Outcome of psychogenic non-epileptic seizures following diagnosis in the epilepsy monitoring unit

ObjectiveTo study the outcome of patients with psychogenic non-epileptic seizures (PNES) after their diagnosis in the epilepsy monitoring unit (EMU).MethodsPatients diagnosed in our EMU with definite PNES between January 2009 and May 2023 were contacted by phone, and those who agreed to participate were asked a set of predetermined questions. Comparative analyses were carried out on several variables before and after diagnosis: number of participants with daily PNES, number of visits to the emergency department, number of participants who consulted their general practitioner or a neurologist outside of a scheduled follow-up, number of participants who took antiseizure medications (ASMs) or psychotropic drugs, and employment status.ResultsOut of the 103 patients with a definite diagnosis of PNES, 61 patients (79% female) accepted to participate in our study. The median age at PNES onset was 35 years, and the median delay to diagnosis was 3 years. Almost two-thirds (62%) were receiving ASMs and 40% psychotropic drugs. The mean stay at the EMU was 5 days. PNES diagnosis was explained to almost all patients (97%) by the end of their EMU stay and was well-accepted by most (89%). When contacted, 46% of participants no longer had PNES; 32% mentioned that their PNES had ceased immediately upon communication of the diagnosis. The median follow-up duration was 51 months. Fewer patients had daily seizures after the diagnosis (18 vs. 38%; p < 0.0455). Similarly, the median number of emergency department visits was significantly lower (0 vs. 2; p < 0.001). Only 17 patients consulted their general practitioner (vs. 40, p < 0.001) and 20 a neurologist (vs. 55, p < 0.001) after a PNES attack outside of a scheduled follow-up. The use of ASMs was also significantly reduced from 70 to 33% (p < 0.01), with only one still taking an ASM for its antiseizure properties. Significantly more participants were working at last follow-up than at PNES diagnosis (49 vs. 25%; p < 0.001).ConclusionOur study revealed a relatively favorable long-term outcome of definite PNES diagnosed in the EMU that translated in significant reductions in PNES frequency, health care utilization and ASM use, as well as a significant increase in employment rate

Clinical heterogeneity of neuro-inflammatory PET profiles in early Alzheimer’s disease

The relationship between neuroinflammation and cognition remains uncertain in early Alzheimer’s disease (AD). We performed a cross-sectional study to assess how neuroinflammation is related to cognition using TSPO PET imaging and a multi-domain neuropsychological assessment. A standard uptake value ratio (SUVR) analysis was performed to measure [18F]-DPA-714 binding using the cerebellar cortex or the whole brain as a (pseudo)reference region. Among 29 patients with early AD, the pattern of neuroinflammation was heterogeneous and exhibited no correlation with cognition at voxel-wise, regional or whole-brain level. The distribution of the SUVR values was independent of sex, APOE phenotype, early and late onset of symptoms and the presence of cerebral amyloid angiopathy. However, we were able to demonstrate a complex dissociation as some patients with similar PET pattern had opposed neuropsychological profiles while other patients with opposite PET profiles had similar neuropsychological presentation. Further studies are needed to explore how this heterogeneity impacts disease progression

Pronostic cognitif dans les arrêts cardiorespiratoires : place de l'IRM cérébrale ?

L’ACR est responsable de lésions cérébrales d’hypoxie-ischémie entrainant un décès à court terme et des troubles cognitifs à long terme. L’IRM cérébrale effectuée en phase aiguë permettrait de prédire un mauvais pronostic de survie globale à court terme. Le rôle prédictif de l’IRM cérébrale dans le devenir neuropsychologique à distance d’un ACR reste peu investigué. Seules cinq études, dont quatre en VBM, ont spécifiquement étudié les corrélations entre IRM cérébrale et cognition post ACR. Ces études sont cependant limitées par des évaluations neuropsychologiques succinctes, un faible effectif et/ou une analyse a priori en imagerie. Objectif : Déterminer le caractère pronostic de l’IRM cérébrale réalisée en phase aigüe d’un ACR dans la persistance de troubles neuropsychologiques à plus de 3 mois. Matériels et méthodes : Une IRM cérébrale et une batterie extensive et standardisée de tests neuropsychologiques étaient proposées dans le premier mois d’un ACR extra hospitalier. L’IRM permettait : (1) une évaluation lésionnelle vasculaire et (2) une analyse volumétrique par VBM en comparaison à un groupe de 21 sujets contrôles sains. Une 2ème évaluation neuropsychologique était répétée à plus de 3 mois à partir de laquelle deux groupes étaient constitués : déficitaire Vs. préservé. Les patients étaient classés déficitaires s’ils présentaient un troubles mnésique et/ou dysexécutif et/ou attentionnel. Résultats : Vingt-cinq patients ont été inclus (14 dans le groupe « préservé » et 11 « déficitaires »). La durée de low flow était supérieure dans le groupe déficitaire (20 ± 21.14 Vs. 10 ± 10.77, p= .045). Les lésions vasculaires ne différaient pas entre les deux groupes ACR (p=.41). Le volume thalamique D des ACR déficitaires était inférieur à celui des contrôles et des ACR préservés (respectivement 0.48 ± 0.12 Vs. 0.72 ± 0.1 Vs. 0.69 ± 0.09 ; p Discussion : Un volume thalamique D diminué plutôt qu’une atteinte diffuse du volume cérébral pourrait rendre compte des déficits cognitifs observés à plus de 3 mois de l’ACR. Il pourrait résulter de deux mécanismes : (1) responsabilité directe de l’hypoxie-ischémie dans l’apparition d’une atrophie précoce ou (2) fragilité antérieure à l’ACR avec atrophie préexistante. Conclusion et perspectives : Notre étude souligne l’intérêt potentiel de l’IRM cérébrale en VBM dans l’évaluation pronostique des troubles cognitifs à distance d’un ACR. La réalisation d’une étude longitudinale incluant des patients coronariens avec des FRV permettrait d’évaluer les volumes cérébraux chez une population à risque d’ACR et la réalisation de séquences complémentaires en connectivité structurale et fonctionnelle permettrait d’étudier la connectivité et les anomalies de réseaux induits par l’ACR

Isoform diversity in the Arp2/3 complex determines actin filament dynamics.

International audienceThe Arp2/3 complex consists of seven evolutionarily conserved subunits (Arp2, Arp3 and ARPC1-5) and plays an essential role in generating branched actin filament networks during many different cellular processes. In mammals, however, the ARPC1 and ARPC5 subunits are each encoded by two isoforms that are 67% identical. This raises the possibility that Arp2/3 complexes with different properties may exist. We found that Arp2/3 complexes containing ARPC1B and ARPC5L are significantly better at promoting actin assembly than those with ARPC1A and ARPC5, both in cells and in vitro. Branched actin networks induced by complexes containing ARPC1B or ARPC5L are also disassembled ∼2-fold slower than those formed by their counterparts. This difference reflects the ability of cortactin to stabilize ARPC1B- and ARPC5L- but not ARPC1A- and ARPC5-containing complexes against coronin-mediated disassembly. Our observations demonstrate that the Arp2/3 complex in higher eukaryotes is actually a family of complexes with different properties

Data_Sheet_1_Outcome of psychogenic non-epileptic seizures following diagnosis in the epilepsy monitoring unit.pdf

ObjectiveTo study the outcome of patients with psychogenic non-epileptic seizures (PNES) after their diagnosis in the epilepsy monitoring unit (EMU).MethodsPatients diagnosed in our EMU with definite PNES between January 2009 and May 2023 were contacted by phone, and those who agreed to participate were asked a set of predetermined questions. Comparative analyses were carried out on several variables before and after diagnosis: number of participants with daily PNES, number of visits to the emergency department, number of participants who consulted their general practitioner or a neurologist outside of a scheduled follow-up, number of participants who took antiseizure medications (ASMs) or psychotropic drugs, and employment status.ResultsOut of the 103 patients with a definite diagnosis of PNES, 61 patients (79% female) accepted to participate in our study. The median age at PNES onset was 35 years, and the median delay to diagnosis was 3 years. Almost two-thirds (62%) were receiving ASMs and 40% psychotropic drugs. The mean stay at the EMU was 5 days. PNES diagnosis was explained to almost all patients (97%) by the end of their EMU stay and was well-accepted by most (89%). When contacted, 46% of participants no longer had PNES; 32% mentioned that their PNES had ceased immediately upon communication of the diagnosis. The median follow-up duration was 51 months. Fewer patients had daily seizures after the diagnosis (18 vs. 38%; p ConclusionOur study revealed a relatively favorable long-term outcome of definite PNES diagnosed in the EMU that translated in significant reductions in PNES frequency, health care utilization and ASM use, as well as a significant increase in employment rate.</p

Penetrance estimation of Alzheimer disease in SORL1 loss-of-function variant carriers using a family-based strategy and stratification by APOE genotypes

International audienceAbstract Background Alzheimer disease (AD) is a common complex disorder with a high genetic component. Loss-of-function (LoF) SORL1 variants are one of the strongest AD genetic risk factors. Estimating their age-related penetrance is essential before putative use for genetic counseling or preventive trials. However, relative rarity and co-occurrence with the main AD risk factor, APOE -ε4, make such estimations difficult. Methods We proposed to estimate the age-related penetrance of SORL1 -LoF variants through a survival framework by estimating the conditional instantaneous risk combining (i) a baseline for non-carriers of SORL1- LoF variants, stratified by APOE-ε4 , derived from the Rotterdam study ( N = 12,255), and (ii) an age-dependent proportional hazard effect for SORL1- LoF variants estimated from 27 extended pedigrees (including 307 relatives ≥ 40 years old, 45 of them having genotyping information) recruited from the French reference center for young Alzheimer patients. We embedded this model into an expectation-maximization algorithm to accommodate for missing genotypes. To correct for ascertainment bias, proband phenotypes were omitted. Then, we assessed if our penetrance curves were concordant with age distributions of APOE -ε4-stratified SORL1- LoF variant carriers detected among sequencing data of 13,007 cases and 10,182 controls from European and American case-control study consortia. Results SORL1- LoF variants penetrance curves reached 100% (95% confidence interval [99–100%]) by age 70 among APOE -ε4ε4 carriers only, compared with 56% [40–72%] and 37% [26–51%] in ε4 heterozygous carriers and ε4 non-carriers, respectively. These estimates were fully consistent with observed age distributions of SORL1- LoF variant carriers in case-control study data. Conclusions We conclude that SORL1- LoF variants should be interpreted in light of APOE genotypes for future clinical applications