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.

[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.

[Percutaneous closure of three septal defects by two Amplatz occluders implanted during the same procedure]. / Fermeture percutanée de 3 communications interauriculaires par 2 dispositifs d'Amplatz implantés au cours d'un même cathétérisme.

Multiple atrial septal defects can be closed by interventional catheterisation. The procedure requires an accurate morphological evaluation: number of defects, distance from their edges to the main cardiac structures, resistance of the septum. The authors report the case of a 63 year old woman presenting with cardiac failure in whom 3 atrial septal defects were diagnosed. All 3 defects were successfully closed by the implantation of two Amplatz devices. Control echocardiography at 6 months showed the occluders in a normal position with no residual shunt and the patient was asymptomatic.

[New approach to perimembranous ventricular septal defect by real-time 3D echocardiography]. / Nouvelle approche des communications interventriculaires périmembraneuses par échocardiographie 3D temps réel.

Perimembranous ventricular septal defects (VSD) have a close anatomical relationship to the aortic and tricuspid valve which may make percutaneous closure difficult. The authors' objective was to study the anatomy of perimembranous VSD by real-time 3D echocardiography. Fourteen patients aged 1 day to 3 years (mean 3 months) underwent transthoracic 2D and 3D echocardiography. Two patients (> 10 kg) underwent closure of the perimembranous VSD with an Amplatzer occluder. The other 12 patients were operated (surgical closure in 11 and circling suture with resorbable thread in 1 patient). The 3D echocardiography showed variations in the geometry of the perimembranous VSD (eccentric, oval, cleft). The maximal diameter of the septal defect by 3D echocardiography was on average 2 mm greater than the diameter by 2D echocardiography. The 3D echo enabled visualisation of the close relationship of the septal tricuspid leaflet, the aortic valve and the perimembranous VSD, showing the mechanism of its closure and the associated aortic regurgitant lesions. The profile of the prosthesis implanted percutaneously was well shown in the different 3D views. The authors conclude that real-time 3D echocardiography is a technique which allows accurate anatomic description of perimembranous VSD. As a complement to classical 2D methods, it gives a better appreciation of the maximal diameter of the septal defect and of its relationship to the aortic and tricuspid valves.

[Unusual outcome of mitral valve infectious endocarditis in a premature infant]. / Evolution inhabituelle d'une endocardite infectieuse mitrale chez un prématuré.

The authors report a case of Staphylococcus Aureus infectious endocarditis in a premature baby. Echocardiography on the 8th day of life showed a large vegetation on the anterior mitral leaflet without significant regurgitation. Intravenous antibiotics and platelet antiaggregant therapy were given. At three weeks of age the vegetation split into two, one part attached to the foramen ovale and the other to the anterior mitral leaflet. At one month, the development of severe mitral regurgitation led to surgical valvuloplasty in a 2 kg neonate, the vegetation on the foramen ovale having spontaneously fragmented. The ablation of the mitral vegetation associated with commissuroplasty reduced the mitral regurgitation. At 3 months after surgery, the child was asymptomatic with a minimal mitral regurgitation.

[A rare association of double discordance with aortic arch anomalies: value of multislice CT scan]. / Association exceptionnelle d'une double discordance avec anomalie des arcs aortiques: apport du scanner multicoupe.

The authors report the case of a 14 month old infant admitted for intermittent stridor. Routine echocardiography showed atrioventricular and ventriculo-arterial discordance with an intact septum and situs solitus with levocardia. Multislice CT scan showed tracheal compression due to a Neuhauser anomaly of the aortic arches. The paucity of symptoms led to surgical abstention.

[B-natriuretic peptide and cardiological emergencies in childhood]. / Peptide natriurétique de type B et urgences cardiologiques chez l'enfant.

The increase in B-natiuretic peptide (BNP) is well correlated with cardiovascular symptoms in adults. Its use in children is recent and only partially evaluated. The authors undertook a prospective study of BNP concentrations and its kinetics in 54 children with an average age of 15 months (5 days to 11 years) admitted as paediatric emergencies. The symptoms were dyspnoea (60%), shock (15%), suspicion of Kawasaki disease (15%) and other (10%). Twenty children had BNP levels of more than 100 pg/ml related to decompensation of known congenital heart disease in 7 patients (average BNP 462 +/- 323 pg/ml), due to neonatal coarctation in 2 patients (BNP > 3000 pg/ml), due to cardiomyopathy in 6 patients (BNP= 2576 +/- 1215 pg/ml), due to an arrhythmia in 1 patient (BNP= 3754 pg/ml) and to Kawasaki disease in 4 patients (BNP= 521 +/- 448 pg/ml). Thirty-four children had BNP values of less than 100 pg/ml; 29 had no cardiac disease and 5 had known congenital heart disease with other symptoms. Measuring BNP is quick and economical and is a valuable aid in the diagnosis of cardiac dysfunction in symptomatic children in the emergency room. High BNP values seem to be correlated with the severity of the cardiac disease. Low BNP values seem to have a good negative predictive value in children without underlying cardiac disease. The interpretation of intermediary values, especially when there is previous cardiac disease, is more difficult in view of the absence of known threshold values for different haemodynamic situations. Further studies are required to determine the value of this test for the follow-up and setting up of prognostic values in children with congenital heart disease.

[Three-dimensional echocardiography in congenital heart disease]. / Apports et limites de l'échocardiographie tridimensionnelle dans les cardiopathies congénitales.

The introduction of real time three-dimensional (3D) echocardiography has led to its use in everyday clinical practice. The 3D matrix probe enables the instantaneous acquisition of transthoracic volumes. Several modes of 3D are available: 3D volume, biplan and 3D color Doppler. Real time 3D echocardiography gave more accurate description of various congenital heart diseases as well as valvulopathy, shunt and aorta pathology. Fetal 3D echocardiography is available. Quantitative measurement of ventricular volumes could be obtain by 3D echocardiography. The facility of utilisation of the matrix probe should lead to routine usage of 3D echocardiography as with 2D and Doppler method. Its values should be decisive in many congenital cardiac lesions requiring surgery or interventional catheterisation.

[Fulminant myocarditis presenting like acute myocardial infarction in a 6-year-old girl]. / Myocardite aiguë fulminante mimant un infarctus du myocarde chez une enfant de 6 ans.

Acute myocarditis is a rare inflammatory cardiac disease in children with potentially fatal issue. Clinical findings are very variable from nausea and vomiting to acute cardiovascular collapse. The cardiac function can be reversible with circulatory support. We report the case of a 6-year-old girl with ECG changes like myocardial infarction and diagnosis of fulminant myocarditis. She developped rapidly a cardiogenic shock and died before treatment with mechanical circulatory support.

[Very large cardiac tumor revealed by ventricular arrhythmia in a 18-month-old infant]. / Volumineuse tumeur cardiaque révélée par un trouble du rythme ventriculaire chez un nourrisson de 18 mois.

Cardiac tumors are rare in childhood and can be revealed by arrhythmias. We report the observation of an 18-month-old infant who had an episode of ventricular tachycardia (VT) which resulted in a large intramyocardic tumour diagnosis evocating a left ventricular fibroma. A treatment by amiodarone allowed a stable reduction of the VT. The presence of an intracardiac obstruction or uncontrollable arrhythmias would lead to a surgical resection.

[Cor triatriatum sinister: unusual cause of neonatal respiratory distress]. / Coeur triatrial gauche: une cause inhabituelle de détresse respiratoire néonatale.

We report the case of a newborn presenting with neonatal respiratory distress due to acute pulmonary edema, the underlying diagnosis being cor triatriatum sinister. This rare anomaly can be lethal in the short term. However, it can be completely cured surgically provided that diagnosis is made on time.

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.

[A new approach to the tricuspid valve in Ebstein's anomaly by real time 3D echocardiography]. / Nouvelle approche de la valve tricuspide par échocardiographie 3D temps réel dans la maladie d'Ebstein.

Ebstein's anomaly affects the tricuspid valve with a large range of anatomical forms. Successful tricuspid valvuloplasty depends mainly on the ability to mobilise the leaflets. Evaluation of the leaflet surface is difficult with 2D echocardiography whereas 3D echocardiography provides intracardiac views of the valve. The authors used this method in 10 patients with 3 modes of imaging: biplane, real time and total volume. The study population (age: 1 day to 30 years) included: 1 prenatal diagnosis, 1 neonate with refractory cyanosis, 5 patients with mild tricuspid regurgitation, 3 patients with severe tricuspid regurgitation, 2 of whom underwent valvuloplasty. 3D echocardiography was disappointing in the foetus and neonate because of poor spatial resolution. The ventricular view of the tricuspid valve in older children and adults allowed analysis of tricuspid leaflet coaptation and of the mechanism of regurgitation. The commissures and leaflet surfaces were assessed. The results of surgical valvuloplasty could be evaluated by 3D echocardiography. 3D echocardiography is now transthoracic and a real time investigation. Technical advances are required before it comes into routine usage: a more manoeuvrable matricial probe (integrating pulsed and continuous wave Doppler) and larger volume real time 3D imaging with better resolution. Its role in the assessment of Ebstein's anomaly should be evaluated in a larger series of patients.

[Spiral CT scan imaging of the coronary vessels six years after complete repair of a Taussig-Bing malformation]. / Imagerie coronaire par scanner spiralé 6 ans après correction complete d'une malformation de Taussig-Bing.

The Taussig-Bing malformation is a rare form of transposition of the great arteries with a ventricular septal defect. Associated cardiac abnormalities are common: hypoplasia of the aorta and especially coronary anomalies which may complicate surgical repair. The authors report the case of a patient with this malformation diagnosed in utero and who underwent anatomical repair on the 11th day of life. The coronary anatomy described by the surgeon was type E of Yacoub and Radley-Smith's classification. The postoperative course was uncomplicated. At the age of 6, a spiral CT scan was performed routinely under betablocker therapy. The coronary trajectory with a double loop, the patency of the coronary ostia and of the aortic isthmus were accurately demonstrated by this form of imaging.

[3D echocardiography of the ascending aorta in Marfan's syndrome]. / Echocardiographie 3D de l'aorte ascendante dans le syndrome de Marfan.

Marfan's syndrome is a cause of dilatation of the aorta, the main complication of which is dissection of the aorta. 2D echocardiography is the reference investigation for measuring the ascending aorta. Asymmetry of sinus dilatation makes a 3D approach necessary. Real time 3D echocardiography is a simple, non-invasive method which, by a biplane mode, allows measurement of the 3 sinuses of Valsalva. The aim of the study was to compare the 2D and 3D echocardiographic methods for measuring the ascending aorta. Fifteen patients (average age 12 +/- 8 years) with Marfan's syndrome were studied prospectively. The maximal 3D diameter was significantly greater than the 2D measurement (31.7 +/- 6.8 mm vs 29.9 +/- 6.6 mm, p< 0.005). In 4 patients, the difference was over 3 mm. The diameter between the right coronary and left coronary sinus was greater than the two others (right coronary-non coronary and left coronary-non coronary). The oldest 5 patients had an MRI aortic measurement very similar to that of 3D echocardiography (36.6 vs 36.7 mm). Real time 3D echocardiography in the biplane mode enables reliable and reproducible measurement of the aortic root in patients with Marfan's syndrome. Larger and multicenter studies are required to allow confirmation of the value of 3D echocardiography in the follow-up of these patients.

[Unusual association of chylopericardium and aortic hypoplasia in a neonate]. / Association inhabituelle chez un nouveau-né d'un chylopéricarde et d'une hypoplasie aortique.

We report the case of a neonate with two very rare anomalies: primary chylopericardium and diffuse hypoplasia of the thoraco-abdominal aorta. The presentation on the 16th post-natal day was with dyspnoea and refusal to feed. The initial clinical examination revealed hepatomegaly and weak femoral pulses. 2D ultrasound gave a diagnosis of a large compressive pericardial effusion combined with moderate hypoplasia of the aortic isthmus. Emergency pericardial drainage removed 80ml of chylous liquid. Following prolonged parenteral nutrition, the pericardial effusion stabilised. A mechanism of diffuse vascular disease affecting the aorta and the lymphatic system is suggested.