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The French migraine management recommendations were published in 2021. However, in the last three years, new data have come to light and new drugs have been approved (eptinezumab, rimegepant and atogepant) by the European Medicines Agency that require us to take a position on their use and to update certain elements of the recommendations. The first important message concerns the position of the French Headache Society on the use of preventive treatments (monoclonal antibodies and gepants) targeting the calcitonin gene-related peptide (CGRP) pathway. In terms of efficacy and safety, and as suggested by other national headache societies, these treatments can be offered as first-line treatment, although the scope defined by the French national health authority for possible reimbursement is limited to patients with severe migraine, at least eight headache days per month and for whom two previous preventive treatments have failed. Another important change concerns the position of topiramate as a preventive treatment for migraine in women of childbearing age. This treatment has been proposed as a first-line treatment for chronic migraine. However, recent pharmacovigilance data have highlighted a potential adverse effect on neurodevelopment in children exposed in utero. As a result, this treatment is formally contraindicated during pregnancy and must be used with extreme caution in women of childbearing age (effective contraception, no therapeutic alternative available and annual follow-up as with valproate). It can therefore no longer be offered as first-line treatment for women of childbearing age., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Background and Objectives: Because myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a recently identified autoimmune disorder, the natural history of MOGAD is still not well described. The objective of this study was to describe the long-term outcomes of adult patients with MOGAD. In addition, we aimed to identify factors affecting relapse risk and neurologic outcomes., Methods: Clinical and biological data were obtained from patients with a first event of MOGAD and included in the French nationwide incident cohort between February 2014 and March 2017. Only patients aged 18 years or older at disease onset and with observation period of at least 3 months were included. Data were collected prospectively until July 2023 and registered in the dedicated French nationwide database. This form includes every relapse with phenotype description during follow-up, date of last assessment, final clinical outcome with Expanded Disability Status Scale score and visual acuity, and maintenance therapy. The probability of recurrence-free survival was assessed using the Kaplan-Meier method., Results: We included 128 patients. The onset phenotype was isolated optic neuritis in 81 patients (63.3%) and isolated myelitis in 25 patients (19.5%). The median follow-up duration was 77.8 months (range 3.2-111.2), with 49 patients (38.3%) experienced at least one relapse. Median times from onset to second and third attacks were 3.2 (1.0-86.2) and 13.0 (2.6-64.4) months, respectively. At the last assessment, Expanded Disability Status Scale Score was ≥3 and ≥6 in 22 (17.2%) and 6 (4.7%) patients, respectively. Eighty patients received at least one maintenance treatment. This treatment was initiated after the first attack in 47 patients (36.7% of the whole cohort) and at the time of a second attack in 25 (19.5%). Multivariate analysis revealed that initiating maintenance treatment after the first attack was associated with a lower relapse risk (OR = 0.26 [95% CI 0.11-0.62], p = 0.002). In patients receiving maintenance therapy after first attack, the 2-year, 4-year, 6-year, and 8-year relapse risks were 11%, 15%, 20%, and 20%, respectively. In other patients, the risks were 41%, 46%, 51%, and 56%., Discussion: The highest risk of a relapse in MOGAD occurs early, and initiating maintenance therapy from the first attack substantially reduced the relapse risk., Classification of Evidence: This study provides Class III evidence that initiating maintenance therapy from the first attack in patients with MOGAD reduces the relapse risk.

Objective: Eco-anxiety is a complex construct that has been created to grasp the psychological impact of the consequences of global warming. The concept needs a reliably valid questionnaire to better evaluate its impact on the risk of anxiety and depressive disorders. The Eco-Anxiety Questionnaire (EAQ-22) evaluates two dimensions: 'habitual ecological anxiety' and 'distress related to eco-anxiety'. However, a version in French, one of the world's widely spoken languages, was until now lacking. We aimed to translate and validate the French EAQ-22 and to evaluate the prevalence of the level of the two dimensions of eco-anxiety and the relationship with anxiety and depressive symptoms in a representative adult sample of the French general population., Methods: This study was performed under the auspices of the Institut national du sommeil et de la vigilance (INSV). Participants (18-65 years) were recruited by an institute specialized in conducting online surveys of representative population samples (quota sampling). Two native French speakers and two native English speakers performed a forward-backward translation of the questionnaire. The Hospital Anxiety and Depression scale (HAD) was administered to assess anxiety (HAD-A) and depressive (HAD-D) symptoms and for external validity. Internal structural validity and external validity were analysed., Results: Evaluation was performed on 1004 participants: mean age 43.47 years (SD=13.41, range: [19-66]); 54.1% (n=543) women. Using the HAD, 312 (31.1%) patients had current clinically significant anxiety symptoms (HAD-A>10) and 150 (14.9%) had current clinically significant depressive symptoms (HAD-D>10). Cronbach's alpha coefficient was 0.934, indicating very good internal consistency. Correlation between EAQ-22 and HAD scores was low (r[1004]=0.209, P<0.001), 'habitual ecological anxiety' was correlated less with HAD-A and HAD-D than 'distress related to eco-anxiety', indicating good external validity., Conclusion: This study validates the French EAQ-22 and paves the way for using the EAQ-22 as a global tool for assessing eco-anxiety. Further prospective studies are now required to better evaluate the impact of eco-anxiety on the occurrence of anxiety and depressive disorder., (Copyright © 2023 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: In older patients, medication exposure [i.e. polypharmacy, potentially inappropriate medications (PIMs), medications with anticholinergic and/or sedative properties] is a modifiable risk factor associated with cognitive iatrogenic risk and dementia., Aim: To assess the potential clinical impact of the implementation of an individualised clinical pharmacy programme at the initiation of the Memory care pathway in older patients with a cognitive complaint., Method: This prospective observational study included older patients with high-risk of adverse drug event (HR) admitted in a French geriatric university hospital to explore the cognitive complaint or the cognitive disorder between January and November 2021. Drug-related problems (DRPs) were identified during a medication review performed in HR patients, and pharmaceutical interventions (PIs) notified in the patient's hospitalisation report were collected. The clinical impact of PIs was assessed by an expert panel (geriatricians and clinical pharmacists) using the Clinical, Economic, and Organisational (CLEO) tool., Results: Overall, 326 patients were eligible and 207 (63.5%) were considered as HR patients. Among HR patients, 88.9% (n = 184) were treated using at least 5 medications (polypharmacy), and 36.7% (n = 76) received at least one PIM with cognitive iatrogenic risk. During the medication review, 490 PIs were provided and their clinical impact was rated as minor for 57.3% (n = 281), moderate for 26.7% (n = 131), and major for 2.5% (n = 12)., Conclusion: The integration of clinical pharmacist secured the Memory care pathway of older patients with a cognitive complaint by identifying an important number of DRPs and PIMs with potential cognitive iatrogenic risk., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Long-term exposure to anticholinergic and sedative drugs could be a modifiable risk factor for cognitive decline. The objective of this study was to measure the association between previous cumulative anticholinergic and sedative drug exposure (Drug Burden Index) and cognitive decline., Methods: A cohort study (MEMORA cohort) was conducted in a French memory clinic for patients attending a consultation between November 2014 and December 2020, with at least 2 Mini-Mental State Examination (MMSE) measurements (≥ 6 months apart) and available medication data from the local Primary Health Insurance Fund database (n = 1,970). Drug Burden Index was linearly cumulated until each MMSE measurement and was used to categorise patients according to their level of exposure (no exposure, moderate, or high). The longitudinal association between Drug Burden Index and MMSE was assessed using a multivariate linear mixed model, adjusted for age, education level, anxiety disorders, depressive disorders, functional autonomy, and behavioural disorders., Results: Overall, 1,970 patients were included with a mean follow-up duration of 2.78 years (± 1.54) and 2.99 visits per patients (5,900 MMSE + Drug Burden Index measurements collected). At baseline, 68.0% of patients had moderate cumulative anticholinergic and sedative drug exposure and a mean MMSE of 21.1. MMSE decrease was steeper in patients with moderate and high Drug Burden Index ( -1.74 and -1.70/year, respectively) than in patients with no exposure (-1.26/year) after adjusting for age, education, anxiety and depressive disorders, functional autonomy, and behavioural disorders (p < 0.01)., Conclusions: Long-term exposure to anticholinergic and sedative drugs is associated with steeper cognitive decline. Medication review focusing on de-prescribing these drugs could be implemented early to reduce cognitive impairment., (© 2024. The Author(s).)

Objective: In Alzheimer's disease (AD), the burden on caregivers is influenced by various factors, including the stage of disease progression and neuropsychiatric symptoms (NPS). To date, there has been limited research examining how patient's premorbid personality could affect this burden. The objective of this study was to investigate the impact of both premorbid personality and NPS in individuals with prodromal to mild AD on their caregivers' burden., Method: One hundred eighty participants with prodromal or mild AD drown from the PACO (in French: Personnalité Alzheimer COmportement) cohort were included. Personality was assessed by the Revised NEO Personality Inventory (NEO-PI-R). Neuropsychiatric symptoms were measured with the short version of the Neuropsychiatric Inventory (NPI-Q), and caregiver burden was evaluated with the Zarit burden scale. Relationships between personality, Neuro-Psychiatric Inventory (NPI) scores, and caregiver burden were determined using multivariate linear regressions controlled for age, sex, educational level, and Mini Mental State Examination., Results: The total NPI score was related to increased burden (beta = 0.45; p < 0.001). High level of neuroticism (beta = 0.254; p = 0.003) et low level of conscientiousness (beta = - 0.233; p = 0.005) were associated higher burden. Extraversion (beta = -0.185; p = 0.027) and conscientiousness (beta = -0.35; p = 0.006) were negatively associated with burden. In contrast, neuroticism, openness and agreeableness were not correlated with burden. When adjusted on total NPI score, the relationship between extraversion and conscientiousness didn't persist., Conclusion: Our results suggest that premorbid personality of patients with prodromal to mild Alzheimer influence caregivers's burden, with a protective effect of a high level of extraversion and conscientiousness., (© 2024 The Author(s). International Journal of Geriatric Psychiatry published by John Wiley & Sons Ltd.)

ANTI-CALCITONIN GENE-RELATED PEPTIDE (CGRP) THERAPIES FOR MIGRAINE. Currently, four monoclonal antibodies targeting the CGRP (calcitonin gene-related peptide) pathway have been shown to be effective as migraine prophylactics: eptinezumab, erenumab, fremanezumab and galcanezumab. Unlike the usual preventive treatments, they are administered parenterally: subcutaneously (monthly or quarterly) or by quarterly IV infusion for eptinezumab. They reduce the frequency of attacks by at least 50% in 50 to 60% of migraine patients, even in cases of failure of several conventional preventive treatments, in cases of chronic migraine and medication overuse. Their tolerance is better than that of conventional oral treatments and the discontinuation rates are very low. They can be proposed after failure of at least two conventional prophylactic treatments, in patients with at least 8 migraine days per month and without cardiovascular pathology. Indeed, these drugs present a risk in case of cardiovascular disease, by inhibiting vasodilation, and are therefore contraindicated in this population. The main limitation to the use of these treatments in France at present is the lack of reimbursement, the cheapest molecule being available at a price of 245 € per injection., Competing Interests: X. Moisset déclare avoir reçu des honoraires de la part des entreprises Allergan-AbbVie, Biogen, Bristol Myers Squibb, Grünenthal, Lilly, Lundbeck, Teva, Merck Serono, Novartis, Pfizer, Roche et Sanofi Genzyme, ainsi qu’un soutien non financier de SOS Oxygène. G. Demarquay déclare avoir reçu des honoraires de la part des entreprises Allergan-AbbVie, Lilly, Lundbeck, Novartis, Pfizer, Teva

Background: Overcrowded housing, as well as inadequate sanitary conditions, contribute to making homeless people particularly vulnerable to the SARS-CoV-2 infection. We aimed to assess the seroprevalence of the SARS-CoV-2 infection among people experiencing homelessness on a large city-wide scale in Marseille, France, taking into account different types of accommodation., Methods: A consortium of outreach teams in 48 different locations including streets, slums, squats, emergency or transitional shelters and drop-in centres participated in the inclusion process. All participants consented to have a validated rapid antibody assay for immunoglobulins M (IgM) and G (IgG) and to answer a questionnaire on medical health conditions, comorbidities, and previous COVID-19 symptoms. Information on their housing conditions since the COVID-19 crisis was also collected from the participants., Results: From June 01 to August 05, 2020, 1,156 homeless participants were enrolled in the study and tested. The overall seroprevalence of SARS-CoV-2 IgG/IgM antibodies was 5.6% (95%CI 2.3-7.0), ranging from 2.2% in people living on the streets to 8.1% in people living in emergency shelters (P = 0.009). Around one third of the seropositive participants reported COVID-19 symptoms. Compared to the general population in Marseille (3.6%), the homeless population living in the same urban area experienced a significantly increased risk of SARS-CoV-2 infection (|z| = 3.65 > 1.96)., Conclusion: These findings highlight the need for regular screening among the homeless to prevent clustering in overcrowded or inadequate accommodations. It is also necessary to provide essential resources to keep homeless people healthy, the vast majority of whom have cumulative risk factors for SARS-CoV-2 infection., Competing Interests: The authors have declared that no competing interests exist.

Treatment with human pituitary-derived growth hormone (hGH) was responsible for a significant proportion of iatrogenic Creutzfeldt-Jakob disease (iCJD) cases. France and the UK experienced the largest case numbers of hGH-iCJD, with 122 and 81 cases respectively. Differences in the frequency of the three PRNP codon 129 polymorphisms (MM, MV and VV) and the estimated incubation periods associated with each of these genotypes in the French and the UK hGH-iCJD cohorts led to the suggestion that the prion strains responsible for these two hGH-iCJD cohorts were different. In this study, we characterized the prion strains responsible for hGH-iCJD cases originating from UK (n = 11) and France (n = 11) using human PrP expressing mouse models. The cases included PRNP MM, MV and VV genotypes from both countries. UK and French sporadic CJD (sCJD) cases were included as controls. The prion strains identified following inoculation with hGH-iCJD homogenates corresponded to the two most frequently observed sCJD prion strains (M1 CJD and V2 CJD ). However, in clear contradiction to the initial hypothesis, the prion strains that were identified in the UK and the French hGH-iCJD cases were not radically different. In the vast majority of the cases originating from both countries, the V2 CJD strain or a mixture of M1 CJD  + V2 CJD strains were identified. These data strongly support the contention that the differences in the epidemiological and genetic profiles observed in the UK and France hGH-iCJD cohorts cannot be attributed only to the transmission of different prion strains., (© 2021. The Author(s).)

Objective Evaluate the clinical, economic, and organizational impact of pharmaceutical interventions performed during medication review in a cognitive-behavioral unit. Setting Study conducted in a cognitive-behavioral unit with retrospective data from January 2011 to june 2017. Methods This study was conducted from retrospective data of medication review in a cognitive-behavioral unit. During medication review, pharmacists identified relevant drug related problems lead to a pharmaceutical intervention which is submitted to the physician. All pharmaceutical interventions carried out from January 2011 to june 2017 were retrospectively analyzed to evaluate their clinical, economic and organizational impact using a multidimensional tool. Main outcome measure CLinical, Economic and Organizational impact using the CLEO tool. Results During the study period, 543 drug related problems and pharmaceutical interventions were recorded for patients hospitalized in the cognitive-behavioral unit (79.0 ± 9.5 years, 59% female). The most common types of drug related problems identified were 'non conformity to guidelines / contra-indication' (28.7%), 'drug without indication' (21.7%), and 'improper administration' (15.1%). The majority of pharmaceutical interventions were considered to have at least a clinical significant impact from the pharmacist's perspective (74%). Regarding the economic and organizational dimensions, 55.2% of pharmaceutical interventions would decrease the costs of care and 35.9% of pharmaceutical interventions would be favorable on the quality of care process. Conclusions The present study shows that the pharmacist may detect a high number of drug related problems with significant clinical relevance during medication review in a cognitive-behavioral unit. Describing and identifying significant pharmaceutical interventions in cognitive-behavioral unit patients allow us to better understand and improve clinical practice in this population.

Lockdown measures can differentially affect mental wellbeing in populations depending on individual determinants. We aim to investigate the sociodemographic and environmental determinants of wellbeing on the French population during lockdown due to the SARS-CoV-2 pandemic with an online survey. Among 11,391 participants who completed the questionnaire, various factors negatively impacted wellbeing: being a female, a student, disabled, having no access to outdoor spaces, or living in a small home. Conversely, being employed and having more social contacts had a positive impact. During lockdowns, authorities should consider the vulnerability of specific populations, especially when they live in constrained housing conditions., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

In response to the COVID-19 pandemic, many governments have taken drastic measures to avoid an overflow of intensive care units. Accurate metrics of disease spread are critical for the reopening strategies. Here, we show that self-reports of smell/taste changes are more closely associated with hospital overload and are earlier markers of the spread of infection of SARS-CoV-2 than current governmental indicators. We also report a decrease in self-reports of new onset smell/taste changes as early as 5 days after lockdown enforcement. Cross-country comparisons demonstrate that countries that adopted the most stringent lockdown measures had faster declines in new reports of smell/taste changes following lockdown than a country that adopted less stringent lockdown measures. We propose that an increase in the incidence of sudden smell and taste change in the general population may be used as an indicator of COVID-19 spread in the population.

Background: Several studies have investigated the value of alpha-synuclein assay in the cerebrospinal fluid (CSF) of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) patients in the differential diagnosis of these two pathologies. However, very few studies have focused on this assay in AD and DLB patients at the MCI stage., Methods: All patients were enrolled under a hospital clinical research protocol from the tertiary Memory Clinic (CM2R) of Alsace, France, by an experienced team of clinicians. A total of 166 patients were included in this study: 21 control subjects (CS), 51 patients with DLB at the prodromal stage (pro-DLB), 16 patients with DLB at the demented stage (DLB-d), 33 AD patients at the prodromal stage (pro-AD), 32 AD patients at the demented stage (AD-d), and 13 patients with mixed pathology (AD+DLB). CSF levels of total alpha-synuclein were assessed using a commercial enzyme-linked immunosorbent assay (ELISA) for alpha-synuclein (AJ Roboscreen). Alzheimer's biomarkers (t-Tau, P-Tau, Aβ42, and Aβ40) were also measured., Results: The alpha-synuclein assays showed a significant difference between the AD and DLB groups. Total alpha-synuclein levels were significantly higher in AD patients than in DLB patients. However, the ROC curves show a moderate discriminating power between AD and DLB (AUC = 0.78) which does not improve the discriminating power of the combination of Alzheimer biomarkers (AUC = 0.95 with or without alpha-synuclein). Interestingly, the levels appeared to be altered from the prodromal stage in both AD and DLB., Conclusions: The modification of total alpha-synuclein levels in the CSF of patients occurs early, from the prodromal stage. The adding of alpha-synuclein total to the combination of Alzheimer's biomarker does not improve the differential diagnosis between AD and DLB., Trial Registration: ClinicalTrials.gov, NCT01876459 (AlphaLewyMa).

Intraoral surgery for tongue cancer usually induces speech disorders that have a negative impact on communication and quality of life. Studies have documented the benefit of tongue ultrasound imaging as a visual articulatory feedback for speech rehabilitation. This study aims to assess specifically the complementary contribution of visual feedback to visual illustration (i.e. the display of ultrasound video of target language movements) for the speech rehabilitation of glossectomised patients. Two therapy conditions were used alternately for ten glossectomised French patients randomly divided into two cohorts. The IF cohort benefitted from 10 sessions using illustration alone (IL condition) followed by 10 sessions using illustration supplemented by visual feedback (IL+F condition). The FI cohort followed the opposite protocol, i.e. the first 10 sessions with the IL+F condition, followed by 10 sessions with the IL condition. Phonetic accuracy (Percent Consonants Correct) was monitored at baseline (T0, before the first series) and after each series (T1 and T2) using clinical speech-language assessments. None of the contrasts computed between the two conditions, using logistic regression with random effects models, were found to be statistically significant for the group analysis of assessment scores. Results were significant for a few individuals, with balanced advantages in both conditions. In conclusion, the use of articulatory visual feedback does not seem to bring a decisive advantage over the use of visual illustration, though speech therapists and patients reported that ultrasound feedback was useful at the beginning. This result should be confirmed by similar studies involving other types of speech disorders.

Objective To investigate the association between the medication exposure, measured by the polypharmacy/excessive polypharmacy and the anticholinergic and/or sedative drug exposure, on frailty status among French older community-dwelling patients. Setting day-care unit in France (Lyon), with retrospective data from July, 2017 to March, 2018. Method This monocentric cross-sectional study included community-dwelling patients aged 65 years and over and admitted at the day-care unit for a geriatric evaluation. Frailty was assessed according to the frailty phenotype, described by Fried et al. Polypharmacy and excessive polypharmacy were defined as the concomitant use of 5-9 and 10 or more drugs, respectively. The cumulative anticholinergic and sedative exposure was measured using the drug burden index (DBI). The DBI score was presented in 4 differentiated scores: a null score (DBI = 0), a combined score (anticholinergic and sedative score), an anticholinergic score, and a sedative score. The association between medication and frailty was assessed by logistic regression models controlled for multiple potential confounders. Main outcome measure Association between medication exposure (polypharmacy, anticholinergic and sedative exposure) and frailty. Results In this study, 403 patients were included: 44.7% were frail and 40.7% were pre-frail. Polypharmacy and excessive polypharmacy affected 44.7% and 17.1% of the population respectively. The mean DBI was 0.33 ± 0.43, with 16.4% of patients with only sedative exposure, 9.7% with only anticholinergic exposure and 33.0% with both exposures. After adjustment, polypharmacy and excessive polypharmacy were associated with frailty with adjusted odds ratios (95% confidence interval) of 2.18 (1.03-4.22) and 2.72 (1.01-7.37) respectively. The cumulative exposure to anticholinergic and sedative drugs (combined score) was significantly associated to an increased risk for frailty with adjusted odds ratios (95% confidence interval) of 3.54 (1.47-8.57). Conclusion The study showed that polypharmacy and cumulative anticholinergic and sedative exposure are associated with frailty. Further research should address the potential benefit of collaborative medication review for preventing medication-associated frailty.

Background: Non-invasive brain stimulation techniques are becoming a part of psychiatrists' therapeutic arsenal. Proof of TMS effectiveness and its indications are becoming clearer. While international recommendations exist, and many countries have already recognized the use of these techniques, the French situation is peculiar since no recommendation has been published by the High Authority of Health. Consequently, those techniques are not reimbursed by the healthcare service, few practitioners are trained, some are criticized for using it, and practices remain very heterogeneous. It is therefore important to investigate what slows down the development of these techniques. The objective of this study was to determine the acceptability of TMS by psychiatrists and to analyze the factors influencing it., Method: A sample of psychiatrists was recruited in order to complete an online quantitative acceptability study using a four variable domain model (utility, intention of use, facility, risk) allowing an acceptability score calculation., Result: Four hundreds and seventy-six observations were included in the analysis. Regarding the main objective, the overall TMS acceptability score was high for 47.2% of psychiatrists, average for 40.6% and low for 12.1% of them. The main factors influencing it were theoretical orientation (psychoanalytic vs neurobiological) and training level (only one in three psychiatrists acknowledge having been trained in this technique)., Discussion: The majority of practitioners consider TMS to be a credible alternative to current therapies, especially for depressive disorders. Yet psychiatrists are uninformed and poorly trained in these techniques and report very clearly a desire for more training and information. Our study highlights a significant lack of training that negatively impacts the accessibility of these techniques., (Copyright © 2019 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.)

Background: Clear guidance for successive antidepressant pharmacological treatments for non-responders in major depression is not well established., Method: Based on the RAND/UCLA Appropriateness Method, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of treatment-resistant depression. The expert guidelines combine scientific evidence and expert clinicians' opinions to produce recommendations for treatment-resistant depression. A written survey comprising 118 questions related to highly-detailed clinical presentations was completed on a risk-benefit scale ranging from 0 to 9 by 36 psychiatrist experts in the field of major depression and its treatments. Key-recommendations are provided by the scientific committee after data analysis and interpretation of the results of the survey., Results: The scope of these guidelines encompasses the assessment of pharmacological resistance and situations at risk of resistance, as well as the pharmacological and psychological strategies in major depression., Conclusion: The expert consensus guidelines will contribute to facilitate treatment decisions for clinicians involved in the daily assessment and management of treatment-resistant depression across a number of common and complex clinical situations.

Background: Recommendations for pharmacological treatments of major depression with specific comorbid psychiatric conditions are lacking., Method: The French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental developed expert consensus guidelines for the management of depression based on the RAND/UCLA Appropriatneness Method. Recommendations for lines of treatment are provided by the scientific committee after data analysis and interpretation of the results of a survey of 36 psychiatrist experts in the field of major depression and its treatments., Results: The expert guidelines combine scientific evidence and expert clinician's opinion to produce recommendations for major depression with comorbid anxiety disorders, personality disorders or substance use disorders and in geriatric depression., Conclusion: These guidelines provide direction addressing common clinical dilemmas that arise in the pharmacologic treatment of major depression with comorbid psychiatric conditions.

This article focuses on the contributions made by Michel Jouvet about the neurons responsible for generating the muscle atonia of paradoxical sleep (REM sleep). He was the first to describe the neurons responsible for muscle atonia during paradoxical sleep using "pontine" cats (in which the forebrain has been removed down to the pons) and localized pontine lesions. Also discussed is the research going on in the 1980s, when Michel Jouvet was hunting for the hypnogenic factor. At that time, he thought that it was secreted by the hypophysis; but this factor finally turned out to be controlled by the hypocretin/orexin and melanin concentrating hormone neurones located in the lateral hypothalamus. Several unforgettable moments with Michel Jouvet are described which occurred between 1983 and his last moments with us., (© Société de Biologie, 2019.)

What Is Known and Objective: Benzodiazepines are widely consumed in prisons, despite the iatrogenic risks associated with this therapeutic class. A multidisciplinary pharmacotherapy programme was therefore initiated by pharmacists in 2001. The aim of this study was to demonstrate the efficacy of teamwork between psychiatrists and pharmacists in benzodiazepine dose adjustment, with 15 years of hindsight., Method: In this retrospective study, daily prescribed benzodiazepine doses were compared between a reference group of patients in prisons in Lyon, France, in 2000, and four groups after psychiatrist-pharmacist teamwork in 2004, 2008, 2012 and 2016., Results and Discussion: A number of 1249 patients were included. Prescribed doses of benzodiazepine decreased in the intervention groups, to a mean of 29-35 mg diazepam equivalent per day, compared to the control group (42 mg/day) (P < .001). The first 4-year period (2000-2004) demonstrated that monthly meetings and systematic pharmaceutical medication review had an impact on prescribed benzodiazepines, limiting consumed doses. The others (2004-2008, 2008-2012 and 2012-2016) confirmed that physicians' adherence to prescription guidelines and the efficacy of pharmacotherapy programme was maintained, particularly in those inmates taking high doses., What Is New and Conclusion: A continuous quality programme conducted by psychiatrists and pharmacists showed positive impact in reducing doses of benzodiazepine prescribed to prisoner patients and contributing to reduce risk of benzodiazepine-related problems., (© 2018 John Wiley & Sons Ltd.)

There is a lack of up-to-date data on sleep and dream habits of college students. To fill in this gap, we used an online questionnaire sent to the student mailing lists of two major universities of Lyon (Lyon 1 and Lyon 2) for the recruitment of an functional magnetic resonance imaging study with sleep disorders as exclusion criteria. In the sample (1,137 French college students, 411 males, mean age = 22.2 ± 2.4 years, body mass index = 22.0 ± 3.2 kg m -2 ), on average, the participants reported spending about 8 hr in bed during weekdays, 9 hr during the weekends, and 90.9% of them reported no difficulty falling asleep. Less than 0.4% of students reported to have sleep-walking episodes regularly, but nearly 7% reported regular sleep-talking episodes. The average dream recall frequency was about 3 mornings per week with a dream in mind. Dream recall frequency was positively correlated with the clarity of dream content and the frequency of lucid dreaming, and was negatively correlated with age. Fourteen percent of the students reported frequent lucid dreams, and 6% reported frequent recurrent dreams. We found a gender effect for several sleep and dream parameters, including dream recall frequency and time in bed, both of which were higher in women than in men. We have also observed differences between academic disciplines, namely humanities students (Lyon 2) reported spending more time in bed than sciences students (Lyon 1). These results confirm a gender difference for several sleep and dream parameters, and suggest a link between academic disciplines and sleep duration., (© 2018 European Sleep Research Society.)

This article focuses on the contributions made by Michel Jouvet concerning the systems responsible for the muscle atonia of paradoxical sleep (REM sleep). He was the first to describe the brainstem system mechanisms responsible for muscle atonia during paradoxical sleep using pontine cats and localized pontine lesions. Also discussed is the research going on in the eighties, when Michel Jouvet was hunting for the hypnogenetic factor. At that time, he thought that it was secreted by the hypophysis; but it finally turned out to be controlled by the hypocretin/orexin and melanin concentrating hormone neurones located in the lateral hypothalamus. Several unforgettable moments with Michel Jouvet are described which occurred between 1983 as well as his last moments with us., (Copyright © 2018. Published by Elsevier B.V.)

Background/aims: The aim of the study was to assess the theory of haploinsufficiency in C9ORF72 expansion carriers, the most frequent causative gene of frontotemporal dementia., Methods: Plasmatic concentrations of C9orf72 protein were measured in 33 patients suspected of familial frontotemporal dementia using an enzyme-linked immunosorbent assay., Results: No difference was observed between C9ORF72 expansion carriers (21.2% of patients) and noncarriers (78.8% of patients). C9orf72 protein determination is not a suitable biomarker for screening C9ORF72 expansion carriers., Conclusion: Our results provide new evidence against the hypothesis of haploinsufficiency leading to frontotemporal dementia in C9ORF72 expansion carriers., (© 2018 S. Karger AG, Basel.)

Objectives: To validate a French-language version of the spatial hearing questionnaire (SHQ), including investigating its internal structure using cluster analysis and exploring its construct validity on a large population of hearing-impaired (HI) and normal-hearing (NH) subjects, and to compare the SHQ with the speech, spatial, and qualities of hearing scale (SSQ) in the same population., Design: The SHQ was translated in accordance with the principles of the Universalist Model of cross-cultural adaptation of patient-reported outcome instruments. The SSQ and SHQ were then presented in a counterbalanced order, in a self-report mode, in a population of 230 HI subjects (mean age = 54 years and pure-tone audiometry [PTA] on the better ear = 28 dB HL) and 100 NH subjects (mean age = 21 years). The SHQ feasibility, readability, and psychometric properties were systematically investigated using reliability indices, cluster, and factor analyses and multiregression analyses. SHQ characteristics were compared both to different literature data obtained with different language versions and to the SSQ scores obtained in the same population., Results: Internal validity was high and very good reproducibility of scores and intersubject variability were obtained across the 24 items between the English and French SHQ for NH subjects. Factor and cluster analyses concurred in identifying five correlated factors, corresponding to several SHQ subscales: (1) speech in noise (corresponding to SHQ subscales 7 and 8), (2) localization of voice sounds from behind, (3) speech in quiet (corresponding to SHQ subscale 1), (4) localization of everyday sounds, and (5) localization of voices and music (corresponding to parts of the SHQ localization subscale). Correlations between SSQ subscales and SHQ factors identified the greatest correlations between SHQ factors 2, 4, and 5 and SSQ spatial subscales, whereas SHQ factor 1 had the greatest correlation with SSQ&#95;speech. SHQ and SSQ scores were similar, whether in NH subjects (8.5 versus 8.4) or in HI subjects (6.6 for both), sharing more than 80% of variance. The SHQ localization subscale gave similar scores as the SSQ spatial subscale, sharing more than 75% of variance. Construct validity identified better ear PTA and PTA asymmetry as the two main predictors of SHQ scores, to a degree similar to that seen for the SSQ. The SHQ was shorter, easier to read and less sensitive to the number of years of formal education than the SSQ, but this came at a cost of ecological validity, which was rated higher for the SSQ than for the SHQ., Conclusions: A comparison of factor analysis outcomes among the English, Dutch, and French versions of the SHQ confirmed good conceptual equivalence across languages and robustness of the SHQ for use in international settings. In addition, SHQ and SSQ scores showed remarkable similarities, suggesting the possibility of extrapolating the results from one questionnaire to the other. Although the SHQ was originally designed in a population of cochlear implant patients, the present results show that its usefulness could easily be extended to noncochlear-implanted, HI subjects.

We prospectively studied early bedside standard EEG characteristics in 61 acute postanoxic coma patients. Five simple EEG features, namely, isoelectric, discontinuous, nonreactive to intense auditory and nociceptive stimuli, dominant delta frequency, and occurrence of paroxysms were classified yes or no. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC) of each of these variables for predicting an unfavorable outcome, defined as death, persistent vegetative state, minimally conscious state, or severe neurological disability, as assessed 1 year after coma onset were computed as well as Synek's score. The outcome was unfavorable in 56 (91.8%) patients. Sensitivity, specificity, PPV, NPV, and AUC of nonreactive EEG for predicting an unfavorable outcome were 84%, 80%, 98%, 31%, and 0.82, respectively; and were all very close to the ones of Synek score>3, which were 82%, 80%, 98%, 29%, and 0.81, respectively. Specificities for predicting an unfavorable outcome were 100% for isoelectric, discontinuous, or dominant delta activity EEG. These 3 last features were constantly associated to unfavorable outcome. Absent EEG reactivity strongly predicted an unfavorable outcome in postanoxic coma, and performed as accurate as a Synek score>3. Analyzing characteristics of some simple EEG features may easily help nonneurophysiologist physicians to investigate prognostic issue of postanoxic coma patient. In this study (a) discontinuous, isoelectric, or delta-dominant EEG were constantly associated with unfavorable outcome and (b) nonreactive EEG performed prognostic as accurate as a Synek score>3., (© EEG and Clinical Neuroscience Society (ECNS) 2015.)

Background: For 60% of acute febrile encephalitis cases, the cause is unknown. Autoantibodies directed against different synaptic proteins or receptors in patients with autoimmune encephalitis have recently been described and could indicate a differential diagnosis of infectious encephalitis., Objective: The aim of this study was to retrospectively investigate the presence of autoantibodies directed against synaptic proteins or receptors in patients with acute febrile encephalitis. Samples were collected in France in 2007 during a national prospective study., Methods: A total of 253 patients with acute febrile encephalitis were enrolled in 2007. Clinical data were collected with a standardized questionnaire. When possible, cerebrospinal fluid CSF was collected and stored at -80 °C. A total of 108 CSF samples were available for retrospective autoantibody screening. Among the 108 patients, infectious etiology had been detected in 38 cases (35%); of these 38 patients, 29 (27%) had viral encephalitis, and 9 (8%) had bacterial encephalitis. No specific diagnosis was indicated for the other 70 patients (65%). Autoantibodies were detected using a cell-based assay in which HEK293 cells were transfected with plasmids coding for different synaptic proteins or receptors., Results: Two patients had anti-NMDA receptor antibodies (NMDAR-Abs), and all patients were negative for anti-Lgi1, CASPR2, GABABR, AMPAR, and mGluR5 antibodies. The two patients with NMDAR-Abs presented neurological and psychiatric symptoms typical of NMDAR-Abs encephalitis., Conclusions: Autoimmune etiology seems to be rare (less than 2%) in patients with acute febrile encephalitis. However, patients should be systematically screened for the presence of NMDAR-Abs, particularly patients presenting with psychiatric symptoms., (Copyright © 2014 The British Infection Association. Published by Elsevier Ltd. All rights reserved.)

Implicit learning is the acquisition of complex information without the intention to learn. The aim of this study was to investigate the influence of temporal regularities on the implicit learning of an artificial pitch grammar. According to the dynamic attending theory (DAT) external regularities can entrain internal oscillators that guide attention over time, inducing temporal expectations that influence perception of future events. In the present study, the presentation of the artificial pitch grammar in the exposure phase was temporally either regular or irregular for one of two participant groups. Based on the DAT, it was hypothesized that the regular temporal presentation would favour implicit learning of tone structures in comparison to the irregular temporal presentation. Results demonstrated learning of the artificial grammar for the group with the regular exposure phase and partial learning for the group with the irregular exposure phase. These findings suggest that the regular presentation helps listeners to develop perceptual expectations about the temporal occurrence of future tones and thus facilitates the learning of the artificial pitch grammar.

Objective: The objective of this article is to evaluate in multiple sclerosis (MS) patients the prevalence of persistent complaints of visual disturbances and the mechanisms and resulting functional disability of persistent visual complaints (PVCs)., Methods: Firstly, the prevalence of PVCs was calculated in 303 MS patients. MS-related data of patients with or without PVCs were compared. Secondly, 70 patients with PVCs performed an extensive neuro-ophthalmologic assessment and a vision-related quality of life questionnaire, the National Eye Institute Visual Functionary Questionnaire (NEI-VFQ-25)., Results: PVCs were reported in 105 MS patients (34.6%). Patients with PVCs had more frequently primary progressive MS (30.5% vs 13.6%) and more neuro-ophthalmologic relapses (1.97 vs 1.36) than patients without PVCs. In the mechanisms/disability study, an afferent visual and an ocular-motor pathways dysfunction were respectively diagnosed in 41 and 59 patients, mostly related to bilateral optic neuropathy and bilateral internuclear ophthalmoplegia. The NEI-VFQ 25 score was poor and significantly correlated with the number of impaired neuro-ophthalmologic tests., Conclusion: Our study emphasizes the high prevalence of PVC in MS patients. Regarding the nature of neuro-ophthalmologic deficit, our results suggest that persistent optic neuropathy, as part of the progressive evolution of the disease, is not rare. We also demonstrate that isolated ocular motor dysfunctions induce visual disability in daily life.