Search

International audience; Secondary neurulation is a morphological process described since the second half of the 19th century; it accounts for the formation of the caudal spinal cord in mammals including humans. A similar process takes place in birds. This form of neurulation is caused by the growth of the tail bud region, the most caudal axial region of the embryo. Experimental work in different animal species leads to questioning dogmas widely disseminated in the medical literature. Thus, it is clearly established that the tail bud is not a mass of undifferentiated pluripotent cells but is made up of a juxtaposition of territories whose fate is different. The lumens of the two tubes generated by the two modes of neurulation are continuous. There seem to be multiple cavities in the human embryo, but discrepancies exist according to the authors. Finally, the tissues that generate the secondary neural tube are initially located in the most superficial layer of the embryo. These cells must undergo internalization to generate the secondary neurectoderm. A defect in internalization could lead to an open neural tube defect that contradicts the dogma that a secondary neurulation defect is closed by definition.

Meninges have long been considered as a protective and supportive tissue for the central nervous system. Nevertheless, new developmental roles are now attributed to them. The meninges that surround the cerebellum come from the cephalic mesoderm. They are essential for the cerebellum to develop normally. They induce and maintain the basal lamina and glia limitans. In the absence of these structures, the external granular cells of the cerebellum migrate aberrantly and penetrate the subarachnoid space. The molecules involved in the recognition between the cerebellar primordium and the basal lamina belong to two groups in humans: dystroglycan and laminin on the one hand, and GPR56 and collagen III on the other. Finally, molecules secreted by the meninges and acting on the cerebellum begin to be demonstrated; such is the case of SDF1 secreted under the action of FOXC1.

Introduction La maladie d’Alexander debutant a l’âge adulte a un phenotype clinico-radiologique different de la forme infantile. Nous rapportons ici deux observations. Observation Premier cas : Femme de 45 ans presentant depuis un an une ataxie, une dysarthrie, une tetraparesie pyramidale, une dysautonomie avec incontinence urinaire et fecale. Des troubles du comportement ont precede ces signes justifiant une mise sous curatelle. Deces a 47 ans. Sa mere, decedee a 62 ans, presentait des troubles similaires. Second cas : Homme de 49 ans consultant pour une tetraparesie pyramidale asymetrique a predominance gauche avec grabatisation rapide, suivie d’une incontinence urinaire et fecale. Des troubles de l’humeur et un syndrome frontal etaient decrits. Son pere etait decede a 65 ans dans les suites d’une paraplegie spastique evoluant sur 15 ans. Dans les deux cas, l’IRM cerebrale etait caracteristique : – atrophie prononcee de la moelle allongee et de la moelle cervicale avec un aspect de tetard du tronc cerebral en coupe sagittale T1 ; – hypersignal mesencephalique peripherique FLAIR sous pial evocateur ; – hypersignaux T2 de la substance blanche periventriculaires, mesencephaliques, des noyaux denteles, de la moelle allongee et de la moelle cervicale. Une mutation du gene codant la proteine GFAP a ete retrouvee dans ces deux cas. Discussion L’aspect clinique de la maladie d’Alexander a debut adulte est parfois deroutant. Neanmoins, les images d’IRM cerebrale, en particulier en fosse posterieure, sont assez stereotypees et tres evocatrices et doivent conduire a la recherche d’une mutation du gene GFAP surtout en cas d’antecedents familiaux suggerant une affection autosomique dominante. Conclusion La maladie d’Alexander debutant chez l’adulte est de diagnostic clinique difficile mais les anomalies cerebrales IRM sont tres evocatrices et doivent faire rechercher une mutation du gene GFAP.

International audience; OBJECTIVE:C9orf72 hexanucleotide repeats expansions account for almost half of familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases. Recent imaging studies in asymptomatic C9orf72 carriers have demonstrated cerebral white (WM) and gray matter (GM) degeneration before the age of 40 years. The objective of this study was to characterize cervical spinal cord (SC) changes in asymptomatic C9orf72 hexanucleotide carriers.METHODS:Seventy-two asymptomatic individuals were enrolled in a prospective study of first-degree relatives of ALS and FTD patients carrying the c9orf72 hexanucleotide expansion. Forty of them carried the pathogenic mutation (C9+ ). Each subject underwent quantitative cervical cord imaging. Structural GM and WM metrics and diffusivity parameters were evaluated at baseline and 18 months later. Data were analyzed in C9+ and C9- subgroups, and C9+ subjects were further stratified by age.RESULTS:At baseline, significant WM atrophy was detected at each cervical vertebral level in C9+ subjects older than 40 years without associated changes in GM and diffusion tensor imaging parameters. At 18-month follow-up, WM atrophy was accompanied by significant corticospinal tract (CST) fractional anisotropy (FA) reductions. Intriguingly, asymptomatic C9+ subjects older than 40 years with family history of ALS (as opposed to FTD) also exhibited significant CST FA reduction at baseline.INTERPRETATION:Cervical SC imaging detects WM atrophy exclusively in C9+ subjects older than 40 years, and progressive CST FA reductions can be identified on 18-month follow-up. Cervical SC magnetic resonance imaging readily captures presymptomatic pathological changes and disease propagation in c9orf72-associated conditions. ANN NEUROL 2019;86:158-167.

Background Learning surgical anatomy of the petrous pyramid can be a challenge, especially in the beginning of the training process. Providing an easier, holistic approach can be of help to everyone with interest in learning and teaching skull base anatomy. We present the complex organization of petrous pyramid anatomy using a new compartmental approach that is simple to understand and remember. Methods The surfaces of the petrous pyramid of two temporal bones were examined; and the contents of the petrous pyramid of 8 temporal bones were exposed through progressive drilling of the superior surface. Results The petrous pyramid is made up of a bony container, and its contents were grouped into 4 compartments (mucosal, cutaneous, neural, and vascular). Two reference lines were identified (mucosal and external-internal auditory canal lines) intersecting at the level of the middle ear. The localization of contents relative to these reference lines was then described, and 2 methods of segmentation (the X method and the V method) were then proposed. This description was then used to describe middle ear relationships, facial nerve anatomy, and air cell distribution. Conclusions This new compartmental approach allows a comprehensive understanding of the distribution of petrous pyramid contents. Dividing it into anatomic compartments, and then navigating this mental map along specific reference points, lines, spaces, and segments, could create a useful tool to teach or learn its complex tridimensional anatomy.

Spinal muscular atrophy (SMA) type III and IV are autosomal recessive, slowly progressive lower motor neuron syndromes. Nevertheless, wider cerebral involvement has been consistently reported in mouse models. The objective of this study is the characterisation of spinal and cerebral pathology in adult forms of SMA using multimodal quantitative imaging. Methods Twenty-five type III and IV adult SMA patients and 25 age-matched healthy controls were enrolled in a spinal cord and brain imaging study. Structural measures of grey and white matter involvement and diffusion parameters of white matter integrity were evaluated at each cervical spinal level. Whole-brain and region-of-interest analyses were also conducted in the brain to explore cortical thickness, grey matter density and tract-based white matter alterations. Results In the spinal cord, considerable grey matter atrophy was detected between C2-C6 vertebral levels. In the brain, increased grey matter density was detected in motor and extra-motor regions of SMA patients. No white matter pathology was identified neither at brain and spinal level. Conclusions Adult forms of SMA are associated with selective grey matter degeneration in the spinal cord with preserved white matter integrity. The observed increased grey matter density in the motor cortex may represent adaptive reorganisation., Highlights • (SMA) type 3 and 4 is a lower motor neuron syndrome. Nevertheless, wider involvement of the nervous system might be possible. • 25 adults type 3 and 4 SMA patients were studied using brain and cervical spinal cord neuroimaging techniques. • Grey matter atrophy was observed in the spinal cord. No white matter degeneration was present at brain and spinal level. • Increased grey matter density was detected in cerebral motor regions and explained as compensatory mechanism.

International audience; The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance of a stable CNS internal environment. The CSF circulation plays an important role in volume transmission within the developing and adult brain, and CSF compartments are key to the immune surveillance of the CNS. In these contexts, the choroid plexuses are an important source of biologically active molecules involved in brain development, stem cell proliferation and differentiation, and brain repair. By sensing both physiological changes in brain homeostasis and peripheral or central insults such as inflammation, they also act as sentinels for the CNS. Finally, their role in the control of immune cell traffic between the blood and the CSF confers on the choroid plexuses a function in neuroimmune regulation and implicates them in neuroinflammation. The choroid plexuses, therefore, deserve more attention while investigating the pathophysiology of CNS diseases and related comorbidities.

International audience; no abstract

International audience; Subcutaneous tumors with extra limbs are very rare, and they are considered either as fetus in fetu or fetiform teratoma. We report here the case of a 6-day-old presenting a mass extending at the level of the occipital bone. This mass is developed in the extracranial region and contains two forelimbs including hands with digits. CT shows that the squamous part of the occipital bone is involved with several defects through which a part of the cerebellum herniates. The boy was operated on and the tumor was removed. The herniated region of the cerebellum has also been removed. After surgery, the boy develops normally. This type of tumor is extremely rare and is only the second case that has been reported at this exact location. This could be the so-called c,phalom,lie described by Isidore Geoffroy Saint-Hilaire in a duck in his famous Treatise of Teratology (1836). The cause of this malformation is still a matter for debate.

Introduction Un patient, âge de 31 ans, issu d’une famille marocaine consanguine, nous a ete adresse pour troubles neurologiques jamais investigues evoluant depuis l’enfance, associes a un contexte de photosensibilite. Observation Le patient est ne a terme, avec developpement psychomoteur initial normal. A l’âge de 6 mois, est notee une photosensibilite avec eruption cutanee a l’ensoleillement responsable de phlyctenes et de cicatrices lentigineuses. Un trouble du langage avec begaiement apparait a l’âge de 6 ans, puis a 8 ans une deformation des pieds en varus equin. Sa scolarite est perturbee des le CE1, avec mise en secteur protege necessaire. Depuis 2012, une majoration des troubles de la marche et des troubles vesico-sphincteriens compromet l’autonomie. Il est adresse en neurologie, ou l’examen clinique retrouve un retard mental, une abolition diffuse des reflexes osteotendineux, un signe de Babinski bilateral et un syndrome cerebelleux. L’examen cutane montre des lentigines avec cicatrices hypopigmentees dans les zones photo-exposees. Le bilan etiologique retrouve une atrophie diffuse et une hyperostose crânienne a l’IRM cerebrale, l’EMG une polyneuropathie axonale (PRN) sensitivomotrice, un bilan biologique normal et le bilan genetique une mutation homozygote c.682C>T dans l’exon 6 du gene XPA codant une proteine tronquee p.Arg228 * (la plus frequente parmi les mutations de XPA en Afrique du Nord). Ces donnees confirment le diagnostic de Xeroderma pigmentosum (XP) de type A. Discussion Le XP est une genodermatose autosomique recessive rare liee a un defaut de reparation de l’ADN. L’atteinte principale est cutanee (photosensibilite et risque eleve de cancer). Cinq des 8 groupes comportent des symptomes neurologiques (deficit cognitif, microcephalie, epilepsie, syndrome cerebelleux, PRN, surdite). La mutation de XPA presentee ici donne une atteinte neurologique predominante et une atteinte cutanee secondaire avec rarete des cancers. Conclusion 30 % des patients XP ont une atteinte neurologique. Le diagnostic est genetique. La prise en charge multidisciplinaire avec depistage des cancers, protection anti-UV et traitement symptomatique ameliorent le pronostic cutane.

Notomelia associated with neural tube defects are rare diseases. A baby was born in Niger with multiple congenital embryonic malformations on the posterior midline. The most rostral malformation was an accessory limb (polymelia) at the level of the lumbar vertebrae composed of two long bones, a foot and three toes. Accessory male genitalia were present at the base of this malformed accessory limb which had no apparent motor or sensory innervation. The second malformation was a sacral vestigial appendage with an adjacent dermal sinus opening onto the posterior midline and extending internally to the dura through a defect of the vertebral arches. From the published literature and this particular case, we conclude that notomelia is a rare clinical sequela of a neural tube defect (NTD) and is correctly classified as a dysraphic appendage. The recent occurrence of three similar cases in the same ethnic group from Niger, three from consanguineous parents, suggests that genetic factors are likely to contribute significantly to the genesis of this syndrome, consistent with a recent report that mutation of the bovine NHLRC2 gene resulting in a V311A substitution at a highly conserved locus in the NHLRC2 protein is, when homozygous, causally associated with several forms of polymelia including notomelia, with heteropagus conjoined twinning and with other NTD-related embryonic malformations. Detailed genome-wide studies of children with dysraphic appendages are indicated.

The genetic studies of syndromic craniosynostoses lead to the characterisation of genes that regulate the correct development of the bones of the skull. From these studies, it appears that FGF/FGFR signalling has a crucial role in this problem. Numerous mutations affecting the genes coding for FGFR1, 2 or 3 are responsible for these syndromes. It is interesting to note that some identical mutations produced various different phenotypes, suggesting that other genes modulate the phenotypic expressivity. The other involved genes in these syndromes code for such proteins as Msx2 or Twist that interact in the cellular pathways responsible for FGF action. From these genetic studies, it is now important to establish the role of these proteins during the development of the skull. Msx2 plays a repressive role in osteogenesis, whereas FGFRs act as promoting proteins. In the near future, it will be very important to improve our understanding of these phenomena in order to test specific treatments to prevent the development of such syndromes.

Epilepsy with myoclonus is thought to be linked to the motor system. At birth, development of the central nervous system in humans is far from being achieved. Post-natal changes take place at different levels in this neuronal system. These modifications suggest that the motor cortex is a highly dynamic structure during post-natal development. They may account for the age-dependence of various epileptic syndromes. (1) The number of synapses increases during the early post-natal years and then decreases to reach the adult level around puberty. (2) Neurons differentiate and synthesize various neurotransmitters. (3) Dendrites grow actively and participate in the formation of local cortical circuits. (4) Electrophysiological properties of cortical neurons change during the first months of rodent development. This could reflect modifications of the ion channels present in the cell membrane. (5) The pyramidal tract myelinate and exuberant collaterals are selectively removed. These two processes are dependent on neuronal electrical activity. It has been demonstrated that selective collateral stabilization is promoted by glutamate release and stimulation of the N-methyl- d -aspartate (NMDA) receptor. So, seizures occurring during the neonatal period may interact with these normal developmental features. Furthermore, neuronal electrical activity and seizures stimulate the transcription of specific messenger RNAs coding for neurotrophic factors like nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF). The overproduction of neurotrophic factors leads to maldevelopment of the cortex.

Spina bifida with lipoma is a human malformation that most often affects the lumbosacral area. It is a complex morphological type. Its origin is controversial, and none of the previous hypotheses can be retained in view of the most recent advances in experimental embryogenesis. Contrary to earlier opinons, adipocytes cannot arise from meninges, vessels or glial cells and spina bifida cannot be explained by incarceration of mesodermal tissues during primary neurulation or developmental defect at the level of the tail bud. Spina bifida with lipoma, which actually involves all the derivatives of the so-called dorsal mesoderm, must therefore result from abnormal development of this mesoderm, which is induced by the dorsal neural tube. The location of the primary defect (dorsal mesoderm or neural tube) remains to be established.

A male fetus presenting with prenatal hydrocephalus is reported. The fetus died during labor. Pathological examination disclosed four accessory spleens without any abnormalities of the situs. Hydrocephalus was secondary to aqueductal stenosis. Histological features of the aqueduct were consistent with a developmental defect. The association of such malformations has already been reported and could be explained by common regulatory mechanisms which control the splenic and neural tube development.

Introduction Les microdeletions 6p25 sont a l’origine de phenotypes variables : atteinte ophtalmologique, surdite, retard mental, malformations cranio-faciales… Des anomalies de la substance blanche sont plus rarement decrites. Observation Nous rapportons le cas d’une patiente de 24 ans, issue d’une union consanguine, suivie depuis la petite enfance pour un glaucome congenital bilateral (syndrome d’Axenfeld Rieger clinique) et une surdite bilaterale. Elle presente egalement des migraines avec aura depuis l’adolescence. A l’occasion d’un bilan d’hirsutisme, une IRM cerebrale est realisee, retrouvant de nombreux hypersignaux de la substance blanche peri-ventriculaire et sous corticaux ne prenant pas le contraste. La patiente est hospitalisee pour suspicion de sclerose en plaques. L’examen clinique retrouve des reflexes osteotendineux vifs, la surdite et une dysmorphie faciale. Le bilan biologique standard, immunologique, infectieux, metabolique et carentiel est normal ainsi que le bilan neuropsychologique. L’IRM cerebrale a 6 mois est inchangee et l’IRM medullaire ne retrouve pas d’anomalie. L’analyse du LCR n’a pas pu etre realisee. Une surdite et/ou des anomalies du parenchyme cerebral n’etant pas habituellement associees au syndrome d’Axenfeld Rieger, l’hypothese d’un syndrome des genes contigus a ete soulevee. Une deletion en 6p25.3 emportant le gene FOXC1 , responsable quand il est mute du syndrome d’Axenfeld Rieger, a ete mise en evidence par CGH Array. Discussion Un certain nombre d’anomalies cerebrales ont ete decrites associees aux microdeletions 6p25 : malformation de Dandy-Walker, hypoplasie du corps calleux, hydrocephalie, dilatation des espaces perivasculaires. Des hypersignaux de la substance blanche ont ete rapportes de facon plus recente dans environ 20 % des cas, conduisant chez certains, comme chez notre patiente a un diagnostic errone de sclerose en plaques. Conclusion Des hypersignaux de la substance blanche peuvent faire evoquer a tort une maladie inflammatoire du systeme nerveux central. Associes a un syndrome malformatif, ils doivent faire rechercher une cause genetique.

International audience; no abstract

Prenatal thrombocytopenia is a rare event and is generally due to fetal infection. In very rare cases, fetal thrombocytopenia is induced by maternal IgG directed against the fetal platelets. This alloimmunisation could lead to in utero bleeding. We now report such a case, in which fetal thrombocytopenia was complicated by a huge temporal lobe haematoma. Such a prenatal event is rare: only eight cases have been published, with only one pathologically confirmed case. Our patient is the second one in which neuropathological examination demonstrated prenatal intracerebral bleeding.

An attempt to present all the data that account for the progressive transformation of a fertilized zygote into a child at birth is obviously a herculean work. In this review, I focus on four aspects of central nervous system development in which our understanding has considerably been enhanced during the last century. The first part concerns the phenomenon of neural induction, a process devoted to the acquisition of neural identity. It was classically considered that active molecules were secreted by the organizer (the dorsal lip of the blastopore in amphibians and the node in amniotes) and that these molecules induced the neural induction. Nowadays, the model is much more complex, based upon both positive and negative regulatory mechanisms. The positive inductor is BMP4, and this induces the epidermal induction. The organizer secretes negative signals that can bind BMP4 and prevent its action. The second part is devoted to the morphogenetic movements that allow formation of the neural tube. Classically, primary and secondary neurulations are opposed. It is now well established that the two modes of neurulation obey the same basic rules. The problem of segmentation of the central nervous system during embryogenesis could be easily studied for the rhombencephalon. This structure is formed by repetitive subunits called rhombomeres. Each rhombomere corresponds to a compartment separated from the others. In addition, each rhombomere expresses specific genes, and the invalidation of some of them leads to the absence of these rhombomeres. However, the situation is much more complex with regions specified very early during development and acting on adjacent regions to induce a specific pattern. The last part of my paper concerns the development of the cortex. During the last 50 years, all the classic concepts have been challenged. The fixed law of radial migration has been extensively discussed, and it is now admitted that other kinds of migration do take place during corticogenesis. These results force us to reconsider the interpretations of some cortical malformations. It seems reasonable to adopt descriptive terms for a malformative syndrome instead of terms based on putative mechanisms.

Intracranial lipomas are rare lesions the pathogenesis of which is still a matter of debate. We report the case of a patient presenting an asymptomatic lipoma located in the quadrigeminal and supra-cerebellar cisterns. The lipoma was associated with hypoplasia of the right inferior colliculus and of the rostral part of the vermis. Analysis of the relationships between neural tube and meninges prompts us to propose that the primary event of this malformation is a defect of the neural anlage which gives rise to both nervous dysplasia and lack of meningeal induction responsible for lipoma development.

Carbonic anhydrase is one of the key enzymes responsible for the secretion of cerebrospinal fluid. This secretion increases dramatically during postnatal life in mammals. Nothing is known that can account for this regulation in the neonatal choroid plexus. However, the expression of carbonic anhydrase is developmentally regulated in several cells, such as erythrocytes and striated muscle fibers. The aim of our study was to assess the presence of carbonic anhydrase in epithelial cells of the choroid plexus during human development. We performed both histochemical and immunohistochemical detections of the enzyme on choroid plexuses between 9 and 34 weeks of gestation. We found that both carbonic anhydrase activity and the isozyme II were present as early as the 9th week of gestation. Expression of carbonic anhydrase is thus a very early event during plexus differentiation, and this enzymatic system could account for the secretion of cerebrospinal fluid during fetal life.