiosurgery. Six patients had bilateral HOD and the remaining five patients had unilateral HOD. Overall HOD-associated symptoms presented in four patients, including three palatal tremors and one ataxia. In all four patients with symptoms, these symptoms disappeared incompletely within the clinical follow-up period. The size of the cavernous malformation, age of patient, and treatment methods were not significantly correlated with the development of HOD. A significantly higher incidence of HOD was associated with midbrain cavernous malformations than with pontine or medulla cavernous malformations. HOD should be recognized as a non-infrequent complication of surgical resection or gamma knife radiosurgery within the brainstem, especially for midbrain cavernous malformations. In addition, to the best of our knowledge, this is the first report on HOD development after radiosurgery.

Maternal Use of Opioids During Pregnancy and Congenital Malformations: A Systematic Review

PubMed Central

Lind, Jennifer N.; Interrante, Julia D.; Ailes, Elizabeth C.; Gilboa, Suzanne M.; Khan, Sara; Frey, Meghan T.; Dawson, April L.; Honein, Margaret A.; Dowling, Nicole F.; Razzaghi, Hilda; Creanga, Andreea A.; Broussard, Cheryl S.

2017-01-01

CONTEXT Opioid use and abuse have increased dramatically in recent years, particularly among women. OBJECTIVES We conducted a systematic review to evaluate the association between prenatal opioid use and congenital malformations. DATA SOURCES We searched Medline and Embase for studies published from 1946 to 2016 and reviewed reference lists to identify additional relevant studies. STUDY SELECTION We included studies that were full-text journal articles and reported the results of original epidemiologic research on prenatal opioid exposure and congenital malformations. We assessed study eligibility in multiple phases using a standardized, duplicate review process. DATA EXTRACTION Data on study characteristics, opioid exposure, timing of exposure during pregnancy, congenital malformations (collectively or as individual subtypes), length of follow-up, and main findings were extracted from eligible studies. RESULTS Of the 68 studies that met our inclusion criteria, 46 had an unexposed comparison group; of those, 30 performed statistical tests to measure associations between maternal opioid use during pregnancy and congenital malformations. Seventeen of these (10 of 12 case-control and 7 of 18 cohort studies) documented statistically significant positive associations. Among the case-control studies, associations with oral clefts and ventricular septal defects/atrial septal defects were the most frequently reported specific malformations. Among the cohort studies, clubfoot was the most frequently reported specific malformation. LIMITATIONS Variabilities in study design, poor study quality, and weaknesses with outcome and exposure measurement. CONCLUSIONS Uncertainty remains regarding the teratogenicity of opioids; a careful assessment of risks and benefits is warranted when considering opioid treatment for women of reproductive age. PMID:28562278

Syringohydromyelia in Patients with Chiari I Malformation: A Retrospective Analysis.

PubMed

Gad, K A; Yousem, D M

2017-09-01

The association of syringohydromyelia with Chiari I malformation has a wide range, between 23% and 80% of cases in the current literature. In our experience, this range might be overestimated compared with our observations in clinical practice. Because there is an impact of Chiari I malformation-associated syringohydromyelia on morbidity and surgical intervention, its diagnosis is critical in this patient population. Identifying related variables on the basis of imaging would also help identify those patients at risk of syrinx formation during their course of disease. We performed a retrospective analysis of the MR imaging studies of 108 consecutive cases of Chiari I malformation. A multitude of factors associated with syrinx formation were investigated, including demographic, morphometric, osseous, and dynamic CSF flow evaluation. Thirty-nine of 108 (36.1%) patients with Chiari I malformation had syringohydromyelia. On the basis of receiver operating characteristic curve analysis, a skull base angle (nasion-sella-basion) of 135° was found to be a statistically significant classifier of patients with Chiari I malformation with or without syringohydromyelia. Craniocervical junction osseous anomalies (OR = 4.3, P = .001) and a skull base angle of >135° (OR = 4.8, P = .0006) were most predictive of syrinx formation. Pediatric patients (younger than 18 years of age) who developed syringohydromyelia were more likely to have associated skull base osseous anomalies than older individuals ( P = .01). Our findings support evidence of the role of foramen magnum blockage from osseous factors in the development of syringohydromyelia in patients with Chiari I malformation. © 2017 by American Journal of Neuroradiology.

Antipsychotic Use in Pregnancy and the Risk for Congenital Malformations

PubMed Central

Huybrechts, Krista F.; Hernández-Díaz, Sonia; Patorno, Elisabetta; Desai, Rishi J.; Mogun, Helen; Dejene, Sara Z.; Cohen, Jacqueline M.; Panchaud, Alice; Cohen, Lee; Bateman, Brian T.

2017-01-01

IMPORTANCE The frequency of antipsychotic (AP) use during pregnancy has approximately doubled during the last decade. However, little is known about their safety for the developing fetus, and concerns have been raised about a potential association with congenital malformations. OBJECTIVE To examine the risk for congenital malformations overall and cardiac malformations associated with first-trimester exposure to APs. DESIGN, SETTING, AND PARTICIPANTS This nationwide sample of 1 360 101 pregnant women enrolled in Medicaid with a live-born infant constituted the pregnancy cohort nested in the Medicaid Analytic Extract database, which included data from January 1, 2000, to December 31, 2010. Participants were enrolled in Medicaid from 3 months before their last menstrual period through at least 1 month after delivery. Relative risks (RRs) were estimated using generalized linear models with fine stratification on the propensity score to control for the underlying psychiatric disorders and other potential confounders. Data were analyzed during 2015. EXPOSURES Use of APs during the first trimester, the etiologically relevant period for organogenesis. MAIN OUTCOMES AND MEASURES Major congenital malformations overall and cardiac malformations identified during the first 90 days after delivery. RESULTS Of the 1 341 715 pregnancies that met inclusion criteria (mean [SD] age of women, 24.02 [5.77] years), 9258 (0.69%) filled at least 1 prescription for an atypical AP and 733 (0.05%) filled at least 1 prescription for a typical AP during the first trimester. Overall, 32.7 (95% CI, 32.4–33.0) per 1000 births not exposed to APs were diagnosed with congenital malformations compared with 44.5 (95% CI, 40.5–48.9) per 1000 births exposed to atypical and 38.2 (95% CI, 26.6–54.7) per 1000 births exposed to typical APs. Unadjusted analyses suggested an increased risk for malformations overall for atypical APs (RR, 1.36; 95% CI, 1.24–1.50) but not for typical APs (RR, 1.17; 95% CI, 0.81–1.68). After confounding adjustment, the RR was reduced to 1.05 (95% CI, 0.96–1.16) for atypical APs and 0.90 (95% CI, 0.62–1.31) for typical APs. The findings for cardiac malformations were similar. For the individual agents examined, a small increased risk in overall malformations (RR, 1.26; 95% CI, 1.02–1.56) and cardiac malformations (RR, 1.26; 95% CI, 0.88–1.81) was found for risperidone that was independent of measured confounders. CONCLUSIONS AND RELEVANCE Evidence from this large study suggests that use of APs early in pregnancy generally does not meaningfully increase the risk for congenital malformations overall or cardiac malformations in particular. The small increase in the risk for malformations observed with risperidone requires additional study. PMID:27540849

The health impacts of semiconductor production: an epidemiologic review

PubMed Central

Kim, Myoung-Hee; Kim, Hyunjoo; Paek, Domyung

2014-01-01

Background: Despite concerns over the harmful health effects of semiconductor production, epidemiological studies have shown mixed results. Objectives: We aim to critically appraise epidemiologic studies to date, and to suggest future research and actions to protect workers in semiconductor industry. Methods: Epidemiologic studies were identified through electronic database searches, review of reference lists of relevant published works, and expert consultations, and were narratively reviewed. Results: Most evidence suggests reproductive risks from fabrication jobs, including spontaneous abortion (SAB), congenital malformation, and reduced fertility. Although chemicals have been suspected as causal agents, knowledge of the likely contribution(s) from specific exposures is still limited. Evidence of cancer risk seems to be equivocal. However, the available studies had serious limitations including healthy worker effects (HWEs), information bias, and insufficient power, all of which are associated with underestimation. Nevertheless, excess risks for non-Hodgkin's lymphoma (NHL), leukemia, brain tumor, and breast cancer were observed. Conclusions: Monitoring and innovative research based on international collaboration with a focus on sentinel events are required. PMID:24999845

The health impacts of semiconductor production: an epidemiologic review.

PubMed

Kim, Myoung-Hee; Kim, Hyunjoo; Paek, Domyung

2014-01-01

Despite concerns over the harmful health effects of semiconductor production, epidemiological studies have shown mixed results. We aim to critically appraise epidemiologic studies to date, and to suggest future research and actions to protect workers in semiconductor industry. Epidemiologic studies were identified through electronic database searches, review of reference lists of relevant published works, and expert consultations, and were narratively reviewed. Most evidence suggests reproductive risks from fabrication jobs, including spontaneous abortion (SAB), congenital malformation, and reduced fertility. Although chemicals have been suspected as causal agents, knowledge of the likely contribution(s) from specific exposures is still limited. Evidence of cancer risk seems to be equivocal. However, the available studies had serious limitations including healthy worker effects (HWEs), information bias, and insufficient power, all of which are associated with underestimation. Nevertheless, excess risks for non-Hodgkin's lymphoma (NHL), leukemia, brain tumor, and breast cancer were observed. Monitoring and innovative research based on international collaboration with a focus on sentinel events are required.

[Treatment with sublingual desmopressin in two infants with hydranencephaly and central diabetes insipidus].

PubMed

Marín, Gustavo R; Baspineiro, Berta; Vilca, Iris

2018-02-01

Central diabetes insipidus is a rare disease in children caused by a deficiency of vasopressin. Its main clinical manifestations are polyuria and polydipsia. Brain malformations are one of the main causes. Desmopressin is the synthetic drug of choice for the treatment. One of the routes of administration is sublingual and its use in infants is very limited. We describe two infants with central diabetes insipidus and hydranencephaly who were successfully treated with sublingual desmopressin. Sociedad Argentina de Pediatría.

Chiari I malformation presenting as downbeat nystagmus: clinical presentation, diagnosis, and management.

PubMed

Goodwin, Denise; Halvorson, Ami R

2012-02-15

Chiari I malformation is a congenital, neurological condition that is characterized by defects of the skull base resulting in herniation of the cerebellum through the foramen magnum into the cervical spinal canal. Because the condition can result in visual symptoms, patients will often search for answers from their eye care providers; A 28-year-old Hispanic diabetic male with a 10-year history of nystagmus was referred to the neuro-ophthalmic disease clinic following the initiation of oscillopsia 1 year previous. Downbeat nystagmus, which worsened in right and down gaze, was evident. Cranial nerve testing was unremarkable, but the patient did report trouble with choking on food and drink. Neuroimaging revealed Chiari I malformation. The patient underwent a suboccipital craniectomy which resulted in lessened nystagmus and improved symptoms; The majority of patients with Chiari I malformation have an onset of symptoms in the second or third decade of life. Most commonly, a suboccipital headache that worsens with Valsalva maneuver is present. Visual symptoms include retro-orbital pain, flashing lights or floaters, blurred vision, photophobia, diplopia, transient vision loss, and peripheral vision loss. Objective evidence is often lacking in these patients; however, horizontal or vertical nystagmus is present in up to 45% of those with Chiari I malformation. Surgery has proven to be an effective and safe method to treat symptomatic Chiari I malformation. American Optometric Association.

Deletion of Rbpj from postnatal endothelium leads to abnormal arteriovenous shunting in mice

PubMed Central

Nielsen, Corinne M.; Cuervo, Henar; Ding, Vivianne W.; Kong, Yupeng; Huang, Eric J.; Wang, Rong A.

2014-01-01

Arteriovenous malformations (AVMs) are tortuous vessels characterized by arteriovenous (AV) shunts, which displace capillaries and shunt blood directly from artery to vein. Notch signaling regulates embryonic AV specification by promoting arterial, as opposed to venous, endothelial cell (EC) fate. To understand the essential role of endothelial Notch signaling in postnatal AV organization, we used inducible Cre-loxP recombination to delete Rbpj, a mediator of canonical Notch signaling, from postnatal ECs in mice. Deletion of endothelial Rbpj from birth resulted in features of AVMs by P14, including abnormal AV shunting and tortuous vessels in the brain, intestine and heart. We further analyzed brain AVMs, as they pose particular health risks. Consistent with AVM pathology, we found cerebral hemorrhage, hypoxia and necrosis, and neurological deficits. AV shunts originated from capillaries (and possibly venules), with the earliest detectable morphological abnormalities in AV connections by P8. Prior to AV shunt formation, alterations in EC gene expression were detected, including decreased Efnb2 and increased Pai1, which encodes a downstream effector of TGFβ signaling. After AV shunts had formed, whole-mount immunostaining showed decreased Efnb2 and increased Ephb4 expression within AV shunts, suggesting that ECs were reprogrammed from arterial to venous identity. Deletion of Rbpj from adult ECs led to tortuosities in gastrointestinal, uterine and skin vascular beds, but had mild effects in the brain. Our results demonstrate a temporal requirement for Rbpj in postnatal ECs to maintain proper artery, capillary and vein organization and to prevent abnormal AV shunting and AVM pathogenesis. PMID:25209249

Zika Virus Infection in Pregnancy, Microcephaly, and Maternal and Fetal Health: What We Think, What We Know, and What We Think We Know.

PubMed

Alvarado, Maria Gabriela; Schwartz, David A

2017-01-01

-The global epidemic of Zika virus (ZIKV) infection has emerged as an important public health problem affecting pregnant women and their infants. -To review the causal association between ZIKV infection during pregnancy and intrauterine fetal infection, microcephaly, brain damage, congenital malformation syndrome, and experimental laboratory models of fetal infection. Many questions remain regarding the risk factors, pathophysiology, epidemiology, and timing of maternal-fetal transmission and disease. These include mechanisms of fetal brain damage and microcephaly; the role of covariables, such as viral burden, duration of viremia, and host genetics, on vertical transmission; and the clinical and pathologic spectrum of congenital Zika syndrome. Additional questions include defining the potential long-term physical and neurobehavioral outcomes for infected infants, whether maternal or fetal host genetics influence the clinical outcome, and whether ZIKV infection can cause maternal morbidity. Finally, are experimental laboratory and animal models of ZIKV infection helpful in addressing maternal-fetal viral transmission and the development of congenital microcephaly? This communication provides current information and attempts to address some of these important questions. -Comprehensive review of published scientific literature. -Recent advances in epidemiology, clinical medicine, pathology, and experimental studies have provided a great amount of new information regarding vertical ZIKV transmission and the mechanisms of congenital microcephaly, brain damage, and congenital Zika syndrome in a relatively short time. However, much work still needs to be performed to more completely understand the maternal and fetal aspects of this new and emerging viral disease.

Oral-facial-digital syndrome type IX in a patient with Dandy-Walker malformation.

PubMed Central

Nagai, K; Nagao, M; Nagao, M; Yanai, S; Minagawa, K; Takahashi, Y; Takekoshi, Y; Ishizaka, A; Matsuzono, Y; Kobayashi, O; Itagaki, T

1998-01-01

We report a girl with oral, facial, and digital anomalies including multiple alveolar frenula, lobulated tongue with nodules, a posterior cleft palate, hypertelorism, a prominent forehead with a large anterior fontanelle, and postaxial polydactyly in both hands and the right foot, features compatible with the oral-facial-digital syndrome (OFDS). In addition, she had bilateral microphthalmia, optic disc coloboma, and retinal degeneration with partial detachment, thus establishing a diagnosis of OFDS type IX. Dandy-Walker malformation and retrobulbar cysts were observed on MRI. These additional malformations have not been reported in OFDS type IX. The frequent apnoeic spells which occurred immediately after birth were relieved after cystoperitoneal shunt implantation for hydrocephalus. Considering our case and previous reports of OFDS type IX, including two male sibs, a boy born to consanguineous parents, and three females, inheritance is probably autosomal recessive. Images PMID:9598735

A novel mutation in two Hmong families broadens the range of STRA6-related malformations to include contractures and camptodactyly.

PubMed

Marcadier, Julien L; Mears, Alan J; Woods, Elizabeth A; Fisher, Jamie; Airheart, Cory; Qin, Wen; Beaulieu, Chandree L; Dyment, David A; Innes, A Micheil; Curry, Cynthia J

2016-01-01

PDAC (also termed Matthew Wood) syndrome is a rare, autosomal recessive disorder characterized by pulmonary hypoplasia/aplasia, diaphragmatic defects, bilateral anophthalmia, and cardiac malformations. The disorder is caused by mutations in STRA6, an important regulator of vitamin A and retinoic acid metabolism. We describe six cases from four families of Hmong ancestry, seen over a 30 years period in California. These include: (i) consanguineous siblings with a combination of bilateral anophthalmia, diaphragmatic abnormalities, truncus arteriosus, and/or pulmonary agenesis/hypoplasia; (ii) a singleton fetus with bilateral anophthalmia, pulmonary agenesis, cardiac malformation, and renal hypoplasia; (iii) a sibling pair with a combination of antenatal contractures, camptodactyly, fused palpebral fissures, pulmonary agenesis, and/or truncus arteriosus; (iv) a fetus with bilateral anophthalmia, bushy eyebrows, pulmonary agenesis, heart malformation, and abnormal hand positioning. The phenotypic spectrum of PDAC syndrome has until now not included contractures or camptodactyly. Sequencing of STRA6 in unrelated members of families three and four identified a novel, shared homozygous splice site alteration (c.113 + 3_4delAA) that is predicted to be pathogenic. We hypothesize this may represent a unique disease allele in the Hmong. We also provide a focused review of all published PDAC syndrome cases with confirmed or inferred STRA6 mutations, illustrating the phenotypic and molecular variability that characterizes this disorder. © 2015 Wiley Periodicals, Inc.

Computational and Organotypic Modeling of Microcephaly ...

EPA Pesticide Factsheets

Microcephaly is associated with reduced cortical surface area and ventricular dilations. Many genetic and environmental factors precipitate this malformation, including prenatal alcohol exposure and maternal Zika infection. This complexity motivates the engineering of computational and experimental models to probe the underlying molecular targets, cellular consequences, and biological processes. We describe an Adverse Outcome Pathway (AOP) framework for microcephaly derived from literature on all gene-, chemical-, or viral- effects and brain development. Overlap with NTDs is likely, although the AOP connections identified here focused on microcephaly as the adverse outcome. A query of the Mammalian Phenotype Browser database for ‘microcephaly’ (MP:0000433) returned 85 gene associations; several function in microtubule assembly and centrosome cycle regulated by (microcephalin, MCPH1), a gene for primary microcephaly in humans. The developing ventricular zone is the likely target. In this zone, neuroprogenitor cells (NPCs) self-replicate during the 1st trimester setting brain size, followed by neural differentiation of the neocortex. Recent studies with human NPCs confirmed infectivity with Zika virions invoking critical cell loss (apoptosis) of precursor NPCs; similar findings have been shown with fetal alcohol or methylmercury exposure in rodent studies, leading to mathematical models of NPC dynamics in size determination of the ventricular zone. A key event

Correlation of pressure measurements with angiographic characteristics predisposing to hemorrhage and steal in cerebral arteriovenous malformations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Norbash, A.M.; Marks, M.P.; Lane, B.

1994-05-01

To determine whether there is a physiologic explanation for the predisposition of patients with certain angiographic characteristics to symptoms of hemorrhage and steal. Superselective transcatheter feeding arterial pressure and mean arterial pressure measurements were obtained before embolotherapy in 32 patients with cerebral arteriovenous malformations. Pressures were correlated with previously described angioarchitectural characteristics predisposing to hemorrhage and steal. These included size of the arteriovenous malformation, feeding artery length, venous drainage pattern, and angiomatous change. The feeding arterial pressure and feeding arterial pressure/mean arterial pressure ratios were significantly decreased in patients with angiomatous change. Feeding arterial pressure and feeding arterial pressure/mean arterialmore » pressure ratios progressively decreased as lesions went from peripheral, to mixed, to central venous drainage. A trend for lower feeding arterial pressure was also demonstrated with greater feeding pedicle length. A statistically significant correlation could not be demonstrated between feeding arterial pressure or feeding arterial pressure/mean arterial pressure ratios and size of the arteriovenous malformation, hemorrhage, or symptoms of steal. Feeding arterial pressure measurements help provide a physiologic basis for the relationship between certain angiographic characteristics and hemorrhage and steal symptoms in patients with arteriovenous malformation. 27 refs., 1 fig.« less

Baseline Prevalence of Birth Defects Associated with Congenital Zika Virus Infection - Massachusetts, North Carolina, and Atlanta, Georgia, 2013-2014.

PubMed

Cragan, Janet D; Mai, Cara T; Petersen, Emily E; Liberman, Rebecca F; Forestieri, Nina E; Stevens, Alissa C; Delaney, Augustina; Dawson, April L; Ellington, Sascha R; Shapiro-Mendoza, Carrie K; Dunn, Julie E; Higgins, Cathleen A; Meyer, Robert E; Williams, Tonya; Polen, Kara N D; Newsome, Kim; Reynolds, Megan; Isenburg, Jennifer; Gilboa, Suzanne M; Meaney-Delman, Dana M; Moore, Cynthia A; Boyle, Coleen A; Honein, Margaret A

2017-03-03

Zika virus infection during pregnancy can cause serious brain abnormalities, but the full range of adverse outcomes is unknown (1). To better understand the impact of birth defects resulting from Zika virus infection, the CDC surveillance case definition established in 2016 for birth defects potentially related to Zika virus infection* (2) was retrospectively applied to population-based birth defects surveillance data collected during 2013-2014 in three areas before the introduction of Zika virus (the pre-Zika years) into the World Health Organization's Region of the Americas (Americas) (3). These data, from Massachusetts (2013), North Carolina (2013), and Atlanta, Georgia (2013-2014), included 747 infants and fetuses with one or more of the birth defects meeting the case definition (pre-Zika prevalence = 2.86 per 1,000 live births). Brain abnormalities or microcephaly were the most frequently recorded (1.50 per 1,000), followed by neural tube defects and other early brain malformations † (0.88), eye abnormalities without mention of a brain abnormality (0.31), and other consequences of central nervous system (CNS) dysfunction without mention of brain or eye abnormalities (0.17). During January 15-September 22, 2016, the U.S. Zika Pregnancy Registry (USZPR) reported 26 infants and fetuses with these same defects among 442 completed pregnancies (58.8 per 1,000) born to mothers with laboratory evidence of possible Zika virus infection during pregnancy (2). Although the ascertainment methods differed, this finding was approximately 20 times higher than the proportion of one or more of the same birth defects among pregnancies during the pre-Zika years. These data demonstrate the importance of population-based surveillance for interpreting data about birth defects potentially related to Zika virus infection.

[Arnold-Chiari malformation in Noonan syndrome and other syndromes of the RAS/MAPK pathway].

PubMed

Ejarque, Ismael; Millán-Salvador, José M; Oltra, Silvestre; Pesudo-Martínez, José V; Beneyto, Magdalena; Pérez-Aytés, Antonio

2015-05-01

Noonan syndrome (NS) and other syndromes with a similar phenotype, such as LEOPARD, cardiofaciocutaneous, Costello and Legius, are associated to mutations in genes included in the RAS/MAPK pathway (RASopathies), which is an important signalling pathway related to cell proliferation. Tonsillar descent into the upper cervical spinal canal, known as Arnold-Chiari malformation (ACM), has been reported in patients with NS and this has led some researchers to suggest that ACM could be part of the phenotypic spectrum of NS. We report two cases of NS and ACM. Case 1: 29-year-old female with Noonan phenotype who underwent surgery at the age of nine years due to pulmonary valve stenosis. At the age of 27, she presented symptomatic ACM that required surgical decompression. She presented the c.922A>G (N308D) mutation in the gene PTPN that belongs to the RAS/MAPK pathway. Case 2: a 10-year-old female with Noonan phenotype and asymptomatic ACM detected in magnetic resonance imaging of the brain. She was a carrier of the c.923A>G (N308S) mutation in gene PTPN11. Six patients with this association have been found in the literature, four with the Noonan phenotype and two with LEOPARD. Our two patients provide supplementary evidence that backs up the hypothesis by which ACM would be part of the phenotypic spectrum of NS. The small number of reported cases of patients with this association does not allow us to draw up recommendations about when and how often neuroimaging studies should be performed; a careful neurological examination, however, should be included in the anticipatory health guidelines in syndromes involving the RAS/MAPK pathway.

Contralateral Supracerebellar-Infratentorial Approach for Resection of Thalamic Cavernous Malformations.

PubMed

Mascitelli, Justin; Burkhardt, Jan-Karl; Gandhi, Sirin; Lawton, Michael T

2018-02-26

Surgical resection of cavernous malformations (CM) in the posterior thalamus, pineal region, and midbrain tectum is technically challenging owing to the presence of adjacent eloquent cortex and critical neurovascular structures. Various supracerebellar infratentorial (SCIT) approaches have been used in the surgical armamentarium targeting lesions in this region, including the median, paramedian, and extreme lateral variants. Surgical view of a posterior thalamic CM from the traditional ipsilateral vantage point may be obscured by occipital lobe and tentorium. To describe a novel surgical approach via a contralateral SCIT (cSCIT) trajectory for resecting posterior thalamic CMs. From 1997 to 2017, 75 patients underwent the SCIT approach for cerebrovascular/oncologic pathology by the senior author. Of these, 30 patients underwent the SCIT approach for CM resection, and 3 patients underwent the cSCIT approach. Historical patient data, radiographic features, surgical technique, and postoperative neurological outcomes were evaluated in each patient. All 3 patients presented with symptomatic CMs within the right posterior thalamus with radiographic evidence of hemorrhage. All surgeries were performed in the sitting position. There were no intraoperative complications. Neuroimaging demonstrated complete CM resection in all cases. There were no new or worsening neurological deficits or evidence of rebleeding/recurrence noted postoperatively. This study establishes the surgical feasibility of a contralateral SCIT approach in resection of symptomatic thalamic CMs It demonstrates the application for this procedure in extending the surgical trajectory superiorly and laterally and maximizing safe resectability of these deep CMs with gravity-assisted brain retraction.

[Cloverleaf skull and bilateral facial clefts].

PubMed

Alvarez-Manassero, Denisse; Manassero-Morales, Gioconda

2015-01-01

Cloverleaf skull syndrome, or Kleeblattschädel syndrome, is a rare malformation in which the skull has a cloverleaf appearance. It is caused by the premature closure of several sutures, being evident before birth. To present our experience in a case of cloverleaf skull syndrome, and update the information from the literature. A female infant of 5 months of age, diagnosed at birth with cleft lip and palate and hydrocephaly. A peritoneal ventricle valve was implanted at 30 days of life, and an ocular enucleation was performed due to an infectious process. The patient was followed-up in Genetics, where it confirmed a macrocephaly and craniosynostosis type cloverleaf skull. The 46XX cytogenetic study and echocardiography were normal. The brain CT scan showed multiple anomalies associated with hydrocephaly and non-specific malformations. Cloverleaf skull may be present in isolated form or associated with other congenital abnormalities, leading to various craniosynostosis syndromes, such as Crouzon, Pfeiffer or Carpenter. It may also be a component of the amniotic rupture sequence or to different dysplasias, such as campomelic dysplasia, thanatophoric dysplasia type 2, or the asphyxiating thoracic dystrophy of Jeune. The case presented does not fulfil all the characteristics needed to be included within a specific syndrome, and on not having a family history that suggests a hereditary pattern or chromosome abnormalities, it is concluded that it is a case of a congenital anomaly of sporadic presentation. Copyright © 2015 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

Parasite (Ribeiroia ondatrae) infection linked to amphibian malformations in the western United States

USGS Publications Warehouse

Johnson, P.T.J.; Lunde, K.B.; Thurman, E.M.; Ritchie, E.G.; Wray, S.N.; Sutherland, D.R.; Kapfer, J.M.; Frest, T.J.; Bowerman, J.; Blaustein, A.R.

2002-01-01

Parasites and pathogens can influence the survivorship, behavior, and very structure of their host species. For example, experimental studies have shown that trematode parasites can cause high frequencies of severe limb malformations in amphibians. In a broad-scale field survey covering parts of California, Oregon, Washington, Idaho, and Montana, we examined relationships between the frequency and types of morphological abnormalities in amphibians and the abundance of trematode parasite infection, pH, concentrations of 61 pesticides, and levels of orthophosphate and total nitrate. We recorded severe malformations at frequencies ranging from 1% to 90% in nine amphibian species from 53 aquatic systems. Infection of larvae by the trematode Ribeiroia ondatrae was associated with, and functionally related to, higher frequencies of amphibian limb malformations than found in uninfected populations (≤5%). Parasites were concentrated around the basal tissue of hind limbs in infected anurans, and malformations associated with infection included skin webbings, supernumerary limbs and digits, and missing or malformed hind limbs. In the absence of Ribeiroia, amphibian populations exhibited low (0-5%) frequencies of abnormalities involving missing digits or distal portions of a hind limb. Species were affected differentially by the parasite, and Ambystoma macrodactylum, Hyla regilla, Rand aurora, R. luteiventris, and Taricha torosa typically exhibited the highest frequencies of abnormalities. None of the water-quality variables measured was associated with malformed amphibians, but aquatic snail hosts (Planorbella spp.) were significant predictors of the presence and abundance of Ribeiroia infection. Morphological comparisons of adult specimens of Ribeiroia collected from different sites and raised in experimental definitive hosts suggested that all samples represented the same species - R. ondatrae. These field results, coupled with experimental research on the effects of Ribeiroia on amphibians, demonstrate that Ribeiroia infection is an important and widespread cause of amphibian limb malformations in the western United States. The relevance of trematode infection to declines of amphibian populations and the influence of habitat modification on the pathology and life cycle of Ribeiroia are emphasized as areas requiring further research.

Congenital malformations among babies born following letrozole or clomiphene for infertility treatment.

PubMed

Sharma, Sunita; Ghosh, Sanghamitra; Singh, Soma; Chakravarty, Astha; Ganesh, Ashalatha; Rajani, Shweta; Chakravarty, B N

2014-01-01

Clomiphene citrate (CC) is the first line drug for ovulation induction but because of its peripheral antiestrogenic effect, letrozole was introduced as the 2nd line drug. It lacks the peripheral antiestrogenic effect and is associated with similar or even higher pregnancy rates. Since letrozole is a drug for breast cancer, its use for the purpose of ovulation induction became controversial in the light of studies indicating an increased incidence of congenital malformations. To evaluate and compare the incidence of congenital malformations among offsprings of infertile couples who conceived naturally or with clomiphene citrate or letrozole treatment. A retrospective cohort study done at a tertiary infertility centre. A total of 623 children born to infertile women who conceived naturally or following clomiphene citrate or letrozole treatment were included in this study. Subjects were sorted out from medical files of both mother and newborn and follow up study was done based on the information provided by parents through telephonic conversations. Babies with suspected anomaly were called and examined by specialists for the presence of major and minor congenital malformations. Other outcomes like multiple pregnancy rate and birth weight were also studied. Overall, congenital malformations, chromosomal abnormalities were found in 5 out of 171 (2.9%) babies in natural conception group and 5 out of 201 babies in the letrozole group (2.5%) and in 10 of 251 babies in the CC group (3.9%). There was no significant difference in the overall rate of congenital malformations among children born to mothers who conceived naturally or after letrozole or CC treatment. Congenital malformations have been found to be comparable following natural conception, letrozole and clomiphene citrate. Thus, the undue fear against letrozole may be uncalled for.

OK-432 sclerotherapy of lymphatic malformation in the head and neck: factors related to outcome.

PubMed

Kim, Dong Wook

2014-07-01

No previous study to the best of our knowledge has examined the multiple factors related to the outcome of OK-432 sclerotherapy of lymphatic malformations. This study aimed to assess factors related to the successful outcome of OK-432 sclerotherapy for lymphatic malformations in the head and neck region. During a 6-year period, OK-432 sclerotherapy was performed in 26 patients with lymphatic malformations. Several factors related to the efficacy of OK-432 sclerotherapy were evaluated, including the type (macrocystic or microcystic), the maximum lesion diameter, amount and hemorrhagic cytology of the aspirate, degree of aspiration, injected dose of OK-432 and post-therapy inflammation-related symptom. In all cases, ultrasound (US) follow-up was performed. Of the 26 cases, 13 (50%) showed successful elimination of the lymphatic malformations in the follow-up US after the initial session, and all successful cases were of the macrocystic type. The type of lymphatic malformation and the success of OK-432 sclerotherapy were significantly related (P = 0.0149). Of the 16 cases of complete aspiration, 11 (68.8%) showed a successful outcome. Further, of the 17 cases with inflammation-related symptom, 13 (76.5%) showed a successful outcome. While the degree of aspiration and presence of inflammation-related symptom showed a significant relationship with the success of OK-432 sclerotherapy (P < 0.05), no other factors showed a significant relationship. The study results suggest that the macrocystic type and complete aspiration of cystic contents were important factors for the success of OK-432 sclerotherapy of lymphatic malformations, and that inflammation-related symptom was a predictor of a successful outcome.

Emerging Viral Infections in Sub-Saharan Africa and the Developing Nervous System: A Mini Review.

PubMed

Kakooza-Mwesige, Angelina; Mohammed, Abdul H; Kristensson, Krister; Juliano, Sharon L; Lutwama, Julius J

2018-01-01

The global public health concern is heightened over the increasing number of emerging viruses, i.e., newly discovered or previously known that have expanded into new geographical zones. These viruses challenge the health-care systems in sub-Saharan Africa (SSA) countries from which several of them have originated and been transmitted by insects worldwide. Some of these viruses are neuroinvasive, but have been relatively neglected by neuroscientists. They may provide experiments by nature to give a time window for exposure to a new virus within sizeable, previously non-infected human populations, which, for instance, enables studies on potential long-term or late-onset effects on the developing nervous system. Here, we briefly summarize studies on the developing brain by West Nile, Zika, and Chikungunya viruses, which are mosquito-borne and have spread worldwide out of SSA. They can all be neuroinvasive, but their effects vary from malformations caused by prenatal infections to cognitive disturbances following perinatal or later infections. We also highlight Ebola virus, which can leave surviving children with psychiatric disturbances and cause persistent infections in the non-human primate brain. Greater awareness within the neuroscience community is needed to emphasize the menace evoked by these emerging viruses to the developing brain. In particular, frontline neuroscience research should include neuropediatric follow-up studies in the field on long-term or late-onset cognitive and behavior disturbances or neuropsychiatric disorders. Studies on pathogenetic mechanisms for viral-induced perturbations of brain maturation should be extended to the vulnerable periods when neurocircuit formations are at peaks during infancy and early childhood.

Mouse IDGenes: a reference database for genetic interactions in the developing mouse brain

PubMed Central

Matthes, Michaela; Preusse, Martin; Zhang, Jingzhong; Schechter, Julia; Mayer, Daniela; Lentes, Bernd; Theis, Fabian; Prakash, Nilima; Wurst, Wolfgang; Trümbach, Dietrich

2014-01-01

The study of developmental processes in the mouse and other vertebrates includes the understanding of patterning along the anterior–posterior, dorsal–ventral and medial– lateral axis. Specifically, neural development is also of great clinical relevance because several human neuropsychiatric disorders such as schizophrenia, autism disorders or drug addiction and also brain malformations are thought to have neurodevelopmental origins, i.e. pathogenesis initiates during childhood and adolescence. Impacts during early neurodevelopment might also predispose to late-onset neurodegenerative disorders, such as Parkinson’s disease. The neural tube develops from its precursor tissue, the neural plate, in a patterning process that is determined by compartmentalization into morphogenetic units, the action of local signaling centers and a well-defined and locally restricted expression of genes and their interactions. While public databases provide gene expression data with spatio-temporal resolution, they usually neglect the genetic interactions that govern neural development. Here, we introduce Mouse IDGenes, a reference database for genetic interactions in the developing mouse brain. The database is highly curated and offers detailed information about gene expressions and the genetic interactions at the developing mid-/hindbrain boundary. To showcase the predictive power of interaction data, we infer new Wnt/β-catenin target genes by machine learning and validate one of them experimentally. The database is updated regularly. Moreover, it can easily be extended by the research community. Mouse IDGenes will contribute as an important resource to the research on mouse brain development, not exclusively by offering data retrieval, but also by allowing data input. Database URL: http://mouseidgenes.helmholtz-muenchen.de. PMID:25145340

Emerging Viral Infections in Sub-Saharan Africa and the Developing Nervous System: A Mini Review

PubMed Central

Kakooza-Mwesige, Angelina; Mohammed, Abdul H.; Kristensson, Krister; Juliano, Sharon L.; Lutwama, Julius J.

2018-01-01

The global public health concern is heightened over the increasing number of emerging viruses, i.e., newly discovered or previously known that have expanded into new geographical zones. These viruses challenge the health-care systems in sub-Saharan Africa (SSA) countries from which several of them have originated and been transmitted by insects worldwide. Some of these viruses are neuroinvasive, but have been relatively neglected by neuroscientists. They may provide experiments by nature to give a time window for exposure to a new virus within sizeable, previously non-infected human populations, which, for instance, enables studies on potential long-term or late-onset effects on the developing nervous system. Here, we briefly summarize studies on the developing brain by West Nile, Zika, and Chikungunya viruses, which are mosquito-borne and have spread worldwide out of SSA. They can all be neuroinvasive, but their effects vary from malformations caused by prenatal infections to cognitive disturbances following perinatal or later infections. We also highlight Ebola virus, which can leave surviving children with psychiatric disturbances and cause persistent infections in the non-human primate brain. Greater awareness within the neuroscience community is needed to emphasize the menace evoked by these emerging viruses to the developing brain. In particular, frontline neuroscience research should include neuropediatric follow-up studies in the field on long-term or late-onset cognitive and behavior disturbances or neuropsychiatric disorders. Studies on pathogenetic mechanisms for viral-induced perturbations of brain maturation should be extended to the vulnerable periods when neurocircuit formations are at peaks during infancy and early childhood. PMID:29527187

Mouse IDGenes: a reference database for genetic interactions in the developing mouse brain.

PubMed

Matthes, Michaela; Preusse, Martin; Zhang, Jingzhong; Schechter, Julia; Mayer, Daniela; Lentes, Bernd; Theis, Fabian; Prakash, Nilima; Wurst, Wolfgang; Trümbach, Dietrich

2014-01-01

The study of developmental processes in the mouse and other vertebrates includes the understanding of patterning along the anterior-posterior, dorsal-ventral and medial- lateral axis. Specifically, neural development is also of great clinical relevance because several human neuropsychiatric disorders such as schizophrenia, autism disorders or drug addiction and also brain malformations are thought to have neurodevelopmental origins, i.e. pathogenesis initiates during childhood and adolescence. Impacts during early neurodevelopment might also predispose to late-onset neurodegenerative disorders, such as Parkinson's disease. The neural tube develops from its precursor tissue, the neural plate, in a patterning process that is determined by compartmentalization into morphogenetic units, the action of local signaling centers and a well-defined and locally restricted expression of genes and their interactions. While public databases provide gene expression data with spatio-temporal resolution, they usually neglect the genetic interactions that govern neural development. Here, we introduce Mouse IDGenes, a reference database for genetic interactions in the developing mouse brain. The database is highly curated and offers detailed information about gene expressions and the genetic interactions at the developing mid-/hindbrain boundary. To showcase the predictive power of interaction data, we infer new Wnt/β-catenin target genes by machine learning and validate one of them experimentally. The database is updated regularly. Moreover, it can easily be extended by the research community. Mouse IDGenes will contribute as an important resource to the research on mouse brain development, not exclusively by offering data retrieval, but also by allowing data input. http://mouseidgenes.helmholtz-muenchen.de. © The Author(s) 2014. Published by Oxford University Press.

Chitosan nanoparticles and their Tween 80 modified counterparts disrupt the developmental profile of zebrafish embryos.

PubMed

Yuan, Zhongyue; Li, Ying; Hu, Yulan; You, Jian; Higashisaka, Kazuma; Nagano, Kazuya; Tsutsumi, Yasuo; Gao, Jianqing

2016-12-30

Chitosan nanoparticles (CS-NPs) and their Tween 80 modified counterparts (TmCS-NPs) are among the most commonly used brain-targeted vehicles. However, their potential developmental toxicity is poorly understood. In this study, zebrafish embryos are introduced as an in vivo platform. Both NPs showed a dose-dependent increase in developmental toxicity (decreased hatching rate, increased mortality and incidences of malformation). Neurobehavioral changes included decreased spontaneous movement in TmCS-NP treated embryos and hyperactive effect in CS-NP treated larvae. Both NPs remarkably inhibited axonal development of primary and secondary motor neurons, and affected the muscle structure. Overall, this study demonstrated that CS-NPs and TmCS-NPs could affect embryonic development, disrupt neurobehavior of zebrafish larvae and affect muscle and neuron development, suggesting more attention on biodegradable chitosan nanoparticles. Copyright © 2016 Elsevier B.V. All rights reserved.

Autoimmune central diabetes insipidus in a patient with ureaplasma urealyticum infection and review on new triggers of immune response.

PubMed

Murdaca, Giuseppe; Russo, Rodolfo; Spanò, Francesca; Ferone, Diego; Albertelli, Manuela; Schenone, Angelo; Contatore, Miriam; Guastalla, Andrea; De Bellis, Annamaria; Garibotto, Giacomo; Puppo, Francesco

2015-12-01

Diabetes insipidus is a disease in which large volumes of dilute urine (polyuria) are excreted due to vasopressin (AVP) deficiency [central diabetes insipidus (CDI)] or to AVP resistance (nephrogenic diabetes insipidus). In the majority of patients, the occurrence of CDI is related to the destruction or degeneration of neurons of the hypothalamic supraoptic and paraventricular nuclei. The most common and well recognized causes include local inflammatory or autoimmune diseases, vascular disorders, Langerhans cell histiocytosis (LCH), sarcoidosis, tumors such as germinoma/craniopharyngioma or metastases, traumatic brain injuries, intracranial surgery, and midline cerebral and cranial malformations. Here we have the opportunity to describe an unusual case of female patient who developed autoimmune CDI following ureaplasma urealyticum infection and to review the literature on this uncommon feature. Moreover, we also discussed the potential mechanisms by which ureaplasma urealyticum might favor the development of autoimmune CDI.

Identification of arteries and veins in cerebral angiography fluoroscopic images

NASA Astrophysics Data System (ADS)

Andra Tache, Irina

2017-11-01

In the present study a new method for pixels tagging into arteries and veins classes from temporal cerebral angiography is presented. This need comes from the neurosurgeon who is evaluating the fluoroscopic angiography and the magnetic resonance images from the brain in order to locate the fistula of the patients who suffer from arterio-venous malformation. The method includes the elimination of the background pixels from a previous segmentation and the generation of the time intensity curves for each remaining pixel. The later undergo signal processing in order to extract the characteristic parameters needed for applying the k-means clustering algorithm. Some of the parameters are: the phase and the maximum amplitude extracted from the Fourier transform, the standard deviation and the mean value. The tagged classes are represented into images which then are re-classified by an expert into artery and vein pixels.

WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility

PubMed Central

Yan, Catherine; Martinez-Quiles, Narcisa; Eden, Sharon; Shibata, Tomoyuki; Takeshima, Fuminao; Shinkura, Reiko; Fujiwara, Yuko; Bronson, Roderick; Snapper, Scott B.; Kirschner, Marc W.; Geha, Raif; Rosen, Fred S.; Alt, Frederick W.

2003-01-01

The Wiskott–Aldrich syndrome related protein WAVE2 is implicated in the regulation of actin-cytoskeletal reorganization downstream of the small Rho GTPase, Rac. We inactivated the WAVE2 gene by gene-targeted mutation to examine its role in murine development and in actin assembly. WAVE2-deficient embryos survived until approximately embryonic day 12.5 and displayed growth retardation and certain morphological defects, including malformations of the ventricles in the developing brain. WAVE2-deficient embryonic stem cells displayed normal proliferation, whereas WAVE2-deficient embryonic fibroblasts exhibited severe growth defects, as well as defective cell motility in response to PDGF, lamellipodium formation and Rac-mediated actin polymerization. These results imply a non-redundant role for WAVE2 in murine embryogenesis and a critical role for WAVE2 in actin-based processes downstream of Rac that are essential for cell movement. PMID:12853475

WAVE2 deficiency reveals distinct roles in embryogenesis and Rac-mediated actin-based motility.

PubMed

Yan, Catherine; Martinez-Quiles, Narcisa; Eden, Sharon; Shibata, Tomoyuki; Takeshima, Fuminao; Shinkura, Reiko; Fujiwara, Yuko; Bronson, Roderick; Snapper, Scott B; Kirschner, Marc W; Geha, Raif; Rosen, Fred S; Alt, Frederick W

2003-07-15

The Wiskott-Aldrich syndrome related protein WAVE2 is implicated in the regulation of actin-cytoskeletal reorganization downstream of the small Rho GTPase, Rac. We inactivated the WAVE2 gene by gene-targeted mutation to examine its role in murine development and in actin assembly. WAVE2-deficient embryos survived until approximately embryonic day 12.5 and displayed growth retardation and certain morphological defects, including malformations of the ventricles in the developing brain. WAVE2-deficient embryonic stem cells displayed normal proliferation, whereas WAVE2-deficient embryonic fibroblasts exhibited severe growth defects, as well as defective cell motility in response to PDGF, lamellipodium formation and Rac-mediated actin polymerization. These results imply a non-redundant role for WAVE2 in murine embryogenesis and a critical role for WAVE2 in actin-based processes downstream of Rac that are essential for cell movement.

Neurotransmitter signaling pathways required for normal development in Xenopus laevis embryos: a pharmacological survey screen

PubMed Central

Sullivan, Kelly G.; Levin, Michael

2016-01-01

Neurotransmitters are not only involved in brain function but are also important signaling molecules for many diverse cell types. Neurotransmitters are widely conserved, from evolutionarily ancient organisms lacking nervous systems through man. Here, we report results from a loss- and gain-of-function survey, using pharmacologic modulators of several neurotransmitter pathways to examine possible roles in normal embryogenesis. Applying reagents targeting the glutamatergic, adrenergic, and dopaminergic pathways to embryos of Xenopus laevis from gastrulation to organogenesis stages, we observed and quantified numerous malformations including craniofacial defects, hyperpigmentation, muscle mispatterning, and miscoiling of the gut. These data implicate several key neurotransmitters in new embryonic patterning roles, reveal novel earlier stages for processes involved in eye development, suggest new targets for subsequent molecular-genetic investigation, and highlight the necessity for in-depth toxicology studies of psychoactive compounds to which human embryos might be exposed during pregnancy. PMID:27060969

Microcatheter entrapment retrieval from Onyx embolization in brain arteriovenous malformations: A technical note.

PubMed

Vu, Phat D; Grigorian, Arthur A

2015-10-01

Many techniques have been use for retrieval of an entrapped microcatheter during Onyx (eV3 Neurovascular) embolization of brain arteriovenous malformations (BAVMs). We report our technique that we term "pull-push-pull" that can be utilized as first management in retrieving the microcatheter. We analyzed a total of 37 patients that underwent BAVM embolization with either Onyx 18 or 34 at our institution. Standard embolization techniques were utilized with the use of Marathon (eV3 Neurovascular) microcatheter. When difficulty in retrieving the microcatheter arose, we used the "pull-push-pull" technique. The technique comprises the eV3 protocol of retraction. In addition, the microcatheter is stretched causing the Onyx cast to stretch in its inner core, creating a more thorough cohesive property amongst the Onyx mixture. Then the microcatheter is pushed back and to its point of embolization origin. Afterwards, retraction of the microcatheter is enabled as it can be easily dislodged from the cast. Multiple attempts can be repeated as needed. We had three patients that had difficulty with removal of microcatheter (8.1%). Utilization of the "pull-push-pull" technique was used on two of those patients. No neurological complication was observed with our technique. We believe the cohesive property of Onyx solution helps in the retrieval of the catheter by our method and technique. We believe the "pull-push-pull" can be utilized and be an additional technique before attempting other catheter retrieval techniques in Onyx BAVM embolization. © The Author(s) 2015.

Elaboration of a semi-automated algorithm for brain arteriovenous malformation segmentation: initial results.

PubMed

Clarençon, Frédéric; Maizeroi-Eugène, Franck; Bresson, Damien; Maingreaud, Flavien; Sourour, Nader; Couquet, Claude; Ayoub, David; Chiras, Jacques; Yardin, Catherine; Mounayer, Charbel

2015-02-01

The purpose of our study was to distinguish the different components of a brain arteriovenous malformation (bAVM) on 3D rotational angiography (3D-RA) using a semi-automated segmentation algorithm. Data from 3D-RA of 15 patients (8 males, 7 females; 14 supratentorial bAVMs, 1 infratentorial) were used to test the algorithm. Segmentation was performed in two steps: (1) nidus segmentation from propagation (vertical then horizontal) of tagging on the reference slice (i.e., the slice on which the nidus had the biggest surface); (2) contiguity propagation (based on density and variance) from tagging of arteries and veins distant from the nidus. Segmentation quality was evaluated by comparison with six frame/s DSA by two independent reviewers. Analysis of supraselective microcatheterisation was performed to dispel discrepancy. Mean duration for bAVM segmentation was 64 ± 26 min. Quality of segmentation was evaluated as good or fair in 93% of cases. Segmentation had better results than six frame/s DSA for the depiction of a focal ectasia on the main draining vein and for the evaluation of the venous drainage pattern. This segmentation algorithm is a promising tool that may help improve the understanding of bAVM angio-architecture, especially the venous drainage. • The segmentation algorithm allows for the distinction of the AVM's components • This algorithm helps to see the venous drainage of bAVMs more precisely • This algorithm may help to reduce the treatment-related complication rate.

Spontaneous renal hemorrhage secondary to choriocarcinoma in a man with congenital hypospadias and cryptorchidism: a case report and literature review.

PubMed

Li, Yi; Chen, Gang; Chen, Han; Wen, Shuang; Xiong, Chao-Yu; Yang, Zi-Yi; Zhu, Yun-Xiao; Jeffreys, Nathan

2018-05-08

Choriocarcinoma is a rare malignant germ-cell tumour, most commonly found in adult women. It infrequently presents as spontaneous renal haemorrhage (SRH). Genital malformation and SRH secondary to choriocarcinoma has previously been only reported in females. We present what we believe to be the first case of a male patient with genital malformation (hypospadias and cryptorchidism) and SRH at presentation of choriocarcinoma. A 25-year-old man presented to the department with intense pain in the right flank region and lower back. Initial investigations showed spontaneous renal haemorrhage, for which an emergency partial nephrectomy was performed. Clinical, radiological, and pathological investigations suggested a diagnosis of testicular choriocarcinoma with metastases to the right kidney, both lungs, and brain. Initial treatment was with a chemotherapy regimen of cisplatin, etoposide and bleomycin and whole brain radiotherapy; however, 6 months after diagnosis the patient developed liver metastasis, after which time the BEP protocol was switched to ITP with oral apatinib. Despite best efforts, the liver and lung metastasis continued to grow and a decision was made to discontinue active treatment and provide only palliative care until the patient passed away. Choriocarcinoma is a difficult cancer to diagnose pre-operatively. In male patients with early metastasis, prognosis may be much poorer than in the commoner gestational choriocarcinoma. A multidisciplinary with comprehensive post-surgical intervention is of great importance in the treatment of these patients.

Comprehensive genomic analysis of patients with disorders of cerebral cortical development.

PubMed

Wiszniewski, Wojciech; Gawlinski, Pawel; Gambin, Tomasz; Bekiesinska-Figatowska, Monika; Obersztyn, Ewa; Antczak-Marach, Dorota; Akdemir, Zeynep Hande Coban; Harel, Tamar; Karaca, Ender; Jurek, Marta; Sobecka, Katarzyna; Nowakowska, Beata; Kruk, Malgorzata; Terczynska, Iwona; Goszczanska-Ciuchta, Alicja; Rudzka-Dybala, Mariola; Jamroz, Ewa; Pyrkosz, Antoni; Jakubiuk-Tomaszuk, Anna; Iwanowski, Piotr; Gieruszczak-Bialek, Dorota; Piotrowicz, Malgorzata; Sasiadek, Maria; Kochanowska, Iwona; Gurda, Barbara; Steinborn, Barbara; Dawidziuk, Mateusz; Castaneda, Jennifer; Wlasienko, Pawel; Bezniakow, Natalia; Jhangiani, Shalini N; Hoffman-Zacharska, Dorota; Bal, Jerzy; Szczepanik, Elzbieta; Boerwinkle, Eric; Gibbs, Richard A; Lupski, James R

2018-04-30

Malformations of cortical development (MCDs) manifest with structural brain anomalies that lead to neurologic sequelae, including epilepsy, cerebral palsy, developmental delay, and intellectual disability. To investigate the underlying genetic architecture of patients with disorders of cerebral cortical development, a cohort of 54 patients demonstrating neuroradiologic signs of MCDs was investigated. Individual genomes were interrogated for single-nucleotide variants (SNV) and copy number variants (CNV) with whole-exome sequencing and chromosomal microarray studies. Variation affecting known MCDs-associated genes was found in 16/54 cases, including 11 patients with SNV, 2 patients with CNV, and 3 patients with both CNV and SNV, at distinct loci. Diagnostic pathogenic SNV and potentially damaging variants of unknown significance (VUS) were identified in two groups of seven individuals each. We demonstrated that de novo variants are important among patients with MCDs as they were identified in 10/16 individuals with a molecular diagnosis. Three patients showed changes in known MCDs genes  and a clinical phenotype beyond the usual characteristics observed, i.e., phenotypic expansion, for a particular known disease gene clinical entity. We also discovered 2 likely candidate genes, CDH4, and ASTN1, with human and animal studies supporting their roles in brain development, and 5 potential candidate genes. Our findings emphasize genetic heterogeneity of MCDs disorders and postulate potential novel candidate genes involved in cerebral cortical development.

Brainstem cavernous malformations: Natural history versus surgical management.

PubMed

Walcott, Brian P; Choudhri, Omar; Lawton, Michael T

2016-10-01

While brainstem cavernous malformations were once considered inoperable, improvements in patient selection, surgical exposures, intraoperative MRI-guidance, MR tractography, and neurophysiologic monitoring have resulted in good outcomes in the majority of operated patients. In a consecutive series of 104 patients with brainstem cavernous malformations, only 14% of patients experienced cranial nerve or motor dysfunction that was worse at late follow-up, relative to their preoperative condition. Outcomes were predicted by several factors, including larger lesion size, lesions that crossed the midline, the presence of a developmental venous anomaly, older age, and greater time interval from lesion hemorrhage to surgery. The 14% of patients who experienced a persistent neurological deficit as a result of surgery, while substantial from any perspective, compares favorably with the risks of observation based on a recent meta-analysis. Curative resection is a safe and effective treatment for brainstem cavernous malformations that will prevent re-hemorrhage in symptomatic patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Zika virus infection and pregnancy: what we do and do not know

PubMed Central

Ticconi, Carlo; Pietropolli, Adalgisa; Rezza, Giovanni

2016-01-01

Recent data strongly suggest an association between the current outbreak of ZIKA virus (ZIKV) in many countries of Central and South America and a sharp increase in the detection of microcephaly and fetal malformations. The link with brain defect, which has been detected mainly in some areas of Brazil, is supported by the following evidence: (1) ZIKV transmission from infected pregnant women to their fetuses; (2) the potential of ZIKV to determine a specific congenital fetal syndrome characterized by abnormalities involving primarily the developing brain and eye. In particular, the risk of transmission and congenital disease appears to be restricted to mother’s infection during the first trimester of pregnancy. Among brain defects, microcephaly, brain calcifications, and ventriculomegaly are the most frequent abnormalities of the central nervous system detected so far. However, relevant information on effect of maternal infection with ZIKV on the fetus is still limited. In this review, we focus our attention on current knowledge about ZIKV infection in pregnancy, discussing relevant issues and open problems which merit further investigation. PMID:27690200

Genital malformations in newborns of female nickel-refinery workers.

PubMed

Vaktskjold, Arild; Talykova, Ljudmila Vasiljevna; Chashchin, Valerij Petrovitsj; Nieboer, Evert; Thomassen, Yngvar; Odland, Jon Oyvind

2006-02-01

This study investigated whether pregnant women employed in nickel-exposed work areas are at elevated risk of delivering a newborn with a genital malformation. In this register-based cohort study, data about pregnancy outcome and occupation were obtained using the Kola Birth Registry. Each record in the Registry was assigned a categorical nickel exposure rating according to the occupation the delivering woman had at the time of becoming pregnant, using, as guidelines, the water-soluble nickel subfraction of the inhalable aerosol fraction obtained by personal monitoring for nickel-refinery workers or the measured urinary nickel concentrations. The reference population comprised delivering women from Moncegorsk with a background exposure level. The association of the outcome with the assigned exposure ratings was analyzed in a logistic regression model, adjusted for parity, maternal malformation, exposure to solvents, and infection in early pregnancy. The odds ratio for nickel-exposed women delivering a newborn with a genital malformation was 0.81 [95% confidence interval (95% CI) 0.52-1.26], and that for an undescended testicle was 0.76 (95% CI 0.40-1.47). In this study no negative effect of maternal exposure to water-soluble nickel was found on the risk of delivering a newborn with malformations of the genital organs. The results should be interpreted with caution since there were few cases in the higher exposure groups. The findings do not exclude the possibility of an effect on the risk of other congenital malformations and adverse outcomes (including reduced fertility).