Functional cognitive disorder (FCD) is a frequent and underrecognized cause of cognitive complaints. Long regarded as a diagnosis of exclusion, conceptual advances have allowed this condition to be integrated within the nosological framework of functional neurological disorders, and to be approached through a positive definition based on the identification of internal inconsistency signs. Nevertheless, establishing a diagnosis of FCD can prove challenging in clinical practice, particularly due to overlapping features with the main differential diagnoses. Through the illustration of a typical clinical case, this article aims to support the positive diagnostic criteria for FCD, and to highlight the key arguments allowing FCD to be distinguished from its main differential diagnoses: cognitive symptoms related to depressive disorder, neurodegenerative diseases at the prodromal stage, and malingering. Diagnosing FCD requires a comprehensive patient evaluation, integrating a qualitative analysis of the interview and the patient's conversational profile alongside the assessment of symptoms, physical examination, and neuropsychological testing.
L’encéphalite auto-immune à anticorps anti-LGI1 est une affection neurologique rare, caractérisée par des auto-anticorps dirigés contre la protéine LGI1, responsables d’une dysfonction synaptique prédominant au niveau des régions temporales et hippocampiques. Elle se manifeste principalement par des troubles cognitifs, des crises épileptiques focales et des dystonies brachio-faciales. L’objectif de cette étude était de décrire les caractéristiques cliniques, paracliniques, thérapeutiques et évolutives des patients pris en charge dans notre centre. Nous avons réalisé une étude rétrospective incluant sept patients diagnostiqués entre 2016 et 2024. L’âge médian au diagnostic était de 71 ans. Les troubles cognitifs, dominés par les troubles mnésiques, constituaient le principal mode de révélation. L’IRM cérébrale était anormale chez six patients (85,7 %). Le diagnostic était confirmé par la détection d’anticorps anti-LGI1 dans le sérum et/ou le liquide céphalorachidien. Un traitement de première ligne associant corticothérapie et immunoglobulines intraveineuses a permis une amélioration clinique précoce chez cinq patients (71,4 %). Toutefois, plusieurs patients ont nécessité un traitement immunosuppresseur de seconde ligne en raison d’une réponse insuffisante ou d’une rechute. Des séquelles neurocognitives persistaient chez certains patients au cours du suivi. Cette série souligne l’importance d’un diagnostic précoce et de l’instauration rapide d’une immunothérapie afin d’améliorer le pronostic fonctionnel et de limiter les séquelles cognitives à long terme. Un suivi prolongé apparaît indispensable pour détecter les rechutes et adapter la stratégie thérapeutique.
Neonatal lupus (NL) is a rare syndrome resulting from the transplacental transfer of maternal anti-Ro/SSA autoantibodies, with or without anti-La/SSB antibodies, and is clinically characterized by cutaneous, hematological, hepatic, and especially cardiac manifestations. The most severe manifestation is congenital heart block (CHB), which occurs in structurally normal fetal hearts, is most often complete and irreversible, and is associated with substantial morbidity and mortality. Although anti-Ro/SSA antibodies are common in women with systemic lupus erythematosus and Sjögren disease, most cases of CHB occur in asymptomatic women, the fetal diagnosis leading to the discovery of the maternal autoantibodies. The pathophysiology of NL is multifactorial, involving autoantibodies, inflammation, and genetic and environmental factors, ultimately leading to fibrosis of the fetal cardiac conduction system. Cutaneous NL is more frequent but transient and generally associated with a favorable prognosis. CHB is usually diagnosed before 24 weeks of gestation and often requires pacemaker implantation during childhood. Screening strategies have evolved, with less emphasis on systematic echocardiographic surveillance. There is growing interest in identifying predictive factors for CHB in order to enable the development of a curative treatment, which to date remains undefined. Indeed, corticosteroid therapy has not demonstrated clear efficacy in this indication and may be associated with substantial adverse effects. In the absence of curative treatment, the management of cardiac NL relies on specialized obstetric and pediatric coordination and long-term cardiology follow-up. Hydroxychloroquine may reduce the risk of recurrence in women who had a first pregnancy complicated with CHB.
Le lupus néonatal (LN) est un syndrome rare lié au passage transplacentaire d’anticorps anti-Ro/SSA maternels, avec ou sans anticorps anti-La/SSB, et qui se manifeste cliniquement par des atteintes cutanées, hématologiques, hépatiques et surtout cardiaques. L’atteinte la plus sévère est le bloc atrioventriculaire congénital (BAVc), qui survient sur cœur fœtal sain, est le plus souvent complet et irréversible, et est responsable d’une morbidité et d’une mortalité significatives. Bien que les anticorps anti-Ro/SSA soient fréquents chez les patientes atteintes de lupus systémique et de maladie de Sjögren, la majorité des BAVc surviennent chez des femmes asymptomatiques, le diagnostic fœtal conduisant alors à la découverte des autoanticorps maternels. La physiopathologie du LN est multifactorielle, impliquant les autoanticorps, l’inflammation, des facteurs génétiques et environnementaux, aboutissant à une fibrose du tissu de conduction cardiaque fœtale. Le LN cutané est plus fréquent mais transitoire et de bon pronostic. Le BAVc est le plus souvent diagnostiqué avant 24 semaines d’aménorrhée et nécessite fréquemment l’implantation d’un pacemaker dans l’enfance. Les stratégies de dépistage ont évolué, limitant la surveillance échographique systématique. La recherche actuelle vise à identifier les facteurs de risque du BAVc, afin de repérer parmi les femmes porteuses d’anticorps anti-Ro/SSA celles présentant un risque élevé et pouvant bénéficier d’une surveillance renforcée, dans l’optique de mettre en place un traitement curatif, malheureusement non défini à ce jour. L’efficacité des corticoïdes fluorés dans cette indication n’est pas démontrée, avec de potentiels effets secondaires importants. En l’absence de traitement curatif, la prise en charge du LN cardiaque repose à ce jour sur une coordination spécialisée obstétricale et pédiatrique et un suivi cardiologique prolongé. L’hydroxychloroquine pourrait diminuer le risque de récidive chez les patientes ayant eu une première grossesse compliquée par un BAVc.
INTRODUCTION:The transition from the French national ranking exam (ECN) to the new fully digital national exam (EDN) has changed evaluation methods by diversifying assessment approaches. This study aimed to evaluate the characteristics of an inter-university EDN-type practice exam. METHODS:We included questions from the EDN practice sessions conducted in April 2024 across 12 French medical universities. Data collected for each question included: context and question type, theme, specialty, Bloom's taxonomy level, knowledge rank, success rate, and discrimination index. RESULTS:Of the 324 questions included in the mixed-format exams administered to students, 304 were analyzed. Multiple-choice questions (MRQs) accounted for 48% of the questions, followed by single-best-answer questions (SRQs, 17%) and short-answer questions (SAQs, 13%). Medical specialties were the most represented (82%). Most questions targeted level A of knowledge (65%) and Bloom's level 2 (53%). The overall success rate was 44%. SAQs showed the highest discriminatory capacity compared to other types. An inverted U-shaped relationship was observed between question success rate and discrimination index: questions with intermediate success rates (45-65%) best discriminated between students. CONCLUSION:Despite greater diversity in assessment methods introduced by the new reform, MRQs remain predominant in interfaculty practice exams EDN-type exams. SAQs provide stronger discriminatory power. These findings highlight the value of expanding assessment formats to strengthen the validity of the EDN.
Le syndrome des anti-synthétases (SAS) est une maladie auto-immune systémique associée à la présence d’anticorps anti-ARNt synthétase, essentiellement anti-Jo1, PL7 et PL12. Il peut être limité à un organe et touche le poumon dans environ 75 % des cas. L’atteinte pulmonaire et sa sévérité conditionnent le pronostic et le traitement. Le traitement est basé sur la corticothérapie à forte dose qui est efficace pour induire la rémission mais les rechutes surviennent dans environ 50 % en cas de monothérapie, et l’ajout d’un immunosuppresseur d’emblée a montré un bénéfice sur la survie et la réduction des rechutes. Les immunosuppresseurs les plus fréquemment utilisés sont l’azathioprine (AZA), le mycophénolate mofétil (MMF), le méthotrexate (MTX), le tacrolimus (TAC), le rituximab (RTX) et le cyclophosphamide (CYC). Les CAR-T (Chimeric Antigen Receptor T) cells et anticorps bispécifiques sont des traitements innovants prometteurs. Les anti-fibrosants peuvent être utilisés en cas de fibrose pulmonaire progressive. Cependant il n’y a pas de recommandation thérapeutique dédiée au SAS, les données étant essentiellement basées sur des études rétrospectives ou extrapolées à partir d’essais cliniques incluant des patients atteints de myopathie inflammatoire ou de pneumopathie interstitielle diffuse associée aux connectivites. Cette mise au point vise à synthétiser les données existantes d’efficacité et de tolérance des traitements dans le SAS, et à présenter un algorithme de traitement actualisé.
Acute pericarditis is generally a benign condition, yet 15-30% of patients will develop recurrent pericarditis. Standard first-line therapy combines non-steroidal anti-inflammatory drugs or aspirin with colchicine, which reduces but does not eliminate the risk of recurrence. Patients presenting with a high inflammatory burden, subacute evolution or large pericardial effusion are particularly prone to recurrence, and corticosteroid exposure - still frequent in clinical practice - further increases this risk. Over the last decade, the central role of interleukin-1 (IL-1) in pericardial inflammation has been demonstrated, and IL-1 inhibitors have emerged as the most effective treatment for colchicine-resistant or corticosteroid-dependent recurrent pericarditis. Anakinra, rilonacept and other IL-1-targeting agents provide rapid symptom resolution and dramatically reduce recurrences, thereby transforming the management of difficult-to-treat forms of the disease. This review summarizes current knowledge on the IL-1 pathway in pericarditis and examines whether earlier, targeted intervention could modify disease trajectory, particularly in patients identified as having a high risk of recurrence at presentation. Drawing parallels with Still's disease, in which early IL-1 inhibition improves long-term outcomes, these data support the need for high-quality trials evaluating IL-1 blockade as a first-line strategy in selected patients with acute pericarditis.
Uveitis encompasses a heterogeneous spectrum of etiologies, including systemic inflammatory diseases, infections, specific ophthalmologic entities, and pseudo-uveitis. The diagnostic approach relies on an algorithmic strategy aimed at the early identification of a curable etiology and/or an underlying condition suitable for targeted therapy, while taking into account the severity and relative frequency of the various causes. The prospective ULISSE study showed that a standardized diagnostic approach based on the anatomo-clinical classification of uveitis achieved a diagnostic yield comparable to unrestricted testing, while substantially reducing both the number and cost of investigations. Etiological diagnosis is primarily based on anatomo-clinical analysis of uveitis, integrating the site of inflammation, disease course, laterality, and specific ophthalmologic features. Subsequently, consideration of epidemiological and demographic factors, medical history, and extra-ophthalmologic clinical examination allows further refinement of the diagnostic workup. Complementary investigations should be prioritized and targeted, except for a minimal systematic baseline evaluation, as the diagnostic yield of non-directed testing is very low. Clinical decision-support tools based on artificial intelligence (AI) represent a major advancement. Machine learning models integrating clinical, ophthalmologic, laboratory, and imaging data available from the initial consultation achieve etiological prediction performances comparable to those of experts with access to a complete diagnostic workup. These multimodal AI models could transform diagnostic strategies by enabling a personalized etiological assessment based on the prioritization and dynamic adaptation of complementary investigations. However, their implementation in routine clinical practice will require prior medico-economic validation through controlled comparative studies.
INTRODUCTION:Rituximab is used for treating autoimmune cytopenia and associated diseases including autoimmune haemolytic anaemia; immune thrombopenia, systemic lupus erythematosus and antiphospholipid syndrome. However, rituximab may induce acquired immune deficiency in some patients, particularly hypogammaglobulinemia (HG), whose risk factors remain poorly defined. PATIENTS AND METHODS:We conducted a retrospective multicentre study including patients with autoimmune cytopenia and related diseases who received at least one rituximab infusion to validate serum protein electrophoresis (SE) as a screening tool for HG and to assess its incidence, risk factors, and clinical outcomes. Univariate and multivariate Cox analysis were performed to characterize predictor of HG. RESULTS:Among 47 patients (391.89 person-years follow-up), Gammaglobulin evaluation on SE strongly correlated with IgG (ρ = 0.97, P=2.2×10-16). HG, defined as gammaglobulin levels <7g/L on SE after rituximab exposure, occurred in 14.9% of patients and was associated with a higher cumulative number of rituximab injections (median 11 vs. 1.5; P=0.033). All immunoglobulin isotypes declined after treatment, and severe infections were more frequent in HG patients. Although cumulative rituximab dose and corticosteroid exposure were associated with HG in univariate analysis, these findings were not confirmed in multivariate models. CONCLUSION:SE appears to be a reliable screening tool for HG, but larger studies are needed to clarify risk factors.
Les uvéites regroupent des étiologies hétérogènes, incluant des maladies inflammatoires systémiques, des infections, des entités ophtalmologiques et des pseudo-uvéites. La démarche diagnostique repose sur une approche algorithmique visant à identifier précocement une étiologie curable et/ou une pathologie sous-jacente susceptible de bénéficier d’un traitement spécifique, tout en tenant compte de la sévérité et de la fréquence des différentes étiologies. L’étude prospective ULISSE a démontré qu’une stratégie diagnostique standardisée, guidée par le type anatomoclinique de l’uvéite, permettait un rendement diagnostique comparable à une prescription non protocolisée, avec une réduction significative du nombre et du coût des examens réalisés. Le diagnostic étiologique s’appuie en première intention sur l’analyse anatomoclinique de l’uvéite, intégrant la localisation de l’inflammation, son évolution, sa latéralité et les signes spécifiques. L’analyse secondaire des données épidémiologiques et démographiques, de l’anamnèse et de l’examen clinique extra-ophtalmologique permet d’affiner l’orientation du bilan. Les examens complémentaires doivent être hiérarchisés et ciblés, à l’exception d’un bilan minimal systématique, puisque la rentabilité d’examens complémentaires non orientés est très faible. Les outils d’intelligence artificielle (IA) d’aide à la décision clinique constituent une avancée majeure. Les modèles d’apprentissage automatique intégrant les données cliniques, ophtalmologiques, paracliniques et d’imagerie disponibles dès la première consultation atteignent des performances de prédiction étiologique comparables à celles d’experts disposant du bilan diagnostique complet. Ces modèles d’IA multimodaux pourraient transformer la stratégie diagnostique en permettant un bilan étiologique personnalisé, fondé sur une hiérarchisation et une adaptation dynamique des examens complémentaires. Leur implémentation en pratique clinique nécessitera toutefois une validation médico-économique par des études contrôlées comparatives.
Primary central nervous system vasculitis (PCNSV) is a rare and heterogeneous disease whose diagnosis relies on a combination of clinical, radiological, and laboratory findings, and which requires a multidisciplinary hospital-based approach involving neurologists, neuroradiologists, and internists (or rheumatologists). This protocol is based on expert consensus and registry data, and aims to optimise and harmonise the diagnostic and therapeutic approach to PCNSV. Diagnosis is challenging due to non-specific clinical and radiological features. The diagnostic process includes (1) confirming vascular involvement (via MRI and angiography), and demonstrating the inflammatory process (via lumbar puncture, contrast-enhanced MRI and vascular wall sequences), (2) excluding more common differential diagnoses (especially intracranial atherosclerosis in patients with vascular stenosis), (3) and as often as possible discussing a brain or meningeal biopsy. Histological evidence obtained from a biopsy remains the gold standard for diagnosis, especially in case of small-vessel involvement. The therapeutic strategy is divided into induction (to achieve remission) and maintenance phases (to prevent relapse). Induction therapy consists of high-dose corticosteroids combined with an immunosuppressant, most often intravenous cyclophosphamide, to achieve remission. The initial corticosteroid dose is maintained for 2-3 weeks, then gradually tapered over 12-18 months. Once remission is achieved, maintenance therapy is introduced, typically using oral or subcutaneous immunosuppressants such as azathioprine, methotrexate, or mycophenolate mofetil, for 18-24 months. Preventive measures address treatment-related complications, including osteoporosis, infections, and metabolic disturbances. Relapses occur in a significant proportion of patients, necessitating prompt reassessment and possible escalation of immunosuppression. These guidelines emphasise the importance of individualised care, regular follow-up, and treatment adjustment based on disease activity and patient tolerance.
Anti-synthetase syndrome (ASS) is a systemic autoimmune disease associated with the presence of anti-aminoacyl tRNA synthetase antibodies, primarily anti-Jo1, PL7, and PL12. It may be limited to a single organ and involves the lungs in approximately 75% of cases. Pulmonary involvement and its severity determine both prognosis and treatment. Management relies on high-dose corticosteroid therapy, which is effective in inducing remission. Nevertheless, relapses occur in roughly 50% of cases with monotherapy by corticosteroid. The early addition of an immunosuppressant has demonstrated benefits in terms of survival and relapse reduction. The most commonly used immunosuppressants are azathioprine (AZA), mycophenolate mofetil (MMF), methotrexate (MTX), tacrolimus (TAC), rituximab (RTX), and cyclophosphamide (CYC). Chimeric Antigen Receptor T (CAR-T) cells and bispecific antibodies are promising innovative therapies. Antifibrotic drugs can be used in cases of progressive pulmonary fibrosis. However, there are currently no dedicated treatment guidelines for ASS, as available data are mainly derived from retrospective studies or extrapolated from clinical trials including patients with inflammatory myopathy or connective tissue disease-associated interstitial lung disease. This review aims to synthesize existing data on the efficacy and safety of treatments in ASS and to present an updated treatment algorithm.
