Two Rhombencephalic Anencephalics

Extract:
One of us systematically examined 78 anencephalics (in the broad sense of the term) in the Central Pathological Laboratory in Rotterdam. On the basis of differences with respect to the closure of the neural tube, the material could be divided into three groups:
(1) In 18 cases there was faulty closure in the rostral portion of the brain;
(2) In 15 cases there was a defect in the caudal portion of the brain and the rostral portion of the spinal cord;
(3) In 45 .cases there was a defect both in the entire brain and in the spinal cord.
In all these cases, the skull and vertebral column participated in the closure-defect.

Localization of Brain Defect	Female	Male	Sex Dominance Statist. Signific
Rostral brain	6	12	Male +
Caudal brain and rostral spinal cord	14	1	Female +
Total brain and spinal cord	36	9	Female +
	56	22

This Table shows that anencephaly clearly preferentially affects the female sex. This was already known, and is confirmed by the Rotterdam material (56 females v. 22 males) but, if we consider the groups of anencephalics separately, then those with a closure defect in the rostral portion of the brain (the so-called hemicephalics or merencephalics) occupy a unique position: here the male sex predominates, in contrast to the other groups, where the caudal part of the CNS is much more extensively involved. This supports the opinion that “hemicephaly" should be considered a special type of anencephaly.

Journal Reference:
V.W.D. Schenk et al. Two Rhombencephalic Anencephalics, BRAIN—VOL. XCI, 497-506

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Polyhydramnios in Anencephaly

In a newborn infant with esophageal stenosis and atresia extending 9 cm, the amniotic fluid volume was found to be normal, yet this infant could not possibly have swallowed. In a case of anencephaly in which the infant had partial esophageal atresia and stenosis extending 1 cm, the infant swallowed sodium diatrizoate (Hypaque Sodium) injected into the amnion, yet the mother had polyhydramnios. Two more cases of anencephaly are presented in which the infants swallowed radiopaque media, yet both mothers had polyhydramnios.
These findings emphasize that polyhydramnios is a complex phenomenon and indicate that "failure to swallow" cannot explain all such cases associated with esophageal atresia and anencephaly.

Journal Reference:
John Nichols, Rosemary Schrepfer. Polyhydramnios in Anencephaly. JAMA, Aug 15, 1966, Vol 197, No 7

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Extract:
It is apparent that a delicate homeostatic mechanism exists which balances amniotic fluid formation and résorption to maintain a normal volume of approximately 1,000 ml at term. Polyhydramnios results when the rate of formation at all sites exceeds the rate of résorption.

Neurulation in the cranial region – normal and abnormal

Cranial neurulation is the embryonic process responsible for formation of the brain primordium. In the mouse embryo, cranial neurulation is a piecemeal process with several initiation sites and two neuropores. Variation in the pattern of cranial neurulation occurs in different mouse strains, and a simpler version of this morphogenetic scheme has been described in human embryos. Exencephaly is more common in females than in males, an unexplained phenomenon seen in both mice and humans. As the cranial neural tube closes, a critical morphogenetic event is the formation of dorsolateral bending points near the neural fold tips, which enables subsequent midline fusion of the neural folds. Many mutant and gene-targeted mouse strains develop cranial neural tube defects, and analysis of the underlying molecular defects identifies several requirements for normal dorsolateral bending. These include a functional actin cytoskeleton, emigration of the cranial neural crest, spatio-temporally regulated apoptosis, and a balance between cell proliferation and the onset of neuronal differentiation. A small number of mouse mutants exhibit craniorachischisis, a combined brain and spine neurulation defect. Recent studies show that disturbance of a single molecular signalling cascade, the planar cell polarity pathway, is implicated in mutants with
this defect.

Journal Reference:
Copp A.J. Neurulation in the cranial region – normal and abnormal. J. Anat. (2005) 207, pp623–635

Subclassification of Anencephalic Human Fetuses According to Morphology of the Posterior Cranial Fossa

Anencephaly is a designation for congenital absence of the cranial vault with cerebral hemispheres completely missing or decreased to small masses attached to the base of the skull. The etiology is unknown. Whether the bony tissue or soft brain tissue is a primary factor is also unknown. The present study has focused on the posterior cranial fossa in anencephaly. The goal is to determine whether differences in the posterior cranial fossa could provide a basis for subclassification of anencephalic fetal skeletons. Twenty-three human anencephalic fetuses, at gestational ages 13 to 22 weeks, were studied. Radiologic and cephalometric analyses, including measurements of bone sizes and different angles, were performed. Permission for autopsy of the central nervous system was not available. For
comparison of anencephalic findings with normal conditions, standards from a recent publication were used. Foot length served as a parameter for age comparison. The study showed 2 morphologic types of the posterior cranial fossa. One type had a fossa cranial morphology close to normal morphology, whereas the other had a malformed and much smaller posterior cranial fossa. The latter condition was presumed to be due to a primary error in chondral and cranial development. The current skeletal subgrouping might be
essential for clinicians’ or pathologists’ future assessment of the autopsy results. The skeletal subgrouping should, if possible, be associated with karyotyping and analysis of the central nervous system. The goal is to distinguish between congenital conditions resulting in anencephaly and acquired conditions resulting in anencephaly.

Journal Reference:
Lomholt J.F. et al. Subclassification of Anencephalic Human Fetuses According to Morphology of the Posterior Cranial Fossa. Pediatric and Developmental Pathology 7, 601–606, 2004 DOI: 10.1007/s10024-004-9098-z

Teratology of the neural tube: history and paleopathology

A lack of closing of the neural tube extremities between the 23rd and 27th days of embryonic life is responsible of various grades in abnormalities, from spina bifida to complete anencephalo-amyelia. Spina bifida is known in osteo-archaeology, but not anencephaly: that is the reason of our study.
Because it was a long time confused with acephaly, the history of anencephaly is very old, since 426 B.C. (Ctesias, Greek physician of Persian king Cambyse), but the most ancient case is an anencephalus-mummy from Thebes (Egypt), described in 1826 by a French naturalist, Etienne Geoffroy Saint-Hilaire.
We present one case of spina bifida associated with the sacralization of L5, proceeding from a recent digging up by Professor J.-L. Heim in Egypt. Eight skulls originate from the Musee de l’Homme in Paris: two anencephalies, two anencephaloamyelias, and four various degrees of encephalo-meningoceles.
The anencephalies have total lack of cranial vault and conservation of the face, the cranial basis and vertebral channel. In the cases of anencephalo-amyelias the posterior arch of a more or less high number of vertebrae also lacks.
Encephalomeningoceles are characterised by an opening of various size in the cranial vault through which, during life, the brain and meninges made herniation.

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Journal Reference:
Charon, P.,Teratology of the neural tube: history and paleopathology, 2005. Antropo, 10, 83-101.

Tératologie du tube neural: histoire et paléopathologie

Anomalies de sévérité variable, dues à un défaut plus ou moins complet de fermeture du tube neural survenu entre le 23ème et le 27ème jour de la vie embryonnaire, elles peuvent aller de la simple spina bifida à l’anencéphalomyélie (anencéphalo-arachie) complète. Historiquement, le cas le plus ancien observé date de l’antiquité égyptienne: c’est celui d’une momie de foetus atteint d’anencéphalo-myélie, qui fut décrit en 1826 par Etienne Geoffroy Saint-Hilaire. C’est cet auteur qui sépara l’anencéphalie de l’acéphalie avec laquelle elle fut longtemps confondue. Si l’ostéo-archéologie de la spina bifida, consécutive à la mauvaise fermeture du neuropore postérieur, est bien documentée de longue date, ce n’est pas le cas des anencéphalies, anencéphalomyélies et encéphaloméningocèles; toutes liées à un trouble de la fermeture du neuropore antérieur.
C’est pourquoi nous présentons une exceptionnelle collection de huit crânes: quatre encéphalo-méningocèles et quatre anencéphalies ou anencéphalomyélies, provenant du Musée de l’Homme de Paris, avec, pour mémoire, une spina bifida d’origine égyptienne qu’a bien voulu nous confier Monsieur Jean-Louis Heim, Professeur d’anthropologie biologique au Museum national d’histoire naturelle. Deux têtes osseuses (n° 1, collection F. J. Gall , et n° 4) illustrent l’anencéphalie vraie, avec conservation du massif facial, de la base du crâne et du canal rachidien. Deux observations (collection R. Verneau) sont des anencéphalomyélies, associant aux malformations précédentes la fente complète de l’arc vertébral postérieur portant sur les quatre (n° 3) ou huit (n° 2) premières vertèbres. Les quatre encéphaloméningocèles se caractérisent par une ouverture étendue, mais non totale, de la voûte crânienne (par laquelle cerveau et méninges étaient extériorisés du vivant du sujet; certaines formes sont compatibles avec une assez longue survie). L’observation n° 5 (collection F. J. Gall) comporte une grande ouverture postérieure et inférieure de l’occipital; celle des crânes n° 6, 7 et 8 (collection E.T. Hamy) siège entre la partie postérieure des pariétaux pour la n° 7, et dans la partie supérieure de l’écaille occipitale, juste derrière la suture lambdoïde pour la n° 8, tandis que celle de l’observation 6, beaucoup plus vaste, pourrait en imposer pour une anencéphalie, mais les frontaux, pariétaux et la partie supérieure de l’occipital, certes réduits, sont surtout refoulés (la description anatomo-clinique publiée par E.T. Hamy confirme qu’il y avait bien extériorisation de l’encéphale).

Texte complèt

Journal Reference:
Charon, P.,Teratology of the neural tube: history and paleopathology, 2005. Antropo, 10, 83-101.

Neural Tube Defect Rates before and after Food Fortification with Folic Acid

BACKGROUND:
Since 1998, enriched cereal grains sold in the United States have been fortified with folic acid, to reduce the incidence of neural tube defects (NTDs). The Centers for Disease Control and Prevention (CDC) recently reported that NTD rates have decreased 26% since fortification, but that additional effort is needed to achieve the national goal of a 50% reduction. However, accurate determination of NTD rates requires counting antenatally detected cases; the CDC study noted that the number of prenatally diagnosed cases was likely underestimated.

METHODS AND RESULTS:
We examined studies from the United States and Canada that compared rates of NTDs before and after very similar fortification programs were instituted in each country. U.S. studies had incomplete ascertainment of prenatally diagnosed NTD cases, and as a result, underreported the number of NTDs prevented. Canadian studies, in which ascertainment was more complete, showed decreases in NTD rates up to 54%.

CONCLUSIONS:
There is a strong correlation between the completeness of ascertainment and the percentage decrease in NTD rates. Studies that identify cases best show that folic acid fortification is preventing around 50% of NTDs. The percentage of NTDs that are folate-preventable in the United States is uncertain, but is probably 50–60%. Thus, we may be quite close to chieving the optimum level of protection at current fortification levels.

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Journal Reference:
Mills J.L, Signore C. Neural Tube Defect Rates before and after Food Fortification with Folic Acid. Birth Defects Research (Part A) 70:844–845, 2004