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BACKGROUND: The aim of this study was to investigate the frequency and characteristics of pediatric epilepsy in the geographic isolate of Sardinia island and to calculate the prevalence of active epilepsy. METHODS: The study was retrospective, observational and involved a systematic review of medical records and computerized archives containing all clinical and EEG recordings of patients with epilepsy referred to the regional structures that could have followed patients with epilepsy in South Sardinia, during the period 2003-2021. RESULTS: The study population included 112,912 children and adolescents (age ≤ 18 years). 618 children and adolescents (women 42.4 %) were identified. Family history of epilepsy was reported in 153 (26.1 %). Etiology was genetic in 64.5 % and structural in 26.7 % subjects. Focal seizures were reported in 51.6 % of subjects, followed by 34.7 % with generalized seizures and 10.6 % of patients experienced both type of seizures. A total of 301 subjects with active epilepsy in 2019 were identified resulting in a prevalence of 2.67 per 1000 (95 % CI 2.37-2.97). Prevalence in the age class 5-14 years was 4.21 per 1000 (95 % CI 3.72-4.76). CONCLUSION: Compared to the previous studies in distinct geographic isolates, the present study showed a significantly low prevalence rate of active epilepsy; a high percentage of focal seizures and genetic etiology.
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Epilepsia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Eletroencefalografia/efeitos adversos , Epilepsia/epidemiologia , Epilepsia/genética , Itália/epidemiologia , Prevalência , Estudos Retrospectivos , Convulsões/complicações , MasculinoRESUMO
AIM: The current study aims to investigate the effect of Executive Functions (EFs) on Health Related Quality of Life (HRQoL) in a cohort of children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and to identify possible factors that impact HRQoL specifically related to epilepsy-related variables and EFs skills. MATERIAL AND METHOD: The Pediatric Quality of Life Inventory 4.0 Generic Core Scales (PedsQL) and The Behavior Rating Inventory of Executive Function (BRIEF-2 and BRIEF-P) were completed by the parents of 129 patients with SeLECTS. Demographic variables and epilepsy-related variables were collected. RESULTS: Our sample performed in the average range across all the subscales and summary scores of the PedsQL and performed in the normal range of the BRIEF questionnaire. We observed that a lower functioning in EFs was associated with lower overall HRQoL scores. We explored the relationship between epilepsy characteristics and scores on the PedsQL. We found that the use of antiseizure medications (ASMs), longer duration of the treatment, and a higher seizure frequency were associated with a lower HRQoL. Moreover, we observed that executive dysfunction was a significant predictor of reduced HRQoL. CONCLUSION: Our results suggest the importance of the identification of patients with SeLECTS with a high level of risk for a poor HRQoL. We may now add executive dysfunction to the list of known risk factors for poor HRQoL in children with SeLECTS, along with such factors as seizure frequency, recent seizures, use of ASMs and longer duration of therapy. The early identification of children with SeLECTS at risk of a poor HRQoL could allow the activation of adequate interventions.
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Disfunção Cognitiva , Epilepsia , Criança , Humanos , Função Executiva/fisiologia , Qualidade de Vida , Epilepsia/tratamento farmacológico , Convulsões , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Rolandic epilepsy (RE) is the most common genetic childhood epilepsy, consisting of focal, nocturnal seizures and frequent neurodevelopmental impairments in speech, language, literacy and attention. A complex genetic aetiology is presumed in most, with monogenic mutations in GRIN2A accounting for >5% of cases. OBJECTIVE: To identify rare, causal CNV in patients with RE. METHODS: We used high-density SNP arrays to analyse the presence of rare CNVs in 186 patients with RE from the UK, the USA, Sardinia, Argentina and Kerala, India. RESULTS: We identified 84 patients with one or more rare CNVs, and, within this group, 14 (7.5%) with recurrent risk factor CNVs and 15 (8.0%) with likely pathogenic CNVs. Nine patients carried recurrent hotspot CNVs including at 16p13.11 and 1p36, with the most striking finding that four individuals (three from Sardinia) carried a duplication, and one a deletion, at Xp22.31. Five patients with RE carried a rare CNV that disrupted genes associated with other epilepsies (KCTD7, ARHGEF15, CACNA2D1, GRIN2A and ARHGEF4), and 17 cases carried CNVs that disrupted genes associated with other neurological conditions or that are involved in neuronal signalling/development. Network analysis of disrupted genes with high brain expression identified significant enrichment in pathways of the cholinergic synapse, guanine-exchange factor activation and the mammalian target of rapamycin. CONCLUSION: Our results provide a CNV profile of an ethnically diverse cohort of patients with RE, uncovering new areas of research focus, and emphasise the importance of studying non-western European populations in oligogenic disorders to uncover a full picture of risk variation.
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Neurônios Colinérgicos , Variações do Número de Cópias de DNA , Epilepsia Rolândica/genética , Predisposição Genética para Doença , Argentina , Feminino , Testes Genéticos , Humanos , Índia , Itália , Masculino , Sinapses , Estados UnidosAssuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Feminino , Humanos , Pré-Escolar , Natalizumab/uso terapêutico , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Fatores Imunológicos/efeitos adversos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológicoRESUMO
Seizures are rarely reported in Williams-Beuren syndrome (WBS)--a contiguous-gene-deletion disorder caused by a 7q11.23 heterozygous deletion of 1.5-1.8 Mb--and no previous study evaluated electro-clinical features of epilepsy in this syndrome. Furthermore, it has been hypothesized that atypical deletion (e.g., larger than 1.8 Mb) may be responsible for a more pronounced neurological phenotypes, especially including seizures. Our objectives are to describe the electro-clinical features in WBS and to correlate the epileptic phenotype with deletion of the 7q11.23 critical region. We evaluate the electro-clinical features in one case of distal 7q11.23 deletion syndrome and in eight epileptic WBS (eWBS) patients. Additionally, we compare the deletion size-and deleted genes-of four epileptic WBS (eWBS) with that of four non-epileptic WBS (neWBS) patients. Infantile spasms, focal (e.g., motor and dyscognitive with autonomic features) and generalized (e.g., tonic-clonic, tonic, clonic, myoclonic) seizures were encountered. Drug-resistance was observed in one patient. Neuroimaging discovered one case of focal cortical dysplasia, one case of fronto-temporal cortical atrophy and one case of periventricular nodular heterotopia. Comparison of deletion size between eWBS and neWBS patients did not reveal candidate genes potentially underlying epilepsy. This is the largest series describing electro-clinical features of epilepsy in WBS. In WBS, epilepsy should be considered both in case of typical and atypical deletions, which do not involve HIP1, YWHAG or MAGI2.
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Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Epilepsia/etiologia , Síndrome de Williams/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Pré-Escolar , Epilepsia/patologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Fenótipo , Síndrome de Williams/complicações , Síndrome de Williams/patologia , Adulto JovemRESUMO
A cohort of 582 Italian primary school teachers underwent a questionnaire survey to test their knowledge and attitudes toward epilepsy and verify whether an intensive and focused educational program could result in improvement of knowledge and attitudes. The program consisted of a presentation of the clinical manifestations of epilepsy and the distribution of informative brochures and an educational kit on the disease and its management to be used with their students. After several months, 317 teachers were retested using the same questions. Upon retest, the number of "don't know" answers decreased significantly for almost all questions. This was not the case for negative attitudes. The same holds true for teachers believing that epilepsy is a source of learning disability and social disadvantage. These findings support the beliefs that education on epilepsy is more likely to affect ignorance than prejudice and that stronger interventions are needed to counteract stigmatizing behaviors.
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Epilepsia , Docentes , Educação em Saúde/métodos , Conhecimentos, Atitudes e Prática em Saúde , Instituições Acadêmicas , Adulto , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Estigma SocialRESUMO
Seizures are observed with a frequency of 3-21% in children with fetal alcohol spectrum disorders (FASD). However, clinical, neuroradiologic, and electroencephalography (EEG) features are poorly described. In this study, 13 patients with FASD and epilepsy or seizures were identified retrospectively from the databases of seven Italian pediatric neurology divisions. Eleven children were affected by epilepsy, and two had at least one documented seizure. Both generalized and focal seizures were observed. EEG showed diffuse or focal epileptic activity; two children developed electric status epilepticus during sleep (ESES). Structural brain anomalies, including polymicrogyria, nodular heterotopia, atrophy, and Arnold-Chiari type 1 malformation, were discovered in almost 50% of patients. Control of seizures was not difficult to obtain in 11 cases; one patient showed pharmacoresistant epilepsy. EEG and clinical follow-up are recommended in children with FASD and epilepsy, since severe conditions requiring aggressive treatment, such as in ESES, may develop. Neuroradiological evaluation is warranted because several types of brain anomalies could be associated with maternal alcohol consumption during pregnancy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.
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Encéfalo/fisiopatologia , Transtornos do Espectro Alcoólico Fetal/fisiopatologia , Convulsões/etiologia , Adolescente , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Criança , Pré-Escolar , Eletroencefalografia , Epilepsias Parciais/diagnóstico por imagem , Epilepsias Parciais/etiologia , Epilepsias Parciais/fisiopatologia , Epilepsia Generalizada/diagnóstico por imagem , Epilepsia Generalizada/etiologia , Epilepsia Generalizada/fisiopatologia , Feminino , Transtornos do Espectro Alcoólico Fetal/diagnóstico por imagem , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Neuroimagem , Radiografia , Estudos Retrospectivos , Convulsões/diagnóstico por imagem , Convulsões/fisiopatologiaRESUMO
BACKGROUND: Epilepsy is a hallmark of IQSEC2-related encephalopathy within a phenotypic variability ranging between early onset epileptic and developmental encephalopathy and X-linked intellectual disability with epilepsy. PATIENTS AND METHODS: Data including demographic aspects, gene variants, seizure semiology and timing, EEG features, neuroimaging and response to therapy were retrospectively collected in patients with IQSEC2-related epilepsy referring to 8 Italian tertiary centres. RESULTS: The reported cohort included 11 patients (8 males and 3 females). Mean age at the onset of epilepsy was 3.90±2.80 years. No cases were reported in the first year of life. No specific epileptic syndromes were recognized. Predominant seizure-types in the age range 12-36 months included focal onset tonic seizures with impaired awareness, myoclonic seizures, and late onset spasms. Generalized motor seizures were predominant in patients between 3 and 6 years and between 12 and 18 years while focal motor seizures with impaired awareness were the most represented types between 6 and 12 years. No patients experienced status epilepticus. EEG patterns included a delayed maturation of EEG organization, irregular focal or diffuse slow activity, multifocal or diffuse epileptiform abnormalities. No structural epileptogenic lesions were detected at MRI. Valproate, lamotrigine, clobazam, topiramate and levetiracetam were the most used antiseizure medication. Complete seizure freedom was achieved only in 2 patients. CONCLUSIONS: Onset of epilepsy after the first year of age, predominance of focal seizures with impaired awareness and generalized motor seizures, no pathognomonic underlying epileptic syndrome and infrequent occurrence of status epilepticus emerged as the main features of IQSEC2-related epilepsy phenotype.
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Eletroencefalografia , Epilepsia , Fatores de Troca do Nucleotídeo Guanina , Fenótipo , Humanos , Masculino , Feminino , Criança , Pré-Escolar , Adolescente , Estudos Retrospectivos , Itália , Epilepsia/fisiopatologia , Epilepsia/tratamento farmacológico , Fatores de Troca do Nucleotídeo Guanina/genética , Lactente , Anticonvulsivantes/uso terapêutico , Idade de InícioRESUMO
BACKGROUND: Acute central nervous system (CNS) complications are common and well described among pediatric patients undergoing haematopoietic cell transplantation (HCT). However, their long-term outcomes are not known. The aim of this study is to describe the incidence, characteristics, and risk factors of long-term epilepsy in pediatric patients with acute CNS complications of HCT. METHODS: This retrospective study included pediatric patients who developed acute CNS complications from autologous or allogeneic HCT between 2000 and 2022. Clinical, therapeutic and prognostic data including long-term outcomes were analyzed. A diagnosis of epilepsy was provided if unprovoked seizures occurred during follow-up. RESULTS: Ninety-four patients (63 males, 31 females, median age 10 years, range 1-21 years) were included. The most common acute CNS complications were posterior reversible encephalopathy syndrome (n = 43, 46 %) and infections (n = 15, 16 %). Sixty-five patients (69 %) had acute symptomatic seizures, with 14 (16 %) having one or more episodes of status epilepticus (SE). Nine patients (9.6 %) were diagnosed with long-term focal epilepsy during the follow-up (5-year cumulative incidence from the acute complication, 13.3 %). Acute symptomatic SE during neurological complications of HCT was associated with an increased risk of long-term epilepsy (OR=14, 95 % CI 2.87-68.97). CONCLUSIONS: A higher occurrence of epilepsy has been observed in our cohort compared to the general population. Acute symptomatic SE during HCT was associated with a higher risk of long-term epilepsy. Pediatric patients with CNS complications during HCT could benefit from specific neurological follow-up. Further studies are needed to characterize mechanisms of epileptogenesis in pediatric patients undergoing HCT.
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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.
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Encefalopatias , Transtornos Cromossômicos , Polimicrogiria , Masculino , Feminino , Humanos , Criança , Lactente , Pré-Escolar , Adolescente , Transtornos Cromossômicos/diagnóstico por imagem , Transtornos Cromossômicos/genética , Neuroimagem , Encéfalo/diagnóstico por imagem , Cromossomos Humanos Par 12 , Estudos Observacionais como AssuntoRESUMO
Reports of childhood epilepsies in temporal association with vaccination have had a great impact on the acceptance of vaccination programs by health care providers, but little is known about this possible temporal association and about the types of seizures following vaccinations. For these reasons the Italian League Against Epilepsy (LICE), in collaboration with other Italian scientific societies, has decided to generate Guidelines on Vaccinations and Epilepsy. The aim of Guidelines on Vaccinations and Epilepsy is to present recent unequivocal evidence from published reports on the possible relationship between vaccines and epilepsy in order to provide information about contraindications and risks of vaccinations in patients with epilepsy. The following main issues have been addressed: (1) whether contraindications to vaccinations exist in patients with febrile convulsions, epilepsy, and/or epileptic encephalopathies; and (2) whether any vaccinations can cause febrile seizures, epilepsy, and/or epileptic encephalopathies. Diphtheria-tetanus-pertussis (DTP) vaccination and measles, mumps, and rubella vaccination (MMR) increase significantly the risk of febrile seizures. Recent observations and data about the relationships between vaccination and epileptic encephalopathy show that some cases of apparent vaccine-induced encephalopathy could in fact be caused by an inherent genetic defect with no causal relationship with vaccination.
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Epilepsia/induzido quimicamente , Epilepsia/epidemiologia , Guias de Prática Clínica como Assunto/normas , Vacinação/efeitos adversos , Ensaios Clínicos como Assunto/normas , Epilepsia/diagnóstico , Humanos , Itália/epidemiologia , Vacina contra Sarampo-Caxumba-Rubéola/efeitos adversosRESUMO
PURPOSE: Absence epilepsy with onset before age 4 years, or early onset absence epilepsy (EOAE), has been rarely reported, and children with onset in the first year of life are considered almost exceptional. We aimed to report the clinical and electrophysiologic features of a cohort of children with absence epilepsy starting within the first year of life. METHODS: This was a multicenter study including patients with absence epilepsy starting within the first year of life and identified over a 20-year period (1991-2011). KEY FINDINGS: We identified 16 patients with absence epilepsy starting within the first year of life with a mean follow-up of 6.4 years. Mean age at seizure onset was 10.3 ± (standard deviation)1.4 months (range 8-12). Two patients experienced rare tonic-clonic seizures that started later than the absences. None of the subjects had episodes of absence status epilepticus. Eleven subjects were seizure-free with the first antiepileptic drug. In eight children, therapy was withdrawn after a mean 3.2 years of treatment. None evolved into a different form of idiopathic generalized epilepsy. SLC2A1 gene analysis in 12 children (75%) failed to reveal glucose transporter 1 deficiency. SIGNIFICANCE: EOAE, including patients with onset within the first year of life, should be no more considered a distinct idiopathic generalized epilepsy (IGE) syndrome, as it shows electroclinical features, response to therapy, and prognosis similar to childhood absence epilepsy. Moreover, early age of onset is not predictive of GLUT-1 deficiency and genetic analysis may be therefore avoided in patients meeting strict inclusion criteria.
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Epilepsia Tipo Ausência/diagnóstico , Epilepsia Tipo Ausência/fisiopatologia , Adolescente , Idade de Início , Criança , Pré-Escolar , Estudos de Coortes , Eletroencefalografia/métodos , Epilepsia Tipo Ausência/epidemiologia , Feminino , Seguimentos , Humanos , MasculinoRESUMO
BACKGROUND: We describe a four-generation Italian family with familial hemiplegic migraine (FHM) and epilepsy due to a novel ATP1A2 missense mutation (R1007W). CASE RESULTS: Mutational analysis revealed a heterozygous nucleotide substitution c.3019C>T resulting in the missense substitution p.Arg1007Trp (p.R1007W) in seven subjects: Three individuals had hemiplegic migraine, two exhibited a clinical overlap between migraine and epilepsy, one had migraine and one was unaffected. The identified ATP1A2 mutation was not found in an ethnically matched control population of 190 individuals and was not reported in a polymorphisms database. In two-electrode voltage-clamp experiments on XENOPUS oocytes, the ATP1A2 R1007W mutant showed (i) reduced ion pumping activity due to a more profound voltage dependence and (ii) decreased apparent affinity for extracellular K⺠at voltages around the cellular resting potential. This distinct type of loss of function has not been reported for other FHM2 mutations and can lead to impaired K⺠clearance and elevated K⺠levels in the CNS. CONCLUSIONS: The functional data and clinical evidence suggest that in FHM2 migraine and epilepsy may originate from the same pathogenic mechanisms associated with genetically determined alterations of ion channels and pumps. Our data also support the hypothesis that the new mutation R1007W in our family may be a susceptibility factor for epilepsy.
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Epilepsia/genética , Enxaqueca com Aura/genética , Mutação de Sentido Incorreto/genética , ATPase Trocadora de Sódio-Potássio/genética , Sequência de Aminoácidos , Análise Mutacional de DNA , Epilepsia/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Enxaqueca com Aura/complicações , Dados de Sequência Molecular , Linhagem , Adulto JovemRESUMO
We present the first video-EEG recording of episodes of "epileptic headache". The case reported is that of a 9-year-old girl with brief episodes (of a few minutes) of severe frontal headache, which corresponded to the presence of concurrent spikes and slow waves, starting in the right temporal area. A dysplastic lesion of the right temporal lobe was observed by MRI and the patient received surgery, with subsequent disappearance of headaches. This case highlights ictal EEG as the main diagnostic tool for epileptic headache. We discuss the terminology regarding this type of manifestation and believe that cases without subsequent epileptic manifestations, as in the present case, should be more appropriately referred to as "pure ictal epileptic headache" or simply "pure epileptic headache". [Published with video sequences].
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Córtex Cerebral/fisiopatologia , Epilepsia/diagnóstico , Cefaleia/diagnóstico , Criança , Eletroencefalografia , Epilepsia/fisiopatologia , Feminino , Cefaleia/fisiopatologia , HumanosRESUMO
OBJECTIVE: This study aimed to describe the intellectual profile based on the Wechsler Intelligence Scale for Children 4th edition (WISC-IV) in children with self-limited epilepsy with centrotemporal spikes (SeLECTS), with an attempt to define possible predictive epilepsy-related variables of cognitive performance. METHODS: The WISC-IV was assessed in 161 children with SeLECTS and their cognitive profiles were compared to a matched sample of healthy control children. RESULTS: Children with SeLECTS performed within normal range across all indices, demonstrating particular strength based on the Perceptual Reasoning Index. Compared to healthy control children, we observed a significant difference in performance based on the Full Scale Intelligence Quotient, Verbal Comprehension Index and Processing Speed Index. Regarding epilepsy-related variables, earlier onset of epilepsy, use of anti-seizure medications, the presence of neurodevelopmental disorders, a higher frequency of seizures, and a longer treatment duration were associated with an overall lower level of performance. SIGNIFICANCE: Children with SeLECTS performed within the average range for cognitive assessment based on the WISC-IV, demonstrating that children had normal levels of global intelligence. However, compared to healthy control children, children with SeLECTS showed a slightly lower level of performance. Reasoning skills represented the relative strengths in children with SeLECTS. Predictors of intellectual performance in patients with SeLECTS include epilepsy-related variables and neurodevelopmental comorbidities.
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Epilepsia Rolândica , Epilepsia , Humanos , Criança , Epilepsia/tratamento farmacológico , Escalas de Wechsler , Inteligência , Velocidade de ProcessamentoRESUMO
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.
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Lissencefalias Clássicas e Heterotopias Subcorticais em Banda , Epilepsia , Humanos , Feminino , Criança , Masculino , Estudos Transversais , Proteínas Associadas aos Microtúbulos , Escala de Resultado de Glasgow , Imageamento por Ressonância MagnéticaRESUMO
OBJECTIVES: We describe the Residras registry, dedicated to Dravet syndrome (DS) and to other phenotypes related to SCN1A mutations, as a paradigm of registry for rare and complex epilepsies. Our primary objectives are to present the tools and framework of the integrative platform, the main characteristics emerging from the patient cohort included in the registry, with emphasis on demographic, clinical outcome, and mortality. METHODS: Standardized data of enrolled pediatric and adult patients were collected in 24 Italian expert centers and regularly updated at least on a yearly basis. Patients were prospectively enrolled, at registry starting, but historical retrospective data were also included. RESULTS: At present, 281 individuals with DS and a confirmed SCN1A mutation are included. Most patients have data available on epilepsy (n = 263) and their overall neurological condition (n = 255), based on at least one follow-up update. Median age at first clinical assessment was 2 years (IQR 0-9) while at last follow-up was 11 years (IQR 5-18.5). During the 7-year activity of the registry, five patients died resulting in a mortality rate of 1.84 per 1000-person-years. When analyzing clinical changes over the first 5-year follow-up, we observed a significant difference in cognitive function (P < 0.001), an increased prevalence of behavioral disorders including attention deficit (P < 0.001), a significant worsening of language (P = 0.001), and intellectual disability (P < 0.001). SIGNIFICANCE: The Residras registry represents a large collection of standardized national data for the DS population. The registry platform relies on a shareable and interoperable framework, which promotes multicenter high-quality data collection. In the future, such integrated platform may represent an invaluable asset for easing access to cohorts of patients that may benefit from clinical trials with emerging novel therapies, for drug safety monitoring, and for delineating natural history. Its framework makes it improvable based on growing experience with its use and easily adaptable to other rare and complex epilepsy syndromes.
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Epilepsias Mioclônicas , Epilepsia , Síndromes Epilépticas , Humanos , Canal de Sódio Disparado por Voltagem NAV1.1/genética , Estudos Retrospectivos , Epilepsias Mioclônicas/tratamento farmacológico , Síndromes Epilépticas/genéticaRESUMO
BACKGROUND: Developmental delay and intellectual disability are two pivotal elements of the phenotype of Pallister-Killian Syndrome (PKS). Our study aims to define the cognitive, adaptive, behavioral, and sensory profile of these patients and to evaluate possible correlations between the different aspects investigated and with the main clinical and demographic variables. METHODS: Individuals of any age with genetically confirmed PKS were recruited. Those ≤ 42 months were administered the Bayley Scales of Infant and Toddler Development Third Edition (Bayley-III), and those > 42 months the Vineland Adaptive Behavior Scales-Second Edition (Vineland-II). Stereotyped behaviors (Stereotypy Severity Scale, SSS) and aggressive behaviors (Behavior Problems Inventory-Short Version, BPIs) were assessed in all subjects > 1 year; sensory profile (Child Sensory Profile 2, C-SP2) in all aged 2-18 years. RESULTS: Twenty-two subjects were enrolled (11 F/11 M; age 9 months to 28 years). All subjects ≤ 42 months had psychomotor developmental delay. Of the subjects > 42 months, 15 had low IQ deviation, and 1 in the normal range. Stereotypies were frequent (median SSS-total score 25/68). Lower Vineland-II values corresponded to greater intensity and frequency of stereotypies (p = 0.004 and p = 0.003), and self-injurious behaviors (p = 0.002 and p = 0.002). Patients with severe low vision had greater interference of stereotypies (p = 0.027), and frequency and severity of aggressive behaviors (p = 0.026; p = 0.032). The C-SP2, while not homogeneous across subjects, showed prevalence of low registration and sensory seeking profiles and hypersensitivity to tactile and auditory stimuli. Lower Vineland-II scores correlated with higher Registration scores (p = 0.041), while stereotypies were more frequent and severe in case of high auditory sensitivity (p = 0.019; p = 0.007). Finally, greater sleep impairment correlated with stereotypies and self-injurious behaviors, and lower Vineland-II scores. CONCLUSIONS: The present study provides a further step in the investigation of the etiopathogenesis of the syndrome. Furthermore, these aspects could guide rehabilitation therapy through the identification of targeted protocols.
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Transtornos Cromossômicos , Deficiência Intelectual , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 12 , Cognição , Humanos , Deficiência Intelectual/genética , Estudos ProspectivosRESUMO
PURPOSE: EEG anomalies and epilepsy are a not so rare clinical manifestation in patients with Phosphatase and tensin homolog (PTEN) variants. The main aim of this study is to analyze the characteristics of EEG traces, neuroimaging findings and epilepsy to better define the neurological aspects in a set of patients with PTEN variants collected in four Italian Centres. As a secondary aim, we describe the neurodevelopmental profile and the psychiatric comorbidities of this cohort. METHODS: Patients with PTEN variants, identified by Sanger sequencing or target resequencing, were enrolled. For each subjects, clinical data were retrospectively extracted from medical charts, with a focus on epilepsy and neuroimaging data. RESULTS: 54 patients with PTEN variants were enrolled, with a mean age of 18.8 years. 72.2% have at least one psychiatric diagnosis, being Autism Spectrum Disorder and Intellectual Disability the most frequent diagnosis (29 and 25 cases, respectively). 22 subjects show an abnormal EEG and 8 received a diagnosis of epilepsy, mainly focal epilepsy (7/8), with a mean age at seizure onset of 3.8 years. 3/8 subjects have a drug resistant epilepsy, independently from the underlying neuroimaging pattern. The finding of a Focal cortical dysplasia is significantly associated with both an abnormal EEG (p = 0.02) and the occurrence of seizures (p = 0.002). CONCLUSION: EEG should be taken into consideration in the first-line diagnostic flowchart of subjects with PTEN variants. The onset of a focal epilepsy, independently from its response to antiepileptic drugs, highly recommends to carry out a neuroimaging exam.
Assuntos
Transtorno do Espectro Autista , Epilepsias Parciais , Epilepsia , Adolescente , Transtorno do Espectro Autista/complicações , Eletroencefalografia , Epilepsias Parciais/complicações , Epilepsia/diagnóstico , Humanos , PTEN Fosfo-Hidrolase/genética , Estudos Retrospectivos , Convulsões/diagnóstico , TensinasRESUMO
Introduction: Stroke-like syndrome (SLS) is a rare subacute neurological complication of intrathecal or high-dose (≥500 mg) Methotrexate (MTX) administration. Its clinical features, evoking acute cerebral ischaemia with fluctuating course symptoms and a possible spontaneous resolution, have elicited interest among the scientific community. However, many issues are still open on the underlying pathogenesis, clinical, and therapeutic management and long-term outcome. Materials and Methods: We retrospectively analyzed clinical, radiological and laboratory records of all patients diagnosed with SLS between 2011 and 2021 at 4 National referral centers for Pediatric Onco-Hematology. Patients with a latency period that was longer than 3 weeks between the last MTX administration of MTX and SLS onset were excluded from the analysis, as were those with unclear etiologies. We assessed symptom severity using a dedicated arbitrary scoring system. Eleven patients were included in the study. Results: The underlying disease was acute lymphoblastic leukemia type B in 10/11 patients, while fibroblastic osteosarcoma was present in a single subject. The median age at diagnosis was 11 years (range 4-34), and 64% of the patients were women. Symptoms occurred after a mean of 9.45 days (± 0.75) since the last MTX administration and lasted between 1 and 96 h. Clinical features included hemiplegia and/or cranial nerves palsy, paraesthesia, movement or speech disorders, and seizure. All patients underwent neuroimaging studies (CT and/or MRI) and EEG. The scoring system revealed an average of 4.9 points (± 2.3), with a median of 5 points (maximum 20 points). We detected a linear correlation between the severity of the disease and age in male patients. Conclusions: SLS is a rare, well-characterized complication of MTX administration. Despite the small sample, we have been able to confirm some of the previous findings in literature. We also identified a linear correlation between age and severity of the disease, which could improve the future clinical management.