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Progression of exencephaly to anencephaly in the human fetus - An ultrasound perspective
Abstract
Exencephaly as a precursor of anencephaly is well delineated in animal studies. In humans, a similar though unproven embryologic sequence is postulated. In the case reported, serial ultrasound studies allowed us to identify a 16-week human exencephalic fetus and observe the cephalic changes during its progression to a classic anencephalic appearance.
... Acrania is a cranial vault defect characterized by the partial or total absence of the cranial bones and the covering skin, with complete but abnormal development of the chondrocranium and the presence of brain tissue that is exposed [3] . The progression from exencephaly to anencephaly was first described by Wilkins-Haug et al. [4] . A standardized protocol in the sonographic evaluation of the developing foetus is necessary for an early prenatal diagnosis of congenital malformations [3] . ...
... NTD is a developmental sequence of events that leads to anencephaly consisting of three phases: [1] dysraphia, or a failure of the neural groove to close in the rostral region; [2] exencephaly, or well-developed brain outside the skull during the embryonic period; and [3] disintegration of the exposed brain during the foetal period, resulting in anencephaly [7] . The progression from exencephaly to anencephaly was first described by Wilkins-Haug et al. [4] . Hegazy and Hegazy suggested that the developments of Gross malformation with cleft lip, cleft palate and exposed brain tissue covered by thin layer of membrane with incompletely formed cranial vault and multiple-haematoma in the exposed brain tissue. ...
Introduction and importance:
Neural tube defect occurs as a result of failure of spontaneous closure of the neural tube between the third and fourth weeks of fetal life. Exencephaly is a rare malformation of the neural tube characterized by a large amount of protruding brain tissue in the absence of the calvarium.
Case presentation:
The authors report a 29-year-old female, non-compliant to iron, calcium and folic acid tablets due to nauseating and itchy sensation after intake for 2 weeks, was admitted in ward Obstetrics ward in view of twin pregnancy. After proper counselling, she was advised for caesarean section, which revealed gross malformation in the form of cleft lip, cleft palate and exposed brain tissue covered by thin layer of membrane with incompletely formed cranial vault and multiple-hematoma and ulcerations in the exposed brain tissue suggestive of Exencephaly. The deformed baby survived for 2 days after birth while the other baby was grossly healthy.
Clinical discussion:
Exencephaly is said to be the embryological precursor anomaly of anencephaly. Exencephaly is a type of cranial malformation that characteristically involves a large disorganized mass of brain tissue. The flat bones of calvaria are absent and the brain mass is left uncovered. This condition is incompatible with life.
Conclusion:
Each and every pregnant lady must be advised to undergo ultrasonography in every trimester, especially second trimester scan (anomaly scan) to diagnose any gross congenital malformations. Each pregnant lady is suggested to take the necessary vitamins (like folic acid) to avoid any Neural tube defects.
... The progression from exencephaly to anencephaly was first described by Wilkins-Haug et al. [5]. A standardized protocol in the sonographic evaluation of the developing fetus is necessary for an early prenatal diagnosis of congenital malformations [4]. ...
Exencephaly is a rare fetal anomaly that is incompatible with extra uterine life. This malformation is characterized by partial or complete absence of the calvaria (cranium) called acrania with abnormal development of brain tissue.
We present a case of a live acrania-exencephalic newborn to a 19 year old of parity 1 plus 1 in a non-consanguineous marriage delivered at 39 weeks of amenorrhea. Early prenatal ultrasound scan (USS), showed a single fetu sat 9 weeks with no deformity however at birth, acrania-exencephaly was diagnosed.The newborn died on the 3rd day of life and autopsy revealed exencephaly with deformed brain under a thick membrane without any other malformation.
We present a rare fetal anomaly of acrania–exencephaly which persisted till term and was not detected by the prenatal ultrasound scan.
... Cranioschisis is therefore linked with anencephaly, which is noncompatible with life. 29 Acrania can be diagnosed as early as the first trimester (►Fig. 4). ...
The musculoskeletal (MSK) system begins to form in the third week of intrauterine development. Multiple genes are involved in the complex different processes to form the skeleton, muscles and joints. The embryonic period, from the third to the eighth week of development, is critical for normal development and therefore the time when most structural defects are induced. Many of these defects have a genetic origin, but environmental factors may also play a very important role. This review summarizes the embryology of the different components of the MSK system and their configuration as an organ-system, analyzes the clinical implications resulting from failures in the process of organogenesis, and describes the first approach to diagnosis of skeletal abnormalities using prenatal ultrasound.
... Cranioschisis is therefore linked with anencephaly, which is noncompatible with life. 29 Acrania can be diagnosed as early as the first trimester (►Fig. 4). ...
The musculoskeletal (MSK) system begins to form in the third week of intrauterine
development. Multiple genes are involved in the complex different processes to form
the skeleton, muscles and joints. The embryonic period, from the third to the eighth
week of development, is critical for normal development and therefore the time when
most structural defects are induced. Many of these defects have a genetic origin, but
environmental factors may also play a very important role. This review summarizes the
embryology of the different components of the MSK system and their configuration as
an organ-system, analyzes the clinical implications resulting from failures in the process
of organogenesis, and describes the first approach to diagnosis of skeletal abnormalities
using prenatal ultrasound.
... Acrania which is absence of the skull along with skin and meningeal coverings represents the first stage of this mal-development sequence that takes place 18-20 days post-fertilization [17] and the progression from exencephaly which is exposed brain as a result of lack of skull and meninges with skin, to anencephaly was first described by Wilkins et al. [18]. When acrania is seen at an early stage, disorganized brain tissue (vasculo-membranous area) is detectable above the orbits, a process called exencephaly [19]. ...
Anencephaly is a common congenital malformation characterised by absence of a major portion of the brain. The sequence of brain degeneration starts around 20 days post fertilization which overlaps with the appearance of optic grooves from the forebrain. A number of ocular malformations associated with anencephaly have been reported. Based on the assumption that eyes, which are derived from the brain, are likely to be abnormal since the organ of origin undergoes degeneration, studies have been carried out on anencephalic retinae. Some of the results have indicated that retinae of anencephalic fetuses are abnormal with absence or diminished presence of ganglion cell layer compared to the fetuses without such a brain malformation. We undertook the present study with an aim to objectively and quantitatively evaluate retinal thickness and numbers of ganglion cell in anencephalic fetuses and fetuses without any malformations. Six anencephalic and six fetuses without malformations were included, all of them from 18 to 21 weeks of gestation. Histopathological evaluation of retinae was done and findings compared. We did not find any atrophy or reduced number of ganglion layer cells in anencephalic fetuses. This evaluation assumes importance since retinae from anencephalic fetuses can be a potential source for retinal tissue or stem cell transplant. Moreover, the contention that normal brain development is essential for retinal development appears to be invalid.
... While the term exencephaly literally means "an outside brain" and anencephaly refers to "the absence of brain," these terms are often used in an interchangeable manner. 1 In exencephalic fetuses, the cranial vault is not present and the neural tissue that is in contact with the external environment presents as an amorphous structure very rich in vessels, known as "area cerebrovasculosa," that includes structures derived from the forebrain and skull. 2 Some have reported that the area cerebrovasculosa comprises vascular tissue, glia, and few neurons surrounded by meninges. 3,4 Others have described the presence of cavities surrounded by epithelium that we interpret as ventricles. ...
The presence and status of progenitor/stem cells in excencephalic brain have not been previously examined.
Brain sections of excencephalic 17-week fetus were stained for specific stem and mature cell markers.
The ventricles were open, the developing cerebral cortex was thin in the radial dimension, and the ventricular surface was undulated. There was a decreased ratio of subventricular/ventricular zone radial glia precursor cells (RGCs; PAX6⁺ and HOPX⁺ cells), a decreased number of intermediate progenitor cells (IPCs; TBR2⁺), a decreased number of neurons (MAP2⁺), and an increased number of astrocytes (S100b⁺), compared to the control. MAP2⁺ neurons, S100b⁺ astrocytes, and OLIG2⁺ oligodendrocytes were present within the subventricular zone.
This indicates that the underlying condition did not initially preclude radial glial cells from undergoing asymmetric divisions that produce IPCs but halted the developmental progression. RGC and IPC presence in the developing cerebral cortex demonstrates that the fundamental building blocks of cortical formation had been established and that a normal sequence of developmental steps had been initiated in this case of exencephaly. These data expand our understanding of exencephaly etiology and highlight the status of cortical progenitor cells that may be linked to the disorder.
... The sequence of acrania, exencephaly and anencephaly is rather well documented which proposes that the primary event is failure of development of flat bones of skull leading to extrusion of brain which is gradually eroded owing to direct exposure to amniotic fluid eventually leading to anencephaly as first described by Wilkings et al. [13]. The sequence is difficult to reconcile with the cases presented here since cranial cavity and contents in all were shielded from amniotic fluid by skin and/or placental membranes however it is quite plausible that 'erosion' of brain was actuated by excessive direct exposure to MMP2 and MMP9 or other related enzymes serving the purpose of parenchymal degradation which are known to be secreted by placenta [14]. ...
Cases of placento-cranial adhesion are rare and most of them are incompatible with life. A few case reports in the literature have included such cases under the overarching rubric of amniotic band syndrome. We present autopsy findings of four cases with gestation period ranging from 16 to 21 weeks. All of them displayed placenta-cranial adhesion, low weight for gestation, absence of flat bones of skull, anencephaly, dysmorphic facial features, short umbilical cord and limb/digit amputation with oligohydrambios. Three out of four showed nasal groove. We propose that there are grounds for syndromic association of the features mentioned above. Furthermore, it is important that whenever such cases are identified termination of pregnancy should be considered. The article also underscores the importance of fetal autopsies.
... Definition.-When the primary defect involves failure to close just the cranial portion of the neural tube, the defect is refered to as exencephaly (anencephaly). The degeneration of the cerebral-neural tissues due to the destructive exposure of the brain to the intra-amniotic environment converts the exencephaly defect to anencephaly (Golden & Harding, 2004;Timor-Tritsch, Greenebaum, & Monteagudo, 1996;Wilkins-Haug & Freedman, 1991) Epidemiology.-The Center for Disease Control and preventin (CDC) estimates that each year, about 3 pregnancies per every 10,000 births in the United States will be affected by anencephaly. ...
Neural tube defects (NTDs) are the second most common congenital malformations in humans affecting the development of the central nervous system. Although NTD pathogenesis has not yet been fully elucidated, many risk factors, both genetic and environmental, have been extensively reported. Classically divided in two main sub‐groups (open and closed defects) NTDs present extremely variable prognosis mainly depending on the site of the lesion. Herein, we review the literature on the histological and pathological features, epidemiology, prenatal diagnosis, and prognosis, based on the type of defect, with the aim of providing important information based on NTDs classification for clinicians and scientists.
... Acrania represents the first stage of this maldevelopment sequence that takes place 18-20 days post-fertilization (14) and the progression from exencephaly to anencephaly was first described by Wilkings et al. (15) . When acrania is seen at an early stage, disorganized brain tissue (vasculo-membranous area) is detectable above the orbits, a process called exencephaly (16) . ...
The study presents a pictorial essay of acrania-exencephaly-anencephaly sequence using two-(2D) and three-dimensional (3D) ultrasonography, documenting the different phenotypic characterization of this rare disease. Normal and abnormal fetuses were evaluated during the first trimester scan. The International Society of Ultrasound in Obstetrics and Gynecology practice guidelines were adopted to standardize first trimester anatomical ultrasound screening. The guidelines outline the importance of systematic fetal head and brain examination including the formation of cranial bones, choroid-plexus and ventricles. Acrania-exencephaly-anencephaly sequence and/or other neural tube defects, such as meningoencephalocele, may be identified during a routine 11-14 week scan. Early first trimester detection of acrania-exencephaly-anencephaly sequence with the characterization of different related phenotypes, 2D and 3D ultrasound imaging as well as differential diagnosis are also presented in this pictorial essay. The main diagnostic ultrasound features of the disease may be characterized by findings of acrania with increased amniotic fluid echogenicity; "Mickey-Mouse" bi-lobular face, cystic, elongated, irregular and overhanging head morphology. Lightening techniques have also been added to 3D ultrasound to enhance anatomical details. Moreover, discordant amniotic fluid echotexture in the setting of twin pregnancies may be the first sign of acrania-exencephaly-anencephaly sequence. Extracranial malformations, aneuploidy and genetic syndromes associated with acrania-exencephaly-anencephaly sequence are also reported and described. First trimester neuroscan by an expert sonographer with appropriate training together with the application of standardized protocol are essential for a high detection rate of this rare type of neural tube defect malformation during a scan performed at 11 and 13 weeks and 6 days.
... ‹kinci trimesterde anensefali tan›s› ultrasonografik olarak serebral hemisferlerin ve kalvarium kemiklerinin yoklu-¤u, birinci trimesterde normal geliflim gösteren serebral hemisferlerin etraf›nda kalsifiye kalvarium yap›s›n›n olmamas› ile karakterizedir. 4,5 Anensefalinin fetal sonuçlarlar›n›n olmas›, anensefaliyi daha erken dönemde tan›mlama, tarama çabalar›na ve sonuçta ebeveynlere daha erken dönemde (11)(12)(13)(14). haftalarda) terminasyon hakk›n› olanakl› k›lacakt›r. ...
Olgu: Otuzdört yafl›nda, 12 haftal›k ilk gebelii olan hastan›n ultrasonografik incelemesinde, fetusun bafl k›sm›n›n gelifltii bölgede düzensiz görünüm izlendi. Bu bölgenin oval flekli yerine, bir flapka gibi uzanarak üçgen biçimini ald›¤› izlendi. Gebeliin 13 haftas›nda tekrar edilen sonografik incelemede bafl›n karakteristik görüntüsüyle anensefali olduu tespit edilip, terminasyonuna karar verildi . Sonuç: Anensefali yaflamla badaflmayan bir malformasyondur. Bu nedenle ne kadar erken tan› konulursa hem hekim hem de aile yönünden tedavide büyük kolayl›k söz konusudur. Kraniyumun gebeliin 11 haftas›ndan itibaren ultrasonografide vizüalize olmas› nedeniyle birinci trimesterde ultrasonla sefalik boy ve flekil bozukluklar›, dezorganize görünüm gibi sonografik bulgular bize erken tan› için uyar›c› iflaret olmakta ve erken tan› konulmas›na imkan vermektedir.
... The exposed neural tissue undergoes secondary degenerative changes that convert it into a mass of vascular connective tissue, the area cerebrovasculosa, which is a flattened remnant of degenerated brain tissue admixed with choroid plexuses, ependyma and mesothelial cells. The exposed base of the skull is covered only by a vascular membrane (Haug & Freedman, 1991; Bronshtein & Ornoy, 1991; Timor-Tritsch et al, 1996; Powers & Horoupian, 1996; Frosch et al, 2004; Crowley, 1999). This defect can be diagnosed during Alphafetoprotein (AFP) screening. ...
Neural tube defect spectrum (NTD) includes anencephaly, spina bifida, craniorachischisis, inencephaly etc. Four cases of craniorachischisis were studied from a collection of 34 aborted fetuses. There was deficiency of scalp and cranial vault in all the four cases. In one case the defect was extending up to the cervical region, in rest of the three cases, vertebral column defect extended upto thoracic region exposing the spinal cord and spinal nerves. All the cases presented with bulging eyes, broad nose, folded ears, protruded tongue and absent neck. These defects result due to failure of closure of the neural tube during early embryonic life.
... Evidence exists to support the belief that anencephaly develops from exencephaly as the exposed brain tissue is disrupted by minor trauma pro- 30 duced by fetal movements [1]. This hypothesis is, therefore, well supported by prenatal imaging studies although it lacks clear histologic confirmation [2][3][4]. Acrania may occur as a single isolated malformation or with co-existing anomalies, including extracranial defects such as rachischisis and congenital diaphragmatic hernia, cleft lip and palate, omphalocele, limb defects, cardiac and kidney malformations [5]. Despite 35 the fact that hypospadias is one of the most common congenital abnormalities of the G. Tonni et al. genitalia and is often missed on prenatal sonograms [6], Hogdall et al. [7] were the first to report the ultrasound findings in a male fetus at 19 weeks with hypertelorism and hypospadias with a small phallus consistent with Opitz syndrome where the ultrasound detected diagnosis was confirmed by necropsy after pregnancy termina-40 tion. ...
Acrania may occur as a single isolated malformation or associated with extracranial defects. Hypospadias is one of the most common congenital abnormalities of the genitalia frequently missed on prenatal sonograms. Second trimester two- and three-dimensional ultrasound and MRI diagnosis with necropsy and folate metabolism pathway analysis. The mechanisms leading to closure of both neural and urethral tubes, are far from being demonstrated, and molecular studies of this very rare association are lacking although it might be based on a common genetic mechanism, leading to a disturbed development pathway at the molecular level.
... Cytological examination of amniotic fluid obtained by amniocentesis has confirmed the presence of neural cells in anencephalic fetuses, in which acrania was diagnosed originally in the first trimester (7). The crown-rump length is smaller in fetuses with anencephaly than in healthy control fetuses (8). It has been confirmed that the specific body segment that is decreased in size is the mentovertex diameter (crown-chin length), attributable to progressive destruction of the brain as pregnancy progresses (9). ...
Acrania is a developmental abnormality characterized by a partial or complete absence of calvaria with complete but abnormal development of brain tissue. Acrania is a relatively common malformation and affects about 1 in 1000 newborns. Meroacrania refers to absence of the cranium with the exception of the occipital bone. Brain stem and cerebellum develop normally, but cerebral parenchyma tissue is covered with a thin membrane and severely dysmorphic supratentorial brain is also seen. The other system findings are normal. Magnetic resonance imaging findings of one neonate with meroacrania have been reported in medical literature. Other radiographic and computed tomography findings have not yet been reported. We report a female neonate with meroacrania with discussion of etiology, pathogenesis, radiological findings, and differential diagnosis.
Acrania–exencephaly–anencephaly sequence has an incidence of 3.6–5.4 for 10,000 live births and has been reported in literature. Exencephaly, described here is a defect of the neural tube which occurs due to the absence of closure of the neural fold. The main diagnostic ultrasound features include that are characterized by acrania, decreased size of cranial pole in comparison with the chest, irregular cranial surface, with increased amniotic fluid echogenicity due to the damaged brain tissue. Associated with amniotic band syndrome, Pentalogy of Cantrell, limb anomalies and ventral body wall defects. It is incompatible with life. Conducting programs training the budding neuro-sonographers about the knowledge in detection, diagnosis of NTD according to the Carnegie Classification is crucial to look forward in pathogenesis and application in the clinical scenario.
Congenital malformations are structural abnormalities due to faulty development, present at birth, and amongst the major causes of prenatal, perinatal and infant mortality and morbidity. They include gross and microscopic malformations, inborn errors of metabolism, intellectual disability and cellular and molecular abnormalities. About 3% of newborns have a single major malformation, and 0.7% have multiple major defects. The frequency is much higher prenatally, the majority aborting spontaneously. More than 80% of malformed conceptuses are lost during the embryonic period, and more than 90% before birth. The importance of congenital malformations as a cause of perinatal mortality has increased as deaths from intrapartum problems and infectious diseases have declined, and better neonatal care has improved the survival of normally developed low-birthweight babies. During the last decades, there has been a rapid expansion of methods for detecting many different types of disorders prenatally.In this introductory chapter, the known causes of congenital malformations (► Sect. 3.2), and possibilities to detect them prenatally (► Sect. 3.3), will be outlined. Some emphasis is given to the increasing group of inborn errors of metabolism affecting the central nervous system (CNS; ► Sect. 3.4), disorders of white matter (► Sect. 3.5), vascular disorders (► Sect. 3.6) and congenital tumours (► Sect. 3.7). Several Clinical cases illustrate these disorders. In ► Sect. 3.8, classifications of CNS malformations are discussed.KeywordsCongenital malformationsInborn errors of metabolismPrenatal detectionDisorders of white matterVascular disordersCongenital tumoursClassification of malformations
There is an increasing demand for high-standard fetal and infant neuropathology examinations. Novel imaging techniques, development of new diagnostic methods and advances in genetics have stimulated the interest in gaining additional knowledge on developmental, perinatal and neonatal neuropathology. Approaching the subject from a practical standpoint, diagnostic templates for reports are provided in this essential guide to aid clinicians with different areas of expertise. Each chapter will includes numerous high-quality images, accompanied by explanatory legends from the authors' own experiences. Covering autopsy and tissue processing techniques, the authors discuss a range of disorders such as neural tube defects, brain tumours, storage disorders and many others. This book provides access to an online version on Cambridge Core, which can be accessed via the code printed on the inside of the cover. Compiling the latest advances in fetal and infant diagnostics and care, this book is a highly valuable educational resource.
Acrania–exencephaly–anencephaly sequence is rare forms of neural tube defects. The progression is from a relatively normal-appearing exposed brain due to an absent cranium called as acrania, to an amorphous brain mass term as exencephaly. We present a case of 20 years female, nonconsaguinous marriage, G1P0A0 having amenorrhea since 3 months. On ultrasonography, a single fetus of gestational age of about 15 weeks gestation showed congenital malformation- acrania with exencephaly. Final impression on fetal autopsy given was acrania–exencephaly with deformed brain, ill-formed cervical C1, 2 spine, bilateral pulmonary immaturity- Grade II with pulmonary congestion and hemorrhage. We are presenting this rare fetal anomaly of acrania–exencephaly–anenecephaly sequence for its clinical, radio imaging, and fetal autopsy findings.
Prenatal detection of fetal anomalies is considered to be an important goal of obstetric care and in many countries fetal ultrasound is an established part of routine care. This chapter provides an overview of the prenatal diagnosis of some of the most common malformations and their associated abnormalities. Neural tube defects develop when a part of the neural tube fails to close before 5 weeks of gestation. The prenatal detection rate is positively influenced by appropriate training and the application of a standardized protocol. One of the most frequent genetic syndromes associated with encephalocele is Meckel–Gruber syndrome. The sonographic findings in Dandy–Walker malformation are an enlarged fossa posterior with hypoplasia of the cerebellar vermis, dilatation of the fourth ventricle and a persistent Blake’s pouch cyst. Congenital pulmonary airway malformation is a mass of abnormal fetal lung tissue that forms in pregnancy. Congenital heart disease is the most common congenital malformation.
Neural tube defects (NTDs) are congenital malformations resulting from the improper or incomplete closure of the neural tube during embryonic development. A number of similar malformations of the protective coverings surrounding the central nervous system are also often included under this umbrella term, which may not strictly fit this definition. A range of NTD phenotypes exist and have been reported in humans and a wide range of domestic and livestock species. In the veterinary literature, these include cases of anencephaly, encephalocele, dermoid sinus, spina bifida, and craniorachischisis. While environmental factors have a role, genetic predisposition may account for a significant part of the risk of NTDs in these animal cases. Studies of laboratory model species (fish, birds, amphibians, and rodents) have been instrumental in improving our understanding of the neurulation process. In mice, over 200 genes that may be involved in this process have been identified and variant phenotypes investigated. Like laboratory mouse models, domestic animals and livestock species display a wide range of NTD phenotypes. They remain, however, a largely underutilized population and could complement already established laboratory models. Here we review reports of NTDs in companion animals and livestock, and compare these to other animal species and human cases. We aim to highlight the potential of nonlaboratory animal models for mutation discovery as well as general insights into the mechanisms of neurulation and the development of NTDs.
Anencephaly is the most severe form of a neural tube defect resulting from the incomplete occlusion of the anterior neuropore in the fourth week of development and associated with a severely underdeveloped brain mass. As desmal ossification of the neurocranium is induced by the presence of soft tissues (brain), no bone develops as direct consequence of the missing brain. The cranial base, by contrast, is formed by chondral ossification, which is genetically determined, and thus present also in anencephaly. Morphometric characteristics of anencephalic skulls, however, have not yet been investigated in sufficient detail before.
In this study we therefore comparatively assessed macroscopic morphological-anatomical and cephalometric CT data on structures and dimensions of 11 macerated anencephalic and 4 normal neonatal skulls highlighting skeletal morphological differences.
The most striking results were the missing skullcap and the greatly changed morphology of the existing skull bones, which were reduced in size. The parameters of the skull base, the transverse orbital diameter and maxillary width were significantly smaller in anencephalic skulls. The morphology of the viscerocranium appeared similar to that of normal neonatal skulls.
The results of this study can be used in diagnosis and skeletal classification for anencephaly. This can help identify bones that are incomplete, fragmented and taphonomically altered, which is often the case in historical and forensic studies.
Objectives:
The acrania-anencephaly sequence is a lethal condition with a high detection rate in experienced hands after 10 weeks' gestation. However, earlier in gestation, many cases remain undetected. Different phenotypic appearances have been described and might help increase the detection rate in less experienced hands and also earlier in gestation. The purpose of this study was to assess interobserver reliability in classifying cases of the acrania-anencephaly sequence during first trimester in 6 different subtypes according to their ultrasound appearances.
Methods:
This was a retrospective descriptive cohort study at 3 centers for fetal imaging. Each case was classified according to its phenotypic appearance by 2 independent operators as "bilobular," "cystic," "elongated," "irregular," "foreshortened," or "overhanging." Frequencies of each type are described, and interoperator agreement was assessed with the intraclass correlation coefficient.
Results:
From the 88 included cases, the frequencies of the different subtypes classified as overhanging, elongated, bilobular, cystic, foreshortened, and irregular were 31%, 25%, 19%, 11%, 8%, and 6%, respectively. The interoperator reliability was good, with an intraclass correlation coefficient of 0.903 (95% confidence interval, 0.853-0.937; P < .001).
Conclusions:
Using different subtypes may improve the detection of the acrania-anencephaly sequence. An accurate early diagnosis could lead to timely, less traumatic, and safer management of affected pregnancies.
Abstract
We
present
xid
discuss
iiiiijor
crirrent
theories
ahout
the
devrlopment;il
natural
history
of
the
anencephalic
human
fetus.
We
confirm previous
observations
made
using transvLiginal
ultrasonography
of
exencephalic
fetuses
which
were
later
imaged
irnd/or
delivered
as
anencephalic
fetuses.
We
explore
the
possihility
of
proving tlie theory
of
the
slowly
ruhhed-off exposed
brain
tissue
by
cytologic
examination
and
special
staining
of
aspirated
cells
in
amniotic
fluid.
Thee
fetuses with
ii
typicJ
sonographic picture
of
exenceplialy
at
1
3-1
5
postmenstrunl
weeks
underwent amniocentesis.
The
aspirated
fluid
contained
pathognc~monic neural
cells.
The
smie
fetuses
later
showed the characteristic sonographic
and
postahortion
picture
of
aneiicephaly.
Our
results
>upport
the
theory
that
exencephaly
is
the
foreriiiiner
of
anencephaly.
excencephaly | Request PDF. Available from: https://www.researchgate.net/publication/327603575_excencephaly [accessed Sep 12 2018].
To study central nervous system development, 18 normally developing embryos or fetuses were examined sonographically between 6 and 16 weeks of pregnancy. Furthermore, in a 5 year period, 693 fetuses with an elevated risk for congenital defects were examined before 16 weeks of gestation. Abnormal development of the central nervous system was found in 28 fetuses. Early in pregnancy, normal central nervous system formation can be recognized, and pathologic cerebral development can be diagnosed already in the first trimester of pregnancy. We recommend routine use of safe and noninvasive transvaginal ultrasonography early in pregnancy for patients at risk.
The first fetal malformation to be detected antenatally by ultrasonography leading to the termination of pregnancy for medical indication was anencephaly. This chapter provides an overview of the prenatal diagnosis of some of the defects and their associated abnormalities. The defects amenable to prenatal diagnosis in the second trimester of pregnancy include: craniospinal defects; cardiovascular defects; pulmonary abnormalities; abdominal wall defects; and gastrointestinal tract defects. Special emphasis is placed on the diagnosis of fetal abnormalities during the first trimester of pregnancy. Indeed, improvement of the techniques and wider access to ultrasound examination for pregnant women has moved the challenge of prenatal diagnosis of fetal abnormalities, especially chromosomal disorders, to the first trimester. The chapter highlights the new developments of an old technique, fetoscopy, which has recently been re-discovered because of the miniaturization of the instruments and the development of endoscopic fetal surgery.
The fetal central nervous system (CNS) has to be evaluated considering two perspectives: one is the careful, systematic analysis of all structures visualized; the second, equally important, is to compare the appearance of each structure with the expected stage of development.
Anancephally is the most commonly diagnosed anomaly of the central nervous system diagnosed in uterus. Current literature describes the possibility of even earlier diagnosis using ultrasound. We describe the most frequent ultrasound findings of this sequence and its prenatal diagnosis.
The changing appearance of the developing fetal brain during pregnancy is remarkable and it is important for evaluating brain morphology accurately. The intracranial structure is one of the organs which should be assessed three-dimensionally. Therefore, the introduction of the transvaginal approach to the fetal brain by using the cranial fontanelles and sutures as ultrasound windows has improved fetal brain assessment. The combination of both transabdominal and transvaginal approaches produces ultrasonic images of the intracranial structure in the median, oblique, coronal and axial sections. Using the basic knowledge of the anatomical structure of the developing fetal brain and the different sonographic appearance at each gestational age of each section, congenital brain anomalies, acquired abnormalities in utero and variations of normality have been evaluated more accurately. It may be possible to differentiate between hydrocephalus and ventriculomegaly by observation of the subarachnoid space. The study of the fetal brain using a transvaginal gray-level histogram may have potential in the evaluation of fetal periventricular changes related to postnatal brain damage. Recent remarkable developments in three-dimensional ultrasound and advances in magnetic resonance imaging technology may enable us to evaluate brain morphology more accurately. A functional evaluation of the intracranial condition and a prenatal prediction of neurological development may be the next task in this field.
Basic ultrasound screening during the first trimester should include evaluation of vitality and site of implantation of the trophoblast, as well as a normal development of the embryo/fetus. To checkthe organ systems for anomalies it seems helpful to use a checklist for a systematic examination. Because of improving technology and education of the physicians early diagnosis of certain anomalies has become feasible enabling planning of further management. Especially structural anomalies of the head, the central nervous system and the abdominal wall and skeleton may be detected early in pregnancy. Anomalies diagnosable in the first and early second trimester of pregnancy are described systematically and their consequences are going to be outlined.
Congenital malformations are structural abnormalities due to faulty development, present at birth, and among the major causes of prenatal, perinatal and infant mortality and morbidity. They include gross and microscopic malformations, inborn errors of metabolism, intellectual disability and cellular and molecular abnormalities. About 3 % of newborns have a single major malformation, and 0.7 % have multiple major defects. The frequency is much higher prenatally, the majority aborting spontaneously. More than 80 % of malformed conceptuses are lost during the embryonic period, and more than 90 % before birth. The importance of congenital malformations as a cause of perinatal mortality has increased as deaths from intrapartum problems and infectuous diseases have declined, and better neonatal care has improved the survival of normally developed low-birthweight babies. During the last decades, there has been a rapid expansion of methods for detecting many different types of disorders prenatally.
In this introductory chapter the known causes of congenital malformations, and possibilities to detect them prenatally, will be outlined. Some emphasis will be given to the increasing group of inborn errors of metabolism affecting the CNS, myelination disorders, vascular disorders and congenital tumours. Several Clinical cases illustrate these disorders. In Sect. 3.8, classifications of CNS malformations are discussed.
With the widespread use of prenatal ultrasonography, increasing numbers of fetal central nervous system anomalies are being detected before birth. Obstetricians should be alert to those anomalies that are incompatible with extrauterine life, such as fetal anencephaly. Furthermore, earlier prenatal diagnosis should be provided to minimize maternal psychologic and physiologic trauma. In this paper, we report the case of a patient in which prenatal ultrasound revealed a cranial defect with free-floating tissue in the amniotic cavity. Transvaginal two-dimensional and three-dimensional ultrasound eventually led to a specific diagnosis of fetal exencephaly at 10 weeks of gestation. Postpartum examination of the fetus confirmed the findings of the antenatal ultrasound.
First trimester ultrasound is commonly performed to establish dates or evaluate early pregnancy complications. With improvement in ultrasound technology, visualization of fetal structures has improved. While the emergent evaluation does not typically focus on detailed fetal anatomic evaluation (since this is typically performed at 18-20 weeks), various fetal structural abnormalities can now be visualized, especially during the late first trimester and early second trimester. We present a pictorial review of potential pitfalls encountered in early obstetric ultrasound with an emphasis on fetal structural abnormalities as well as normal fetal anatomy that can be confused with developmental abnormalities.
Anancephally is the most commonly diagnosed anomaly of the central nervous system diagnosed in uterus. Current literature describes the possibility of even earlier diagnosis using ultrasound. We describe the most frequent ultrasound findings of this sequence and its prenatal diagnosis.
Studienziel: Aus tierexperimentellen Untersuchungen ist be-kannt, daß die Exenzephalie ein embryologisches Vorstadium der Anenzephalie darstellt. Auf die diagnostischen Besonder-heiten dieses Krankheitsbildes in der Frühschwangerschaft wird eingegangen.
Methode: Vaginalsonographisch diagnostizierten wir bei 14 Feten zwischen der 9 + 4 und 22 + 3 Schwangerschaftswoche entweder eine Exenzephalie oder eine Anenzephalie.
Ergebnisse: In frühen Schwangerschaftsstadien fand sich ge-häuft der Befund einer Exenzephalie, während Feten, bei de-nen die Diagnose im zweiten Trimenon erfolgte, eher die klas-sische Anenzephalie aufwiesen. Bei einem ausgetragenen Feten konnte der Übergang einer in der 12 + 2 Schwangerschaftswoche festgestellten Exenzephalie in eine Anenzephalie durch sonographische Verlaufskontrollen beobachtet werden.
Schlußfolgerung: Unsere Befunde sprechen für eine Exen-zephalie-Anenzephalie-Sequenz auch beim Menschen und ha-ben weitreichende Konsequenzen für die Diagnose dieses Krankheitsbildes in frühen Schwangerschaftsstadien mit hoch-auflösendem Vaginalultraschall.
Wir beschreiben die Beobachtung eines Feten mit einer vollständigen Aplasie der Schädelkalotte mit Herniation von mit Leptomeninx bedecktem Hirngewebe in die Fruchthöhle, bei der es bis zur 20. SSW nicht zu einer Degeneration von Hirnsubstanz gekommen war. Unser Fall zeigt, daß die Aplasie der Schädelkalotte eine zwar notwendige, nicht aber hinreichende Voraussetzung für die Entstehung eines Anenzephalus ist: in einzelnen Fällen kann auch im mittleren Trimenon eine Degeneration des Hirnes, eventuell aufgrund der protektiven Wirkung der Hirnhäute, ausbleiben.
Exencephaly is a rare congenital anomaly, thought to be a precursor of anencephaly, thought to be a precursor of anencephaly. Like anencephaly, this abnormality is characterized by absence of the cranial vault above the orbits. However, unlike anencephaly, discrete, sometimes disorganized, brain tissue can be identified above the cranial defect. In this article, the authors report a case of exencephaly diagnosed prenatally during transvaginal ultrasound examination, with anatomic and pathologic correlation.
ABSTRACT We report an autopsy case of acrania with a review of the literature. A 31-year-old woman was admitted in poor genaral condition and diagnosed as pregnant at the 26th week of gestation. The fetus was suspected to be anencephalic or hydrocephalic by ultrasonography. She delivered a stillbirth male baby at the 28th week of gestation. Autopsy showed the cranium lacked the cranial vault The scalp directly covered the hydrocephalic brain without calvaria. No cerebellum was found macroscopically. On histological examination, the thinned cerebral layer was composed of white matter-like brain tissue with glial and ependymal cells. In the cerebral layer near the base of the skull, a few NSE-positive neurons among many GFAP-positive glial cells and oligodendrocyte-like cells were observed. The choroid plexuses were observed inside the ependymal layers. The brain stem and the spinal cord were normally preserved with clusters of NSE-positive neurons. Agnethia and horseshoe kidney were combined as malformations other than the brain. We reviewed 42 cases of acrania from the literature.
The authors review the most common congenital anomalies of the central nervous system (CNS): neural tube defects (NTDs), ventriculomegaly/holoprosencephaly, hydranencephaly, holoprosencephaly sequence, iniencephaly, and microcephaly. They emphasize the importance of the diagnostic tools (biochemical markers of the maternal serum, ultrasound screening, invasive techniques), methods which are complementary to each other.
Exencephaly was diagnosed at 17 weeks in a 27-year-old primigravida with abnormalities of the hands and a family history suggestive of autosomal dominant brachydactyly and clinodactyly. In this family there was also a history of 'anencephaly'. To our knowledge, this is the first report on the association of exencephaly and autosomal dominant brachydactyly. As the relationship between hand and cranial anomalies is well established, we suggest that this association in our case could be due to a defect in the same gene.
Fetal anomalies have been the subject of innumerable publications both in the prenatal and neonatal literature. This has significantly increased in the last 10 years, mainly because of the advent of high-resolution ultrasound equipment and improvement of scanning techniques. In addition, guidelines issued by professional organizations involved in prenatal diagnosis have encouraged a more universal approach to the imaging and documentation of prenatal findings. The fetal central nervous system is the most frequently investigated organ system, mainly because of its easy accessibility and prominence even in the early stages of embryologic development. The biparietal diameter was the first fetal measurement to be widely used in determining gestational age. As investigators gained more experience, the appearance of ultrasound images achieved the resolution that allows direct comparisons with gross specimens and more recent sophisticated techniques of computed tomography and magnetic resonance imaging. Now endovaginal ultrasound can document early first trimester development and compare it to known embryologic landmarks. Interest in demonstrating the ultrasound counterpart of central nervous system structures in the early stages of development has resulted in a plethora of articles proving the unique ability of ultrasound in imaging the developing fetus. In view of all these developments, the beginning ultrasound specialist is faced with the challenge and responsibility not only of being familiar with the literature but also of the mastery of scanning techniques that allow accurate prenatal diagnosis. It is therefore helpful to review key developmental milestones in embryologic life and correlate them with the corresponding prenatal ultrasound appearance. In addition, the changing appearance of the developing fetus has created a need for a systematic approach in the evaluation of structures so routine protocols can be established. This has been the subject of other publications that allow the novice to draw from the cumulative experience of different centers around the world. It is important to pay attention to the specifics described in the literature when duplicating results in one's laboratory. The frustration of not being able to reproduce results is common, especially when technical limitations prevent imaging under ideal conditions. This is especially true in patients who are first seen in the later third trimester with no prior prenatal care.(ABSTRACT TRUNCATED AT 400 WORDS)
This paper presents a sonographic diagnosis of exencephaly made during the last trimester of gestation. The sonogram showed the absence of bones in the cranial vault together with the presence of a disorganized cerebral mass, with loss of its normal anatomy. Post-partum examination of the newborn confirmed the findings of the sonogram. We briefly review the characteristics of exencephaly, its aetiology, and its relationship to anencephaly.
In an ongoing study involving seven hospitals in London and surrounding areas, 55,237 fetuses were examined by ultrasound at 10-14 weeks of gestation. There were 47 fetuses (1 in 1175) with anencephaly which presented with acrania with varying degrees of cerebral degeneration. The first audit of results was performed in April 1995. During the first phase of the study 34,830 fetuses were examined and in eight of the 31 with anencephaly the diagnosis was not made at the 10-14-week scan. Following the audit, 20,407 fetuses were examined and in all 16 with anencephaly the diagnosis was made at the 10-14-week scan (p = 0.03). These findings demonstrate that anencephaly can be reliably diagnosed at the routine 10-14-week ultrasound scan, provided a specific search is made for the sonographic features for this condition.
To document the characteristic sonographic abnormalities of anencephaly and to identify potentially confusing sonographic features, we reviewed 20 cases of anencephaly. All of these cases were diagnosed prenatally with sonography after 14 menstrual weeks in patients who were seen at our institution between 1984 and 1988. In all cases, the correct diagnosis was made on the prenatal sonograms and was confirmed pathologically. The sonographic diagnosis was primarily based on the absence of brain and calvarium superior to the orbits on coronal views of the fetal head. This typical appearance was altered by the presence of echogenic tissue superior to the orbits in nine (45%) of 20 cases. Pathologically, the tissue corresponded to angiomatous stroma (area cerebrovasculosa) and appeared quite sizable on sonograms in four fetuses (20%). It may appear solid or mixed solid and cystic. In one fetus, it appeared brainlike. Despite this appearance, the sonologist should not be dissuaded from the diagnosis of classic anencephaly. Hydramnios occurred in seven (35%) of 20 patients, and oligohydramnios occurred in none of the patients. Anencephaly may be distinguished from the cranial defects associated with the amniotic band syndrome (amputation defects that occur as the sequelae of amniotic disruption) on the basis of the symmetry of the cranial defects (100% of anencephalic fetuses in this series) and the absence of limb, body wall, and spinal abnormalities that typically accompany the amniotic band syndrome. Although there may be minor variations in the sonographic appearance of the cranial defect of anencephalic fetuses (i.e., much or little angiomatous stroma), we conclude that this anomaly can be accurately detected and diagnosed on fetal sonograms obtained after 14 weeks menstrual age and distinguished from the amniotic band syndrome.
In an attempt to help elucidate pathogenetically those human cases exemplifying secondary degeneration of the neural tube causing brain dysraphia, macroscopic and histologic observations of two young human fetuses are described. A nine-week-old anencephalic fetus exhibited an absence of spinal cord (amyelia) with retention of neural crest derivatives (dorsal root ganglion cells and their processes, and sympathetic ganglia) implying the presence of a neural tube in early gestation. The second, ten-week-old exencephalic case exhibited restricted brain hemorrhage and necrosis of the telencephalon and brain stem amongst otherwise normal brain and spinal cord tissue. These two young fetal cases may represent examples of a previously normal neural tube which has undergone degeneration at a stage where neural crest has already undergone differentiation, and thus distinguishes them from cases of complete dysraphism which probably results from primary degeneration during neurulation.
First-trimester diagnosis of fetal exencephaly is reported. Vaginal ultrasonography showed a normal volume of fetal brain with abnormal internal anatomy. The diagnosis was confirmed by repeat ultrasonography at 14 weeks and at subsequent termination of pregnancy. This is the earliest reported diagnosis of exencephaly by prenatal ultrasonography.
The antenatal sonographic diagnosis of exencephaly in four gestations is reported. Exencephaly is an uncommon malformation of the cranium that characteristically involves a large, disorganized mass of cerebral tissue. The flat bones of the calvaria are absent, leaving the brain mass uncovered. Secondarily, anencephaly may develop as a result of prolonged exposure of the developing encephalon to amniotic fluid and trauma in utero. As in anencephaly, facial structures and the bony base of the calvarium are often preserved in exencephaly. Sonographically, the outstanding feature of exencephaly is the cerebral mass, with convolutions or "pseudo" sulcal patterns present. These findings correlate well with the pathologic examination and define a clinical entity that is incompatible with human life.
Exencephaly is a rare precursor of anencephaly in which a large amount of brain tissue is present despite the absence of the calvaria. It was discovered together with hydramnios in a near-term fetus. Sonographic, angiographic, and pathologic findings are discussed.
An anencephalic pregnancy was successfully diagnosed by ultrasound 17 weeks after clomiphene induction of ovulation. The pregnancy was subsequently terminated. It is suggested that ultrasound examination should be carried out in all patients who, in a previous pregnancy, were delivered of an anencephalic fetus or a baby with spina bifida.
Sequential Atlas of Human Congenital Mal,formations Anencephaly
- H Nishimura
- N Okamoto
- J Warkanly
Nishimura, H., Okamoto, N. (1976). Sequential Atlas of Human Congenital Mal,formations, Warkanly, J. (197 1). Anencephaly. In: Warkany, J. (Ed.). Congenital Mal,formations, Baltimore: University Park Press. Chicago: Yearbook Publishers, 189-200.