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Expression of Bgp1a, a glycoprotein that serves as receptor for mouse hepatitis virus-A59 has been analyzed in various mouse tissues and correlated with the pathogenicity that this virus induces in the corresponding organs. Expression of Bgp1a was observed in many cells of epithelial origin, including hepatocytes and endothelial cells. It was also shown on macrophages and B lymphocytes. Bgp1a localization may easily explain infection and lysis of some cell types like hepatocytes. In contrast, other cell types that express the viral receptor are not infected after in vivo inoculation with mouse hepatitis virus-A59, which may be due to inaccessibility of the receptor to the virus during mouse infection, or to resistance to this virus in some cell types. This may account for the ability of the blood-brain barrier to prevent mouse hepatitis virus-A59 spreading into the central nervous system. In other organs, the virus may induce pathogenesis indirectly, resulting in the destruction of cells that do not express Bgp1a, like thymic lymphocytes, or else impair cell functions such as cytokine and immunoglobulin production by macrophages and B lymphocytes, respectively.

We report two patients with non-Hodgkin's lymphoma in whom hypercalcemia and elevated 1,25 dihydroxyvitamin D (1,25-(OH)2D3) levels developed in the absence of any lytic bone lesions. Hypercalcemia responded only transiently to glucocorticoids which were ill tolerated. Intravenous APD administration was needed to circumvene hypercalcemia. Humoral hypercalcemia of malignancy is discussed. Our cases confirm that hypercalcemia associated with elevated 1,25-(OH)2D3 may occur in malignant lymphoma.

Ventricular schwannomas are very uncommon. We report such a tumor in the right lateral ventricle of a 16-year-old young man. The various etiopathogenic hypotheses are discussed.

C57BI/6N mice develop a CNS demyelinating disease when inoculated intracranially at 4 weeks of age with the A59 strain of mouse hepatitis virus (MHV‐A59). In order to explore the virus‐host interactions, the histological features of the demyelinating disease were correlated with the spatial and temporal distribution of viral transcripts and the expression of oligodendrocyte‐specific genes (myelin basic protein, proteolipid protein, myelin‐associated glycoprotein, and 2′, 3′ cyclic nucleotide 3′‐phosphohydrolase) in the spinal cord of diseased mice. Three distinct phases in the disease were identified. In the first phase, 1 week postinfection (1 WPI), virus replication was widespread in both gray and white matter but was preferentially occurring in glial cells. In the ventral and dorsal root zones where viral transcripts were most abundant, all myelin gene transcripts were decreased before demyelination was seen. During the second phase of the disease (2–3 WPI), viral transcripts decreased in abundance and became restricted to the white matter. Numerous demyelinating lesions were observed and were characterized by inflammatory cells, paucity of oligodendrocytes, and a profound decrease of all myelin gene transcripts. In the third phase of the disease (4–6 WPI) no viral transcripts were detected, and remyelination began. In the lesions and the tissue surrounding them, transcripts of all myelin genes increased to levels above normal. The increased expression of myelin gene transcripts occurred in a synchronized manner and with a cellular distribution reminiscent of that seen in developmental myelination. These molecular events correlated with efficient remyelination and clinical recovery in this murine demyelinating disease.

The effects of cyclosporin A (CsA) on neuropathological lesions induced by a chronic viral infection have been tested in the experimental model of the mouse hepatitis virus 3 (MHV3) infection. Daily injections of CsA (50 mg/kg) inhibited the expression of the MHV3-induced ependymitis, meningitis, hydrocephalus and vasculitis. The effect was preserved even if CsA treatment was initiated 15 days after virus infection but was lost if CsA treatment was given later on or for a shorter period of time. Viral titers in brains of chronically infected mice were not affected by CsA treatment. During the first week following MHV3 infection, CsA treatment increased both the percentage of acute death (31 vs. 10%) and the viral titers in brain and liver of infected mice. In this model, the timing of CsA treatment appeared critical for the balance between its beneficial effect on CNS lesions and the risk of increased acute mortality.

Intraperitoneal injection of MHV3 into adult C3H mice results either in early death due to hepatitis or in the development of a chronic disease with neurologic manifestations and virus persistence in surviving animals. The chronic neurologic disease which is described in another report in this volume, leads to meningitis, ependymitis, encephalitis and hydrocephalus followed by a chronic thrombotic vasculitis. In view of the potential therapeutic interest of Cyclosporin A (CsA), we decided to test its effects on the CNS lesions induced by MHV3.

The presence of a receptor for a given virus on the cell membrane is a primary factor in determining the affinity of that virus for the cell and contributes to the pathogenicity of the disease (1). Studies of viral binding to isolated subpopulations of CNS cells provide an in vitro approach to the question of viral tropism in the nervous system and patterns of viral binding in vitro have been found to correlate with the pathologic consequences of viral infection in vivo. This has been well demonstrated in the reovirus system using recombinant viruses (2) as well as in other experimental systems including coronaviruses A59 or JHM-MHV4 (using temperature sensitive mutants) (3–6). The aim of our work was (a) to define the selective affinity of MHV3 for CNS cells and to compare it with that of other coronaviruses; (b) to analyse in vitro the consequences of MHV3 infection in CNS cells such as the ability of infected cells to survive and proliferate, the induction of cellular fusion, the intracyto-plasmic enzymatic activities and the membranal functions of the infected CNS cells.

We describe the case of a 76-year old woman complaining of headaches and progressive sight loss. Cerebral CT scan and MRI disclosed a large sellar tumour. Endocrine evaluation showed no evidence of pituitary hypersecretion, but a slight hyperprolactinemia related to stalk compression. A non-functioning pituitary adenoma was suspected. The pathological diagnosis was however a meningioma. In the literature, about 5% of sellar tumours are not pituitary adenomas and this is an alternate diagnosis to consider in the presence of non-secreting macroadenomas.

The cellular composition of the islets of Langerhans is not constant throughout the pancreas. The basis of the heterogeneity lies in their embryological origin: islets originating from the ventral primordium are rich in pancreatic polypeptide cells and poor in glucagon cells, whereas the reverse holds true for islets derived from the dorsal primordium (Rahier et al., 1979).

Le cancer colorectal est une entité hétérogène, sur le plan clinico-pathologique mais également moléculaire, et les stratégies de traitement permettent actuellement des approches de plus en plus personnalisées. La population des patients atteints de métastases cérébrales est rare et un effort de recherche est nécessaire pour mieux les comprendre et les traiter.Objectifs : l’objectif de cette étude a donc été d’analyser les caractéristiques anatomo-cliniques de métastases cérébrales (MC) de cancers colo-rectaux (CCR) et de couples MC/CCR primitif.Matériel et Méthodes : 70 MC de CCR appartenant à 67 patients opérés entre juin 2007 et juillet 2020, et 26 CCR primitifs associés, provenant de 5 CHU différents, ont été soumis à une analyse histologique et moléculaire (après accord du comité éthique du CHU de St-Étienne). Tous les patients ont été opérés de leurs métastases et l’analyse était réalisée sur pièce opératoire. Les données cliniques et de survie des patients ont été recueillies. Une analyse biostatistique a été entreprise (Jamovi).Résultats : dans cette analyse, les patients atteints de CCR et présentant des MC sont jeunes au diagnostic du CCR primitif (âge médian = 61 ans). Il n’y a pas d’impact du genre. Ces patients présentent majoritairement un CCR distal (79,7%), en particulier rectal (44,1 %), et muté KRAS (72,9 %). Histologiquement, ce sont des tumeurs avec un stroma fibreux abondant pauvre en lymphocytes. La comparaison des 26 couples métastase-primitif n'a pas, de façon évidente, révélé de différences histo-moléculaires. La survenue de l’évènement métastatique cérébral se produit dans les deux ans suivant le diagnostic du primitif (médiane = 22,3 mois). La présence préalable de métastases pulmonaires est particulièrement fréquente (56,5 %). Parmi les MC, 21 % sont révélatrices de la maladie extra-cérébrale. Le délai de survenue de la MC est étroitement associé au stade TNM et une tendance est observée avec les mutations de BRAF et plusieurs paramètres histologiques : emboles néoplasiques, engainements périnerveux et budding tumoral. Ce délai n’est pas influencé par la réponse histologique du CCR à un traitement néoadjuvant. La survie la plus courte est observée pour les tumeurs rectales (survie globale médiane = 11,0 mois, IC = [6,7 ; 21,0], vs 21,9 mois pour les colons gauches, IC = [7,1 ; 40,9], vs 22,3 mois pour les colons droits, IC = [9,70 ; NaN], p = 0,044) et pour les MC histologiquement peu différenciées (survie globale médiane = 3,5 mois, IC = [0,0 ; NaN], vs 20,5 mois pour les MC moyennement différenciées, IC = [11,0 ; 25,6], vs pour les MC moyennement différenciées, IC = [9,7 ; 34,6], p < 0,001). Les patients présentant une MC synchrone sans métastase extra crânienne ont la meilleure survie (survie globale médiane = 38,3 mois, IC = [21,9 ; NaN], vs 13,0 mois si MC synchrone ou métachrone avec métastases extra-crâniennes, IC = [9,7 ; 21,0], p = 0,055). De même, les patients opérés de leur CCR primitif ont tendance à avoir une meilleure survie que ceux non opérés (survie globale médiane = 18,85 mois, IC = [11,77 ; 23,1] vs 6,23 mois si primitif non opéré, IC = [2,4 ; NaN], p = 0,068).Conclusion : cette étude réalisée sur du matériel de résection chirurgicale de MC de CCR, dessine le profil anatomo-clinique des patients atteints de CCR à risque de développer des MC en pointant un certain nombre d’éléments inattendus ou en renforçant d’autres mieux connus : une survenue relativement précoce de l’évènement métastatique cérébral, un âge jeune au diagnostic du CCR primitif, une grande fréquence de métastases pulmonaires, une sous-population particulière de CCR distaux de stade avancé au diagnostic, riches en stroma, peu inflammatoires et présentant des mutations de KRAS. Le bénéfice à opérer ces MC semble évident en termes de survie, en comparaison aux données de la littérature des patients recevant seulement l’irradiation.

Amyloid-β (Aβ) pathology transmission has been described in patients following iatrogenic exposure to compounds contaminated with Aβ proteins. It can induce cerebral Aβ angiopathy resulting in brain hemorrhages and devastating clinical impacts. Iatrogenic transmission of tau pathology is also suspected but not experimentally proven. In both scenarios, lesions were detected several decades after the putatively triggering medico-surgical act. There is however little information regarding the cognitive repercussions in individuals who do not develop cerebral hemorrhages. In the current study, we inoculated the posterior cingulate cortex and underlying corpus callosum of young adult primates (Microcebus murinus) with either Alzheimer’s disease or control brain extracts. This led to widespread Aβ and tau pathologies in all of the Alzheimer-inoculated animals following a 21-month-long incubation period (n = 12) whereas none of the control brain extract-inoculated animals developed such lesions (n = 6). Aβ deposition affected almost all cortical regions. Tau pathology was also detected in Aβ-deposit-free regions distant from the inoculation sites (e.g. in the entorhinal cortex), while some regions adjacent, but not connected, to the inoculation sites were spared (e.g. the occipital cortex). Alzheimer-inoculated animals developed cognitive deficits and cerebral atrophy compared to controls. These pathologies were induced using two different batches of Alzheimer brain extracts. This is the first experimental demonstration that tau can be transmitted by human brain extracts inoculations in a primate. We also showed for the first time that the transmission of widespread Aβ and tau pathologies can be associated with cognitive decline. Our results thus reinforce the need to organize a systematic monitoring of individuals who underwent procedures associated with a risk of Aβ and tau iatrogenic transmission. They also provide support for Alzheimer brain-inoculated primates as relevant models of Alzheimer pathology.

L’évolution de l’oncologie médicale permet de se demander, si l’amélioration des traitements se répercute sur le type ou, sur la fréquence des métastases cérébrales observées. Ceci, et le fait que les données épidémiologiques concernant cette pathologie restent aujourd’hui encore imprécises, nous a incité à analyser les données anatomo-cliniques des patients atteints de métastases cérébrales et traités à Clermont-Ferrand, sur 10 ans.Notre analyse a étudié 1047 patients diagnostiqués comme porteur d’une ou de plusieurs métastases cérébrales. Parmi eux, 348 ont été traités par une chirurgie suivie d’une radiothérapie et, 699 l’ont été par radiothérapie seule. Les données anatomo-cliniques recueillies incluaient : le délai d’apparition des métastases cérébrales, le délai de survie des patients, le caractère unique ou multiple des métastases cérébrales, la topographie des lésions, le type histologique de la métastase, l’organe d’origine, les mutations théranostiques et le choix thérapeutique.Cette étude a permis de montrer qu’en dix ans, les pratiques thérapeutiques locales ne se sont pas modifiées de façon statistiquement significative même si, on perçoit une décroissance de la radiothérapie seule en faveur de la neurochirurgie. En revanche, dans cette série, la survie des patients traités par chirurgie suivie de radiothérapie étaient significativement meilleure (HR=13.5 mois, IC=[5.8 ; 32.6], p