Natural history and outcomes in paediatric RASopathy-associated hypertrophic cardiomyopathy.

AIMS: This study aimed to describe the natural history and predictors of all-cause mortality and sudden cardiac death (SCD)/equivalent events in children with a RASopathy syndrome and hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: This is a retrospective cohort study from 14 paediatric cardiology centres in the United Kingdom and Ireland. We included children <18 years with HCM and a clinical and/or genetic diagnosis of a RASopathy syndrome [Noonan syndrome (NS), NS with multiple lentigines (NSML), Costello syndrome (CS), cardiofaciocutaneous syndrome (CFCS), and NS with loose anagen hair (NS-LAH)]. One hundred forty-nine patients were recruited [111 (74.5%) NS, 12 (8.05%) NSML, 6 (4.03%) CS, 6 (4.03%) CFCS, 11 (7.4%) Noonan-like syndrome, and 3 (2%) NS-LAH]. NSML patients had higher left ventricular outflow tract (LVOT) gradient values [60 (36-80) mmHg, P = 0.004]. Over a median follow-up of 197.5 [inter-quartile range (IQR) 93.58-370] months, 23 patients (15.43%) died at a median age of 24.1 (IQR 5.6-175.9) months. Survival was 96.45% [95% confidence interval (CI) 91.69-98.51], 90.42% (95% CI 84.04-94.33), and 84.12% (95% CI 75.42-89.94) at 1, 5, and 10 years, respectively, but this varied by RASopathy syndrome. RASopathy syndrome, symptoms at baseline, congestive cardiac failure (CCF), non-sustained ventricular tachycardia (NSVT), and maximal left ventricular wall thickness were identified as predictors of all-cause mortality on univariate analysis, and CCF, NSVT, and LVOT gradient were predictors for SCD or equivalent event. CONCLUSIONS: These findings highlight a distinct category of patients with Noonan-like syndrome with a milder HCM phenotype but significantly worse survival and identify potential predictors of adverse outcome in patients with RASopathy-related HCM.

Neonatal sepsis and cardiovascular dysfunction I: mechanisms and pathophysiology.

The highest incidence of sepsis across all age groups occurs in neonates leading to substantial mortality and morbidity. Cardiovascular dysfunction frequently complicates neonatal sepsis including biventricular systolic and/or diastolic dysfunction, vasoregulatory failure, and pulmonary arterial hypertension. The haemodynamic response in neonatal sepsis can be hyperdynamic or hypodynamic and the underlying pathophysiological mechanisms are heterogeneous. The diagnosis and definition of both neonatal sepsis and cardiovascular dysfunction complicating neonatal sepsis are challenging and not consensus-based. Future developments in neonatal sepsis management will be facilitated by common definitions and datasets especially in neonatal cardiovascular optimisation. IMPACT: Cardiovascular dysfunction is common in neonatal sepsis but there is no consensus-based definition, making calculating the incidence and designing clinical trials challenging. Neonatal cardiovascular dysfunction is related to the inflammatory response, which can directly target myocyte function and systemic haemodynamics.

Sudden cardiac death in childhood RASopathy-associated hypertrophic cardiomyopathy: Validation of the HCM risk-kids model and predictors of events.

BACKGROUND: RASopathies account for nearly 20% of cases of childhood hypertrophic cardiomyopathy (HCM). Sudden cardiac death (SCD) occurs in patients with RASopathy-associated HCM, but the risk factors for SCD have not been systematically evaluated. AIM: To validate the HCM Risk-Kids SCD risk prediction model in children with RASopathy-associated HCM and investigate potential specific SCD predictors in this population. METHODS: Validation of HCM Risk-Kids was performed in a retrospective cohort of 169 patients with a RASopathy-associated HCM from 15 international paediatric cardiology centres. Multiple imputation by chained equations was used for missing values related to the HCM Risk-Kids parameters. RESULTS: Eleven patients (6.5%) experienced a SCD or equivalent event at a median age of 12.5 months (IQR 7.7-28.64). The calculated SCD/equivalent event incidence was 0.78 (95% CI 0.43-1.41) per 100 patient years. Six patients (54.54%) with an event were in the low-risk category according to the HCM Risk-Kids model. Harrell's C index was 0.60, with a sensitivity of 9.09%, specificity of 63.92%, positive predictive value of 1.72%, and negative predictive value of 91%; with a poor distinction between the different risk groups. Unexplained syncope (HR 42.17, 95% CI 10.49-169.56, p < 0.001) and non-sustained ventricular tachycardia (HR 5.48, 95% CI 1.58-19.03, p < 0.007) were predictors of SCD on univariate analysis. CONCLUSION: Unexplained syncope and the presence of NSVT emerge as predictors for SCD in children with RASopathy-associated HCM. The HCM Risk-Kids model may not be appropriate to use in this population, but larger multicentre collaborative studies are required to investigate this further.

Isolated left ventricular apical hypoplasia: Systematic review and analysis of the 37 cases reported so far.

BACKGROUND: Isolated left ventricular apical hypoplasia (ILVAH), also known as truncated left ventricle (LV), is a very unusual cardiomyopathy. It is characterised by a truncated, spherical, and non-apex forming LV. The true apex is occupied by the right ventricle. Due to the rarity of the disease, just a few case reports and limited case series have been published in the field. AIM: To analysing the so far 37 reported ILVAH cases worldwide. METHODS: The electronic databases PubMed and Scopus were investigated from their establishment up to December 13, 2022. RESULTS: The majority of cases reported occurred in males (52.7%). Mean age at diagnosis was 26.1 ± 19.6 years. More than a third of the patients were asymptomatic (35.1%). The most usual clinical presentation was breathlessness (40.5%). The most commonly detected electrocardiogram changes were T wave abnormalities (29.7%) and right axis deviation with poor R wave progression (24.3%). Atrial fibrillation/flutter was detected in 24.3%. Echocardiography was performed in 97.3% of cases and cardiac MRI in 91.9% of cases. Ejection fraction was reduced in more than a half of patients (56.7%). An associated congenital heart disease was found in 16.2%. Heart failure therapy was administered in 35.1% of patients. The outcome was favorable in the vast majority of patients, with just one death. CONCLUSION: ILVAH is a multifaceted entity with a so far unpredictable course, ranging from benign until the elderly to sudden death during adolescence.

Protocol for a prospective cohort study exploring the gut microbiota of infants with congenital heart disease undergoing cardiopulmonary bypass (the GuMiBear study).

INTRODUCTION: The gut microbiota develops from birth and matures significantly during the first 24 months of life, playing a major role in infant health and development. The composition of the gut microbiota is influenced by several factors including mode of delivery, gestational age, feed type and treatment with antibiotics. Alterations in the pattern of gut microbiota development and composition can be associated with illness and compromised health outcomes.Infants diagnosed with 'congenital heart disease' (CHD) often require surgery involving cardiopulmonary bypass (CPB) early in life. The impact of this type of surgery on the integrity of the gut microbiome is poorly understood. In addition, these infants are at significant risk of developing the potentially devastating intestinal condition necrotising enterocolitis. METHODS AND ANALYSIS: This study will employ a prospective cohort study methodology to investigate the gut microbiota and urine metabolome of infants with CHD undergoing surgery involving CPB. Stool and urine samples, demographic and clinical data will be collected from eligible infants based at the National Centre for Paediatric Cardiac Surgery in Ireland. Shotgun metagenome sequencing will be performed on stool samples and urine metabolomic analysis will identify metabolic biomarkers. The impact of the underlying diagnosis, surgery involving CPB, and the influence of environmental factors will be explored. Data from healthy age-matched infants from the INFANTMET study will serve as a control for this study. ETHICS AND DISSEMINATION: This study has received full ethical approval from the Clinical Research Ethics Committee of Children's Health Ireland, GEN/826/20.

Echocardiographic scores for biventricular repair risk prediction of congenital heart disease with borderline left ventricle: a review.

The aim of this review is to highlight the strengths and limitations of major echocardiographic biventricular repair (BVR) prediction models for borderline left ventricle (LV) in complex congenital heart disease (CHD). A systematic search in the National Library of Medicine for Medical Subject Headings and free text terms including echocardiography, CHD, and scores, was performed. The search was refined by adding keywords for critical aortic stenosis (AS), borderline LV, complex left ventricular outflow tract (LVOT) obstruction, hypoplastic left heart syndrome/complex (HLHS/HLHC), and unbalanced atrio-ventricular septal defects (uAVSD). Fifteen studies were selected for the final analysis. We outlined what echocardiographic scores for different types of complex CHD with diminutive LV are available. Scores for CHD with LVOT obstruction including critical AS, HLHS/HLHC, and aortic arch hypoplasia have been validated and implemented by several studies. Scores for uAVSD with right ventricle (RV) dominance have also been established and implemented, the first being the atrioventricular valve index (AVVI). In addition to AVII, both LV/RV inflow angle and LV inflow index have all been validated for the prediction of BVR. We conclude with a discussion of limitations in the development and validation of each of these scores, including retrospective design during score development, heterogeneity in echocardiographic parameters evaluated, variability in the definition of outcomes, differences in adopted surgical and Interventional strategies, and institutional differences. Furthermore, scores developed in the past two decades may have little clinical relevance now. In summary, we provide a review of echocardiographic scores for BVR in complex CHD with a diminutive LV that may serve as a guide for use in modern clinical practice.

Should We Be Screening for Ischaemic Heart Disease Earlier in Childhood?

Ischaemic heart disease is the most common cause of death in males and the second in the female gender. Yet we often only focus on identification and treatment of this foremost cause of death in adulthood. The review asks the question what form of coronary disease do we encounter in childhood, what predisposing factors give rise to atherosclerosis and what strategies in childhood could we employ to detect and reduce atherosclerosis development in later life.

Severe Restriction of a VSD and Development of Pulmonary Atresia in a Patient with Transposition of the Great Arteries: Fetal Diagnosis.

Pulmonary atresia with an intact ventricular septum typically occurs in patients with concordant atrioventricular and ventriculoarterial connections. When it does occur in patients with discordant connections, it is most frequently seen in association with congenitally corrected transposition. We present a rare case of transposition of the great arteries with a ventricular septal defect (VSD) detected in fetal life which evolved throughout pregnancy resulting in the development of pulmonary atresia and severe restriction of the VSD.

Clinical Features and Natural History of Preadolescent Nonsyndromic Hypertrophic Cardiomyopathy.

BACKGROUND: Up to one-half of childhood sarcomeric hypertrophic cardiomyopathy (HCM) presents before the age of 12 years, but this patient group has not been systematically characterized. OBJECTIVES: The aim of this study was to describe the clinical presentation and natural history of patients presenting with nonsyndromic HCM before the age of 12 years. METHODS: Data from the International Paediatric Hypertrophic Cardiomyopathy Consortium on 639 children diagnosed with HCM younger than 12 years were collected and compared with those from 568 children diagnosed between 12 and 16 years. RESULTS: At baseline, 339 patients (53.6%) had family histories of HCM, 132 (20.9%) had heart failure symptoms, and 250 (39.2%) were prescribed cardiac medications. The median maximal left ventricular wall thickness z-score was 8.7 (IQR: 5.3-14.4), and 145 patients (27.2%) had left ventricular outflow tract obstruction. Over a median follow-up period of 5.6 years (IQR: 2.3-10.0 years), 42 patients (6.6%) died, 21 (3.3%) underwent cardiac transplantation, and 69 (10.8%) had life-threatening arrhythmic events. Compared with those presenting after 12 years, a higher proportion of younger patients underwent myectomy (10.5% vs 7.2%; P = 0.045), but fewer received primary prevention implantable cardioverter-defibrillators (18.9% vs 30.1%; P = 0.041). The incidence of mortality or life-threatening arrhythmic events did not differ, but events occurred at a younger age. CONCLUSIONS: Early-onset childhood HCM is associated with a comparable symptom burden and cardiac phenotype as in patients presenting later in childhood. Long-term outcomes including mortality did not differ by age of presentation, but patients presenting at younger than 12 years experienced adverse events at younger ages.

Relationship Between Maximal Left Ventricular Wall Thickness and Sudden Cardiac Death in Childhood Onset Hypertrophic Cardiomyopathy.

BACKGROUND: Maximal left ventricular wall thickness (MLVWT) is a risk factor for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). In adults, the severity of left ventricular hypertrophy has a nonlinear relationship with SCD, but it is not known whether the same complex relationship is seen in childhood. The aim of this study was to describe the relationship between left ventricular hypertrophy and SCD risk in a large international pediatric HCM cohort. METHODS: The study cohort comprised 1075 children (mean age, 10.2 years [±4.4]) diagnosed with HCM (1-16 years) from the International Paediatric Hypertrophic Cardiomyopathy Consortium. Anonymized, noninvasive clinical data were collected from baseline evaluation and follow-up, and 5-year estimated SCD risk was calculated (HCM Risk-Kids). RESULTS: MLVWT Z score was <10 in 598 (58.1%), ≥10 to <20 in 334 (31.1%), and ≥20 in 143 (13.3%). Higher MLVWT Z scores were associated with heart failure symptoms, unexplained syncope, left ventricular outflow tract obstruction, left atrial dilatation, and nonsustained ventricular tachycardia. One hundred twenty-two patients (71.3%) with MLVWT Z score ≥20 had coexisting risk factors for SCD. Over a median follow-up of 4.9 years (interquartile range, 2.3-9.3), 115 (10.7%) had an SCD event. Freedom from SCD event at 5 years for those with MLVWT Z scores <10, ≥10 to <20, and ≥20 was 95.6%, 87.4%, and 86.0, respectively. The estimated SCD risk at 5 years had a nonlinear, inverted U-shaped relationship with MLVWT Z score, peaking at Z score +23. The presence of coexisting risk factors had a summative effect on risk. CONCLUSIONS: In children with HCM, an inverted U-shaped relationship exists between left ventricular hypertrophy and estimated SCD risk. The presence of additional risk factors has a summative effect on risk. While MLVWT is important for risk stratification, it should not be used either as a binary variable or in isolation to guide implantable cardioverter defibrillator implantation decisions in children with HCM.

Post-transplant lymphoproliferative disorder presenting as supraglottitis following pediatric heart transplantation treated with EBV-specific cytotoxic T-lymphocytes.

We present the case of a 4 year-old boy post heart transplantation who presented with signs and symptoms of critical airway obstruction and was initially diagnosed with infective supraglottitis. Following re-presentation and biopsy, this was confirmed as post-transplant lymphoproliferative disorder (PTLD) in an unusual site; laryngeal PTLD is rare. The patient failed standard therapy and ultimately was successfully treated with EBV-specific cytotoxic T lymphocytes (CTL). This case describes a rare presentation of PTLD which required a novel treatment approach including elective tracheostomy prior to CTL therapy. The treatment was successful and the patient was decannulated prior to discharge following 4 negative biopsies, the most recent 6 months following treatment completion. The case also highlights the importance of extra-vigilance in the post-transplant population and of a collaborative approach between multiple specialties across two separate countries including the transplant center and the referral center.

The role of the electrocardiographic phenotype in risk stratification for sudden cardiac death in childhood hypertrophic cardiomyopathy.

AIMS: The 12-lead electrocardiogram (ECG) is routinely performed in children with hypertrophic cardiomyopathy (HCM). An ECG risk score has been suggested as a useful tool for risk stratification, but this has not been independently validated. This aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events. METHODS AND RESULTS: Data from 356 childhood HCM patients with a mean age of 10.1 years (±4.5) were collected from a retrospective, multi-centre international cohort. Three hundred and forty-seven (97.5%) patients had ECG abnormalities at baseline, most commonly repolarization abnormalities (n = 277, 77.8%); left ventricular hypertrophy (n = 240, 67.7%); abnormal QRS axis (n = 126, 35.4%); or QT prolongation (n = 131, 36.8%). Over a median follow-up of 3.9 years (interquartile range 2.0-7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93-2.04). No ECG variables were associated with 5-year arrhythmic event on univariable or multivariable analysis. The ECG risk score threshold of >5 had modest discriminatory ability [C-index 0.60 (95% CI 0.484-0.715)], with corresponding negative and positive predictive values of 96.7% and 6.7. CONCLUSION: In a large, international, multi-centre cohort of childhood HCM, ECG abnormalities were common and varied. No ECG characteristic, either in isolation or combined in the previously described ECG risk score, was associated with 5-year sudden cardiac death risk. This suggests that the role of baseline ECG phenotype in improving risk stratification in childhood HCM is limited.

Nicolaides-Baraitser syndrome in a patient with hypertrophic cardiomyopathy and SMARCA2 gene deletion.

Nicolaides-Baraitser syndrome is a rare, neuro-developmental disorder caused by heterozygous pathogenic variants in the SMARCA2 gene, involved with chromatin regulation. Cardinal features include intellectual disability, short stature, microcephaly, triangular facies, sparse hair, brachydactyly, prominent interphalangeal joints and seizures. Genetic testing demonstrated a loss within SMARCA2 at 9p24.3 inclusive of basepairs 2094861_2141830 (hg19) in our patient. This case highlights a child with Nicolaides-Baraiter syndrome, a SMARCA2 gene deletion and a novel association of hypertrophic obstructive cardiomyopathy.

Efficacy of Sirolimus in Patients Requiring Tracheostomy for Life-Threatening Lymphatic Malformation of the Head and Neck: A Report From the European Reference Network.

Extensive lymphatic malformations (LMs) of the head and neck region may require tracheostomy to secure the airway. Treatment of these life-threatening LMs is usually multimodal and includes sclerotherapy and surgery, among others. Recently, systemic therapy with sirolimus has been introduced as an effective treatment for venous and lymphatic malformations; its efficacy and safety profile in patients with extensive LM requiring tracheostomy are, however, as yet not fully known. We performed a retrospective, multicenter review and identified 13 patients with an extensive LM of the head and neck region, who previously underwent placement of tracheostomy and subsequently received sirolimus treatment with the aim to improve the local respiratory situation and remove the tracheostomy. Under sirolimus therapy, tracheostomy could be reversed in 8/13 (62%) patients, a further 2/13 (15%) patients improved markedly, and removal of the tracheostomy was planned at the time of writing, while 3/13 (23%) patients showed insufficient or absent response to sirolimus, rendering tracheostomy reversal not feasible. The median duration of sirolimus treatment until removal of tracheostomy was 18 months (range, 8 months to 5.6 years). Adverse events of sirolimus therapy were common [10/13 (77%) patients], yet the majority of these were mild [9/10 (90%) patients] and only one severe adverse event was recorded, with ulceration and necrosis at a catheter insertion site. In conclusion, sirolimus can be considered an effective and safe salvage treatment in patients with extensive LM even after placement of a tracheostomy, as closure of the latter was possible in the majority of patients (62%) of our retrospective cohort. A better understanding of when to start sirolimus therapy, of the duration of treatment, and of factors allowing the prediction of treatment response will require further investigation.

Decision-Making in the Catheter Laboratory: The Most Important Variable in Successful Outcomes.

Increasingly the importance of how and why we make decisions in the medical arena has been questioned. Traditionally the aeronautical and business worlds have shed a light on this complex area of human decision-making. In this review we reflect on what we already know about the complexity of decision-making in addition to directing particular focus on the challenges to decision-making in the high-intensity environment of the pediatric cardiac catheterization laboratory. We propose that the most critical factor in outcomes for children in the catheterization lab may not be technical failures but rather human factors and the lack of preparation and robust shared decision-making process between the catheterization team. Key technical factors involved in the decision-making process include understanding the anatomy, the indications and objective to be achieved, equipment availability, procedural flow, having a back-up plan and post-procedural care plan. Increased awareness, pre-catheterization planning, use of standardized clinical assessment and management plans and artificial intelligence may provide solutions to pitfalls in decision-making. Further research and efforts should be directed towards studying the impact of human factors in the cardiac catheterization laboratory as well as the broader medical environment.

Early predictors of epilepsy and subsequent relapse in children with acute disseminated encephalomyelitis.

OBJECTIVE: To identify predictors of epilepsy and clinical relapses in children presenting with acute disseminated encephalomyelitis (ADEM). METHODS: Children presenting with ADEM between 2005 and 2017 and tested clinically for MOG-Ab were identified from three tertiary paediatric neurology centres in the United Kingdom. Patients were followed up for a median of 6 years (range, 1-16 years). RESULTS: A total of 74 children were studied (38 females; median age at first presentation: 4.5 years (range, 1.4-16 years)). MOG-Ab was positive in 50/74 (67.6%) of cases, and 27 (54%) of MOG-Ab positive children presented with a neurological relapse over time. MOG-Ab was more frequently positive in the relapsing group than in the monophasic group (27/31 vs 23/43; odds ratio 5.9 (95% CI: 1.8-19.7); p = 0.002). 16/74 (22%) children had seizures during the acute presentation with ADEM and 12/74 (16.2%) patients were diagnosed with post-ADEM epilepsy. The diagnosis of post-ADEM epilepsy was more frequently observed in children with relapsing disease than monophasic disease (10/31 vs 2/43; odds ratio 9.8 (95% confidence interval (CI): 2.0-48.7); p = 0.003), in children who had positive intrathecal oligoclonal bands than those with negative bands (4/7 vs 4/30; odds ratio 8.7 (95% CI: 1.4-54.0); p = 0.027) and in children who had positive MOG-Ab than negative MOG-Ab cases (11/12 vs 39/62; odds ratio 6.5 (95% CI:0.8-53.6); p = 0.051). CONCLUSION: A higher relapse rate and a greater risk of post-ADEM epilepsy in children with MOG-Ab-associated disease may indicate a chronic disease with immune-mediated seizures in these children.

Refractory Kawasaki disease: diagnostic and management challenges.

Kawasaki disease (KD), an acute, self-limiting, medium-sized arterial vasculitis, is now the most common cause of acquired heart disease in childhood in the developed world. In this review, we discuss the diagnosis of KD, predicting resistance to traditional therapy and treatment options in refractory or high-risk disease. We also highlight ongoing clinical trials and other potential avenues of research which may prove beneficial in managing children, especially those with resistant KD.

Development of a Novel Risk Prediction Model for Sudden Cardiac Death in Childhood Hypertrophic Cardiomyopathy (HCM Risk-Kids).

Importance: Sudden cardiac death (SCD) is the most common mode of death in childhood hypertrophic cardiomyopathy (HCM), but there is no validated algorithm to identify those at highest risk. Objective: To develop and validate an SCD risk prediction model that provides individualized risk estimates. Design, Setting, and Participants: A prognostic model was developed from a retrospective, multicenter, longitudinal cohort study of 1024 consecutively evaluated patients aged 16 years or younger with HCM. The study was conducted from January 1, 1970, to December 31, 2017. Exposures: The model was developed using preselected predictor variables (unexplained syncope, maximal left-ventricular wall thickness, left atrial diameter, left-ventricular outflow tract gradient, and nonsustained ventricular tachycardia) identified from the literature and internally validated using bootstrapping. Main Outcomes and Measures: A composite outcome of SCD or an equivalent event (aborted cardiac arrest, appropriate implantable cardioverter defibrillator therapy, or sustained ventricular tachycardia associated with hemodynamic compromise). Results: Of the 1024 patients included in the study, 699 were boys (68.3%); mean (interquartile range [IQR]) age was 11 (7-14) years. Over a median follow-up of 5.3 years (IQR, 2.6-8.3; total patient years, 5984), 89 patients (8.7%) died suddenly or had an equivalent event (annual event rate, 1.49; 95% CI, 1.15-1.92). The pediatric model was developed using preselected variables to predict the risk of SCD. The model's ability to predict risk at 5 years was validated; the C statistic was 0.69 (95% CI, 0.66-0.72), and the calibration slope was 0.98 (95% CI, 0.59-1.38). For every 10 implantable cardioverter defibrillators implanted in patients with 6% or more of a 5-year SCD risk, 1 patient may potentially be saved from SCD at 5 years. Conclusions and Relevance: This new, validated risk stratification model for SCD in childhood HCM may provide individualized estimates of risk at 5 years using readily obtained clinical risk factors. External validation studies are required to demonstrate the accuracy of this model's predictions in diverse patient populations.

Paediatric multiple sclerosis: a new era in diagnosis and treatment.

Multiple sclerosis is a chronic immune-mediated demyelinating disease of the central nervous system. The diagnosis of multiple sclerosis in children, as in adults, requires evidence of dissemination of inflammatory activity in more than one location in the central nervous system (dissemination in space) and recurrent disease over time (dissemination in time). The identification of myelin oligodendrocyte glycoprotein antibodies (MOG-Ab) and aquaporin-A antibodies (AQP4-Ab), and the subsequent discovery of their pathogenic mechanisms, have led to a shift in the classification of relapsing demyelinating syndromes. This is reflected in the 2017 revised criteria for the diagnosis of multiple sclerosis, which emphasizes the exclusion of multiple sclerosis mimics and aims to enable earlier diagnosis and thus treatment initiation. The long-term efficacy of individual therapies initiated in children with multiple sclerosis is hard to evaluate, owing to the small numbers of patients who have the disease, the relatively high number of patients who switch therapy, and the need for long follow-up studies. Nevertheless, an improvement in prognosis with a globally reduced annual relapse rate in children with multiple sclerosis is now observed compared with the pretreatment era, indicating a possible long-term effect of therapies. Given the higher relapse rate in children compared with adults, and the impact multiple sclerosis has on cognition in the developing brain, there is a question whether rapid escalation or potent agents should be used in children, while the short- and long-term safety profiles of these drugs are being established. With the results of the first randomized controlled trial of fingolimod versus interferon-ß1a in paediatric multiple sclerosis published in 2018 and several clinical trials underway, there is hope for further progress in the field of paediatric multiple sclerosis. WHAT THIS PAPER ADDS: Early and accurate diagnosis of multiple sclerosis is crucial. The discovery of antibody-mediated demyelination has changed the diagnosis and management of relapsing demyelination syndromes. Traditional escalation therapy is being challenged by induction therapy.

ESCLEROSIS MÚLTIPLE PEDIÁTRICA: UNA NUEVA ERA EN EL DIAGNÓSTICO Y TRATAMIENTO: La esclerosis múltiple es una enfermedad desmielinizante crónica mediada por el sistema inmunitario del sistema nervioso central. El diagnóstico de esclerosis múltiple en niños, como en adultos, requiere evidencia de diseminación de actividad inflamatoria en más de un lugar en el sistema nervioso central (diseminación en el espacio) y enfermedad recurrente a lo largo del tiempo (diseminación en el tiempo). La identificación de los anticuerpos de la glicoproteína oligodendrocítica de la mielina (MOG-Ab) y los anticuerpos de la acuaporina-A (AQP4-Ab), y el posterior descubrimiento de sus mecanismos patógenos, han conducido a un cambio en la clasificación de los síndromes desmielinizantes recurrentes. Esto se refleja en los criterios revisados ​​de 2017 para el diagnóstico de esclerosis múltiple, que enfatiza la exclusión de los imitadores de la esclerosis múltiple y tiene como objetivo permitir un diagnóstico más temprano y, por lo tanto, el inicio del tratamiento. La eficacia a largo plazo de las terapias individuales iniciadas en niños con esclerosis múltiple es difícil de evaluar, debido a la pequeña cantidad de pacientes que tienen la enfermedad, la cantidad relativamente alta de pacientes que cambian de terapia y la necesidad de estudios de seguimiento prolongados. Sin embargo, ahora se observa una mejora en el pronóstico con una tasa de recaída anual globalmente reducida en niños con esclerosis múltiple en comparación con la era anterior al tratamiento previo, lo que indica un posible efecto a largo plazo de las terapias. Debido a la mayor tasa de recaída en niños en comparación con los adultos, y el impacto que tiene la esclerosis múltiple en la cognición en el cerebro en desarrollo, existe la duda de si se deben usar agentes de aumento rápido o potentes en niños, mientras que los perfiles de seguridad a corto y largo plazo de estos medicamentos se están estableciendo. Con los resultados del primer ensayo controlado aleatorio de fingolimod versus interferón-ß1a en esclerosis múltiple pediátrica publicado en 2018 y varios ensayos clínicos en curso, existe la esperanza de un mayor progreso en el campo de la esclerosis múltiple pediátrica.

ESCLEROSE MÚLTIPLA PEDIÁTRICA: UMA NOVA ERA NO DIAGNÓSTICO E TRATAMENTO: A esclerose múltipla é uma doença desmielinizante imunomediada crônica do sistema nervoso central. O diagnóstico de esclerose múltipla em crianças, como em adultos, exige evidência de disseminação da atividade inflamatória em mais de um local no sistema nervoso central (disseminação no espaço) e doença recorrente ao longo do tempo (disseminação no tempo). A identificação de anticorpos anti-glicoproteína de mielina do oligodendrócito (MOG-Ab) e anticorpos anti-aquaporina A (AQP4-Ab), e a subsequente descoberta de seus mecanismos patogênicos, levaram a uma mudança na classificação das síndromes desmielinizantes recidivantes. Isso se reflete nos critérios revisados de 2017 para o diagnóstico de esclerose múltipla, que enfatizam a exclusão de transtornos que mimetizam esclerose múltipla e visam permitir o diagnóstico precoce e, portanto, o início do tratamento. É difícil avaliar a eficácia a longo prazo de terapias individuais iniciadas em crianças com esclerose múltipla, devido ao pequeno número de pacientes que têm a doença, o número relativamente alto de pacientes que trocam de terapia e a necessidade de estudos de acompanhamento a longo prazo. No entanto, uma melhora no prognóstico com uma taxa de recaída anual globalmente reduzida em crianças com esclerose múltipla é agora observada em comparação com a era pré-tratamento, indicando um possível efeito a longo prazo das terapias. Dada a maior taxa de recaída em crianças em comparação com adultos, e o impacto da esclerose múltipla na cognição no cérebro em desenvolvimento, há uma questão se a escalada rápida ou agentes potentes devem ser usados em crianças, enquanto os perfis de segurança de curto e longo prazo destas drogas estão sendo estabelecidos. Com os resultados do primeiro estudo controlado randomizado de fingolimode versus interferon-ß1a na esclerose múltipla pediátrica publicado em 2018 e vários ensaios clínicos em andamento, há esperança de mais progressos no campo da esclerose múltipla pediátrica.