Homa Adle-Biassette

Surgery plays an important role in the treatment of sinonasal cancer. Many surgical approaches have been described, including open, endoscopic, or combined approaches. The choice is based on several criteria: general criteria related to the oncological results and morbidity of each technique, specific criteria related to the tumor (tumor extensions, tumor pathology), the patient, or the surgeon himself. The aims of this review are (i) to provide a complete overview of the surgical techniques available for the management of sinonasal malignant tumors, with a special focus on recent developments in the field of transnasal endoscopic surgery; (ii) to summarize the criteria that lead to the choice of one technique over another. In particular, the oncological outcomes, the morbidity of the different techniques, and the specificities of each histologic subtype will be discussed based on a comprehensive literature review.

Preterm delivery affects 10.6% of all live births ( 1). Despite the improvement in neonatal survival, there is still a high prevalence of motor, neurosensory, cognitive, and behavioral deficits ( 2–4). Neuroprotection of the premature brain is a healthcare priority both in terms of family burden and economy ( 5, 6). Significant progress in our ability to establish the specific diagnosis and an improved understanding of the fundamental mechanisms of neonatal brain injury are needed in order to propose relevant neuroprotective strategies.

Neuropathological conditions might affect adult granulogenesis in the adult human dentate gyrus. However, radial glial cells (RGCs) have not been well characterized during human development and aging. We have previously described progenitor and neuronal layer establishment in the hippocampal pyramidal layer and dentate gyrus from embryonic life until mid-gestation. Here, we describe RGC subtypes in the hippocampus from 13 gestational weeks (GW) to mid-gestation and characterize their evolution and the dynamics of neurogenesis from mid-gestation to adulthood in normal and Alzheimer’s disease (AD) subjects. In the pyramidal ventricular zone (VZ), RGC density declined with neurogenesis from mid-gestation until the perinatal period. In the dentate area, morphologic and antigenic differences among RGCs were observed from early ages of development to adulthood. Density and proliferative capacity of dentate RGCs as well as neurogenesis were strongly reduced during childhood until 5 years, few DCX⁺ cells are seen in adults. The dentate gyrus of both control and AD individuals showed Nestin⁺ and/or GFAPδ⁺ cells displaying different morphologies. In conclusion, pools of morphologically, antigenically, and topographically diverse neural progenitor cells are present in the human hippocampus from early developmental stages until adulthood, including in AD patients, while their neurogenic potential seems negligible in the adult.

The molecular mechanisms that orchestrate the development of the human dentate gyrus are not known. In this study, we characterized the formation of human dentate and fimbrial progenitors and postmitotic neurons from 9 gestational weeks (GW9) to GW25. PAX6⁺ progenitor cells remained proliferative until GW16 in the dentate ventricular zone. By GW11, the secondary dentate matrix had developed in the intermediate zone, surrounding the dentate anlage and streaming toward the subpial layer. This secondary matrix contained proliferating PAX6⁺ and/or TBR2⁺ progenitors. In parallel, SOX2⁺ and PAX6⁺ fimbrial cells were detected approaching the dentate anlage, representing a possible source of extra-dentate progenitors. By GW16, when the granule cell layer could be delineated, a hilar matrix containing PAX6⁺ and some TBR2⁺ progenitors had become identifiable. By GW25, when the 2 limbs of the granule cell layer had formed, the secondary dentate matrix was reduced to a pool of progenitors at the fimbrio-dentate junction. Although human dentate development recapitulates key steps previously described in rodents, differences seemed to emerge in neuron layer markers expression. Further studies are necessary to better elucidate their role in dentate formation and connectivity.

L1 syndrome results from mutations in the L1CAM gene located at Xq28. It encompasses a wide spectrum of diseases, X-linked hydrocephalus being the most severe phenotype detected in utero, and whose pathophysiology is incompletely understood. The aim of this study was to report detailed neuropathological data from patients with mutations, to delineate the neuropathological criteria required for L1CAM gene screening in foetuses by characterizing the sensitivity, specificity and positive predictive value of the cardinal signs, and to discuss the main differential diagnoses in non-mutated foetuses in order to delineate closely related conditions without L1CAM mutations. Neuropathological data from 138 cases referred to our genetic laboratory for screening of the L1CAM gene were retrospectively reviewed. Fifty-seven cases had deleterious L1CAM mutations. Of these, 100 % had hydrocephalus, 88 % adducted thumbs, 98 % pyramidal tract agenesis/hypoplasia, 90 % stenosis of the aqueduct of Sylvius and 68 % agenesis/hypoplasia of the corpus callosum. Two foetuses had L1CAM mutations of unknown significance. Seventy-nine cases had no L1CAM mutations; these were subdivided into four groups: (1) hydrocephalus sometimes associated with corpus callosum agenesis (44 %); (2) atresia/forking of the aqueduct of Sylvius/rhombencephalosynapsis spectrum (27 %); (3) syndromic hydrocephalus (9 %), and (4) phenocopies with no mutations in the L1CAM gene (20 %) and in whom family history strongly suggested an autosomal recessive mode of transmission. These data underline the existence of closely related clinical entities whose molecular bases are currently unknown. The identification of the causative genes would greatly improve our knowledge of the defective pathways involved in these cerebral malformations.

Congenital cytomegalovirus (CMV) infection is the leading cause of non-hereditary congenital sensorineural hearing loss (SNHL). The natural course and the pathophysiology of inner ear lesions during human fetal CMV infection have not yet been reported. Inner ear lesions were investigated in six CMV-infected fetuses aged 19–35 postconceptional weeks and correlated with central nervous system (CNS) lesions. All the fetuses had high viral loads in the amniotic fluid and severe visceral and CNS lesions visible by ultrasound. Diffuse lesions consisting of both cytomegalic cells containing inclusion bodies and inflammation were found within all studied structures including the inner ear, brain, other organs, and placenta, suggesting hematogenous dissemination. Cochlear infection was consistently present and predominated in the stria vascularis (5/6), whereas the supporting cells in the organ of Corti were less often involved (2/6). Vestibular infection, found in 4/6 cases, was florid; the non-sensory epithelia, including the dark cells, were extensively infected. The endolymphatic sac was infected in 1 of 3 cases. The severity of inner ear infection was correlated with the CNS lesions, confirming the neurotropism of CMV. This study documenting infection of the structures involved in endolymph secretion and potassium homeostasis in fetuses with high amniotic fluid viral loads suggests that potassium dysregulation in the endolymphatic compartment of the inner ear may lead to secondary degeneration of the sensory structures. In addition, the occurrence of SNHL depends on the intensity and duration of the viral infection and inflammation.