RESUMO
Neurodevelopmental disorders have been linked to numerous genes, particularly pathogenic variants in genes encoding postsynaptic scaffolding proteins, like SHANK3. This study aims to provide insights into the cardiovascular profile of patients with pathogenic SHANK3 variants, expanding beyond the well-established associations with neurodevelopmental disorders and epilepsy. We conducted a prospective study involving patients affected by neurodevelopmental disorders with pathogenic SHANK3 variants. Comprehensive cardiovascular assessments were performed and molecular genetic testing included chromosomal microarray followed by clinical exome sequencing. We identified five patients with de novo SHANK3 variants, all of whom exhibited cardiac involvement, including myocardial dysfunction, congenital heart disease (patent ductus arteriosus), and a case of postictal atrial fibrillation. Our findings emphasize an elevated risk of cardiovascular abnormalities in patients with SHANK3 pathogenic variants compared to prior reports. Despite their young age, these patients displayed significant cardiac abnormalities. The study highlights the necessity of integrating cardiac evaluation and ongoing cardiovascular monitoring into multidisciplinary care, facilitating early detection of heart failure and assessment of the risk of sudden unexpected death in epilepsy (SUDEP). Further research is needed to elucidate the underlying mechanisms of cardiac manifestations in SHANK3 mutation carriers.
RESUMO
BACKGROUND: Acute ischemic stroke is a leading cause of pediatric death and disability. A clinical scale adapted for children can ensure early detection of candidates for urgent acute ischemic stroke treatment. The Rapid Arterial Occlusion Evaluation (RACE) scale for adults, which scores 5 items (facial palsy 0-2; arm motor function 0-2; leg motor function 0-2; head/gaze deviation 0-1; and aphasia or agnosia 0-2), has good sensitivity and specificity in detecting large vessel occlusion. METHODS: We adapted the previously validated RACE scale for use in children as the Pediatric RACE scale. This adapted scale was tested by prehospital/emergency room staff attending to patients covered by the Catalan Pediatric Stroke Code and child neurologists for its correlation with the Pediatric National Institutes of Health Stroke Scale and for interrater reliability. RESULTS: The study included 50 children, 18 with confirmed strokes (7 acute ischemic strokes and 11 hemorrhagic strokes). Prehospital/emergency staff and child neurologists agreed fully regarding 82% of patients and 100% regarding head/gaze deviation and agnosia. The Pediatric RACE scale correlated strongly with the Pediatric National Institutes of Health Stroke Scale in evaluations by child neurologists (Spearman ρ, 0.852; P<0.001) and prehospital/emergency staff (Spearman ρ, 0.781; P<0.001). The median Pediatric RACE score was significantly higher in patients with large vessel occlusion (6.5; interquartile range, 6-7) than with other etiologies. CONCLUSIONS: Pediatric RACE, showing good interrater reliability and correlation with the Pediatric National Institutes of Health Stroke Scale, is a simple scale to detect candidates for pediatric acute stroke treatment, designed for both prehospital and in-hospital use by non-neurologist medical staff.
RESUMO
Objective: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are used to assess disease activity in juvenile idiopathic arthritis (JIA). However, because these biomarkers do not always differentiate between active and inactive disease, there is a need for alternative markers such as serum calprotectin (sCal). The main aim of this proof-of-concept study was to assess the diagnostic accuracy of sCal in patients with JIA. Secondary aims were to identify the optimal sCal cut-off levels to define active disease and evaluate the association between these biomarkers and disease activity status. Methods: Serum samples were obtained from 25 pediatric patients with JIA. Serum calprotectin levels were determined by two different assays, the QUANTA FLASH chemiluminescence immunoassay (CLIA) from Inova Diagnostics and the solid-phase enzyme immunoassay (EIA) from Bühlmann Laboratories. Diagnostic accuracy was assessed for sCal CLIA, sCal EIA, CRP, and ESR. The results obtained by the CLIA and EIA methodologies were compared. We also evaluated the association between the individual each biomarkers (sCal CLIA, sCal EIA, CRP, and ESR) and disease activity (according to JADAS-27 criteria and the ACR criteria modified by Anink and colleagues). Results: For both sCal assays (CLIA and EIA), the optimal cut-off level (ROC analysis) was the same (2.3â µg/ml). Serum calprotectin levels measured by CLIA and EIA were strongly correlated with each other (Kendall's tau-b, 0.71; p < 0.001). Compared to ESR and CRP, sCal CLIA and EIA were both more accurate (i.e., greater sensitivity) in identifying patients with active disease. By contrast, ESR and CRP were more effective in identifying patients in remission (i.e., better specificity). Conclusion: This proof-of-concept study shows that determination of serum calprotectin levels with CLIA or EIA can accurately identify the presence of active disease in patients with JIA.
Assuntos
Esofagite , Humanos , Esofagite/diagnóstico , Esofagite/patologia , Masculino , Criança , Esôfago/diagnóstico por imagem , Esôfago/patologia , FemininoRESUMO
Pathogenic variants in KANSL1 and 17q21.31 microdeletions are causative of Koolen-de Vries syndrome (KdVS), a neurodevelopmental syndrome with characteristic facial dysmorphia. Our previous work has shown that syndromic conditions caused by pathogenic variants in epigenetic regulatory genes have identifiable patterns of DNA methylation (DNAm) change: DNAm signatures or episignatures. Given the role of KANSL1 in histone acetylation, we tested whether variants underlying KdVS are associated with a DNAm signature. We profiled whole-blood DNAm for 13 individuals with KANSL1 variants, four individuals with 17q21.31 microdeletions, and 21 typically developing individuals, using Illumina's Infinium EPIC array. In this study, we identified a robust DNAm signature of 456 significant CpG sites in 8 individuals with KdVS, a pattern independently validated in an additional 7 individuals with KdVS. We also demonstrate the diagnostic utility of the signature and classify two KANSL1 VUS as well as four variants in individuals with atypical clinical presentation. Lastly, we investigated tissue-specific DNAm changes in fibroblast cells from individuals with KdVS. Collectively, our findings contribute to the understanding of the epigenetic landscape related to KdVS and aid in the diagnosis and classification of variants in this structurally complex genomic region.
Assuntos
Anormalidades Múltiplas , Deleção Cromossômica , Deficiência Intelectual , Humanos , Anormalidades Múltiplas/genética , Cromossomos Humanos Par 17 , Metilação de DNA , Genes Reguladores , Deficiência Intelectual/genética , Deficiência Intelectual/diagnósticoRESUMO
BACKGROUND: Neurological complications (NCs) are of major concern following hematological stem cell transplantation (HSCT), most of which present with seizures. PROCEDURES: We performed a retrospective study (2002-2018) of patients undergoing HSCT in order to analyze the incidence and aetiologies related to seizures. RESULTS: Of 155 children undergoing HSCT, 27 (17.4%) developed seizures at some point in 2 years of follow-up. The most frequent etiologies were central nervous system (CNS) infection (n = 10), drug toxicity (n = 8), and vascular disease (n = 5). A statistically significant association was found between seizure and the HSCT type (lower risk for a related identical donor, p = .010), prophylactic or therapeutic mycophenolate use (p = .043 and .046, respectively), steroid use (p = .023), selective CD45RA+ depletion (p = .002), pre-engraftment syndrome (p = .007), and chronic graft-versus-host disease (GVHD) severity (p = .030). Seizures predicted evolution to life-threatening complications and admission to intensive care (p < .001) and higher mortality (p = .023). A statistically significant association was also found between seizures and sequelae in survivors (p = .029). Children who developed seizures had a higher risk of CNS infection and vascular disease (odds ratio 37.25 [95% CI: 7.45-186.05] and 12.95 [95% CI 2.24-74.80], respectively). CONCLUSIONS: Neurological complications highly impact survival and outcomes and need to be addressed when facing an HSCT procedure.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doenças Vasculares , Criança , Humanos , Estudos Retrospectivos , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Convulsões/etiologia , Convulsões/complicações , Doenças Vasculares/complicaçõesRESUMO
OBJECTIVE: Dravet syndrome (DS) is a developmental and epileptic encephalopathy characterized by high seizure burden, treatment-resistant epilepsy, and developmental stagnation. Family members rate communication deficits among the most impactful disease manifestations. We evaluated seizure burden and language/communication development in children with DS. METHODS: ENVISION was a prospective, observational study evaluating children with DS associated with SCN1A pathogenic variants (SCN1A+ DS) enrolled at age ≤5 years. Seizure burden and antiseizure medications were assessed every 3 months and communication and language every 6 months with the Bayley Scales of Infant and Toddler Development 3rd edition and the parent-reported Vineland Adaptive Behavior Scales 3rd edition. We report data from the first year of observation, including analyses stratified by age at Baseline: 0:6-2:0 years:months (Y:M; youngest), 2:1-3:6 Y:M (middle), and 3:7-5:0 Y:M (oldest). RESULTS: Between December 2020 and March 2023, 58 children with DS enrolled at 16 sites internationally. Median follow-up was 17.5 months (range = .0-24.0), with 54 of 58 (93.1%) followed for at least 6 months and 51 of 58 (87.9%) for 12 months. Monthly countable seizure frequency (MCSF) increased with age (median [minimum-maximum] = 1.0 in the youngest [1.0-70.0] and middle [1.0-242.0] age groups and 4.5 [.0-2647.0] in the oldest age group), and remained high, despite use of currently approved antiseizure medications. Language/communication delays were observed early, and developmental stagnation occurred after age 2 years with both instruments. In predictive modeling, chronologic age was the only significant covariate of seizure frequency (effect size = .52, p = .024). MCSF, number of antiseizure medications, age at first seizure, and convulsive status epilepticus were not predictors of language/communication raw scores. SIGNIFICANCE: In infants and young children with SCN1A+ DS, language/communication delay and stagnation were independent of seizure burden. Our findings emphasize that the optimal therapeutic window to prevent language/communication delay is before 3 years of age.
Assuntos
Epilepsias Mioclônicas , Lactente , Humanos , Pré-Escolar , Recém-Nascido , Estudos Prospectivos , Mutação , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/complicações , Convulsões/tratamento farmacológico , Convulsões/genética , Convulsões/complicações , Canal de Sódio Disparado por Voltagem NAV1.1/genética , ComunicaçãoRESUMO
Arterial tortuosity syndrome (ATS) is an autosomal recessive connective tissue disease caused by biallelic variants in the SLC2A10 gene (NG_016284.1) and characterised by tortuosity and elongation of the aorta and medium-sized arteries. It is considered an extremely rare disease; only 106 individuals with genetically confirmed ATS have been identified to date. Four cases of ATS from two families are described, contributing to the clinical delineation of this condition. A patient with microcephaly and a complex uropathy and two cases with diaphragmatic hernia are noticed. Regarding the vascular involvement, a predominant supra-aortic involvement stands out and only 1 patient with significant arterial stenoses was described. All presented severe tortuosity of the intracranial arteries. To reduce hemodynamic stress on the arterial wall, beta-adrenergic blocking treatment was prescribed. A not previously described variant (NM_030777.4:c.899T>G (p.Leu300Trp)) was detected in a proband; it has an allegedly deleterious effect in compound heterozygous state with the pathogenic variant c.417T>A (p.Tyr139Ter). The other 3 patients, siblings born to healthy consanguineous parents, had a variant in homozygous state: c.510G>A (p.Trp170Ter).
Assuntos
Artérias , Dermatopatias Genéticas , Humanos , Dermatopatias Genéticas/genética , Aorta , ConsanguinidadeRESUMO
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder that can involve multiple organ systems. Diagnosis is based on independent clinical diagnostic criteria and genetic diagnostic criteria (pathogenic variants on TSC1 and TSC2 genes). To make a definitive diagnosis can be especially difficult in oligosymptomatic or asymptomatic patients and in those patients with genetic variants of uncertain significance (VUS). Early diagnosis and lifelong surveillance are paramount to avoid morbidity and potentially life-threatening complications. To increase diagnostic sensibility, less known manifestations of TSC can be helpful. Herein we show a case in which SBLs were used as a diagnostic clue to help diagnose three generations of oligosymptomatic TSC carrying a VUS in TSC1. SBLs are commonly detected in imaging studies of patients with TSC and have been recently included as a minor clinical diagnostic criterion. Clinicians and radiologists should be aware of their significance as they can be mistaken with osteoblastic metastases.
Assuntos
Doenças Ósseas , Esclerose Tuberosa , Humanos , Proteína 1 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/genética , Esclerose Tuberosa/diagnóstico por imagem , Esclerose Tuberosa/genética , MutaçãoRESUMO
Background: Congenital deafness could be the first manifestation of a syndrome such as in Usher, Pendred, and Wolfram syndromes. Therefore, a genetic study is crucial in this deficiency to significantly improve its diagnostic efficiency, to predict the prognosis, to select the most adequate treatment required, and to anticipate the development of other associated clinical manifestations. Case presentation: We describe a young girl with bilateral congenital profound deafness, who initially received a single cochlear implant. The genetic study of her DNA using a custom-designed next-generation sequencing (NGS) panel detected a de novo pathogenic heterozygous variant in the WFS1 gene related to Wolfram-like syndrome, which is characterized by the presence of other symptoms such as optic atrophy. Due to this diagnosis, a second implant was placed after the optic atrophy onset. The speech audiometric results obtained with both implants indicate that this work successfully allows the patient to develop normal speech. Deterioration of the auditory nerves has not been observed. Conclusion: The next-generation sequencing technique allows a precise molecular diagnosis of diseases with high genetic heterogeneity, such as hereditary deafness, while this was the only symptom presented by the patient at the time of analysis. The NGS panel, in which genes responsible for both syndromic and non-syndromic hereditary deafness were included, was essential to reach the diagnosis in such a young patient. Early detection of the pathogenic variant in the WFS1 gene allowed us to anticipate the natural evolution of the disease and offer the most appropriate management to the patient.
RESUMO
Objective: The appropriate management of patients with Dravet Syndrome (DS) is challenging, given the severity of symptoms and the burden of the disease for patients and caregivers. This study aimed to identify, through a qualitative methodology and a Delphi consensus-driven process, a set of recommendations for the management of DS to guide clinicians in the assessment of the clinical condition and quality of life (QoL) of DS patients, with a special focus on patient- and caregiver-reported outcomes (PROs). Methods: This study was conducted in five phases, led by a multidisciplinary scientific committee (SC) including pediatric neurologists, epileptologists, a neuropsychologist, an epilepsy nurse, and members of DS patient advocates. In phases 1 and 2, a questionnaire related to patients' QoL was prepared and answered by caregivers and the SC. In phase 3, the SC generated, based on these answers and on a focus group discussion, a 70-item Delphi questionnaire, covering six topic categories on a nine-point Likert scale. In phase 4, 32 panelists, from different Spanish institutions and with a multidisciplinary background, answered the questionnaire. Consensus was obtained and defined as strong or moderate if ≥80% and 67-79% of panelists, respectively, rated the statement with ≥7. Phase 5 consisted of the preparation of the manuscript. Results: The panelists agreed on a total of 69 items (98.6%), 54 (77.14%), and 15 (21.43%) with strong and moderate consensus, respectively. The experts' recommendations included the need for frequent assessment of patient and caregivers QoL parameters. The experts agreed that QoL should be assessed through specific questionnaires covering different domains. Likewise, the results showed consensus regarding the regular evaluation of several clinical parameters related to neurodevelopment, attention, behavior, other comorbidities, and sudden unexpected death in epilepsy (SUDEP). A consensus was also reached on the instruments, specific parameters, and caregivers' education in the routine clinical management of patients with DS. Conclusions: This consensus resulted in a set of recommendations for the assessment of clinical and QoL parameters, including PROs, related to the general evaluation of QoL, neurodevelopment, attention, behavior, other comorbidities affecting QoL, SUDEP, and QoL of caregivers/relatives and patients with DS.
RESUMO
Spinal muscular atrophy (SMA) is a severe neuromuscular disorder caused by biallelic loss or pathogenic variants in the SMN1 gene. Copy number and modifier intragenic variants in SMN2, an almost identical paralog gene of SMN1, are known to influence the amount of complete SMN proteins. Therefore, SMN2 is considered the main phenotypic modifier of SMA, although genotype−phenotype correlation is not absolute. We present eleven unrelated SMA patients with milder phenotypes carrying the c.859G>C-positive modifier variant in SMN2. All were studied by a specific NGS method to allow a deep characterization of the entire SMN region. Analysis of two homozygous cases for the variant allowed us to identify a specific haplotype, Smn2-859C.1, in association with c.859G>C. Two other cases with the c.859G>C variant in their two SMN2 copies showed a second haplotype, Smn2-859C.2, in cis with Smn2-859C.1, assembling a more complex allele. We also identified a previously unreported variant in intron 2a exclusively linked to the Smn2-859C.1 haplotype (c.154-1141G>A), further suggesting that this region has been ancestrally conserved. The deep molecular characterization of SMN2 in our cohort highlights the importance of testing c.859G>C, as well as accurately assessing the SMN2 region in SMA patients to gain insight into the complex genotype−phenotype correlations and improve prognostic outcomes.
Assuntos
Atrofia Muscular Espinal , Estudos de Associação Genética , Homozigoto , Humanos , Íntrons , Atrofia Muscular Espinal/genética , Mutação , Fenótipo , Proteína 1 de Sobrevivência do Neurônio Motor/genética , Proteína 2 de Sobrevivência do Neurônio Motor/genéticaRESUMO
Introduction: SARS-CoV-2 infection during pregnancy and its impact on the newborn were, in the first months of the pandemic, unknown. Recent studies have provided information on the clinical involvement in the newborn and its evolution.This work shows how passive immunity varies in the newborn in relation to the moment of maternal SARS-CoV-2 infection during pregnancy. Population and method: Observational, prospective and longitudinal study in a third level hospital. Epidemiological and clinical data from mothers and their newborns were collected from May 2020 to June 2021. Results: A total of 109 mothers and 109 neonates have been included. 28.4% of maternal infections were in the first trimester, 24.8% during the second and 58.8% in the third. 56% of maternal infections were symptomatic and only one pregnant woman with severe respiratory infection was admitted to intensive care. The mean gestational age of the newborns was 39 weeks, with a mean weight of 3232 g and a head circumference of 35 cm. Eight newborns born from mothers with SARS-CoV-2 required admission to the neonatal ICU: 2 due to jaundice, 2 due to respiratory distress, 1 due to moderate prematurity, and 3 due to other causes unrelated to infection attributable to SARS-CoV-2. IgG-type antibodies were positive in 56.9% of newborns. Of the mothers infected during the 1 st trimester, IgG were positive in 32.2% of the newborns, in the second trimester 81.5% were positive and in the third 58.8%. No neonate had positive IgM. Conclusions: SARS-CoV-2 infection during pregnancy provides IgG antibodies to half of newborns. The presence of antibodies in the newborn is more likely when the infection has occurred in the second trimester of pregnancy.
RESUMO
Neurologic complications following stem cell transplantation are of utmost importance owing to their high morbimortality. Although many studies have been performed in the adult population, reports in children are scarce. Our objective was to determine the most common neurologic complications in a pediatric population and to analyze possible risk factors for their development. We performed an exploratory retrospective study of neurologic complications in pediatric patients who had allogeneic stem cell transplantation over the last 18 years. We identified 66 neurologic complications in 178 allogeneic stem cell transplantations. The most frequent neurologic complications were those involving the peripheral nervous system and those related to drug toxicity. Survival decreased significantly in the presence of neurologic complications. Multivariate logistic regression analysis showed that independent risk factors for developing neurologic complications were development of chronic extensive graft-vs-host disease requiring treatment, cytomegalovirus reactivation, and central nervous system radiation. Prompt diagnosis and preemptive treatment, if possible, are necessary to avoid long-term sequelae or mortality.
Assuntos
Doenças do Sistema Nervoso/etiologia , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Células-Tronco , Transplante Homólogo/efeitos adversos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Avaliação de Resultados em Cuidados de Saúde/métodos , Estudos Retrospectivos , Fatores de Risco , Transplante Homólogo/estatística & dados numéricosRESUMO
Dravet syndrome is a genetic developmental and epileptic encephalopathy (DEE) mostly due to mutations in SCN1A gene. Perampanel is a selective and non-competitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist. There is increasing experience in the use of perampanel in this syndrome; however, there is still a lack of evidence of sustained benefit years after the beginning of the treatment. We report a twelve-year-old girl who was diagnosed with Dravet Syndrome when she was 2 years old and has been on perampanel since she was 7. Her genetic test showed a de novo previously described heterozygous SCN1A mutation in the 24th exon (c.4547C>A, p.Ser1516*). She received previous antiseizure drug combinations with little benefit. When perampanel was started, there was a complete resolution of her spontaneous seizures that has continued five years later. More studies are needed to investigate if there is an association between this excellent response and the genotype of our patient.
RESUMO
We report a 6-year-old female with linear skin hyperpigmentation on the axillae and groin, intellectual disability, dysplastic teeth and nails, and facial dysmorphism who was diagnosed with a novel PHF6 pathogenic splicing variant. Males with PHF6 mutations have been associated with the X-linked recessive disorder Börjeson-Forssman-Lehmann, but females have a distinct phenotype which is likely modulated by X-inactivation.
Assuntos
Epilepsia , Hipogonadismo , Deficiência Intelectual , Deficiência Intelectual Ligada ao Cromossomo X , Proteínas de Transporte/genética , Criança , Face , Feminino , Dedos , Transtornos do Crescimento , Humanos , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/genética , Masculino , Mosaicismo , Proteínas RepressorasRESUMO
BACKGROUND: The ATP7A gene encodes a copper transporter whose mutations cause Menkes disease, occipital horn syndrome (OHS), and, less frequently, ATP7A-related distal hereditary motor neuropathy (dHMN). Here we describe a family with OHS caused by a novel mutation in the ATP7A gene, including a patient with a comorbid dHMN that worsened markedly after being treated with copper histidinate. METHODS: We studied in detail the clinical features of the patients and performed a genomic analysis by using TruSight One Expanded Sequencing Panel. Subsequently, we determined the ATP7A and ATP7B expression levels, mitochondrial membrane potential, and redox balance in cultured fibroblasts of Patient 1. RESULTS: We found a novel ATP7A late truncated mutation p.Lys1412AsnfsX15 in the two affected members of this family. The co-occurrence of OHS and dHMN in Patient 1 reveals the variable phenotypic expressivity of the variant. A severe clinical and neurophysiologic worsening was observed in the dHMN of Patient 1 when he was treated with copper replacement therapy, with a subsequent fast recovery after the copper histidinate was withdrawn. Functional studies revealed that the patient had low levels of both ATP7A and ATP7B, the other copper transporter, and high levels of superoxide ion in the mitochondria. CONCLUSIONS: Our findings broaden the clinical spectrum of ATP7A-related disorders and demonstrate that two clinical phenotypes can occur in the same patient. The copper-induced toxicity and low levels of both ATP7A and ATP7B in our patient suggest that copper accumulation in motor neurons is the pathogenic mechanism in ATP7A-related dHMN.
Assuntos
ATPases Transportadoras de Cobre/genética , Cobre/toxicidade , Cútis Laxa/genética , Síndrome de Ehlers-Danlos/genética , Adulto , Criança , Cobre/sangue , Cútis Laxa/sangue , Cútis Laxa/diagnóstico , Cútis Laxa/fisiopatologia , Síndrome de Ehlers-Danlos/sangue , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/fisiopatologia , Humanos , Masculino , Linhagem , Adulto JovemRESUMO
Most children with SARS-CoV-2 infection have relatively mild clinical symptoms without fever or pneumonia, although severe cases with multiple-organ failure have been reported. Neurological symptoms, which have been mainly reported in adults, are very rare in children. This article will review 2 different aspects of neurological involvement related to this infection in children. In the first part, we will review the neurological abnormalities reported in children caused by this viral infection. Adults frequently report muscle pain, headache, anosmia, dysgeusia, and occasionally more severe central or peripheral nervous system damage. Neurological involvement seems infrequent in children, although some cases have been reported. In the second part, we will discuss the COVID-19 pandemic impact on the healthcare system of some countries, causing collateral damage to general pediatric care and in particular to those children affected with chronic diseases, mainly neurological conditions, including autism, intellectual disability, attention deficit and hyperactivity disorder (ADHD), neuromuscular disorders, cerebral palsy, and epilepsy, and patients needing neurosurgical procedures.