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Importance: There are suggestions that school pressure may be stressful and a factor in child and adolescent mental health disturbances, but data about this association are scarce and inconclusive. Objective: To assess whether varying degrees of school interruption were associated with changes in emergency department (ED) psychiatric visits of children and adolescents before and after the COVID-19 outbreak. Design, Setting, and Participants: A cross-sectional observational study was conducted at 9 urban university hospitals in Italy. All ED visits from January 1, 2018, to December 31, 2021, for psychiatric reasons of patients younger than 18 years were examined for demographic characteristics and type of psychopathologic factors. Data analysis was conducted from July 1 to August 31, 2023. Exposure: The disruption in the usual succession of school and holiday periods brought on by the COVID-19 pandemic at different times and with various degrees of intensity. Main Outcomes and Measures: Total number of pediatric ED visits, psychiatric ED visits, and psychiatric ED visits categorized by specific reasons (eg, psychomotor agitation, suicide ideation [SI] or suicide attempt [SA], and eating disorders) on a weekly basis. Results: A total of 13â¯014 psychiatric ED visits (1.3% of all pediatric ED visits) were recorded (63.2% females; mean [SD] age, 13.8 [3.8] years). The number of ED psychiatric visits increased over time (incidence rate ratio [IRR], 1.19; 95% CI, 1.16-1.22 for each year). Significant increases in ED visits were observed for eating disorders (294.8%), SI (297.8%), and SA (249.1%). School opening, but not social lockdown restriction, was associated with an increase in the number of ED psychiatric visits (IRR, 1.29; 95% CI, 1.23-1.34), which was evident for females and for SI with SA. Socioeconomic status was associated with an increase in psychiatric visits for males (IRR, 1.12; 95% CI, 1.04-1.20) but not females (IRR, 1.04; 95% CI, 0.98-1.10). Conclusions and Relevance: In this study, school opening was associated with an increased incidence of acute psychiatric emergencies among children and adolescents, suggesting that school can be a substantial source of stress with acute mental health implications.
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COVID-19 , Serviço Hospitalar de Emergência , Instituições Acadêmicas , Humanos , COVID-19/epidemiologia , COVID-19/psicologia , Feminino , Masculino , Criança , Adolescente , Estudos Transversais , Itália/epidemiologia , Serviço Hospitalar de Emergência/estatística & dados numéricos , Saúde Mental/estatística & dados numéricos , Transtornos Mentais/epidemiologia , SARS-CoV-2 , Pandemias , Ideação SuicidaRESUMO
Besides recent advances in neonatal care, preterm newborns still develop sex-biased behavioral alterations. Preterms fail to receive placental insulin-like growth factor-1 (IGF-1), a major fetal growth hormone in utero, and low IGF-1 serum levels correlate with preterm poor neurodevelopmental outcomes. Here, we mimicked IGF-1 deficiency of preterm newborns in mice by perinatal administration of an IGF-1 receptor antagonist. This resulted in sex-biased brain microstructural, functional, and behavioral alterations, resembling those of ex-preterm children, which we characterized performing parallel mouse/human behavioral tests. Pharmacological enhancement of GABAergic tonic inhibition by the U.S. Food and Drug Administration-approved drug ganaxolone rescued functional/behavioral alterations in mice. Establishing an unprecedented mouse model of prematurity, our work dissects the mechanisms at the core of abnormal behaviors and identifies a readily translatable therapeutic strategy for preterm brain disorders.
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Encefalopatias , Fator de Crescimento Insulin-Like I , Estados Unidos , Criança , Humanos , Recém-Nascido , Gravidez , Feminino , Animais , Camundongos , Receptor IGF Tipo 1 , Placenta , Recém-Nascido Prematuro , Encefalopatias/tratamento farmacológicoRESUMO
Extra-uterine growth restriction (EUGR) is a common complication and a known risk factor for impaired development in very-low-birth-weight (VLBW) neonates. We report a population of 288 patients with no or with low-grade MRI lesions scanned at a term equivalent age (TEA) born between 2012 and 2018. Griffiths Mental Development Scale II (GMDS II) at 2 and 3 years, preterm complications and weight growth were retrospectively analyzed. EUGR was defined for weight z-score Ë 10 percentile at TEA, 6 and 12 months of correct age or as z-score decreased by 1-point standard deviation (SDS) from birth to TEA and from TEA to 6 months. Multivariate analysis showed that a higher weight z-score at 6 months is protective for the global developmental quotient (DQ) at 2 years (OR 0.74; CI 95% 0.59-0.93; p = 0.01). EUGR at 6 months was associated with worse locomotor, personal/social, language and performance DQ at 2 years and worse language and practical reasoning DQ at 3 years. In conclusion, a worse weight z-score at 6 months of age seems to be an independent risk factor for significantly reduced GMDS in many areas. These results suggest that we should invest more into post-discharge nutrition, optimizing family nutritional education.
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Assistência ao Convalescente , Recém-Nascido Prematuro , Recém-Nascido , Humanos , Lactente , Estudos Retrospectivos , Alta do Paciente , Recém-Nascido de muito Baixo Peso , Peso ao Nascer , Encéfalo/diagnóstico por imagemRESUMO
We report the case of a preterm of 27 weeks of gestation who developed posthemorrhagic ventricular dilatation associated to a complete thrombosis of the superior sagittal sinus, for its peculiar interest in clarifying the physiology of the cerebrospinal fluid (CSF) dynamics. The exact CSF volume that must be removed to improve cerebral hemodynamics and outcomes in infants with posthemorrhagic ventricular dilatation is unknown. According to Volpe's studies, a volume of 10 to 15 mL/kg/die of body weight is commonly chosen. The subject we report needed an excessive CSF drainage (up to 32 mL/kg/d), in presence of a functioning external ventricular drain. We review the literature on the topic, and we postulate that the superior sagittal sinus may play an active role in the CSF dynamics of the immature brain (as it happens for the adult brain).
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Hidrocefalia , Recém-Nascido Prematuro , Lactente , Adulto , Recém-Nascido , Humanos , Seio Sagital Superior/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Hemodinâmica , Vazamento de Líquido Cefalorraquidiano/complicações , Hemorragia CerebralRESUMO
Sleep changes significantly throughout the human lifespan. Physiological modifications in sleep regulation, in common with many mammals (especially in the circadian rhythms), predispose adolescents to sleep loss until early adulthood. Adolescents are one-sixth of all human beings and are at high risk for mental diseases (particularly mood disorders) and self-injury. This has been attributed to the incredible number of changes occurring in a limited time window that encompasses rapid biological and psychosocial modifications, which predispose teens to at-risk behaviors. Adolescents' sleep patterns have been investigated as a biunivocal cause for potential damaging conditions, in which insufficient sleep may be both a cause and a consequence of mental health problems. The recent COVID-19 pandemic in particular has made a detrimental contribution to many adolescents' mental health and sleep quality. In this review, we aim to summarize the knowledge in the field and to explore implications for adolescents' (and future adults') mental and physical health, as well as to outline potential strategies of prevention.
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AIM: To determine whether isolated low-grade germinal matrix-intraventricular haemorrhages (LG-GMH-IVH) and low-grade punctate cerebellar haemorrhages (LG-CBH) contribute to the neurodevelopment of infants born preterm with very low birthweight (VLBW). METHOD: A prospective observational cohort study was conducted on infants born with VLBW hospitalized from January 2012 to July 2017 who had undergone serial cranial ultrasounds since birth and magnetic resonance susceptibility-weighted imaging of the brain at term-corrected age. Only those with VLBW carrying isolated LG-GMH-IVH (grades 1 or 2) or isolated LG-CBH (punctate cerebellar haemorrhages ≤4 mm in diameter) or absence of lesions (no-lesion) were enrolled and followed up to 3 years. The Griffiths Mental Development Scales, Extended and Revised version (GMDS-ER), were used to assess neurodevelopment, considering unsatisfactory scores less than 85. Behaviour, according to the criteria of the International Classification of Diseases, 10th Revision, and rehabilitation data were noted. RESULTS: Two-hundred and forty infants with VLBW were enrolled: 34 with LG-GMH-IVH, 17 with LG-CBH, and 189 as no-lesion. The LG-GMH-IVH and LG-CBH groups scored worse than the no-lesion group on all GMDS-ER scores for 1 year, 2 years, and 3 years. The LG-CBH group scored lower than the LG-GMH-IVH group for total GMDS-ER scores at 1 year and 2 years but not at 3 years. At 3 years, compared with the LG-CBH group, those with LG-GMH-IVH received less and later physical therapy, with more frequent attention problems. The odds ratio for unsatisfactory GMDS-ER scores corrected for gestational age was 5.75 for LG-CBH (95% confidence interval 1.92-17.25; p = 0.002) and 2.67 for LG-GMH-IVH (95% confidence interval 1.16-6.13; p = 0.02). INTERPRETATION: Low-grade haemorrhages affect the neurodevelopment of very-low-birthweight infants. Early rehabilitation might have contributed to their development.
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OBJECTIVE: To compare psychiatric emergencies and self-harm at emergency departments (EDs) 1 year into the pandemic, to early pandemic and pre-pandemic, and to examine the changes in the characteristics of self-harm presentations. METHOD: This retrospective cohort study expanded on the Pandemic-Related Emergency Psychiatric Presentations (PREP-kids) study. Routine record data in March to April of 2019, 2020, and 2021 from 62 EDs in 25 countries were included. ED presentations made by children and adolescents for any mental health reasons were analyzed. RESULTS: Altogether, 8,174 psychiatric presentations were recorded (63.5% female; mean [SD] age, 14.3 [2.6] years), 3,742 of which were self-harm presentations. Rate of psychiatric ED presentations in March to April 2021 was twice as high as in March to April 2020 (incidence rate ratio [IRR], 1.93; 95% CI, 1.60-2.33), and 50% higher than in March to April 2019 (IRR, 1.51; 95% CI, 1.25-1.81). Rate of self-harm presentations doubled between March to April 2020 and March to April 2021 (IRR, 1.98; 95% CI, 1.68-2.34), and was overall 1.7 times higher than in March to April 2019 (IRR, 1.70; 95% CI, 1.44-2.00). Comparing self-harm characteristics in March to April 2021 with March to April 2019, self-harm contributed to a higher proportion of all psychiatric presentations (odds ratio [OR], 1.30; 95% CI, 1.05-1.62), whereas female representation in self-harm presentations doubled (OR, 1.98; 95% CI, 1.45-2.72) and follow-up appointments were offered 4 times as often (OR, 4.46; 95% CI, 2.32-8.58). CONCLUSION: Increased pediatric ED visits for both self-harm and psychiatric reasons were observed, suggesting potential deterioration in child mental health. Self-harm in girls possibly increased and needs to be prioritized. Clinical services should continue using follow-up appointments to support discharge from EDs. DIVERSITY & INCLUSION STATEMENT: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.
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COVID-19 , Comportamento Autodestrutivo , Criança , Humanos , Feminino , Adolescente , Masculino , Pandemias , Estudos Retrospectivos , COVID-19/epidemiologia , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/psicologia , Serviço Hospitalar de EmergênciaRESUMO
Interstitial 2q24.2q24.3 microdeletions are rare cytogenetic aberrations associated with heterogeneous clinical features depending on the size of the deletion. Here, we describe 2 patients with overlapping de novo 2q24.2q24.3 deletions, characterized by array-CGH. This is the smallest 2q24.2q24.3 region of overlap described in the literature encompassing only 9 genes (SLC4A10, DPP4, GCG, FAP, IFIH1, GCA, KCNH7, FIGN, GRB14). We focused our attention on SLC4A10, DPP4, and KCNH7, genes associated with neurological features. Our patients presented similar features: intellectual disability, developmental and language delay, hypotonia, joint laxity, and dysmorphic features. Only patient 2 showed profound deafness and also carried a heterozygous mutation of the GJB2 gene responsible for autosomal recessive deafness 1A (DFNB1A: OMIM 220290). Could the disruption of a gene present in the 2q24.2q24.3 deleted region be responsible for her profound hearing loss?
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Surdez , Deficiência Intelectual , Deleção Cromossômica , Surdez/genética , Dipeptidil Peptidase 4/genética , Feminino , Humanos , Deficiência Intelectual/genética , Helicase IFIH1 Induzida por Interferon/genética , Hipotonia Muscular/genéticaRESUMO
BACKGROUND: COVID-19 is having a significant impact on long term children' and adolescents' psychological health. We aimed to evaluate the direct early psychological and behavioural signs related to the COVID-19 pandemic outbreak and related confinement on children and adolescents. METHODS: Children and adolescents' drawings were collected for a limited time window (16th March-10th April 2020) and analyzed. Their parents were asked in the following month to answer a qualitative e-survey on somatic complaints and behavioral changes of the participating children/adolescents. RESULTS: Ninety-eight drawings by children/adolescents (mean age 7.01±2.83 years) were analysed. Analyses of the 98 drawings reported signs of trauma in all (of them, 60.2% with moderate-to high levels). Children aged 3-5 years were more impacted, followed by preadolescents/adolescents aged 11-17 years. Parents reported somatic complaints in the 71.1% of their children/adolescents: the most frequent were increased appetite (35.6%), abdominal pain (20.0%) and headache (20.0%). Behavioral changes were observed in 77.8% of subjects: increased appetite (35.6%), abdominal pain (20.0%) and headache (20.0%) were more represented. CONCLUSIONS: Early psychological distress related to COVID-19 pandemic was observed both in children and in adolescents by the analysis of drawings and confirmed by their parents. Implementation of mental health-care services for preventing future psychopathological problems is mandatory.
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PURPOSE: To explore the relationships between clinical-radiological features and surgical outcomes in subjects with interhemispheric cysts (IHC) and corpus callosum anomalies. METHODS: We reviewed the clinico-radiological and neurosurgical data of 38 patients surgically treated with endoscopic fenestration, shunting, or combined approaches from 2000 to 2018 (24 males, median age 9 years). Pre- and postoperative changes in IHC volume were calculated. Outcome assessment was based on clinico-radiological data. Group comparisons were performed using χ2, Fisher exact, Mann-Whitney U, and Kruskal-Wallis tests. RESULTS: Median age at first surgery was 4 months (mean follow-up 8.3 years). Eighteen individuals (47.3%) required > 1 intervention due to IHC regrowth and/or shunt malfunction. Larger preoperative IHC volume (P = .008) and younger age at surgery (P = .016) were associated with cyst regrowth. At last follow-up, mean cystic volume was 307.8 cm3, with IHC volume reduction > 66% in 19/38 (50%) subjects. The neurological outcome was good in 14/38 subjects (36.8%), fair in 18/38 (47.3%), and poor in 6/38 (15.7%). There were no differences in the postoperative cyst volume with respect to either the type of first surgery or overall surgery type. Higher absolute postoperative IHC reduction was observed in subjects who underwent both IHC fenestration and shunting procedures (P < .0001). No differences in neurological outcome were found according to patient age at surgery or degree of IHC reduction. CONCLUSION: Endoscopic fenestration and shunting approaches are both effective but often require multiple procedures especially in younger patients. Larger IHC are more frequently complicated by cyst regrowth after surgery.
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Corpo Caloso , Cistos , Criança , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/cirurgia , Cistos/diagnóstico por imagem , Cistos/cirurgia , Endoscopia/métodos , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Procedimentos Neurocirúrgicos/métodos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Background: We investigated the COVID19-related psychological impact on healthcare workers in Italy and in Italian-speaking regions of Switzerland, three weeks after its outbreak. All professional groups of public hospitals in Italy and Switzerland were asked to complete a 38 questions online survey investigating demographic, marital and working status, presence of stress symptoms and need for psychological support. Results: Within 38 h a total of 3,038 responses were collected. The subgroup analysis identified specific categories at risk according to age, type of work and region of origin. Critical care workers, in particular females, reported an increased number of working hours, decline in confidence in the future, presence of stress symptoms and need for psychological support. Respondents reporting stress symptoms and those with children declared a higher need for psychological support. Conclusions: The large number of participants in such a short time indicates for a high interest on topic among health-care workers. The COVID19 outbreak has been experienced as a repeated trauma for many health-care professionals, especially among female nurses' categories. Early evidence of the need of implementating short and long-term measures to mitigate impact of the emotional burden of COVID-19 pandemic are still relevant.
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COVID-19 , Teorema de Bayes , COVID-19/epidemiologia , Criança , Feminino , Pessoal de Saúde , Humanos , Pandemias , SARS-CoV-2 , Suíça/epidemiologiaRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) related confinement severely impacted people wellbeing. Many studies focused on general population, although it is reasonable to expect that patients with neurodevelopmental disorders might have been at higher risk. Children/adolescents with Attention Deficit/Hyperactivity Disorder (ADHD) might be potentially more vulnerable, due to their intolerance to forced restrictions that limit stimulating experiences, to obligation to follow instructions and to acceptation of imposed rules We aimed to compare stress-related behavioral changes of the first COVD-19 related confinement among 6-18 years old ADHD and typically developing subjects. METHODS: Two parent-proxy online surveys have been employed, shared via social media. Symptoms of acute stress related to the pandemic and a question about family members/households' COVID-19 positivity have been listed in 8 yes/no items. Chi-squared tests were applied. RESULTS: Final sample consisted of 1078 typically developing subjects and 979 ADHD. Exaggerated startle response, difficulties in waking-up, angry mood as well as COVID-19 related fears were more prevalent among ADHD vs. typically developing subjects. typically developing subjects showed higher prevalence of research for information about COVID-19 and worries about death. CONCLUSIONS: In conclusion, the COVID-19 experience significantly impacted children and adolescents with ADHD to a great extent, similarly to typically developing subjects. ADHD showed more anxious-phobic responses, while typically developing subjects demonstrate more depressive attitudes. Differences in stress symptoms profiles between ADHD and T typically developing subjects warrant to develop distinct strategies of therapeutic interviews.
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Interstitial 6p25.1p24.3 microdeletions are rare events and a clear karyotype/phenotype correlation has not yet been determined. In this study, we present the clinical and molecular description of a child with a de novo 6p25.1p24.3 microdeletion, characterized by array-CGH, associated with mild intellectual disability, facial dysmorphisms, hypopigmentation of the skin of the abdomen, heart defects, mild pontine hypoplasia and hypotonia. This deleted region contains 14 OMIM genes (NRN1, F13A1, RREB1, SSR1, RIOK1, DSP, BMP6, TXNDC5, BLOC1S5, EEF1E1, SLC35B3 and HULC). To the best of our knowledge until now only six cases have been reported presenting an interstitial microdeletion, but a unique case carries a deleted region containing the same genes of our patient. We compared clinical features and genetic data with that of the previously reported patient. We also analysed the gene content of the deleted region to investigate the possible role of specific genes in the clinical phenotype of our patient.
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Anormalidades Múltiplas/genética , Deleção Cromossômica , Cromossomos Humanos Par 6 , Anormalidades Múltiplas/diagnóstico por imagem , Adolescente , Pré-Escolar , Feminino , Humanos , FenótipoRESUMO
Mutations in AarF domain-containing kinase 3 (ADCK3) are responsible for the most frequent form of hereditary coenzyme Q10 (CoQ10) deficiency (Q10 deficiency-4), which is mainly associated with autosomal recessive cerebellar ataxia type 2 (ARCA2). Clinical presentation is characterized by a variable degree of cerebellar atrophy and a broad spectrum of associated symptoms, including muscular involvement, movement disorders, neurosensory loss, cognitive impairment, psychiatric symptoms and epilepsy. In this report, we describe, for the first time, a case of photoparoxysmal response in a female patient with a mutation in ADCK3. Disease onset occurred in early childhood with gait ataxia, and mild-to-moderate degeneration. Seizures appeared at eight years and six months, occurring only during sleep. Photoparoxysmal response was observed at 14 years, almost concomitant with the genetic diagnosis (c.901C>T;c.589-3C>G) and the start of CoQ10 oral supplementation. A year later, disease progression slowed down, and photosensitivity was attenuated. A review of the literature is provided focusing on epileptic features of ADCK3-related disease as well as the physiopathology of photoparoxysmal response and supposed cerebellar involvement in photosensitivity. Moreover, the potential role of CoQ10 oral supplementation is discussed. Prospective studies on larger populations are needed to further understand these data.
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Ataxia Cerebelar , Epilepsia Reflexa , Proteínas Mitocondriais/genética , Ubiquinona/análogos & derivados , Adolescente , Ataxia Cerebelar/complicações , Ataxia Cerebelar/tratamento farmacológico , Ataxia Cerebelar/genética , Ataxia Cerebelar/fisiopatologia , Epilepsia Reflexa/tratamento farmacológico , Epilepsia Reflexa/etiologia , Epilepsia Reflexa/genética , Epilepsia Reflexa/fisiopatologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Ubiquinona/farmacologiaRESUMO
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 (p<0.001). Sleep difficulties were present in the 61.6% of the non-caregivers and in the 64.4% of the caregivers (p < 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 <6 years old and in 72.5% of 6-18 years old. Caregivers' discomfort related to quarantine (COVIDStress, SleepScore) was strongly associated to behavioral changes in both age groups of <6 and 6-18 (p < 0.001). Presence of caregivers' coping strategies was less associated to behavioral changes in the <6 sample (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 <6 years. While coping strategies functioned as protective factors, a wide array of stress symptoms had implications for children's and adolescents' behaviors. It is recommended that public children welfare strategies be implemented, especially for higher-psychosocial-risk categories.
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Comportamento do Adolescente , COVID-19/psicologia , Comportamento Infantil , Família/psicologia , Adolescente , Comportamento do Adolescente/psicologia , Adulto , Idoso , COVID-19/epidemiologia , Criança , Comportamento Infantil/psicologia , Pré-Escolar , Feminino , Inquéritos Epidemiológicos , Humanos , Itália/epidemiologia , Masculino , Saúde Mental , Transtornos do Sono-Vigília/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologiaRESUMO
OBJECTIVE: CASK pathogenic variants are associated with variable features, as intellectual disability, optic atrophy, brainstem/cerebellar hypoplasia, and epileptic encephalopathy. Few studies describe the electroclinical features of epilepsy in patients with CASK pathogenic variants and their relationship with developmental delay. METHODS: this national multicentre cohort included genetically confirmed patients with different CASK pathogenic variants. Our findings were compared with cohorts reported in the literature. RESULTS: we collected 34 patients (29 females) showing from moderate (4 patients) to severe (22) and profound (8) developmental delay; all showed pontine and cerebellar hypoplasia, all except three with microcephaly. Seventeen out of 34 patients (50%) suffered from epileptic seizures, including spasms (11 patients, 32.3%), generalized (5) or focal seizures (1). In 8/17 individuals (47.1%), epilepsy started at or beyond the age of 24 months. Seven (3 males) out of the 11 children with spasms showed EEG features and a course supporting the diagnosis of a developmental and epileptic encephalopathy (DEE). Drug resistance was frequent in our cohort (52.9% of patients with epilepsy). EEG abnormalities included poorly organized background activity with diffuse or multifocal epileptiform abnormalities and sleep-activation, with possible appearance over the follow-up period. Developmental delay degree was not statistically different among patients with or without seizures but feeding difficulties were more frequent in patients with epilepsy. CONCLUSIONS: epilepsy is a frequent comorbidity with a high incidence of spasms and drug resistance. Overall developmental disability does not seem to be more severe in the group of patients with epilepsy nor to be linked to specific epilepsy/EEG characteristics. A childhood onset of epilepsy is frequent, with possible worsening over time, so that serial and systematic monitoring is mandatory.
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Deficiências do Desenvolvimento/genética , Epilepsia/genética , Guanilato Quinases/genética , Encefalopatias/genética , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Mutação , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVES: The number of preterm babies is steadily growing world-wide and these neonates are at risk of neuro-motor-cognitive deficits. The observation of spontaneous movements in the first three months of age is known to predict such risk. However, the analysis by specifically trained physiotherapists is not suited for the clinical routine, motivating the development of simple computerized video analysis systems, integrated with a well-structured Biobank to make available for preterm babies a growing service with diagnostic, prognostic and epidemiological purposes. METHODS: MIMAS (Markerless Infant Movement Analysis System) is a simple, low-cost system of video analysis of spontaneous movements of newborns in their natural environment, based on a single standard RGB camera, without markers attached to the body. The original videos are transformed into binarized sequences highlighting the silhouette of the baby, in order to minimize the illumination effects and increase the robustness of the analysis; such sequences are then coded by a large set of parameters (39) related to the spatial and spectral changes of the silhouette. The parameter vectors of each baby were stored in the Biobank together with related clinical information. RESULTS: The preliminary test of the system was carried out at the Gaslini Pediatric Hospital in Genoa, where 46 preterm (PT) and 21 full-term (FT) babies (as controls) were recorded at birth (T0) and 8-12 weeks thereafter (T1). A simple statistical analysis of the data showed that the coded parameters are sensitive to the degree of maturation of the newborns (comparing T0 with T1, for both PT and FT babies), and to the conditions at birth (PT vs. FT at T0), whereas this difference tends to vanish at T1. Moreover, the coding method seems also able to detect the few 'abnormal' preterm babies in the PT populations that were analyzed as specific case studies. CONCLUSIONS: Preliminary results motivate the adoption of this tool in clinical practice allowing for a systematic accumulation of cases in the Biobank, thus for improving the accuracy of data analysis performed by MIMAS and ultimately allowing the adoption of data mining techniques.
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Recém-Nascido Prematuro , Movimento , Criança , Humanos , Lactente , Recém-NascidoRESUMO
INTRODUCTION: Schimke Immuno-Osseous Dysplasia (SIOD) is an autosomal recessive multisystem disorder caused by pathogenic variants in the gene SMARCAL1. The clinical picture is characterized by spondyloepiphyseal dysplasia resulting in growth failure, nephropathy and T-cell deficiency. Neurologic manifestations include microcephaly, cognitive impairment, migraine-like headaches and cerebrovascular manifestations such as cerebral atherosclerotic vascular disease and reversible cerebral vasoconstriction. The role of SMARCAL1 deficiency in non-vascular neurological complications is still under debate. Epilepsy has been reported in a few patients, even in the absence of brain abnormalities. Data regarding electroencephalographic (EEG) patterns in SIOD are scarce METHODS: We describe the clinical, neuroradiological and EEG findings in two unrelated patients with SIOD showing a peculiar pseudo-periodic EEG pattern apparently not related to the cerebrovascular complications, since it was recognized both before and after cerebrovascular events CONCLUSION: Our observations support the hypothesis that SMARCAL1plays an important role in neurodevelopment and brain function and expand the spectrum of neurological abnormalities related to SIOD.
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Arteriosclerose/fisiopatologia , Encéfalo/fisiopatologia , Síndrome Nefrótica/fisiopatologia , Osteocondrodisplasias/fisiopatologia , Doenças da Imunodeficiência Primária/fisiopatologia , Embolia Pulmonar/fisiopatologia , Arteriosclerose/genética , Criança , DNA Helicases/genética , Eletroencefalografia , Feminino , Humanos , Mutação , Síndrome Nefrótica/genética , Osteocondrodisplasias/genética , Fenótipo , Doenças da Imunodeficiência Primária/genética , Embolia Pulmonar/genética , Adulto JovemRESUMO
Neuronal growth regulator 1 (NEGR1), a member of the immunoglobulin superfamily cell adhesion molecule subgroup IgLON, has been involved in neuronal growth and connectivity. Genetic variants, in or near the NEGR1 locus, have been associated with obesity and, more recently, with learning difficulties, intellectual disability, and psychiatric disorders. Here, we described the only second report of NEGR1 gene disruption in 1p31.1 microdeletion in two patients. Patient 1 is a 14-year-old female with neurological and psychiatric features present also in her family. Patient 2 is a 5-month-old infant showing global hypotonia as unique neurological features till now. This patient also carries 7p22.1 duplication, of paternal origin, that could be responsible for some malformations present in the child. We hypothesize a role of NEGR1 in producing the phenotype of our patients and compare them with other cases previously reported in the literature and DECIPHER database to better identify a possible genotype-phenotype correlation.
Assuntos
Moléculas de Adesão Celular Neuronais/genética , Deleção de Genes , Transtornos Mentais/genética , Doenças do Sistema Nervoso/genética , Adolescente , Cromossomos Humanos Par 1/genética , Feminino , Proteínas Ligadas por GPI/genética , Humanos , Lactente , Masculino , Transtornos Mentais/patologia , Doenças do Sistema Nervoso/patologia , FenótipoRESUMO
BACKGROUND: Early exposure to nociceptive events may cause brain structural alterations in preterm neonates, with long-lasting consequences on neurodevelopmental outcome. Little is known on the extent to which early pain may affect brain connectivity. We aim to evaluate brain functional connectivity changes in preterm neonate that underwent multiple invasive procedures during the postnatal period, and to correlate them with the neurodevelopmental outcome at 24 months. METHODS: In this prospective case-control study, we collected information about exposure to painful events during the early postnatal period and resting-state BOLD-fMRI data at term equivalent age from two groups of preterm neonate: 33 subjected to painful procedures during the neonatal intensive care (mean gestational age 27.9 ± 1.8 weeks) and 13 who did not require invasive procedures (average gestational age 31.2 ± 2.1 weeks). A data-driven principal-component-based multivariate pattern analysis (MVPA) was used to investigate the effect of early pain exposure on brain functional connectivity, and the relationship between connectivity changes and neurodevelopmental outcome at 24 months, assessed with Griffiths, Developmental Scale-Revised: 0-2. RESULTS: Early pain was associated with decreased functional connectivity between thalami and bilateral somatosensory cortex, and between the right insular cortex and ipsilateral amygdala and hippocampal regions, with a more evident effect in preterm neonate undergoing more invasive procedures. Functional connectivity of the right thalamocortical pathway was related to neuromotor outcome at 24 months (P = 0.003). CONCLUSION: Early exposure to pain is associated with abnormal functional connectivity of developing networks involved in the modulation of noxious stimuli in preterm neonate, contributing to the neurodevelopmental consequence of preterm birth.