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Background: Myelin oligodendrocyte glycoprotein (MOG) may be implicated in the immunopathogenesis of multiple sclerosis (MS) inducing demyelination in the animal model of MS. In adults reported anti-MOG antibody frequencies have been variable across a number of studies and can also be detected in controls.Objective: To measure antibodies against MOG in paediatric patients with demyelinating disorders of the central nervous system and in controls.Methods: Serum antibodies against MOG and myelin basic protein were measured by ELISA, flow cytometry (FACS) and in the liquid phase in 11 children with acute disseminated encephalomyelitis (ADEM), 22 children with MS, seven children with acute viral encephalitis and 13 healthy controls. The serostatus of Epstein—Barr virus (EBV) infections were assessed.Results: Anti-MOG antibodies, measured either by ELISA or FACS were exclusively detected in children with demyelination. In ADEM these antibodies were highly reactive. Anti-MBP reactivity was detectable equally in all groups. The presence of either autoantibodies did not associate with EBV serostatus, age, gender or disease course.Conclusions: This study independently corroborates recently published results of seroprevalence and specificity of the assay. Due to their low sensitivity anti-MOG antibodies will not serve as disease-specific biomarkers, but could help to support the diagnosis of ADEM in difficult cases. [ABSTRACT FROM PUBLISHER]

The authors conducted a population-based case-control study to investigate whether clinically observed chickenpox, linked with a level of intensity for clinical expression, increases the risk of multiple sclerosis (MS) in childhood. The cases were MS patients whose disease onset occurred between 1994 and 2003, before age 16 years, in France. Each case was matched for age, sex, and geographic origin with as many as 12 controls randomly selected from the general population. Information about clinically observed chickenpox in cases and controls before the index date regarding onset of MS was collected with a standardized questionnaire and was checked against health certificates. Conditional logistic regression was used to estimate the odds ratio for an association between MS and chickenpox. The 137 MS cases were matched with 1,061 controls. Clinically observed chickenpox had occurred in 76.6% of the cases and 84.9% of their matched controls. The adjusted odds ratio of MS onset associated with chickenpox occurrence was 0.58 (95% confidence interval: 0.36, 0.92). The authors concluded that clinically observed chickenpox was associated with a lower risk of childhood-onset MS in a French population. [ABSTRACT FROM AUTHOR]

Guillain-Barré syndrome (GBS) is the leading cause of acute flaccid paralysis in developed countries and is characterized by various degrees of weakness, sensory abnormalities and autonomic dysfunction. Although the underlying aetiology and pathophysiology of GBS are not completely understood, it is broadly believed that immune stimulation plays a role in its pathogenesis. Thus, since vaccines have an effect on the immune system it is biologically plausible that immunizations may be associated with subsequent GBS. The objective of this article is to review the current body of evidence that either supports or does not support a causal, rather than just temporal, association between various vaccines and GBS, and to provide an evidence-based review of this issue. The scope of the article includes published reports that, regardless of method of case ascertainment, appeared in peer-reviewed literature between 1950 and 2008. Our review indicates that, with rare exceptions, associations between vaccines and GBS have been only temporal. There is little evidence to support a causal association with most vaccines. The evidence for a causal association is strongest for the swine influenza vaccine that was used in 1976-77. Studies of influenza vaccines used in subsequent years, however, have found small or no increased risk of GBS. Older formulations of rabies vaccine cultured in mammalian brain tissues have been found to have an increased risk of GBS, but newer formulations of rabies vaccine, derived from chick embryo cells, do not appear to be associated with GBS at a greater than expected rate. In an earlier review, the Institute of Medicine concluded that the evidence favoured a causal association between oral polio vaccine and tetanus toxoid-containing vaccines and GBS. However, recent evidence from large epidemiological studies and mass immunization campaigns in different countries found no correlation between oral polio vaccine or tetanus toxoid-containing vaccines and GBS. Spontaneous reports to the US Vaccine Adverse Events Reporting System shortly after the introduction of quadrivalent conjugated meningococcal vaccine (MCV4) raised concerns of a possible association with GBS. Comparisons with expected rates of GBS, however, were inconclusive for an increased risk, and lack of controlled epidemiological studies makes it difficult to draw conclusions about a causal association. For other vaccines, available data are based on isolated case reports or very small clusters temporally related to immunizations, and no conclusion about causality can be drawn. There are certain circumstances in which immunizing individuals, particularly those with a prior history of GBS, may require caution. However, the benefit of vaccines in preventing disease and decreasing morbidity and mortality, particularly for influenza, needs to be weighed against the potential risk of GBS. [ABSTRACT FROM AUTHOR]

Epilepsy may contribute to memory deficits in children, but these deficits are generally mild. We describe the neuropsychological profile of a female who had prolonged status epilepticus at 5 years of age, and then developed temporal lobe epilepsy. Brain magnetic resonance imaging 1 month after the onset of status epilepticus showed marked bilateral hippocampal atrophy that seemed disproportionate to the mild cortico-subcortical atrophy. At the age of 7 years, this child had cognitive impairment (an IQ of 62), which particularly affected her memory. This included short-term memory, and immediate and delayed memory deficits for verbal and visual materials that had a profound impact on everyday life. This observation demonstrates that severe status epilepticus can cause predominant bilateral hippocampal atrophy in childhood. In contrast with children who develop such damage after anoxia, this may result in general cognitive impairment but also in more severe episodic memory deficit. [ABSTRACT FROM AUTHOR]

Aim. – We studied the use of premixed nitrous oxide and oxygen in 80 patients with neurologic diseases.Patients and methods. – Mean ages ranged 10 ± 5 yrs. Twenty-three patients (29%) were mentally retardated among which 17 of them presented with severe epilepsy. Painful procedures consisted of: lumbar punctures (80%), intravenous access (7), gastric endoscopy (6), skin biopsy (4), gastrostomy tube management (3). High-risk children were continuously monitored using ECG, non invasive blood pressure and transcutaneous oxygen saturation. We studied acceptation of the inhalation, vital signs, satisfaction of children, parents, medical and nursing staffs; side effects were compared with a group of healthy children undergoing venous access before induction of anesthesia.Results and discussion. – Acceptation increased with age. No significant changes in vital signs variables were observed. Satisfaction rate regarding the method was 88% for all children, parents, physicians and nurses. No serious undesirable event (as respiratory depression, seizure, inhalation of gastric content) occurred in these patients. The more frequent side-effects were : drowsiness during and after inhalation (35 and 9% respectively in the handicapped patients); nausea and vomiting (8%), headaches (3%), were more frequent than reported in literature but there were 25% of meningitis among our patients.Conclusion. – Premixed nitrous oxide and oxygen was effective for reducing procedural pain and anxiety in children with neurological disorders, even in severely handicapped patients, with minor side-effects. [Copyright &y& Elsevier]

Abstract Background Little is known concerning risk factors for herpes zoster in the general population. We hypothesised that inhaled corticosteroids (ICS) are a risk factor for herpes zoster especially among users of inhibitors of cytochrome P450 enzymes involved in their metabolism. Methods We identified a cohort of adult users of respiratory medications in the General Practice Research Database and carried out a nested case control analysis of inhaled corticosteroid use among 8900 new cases of herpes zoster and 88032 controls matching on age and calendar time. Results The adjusted odds ratio for the relationship between current use of ICS and the occurrence of herpes zoster was 1.00 (95% confidence interval (CI), 0.94-1.07). There was no increase in risk of herpes zoster even at higher ICS doses; odds ratio 1.05 (95% CI, 0.96-1.14). Among subjects with concomitant prescriptions for an ICS and an inhibitor of cytochrome P450 3A4, the point estimate for the association between herpes zoster and the use of higher doses of inhaled corticosteroids was 1.23 (95% CI, 0.81-1.88). Conclusions The use of inhaled corticosteroids, even at high doses and in conjunction with inhibitors of their metabolism, was not a significant risk factor for the occurrence of herpes zoster in adults.

Background: Although still incomplete, the epidemiology of epilepsy shows substantial variations in the burden of the condition according to demographic, social and territorial characteristics. This study aimed to estimate the prevalence of treated epilepsy and to investigate its demographic and spatial distribution in 2020 in France, a country where the nationwide epidemiological situation of the condition remains largely unknown., Methods: We used the French national health data system, which covers nearly the entire population residing in France (over 67 million of inhabitants in metropolitan and overseas departments). Prevalent cases were identified using long-term disease status, hospitalisation for epilepsy (ICD-10 codes G40 or G41), and reimbursements for antiseizure medications and electroencephalograms., Results: In 2020, we identified 685,122 epilepsy cases, corresponding to an overall prevalence of 10.2 per 1000 inhabitants [95% confidence interval 10.1-10.2], with similar rates in men and women. Estimates were found to increase with age, with an accelerated rise in the second half of the life, which occurred earlier in men than in women. We observed a monotonic gradient of variation with socio-economic deprivation (in non-military metropolitan subjects aged 18-54 years) as well as territorial heterogeneity, with the mountainous centre of France as well as some French overseas departments having the highest prevalence., Conclusions: Our results revise upwards the estimation of epilepsy prevalence in France, showing that it now ranks among the highest in developed countries. Our study also confirms the important socio-territorial heterogeneity of the condition that reflects health inequalities in this country., (© 2023. The Author(s).)

Background: Medical child abuse (MCA; or Munchausen syndrome by proxy) is a severe form of adult and medical maltreatment of children. Currently, few data on MCA in adolescents exist., Objective: To describe the clinical characteristics and medical history of children and adolescents aged 10 to 18 years with suspected or confirmed MCA in the pediatric hospital setting., Methods: We included patients aged 10 to 18 years who were seen in five tertiary care hospitals in the Paris area and identified by physician recall such as suspected MCA between 2015 and 2021., Results: We included 29 adolescents; the mean (SD) age was 12.9 (10.8-15.0) years at suspected diagnosis. Medical wandering was common, with a mean of 23 (12.8-33.2) alleged symptoms and 33 (9.2-56.8) specialized consultations in a mean of six different hospitals. The mean number of emergency visits was 11.8 (0-25.9) and radiologic exams 24.3 (5-43.6). Overall, 62 % (18/29) of the adolescents had an underlying organic pathology. The impact of MCA on quality of life was major, with a high rate of school dropout (96 %). The mean delay to the suspected diagnosis was 5.8 (2.6-9) years, and even when recognized, it was rarely the subject of a social or judiciary report (only 42 % of adolescents). In total, 50 % of the adolescents subsequently exhibited Munchausen syndrome., Conclusion: Adolescent MCA is poorly known among the medical profession. Increasing awareness, education and knowledge of risk factors could contribute to better care., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The fight against the SARS-CoV-2 pandemic was carried out through strong restrictive measures, including general population lockdown, which allowed the convergence of risk factors for child abuse. During this period, the French national hotline for children in danger recorded a 56% increase in calls. Calls followed by an alert to departmental child protection services increased by 30%. Through an algorithm created by our team, we showed a 50% increase in the relative frequency of hospitalizations for physical abuse in children aged 0-5 years during the lockdown. This has fueled thinking about subsequent health measures to protect the youngest children. Our goal is now to use this algorithm for epidemiological purposes as a barometer of abuse or in daily practice to help the diagnosis of physical abuse in young children., (© 2023 médecine/sciences – Inserm.)

Numerical inversion is the ability to understand that addition is the opposite of subtraction and vice versa. Three-term arithmetic problems can be solved without calculation using this conceptual shortcut. To verify that this principle is used, inverse problems (a + b - b) can be compared with standard problems (a + b - c). If this principle is used, performance on inverse problems will be higher than performance on standard problems because no calculation is required. To our knowledge, this principle has not been previously studied in children with mathematical learning disabilities (MLD). Our objectives were (a) to study whether 10-year-olds with MLD are able to use this conceptual principle in three-term arithmetic problems and (b) to evaluate the impact of the presentation mode. A total of 64 children with or without MLD solved three-term arithmetic problems (inverse and standard) in two presentation modes (symbolic and picture). The results showed that even though children with MLD have difficulties in performing arithmetic problems, they can do so when the inverse problem is presented with pictures. The picture presentation mode allowed children with MLD to efficiently identify and use the conceptual inversion shortcut and thus to achieve a similar performance to that of typically developing children. These results provide interesting perspectives for the care of children with MLD., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: In France, the COVID-19 pandemic led to a general lockdown from mid-March to mid-May 2020, forcing families to remain confined. We hypothesized that children may have been victims of more physical abuse during the lockdown, involving an increase in the relative frequency of hospitalization., Methods: Using the national administrative database on all admissions to public and private hospitals (PMSI), we selected all children aged 0-5 years hospitalized and identified physically abused children based on ICD-10 codes. We included 844,227 children hospitalized in March-April 2017-2020, of whom 476 (0.056%) were admitted for physical abuse. Relative frequency of hospitalization for physical abuse observed in March to April 2020 were compared with those from the same months in the three previous years (2017-2019)., Findings: Even if absolute number of children exposed to physical abuse did not fluctuate significantly, we found a significant increase in the relative frequency of young children hospitalized for physical abuse from 2017 (0.053%) to 2020 (0.073%). Compared with the 2017-2019 period, and considering the observed decrease in the number of overall hospital admissions during the first lockdown, the number of children exposed to physical violence was 40% superior to what would be expected., Interpretation: The sharp increase in the relative frequency of hospitalizations for physical abuse in children aged 0-5 years in France is alarming. As only the most severe cases were brought to the hospital for treatment during the lockdown, our figures probably only represent the tip of the iceberg of a general increase of violence against young children., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Recent data suggest that the COVID-19 pandemic and associated restrictions may have influenced alcohol use and promoted addictive behavior. We aimed to investigate the impact of the pandemic on acute alcohol intoxication (AAI) in France., Methods: We identified all hospital stays related to alcohol abuse in 2018-2020. Differences in number of hospitalizations between 2019 and 2020 were tested using Poisson regressions. Differences between observed and expected deliveries of drugs used in alcohol dependence in 2020 were also studied., Results: There was a decrease in the number of hospitalizations for AAI between 2019 and 2020 (-9677[-11·4%],RR:0·89[0·88-0·89]). This decrease was observed among men and women of all age groups, except women ≥ 85 years. We observed an increase in in-hospital mortality during 2020 and more hospitalizations for AAI with certain medical complications, especially during the first 2020 lockdown. There was a drop in observed deliveries of drugs used in alcohol dependence during the first 2020 lockdown., Conclusions: The decrease in the number of hospitalizations for AAI in 2020 could be explained by several factors: fewer available hospital beds due to COVID-19, individuals with AAI delaying or avoiding medical care due to COVID-19 fears, and decreases driven by younger age groups returning to live with parents and socializing less. While alcohol consumption patterns have changed with the implementation of social distancing measures and lockdowns, the increase in mortality and the share of hospitalizations with complications suggest that these measures had an impact on event severity in a context of strained access to healthcare., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Little is known to date about the impact of COVID-19 pandemic on self-harm., Methods: The number of hospitalizations for self-harm (ICD-10 codes X60-X84) in France from 1st January to 31st August 2020 (including a two-month confinement) was compared to the same periods in 2017-2019. Statistical methods comprised Poisson regression, Cox regression and Student's t -test, plus Spearman's correlation test relating to spatial analysis of hospitalizations., Outcomes: There were 53,583 self-harm hospitalizations in France during January to August 2020. Compared to the same period in 2019, this represents an overall 8·5% decrease (Relative Risk [95% Confidence Interval] = 0·91 [0·90-0·93]).This decrease started in the first week of confinement and persisted until the end of August. Similarly, decrease was found in both women (RR=0·90 [0·88-0·92]) and men (RR=0·94 [0·91-0·95]), and in all age groups, except 65 years and older. Regarding self-harm hospitalizations by means category, increases were found for firearm (RR=1·20 [1·03-1·40]) and for jumping from heights (RR=1·10 [1·01-1·21]). There was a trend for more hospitalizations in intensive care (RR=1·03 [0·99-1·07]). The number of deaths at discharge from hospital also increased (Hazard Ratio = 1·19 [1·09-1·31]). Self-harm hospitalizations were weakly correlated with the rates of hospitalization for COVID-19 across administrative departments (Spearman's rho =-0·21; p  = 0·03), but not with overall hospitalizations., Interpretation: The COVID-19 pandemic had varied effects on self-harm hospitalizations during the early months in France. Active suicide prevention strategies should be maintained., Funding: French National Research Agency., Competing Interests: All authors have nothing to declare., (© 2021 The Authors.)

Information available on the risks of neurodevelopmental disorders (NDs) associated with in utero exposure to valproate (VPA) and to other antiepileptic drugs (AEDs) is limited. A nationwide population-based cohort study was conducted based on comprehensive data of the French National Health Data System (SNDS). Liveborn infants without brain malformation, born between January 2011 and December 2014, were followed from birth up to December 2016. NDs were identified based on diagnoses of mental or behavioural disorders and utilization of speech therapy, orthoptic or psychiatric services. The risk of NDs was compared between children exposed in utero to AED monotherapy and unexposed children, using Cox proportional hazard models adjusted for maternal and neonatal characteristics. The cohort included 1,721,990 children, 8848 of whom were exposed in utero to AED monotherapy. During a mean follow-up of 3.6 years, 15,458 children had a diagnosis of mental or behavioural disorder. In utero exposure to VPA was associated with an increased risk of NDs overall (aHR: 3.7; 95% CI 2.8-4.9) and among children born to a mother without mental illness (aHR 5.1; 95% CI 3.6-7.3). A dose-response relationship was demonstrated and the risk of NDs was more particularly increased for an exposure to VPA during the second or third trimesters of pregnancy. Among the other AEDs, only pregabalin was consistently associated with an increased risk of NDs (aHR: 1.5; 95% CI 1.0-2.1). This study confirms a four to fivefold increased risk of early NDs associated with exposure to VPA during pregnancy. The risk associated with other AEDs appears much lower.

Objectives: To assess the association between prenatal exposure to monotherapy with the antiepileptic drugs (AEDs) most commonly used during pregnancy and the risk of various neurodevelopmental outcomes compared with lamotrigine., Design: Nationwide population-based cohort study., Setting: French national healthcare databases., Participants: Children born alive between 2011 and 2014 and prenatally exposed to AED monotherapy., Primary and Secondary Outcome Measures: Outcomes included neurodevelopmental disorders (NDD), defined by International Classification of Diseases, 10th Revision codes F70-F98-pervasive developmental disorders (PDD, F84) and mental retardation (MR, F70-F79) were studied separately-and visits to speech therapists. The reference group comprised children prenatally exposed to lamotrigine. Children were followed until outcome, loss to follow-up, death or 31 December 2016. We performed inverse probability of treatment weighting analyses using the propensity score, which included maternal and infant characteristics. Hazard ratios (HRs) were calculated using Cox models., Results: The cohort comprised 9034 children, 2916 of which were exposed to lamotrigine, 1627 to pregabalin, 1246 to clonazepam, 991 to valproic acid (VPA), 621 to levetiracetam, 502 to carbamazepine, 477 to topiramate, 378 to gabapentin and 143 to oxcarbazepine. None of these AEDs, except VPA, was associated with an increased risk of any of the four neurodevelopmental outcomes investigated. Exposure to VPA was associated with increased risks of NDDs (HR=2.7, 95% CI (1.8 to 4.0)), PDD (HR=4.4 (2.1 to 9.3)), MR (HR=3.1 (1.5 to 6.2)) and visits to speech therapists (HR=1.5 (1.1 to 1.9)), with a dose-response relationship., Conclusions: No increased risk of any of the neurodevelopmental outcomes investigated in this study was observed with prenatal exposure to levetiracetam, pregabalin, oxcarbazepine, topiramate, gabapentin, clonazepam or carbamazepine, compared with lamotrigine. However, this study corroborates the well-known association between maternal use of VPA during pregnancy and the risk of neurodevelopmental disorders in the offspring. Longer follow-up is necessary to confirm these findings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the risk of Guillain-Barré syndrome (GBS) following seasonal influenza vaccination based on French nationwide data., Methods: All cases of GBS occurring in metropolitan France between September 1 and March 31 from 2010 to 2014 were identified from the French national health data system. Data were analyzed according to the self-controlled case series method. The risk period started 1 day after the patient received vaccine (D1) until 42 days after vaccination (D42). The incidence of GBS during this risk period was compared to that of the control period (D43-March 31). The incidence rate ratio (IRR) was estimated after adjusting for seasonality and presence or not of acute infections., Results: Between September and March, of the 2010/2011 to 2013/2014 influenza vaccination seasons, 3,523 cases of GBS occurred in metropolitan France and were included in the study. Among them, 15% (527 patients) had received influenza vaccination. A total of 140 patients developed GBS during the 42 days following influenza vaccination. The crude risk of developing GBS was not significantly increased during the 42 days following influenza vaccination (IRR, 1.02; 95% confidence interval [CI], 0.83-1.25; p = 0.85). This result remained nonsignificant after adjustment for calendar months and the incidence of acute gastrointestinal and respiratory tract infections (IRR, 1.10; 95% CI, 0.89-1.37; p = 0.38). In contrast, the risk of GBS was fourfold higher after acute respiratory tract infection (IRR, 3.89; 95% CI, 3.52-4.30; p < 0.0001) or gastrointestinal infection (IRR, 3.64; 95% CI, 3.01-4.40; p < 0.0001)., Conclusions: No association between seasonal influenza vaccination and GBS was shown during the 42 days following vaccination., (© 2020 American Academy of Neurology.)