Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Macro-adénomes hypophysaires non-fonctionnels‎ : analyse rétrospective chez 130 patients consécutifs opérés au CHU de Rouen

Les adénomes hypophysaires représentent environ 15% de l'ensemble des tumeurs intracrâniennes. Les macro-adénomes non-fonctionnels sont le plus souvent diagnostiqués sur le syndrome tumoral et la compression des voies optiques. La chirurgie, essentiellement trans-sphénoïdale a pour but d'améliorer les symptômes neurologiques sans aggraver la fonction endocrinienne, tout en optimisant la qualité de l'exérèse tumorale afin de limiter le risque de récidive. OBJECTIFS : L'objectif principal de ce travail rétrospectif, conduit au CHU de Rouen, était d'évaluer la qualité d'exérèse tumorale et d'identifier les facteurs pronostiques influençant cette exérèse. Nous évaluions également les complications péri-opératoires, les résultats visuels et endocriniens ainsi que la récidive tumorale. PATIENTS ET MÉTHODES : 130 patients consécutifs (âge moyen = 58,8 ± 14,9 ans) ont été opérés par voie trans-sphénoïdale de macro-adénomes hypophysaires non-secrétant entre le 01/01/2009 et le 31/12/2013. RÉSULTATS : Nous observions 37,7 % d'exérèse complète et 56,4 % d'exérèse incomplète. La taille tumorale, l'envahissement des sinus caverneux de grade 3 et 4 de Knosp et une expansion de type IV selon la classification de Wilson-Hardy étaient prédictifs d'une exérèse incomplète (p < 0,0001). Parmi les 123 évaluations ophtalmologiques disponibles, 72 patients (55,4 %) présentaient une fonction visuelle (campimétrie et acuité visuelle) normale versus 36 (27,7 %) en préopératoire (p < 0,0001). Pour la majorité des patients, en postopératoire, la fonction visuelle était soit améliorée (n = 74 ; 56,9 %) soit stabilisée (n = 48 ; 36,9 %). Nous observions en postopératoire précoce un diabète insipide chez 22 patients (16,9 %), mais permanent chez seulement 3 (2,3 %). Seuls 20 % des patients présentaient un pan-hypopituitarisme et 41 patients (31,5 %) prenaient un ou plusieurs traitement hormonaux substitutifs. Deux décès sont survenus après intervention (un vasospasme concomitant d'une apoplexie sévère et une perforation d'ulcère), 5 rhinorrhées, 3 hématomes compressifs. Six patients (4,6 %) ont nécessité une ré-intervention précoce. La récidive tumorale était observée chez 15 patients sur 125, qui présentaient tous un reliquat postopératoire, à un délai moyen de 28,3 mois. Dans le groupe avec reliquat et dans celui sans reliquat, la survie sans récidive était respectivement, à 12 mois de 95,5 % versus 100%, à 24 mois de 85,6 % versus 100 % et à 36 mois de74,5 % versus 100 % (p = 0,0067). CONCLUSION : Nous retrouvions un taux d'exérèse comparable à ceux des grandes séries microchirurgicales. L'exérèse incomplète était significativement associée au risque de récidive tumorale. Les résultats ophtalmologiques étaient très satisfaisants car plus de la moitié des patients étaient améliorés en postopératoire et la morbidité endocrinienne était faible

Intérêt de la spectroscopie par résonance magnétique in vivo à l'hydrogène 1H dans l'étude de l'hépatopathie chronique (étude préliminaire)

POITIERS-BU Médecine pharmacie (861942103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Validation of the superior interhemispheric approach for tuberculum sellae meningioma

International audienceObjectThe objective of this study was to evaluate the ophthalmological outcome, nonvisual morbidity, and surgical complications after tuberculum sellae meningioma (TSM) removal using a superior interhemispheric approach.MethodsIn the last decade, 20 consecutive patients with TSM underwent operations using the superior interhemispheric approach. Visual acuity, visual field, and ocular fundus examination were assessed both preoperatively and 6-months postoperatively. Nonvisual morbidity was determined at an early postoperative period and at 6 months based on assessment of the Karnofsky Performance Scale score, leakage of CSF, endocrinological status, and olfactory function, which was assessed using a visual analog scale (VAS). The potential brain injury related to the approach was assessed by MRI at 6 months. Magnetic resonance imaging was then performed yearly to detect a recurrence. The mean follow up was 56.3 ± 34 months.ResultsThe primary presenting symptom for diagnosis of TSM in 20 patients (female:male ratio of 6.6:1, mean age 59.1 ± 11.1 years) was visual disturbance in 12 patients (60%), headache in 4 (20%), cognitive alteration in 1 (5%), epilepsy in 2 (10%), and accidental in 1 (5%). In a total of 40 eyes, 17 eyes in 11 patients presented with preoperative deterioration of visual acuity. Postoperatively, the visual acuity improved in 13 eyes in 8 patients (72.8%), remained unchanged in 3 eyes in 2 patients (18.2%) and deteriorated in 1 patient (9%). The nonvisual morbidity included olfactory deterioration in 7 patients (35%), and panhypopituitarism in 1 patient (5%). No patients experienced a CSF leak. The impact of olfactory deterioration on the quality of life, as estimated by a VAS score (range 0–10), was a mean of 5.7 ± 2.2 (95% CI 4.1–7.3). On the follow-up MRI, no additional lesions or recurrences were observed on the medial aspect of the frontal lobe along the surgical corridor.ConclusionsThe superior interhemispheric approach appears to be effective in resolving the problem of visual deterioration due to a TSM, without inducing surgical injury on the brain surface along the surgical corridor. Olfactory deterioration remained the challenging predominant nonvisual morbidity using this approach

Brain Calcifications in Adult-Onset Genetic Leukoencephalopathies: A Review

International audienceImportance: Adult-onset genetic leukoencephalopathies and leukodystrophies are increasingly recognized as a heterogeneous group of disorders with new diagnostic approaches and potential treatments. In the new era of genomics, the challenging interpretation of individual genetic variations requires an accurate phenotypic description and classification. Clinical and magnetic resonance imaging (MRI)-based approaches have been proposed to improve the diagnostic process of adult-onset leukoencephalopathies. Cerebral calcifications, when associated with white matter hyperintensities, are of major importance in the decision-making process to focus the diagnosis among the diversity of rare causes. Observations: This literature review demonstrated that the morphologic features and topography of the calcifications observed in a careful combined analysis of computed tomographic and MRI scans may help indicate the diagnosis of adult-onset genetic leukoencephalopathies. Vascular genetic leukoencephalopathies are an important cause of leukoencephalopathy with calcifications. Among them, COL4A1-related disorders are frequently associated with spotlike calcifications in the basal ganglia. Adult-onset leukoencephalopathy with axonal spheroids, a probably underestimated disorder, is associated with a specific pattern of calcifications: small, symmetric, sparing the basal ganglia, and a stepping stone appearance in the frontal pericallosal region. Moreover, disorders primarily associated with basal ganglia calcifications, such as primary familial brain calcifications, can be associated with marked leukoencephalopathy. Conclusions and Relevance: The number of identified causes of adult-onset genetic leukoencephalopathies has recently increased. A diagnostic algorithm should take into account the pattern of calcifications to better target the genetic analyses

Comparison of electromagnetic neuronavigation system and free-hand method for ventricular catheter placement in internal shunt

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[Multiple cervical arterial dissections in two brothers: fibro-muscular dysplasia or connective tissue disease?]

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Brain perfusion in adult patients with acute myeloblastic leukemia before and after cytosine arabinoside

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Brain perfusion in adult patients with acute myeloblastic leukemia before and after cytosine arabinoside

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