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Introduction Most coronavirus disease 2019 (COVID-19) pediatric patients are asymptomatic; however, several neurological manifestations associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection have been reported. Demyelinating events such as acute disseminated encephalomyelitis have been recently included among potential complications of COVID-19. Case Report We describe the case of a 12-year-old boy who developed central nervous system demyelinating lesions following SARS-CoV-2 infection. Two months prior he had been diagnosed with panuveitis but was otherwise healthy. Three weeks after testing positive for SARS-CoV-2, he started to complain of right temporal headache associated with right orbital pain without vision impairment. Brain magnetic resonance imaging showed large leukodystrophy-like demyelinating lesions. Standard electroencephalogram revealed a slow activity on the right hemisphere. His clinical and electroencephalographic course was favorable, with a good response to corticosteroid therapy and infusions of intravenous immunoglobulins. Delayed but complete resolution of brain lesions was noted on imaging. Conclusion Our case contributes to broaden the knowledge regarding the spectrum of possible complications of SARS-CoV-2 infection. The relative lack of clinical manifestations in our patient can be seen as a warning not to underestimate even mild neurological symptoms correlated with COVID-19.

A 13-year-old female patient was admitted for acute psychotic symptoms after two months of non-periodic mild fever and progressive behavioral changes. Hallucinations, delirium, disinhibition, coprolalia, and defiant behavior required admission to the Psychiatric Unit. Neurological examination and EEG werenormal. An extensive lesion involving the right frontal lobe was depicted in brain MRI. Psychiatric symptoms completely resolved after surgery. Histological diagnosis was of an Oligodendroglioma grade II, IDH mutant, and 1p/19q co-deleted. Presentation of a brain tumor with isolated psychiatric symptoms is exceptional in pediatric ages. Since acute psychotic symptoms may be misdiagnosed with a purely psychiatric disorder, the possibility of an underlying cerebral lesion must be kept in mind whatever the patient's age.

Background Pathogenic variants in the dynamin 1 like gene are related to abnormal mitochondrial dynamics and distributions and are associated to variable clinical phenotypes. A few patients harboring the p.Arg403Cys missense variant appears to be different from the classical, more severe phenotypes, showing sudden onset of drug resistant seizures after a previously normal or slightly delayed development. Case report We report on a boy with abrupt onset of focal status and coma at the age of 13, initially treated as autoimmune encephalitis, with final diagnosis of de novo missense p.Arg403Cys variant in the DNM1L gene. Discussion We compare his clinical, electrophysiological, biochemical, neuroradiological and histopathological picture to the rare cases reported to date and provide diagnostic clues that can help clinicians in differentiate p.Arg403Cys-related phenotype from that of immune-mediated encephalopathies. Conclusion The clinical picture related to p.Arg403Cys mutations should be considered alongside acquired pathologies in the differential diagnosis of young patients with focal refractory epilepsy and encephalopathy, also occurring during late childhood or adolescence. Prompt genetic testing allows to avoid unnecessary treatments and procedures and to better define the prognosis and management strategies.

A pesar de las ventajas del e-learning, esta modalidad de aprendizaje es proclive a la deserción. Estudios anteriores mostraron que se pueden aplicar técnicas de aprendizaje automático a los registros de interacciones entre estudiantes y la plataforma para predecir el abandono. En esa línea, este trabajo intenta encontrar modelos predictivos de deserción en cursos virtuales que duran entre seis y dieciséis semanas, utilizando registros de Moodle correspondientes a las dos primeras. Se evaluó la sensibilidad, especificidad y precisión de los modelos, pero se priorizó más en qué medida dichos modelos facilitaban evitar la deserción mediante acciones de retención efectivas en costo. Específicamente, se usaron datos de varias cohortes de cuatro cursos de temáticas y duraciones distintas, dictados por la Secretaría de Extensión de la Universidad Tecnológica Nacional de la República Argentina, Regional Buenos Aires, entre febrero de 2018 y octubre de 2019. Se usaron distintos algoritmos para generar modelos predictivos y optimizarlos hacia la mitigación de la pérdida económica causada por la deserción. Se analizó si alguno en particular generaba los mejores modelos para todos los cursos. Se estudió si convenía construir modelos separados por curso o bien uno para todo el conjunto de los datos de los cuatro cursos. Como conclusión, se encontró que sí es posible construir modelos predictivos exitosos y que el algoritmo que produjo los mejores modelos fue una red neuronal en tres de los cuatro cursos. Asimismo, resultó mejor el modelo que ajustó cada uno por separado.

The COVID-19 pandemic has changed individuals' lifestyles to a great extent, particularly in Italy. Although many concerns about it have been highlighted, its impact on children and adolescents has scarcely been examined. The purpose of this study was to explore behavioral consequences and coping strategies related to the pandemic among families in Italy, by focusing on developmental ages from the caregivers' perspective, 3 weeks into quarantine. An exploratory cross-sectional online survey was conducted over 14 days. Google Forms was employed to conduct the survey. Demographic variables and pre-existing Psychological Weaknesses (PsW) were asked. Adults' sleep difficulties (SleepScore) and coping strategies during quarantine were assessed. Behavioral changes related to quarantine of both subjects completing the form (COVIDStress) and their children (when present) were questioned. Of the 6,871 respondents, we selected 6,800 valid questionnaires; 3,245 declared children aged under 18 years of age (caregivers). PsWs were recognizable in 64.9% among non-caregivers and in 61.5% of caregivers, with a mean PsW score of 1.42 ± 1.26 and 1.30 ± 1.25 over 3 points, respectively. The 95.5% of the non-caregivers and the 96.5% of caregivers presented behavioral changes with a mean COVIDStress of 3.85 ± 1.82 and 4.09 ± 1.79 over 8, respectively (pp < 0.001), who showed higher SleepScores (2.41 ± 1.26 against 2.57 ± 1.38 points over 6, p < 0.001). COVIDStress (and SleepScore) strongly correlated with PsW (p < 0.001). Caregivers observed behavioral changes in their children in the 64.3% of the p < 0.001). Presence of caregivers' coping strategies was less associated to behavioral changes in the p = 0.001) but not in the 6–18 (p = 0.06). The COVID-19 pandemic has adversely impacted families in Italy with regard to behavioral changes, especially in high-risk categories with PsWs and caregivers, especially the ones with children aged

Eating epilepsy (EE) is a form of reflex epilepsy in which seizures are triggered by eating. It is a rare condition but a high prevalence has been reported in Sri Lanka. In EE, the ictal semiology includes focal seizures with or without secondary generalization or generalized seizures. Some cases are idiopathic while focal structural changes on imaging, if present, are often confined to the temporal lobe or perisylvian region. On the other hand, some cases support the hypothesis of a genetic aetiology. The prognosis of EE is extremely variable due to the different nature of the underlying disorder. We describe two patients with symptomatic eating epilepsy, a 13-year-old boy with a bilateral perisylvian polymicrogyria and a 2-year-old boy with a genetic cause. The presence of structural lesions or the dysfunction of specific cortical regions in the context of a germline genetic alteration might lead to a hyperexcitation fostering the epileptogenesis. We review the available literature to clarify the aetiopathogenesis and the mechanisms underlying EE to improve the diagnosis and the management of these rare conditions.

BACKGROUND: Continuous spike-wave during slow wave sleep syndrome (CSWS) and Landau-Kleffner syndrome (LKS) are two epileptic encephalopathies that present with neurocognitive regression, aphasia, and clinical seizures, typically presenting in children around five years of age. The pathophysiology of these conditions is not completely understood. Some studies suggest a common origin for both. No systematic reviews have assessed the efficacy of pharmacological interventions for these conditions. OBJECTIVES: To assess the benefit and adverse effects of pharmacological interventions for the treatment of CSWS and LKS. SEARCH METHODS: On 8 September 2020, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (1946 to September 04, 2020). We applied no language restrictions. CRS Web includes randomised or quasi-randomised, controlled trials from CENTRAL, PubMed, Embase, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. SELECTION CRITERIA: Randomised controlled trials, quasi-randomised controlled trials, and cluster-randomised trials comparing antiepileptic drugs alone, or with steroids or intravenous immunoglobulins, or both versus other antiepileptic drugs, or placebo, or no treatment, administered to children with CSWS and LKS. We planned to compare treatments for the two conditions separately. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies identified by the search strategy for inclusion. The primary outcomes considered in this review were neuropsychological-neurolinguistic functions. MAIN RESULTS: Our search strategy yielded 18 references. Two review authors independently assessed all references. We did not find any completed studies to include. We identified one ongoing trial, which was terminated because of lack of enrolment. AUTHORS' CONCLUSIONS: There was no evidence from trials to support or refute the use of pharmacological treatment for continuous spike-wave during slow wave sleep syndrome or Landau-Kleffner syndrome. Well-designed randomised controlled trials are needed to inform practice. (Less)

Background Childhood epilepsies are a heterogeneous group of conditions differing in diagnostic criteria, management, and outcome. Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) is a neurodegenerative condition caused by biallelic TPP1 variants. This disorder presents with subtle and relatively non-specific symptoms, mimicking those observed in more common paediatric epilepsies and followed by rapid psychomotor deterioration and drug-resistant epilepsy. A prompt diagnosis is essential to adopt appropriate treatment and disease management strategies. Methods This is a prospective, multicentre study on the efficiency of targeted re-sequencing in the early identification of the genetic causes of childhood epilepsy, with particular regard to CLN2. After phenotypic characterization, a 283-gene Next Generation Sequencing panel was performed in 21 Italian children with neurodevelopmental abnormalities, aged between 24 and 60 months, experiencing first unprovoked seizure after 2 years of age. Results The average age at enrolment was 39.9 months, with a mean age at seizure onset of 30.9 months and a mean time interval between seizure onset and targeted resequencing of 9 months. Genetic confirmation was achieved in 4 out of 21 patients, with a diagnostic yield of 19%. In one case, the homozygous splice acceptor variant c.509-1G > C in TPP1 was identified, leading to a CLN2 diagnosis. Three pathogenic variants in MECP2 were also detected in three patients, including the frameshift variant c.1157_1186delinsA (p.Leu386Hisfs*9) in a girl with negative single gene sequencing. Variants of unknown significance (VUS) were found in 11 out of 21 (52.4%) individuals, whereas no clinically significant variants were observed in the remaining 6 subjects. Conclusions Our findings support the efficacy of target re-sequencing in the identification of the genetic causes of childhood epilepsy and suggest that this technique might prove successful in the early detection of CLN2 as well as other neurodevelopmental conditions.

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy and tolerability of pharmacological interventions for the treatment of CSWS and LKS.

Heterogeneous clinical and neuropsychological features, such as intellectual disability, developmental and language delay, hypotonia, and, to a lesser extent, microcephaly that is present in about the half of the reported patients, characterize the 3q29 microduplication syndrome with usually a milder phenotype compared with the corresponding 3q29 microdeletion syndrome. The duplications described so far range from 2.3 Mb to 1.6 Mb, spanning from TFRC to BDH1 genes. Here we report on two patients with overlapping interstitial duplications of the 3q29 region differing in size. Patient 1 harboured a common-seized 3q29 microduplication spanning ∼1.6 Mb, while patient 2 carried a very small 3q29 microduplication of 448.8 Kb encompassing only two genes, DLG1 and BDH1. Both patients presented clinical characteristics similar to those reported in the literature in 3q29 microduplication syndrome. Interestingly, heterotopic gray matter nodules were found along the right lateral ventricle on brain MRI in patient 1, thus expanding the neuroradiological phenotype in 3q29 microduplication syndrome, while patient 2 allowed us to define with more precision the smallest region of overlap (SRO). Gene content analysis of the duplicated region suggests that gain-of-dosage of DLG1 and BDH1 may be a good candidate for the main clinical features of this syndrome.

Prosaposin (PSAP) gene mutations, affecting saposin B (Sap-B) domain, cause a rare metachromatic leukodystrophy (MLD) variant in which arylsulfatase A (ARSA) activity is normal. To date, only 10 different PSAP mutations have been associated with a total of 18 unrelated MLD patients worldwide. In this study, we report for the first time a family with Moroccan origins in which the proband, presenting with a late-infantile onset of neurological involvement and a brain MRI with the typical tigroid MLD pattern, showed normal values of ARSA activity in the presence of an abnormal pattern of urinary sulfatides. In view of these findings, PSAP gene was analyzed, identifying the newly genomic homozygous c.909 + 1G > A mutation occurring within the invariant GT dinucleotide of the intron 8 donor splice site. Reverse transcriptase-polymerase chain reaction (RT-PCR), showing the direct junction of exon 7 to exon 9, confirmed the skipping of the entire exon 8 (p.Gln260_Lys303) which normally contains two cysteine residues (Cys271 and Cys265) involved in disulfide bridges. Our report provides further evidence that phenotypes of patients with Sap-B deficiency vary widely depending on age of onset, type, and severity of symptoms. Awareness of this rare MLD variant is crucial to prevent delayed diagnosis or misdiagnosis and to promptly provide an accurate genetic counseling, including prenatal diagnosis, to families.

Introduction Variants in the CACNA1A gene on chromosome 19p13 result in a spectrum of neurological phenotypes ranging from familial or sporadic hemiplegic migraine to congenital or progressive encephalopathies. Patients with CACNA1A variants often show acute attacks with ataxia or hemiplegia till coma, sometimes related to unilateral brain oedema. No guidelines for the medical management of these attacks are available since treatment is empiric, and many cases do not respond to common antimigraine drugs. Case description We report on the emergency personalized treatment protocol used in an 11 year-old girl with CACNA1A-related encephalopathy for the management of acute attacks of headache, hemiconvulsions and hemiplegia with coma. Discussion Combined corticosteroid pulses and hypertonic solution led to a reduction in severity and duration of acute attacks when administered in the early stages, characterized by migraine, seizure, fever, vomiting and impairment of consciousness associated to hemispheric slowing on the EEG.

Classic Sturge-Weber syndrome (SWS) is characterized by presence of flammeus nevus involving the first sensory branch of trigeminal nerve, ipsilateral leptomeningeal angiomatosis, and choroidal angioma. Sporadic cases of SWS without facial nevus (SWS type III) have been rarely reported. Here we report the clinical and neuroradiological findings of five patients with SWS type III and compare their findings with those described in the literature. This study confirmed that SWS type III should be considered in any child or young adult presenting with seizures or complicated migraine and intracranial unilateral calcification. The diagnosis must be confirmed with contrast-enhanced MRI images of the brain. Surgical therapy should be considered in patients with drug-resistant and persistent epileptic seizures.

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a well-defined autoimmune disorder. Hashimoto's encephalopathy (HE) is a still controversial entity, lacking definite diagnostic criteria. We described a 14-year-old-girl presenting with a clinical picture consistent with the diagnosis of anti-NMDAR encephalitis, confirmed by NMDAR antibody testing. Four years earlier, she had presented a similar episode of acute encephalopathy diagnosed as HE. Anti-NMDAR encephalitis and HE share similar clinical features so that the differential diagnosis can be difficult if specific antibodies are not tested. The correct diagnosis of anti-NMDAR encephalitis is crucial to plan the appropriate management and follow-up, namely in term of oncological screening, since it can be paraneoplastic in origin. We suggest to re-evaluate the clinical history of all subjects with previous HE diagnosis in order to evaluate the possible diagnosis of anti-NMDAR encephalitis and plan the appropriate management of these patients. © 2013 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Summary: Introduction: To determine the occurrence of neuroradiological abnormalities and to perform genotype–phenotype correlations in severe myoclonic epilepsy of infancy (SMEI, Dravet syndrome). Patients and Methods: Alpha-subunit type A of voltage-gated sodium channel (SCN1A) mutational screening was performed by denaturing high-performance liquid chromatography (DHPLC) and multiplex ligation probe amplification (MLPA). MRI inclusion criteria were: last examination obtained after the age of 4 years on 1.5-T systems; hippocampal cuts acquired perpendicular to the long axis of the hippocampus; qualitative assessment was performed on T1-weighted, T2-weighted, proton density, and 1–3 mm thick coronal FLAIR images. Results: We collected 58 SMEI patients in whom last MRI was performed at or later than 4 years of age. SCN1A mutations occurred in 35 (60%) cases. Thirteen (22.4%) out of 58 patients showed abnormal MRIs. Eight patients showed cortical brain atrophy of which 3 associated to ventricles abnormalities, 1 to cerebellar atrophy, 1 to white matter hyperintensity; 3 patients had ventricles enlargement only; 1 patient showed hippocampal sclerosis (HS); 1 had focal cortical dysplasia. Genotype–phenotype analysis indicated that abnormal MRIs occurred more frequently in patients without SCN1A mutations (9/23; 39.1%) compared to those carrying SCN1A mutations (4/35; 11.4%) (p = 0.02). Conclusion: Different brain abnormalities may occur in SMEI. Only one case with HS was observed; thus, our study does not support the association between prolonged febrile seizures and HS in SMEI. Abnormal MRIs were significantly more frequent in patients without SCN1A mutations. Prospective MRI studies will assess the etiological role of the changes observed in these patients.