Mutations and Deletions in PCDH19 Account for Various Familial or Isolated Epilepsies in Females

Mutations in PCDH19, encoding protocadherin 19 on chromosome X, cause familial epilepsy and mental retardation limited to females or Dravet-like syndrome. Heterozygous females are affected while hemizygous males are spared, this unusual mode of inheritance being probably due to a mechanism called cellular interference. To extend the mutational and clinical spectra associated with PCDH19, we screened 150 unrelated patients (113 females) with febrile and afebrile seizures for mutations or rearrangements in the gene. Fifteen novel point mutations were identified in 15 female patients (6 sporadic and 9 familial cases). In addition, qPCR revealed two whole gene deletions and one partial deletion in 3 sporadic female patients. Clinical features were highly variable but included almost constantly a high sensitivity to fever and clusters of brief seizures. Interestingly, cognitive functions were normal in several family members of 2 families: the familial condition in family 1 was suggestive of Generalized Epilepsy with Febrile Seizures Plus (GEFS+) whereas all three affected females had partial cryptogenic epilepsy. These results show that mutations in PCDH19 are a relatively frequent cause of epilepsy in females and should be considered even in absence of family history and/or mental retardation. © 2010 Wiley-Liss, Inc

Large-scale real-world data on a multidisciplinary approach to spinal cord stimulation for persistent spinal pain syndromes: first evaluation of the Neuro-Pain® nationwide screening and follow-up interactive register

IntroductionSpinal cord stimulation is a common treatment option for neuropathic pain conditions. Despite its extensive use and multiple technological evolutions, long term efficacy of spinal cord stimulation is debated. Most studies on spinal cord stimulation include a rather limited number of patients and/or follow-ups over a limited period. Therefore, there is an urgent need for real-world, long-term data.MethodsIn 2018, the Belgian government initiated a nationwide secure platform for the follow-up of all new and existing spinal cord stimulation therapies. This is a unique approach used worldwide. Four years after the start of centralized recording, the first global extraction of data was performed.ResultsHerein, we present the findings, detailing the different steps in the centralized procedure, as well as the observed patient and treatment characteristics. Furthermore, we identified dropouts during the screening process, the reasons behind discontinuation, and the evolution of key indicators during the trial period. In addition, we obtained the first insights into the evolution of the clinical impact of permanent implants on the overall functioning and quality of life of patients in the long-term.DiscussionAlthough these findings are the results of the first data extraction, some interesting conclusions can be drawn. The long-term outcomes of neuromodulation are complex and subject to many variables. Future data extraction will allow us to identify these confounding factors and the early predictors of success. In addition, we will propose further optimization of the current process

Mutations in Eml1 lead to ectopic progenitors and neuronal heterotopia in mouse and human.

Neuronal migration disorders such as lissencephaly and subcortical band heterotopia are associated with epilepsy and intellectual disability. DCX, PAFAH1B1 and TUBA1A are mutated in these disorders; however, corresponding mouse mutants do not show heterotopic neurons in the neocortex. In contrast, spontaneously arisen HeCo mice display this phenotype, and our study revealed that misplaced apical progenitors contribute to heterotopia formation. While HeCo neurons migrated at the same speed as wild type, abnormally distributed dividing progenitors were found throughout the cortical wall from embryonic day 13. We identified Eml1, encoding a microtubule-associated protein, as the gene mutated in HeCo mice. Full-length transcripts were lacking as a result of a retrotransposon insertion in an intron. Eml1 knockdown mimicked the HeCo progenitor phenotype and reexpression rescued it. We further found EML1 to be mutated in ribbon-like heterotopia in humans. Our data link abnormal spindle orientations, ectopic progenitors and severe heterotopia in mouse and human

Douleur et Francophonie : divergences et convergences

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Recommandations diagnostiques et de prise en charge thérapeutique des syndromes douloureux régionaux complexes : les recommandations de Lille

La Société française d’étude et de traitement de la douleur présente les recommandations de diagnostic et de prise en charge des syndromes douloureux régionaux complexes. Ces recommandations ont été élaborées par des experts hos‑ pitaliers et libéraux (rhumatologue, neurologue, anesthésiste, chirurgien orthopédique, médecin nucléaire, algologue, médecin généraliste, psychologue, infirmière, IAD, kinési‑ thérapeute) et un représentant d’association de patients. Une analyse systématique de la littérature a été réalisée. Vingt‑six recommandations sont proposées. Elles mettent en avant l’uti‑ lisation des critères de Budapest pour le diagnostic clinique, la prise en charge réadaptative proposée systématiquemen

Le modèle biopsychosocial: Beaucoup plus qu'un supplément d'empathie

Despite several limits, the biopsychosocial model is the best available medical model today. However, it is still misunderstood and underused. On a theoretical point of view, this system of health-explanatory hypotheses considers biological, psychological and social factors on equal grounds, in a complex, multiple and circular system of causes and effects. A clinical practice derived from this model permanently integrates the biological, psychological and social perspectives. It necessitates active participation of the patient and stresses the importance of educational aspects. The therapeutic relationship is deeply modified. A better diffusion of the biopsychosocial model necessitates changes in teaching, research and increased resources allocated to the clinical encounter

La standardisation des soins : perspectives et propositions

Ne niant pas la standardisation des soins dans la pratique soignante, l'auteur la dénonce parce qu'elle ne tient pas compte de la réalité des situations individuelles. Elle fait aussi part de sa nette préférence pour un modèle biopsychosocial de la santé, qu'elle préfère à la gestion politico-économique actuelle de la sant

La médecine fondée sur les preuves : un outil de contrôle des soins de santé ? Application au traitement de la douleur

Evidence-based medicine (EBM) is described by its proponents as the only tool allowing a valid and unbiased evaluation of diagnostic and therapeutic medical procedures. As a consequence, numerous health-care managers consider it a method of distinguishing between effective procedures deserving funding and those found ineffective. Several authors, however, have questioned the capacity of EBM to achieve these objectives on epistemological, methodological, ethical, political, economical, anthropological and sociological grounds. A review of their objections shows that, although EBM is a powerful tool for analysing specific, well-defined questions, a wide range of clinical problems, such as chronic pain management, cannot be adequately assessed by its methods. The dogmatic use of EBM, therefore, is philosophically and scientifically unsound, alienating for patients and clinicians, and unethical. It contributes to the expansion of the biomedical model of clinical care at the expense of the more appropriate biopsychosocial model

Transition et soins de santé

Les soins de santé sont en crise et ce n’est pas (uniquement) la faute d’un virus... La pandémie que nous traversons actuellement a servi de révélateur à un malaise beaucoup plus profond dont témoigne, par exemple, le collectif « santé en lutte1 ». Le manque de personnel, le sous-financement du temps passé avec le patient et l’inflation administrative induisent épuisement et démotivation. L’essentiel – le soin (« care ») – est de plus en plus réduit à la portion congrue. Qu’une réforme soit nécessaire ne semble heureusement plus contesté. Mais quelle forme prendra celle-ci ? Suffira-il d’augmenter le financement de certaines activités ? Par ailleurs, les modifications environnementales qui s’annoncent – réchauffement climatique, pic pétrolier et leurs conséquences – ont de plus en plus d’impact sur la santé des populations et réduiront les moyens matériels dont nous disposerons pour les soigner. De plus, les soins de santé contribuent à la dégradation de l’environnement, tant en termes d’émissions de CO2 que de largage de divers polluants. Pourtant, la dimension environnementale est habituellement absente des discussions concernant la réforme des soins de santé. Lorsqu’elle est présente2, elle se limite à la question de l’adaptation du système de soins aux modifications climatiques, sans aborder l’autre versant de cette question, la responsabilité environnementale des soins de santé. Cette étude a pour objectif d’ouvrir le débat sur le sujet en abordant successivement les interactions à double sens entre environnement et (soins de) santé, puis quelques paradoxes du système actuel et enfin les grandes lignes d’une stratégie possible de soins de santé durables