Daniel Almeida Do Valle

Background: Dravet syndrome (DS) is a severe developmental and epileptic encephalopathy, and data from low- and middle-income countries remain scarce. We characterized the clinical, genetic, and therapeutic profiles of patients with DS at a Brazilian tertiary referral center. Methods: This retrospective cross-sectional study included 27 patients with clinically and genetically confirmed DS (pathogenic/likely pathogenic SCN1A variants). Outcomes were ≥6-month and ≥12-month seizure freedom and seizure control in the previous month, described by treatment exposure without inferential testing. Results: The median age at seizure onset was 4 months and at diagnosis 42 months; the median individual onset-to-diagnosis interval was 29 months (range, 4–283; n = 14). All patients received polytherapy; 51.9% used cannabidiol, 40.7% vagus nerve stimulation, and 7.4% fenfluramine. Only 2/20 patients (10.0%) achieved ≥6-month and 1/20 (5.0%) ≥ 12-month seizure freedom. All six patients seizure-free in the previous month were receiving valproate, a descriptive finding likely reflecting confounding by indication. Recorded comorbidities, mainly autism spectrum disorder (29.6%), were likely underestimated in the absence of systematic neurodevelopmental assessment. Conclusions: This Brazilian DS cohort showed marked diagnostic delay, high seizure burden, and limited access to DS-specific therapies. These findings support earlier genetic testing and broader access to recommended treatments and generate hypotheses for larger prospective studies.

Background: Visual impairment is associated with mental health difficulties in children, yet emotional and behavioral profiles across different etiologies and levels of visual impairment remain poorly characterized. We investigated whether these outcomes were associated with syndromic etiology or visual impairment severity. Methods: In this cross-sectional study, parents of 69 children and adolescents aged 6–17 years with visual impairment completed the Child Behavior Checklist (CBCL/6–18). Participants were grouped by etiology (syndromic, n = 14; non-syndromic, n = 55) and by visual impairment severity (mild-to-moderate, n = 33; severe-to-profound, n = 36). Group differences were assessed using Mann–Whitney U tests with false discovery rate (FDR) correction, complemented by categorical analyses using scale-specific CBCL clinical thresholds. Results: No significant differences in emotional or behavioral symptoms were observed between the syndromic and non-syndromic groups, although the small syndromic subgroup limited statistical power. In contrast, children with mild-to-moderate visual impairment had significantly higher scores on the Anxious/Depressed and Somatic Complaints scales than those with severe-to-profound impairment, with both differences remaining significant after FDR correction. Categorical analyses also showed a higher prevalence of clinically significant Anxious/Depressed and Internalizing Problems in the mild-to-moderate group. Conclusions: Children with mild-to-moderate visual impairment exhibited higher Anxious/Depressed and Somatic Complaints scores than those with severe-to-profound impairment. These findings suggest that children with residual vision may represent an underrecognized subgroup at risk for emotional difficulties and support routine psychological screening across the spectrum of pediatric visual impairment.

Objective: To characterize neurodevelopmental disorders in children and adolescents with Tuberous Sclerosis Complex (TSC) and explore associations with epilepsy onset and cortical tuber burden. Methods: This exploratory cross-sectional study included 18 children and adolescents with TSC followed at a tertiary pediatric neurology center in Brazil. Standardized neuropsychological, behavioral, and neuroimaging assessments were performed. Participants were stratified according to epilepsy onset and cortical tuber burden. Results: Epilepsy was present in 94.4% of participants, and pharmacoresistance in 52.9%. Neurodevelopmental disorders were highly prevalent, particularly autism spectrum disorder and attention-deficit/hyperactivity disorder, frequently occurring as comorbidities. Children with earlier epilepsy onset demonstrated exploratory trends toward poorer cognitive outcomes, whereas greater cortical tuber burden showed exploratory trends toward greater behavioral and emotional dysregulation, although these differences did not reach statistical significance. Conclusions: Neurodevelopmental disorders are highly prevalent in pediatric TSC. Exploratory findings suggest that epilepsy characteristics and lesion burden may be related to cognitive and behavioral outcomes. These exploratory findings support systematic multidisciplinary neurodevelopmental monitoring in children with TSC.

Objective: This study aimed to compare the diagnostic yield of genome sequencing (GS) versus exome sequencing (ES) in a pediatric population, with a focus on determining whether GS offers a significant advantage over ES in identifying genetic variants. Methods: A retrospective analysis of prospectively allocated pediatric patients was performed on 297 pediatric patients who underwent next-generation sequencing. Of these, 59.6% (177) underwent only ES, 32.3% (96) underwent only GS, and 8.1% (24) had both tests. Diagnostic positivity rates were compared between ES and GS, and subgroup analyses were performed based on clinical characteristics. Results: GS demonstrated a higher positivity rate (51.7%) compared to ES (42.8%), with a 95.8% concordance between tests in patients who underwent both. However, the added diagnostic yield of GS was less than 10%. Greater GS positivity was identified in a group of children with neurological, musculoskeletal, growth disorder and craniofacial anomalies. Deep intronic variants were identified in two cases that underwent GS, but only one had also undergone ES. Limitations in medical record completeness and data quality were noted, which could affect the study’s generalizability. Conclusion: GS offered a modest increase in diagnostic yield over ES, particularly for detecting deep intronic variants. Some conditions had greater GS positivity, but the interpretation deserves caution as issues regarding homogeneity and sample selection may have influenced this result.

This case series provides a detailed description of the coexistence of spinal muscular atrophy (SMA) type 1 and autism spectrum disorder (ASD) in children treated with disease‐modifying therapies. Among 13 patients (2–7 years; mean age 4 years [SD 2 years], eight males), five met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Text Revision criteria for ASD—a proportion substantially higher than expected and exceeding recent reports in SMA cohorts. These findings indicate that ASD may be underrecognized in this population and that traditional screening tools, such as the autism trait assessment, may fail to detect symptoms because of the severe motor and communicative limitations characteristic of SMA. Although all children demonstrated meaningful motor gains after treatment, those with SMA and ASD showed marked cognitive and adaptive impairments, particularly in communication, socialization, and daily living skills. The dissociation between motor improvement and neurodevelopmental outcomes underscores the need for tailored assessments and continuous behavioral surveillance. This report provides clinically relevant insights and highlights the importance of adapted diagnostic approaches for neurodevelopmental evaluation in SMA.

This retrospective observational study investigates the clinical and neuroimaging profiles of children with cerebral palsy and explores the contribution of genetic factors to its etiology. We reviewed 302 pediatric cases diagnosed with cerebral palsy in Southern Brazil during 2023. Neuroimaging abnormalities were present in 92.1% of cases, with leukomalacia being most frequent. Neonatal encephalopathy emerged as the leading etiology, followed by prematurity and genetic conditions. Genetic testing was performed in 68 patients, identifying 29 distinct genes, notably in cases with preserved imaging or kernicterus. Dyskinetic and ataxic cerebral palsy were more often associated with normal neuroimaging, although not necessarily with positive genetic findings. Some patients with kernicterus also had genetic etiology, especially G6PD. The study reinforces that normal imaging does not exclude underlying genetic causes, especially in patients lacking perinatal complications or exhibiting dyskinetic patterns. These findings emphasize the complementary roles of neuroimaging and genetic in the multifactorial nature of cerebral palsy.

Introduction Neuronal ceroid lipofuscinoses (CLNs) are a group of lysosomal storage disorders of genetic origin, characterized by progressive neurodegeneration and intracellular accumulation of autofluorescent lipopigment. Thirteen genes related to CLNs are currently described, showing genetic and allelic heterogeneity, most of them with an autosomal recessive pattern. Due to the few descriptions of cases related to CLNs in Brazil, it is necessary to describe the phenotypic and genotypic characteristics of these patients. This study aims to evaluate the genotypic profile and correlate it with the phenotypic characteristics of patients with CLN in a children's hospital. Methods This study was performed as a descriptive cross-sectional study with analysis of medical records, imaging, and laboratory tests of patients who had a confirmed molecular diagnosis of CLN. Results The sample consisted of 11 patients from nine families with different subtypes of CLNs (CLN2, 5, 6, 7, and 8), with CLN2 being the most prevalent in the study. A total of 16 mutation variants were identified in genes associated with the five CLNs described in this study, with typical and atypical clinical phenotypes depending on the subtype and its variants. Conclusion Novel mutations identified in the patients in this study showed phenotypes of rapid and severe progression in the CLN2 patient and similar characteristics in CLN6 and CLN7 patients, as previously described in the literature.

Background Autoimmune encephalitis (AIE) is a group of inflammatory diseases characterized by the presence of antibodies against neuronal and glial antigens, leading to subacute psychiatric symptoms, memory complaints, and movement disorders. The patients are predominantly young, and delays in treatment are associated with worse prognosis. Objective With the support of the Brazilian Academy of Neurology (Academia Brasileira de Neurologia, ABN) and the Brazilian Society of Child Neurology (Sociedade Brasileira de Neurologia Infantil, SBNI), a consensus on the diagnosis and treatment of AIE in Brazil was developed using the Delphi method. Methods A total of 25 panelists, including adult and child neurologists, participated in the study. Results The panelists agreed that patients fulfilling criteria for possible AIE should be screened for antineuronal antibodies in the serum and cerebrospinal fluid (CSF) using the tissue-based assay (TBA) and cell-based assay (CBA) techniques. Children should also be screened for anti-myelin oligodendrocyte glucoprotein antibodies (anti-MOG). Treatment should be started within the first 4 weeks of symptoms. The first-line option is methylprednisolone plus intravenous immunoglobulin (IVIG) or plasmapheresis, the second-line includes rituximab and/or cyclophosphamide, while third-line treatment options are bortezomib and tocilizumab. Most seizures in AIE are symptomatic, and antiseizure medications may be weaned after the acute stage. In anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis, the panelists have agreed that oral immunosuppressant agents should not be used. Patients should be evaluated at the acute and postacute stages using functional and cognitive scales, such as the Mini-Mental State Examination (MMSE), the Montreal Cognitive Assessment (MoCA), the Modified Rankin Scale (mRS), and the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). Conclusion The present study provides tangible evidence for the effective management of AIE patients within the Brazilian healthcare system.

We present a case study of a patient exhibiting acquired microcephaly along with global developmental delay and drug‐resistant epilepsy. Brain magnetic resonance imaging revealed distinctive features, including a Z‐shaped morphology of the brainstem, volumetric reduction of white matter, diffuse thinning of the corpus callosum, and partial fusion of the cerebellar hemispheres at their most cranial portion. Whole‐exome sequencing uncovered a pathogenic variant in the ARF3 gene c.200A>T, p.(Asp67Val). The neurodevelopmental disorder associated with the ARF3 gene is exceptionally rare, with only two previously documented cases in the literature. This disorder is characterized by global developmental delay and brain malformations, particularly affecting the white matter, cerebellum, and brainstem. It can also manifest as acquired microcephaly and epilepsy. These phenotypic characteristics align with Golgipathies, underscoring the significance of considering this group of conditions in relevant clinical contexts. In cases where a Z‐shaped morphology of the brainstem is observed, ARF3‐associated disorder should be included in the list of differential diagnoses.