Limits of the surgically induced model of myelomeningocele in the fetal sheep.

PURPOSE: The prevention of Chiari type II malformation (CM) is commonly used as a primary outcome for the evaluation of techniques of fetal myelomeningocele (MMC) surgery in the fetal lamb. The aim of our study was to investigate the frequency of the associated CM in the MMC fetal sheep model and to investigate the contribution of prenatal ultrasound evaluation of CM at the time of prenatal repair. METHODS: A MMC-like lesion was surgically created at 75 days of gestation in 21 fetuses performing a L1-L5 laminectomy followed by an excision of the exposed dura and a midline myelotomy. At a 90-day gestation, among the 19 alived fetuses, a conventional repair of the MMC-like lesion was performed in seven, four of whom underwent cerebral ultrasound (US) examination before the repair. Twelve fetuses remained untreated (control group). All fetuses underwent post-mortem examination (PM) at 138 days. RESULTS: At a 90-day gestation, CM was demonstrated by US examination in all four evaluated fetuses. At birth, CM was found in 3/6 control whether CM was absent in all alived fetuses in the prenatal repair group (n = 4). CONCLUSIONS: Creation of a MMC-like lesion with an additional myelotomy does not always lead to hindbrain herniation. Our study suggests that CM should be assessed by ultrasound examination at the time of the prenatal repair to demonstrate the effectiveness of new techniques for the prenatal repair of MMC.

Prenatal abnormal features of the fourth ventricle in Joubert syndrome and related disorders.

Joubert syndrome and related disorders (JSRD) are characterized by absence or underdevelopment of the cerebellar vermis and a malformed brainstem. This family of disorders is a member of an emerging class of diseases called ciliopathies. We describe the abnormal features of the brain, particularly the fourth ventricle, in seven fetuses affected by JSRD. In three cases abnormality of the fourth ventricle was isolated and in four cases there were associated malformations. The molar tooth sign (MTS) was always present and visible on two-dimensional ultrasound and, when performed, on three-dimensional ultrasound and magnetic resonance imaging. The fourth ventricle was always abnormal, in both axial and sagittal views, presenting pathognomonic deformities. It is important to identify JSRD, preferably prenatally or at least postnatally, due to its high risk of recurrence of about 25%. A detailed prenatal assessment of the fourth ventricle in several views may help to achieve this goal.

[Prenatal repair of myelomeningocele: State of the art]. / Thérapie in utero des myéloméningocèles : où en sommes-nous ?

Myelomeningocele is characterized by the extrusion of the spinal cord into a sac filled with cerebrospinal fluid. One part of the postnatal disabilities could be related to the spinal damage and to the cerebral repercussion of the leak of cerebrospinal fluid from the defect. Several experimental studies in animals have demonstrated that a surgical repair of the lesion at middle gestation reduced the postnatal disabilities. These results were confirmed in humans by the Management of Myelomeningocele (MOM) Trial. However, the prenatal surgical repair is associated with maternal and fetal morbidity.

Fetal tumors of the choroid plexus: is differential diagnosis between papilloma and carcinoma possible?

Fetal choroid plexus tumors are uncommon. The prognosis is widely variable and depends on the histological findings: papilloma or carcinoma. We report a case of prenatal diagnosis of choroid plexus mass detected by ultrasound at 33 weeks of gestation. Prenatal (T1, T2, T2* and diffusion weighted sequences) magnetic resonance imaging (MRI) was used to rule out a hematoma. Follow-up examination by ultrasound and MRI revealed a significant increase in the volume of the mass, suggesting a diagnosis of malignant tumor. A healthy neonate was delivered by Cesarean section at 38 weeks of gestation. Full surgical excision of the tumor was performed at 20 days after delivery and histological analysis revealed a papilloma.

[Venous infarction of the neonate]. / L'infarctus veineux hémorragique du nouveau-né

PURPOSE: To determine the imaging features of hemorrhagic infarction in neonates. PATIENTS AND METHODS: Retrospective study (1998-2008) of 19 children (17 premature and 2 term deliveries) with early lobar hyperechogenicity on transfontanel US (TFUS). Group I: 11 born infants with clinical as well as TFUS and MRI follow-up. Group II: 8 premature infants deceased within a week from multisystem pathology, with neuropathological study available in 3 cases. RESULTS: Group I (n=11): periventricular hyperechogenicity in a frontal (7), frontoparietal (2), parietooccipital (1) and temporoparietal (1) distribution with developing cavitary change (n=6). MRI showed a cortex sparing intraparenchymal hematoma. Group II (n=8): periventricular hyperechogenicity in a frontal (4), frontoparietal or parietal (3) and occipital (1) with developing cavitary change (3). Neuropathological examination showed characteristic lesions of venous hemorrhagic infarction. Clinical outcome was generally favorable for the surviving infants with contralateral motor deficit (n=5) non-correlated to the extent of the initial lesions. CONCLUSION: Venous hemorrhagic infarction mainly affetcs premature infants and typically involves the periventricular frontal white matter. Prognosis is generally favorable. It is thus important to differentiate this entity from asymmetrical cystic periventricular leukomalacia with much different prognosis.

Mycobacterium chelonae infection under adalimumab therapy for spondylarthritis.

Tumour necrosis factor (TNF)-alpha antagonists have been prescribed increasingly over the past few years to manage various inflammatory diseases. This widespread use was quickly followed by the heightened frequency of opportunistic mycobacterial infections including environmental non-tuberculous mycobacterial infections (ENTM). We describe a 66-year-old man taking adalimumab for spondyloarthropathy who developed an inflammatory infiltration in his right index finger. A non-necrotising granuloma with epitheloid and giant cells in the dermis and eosinophilic acid-fast bacilli, identified by using Ziehl-Neelsen staining suggested a mycobacterial infection. Cultures for mycobacteria grew positive on Loewenstein-Jensen medium and molecular identification confirmed M. chelonae infection. The outcome was favourable after five months of clarythromycin. In this context of more frequent ENTM infections, chronic non-specific cutaneous lesions of the extremities should evoke systematically cutaneous ENTM infections. Skin biopsy with histological examination and oriented microbiological cultures and molecular identification are mandatory to confirm the diagnosis.

Fetal aqueductal glioneuronal hamartoma: a clinicopathological and physiopathological study of three cases.

UNLABELLED: Fetal hydrocephalus due to aqueductal stenosis is classified into two main groups: congenital (X-linked, atresia, septa and forking) and acquired (post-infectious or post-hemorrhagic, gliosis and tumors). MATERIAL AND METHODS: We report three fetal cases presenting with severe hydrocephalus, two of which being apparently sporadic, and the third possibly inherited. On macroscopic examination, no associated malformations were identified, either craniofacial dysmorphy, or visceral abnormalities. Neuropathological study revealed massive hydrocephalus caused by narrowing of the Aqueduct of Sylvius. Histological examination evidenced a nodular, well-demarcated mass producing into the aqueductal lumen, and containing numerous immature proliferating glioneuronal cells. Immunohistochemical analyses did not suggest a developmental abnormality of the subcommissural organ but rather a hamartomatous malformative process. RESULTS: Hamartoma of the posterior fossa has been rarely reported. Post-natal cases have been described in the cerebello-pontine angle or in the quadrigeminal plate, and have always been diagnosed as pilocytic or low-grade astrocytomas. In our cases, the lesions could be related to so-called pencil glioma, sometimes associated with type 1 neurofibromatosis and, to our knowledge, have never been described prior to birth. The occurrence during fetal life and the progressive maturation of the nodules are more likely in favor of a hamartomatous process. CONCLUSION: Even though they could sporadically occur, an accurate genetic counseling should be required in order to ensure that there is no familial history of Recklinghausen disease, and to provide a more precise evaluation of recurrence risk.

Fetal hemangiopericytoma with an associated cerebral anomaly.

We report the first case of infantile hemangiopericytoma explored prenatally by fetal ultrasonography and magnetic resonance imaging (MRI). It was associated with a developmental cerebral anomaly identified on MRI. The largest lesions of the multifocal hemangiopericytoma were located in the soft tissue adjacent to the left temporal bone, and smaller lesions were found in the lumbar area and in the retroperitoneum. MRI showed no connection between the tumor and the fetal brain but there was anomalous cerebral gyration in the region and the Sylvian fissure beneath the tumor was enlarged. The pregnancy was terminated because of the severe brain anomalies and postmortem examination confirmed the prenatal findings. Microscopic analysis of the tumor tissue showed branching vessels which are typical of hemangiopericytoma. The lesions in our case occurred in association with macrosomia with visceromegaly detected at autopsy, suggesting a possible role of tumor suppressor genes.

Prenatal diagnosis of a small supernumerary, XIST-negative, mosaic ring X chromosome identified by fluorescence in situ hybridization in an abnormal male fetus.

Marker or ring X [r(X)] chromosomes of varying size are often found in patients with Turner syndrome. Patients with very small r(X) chromosomes that did not include the X-inactivation locus (XIST) have been described with a more severe phenotype. Small r(X) chromosomes are rare in males and there are only five previous reports of such cases. We report the identification of a small supernumerary X chromosome in an abnormal male fetus. Cytogenetic analysis from chorionic villus sampling was performed because of fetal nuchal translucency thickness and it showed mosaicism 46,XY/47,XY,+r(X)/48,XY,+r(X),+r(X). Fluorescence in situ hybridizations (FISH) showed the marker to be of X-chromosome origin and not to contain the XIST locus. Additional specific probes showed that the r(X) included a euchromatic region in proximal Xq. At 20 weeks gestation, a second ultrasound examination revealed cerebral abnormalities. After genetic counselling, the pregnancy was terminated. The fetus we describe is the first male with a mosaic XIST-negative r(X) chromosome identified at prenatal diagnosis. The phenotype we observed was probably the result of functional disomy of the genes in the r(X) chromosome, secondary to loss of the XIST locus.

Congenital erythropoietic porphyria (Günther's disease): two cases with very early prenatal manifestation and cystic hygroma.

Congenital erythropoietic porphyria (CEP) or Günther's disease is the rarest form of the porphyrias. The disease is usually diagnosed at birth or during early infancy, but rarely in utero. We describe here the first two cases of very early prenatal expression of CEP with cystic hygroma diagnosed at 14 weeks in the first fetus and at 19 weeks in the second. Both fetuses presented with severe nonimmune hydrops fetalis as early as 19 and 22 weeks, associated with intrauterine growth retardation, hyperechogenic kidneys and bones. Amniotic fluid was dark brown and uro- and coproporphyrin I was dramatically increased. Molecular screening of the CEP gene detected heterozygous C73R mutation in both fetuses, the other parental mutation being as yet unknown.

[Prenatal diagnosis of isolated posterior fossa anomalies: attempt at a simplified approach]. / Diagnostic anténatal des anomalies isolées de la fosse postérieure: tentative d'approche simplifiée.

The authors suggest, after some embryological, anatomical and nosological reviews, a simplified approach mainly based on the appearance of the pons, cerebellar hemispheres and vermis, independently from an associated cystic dilatation of the posterior fossa. Pontocerebellar hypoplasias and partial or total vermian agenesis are detailed because they can be diagnosed with a prenatal MRI. This classification based on our experience and on the literature data should be of value to evaluate the neurological prognosis.

[The "smears" technique for the extemporaneous examination: diagnostic contribution to neurosurgical pathology]. / Technique des "smears" pour l'examen extemporané: apport diagnostiqueen pathologie neurochirurgicale.

Smear preparation is a fairly accurate, simple and reliable tool for rapid intraoperative diagnosis of central nervous system tumors. Compared with frozen sections this technique has the advantage of being both more accurate for cytological details and of requiring less tissue. In addition final histological analysis after direct formalin fixation is of better quality than post freezing fixation. This technique is most helpful in the field of neuro-oncological pathology specially in glial tumors and in stereotactic biopsy procedures. The cytological aspects and smear patterns disclose important complementary diagnostic information for the histopathological examination.

A gene for Meckel syndrome maps to chromosome 11q13.

Meckel syndrome (MKS) is a rare autosomal recessive lethal condition of unknown origin, characterized by (i) an occipital meningo-encephalocele with (ii) enlarged kidneys, with multicystic dysplasia and fibrotic changes in the portal area of the liver and with ductal proliferation, and (iii) postaxial polydactyly. A gene responsible for MKS in Finland has been mapped to chromosome 17q21-q24. Studying a subset of Middle Eastern and northern African MKS families, we have recently excluded the chromosome 17 region and have suggested a genetic heterogeneity. In the present study, we report on the mapping of a second MKS locus (MKS2) to chromosome 11q13, by homozygosity mapping in seven families that do not show linkage to chromosome 17q21-q24 (maximum LOD score 4.41 at recombination fraction .01). Most interestingly, the affected fetuses of southern Tunisian ancestry shared a particular haplotype at loci D11S911 and D11S906, suggesting that a founder effect is involved. Our observation gives support to the clinical and genetic heterogeneity of MKS.

Severe brain and limb defects with possible autosomal recessive inheritance: a series of six cases and review of the literature.

Six fetuses with normal chromosomes were found to have severe craniofacial, limb, and visceral malformations during the second trimester of pregnancy. Two of these fetuses were monozygotic twins while a third one had a healthy dizygotic twin brother. A case with familial recurrence was also observed. Autopsy and skeletal radiographs suggested several diagnoses such as neural tube defect with limb defects or XK aprosencephaly. The development of these severe conditions in monozygotic twins and familial recurrence emphasize the difficulties of genetic counseling in such situations. These cases may suggest autosomal recessive inheritance.

Quantitation of Alzheimer's amyloid peptide and identification of related amyloid proteins by dot-blot immunoassay.

In Alzheimer's disease, the main component of amyloid deposits is a 39-43 amino acid peptide referred to as amyloid peptide or A beta. A crucial issue in the study of this disorder is to define the sequence of events that lead to amyloid deposition. In the present study, a new approach was developed that allows to specifically solubilize A beta peptide trapped within amyloid deposits and to quantify its amount by dot-blot immunoassay. The present method also permits to isolate components tightly bound to A beta and that are likely to catalyze its aggregation. Biochemical A beta quantitation was performed in 4 Brodmann areas from 17 elderly individuals exhibiting different degrees of amyloidosis. In parallel, classical neuropathology was done by histochemical and immunohistochemical methods. A beta amounts (pmol) were correlated to the number of amyloid deposits determined by neuropathology showing high statistical significance. Moreover, amyloid-binding proteins including apolipoprotein E and heparan sulfate proteoglycans were also found associated to A beta in the amyloid preparation. The present biochemical procedure is a new and reliable method to quantify amyloid deposition in brain. Furthermore, it allows to detect amyloid-associated components such as apolipoprotein E, that may be involved in the pathological process of amyloidogenesis.

Syndromal hypothalamic hamartoblastoma with holoprosencephaly sequence, microphthalmia, pulmonary malformations, radial hypoplasia and müllerian regression: further delineation of a new syndrome?

A 24-week-old fetus is described here with holoprosencephaly sequence (arhinencephaly and agenesis of the corpus callosum) associated with brain and meningeal dysplasia, microphthalmia with an ectopic pigmentary layer, hypothalamic hamartoblastoma, preaxial asymmetric limb reduction, lung hypoplasia, gastric hypoplasia, Müllerian regression, intestinal malrotation, asplenia, and normal chromosomes. The differential diagnosis includes the Cerebroacrovisceral-Early lethality (CAVE) phenotype, and the Pallister-Hall syndrome, but the anomalies best fit the severe form of microgastria-limb reduction syndrome. Together with a previous case reported by Meinecke, the pattern of anomalies appears to represent a combination of defects, related to but distinct from the microgastria-limb reduction syndrome.

[Secondary intraspinal localizations of glioblastoma. Apropos of a case]. / Localisations secondaires intra-rachidiennes des glioblastomes. A propos d'un cas.

Metastasis of intracranial glioblastomas have been described for the first time more than fifty years ago. They are exceptional and seem to develop clinically in less than 2% of cases. In fact, microscopic metastasis (necropsic series) of such glioblastomas are much more frequent: from 6% for supratentorial glioblastomas to 60% in infratentorial ones; but patients usually die before clinical symptoms appear. The authors report on an intraspinal metastasis which appeared clinically four years after the removal of a frontal glioblastoma. The metastasis was subdural, T3. Preoperative radiological data (CT-scan, MRI) evoked a meningioma, while surgical findings favoured the diagnosis of neurinoma. The diagnosis of glioblastoma metastasis was suggested by intra-operative pathological findings, and confirmed a few days later on smears and stains studies.