The outcome of a national MS-Covid-19 study: What the Turkish MS cohort reveals?

BACKGROUND: The pandemic of the new type of corona virus infection 2019 [Covid-19] also affect people with Multiple Sclerosis (pwMS). Currently, the accumulating information on the effects of the infection regarding the demographic and clinical characteristics of the disease, as well as outcomes within different DMTs¸ enable us to have better practices on the management of the Covid-19 infection in pwMS. OBJECTIVE: To investigate the incidence of coronavirus disease 2019 (Covid-19) and to reveal the relationship between the demographic-clinical and therapeutic features and the outcome of Covid-19 infection in a multi-center national cohort of pwMS. METHODS: The Turkish Neurological Society-MS Study Group in association with the Italian MuSC-19 Study Group initiated this study. A web-based electronic Case Report Form (eCRF) of Study-MuSC-19 were used to collect the data. The demographic data and MS histories of the patients were obtained from the file tracking forms of the relevant clinics. RESULTS: 309 MS patients with confirmed Covid-19 infection were included in this study. Two hundred nineteen (219) were females (70.9%). The mean age was 36.9, ranging from 18 to 66, 194 of them (62.8%) were under 40. The clinical phenotype was relapsing-remitting in 277 (89.6%) and progressive in 32 (10.4%). Disease duration ranged from 0.2 years to 31.4 years. The median EDSS was 1.5, ranging from 0 to 8.5. The EDSS score was<= 1 in 134 (43%) of the patients. 91.6% of the patients were on a DMT, Fingolimod was the most frequently used drug (22.0%), followed by Interferon (20.1%). The comorbidity rate is 11.7%. We were not able to detect any significant association of DMTs with Covid-19 severity. CONCLUSION: The Turkish MS-Covid-19 cohort had confirmed that pwMS are not at risk of having a more severe COVID-19 outcome irrespective of the DMT that they are treated. In addition, due to being a younger population with less comorbidities most had a mild disease further highlight that the only associated risk factors for having a moderate to severe COVID-19 course are similar with the general population such as having comorbid conditions and being older.

A dynamic relationship between mucosal T helper type 17 and regulatory T-cell populations in nasopharynx evolves with age and associates with the clearance of pneumococcal carriage in humans.

Pneumococcal carriage is common in young children, which may account for the high incidence of disease in this age group. Host factors determining the clearance of carriage in humans remain unclear. We aimed to study the relationships between T helper type 17 (Th17) and Foxp3(+) regulatory T (Treg) cells in nasopharynx-associated lymphoid tissue (NALT) and carriage in children and adults. Frequencies of Th17 and Treg cells in NALT were analysed by flow cytometry in association with age and pneumococcal carriage status. Cytokine responses following pneumococcal stimulation were analysed by cytometric beads array. The frequencies of Th17 and Treg cells in NALT were inversely correlated (R -0.60). Whereas Treg cell frequency decreased with age (R -0.63), both Th17 and the Th17: Treg ratio increased with age (R 0.62 and R 0.64, respectively). Also, the Th17: Treg ratio was higher in carriage-negative than in carriage-positive children (p <0.01). Pneumococcal stimulation of tonsillar cells increased both Th17 and Treg cell numbers, but the Th17: Treg ratio and pattern of cytokine responses differed between carriage-negative and carriage-positive children. The former showed markedly higher Th17: Treg and interleukin-17A: interleukin-10 ratios than in the latter (p <0.01). Pneumococcal stimulation also induces Th17, although the capacity of this Th17 differentiation from naive T cells of young children was low, but increased with age. We demonstrated a dynamic relationship between Th17 and Treg cells in human nasopharynx that evolves with age. The balance between Th17 and Treg cells in NALT appears to be a major host factor closely associated with the clearance of Streptococcus pneumoniae from the nasopharynx.

[Loeys-Dietz syndrome (TGFßR2 mutation) in a 4-year-old child with thoracic aortic aneurysm]. / Syndrome de Loeys-Dietz (mutation TGFßR2) chez une enfant de 4ans avec anévrysme de l'aorte thoracique.

Loeys-Dietz syndrome is a rare form of connective tissue disorder, whose clinical features can resemble those of Marfan syndrome, but with a more unpolished appearance. Recently brought out, this pathology remains little known; however, its consequences may be dramatic. We report on the case of a 4-year-old girl followed for a congenital hip dislocation, in which a systematic exam found increased cutaneous elasticity and a bifid uvula, suggesting a connective tissue disorder. Symptoms were unpolished, as the child's height was normal, without any positive cardiac, rheumatological, or ophthalmological family history. Cardiovascular tests found a thoracic aortic aneurysm at the Valsalva sinus (26mm, Z-score=+4.24). A genetic investigation found a TGFßR2 gene mutation, leading to the diagnosis of Loeys-Dietz syndrome type 2. Skeletal damage associated with bifid uvula and/or hypertelorism and an aneurysm of the ascending aorta should guide the genetic investigation to the search for TGF-ß vasculopathy such as Loeys-Dietz syndrome.

[Embolization of pulmonary arteriovenous malformation causing hypoxemia in a 7-year-old child]. / Fermeture percutanée d'une fistule artério-veineuse pulmonaire responsable d'une hypoxémie chronique chez une enfant de 7 ans.

Pulmonary arteriovenous fistulas are abnormal vessels joining the right pulmonary artery to the pulmonary veins. They lead to an extracardiac right-to-left shunt with refractory hypoxemia. We report the case of a 7-year-old girl with a large pulmonary arteriovenous fistula discovered with refractory hypoxemia diagnosed during general anesthesia for adenoidectomy. Radio-opacity was observed on the upper lobe of the right lung. The diagnosis was made using thoracic angiotomography. The proximal arterial vessel arose from the lobar pulmonary artery. The fistula had developed in the entire right upper lobe and drained into two veins flowing into the right superior pulmonary artery. Given the marked hypoxemia, the potential risks of pulmonary hemorrhage and pulmonary infection, an occlusion of the fistula was indicated. After discussion between surgeons and interventional cardiologists, catheterization was indicated. The occlusion of the fistula was successful at the second attempt after release of a vascular plug in the main proximal vessel. This case illustrates the clinical circumstances of diagnosis of arteriovenous fistula, the diagnostic algorithm for refractory hypoxemia and the therapeutic options, with discussion of the benefits and drawbacks of a catheterization procedure.

[Thiamine deficiency in infants: a case report]. / Béribéri du nourrisson : à propos d'un cas.

Thiamine deficiency is recognized in varied parts of the world. In Asia, it remains an important public health problem where highly polished rice is the major staple food and where other primary dietary sources of thiamine are in short supply. Beriberi, or clinically apparent thiamine deficiency, may present a variety of syndromes including myocardial dysfunction or wet beriberi, dry beriberi with neurological symptoms, and the more severe form Shoshin beriberi with cardiac failure and lactic acidosis. Infantile thiamine deficiency is a very rare condition in developed countries today. It occurs mainly in breastfed infants of mothers who have inadequate intake of thiamine. Clinical symptoms in such infants include gastrointestinal symptoms, cardiac failure, and lactic acidosis. We report the case of a 10-week-old girl, admitted with diarrhea, vomiting, acidosis, and cardiac failure. After excluding other etiologies of cardiomyopathy, biochemical thiamine deficiency confirmed the diagnosis of beriberi in an infant of a thiamine-deficient mother from Reunion Island, a French island where recently, with Mayotte Island, epidemic cases of beriberi have been described. This case is important to highlight the manifestations in young infants and to alert physicians to the possibility of thiamine deficiency in developed countries.

Endothelial function and mechanical arterial properties in children born small for gestational age: comparison with obese children.

BACKGROUND: Early cardiovascular events preceding atherosclerosis have been reported in children born small for gestational age (SGA). AIMS: To describe in detail the mechanical and functional arterial properties of SGA children and to compare the data to those of obese children in order to gain a better understanding of the severity of the dysfunction. A control group was required to overcome the lack of normal values. METHODS: Three groups of 7- to 15-year-old children were included. Sixty children born SGA without obesity, 49 children with obesity and not SGA, and 55 controls underwent complete carotid and brachial arterial measurements using ultrasound and flow-mediated dilation. Biological measurements were performed in the obese and SGA groups. RESULTS: Mean blood pressure and intima-media thickness were lower in SGA children than in the obese group (p < 0.001 and p = 0.004, respectively), but not different from the control group. Flow-mediated dilation was lower in SGA than in obese children and in controls (p < 0.001). CONCLUSION: These data show that children born SGA have endothelial dysfunction with normal intima-media thickness.

[Maternal group B streptococcal bacteriuria and neonatal infective endocarditis: a case report]. / Bactériurie maternelle à streptocoque B et endocardite néonatale : à propos d'un cas.

Bacterial endocarditis is rare in children. We report the case of streptococcal B endocarditis in a newborn whose mother had asymptomatic bacteriuria during pregnancy. This report emphasizes the importance of maternal intrapartum antibiotic therapy when there is a major risk of neonatal infection and underlines the diagnostic value of echocardiography in case of prolonged fever.

[Circular shunting of blood: a complication of neonatal Ebstein anomaly]. / Le shunt circulaire: complication de la maladie d'Ebstein de forme néonatale.

We report a severe neonatal presentation of Ebstein anomaly with homodynamic aggravation at birth attributed to patent ductus arteriosus and circular shunt. Prenatal diagnosis of Ebstein anomaly of the tricuspid valve with functional pulmonary atresia was made at 37 weeks gestation by fetal two- and three-dimensional echocardiography. A cesarean section was performed in view of poor fetal tolerance. The newborn was born with hydrops and multivisceral failure. A post-natal echocardiography demonstrated a left-to-right shunt across the patent ductus arteriosus and functional pulmonary atresia with severe pulmonary insufficiency with absent forward flow. This created a circular shunt, where blood flowed through the ductus to the pulmonary arteries, retrograde through the pulmonary artery and Ebstein valve, across the patent foramen ovale and out the aorta. Prostaglandin E1 infusion was stopped, resulting in clinical and echocardiographic improvement. The management of the phenomenon of a circular shunt across a patent ductus arteriosus with Ebstein malformation involves promoting early ductal closure by stopping prostaglandin therapy.

[Morgagni hernia causing cardiac tamponade]. / Tamponnade néonatale par hernie de Morgagni.

Morgagni hernia is a rare malformation (3% of diaphragmatic hernias). This hernia is usually asymptomatic in children. We report on a case revealed by an unusual complication. Severe cyanosis was due to right-to-left atrial shunt through the foramen ovale assessed by 2D echocardiography. Diagnosis of the Morgagni hernia was made with CT scan. The intrathoracic liver compressed the right chambers of the heart causing tamponade. Cardiac compression was reversed after surgery and replacement of the liver in the abdomen. Six months after the surgery, the infant was symptom-free with normal size right chambers of the heart.

[Fetal myocarditis associated with maternal anti-Ro and anti-La antibodies in the absence of atrioventricular block with good outcome]. / Myocardite fœtale sans trouble conductif chez une femme lupique avec anticorps anti-SSA/Ro et anti-SSB/La d'évolution favorable.

We report a case of fetal myocarditis without conductive abnormality in a pregnant woman with anti-Ro/La antibodies. Fetal echocardiography showed myocarditis with ventricular and valvular hyperechogenicity, which was confirmed by postnatal transthoracic echography. Treatment with dexamethasone (4 mg/day) was started in the 22nd week of gestation. The outcome was good, with the child remaining asymptomatic 2 years later. This observation describes one of the rare forms of fetal myocarditis with favorable outcome.

[Candida albicans endocarditis after pulmonary artery banding]. / Endocardite àCandida albicans sur cerclage de l'artère pulmonaire.

Endocarditis is uncommon in infants and is exceptionally related to Candida albicans on pulmonary banding. We report on a case in a 7-month-old infant who had pulmonary artery banding for a ventricular septal defect and who presented with candidal endocarditis. Banding was chosen because of the patient's poor trophic and unstable status, which could be risky for surgery involving extracorporeal circulation. A few weeks after the banding, the patient developed systemic Candida infection, which was treated successfully. At 7 months, cardiac failure appeared without fever or inflammatory signs. Cardiac echography showed that the banding was not protective as well as a hyperechogenic image on the pulmonary bifurcation. The angioscan showed a hypodense thrombus. Emergency surgery was performed consisting of pulmonary artery exploration, thrombectomy, and ventricular septal defect closure. The exploration showed a pulmonary artery perforation caused by the infected pseudoaneurysm and the migration of the banding into the pulmonary artery. The anatomopathologic analysis of the vegetation identified multisensitive Candida albicans. After surgery and prolonged antifungal treatment, progression was satisfactory.

Videoconference pediatric and congenital cardiology consultations: a new application in telemedicine.

BACKGROUND: The relative rarity of congenital heart disease gives it an orphean disease status, requiring specialised centres. The present maturity of information technology allows telemedicine to be integrated into current medical practice. We report our experience of telemedicine between the cardiology department at St Pierre Hospital on the island of Réunion and the pediatric cardiology department at the teaching hospital in Toulouse. AIMS: The aims of this work were to 1. verify the technical feasibility of transmitting echocardiographic images, 2. determine an optimal therapeutic strategy for each patient, and 3. deliver precise information live to patients and their families. METHODS: Five pediatric cardiology videoconference consultation sessions were transmitted between April 2006 and May 2007. The videoconference equipment, POLYCOM VSX 7000 (R), was used to relay information between the two centres, using six high-debit digital telephone lines, allowing a transfer rate of 384 kbits/s and an image frequency of 25 frames per second. The echocardiographic equipment at St Pierre Hospital was connected to the videoconference equipment by an S-VHS video output. The transmitted sources alternated between the echographic video output and the signal from a video camera, with continuous audio transmission. RESULTS: The telemedicine meeting was made up of three main elements: 1. a consultation with real-time echocardiographic acquisition and transmission, 2. a discussion between medical colleagues, and 3. a discussion with the family. Five videoconference consultation sessions were organised between April 2006 and May 2007. 22 patients were involved (median age 3 years, age range 7 days to 48 years). Heart disease was congenital in 20 patients, and acquired in 2 patients. The aim of the telemedicine consultation was to specify: 1. medical treatment in 7 patients, and 2. an indication for surgery or interventional catheterisation in 15 patients. There was no significant change in diagnosis, but in 2 patients with complex heart disease some anatomical clarifications were made. For 3 patients, the videoconference discussion was essential to get the extremely reticent families to accept the indication for surgery. CONCLUSION: This is the first experience in France of telemedicine consultation for pediatric and congenital cardiology. These videoconferences allowed patients in the south of Réunion to benefit from a specialist opinion on optimal therapeutic strategy, with no delay or need to travel a long distance.

Intracranial hypotension in a girl with Marfan syndrome: case report and review of the literature.

INTRODUCTION: A 14-year-old girl, followed in our department for Marfan syndrome, presented with postural headache for a month. Neurological examination was normal. The diagnosis of intracranial hypotension syndrome was suspected. DISCUSSION: Bilateral subdural hematomas were found on brain magnetic resonance imaging (MRI), and spinal MRI showed large lumbosacral arachnoid diverticula; no cerebrospinal fluid leaks could be found. Despite bed rest and hydration for 2 weeks, postural headache remained. Epidural blood patching was also performed. Subsequently, the patient became asymptomatic and could stand up after 1 day. Brain MRI did not find recurrent subdural hematoma after 1 month. Dural ectasia is one of the major criteria of Marfan syndrome, and it is often poorly symptomatic. Intracranial hypotension is a rare complication especially in children, and management is not standardized. In this case report, blood patching was sufficient. Further research into the diagnosis and management of spontaneous intracranial hypotension is required.

[Evaluation of left ventricular diastolic function in children by doppler tissue imaging]. / Evaluation de la fonction diastolique par Doppler tissulaire chez l'enfant.

Left ventricular diastolic function may change at an early stage in cardiac disease. It is often difficult to assess in daily practice. The use of Doppler tissue imaging at the annulus has been validated in adults. This method is little used in paediatrics and the physiological norms have not been established in children. Forty three children aged 7 days to 241 months were referred for a cardiological opinion with normal echocardiogrammes were included. Myocardial velocities were measured by Doppler tissue imaging of the left and right ventricular walls at different moments of the cardiac cycle in the apical 4-chamber view. A complete study was possible in 39 cases (91%). Doppler tissue imaging was not performed in one case and was incomplete on the right ventricle in 3 children. The median of the lateral mitral tissue E wave (Ea) was 16.3 cm/s and that of the right ventricle was 15.8 cm/s with a tissue Ea/Aa ratio of 2.6 and 1.6 respectively. The median of the tissue S waves was 8.8 cm/s for the left ventricular lateral wall and 13.3 cm/s for the right ventricular lateral wall. The E/Ea ratio of the left ventricular lateral wall was 5.9. Although the velocities of the left ventricular lateral wall were not related to the children's' age or size, the correlations between the E/Ea ratio and age and size were statistically significant. The myocardial velocities of the neonate were characteristic and different to those of the older paediatric population (slower Ea and S waves, faster Aa with a higher E/Ea ratio). The authors conclude that Doppler tissue imaging is feasible in clinical paediatric cardiology. Comparative studies with populations with cardiac disease are necessary to determine pathological values.

[Alveolar capillary dysplasia and persistent pulmonary hypertension of the newborn]. / La dysplasie alvéolo-capillaire: une cause exceptionnelle d'hypertension artérielle pulmonaire persistante du nouveau né. A propos d'un cas.

Alveolar capillary dysplasia is a rare cause of persistent pulmonary hypertension of the newborn. The diagnosis of this condition is made by histological study of a pulmonary biopsy. Familial forms and associated genitor-urinary and gastrointestinal malformations have been reported. Despite optimal management, the prognosis remains poor. The authors report the case of a neonate who developed cyanosis and cardiogenic shock on the 10th day of life. There was no associated neonatal pathology. Echocardiography showed supra-systemic pulmonary hypertension with normal cardiac structure. Pulmonary vasodilator therapies (inhaled NO, prostacyclin, sildenafil, bosentan) were ineffective and the child died on the 25th day of life. Autopsy revealed alveolar capillary dysplasia.

[Transposition of the great arteries with pulmonary valvular stenosis and intact interventricular septum. Discussion of management strategies with respect to one case]. / Transposition des gros vaisseaux avec sténose valvulaire pulmonaire à septum interventriculaire intact. Discussion des enjeux thérapeutiques à propos d'un cas.

The authors report the case of a neonate with transposition of the great arteries (TGA) with pulmonary stenosis (PS) and intact Interventricular septum. The child was born at full term without a prenatal diagnosis with cyanosis developing at the 12th hour. After emergency atrioseptostomy, detransposition was performed on the 6th day. Commissurotomy and shaving of the much thickened bicuspid pulmonary valve was also performed. The postoperative course was complicated by a non-compliant left ventricle. After two months, myocardial ischaemia and persistent obstruction of the outflow tract led to severe cardiac failure and the death of the child. TGA with PS and intact interventricular septum is a very rare cardiac malformation. The prognosis is closely related to the anatomy of the pulmonary valve and the impact on the left ventricle. The therapeutic options are complex and are discussed in relation to this case.

[Arrhythmia follow-up of children and adolescents with neuromuscular diseases]. / Surveillance rythmologique de l'enfant et l'adolescent avec maladie neuro-musculaire.

Much progress has been made over the last few years in understanding and classifying neuromuscular diseases. The heart is frequently affected but often in a dissociated manner with respect to the neuromuscular signs although it has a significant impact on the prognosis. In children and adolescents, the dystrophinopathies, especially Duchenne's muscular dystrophy, are the principal problems but the mild arrhythmic events observed seem to be related to left ventricular dysfunction. On the other hand, in myotonic dystrophies (Steinert's disease), ventricular arrhythmias or conduction defects may appear at an early stage of the disease with serious consequences justifying appropriate follow-up and invasive preventive measures. Emery Dreifuss X-linked dystrophy and other laminopathies are rare conditions but are associated with sudden death and cardiomyopathies of the young adult. Specialised cardiological follow-up is justified in childhood from the time of diagnosis. Medication or implantable electric devices may be justified before the end of the second decade of life. Progressive infra-hisian conduction defects have also been reported in Kearns-Sayre oculo-pharyngeal myopathy. Prospective studies are required at this age to determine the natural history of these pathologies that are probably under diagnosed. The present recommendations, which are based mainly on data from adult series, could then be adapted for younger patients.

Optimal pacing in congenital complete atrioventricular block of immunological origin: interest of multisite stimulation.

An infant with a congenital auriculoventricular block (CAVB) of immunological origin was diagnosed prenatally. The mother had Gougerot-Sjögren disease with positive anti-Sjogren's Syndrome A (SSA) and Sjogren's Syndrome B (SSB) serologies. Cardiac pacing was necessary and the epicardial route was chosen. Considering the left ventricular (LV) dilatation, bi-ventricular (BiV) stimulation was preferred to the usual DDD mode, presumed to have a deleterious long-term effect. Echographic parameters were better with BiV stimulation: the asynchronism induced by mono-RV stimulation was corrected and the QRS complexes were narrower. BiV pacing of a CAVB with LV dilation looks clinically and echographically attractive but needs to be validated in the long term.