COQ7 defect causes prenatal onset of mitochondrial CoQ10 deficiency with cardiomyopathy and gastrointestinal obstruction.

COQ7 pathogenetic variants cause primary CoQ10 deficiency and a clinical phenotype of encephalopathy, peripheral neuropathy, or multisystemic disorder. Early diagnosis is essential for promptly starting CoQ10 supplementation. Here, we report novel compound heterozygous variants in the COQ7 gene responsible for a prenatal onset (20 weeks of gestation) of hypertrophic cardiomyopathy and intestinal dysmotility in a Bangladesh consanguineous family with two affected siblings. The main clinical findings were dysmorphisms, recurrent intestinal occlusions that required ileostomy, left ventricular non-compaction cardiomyopathy, ascending aorta dilation, arterial hypertension, renal dysfunction, diffuse skin desquamation, axial hypotonia, neurodevelopmental delay, and growth retardation. Exome sequencing revealed compound heterozygous rare variants in the COQ7 gene, c.613_617delGCCGGinsCAT (p.Ala205HisfsTer48) and c.403A>G (p.Met135Val). In silico analysis and functional in vitro studies confirmed the pathogenicity of the variants responsible for abolished activities of complexes I + III and II + III in muscle homogenate, severe decrease of CoQ10 levels, and reduced basal and maximal respiration in patients' fibroblasts. The first proband deceased at 14 months of age, whereas supplementation with a high dose of CoQ10 (30 mg/kg/day) since the first days of life modified the clinical course in the second child, showing a recovery of milestones acquirement at the last follow-up (18 months of age). Our study expands the clinical spectrum of primary CoQ10 deficiency due to COQ7 gene defects and highlights the essential role of multidisciplinary and combined approaches for a timely diagnosis.

Efficacy and Safety of Pulse Intravenous Methylprednisolone in Pediatric Epileptic Encephalopathies: Timing and Networks Consideration.

Background: Epileptic encephalopathies (EE) are characterized by severe drug-resistant seizures, early onset, and unfavorable developmental outcomes. This article discusses the use of intravenous methylprednisolone (IVMP) pulse therapy in pediatric patients with EE to evaluate its efficacy and tolerability. Methods: This is a retrospective study from 2020 to 2023. Inclusion criteria were ≤18 years at the time of IVMP pulse therapy and at least 6 months of follow-up. Efficacy and outcome, defined as seizure reduction > 50% (responder rate), were evaluated at 6 and 9 months of therapy, and 6 months after therapy suspension; quality of life (QoL) was also assessed. Variables predicting positive post-IVMP outcomes were identified using statistical analysis. Results: The study included 21 patients, with a responder rate of 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Variables significantly predicting favorable outcome were etiology (p = 0.0475) and epilepsy type (p = 0.0475), with the best outcome achieved in patients with genetic epilepsy and those with encephalopathy related to electrical status epilepticus during slow-wave sleep (ESES). All patients evidenced improvements in QoL at the last follow-up, with no relevant adverse events reported. Conclusions: Our study confirmed the efficacy and high tolerability of IVMP pulse therapy in pediatric patients with EE. Genetic epilepsy and ESES were positive predictors of a favorable clinical outcome. QOL, EEG tracing, and postural-motor development showed an improving trend as well. IVMP pulse therapy should be considered earlier in patients with EE.

Olfactory bulb anomalies in KBG syndrome mouse model and patients.

ANKRD11 (ankyrin repeat domain 11) is a chromatin regulator and the only gene associated with KBG syndrome, a rare neurodevelopmental disorder. We have previously shown that Ankrd11 regulates murine embryonic cortical neurogenesis. Here, we show a novel olfactory bulb phenotype in a KBG syndrome mouse model and two diagnosed patients. Conditional knockout of Ankrd11 in murine embryonic neural stem cells leads to aberrant postnatal olfactory bulb development and reduced size due to reduction of the olfactory bulb granule cell layer. We further show that the rostral migratory stream has incomplete migration of neuroblasts, reduced cell proliferation as well as aberrant differentiation of neurons. This leads to reduced neuroblasts and neurons in the olfactory bulb granule cell layer. In vitro, Ankrd11-deficient neural stem cells from the postnatal subventricular zone display reduced migration, proliferation, and neurogenesis. Finally, we describe two clinically and molecularly confirmed KBG syndrome patients with anosmia and olfactory bulb and groove hypo-dysgenesis/agenesis. Our report provides evidence that Ankrd11 is a novel regulator of olfactory bulb development and neuroblast migration. Moreover, our study highlights a novel clinical sign of KBG syndrome linked to ANKRD11 perturbations in mice and humans.

Structural brain abnormalities in Pallister-Killian syndrome: a neuroimaging study of 31 children.

BACKGROUND: Pallister-Killian syndrome (PKS) is a rare genetic disorder caused by mosaic tetrasomy of 12p with wide neurological involvement. Intellectual disability, developmental delay, behavioral problems, epilepsy, sleep disturbances, and brain malformations have been described in most individuals, with a broad phenotypic spectrum. This observational study, conducted through brain MRI scan analysis on a cohort of patients with genetically confirmed PKS, aims to systematically investigate the neuroradiological features of this syndrome and identify the possible existence of a typical pattern. Moreover, a literature review differentiating the different types of neuroimaging data was conducted for comparison with our population. RESULTS: Thirty-one individuals were enrolled (17 females/14 males; age range 0.1-17.5 years old at first MRI). An experienced pediatric neuroradiologist reviewed brain MRIs, blindly to clinical data. Brain abnormalities were observed in all but one individual (compared to the 34% frequency found in the literature review). Corpus callosum abnormalities were found in 20/30 (67%) patients: 6 had callosal hypoplasia; 8 had global hypoplasia with hypoplastic splenium; 4 had only hypoplastic splenium; and 2 had a thin corpus callosum. Cerebral hypoplasia/atrophy was found in 23/31 (74%) and ventriculomegaly in 20/31 (65%). Other frequent features were the enlargement of the cisterna magna in 15/30 (50%) and polymicrogyria in 14/29 (48%). Conversely, the frequency of the latter was found to be 4% from the literature review. Notably, in our population, polymicrogyria was in the perisylvian area in all 14 cases, and it was bilateral in 10/14. CONCLUSIONS: Brain abnormalities are very common in PKS and occur much more frequently than previously reported. Bilateral perisylvian polymicrogyria was a main aspect of our population. Our findings provide an additional tool for early diagnosis.Further studies to investigate the possible correlations with both genotype and phenotype may help to define the etiopathogenesis of the neurologic phenotype of this syndrome.

Identification of the DNA methylation signature of Mowat-Wilson syndrome.

Mowat-Wilson syndrome (MOWS) is a rare congenital disease caused by haploinsufficiency of ZEB2, encoding a transcription factor required for neurodevelopment. MOWS is characterized by intellectual disability, epilepsy, typical facial phenotype and other anomalies, such as short stature, Hirschsprung disease, brain and heart defects. Despite some recognizable features, MOWS rarity and phenotypic variability may complicate its diagnosis, particularly in the neonatal period. In order to define a novel diagnostic biomarker for MOWS, we determined the genome-wide DNA methylation profile of DNA samples from 29 individuals with confirmed clinical and molecular diagnosis. Through multidimensional scaling and hierarchical clustering analysis, we identified and validated a DNA methylation signature involving 296 differentially methylated probes as part of the broader MOWS DNA methylation profile. The prevalence of hypomethylated CpG sites agrees with the main role of ZEB2 as a transcriptional repressor, while differential methylation within the ZEB2 locus supports the previously proposed autoregulation ability. Correlation studies compared the MOWS cohort with 56 previously described DNA methylation profiles of other neurodevelopmental disorders, further validating the specificity of this biomarker. In conclusion, MOWS DNA methylation signature is highly sensitive and reproducible, providing a useful tool to facilitate diagnosis.

The involvement of the adrenergic system in feeding and eating disorders. A systematic review.

BACKGROUND: Adrenergic dysregulation has been proposed as a possible underlying mechanism in feeding and eating disorders (FED). This review aims to synthesise the current evidence on the role of adrenergic dysregulation in the pathogenesis and management of FED. METHODS: A systematic review was conducted in MEDLINE, Cochrane Library, and Clinicaltrials.gov. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was adopted. Preclinical, clinical, and pharmacological studies assessing the adrenergic system in FED were included. RESULTS: Thirty-one out of 1415 recognised studies were included. Preclinically, studies on adrenaline's anorectic impact, receptor subtypes, and effects on hepatic function in rats show that catecholamine anorexia is primarily alpha-adrenergic, whereas beta-adrenergic anorexia can be obtained only after puberty, implying an impact of sexual hormones. Clinically, catecholamine levels may be higher in FED patients than in healthy controls (HC). Individuals with anorexia nervosa (AN) may show higher epinephrine-induced platelet aggregability response than HC. Pharmacological trials suggest that the alpha-2-adrenergic medication clonidine may not lower AN symptoms, but agents regulating the adrenaline-noradrenaline neurotransmission (bupropion, reboxetine, duloxetine, sibutramine) have been found to improve binge eating symptoms. CONCLUSION: Adrenergic dysregulation may be involved in the pathophysiology of FED. More research is needed to comprehend underlying mechanisms and treatment implications.

NFIA haploinsufficiency: case series and literature review.

Background: NFIA-related disorder (OMIM #613735) is an autosomal dominant neurodevelopmental disorder characterized by a variable degree of cognitive impairment and non-specific dysmorphic features. To date, fewer than thirty patients affected by this disorder have been described. Methods: Our study included three children with NFIA haploinsufficiency recruited from three medical genetics centers. Clinical presentations were recorded on a standardized case report form. Results: All patients presented a variable degree of intellectual disability. None of the individuals in our cohort had urinary tract malformations. Three novel mutations, c.344G>A, c.261T>G, and c.887_888del are reported here. Conclusion: NFIA haploinsufficiency can be suspected through careful observation of specific dysmorphisms, including macrocephaly and craniofacial abnormalities. Instrumental tests such as MRI and renal ultrasound provide further diagnostic clues, while genetic testing can confirm the diagnosis.

Anti-Inflammatory and Immunomodulatory Effect of High-Dose Immunoglobulins in Children: From Approved Indications to Off-Label Use.

BACKGROUND: The large-scale utilization of immunoglobulins in patients with inborn errors of immunity (IEIs) since 1952 prompted the discovery of their key role at high doses as immunomodulatory and anti-inflammatory therapy, in the treatment of IEI-related immune dysregulation disorders, according to labelled and off-label indications. Recent years have been dominated by a progressive imbalance between the gradual but constant increase in the use of immunoglobulins and their availability, exacerbated by the SARS-CoV-2 pandemic. OBJECTIVES: To provide pragmatic indications for a need-based application of high-dose immunoglobulins in the pediatric context. SOURCES: A literature search was performed using PubMed, from inception until 1st August 2023, including the following keywords: anti-inflammatory; children; high dose gammaglobulin; high dose immunoglobulin; immune dysregulation; immunomodulation; immunomodulatory; inflammation; intravenous gammaglobulin; intravenous immunoglobulin; off-label; pediatric; subcutaneous gammaglobulin; subcutaneous immunoglobulin. All article types were considered. IMPLICATIONS: In the light of the current imbalance between gammaglobulins' demand and availability, this review advocates the urgency of a more conscious utilization of this medical product, giving indications about benefits, risks, cost-effectiveness, and administration routes of high-dose immunoglobulins in children with hematologic, neurologic, and inflammatory immune dysregulation disorders, prompting further research towards a responsible employment of gammaglobulins and improving the therapeutical decisional process.

Aromatic L-Amino-Acid Decarboxylase Deficiency Screening by Analysis of 3-O-Methyldopa in Dried Blood Spots: Results of a Multicentric Study in Neurodevelopmental Disorders.

Aromatic L-amino acid decarboxylase deficiency (AADCd) is a rare recessive metabolic disorder caused by pathogenic homozygous or compound heterozygous variants in the dopa decarboxylase (DDC) gene. Adeno-associated viral vector-mediated gene transfer of the human DDC gene injected into the putamen is available. The typical presentation is characterized by early-onset hypotonia, severe developmental delay, movement disorders, and dysautonomia. Recently, mild and even atypical phenotypes have been reported, increasing the diagnostic challenge. The aim of this multicentric study is to identify the prevalence of AADCd in a population of patients with phenotypic clusters characterized by neurodevelopmental disorders (developmental delay/intellectual disability, and/or autism) by 3-O-methyldopa (3-OMD) detection in dried blood spots (DBS). It is essential to identify AADCd promptly, especially within non-typical phenotypic clusters, because better results are obtained when therapy is quickly started in mild-moderate phenotypes. Between 2021 and 2023, 390 patients with non-specific phenotypes possibly associated with AADCd were tested; none resulted in a positive result. This result highlights that the population to be investigated for AADCd should have more defined clinical characteristics: association with common signs (hypotonia) and/or pathognomonic symptoms (oculogyric crisis and dysautonomia). It is necessary to continue to screen selected clusters for reaching diagnosis and improving long-term outcomes through treatment initiation. This underscores the role of newborn screening in identifying AADCd.

Neurodevelopmental Correlates of Brain Magnetic Resonance Imaging Abnormalities in Extremely Low-birth-weight Infants.

OBJECTIVE: To evaluate the relationship between impaired brain growth and structural brain abnormalities at term-equivalent age (TEA) and neurodevelopment in extremely low-birth-weight (ELBW) infants over the first 2 years. METHODS: ELBW infants born from 2009 through 2018 and undergoing brain magnetic resonance imaging (MRI) at TEA were enrolled in this retrospective cohort study. MRI scans were reviewed using a validated quali-quantitative score, including several white and gray matter items. Neurodevelopment was assessed at 6, 12, 18, and 24 months using the Griffiths scales. The independent associations between MRI subscores and the trajectories of general and specific neurodevelopmental functions were analyzed by generalized estimating equations. RESULTS: One hundred-nine ELBW infants were included. White matter volume reduction and delayed myelination were associated with worse general development (b = -2.33, P = .040; b = -6.88, P = .049 respectively), social skills (b = -3.13, P = .019; b = -4.79, P = .049), and eye-hand coordination (b = -3.48, P = .009; b = -7.21, P = .045). Cystic white matter lesions were associated with poorer motor outcomes (b = -4.99, P = .027), while white matter signal abnormalities and corpus callosum thinning were associated with worse nonverbal cognitive performances (b = -6.42, P = .010; b = -6.72, P = .021, respectively). Deep gray matter volume reduction correlated with worse developmental trajectories. CONCLUSIONS: Distinctive MRI abnormalities correlate with specific later developmental skills. This finding may suggest that TEA brain MRI may assist with neurodevelopmental prediction, counseling of families, and development of targeted supportive interventions to improve neurodevelopment in ELBW neonates.

Children under 6 years with acute headache in Pediatric Emergency Departments. A 2-year retrospective exploratory multicenter Italian study.

BACKGROUND: Preschool age (i.e. children under six years of age) represents a red flag for requiring neuroimaging to exclude secondary potentially urgent intracranial conditions (PUIC) in patients with acute headache. We investigated the clinical characteristics of preschoolers with headache to identify the features associated with a greater risk of secondary "dangerous" headache. METHODS: We performed a multicenter exploratory retrospective study in Italy from January 2017 to December 2018. Preschoolers with new-onset non-traumatic headache admitted to emergency department were included and were subsequently divided into two groups: hospitalized and discharged. Among hospitalized patients, we investigated the characteristics linked to potentially urgent intracranial conditions. RESULTS: We included 1455 preschoolers with acute headache. Vomiting, ocular motility disorders, ataxia, presence of neurological symptoms and signs, torticollis and nocturnal awakening were significantly associated to hospitalization. Among the 95 hospitalized patients, 34 (2.3%) had potentially urgent intracranial conditions and more frequently they had neurological symptoms and signs, papilledema, ataxia, cranial nerves paralysis, nocturnal awakening and vomiting. Nevertheless, on multivariable logistic regression analysis, we found that only ataxia and vomiting were associated with potentially urgent intracranial conditions. CONCLUSION: Our study identified clinical features that should be carefully evaluated in the emergency department in order to obtain a prompt diagnosis and treatment of potentially urgent intracranial conditions. The prevalence of potentially urgent intracranial conditions was low in the emergency department, which may suggest that age under six should not be considered an important risk factor for malignant causes as previously thought.

Cannabidiol in the acute phase of febrile infection-related epilepsy syndrome (FIRES).

Febrile infection-related epilepsy syndrome (FIRES) is a prolonged refractory status epilepticus (SE) that develops among healthy individuals after a febrile infection. FIRES treatment is challenging due to its poor response to antiseizure medications (ASMs) and anesthetic drugs. The use of cannabidiol (CBD) as an adjunctive treatment has been suggested, albeit data about its role in the acute phase is lacking. This report describes the use of purified CBD in the acute phase of two pediatric cases of FIRES and their long-term outcome. Both children were treated with several ASMs, immunomodulators, anesthetics, and nonpharmacological treatment (ketogenic diet). CBD was administered, as an adjunctive treatment, through nasogastric tube about 30 days after onset. SE resolved within 3 days of reaching the target dose and both were seizure-free for 1 year after. Although it is difficult to define the extent to which each previous therapy contributed to recovery, in both cases CBD therapy was a turning point, reinforcing its potential role as add-on treatment in the acute phase of FIRES.

Post-Traumatic Headache in Children after Minor Head Trauma: Incidence, Phenotypes, and Risk Factors.

Minor head trauma (MHT) is very frequent in children and post-traumatic headache (PTH) is one of its most common complications; however, its management is still a challenge. We aimed to assess the incidence and clinical characteristics of, and risk factors for, PTH among children referred to our pediatric emergency department (PED) for MHT. A total of 193 patients aged 3-14 years evaluated for MTH were enrolled and followed up for 6 months through phone calls and/or visits. PTH occurred in 25/193 patients (13%). PTH prevalence was significantly higher in school-aged (≥6 years) than in pre-school-aged children (21.6% vs. 4.9%, respectively, p < 0.009). Females were found to be more affected. The median time of onset was 4.6 days after MHT; resolution occurred in a median of 7 weeks. In 83.3% of patients, PTH subsided in <3 months, while in 16.7% it persisted longer. A total of 25% of children exhibited the migraine and 75% the tension-type variant. Our analysis indicates the presence of headache upon arrival in PED, isolated or associated with nausea and dizziness, as a factor predisposing the patient to the development of PTH. Our findings could be useful to identify children at risk for PTH for specific follow-up, family counseling, and treatment.

Down Syndrome: how to communicate the diagnosis.

Communicating the diagnosis of Down Syndrome to a couple of parents is never easy, whether before or after birth. As doctors, we must certainly rely on our own relational skills, but it is also necessary to be confident in some general indications, which are often overlooked in the strict hospital routine. This article is intended as a summary of the main articles published on this subject in the international literature, collecting and summarising the most important indications that have emerged in years of medical practice all over the world as well as in our personal experience. The diffusion of these guidelines is essential to help the doctor in this difficult task, on which there is often little training, and above all to guarantee to the parents the least traumatic communication possible.

Extended Glasgow Outcome Scale to Evaluate the Functional Impairment of Patients With Subcortical Band Heterotopia: A Multicentric Cross-sectional Study.

BACKGROUND: Subcortical band heterotopia (SBH) is a rare malformation of the cortical development characterized by a heterotopic band of gray matter between cortex and ventricles. The clinical presentation typically includes intellectual disability and epilepsy. PURPOSE: To evaluate if the Extended Glasgow Outcome Scale-pediatric version (EGOS-ped) is a feasible tool for evaluating the functional disability of patients with (SBH). METHOD: Cross-sectional multicenter study of a cohort of 49 patients with SBH (female n = 30, 61%), recruited from 23 Italian centers. RESULTS: Thirty-nine of 49 (80%) cases showed high functional disability at EGOS-ped assessment. In the poor result subgroup (EGOS-ped >3) motor deficit, language impairment, and lower intelligence quotient were more frequent (P < 0.001, P = 0.02, and P = 0.01, respectively); the age at epilepsy onset was remarkably lower (P < 0.001); and the prevalence of epileptic encephalopathy (West syndrome or Lennox-Gastaut-like encephalopathy) was higher (P = 0.04). The thickness and the extension of the heterotopic band were associated with EGOS-ped score (P < 0.01 and P = 0.02). Pachygyria was found exclusively among patients with poor outcome (P < 0.01). CONCLUSIONS: The EGOS-ped proved to be a reliable tool for stratifying the functional disability of patients with SBH. According to this score, patients could be dichotomized: group 1 (80%) is characterized by a poor overall functionality with early epilepsy onset, thick heterotopic band, and pachygyria, whereas group 2 (20%) is characterized by a good overall functionality with later epilepsy onset and thinner heterotopic band.

Status Epilepticus in Chromosomal Disorders Associated with Epilepsy: A Systematic Review.

Status Epilepticus (SE) is a neurological emergency resulting from the failure of mechanisms of seizure termination or from the initiation of mechanisms that lead to prolonged seizures. The International League Against Epilepsy (ILAE) identified 13 chromosomal disorders associated with epilepsy (CDAE); data regarding SE occurrence in these patients is lacking. A systematic scoping review was conducted to outline current literature evidence about clinical features, treatments, and outcomes of SE in pediatric and adult patients with CDAE. A total of 373 studies were identified with the initial search; 65 of these were selected and regarded as SE in Angelman Syndrome (AS, n = 20), Ring 20 Syndrome (R20, n = 24), and other syndromes (n = 21). Non-convulsive status epilepticus (NCSE) is frequently observed in AS and R20. No specific, targeted therapies for SE in CDAE are available to date; anecdotal reports about SE treatment are described in the text, as well as various brief- and long-term outcomes. Further evidence is needed to precisely portray the clinical features, treatment options, and outcomes of SE in these patients.

Clinical and psychopathological profiles of children with somatic symptom disorders in a pediatric emergency unit: an observational study before and during the SARS-CoV-2 pandemic.

Somatic symptom disorders (SSDs) are a group of clinical conditions characterized by heterogeneous physical symptoms, not directly supported by a demonstrable organic process. Despite representing a growing problem in the pediatric age, the literature lacks studies assessing the psychopathological and clinical features of subjects with SSD, particularly during the SARS-CoV-2 pandemic. This is a retrospective, observational study, involving two historical cohorts of children admitted to a tertiary referral Italian hospital over the 2 years preceding and following the start of the SARS-CoV-2 pandemic. Demographic, clinical, socio-economical, and psychological variables were investigated. Standardized tests for the developmental age were administered to assess psychopathological variables. Overall rates and trends of accesses for SSD, as compared to the total accesses for any cause at the Pediatric Emergency Room during the same periods, were reported as well. Fifty-one (pre-pandemic, 29; pandemic, 22) children with SSD were enrolled (age, 11.4 ± 2.4 years, F = 66.7%). Subjects in the pandemic historical cohort reported more frequently fever (p < 0.001), headache (p = 0.032), and asthenia (p < 0.001), as well as more chronic conditions in personal and family history, and fewer previous hospital accesses, as compared to the pre-pandemic cohort. Depressed mood and anxious traits were documented in both samples. None of them had an ongoing or a previously reported SARS-CoV-2 infection. During the pandemic, a clinical psychologist was more frequently consulted before the hospital discharge to mental health services, to support the diagnosis.  Conclusion: This study showed the significant burden of SSD in children, highlighting the need to implement pediatricians' education to optimize the management of these patients. Children with SSD who accessed during the SARS-CoV-2 pandemic presented specific clinical features. Future studies, conducted on longitudinal and controlled samples, are indicated to further investigate children with these conditions. What is Known:    â€¢ Somatic symptoms disorders (SSDs) are frequent in the pediatric age, especially in early adolescence.    â€¢ Evidence remains scarce on the impact of the SARS-CoV-2 pandemic on SSDs in children. What is New:    â€¢ Children with SSD who accessed during the SARS-CoV-2 pandemic presented specific clinical features.    â€¢ The implementation of pediatricians' education and a multidisciplinary approach are needed to optimize the management of SSDs.

Early Immunotherapy and Longer Corticosteroid Treatment Are Associated With Lower Risk of Relapsing Disease Course in Pediatric MOGAD.

BACKGROUND AND OBJECTIVES: We sought to identify early factors associated with relapse and outcome in paediatric-onset myelin oligodendrocyte glycoprotein antibody-associated disorders (MOGAD). METHODS: In a multicenter retrospective cohort of pediatric MOGAD (≤18 years), onset features and treatment were compared in patients with monophasic vs relapsing disease (including cases with follow-up ≥12 months after onset or relapse at any time) and in patients with final Expanded Disability Status Scale (EDSS) 0 vs ≥1 at last follow-up (including cases with follow-up >3 months after last event or EDSS0 at any time). Multivariable logistic regression models were used to evaluate factors associated with relapsing disease course and EDSS ≥ 1 at final follow-up. RESULTS: Seventy-five children were included (median onset age 7 years; median 30 months of follow-up). Presentation with acute disseminated encephalomyelitis was more frequent in children aged 8 years or younger (66.7%, 28/42) than in older patients (30.3%, 10/33) (p = 0.002), whereas presentation with optic neuritis was more common in children older than 8 years (57.6%, 19/33) than in younger patients (21.4%, 9/42) (p = 0.001). 40.0% (26/65) of patients relapsed. Time to first relapse was longer in children aged 8 years or younger than in older patients (median 18 vs 4 months) (p = 0.013). Factors at first event independently associated with lower risk of relapsing disease course were immunotherapy <7 days from onset (6.7-fold reduced odds of relapsing course, OR 0.15, 95% CI 0.03-0.61, p = 0.009), corticosteroid treatment for ≥5 weeks (6.7-fold reduced odds of relapse, OR 0.15, 95% CI 0.03-0.80, p = 0.026), and abnormal optic nerves on onset MRI (12.5-fold reduced odds of relapse, OR 0.08, 95% CI 0.01-0.50, p = 0.007). 21.1% (15/71) had EDSS ≥ 1 at final follow-up. Patients with a relapsing course had a higher proportion of final EDSS ≥ 1 (37.5%, 9/24) than children with monophasic disease (12.8%, 5/39) (p = 0.022, univariate analysis). Each 1-point increment in worst EDSS at onset was independently associated with 6.7-fold increased odds of final EDSS ≥ 1 (OR 6.65, 95% CI 1.33-33.26, p = 0.021). DISCUSSION: At first attack of pediatric MOGAD, early immunotherapy, longer duration of corticosteroid treatment, and abnormal optic nerves on MRI seem associated with lower risk of relapse, whereas higher disease severity is associated with greater risk of final disability (EDSS ≥ 1).