Laser interstitial thermal therapy (LITT) is a minimally invasive surgical treatment for drug-resistant, focal epilepsies. With MRI guidance, LITT can also be used to treat hypothalamic hamartoma. Here, we report on the first European case of LITT for hypothalamic hamartoma. No complication occurred except a transitory peripheral facial paralysis. The short- and long term outcomes (for both epilepsy and cognitive development) were excellent.

Objective: Although ketamine analgesia is effective in reducing pain and facilitating the tracheal intubation of newborns in the delivery room, no data on the neurological effects of this treatment are available. This study compared the neurodevelopmental outcomes at 2 years of age in a cohort of preterm newborns having received ketamine prior to tracheal intubation at birth (the ketamine group) and in a control group. Methods: We included newborns delivered at less than 33 weeks gestational age (WGA) having undergone tracheal intubation at birth. The Ages and Stages Questionnaire (ASQ) was completed at 1 and 2 years of age. The development quotient (DQ) was calculated from the revised Brunet-Lezine score assessed at a corrected age of 2 years. Results: There were no statistically significant differences between the ketamine group (n = 54 at 1 year and n = 51 at 2 years) and the control group (n = 16 at 1 and 2 years) in terms of the mean standard deviation DQ at the age of 2 (98 +/- 12 vs. 103 +/- 9, respectively; P = 0.17) and the ASQ score at the age of 2 (221 +/- 44 vs. 230 +/- 39, respectively; P = 0.55). Discussion: This prospective cohort of 51 preterm newborns having received ketamine at birth did not reveal any differences in terms of neurological development at the age of 2 (relative to a control group and the literature data). These preliminary results must be confirmed in a randomized trial with longer follow-up. (C) 2018 Elsevier Masson SAS. All rights reserved.

X-linked myotubular myopathy (XLMTM) is a rare disease of the skeletal muscle due to mutations in the MTM1 gene. It affects approximately 1 in 50 000 male newborns. It is the most severe form of centronuclear myopathy and presents several degrees of phenotype severity. In preparation of clinical development of innovative medicines such as ERT or gene therapy and to choose adequate outcome measures, we set up an international natural history study. Here, we describe the first 6 patients enrolled in this protocol. All patients underwent a muscle biopsy which showed the typical pathological hallmarks of the disease, including central nuclei in muscle fibers. They carried different missense mutations of the MTM1 gene (c.695A > G, C.1A > T, C.775T …). Their first symptoms were commonly related to respiratory failure, general hypotonia and ptosis. The five non-ambulant male patients enrolled presented with an obvious ophthalmoplegia. They lost the ambulation between 3 and 14 years old. None of the patients had ever been able to run or jump. All required ventilatory support (day and/or night) and showed a speech impairment (hypophonia). Two patients had a tracheotomy and underwent a gastrostomy. They had several hospitalizations mostly related to a respiratory distress. Only the distal upper limb could be reliably assessed in these patients because of their profound weakness. We also included a 39-year-old woman who had been diagnosed at the age of 25. At baseline, her FVC was 90% of predicted normal and she walked 284 m in the 6MWT (40% of predicted normal). Several other patients have been identified in Europe and North America and will be included in the coming months.

Objective To evaluate the efectiveness of vagal stimulation in a population of children and adolescent with refractory epilepsy. Methods This is a monocentre, retrospective study, which studied the files of 29 children implanted between 1995 and 2012 with a vagus nerve stimulator. The rate of responders (reduction by more than 50% of the frequency of seizures), the antiepileptic efficacy according to the type of epilepsy or to the age of implantation or to the age of the start of epilepsy, the side effects, the overall quality of life and the number of hospitalisations were studied. Results VNS, for all types of epilepsy, brought a significant reduction of the frequency of seizures throughout the follow-up (p<0.05). The percentage of responder patients ranged between 59% at 3 months, 66% at 6 months, 70% at 18 months, 75% at 24 months then remained more or less stable afterwards Stimulation tended to be more effective on partial epilepsies than on generalised epilepsies. We did not show any other predictive factors of efficacy. An improvement in the overall quality of life was reported in 38% of patients, and a significant reduction in the number of hospitalisations was observed after implantation (p=0.03). Conclusion The stimulation of the vagus nerve is a sure and effective therapeutic alternative that would be discussed for a child with refractory epilepsy when a surgical approach is not possible. To evaluate the efectiveness of vagal stimulation in a population of children and adolescent with refractory epilepsy. This is a monocentre, retrospective study, which studied the files of 29 children implanted between 1995 and 2012 with a vagus nerve stimulator. The rate of responders (reduction by more than 50% of the frequency of seizures), the antiepileptic efficacy according to the type of epilepsy or to the age of implantation or to the age of the start of epilepsy, the side effects, the overall quality of life and the number of hospitalisations were studied. VNS, for all types of epilepsy, brought a significant reduction of the frequency of seizures throughout the follow-up (p<0.05). The percentage of responder patients ranged between 59% at 3 months, 66% at 6 months, 70% at 18 months, 75% at 24 months then remained more or less stable afterwards Stimulation tended to be more effective on partial epilepsies than on generalised epilepsies. We did not show any other predictive factors of efficacy. An improvement in the overall quality of life was reported in 38% of patients, and a significant reduction in the number of hospitalisations was observed after implantation (p=0.03). The stimulation of the vagus nerve is a sure and effective therapeutic alternative that would be discussed for a child with refractory epilepsy when a surgical approach is not possible.

Introduction La varicelle est une maladie benigne et frequente chez l’enfant. Des complications surviennent dans 3% des cas. Cas clinique Nous rapportons le cas d’une enfant de 6ans, hospitalisee pour la survenue aigue d’une hemiplegie droite. L’enfant a presente une varicelle un mois avant le debut de l’episode. L’etude du LCR a mis en evidence une meningite lymphocytaire. La presence du VZV par PCR dans le LCR a ete confirmee. L’IRM cerebrale retrouvait des lesions ischemiques dans differents territoires de l’artere sylvienne gauche. Un traitement intraveineux par aciclovir a ete instaure. Un antiagregant plaquettaire (acide acetylsalicylique) a ete debute devant la complication cerebrale vasculaire postinfectieuse. L’evolution clinique a ete rapidement favorable avec une recuperation neurologique complete. Discussion Il n’existe pas de consensus quant a l’indication d’un traitement antiviral. Un traitement antiagregant plaquettaire doit etre discute devant une complication vasculaire cerebrale. Certains auteurs evoquent l’interet de la vaccination de la population generale des le plus jeune âge dans la prevention des complications post-varicelleuses. Conclusion La vascularite cerebrale post-varicelleuse est une complication rare mais de bon pronostic neurologique.

Les hématomes sous-duraux (HSD) sont fréquents dans la population pédiatrique et sont une cause de morbi-mortalité importante. L'objectif est de décrire la présentation clinique, les caractéristiques TDM et IRM, les examens complémentaires, la prise en charge thérapeutique, le devenir médical et socio-judiciaire chez les enfants souffrant d'HSD. Dans le cadre de cette revue rétrospective, les 88 dossiers d'HSD survenus dans la population pédiatrique, entre 1998 et 2012, ont été étudiés. 72% des enfants avaient moins de 12 mois. Les motifs de consultation et les signes cliniques à l'entrée étaient multiples et non spécifiques. Il n'y avait pas de caractéristique radiologique significative permettant d'affirmer avec certitude l'étiologie de l'HSD. Dans 51% des cas il était également retrouvé des hémorragies rétiniennes. 49% des HSD étaient dus à un traumatisme crânien accidentel, 36% à un syndrome du bébé secoué et 15% à une pathologie identifiée ou non. 37,5% des dossiers ont fait l'objet d'un signalement. 46% souffraient à posteriori de séquelles cliniques de gravité variable. Chaque acteur de santé a un rôle primordial face à un enfant consultant pour HSD et notamment afin de ne pas méconnaître une situation de maltraitance.

L'hamartome hypothalamique (HH) est une tumeur neurale bénigne rare à l'origine d'épilepsie, de troubles du comportement et de puberté précoce. Nous rapportons le cas d'un garçon de 3 ans, adressé pour troubles autistiques et absence de langage. La marche a été acquise à 14 mois. Dès la naissance, il a présenté des crises gélastiques puis des spasmes infantiles dès 6 mois non diagnostiqués. Une avance staturopondérale liée à une puberté précoce centrale a été diagnostiquée. L'IRM cérébrale a mis en évidence une masse tumorale hypothalamique appendue au plancher du 3ème ventricule évocatrice d'un hamartome. Une déconnexion par voie endoscopique a été réalisée permettant la disparition des manifestations épileptiques, une diminution du syndrome autistique et des progrès majeurs sur le langage. L'hamartome hypothalamique est révélé très fréquemment par des crises gélastiques. Les spasmes infantiles précoces sont également des manifestations épileptiques décrites dans l'HH. Le diagnostic d'hamartome hypothalamique doit toujours être évoqué devant des crises gélastiques. Ceci permet d'introduire précocement un traitement antiépileptique afin de limiter le risque de retard psychomoteur et de troubles autistiques.

Upper limb evaluation of patients with Duchenne Muscular Dystrophy is crucially important to evaluate efficacy of new treatments in non-ambulant patients. Adequate outcome measures are scarce for patients who have lost ambulation. In addition, longitudinal data demonstrating sensitivity to clinical evolution of outcome measures on a short term period are lacking. We report here the results of a one-year multicenter study using specifically designed tools to assess grip and key pinch strength and hand function in wheelchair bound patients. Our study recruited 53 non-ambulant patients with Duchenne muscular atrophy aged 17.1 ± 4.8 years (range: 9–28.1 years). The Brooke functional score was 4.6 ± 1.1. The average forced vital capacity was 44.5 % and nineteen patients used non-invasive ventilation. Patients were assessed at baseline, 6 months and one year using the Motor Function Measure and innovative devices (namely the MyoSet composed of MyoGrip, MyoPinch and MoviPlate). Our study confirmed the preliminary data previously reported regarding feasibility, reliability of the MyoSet and correlation between the distal strength and clinical variables. We demonstrated that the use of sensitive dynamometers could capture a 12-month change in non-ambulant Duchenne muscular dystrophy patients of all ages. Upper limb evaluation of patients with Duchenne Muscular Dystrophy is crucially important to evaluate efficacy of new treatments in non-ambulant patients. Adequate outcome measures are scarce for patients who have lost ambulation. In addition, longitudinal data demonstrating sensitivity to clinical evolution of outcome measures on a short term period are lacking. We report here the results of a one-year multicenter study using specifically designed tools to assess grip and key pinch strength and hand function in wheelchair bound patients. Our study recruited 53 non-ambulant patients with Duchenne muscular atrophy aged 17.1 ± 4.8 years (range: 9–28.1 years). The Brooke functional score was 4.6 ± 1.1. The average forced vital capacity was 44.5 % and nineteen patients used non-invasive ventilation. Patients were assessed at baseline, 6 months and one year using the Motor Function Measure and innovative devices (namely the MyoSet composed of MyoGrip, MyoPinch and MoviPlate). Our study confirmed the preliminary data previously reported regarding feasibility, reliability of the MyoSet and correlation between the distal strength and clinical variables. We demonstrated that the use of sensitive dynamometers could capture a 12-month change in non-ambulant Duchenne muscular dystrophy patients of all ages.

La plupart des types d’épilepsie sont susceptibles d’être améliorés par la stimulation du nerf vague et ce à n’importe quel moment de leur évolution. L’objectif de cette étude est d’évaluer son efficacité globale, d’identifier d’éventuels facteurs prédictifs d’efficacité, d’évaluer sa tolérance et ses bénéfices médico-économiques. Dans le cadre de cette revue rétrospective, les dossiers des 29 enfants âgés de 3,5 à 18 ans implantés dans notre CHU entre 1995 et 2012 ont été étudiés. La stimulation du nerf vague a permis une réduction significative de la fréquence des crises et ce à chaque instant du suivi (p < 0,05). Après 3 mois, la stimulation du nerf vague avait tendance à être plus efficace sur les épilepsies partielles. Nous n’avons pas mis en évidence d’autres facteurs prédictifs d’efficacité (p > 0,05). Nous notons une amélioration globale de la qualité de vie chez 38% des patients et une réduction significative du nombre d’hospitalisations après implantation (p=0,03). La stimulation du nerf vague est une alternative thérapeutique sûre et efficace chez les enfants non candidats à la chirurgie souffrant d’une épilepsie partielle pharmacorésistante.

Exon skipping therapy is an emerging approach in Duchenne Muscular Dystrophy (DMD). Antisense oligonucleotides that skip exon 51, 44, 45, and 53 are currently evaluated in clinical trials. Knowing the precise phenotype of potentially eligible patients is important for designing the clinical trials. It is generally believed that there are few if any phenotypic differences between these different groups of patients or between these patients and the general DMD population. In preparation of exon 53 skipping mediated by an AAV8 construct, we recruited 24 patients aged from 6 to 20 years in an observational study of upper limb strength and function, using the Motor Function Measure (MFM), the Myogrip, the MyoPinch and the MoviPlate, three tools already validated in a large non ambulant DMD population. Data of 14 non ambulant DMD patients (13.8 ± 2.7 years) at inclusion were compared with 14 age and size-matched DMD controls (13.7 ± 2.6 years) with all types of mutation. DMD 53 patients scored significantly lower in the MFM (D3: 66 ± 17% vs. 82 ± 13% for DMD 53 vs. DMD control), had significant lower handgrip and key pinch strength on both hands. They had lost ambulation 13 months earlier (Age: 105 ± 20 vs. 118 ± 19 p = 0.04 for DMD 53 vs. DMD control). In order to rule out that this is due to a selection bias, we compared DMD 53 patients with other DMD patients carrying a deletion not involving the 45–55 region and looked at DMD patient cohort identified at the Cochin hospital’s routine diagnostic laboratory. We found that 91 DMD ex53 patients had lost ambulation at 108 ± 15 months, whilst other 400 non 45–55 DMD patients with a deletion had lost ambulation at 139 ± 54 months. Taken together, these preliminary data demonstrate that non-ambulant patients treatable by exon 53 skipping present a more severe phenotype than the general DMD population. This must be taken into account in the design of studies concerning this population. Exon skipping therapy is an emerging approach in Duchenne Muscular Dystrophy (DMD). Antisense oligonucleotides that skip exon 51, 44, 45, and 53 are currently evaluated in clinical trials. Knowing the precise phenotype of potentially eligible patients is important for designing the clinical trials. It is generally believed that there are few if any phenotypic differences between these different groups of patients or between these patients and the general DMD population. In preparation of exon 53 skipping mediated by an AAV8 construct, we recruited 24 patients aged from 6 to 20 years in an observational study of upper limb strength and function, using the Motor Function Measure (MFM), the Myogrip, the MyoPinch and the MoviPlate, three tools already validated in a large non ambulant DMD population. Data of 14 non ambulant DMD patients (13.8 ± 2.7 years) at inclusion were compared with 14 age and size-matched DMD controls (13.7 ± 2.6 years) with all types of mutation. DMD 53 patients scored significantly lower in the MFM (D3: 66 ± 17% vs. 82 ± 13% for DMD 53 vs. DMD control), had significant lower handgrip and key pinch strength on both hands. They had lost ambulation 13 months earlier (Age: 105 ± 20 vs. 118 ± 19 p = 0.04 for DMD 53 vs. DMD control). In order to rule out that this is due to a selection bias, we compared DMD 53 patients with other DMD patients carrying a deletion not involving the 45–55 region and looked at DMD patient cohort identified at the Cochin hospital’s routine diagnostic laboratory. We found that 91 DMD ex53 patients had lost ambulation at 108 ± 15 months, whilst other 400 non 45–55 DMD patients with a deletion had lost ambulation at 139 ± 54 months. Taken together, these preliminary data demonstrate that non-ambulant patients treatable by exon 53 skipping present a more severe phenotype than the general DMD population. This must be taken into account in the design of studies concerning this population.

Globalization has altered the way we live and earn a livelihood. Consequently, trade and travel have been recognized as significant determinants of the spread of disease. Additionally, the rise in urbanization and the closer integration of the world economy have facilitated global interconnectedness. Therefore, globalization has emerged as an essential mechanism of disease transmission. This paper aims to examine the potential impact of COVID-19 on globalization and global health in terms of mobility, trade, travel, and countries most impacted.The effect of globalization were operationalized in terms of mobility, economy, and healthcare systems. The mobility of individuals and its magnitude was assessed using airline and seaport trade data and travel information. The economic impact was measured based on the workforce, event cancellations, food and agriculture, academic institutions, and supply chain. The healthcare capacity was assessed by considering healthcare system indicators and preparedness of countries. Utilizing a technique for order of preference by similarity to ideal solution (TOPSIS), we calculated a pandemic vulnerability index (PVI) by creating a quantitative measure of the potential global health. The pandemic has placed an unprecedented burden on the world economy, healthcare, and globalization through travel, events cancellation, employment workforce, food chain, academia, and healthcare capacity. Based on PVI results, certain countries were more vulnerable than others. In Africa, more vulnerable countries included South Africa and Egypt; in Europe, they were Russia, Germany, and Italy; in Asia and Oceania, they were India, Iran, Pakistan, Saudi Arabia, and Turkey; and for the Americas, they were Brazil, USA, Chile, Mexico, and Peru. The impact on mobility, economy, and healthcare systems has only started to manifest. The findings of this study may help in the planning and implementation of strategies at the country level to help ease this emerging burden.

The need for measures specifically designed to assess the muscle strength and activity of upper limbs of non-ambulatory patients with neuromuscular diseases is a major challenge. Aiming for a regular monitoring of the natural history of these patients, and trying to provide a powerful system for quantitative measurements, a movement Holter monitor is being developed in France at the Institute of Myology in collaboration with SYSNAV Company. The device consists of a watch equipped with sensors and specific software. The measuring principle is based on the use of Micro-Electro-Mechanical Systems inertial sensors and magnetometers operated through magneto-inertial equations. The issue lies in determining reliable variables representing the physical muscle level and in quantification of movement of non-ambulatory patients from the signals recorded by sensors: angular velocity, magnetic field and linear acceleration in 3D. In a preliminary study, we used a wired prototype to record healthy subjects performing Box and Block test. For each task, the exponential regression between the obtained task score and the activity levels as estimated by different computing of recorded linear acceleration and angular velocity indicate a strong correlation (R2 from 0.95 to 0.97). The results from other tests like Minnesota (score), computer typing (number of characters) and number of a standardized movement mimicking spoon elevation to mouth similarly showed strong correlation R2 ranging from 0.88 to 0.96. These data demonstrate that variables issued from the computing of linear acceleration and angular velocities may predict the efficacy of a subject in a quantified task performed in a controlled environment. We therefore produce a wireless prototype that is now being evaluated in non-ambulatory patients at home.