RESUMO
PURPOSE: Our study aimed to evaluate the effectiveness of corticosteroids on seizure control in drug-resistant epilepsies (DREs). Our primary goal was to assess the response to steroids for various underlying etiologies, interictal electroencephalographic (EEG) patterns and electroclinical seizure descriptions. Our second goal was to compare steroid responsiveness to different treatment protocols. METHODS: This is a retrospective multicentre cohort study conducted according to the STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology). The following data were collected for each patient: epilepsy etiology, interictal EEG pattern, seizure types and type of steroid treatment protocol administered. RESULTS: Thirty patients with DRE were included in the study. After 6 months of therapy, 62.7 % of patients experienced reduced seizure frequency by 50 %, and 6.6 % of patients experienced complete seizure cessation. Findings associated with favourable response to steroids included structural/lesional etiology of epilepsy, immune/infectious etiology and focal interictal abnormalities on EEG. Comparing four different steroid treatment protocols, the most effective for seizure control was treatment with methylprednisolone at the dose of 30 mg/kg/day administered for 3 days, leading to greater than 50 % seizure reduction at 6 months in 85.7 % of patients. Treatment with dexamethasone 6 mg/day for 5 days decreased seizure frequency in 71.4 % of patients. Hydrocortisone 10 mg/kg administered for 3 months showed a good response to treatment in 71 %. CONCLUSIONS: In our study, two-thirds of patients with DRE experienced a significant seizure reduction following treatment with steroids. We suggest considering steroids as a potential therapeutic option in children with epilepsy not responding to conventional antiseizure medicines (ASM).
Assuntos
Epilepsia Resistente a Medicamentos , Eletroencefalografia , Humanos , Masculino , Feminino , Estudos Retrospectivos , Epilepsia Resistente a Medicamentos/tratamento farmacológico , Epilepsia Resistente a Medicamentos/fisiopatologia , Adolescente , Criança , Pré-Escolar , Metilprednisolona/uso terapêutico , Metilprednisolona/administração & dosagem , Dexametasona/uso terapêutico , Adulto , Adulto Jovem , Resultado do Tratamento , Anticonvulsivantes/uso terapêutico , Corticosteroides/uso terapêutico , Hidrocortisona/uso terapêuticoRESUMO
Dravet syndrome (DS) is a rare and severe form of genetic epilepsy characterized by cognitive and behavioural impairments and progressive gait deterioration. The characterization of gait parameters in DS needs efficient, non-invasive quantification. The aim of the present study is to apply nonlinear indexes calculated from inertial measurements to describe the dynamics of DS gait. Twenty participants (7 M, age 9-33 years) diagnosed with DS were enrolled. Three wearable inertial measurement units (OPAL, Apdm, Portland, OR, USA; Miniwave, Cometa s.r.l., Italy) were attached to the lower back and ankles and 3D acceleration and angular velocity were acquired while participants walked back and forth along a straight path. Segmental kinematics were acquired by means of stereophotogrammetry (SMART, BTS). Community functioning data were collected using the functional independence measure (FIM). Mean velocity and step width were calculated from stereophotogrammetric data; fundamental frequency, harmonic ratio, recurrence quantification analysis, and multiscale entropy (τ = 1...6) indexes along anteroposterior (AP), mediolateral (ML), and vertical (V) axes were calculated from trunk acceleration. Results were compared to a reference age-matched control group (112 subjects, 6-25 years old). All nonlinear indexes show a disruption of the cyclic pattern of the centre of mass in the sagittal plane, quantitatively supporting the clinical observation of ataxic gait. Indexes in the ML direction were less altered, suggesting the efficacy of the compensatory strategy (widening the base of support). Nonlinear indexes correlated significantly with functional scores (i.e., FIM and speed), confirming their effectiveness in capturing clinically meaningful biomarkers of gait.
Assuntos
Epilepsias Mioclônicas , Dispositivos Eletrônicos Vestíveis , Adolescente , Adulto , Fenômenos Biomecânicos , Criança , Marcha , Humanos , Caminhada , Adulto JovemRESUMO
OBJECTIVE: Patients with epilepsy are at risk for several lifetime problems, in which neuropsychological impairments may represent an impacting factor. We evaluated the neuropsychological functions in children suffering from three main epilepsy categories. Further, we analyzed the longitudinal evolution of the neuropsychological profile over time. METHODS: Patients undergoing neuropsychological evaluation at our Department from 2012 to 2018 were identified retrospectively. We selected patients aged 6-16 years and with at least two evaluations. Three epilepsy categories were considered: focal/structural, focal self-limited, and idiopathic generalized. Each evaluation included the same structured assessment of main neuropsychological domains. The effect of the epilepsy category, illness duration, seizure status, and medication was computed in multilevel models. RESULTS: We identified 103 patients (focal self-limited = 27; focal/structural = 51; and idiopathic generalized = 25), for 233 evaluations. The majority of deficits were reported in attention and executive functions (>30% of patients); the results were dichotomized to obtain global indexes. Multilevel models showed a trend toward statistical significance of category of epilepsy on the global executive index and of illness duration on global attention index. Illness duration predicted the scores of executive and attention tasks, while category and medication predicted executive task performance. Focal/structural epilepsies mostly affected the executive domain, with deficits persisting over time. By contrast, an ameliorative effect of illness duration for attention was documented in all epilepsies. CONCLUSIONS: This study offers lacking information about the evolution of deficits in time, the role of epilepsy category, and possible psychological implications for high-order cognitive skills, central in several social and academic problems.
Assuntos
Epilepsias Parciais , Epilepsia , Criança , Cognição , Epilepsia/complicações , Função Executiva , Humanos , Testes Neuropsicológicos , Estudos RetrospectivosRESUMO
Prrt2 is a neuron-specific protein expressed at axonal and pre-synaptic domains, involved in synaptic neurotransmitter release and modulation of intrinsic excitability. Mutations in PRRT2 cause a spectrum of autosomal dominant paroxysmal neurological disorders including epilepsy, movement disorders, and hemiplegic migraine and show incomplete penetrance and variable expressivity. We assessed the diagnostic rate of PRRT2 in a cohort of Italian patients with epilepsy and/or paroxysmal kinesigenic dyskinesia (PKD) and evaluated genotype-phenotype correlations. Clinical data were collected using a structured questionnaire. Twenty-seven out of 55 (49.1%) probands carried PRRT2 heterozygous pathogenic variants, including six previously known genotypes and one novel missense mutation. A family history of epilepsy starting in the first year of life and/or PKD was strongly suggestive of a PRRT2 pathogenic variant. Epilepsy patients harbouring PRRT2 pathogenic variants showed earlier seizure onset and more frequent clusters compared with PRRT2-negative individuals with epilepsy. Moreover, we did also identify individuals with PRRT2 pathogenic variants with atypical age at onset, i.e. childhood-onset epilepsy and infantile-onset PKD. However, the lack of a clear correlation between specific PRRT2 genotypes and clinical manifestations and the high incidence of asymptomatic carriers suggest the involvement of additional factors in modulating expressivity of PRRT2-related disorders. Finally, our study supports the pleiotropic and multifaceted physiological role of PRRT2 gene which is emerging from experimental neuroscience.
Assuntos
Distonia/genética , Epilepsia/genética , Proteínas de Membrana/genética , Proteínas do Tecido Nervoso/genética , Adolescente , Adulto , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Estudos de Associação Genética , Heterozigoto , Humanos , Lactente , Itália , Masculino , Mutação , Convulsões/genética , Adulto JovemRESUMO
OBJECTIVE: To quantify gait abnormalities in people with Dravet syndrome (DS). METHODS: Individuals with a confirmed diagnosis of DS were enrolled, and stratified according to knee flexion at initial contact (IC) and range of motion (ROM) during stance (atypical crouch: knee flexion >20° at IC and knee ROM >15° during stance; straight: knee flexion <20° at IC). A 1D ANOVA (α = 0.05) was used to test statistical differences among the joint kinematics and spatio-temporal parameters of the cohort and an age-matched control group. Clinical (neurological and orthopaedic evaluation) and anamnestic data (seizure type, drugs, genetic mutation) were collected; distribution between the two gait phenotypes was assessed with the Fisher exact test and, for mutation, with the chi-squared test (p < 0.05). Linear regression between maximum knee flexion and normalised walking speed was calculated. RESULTS: Seventy-one subjects were enrolled and evaluated with instrumented gait analysis. Fifty-two were included in final analysis (mean age 13.8 ± 7.3; M 26). Two gait patterns were detected: an atypical crouch gait (34.6%) with increased ankle, knee and hip flexion during stance, and reduced walking speed and stride length not associated with muscle-tendon retractions; and a pattern resembling those of healthy age-matched controls, but still showing reduced walking speed and stride length. No differences in clinical or anamnestic data emerged between the two groups. SIGNIFICANCE: Objectively quantified gait in DS shows two gait patterns with no clear-cut relation to clinical data. Kinematics abnormalities may be related to stabilization issues. These findings may guide rehabilitative and preventive measures.
Assuntos
Epilepsias Mioclônicas/complicações , Transtornos Neurológicos da Marcha/etiologia , Adolescente , Fenômenos Biomecânicos , Criança , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Articulação do Joelho , MasculinoRESUMO
OBJECTIVES: With this explorative study, we aimed to examine time perception in children with childhood absence epilepsy (CAE) and to compare those children with a matched control group. The study also investigated the association between the neuropsychological performance of the group with CAE and time judgment. We hypothesize that children with CAE could fail in time perception and that this may be because of a common underlying substrate with executive impairments. METHODS: Thirteen children with CAE, aged 6-13â¯years, and 17 healthy children were recruited. All children performed the time bisection task; the children with CAE also performed a cognitive and neuropsychological assessment. We performed a univariate analysis using each parameter of the bisection task (bisection point [BP]) and Weber ratio (WR) as dependent variables, the group (patients vs. controls) as fixed factors and age at evaluation and vocabulary scores as covariates. In the subgroup of patients, we correlated bisection task parameters with neuropsychological tests using a nonparametric partial correlation; the analysis has corrected for age at evaluation. RESULTS: The BP and WR measures differed between controls and patients with CAE. In the subgroup of patients also performing a neuropsychological assessment, we found a correlation between the WR measure and performance on the inhibition test (râ¯=â¯-0.641, pâ¯=â¯.025), coding test (râ¯=â¯-0.815, pâ¯=â¯.014), and Trail Making Test B (TMT B) (râ¯=â¯0.72, pâ¯=â¯.042). CONCLUSIONS: We found an altered time perception in a pilot study of a small group of children with CAE. A neurophysiological mechanism underlying CAE seems to influence cognitive and behavioral deficits and time sensibility.
Assuntos
Epilepsia Tipo Ausência/psicologia , Percepção do Tempo , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , Testes Neuropsicológicos , Projetos PilotoRESUMO
OBJECTIVE: Pathogenic variants in SCN8A have been associated with a wide spectrum of epilepsy phenotypes, ranging from benign familial infantile seizures (BFIS) to epileptic encephalopathies with variable severity. Furthermore, a few patients with intellectual disability (ID) or movement disorders without epilepsy have been reported. The vast majority of the published SCN8A patients suffer from severe developmental and epileptic encephalopathy (DEE). In this study, we aimed to provide further insight on the spectrum of milder SCN8A-related epilepsies. METHODS: A cohort of 1095 patients were screened using a next generation sequencing panel. Further patients were ascertained from a network of epilepsy genetics clinics. Patients with severe DEE and BFIS were excluded from the study. RESULTS: We found 36 probands who presented with an SCN8A-related epilepsy and normal intellect (33%) or mild (61%) to moderate ID (6%). All patients presented with epilepsy between age 1.5 months and 7 years (mean = 13.6 months), and 58% of these became seizure-free, two-thirds on monotherapy. Neurological disturbances included ataxia (28%) and hypotonia (19%) as the most prominent features. Interictal electroencephalogram was normal in 41%. Several recurrent variants were observed, including Ile763Val, Val891Met, Gly1475Arg, Gly1483Lys, Phe1588Leu, Arg1617Gln, Ala1650Val/Thr, Arg1872Gln, and Asn1877Ser. SIGNIFICANCE: With this study, we explore the electroclinical features of an intermediate SCN8A-related epilepsy with mild cognitive impairment, which is for the majority a treatable epilepsy.
Assuntos
Epilepsia/genética , Mutação de Sentido Incorreto , Canal de Sódio Disparado por Voltagem NAV1.6/genética , Anticonvulsivantes/uso terapêutico , Ataxia/genética , Criança , Pré-Escolar , Disfunção Cognitiva/genética , Eletroencefalografia , Epilepsia/tratamento farmacológico , Epilepsia/fisiopatologia , Testes Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Deficiência Intelectual/genética , Transtornos do Desenvolvimento da Linguagem/genética , Transtornos dos Movimentos/genética , Hipotonia Muscular/genética , Linhagem , Índice de Gravidade de DoençaRESUMO
AIM: We aimed to study tuberous sclerosis-associated neuropsychiatric disorders (TAND) in children and adolescents with tuberous sclerosis complex (TSC). METHOD: Retrospective and prospective cohort study conducted at a Paediatric Neurology Unit of an Italian Tertiary Care Hospital. Clinical and neuroimaging data were reviewed. Scores for neurological and epilepsy outcomes (Extended Glasgow Outcome Scale, Paediatric Version and Early Childhood Epilepsy Severity Scale modified), semi-structured interviews (authorized Italian version of the TAND checklist and Vineland Adaptive Behavior Scales) and questionnaires (Child Behavior Checklist [CBCL]) were applied at last follow-up. RESULTS: Thirty-two patients with TSC (age range 1-19y) were enrolled. Eighty-eight per cent had at least one TAND and 47% had intellectual disability. The TAND checklist showed internalizing problems in 25.8% of cases (vs 41.9% by CBCL), and externalizing problems in 41.9% (vs 9.7% by CBCL). TAND prevailed in patients with de novo mutation of TSC2, high tuber load, and severe neurological and epilepsy outcomes. INTERPRETATION: In our cohort, 78% of patients had more than four TAND behavioural problems; nevertheless, they did not show a constant and specific neuropsychiatric profile. Clinical, neurophysiological, and neuroradiological features were associated with several TAND. The TAND checklist appeared more effective than the CBCL, particularly in detecting externalizing problems. WHAT THIS PAPER ADDS: The Tuberous sclerosis-associated neuropsychiatric disorders (TAND) checklist is an effective tool for TAND screening. The TAND checklist helps define psychopathological and neuropsychiatric aspects in paediatric patients with Tuberous sclerosis complex (TSC). TAND were found in 88% of patients with TSC, whilst 78% had more than four TAND. TAND distribution depends on different clinical and neuroradiological features.
Assuntos
Deficiências do Desenvolvimento/etiologia , Transtornos Mentais/etiologia , Esclerose Tuberosa/complicações , Adolescente , Lista de Checagem , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Masculino , Testes Neuropsicológicos , Escalas de Graduação Psiquiátrica , Adulto JovemRESUMO
OBJECTIVE: PCDH19-related epilepsy is an epileptic syndrome with infantile onset, characterized by clustered and fever-induced seizures, often associated with intellectual disability (ID) and autistic features. The aim of this study was to analyze a large cohort of patients with PCDH19-related epilepsy and better define the epileptic phenotype, genotype-phenotype correlations, and related outcome-predicting factors. METHODS: We retrospectively collected genetic, clinical, and electroencephalogram (EEG) data of 61 patients with PCDH19-related epilepsy followed at 15 epilepsy centers. All consecutively performed EEGs were analyzed, totaling 551. We considered as outcome measures the development of ID, autistic spectrum disorder (ASD), and seizure persistence. The analyzed variables were the following: gender, age at onset, age at study, genetic variant, fever sensitivity, seizure type, cluster occurrence, status epilepticus, EEG abnormalities, and cognitive and behavioral disorders. Receiver operating characteristic curve analysis was performed to evaluate the age at which seizures might decrease in frequency. RESULTS: At last follow-up (median = 12 years, range = 1.9-42.1 years), 48 patients (78.7%) had annual seizures/clusters, 13 patients (21.3%) had monthly to weekly seizures, and 12 patients (19.7%) were seizure-free for ≥2 years. Receiver operating characteristic analysis showed a significant decrease of seizure frequency after the age of 10.5 years (sensitivity = 81.0%, specificity = 70.0%). Thirty-six patients (59.0%) had ID and behavioral disturbances. ASD was present in 31 patients. An earlier age at epilepsy onset emerged as the only predictive factor for ID (P = 0.047) and ASD (P = 0.014). Conversely, age at onset was not a predictive factor for seizure outcome (P = 0.124). SIGNIFICANCE: We found that earlier age at epilepsy onset is related to a significant risk for ID and ASD. Furthermore, long-term follow-up showed that after the age of 10 years, seizures decrease in frequency and cognitive and behavioral disturbances remain the primary clinical problems.
Assuntos
Caderinas/genética , Síndromes Epilépticas/genética , Síndromes Epilépticas/terapia , Adolescente , Adulto , Idade de Início , Transtorno Autístico/complicações , Transtorno Autístico/psicologia , Criança , Pré-Escolar , Estudos de Coortes , Eletroencefalografia , Feminino , Humanos , Lactente , Deficiência Intelectual/complicações , Deficiência Intelectual/psicologia , Masculino , Fenótipo , Protocaderinas , Estudos Retrospectivos , Convulsões , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Several studies have confirmed psychiatric comorbidity and a worse quality of life in children with epilepsy, but the clinical assessment and monitoring of these patients often pays insufficient attention to their psychological aspects alongside their neurological issues. The present study aims to describe the distribution of psychopathologies and their clinical evolution over 18 months in a sample of children followed up since the onset of their epilepsy. METHODS: After being diagnosed with epilepsy, 49 subjects (age 4-18 y) were followed up with psychiatric and psychological assessments based on the use of dimensional and categorical psychometric tools. RESULTS: Baseline data (T0) showed a high psychiatric comorbidity in epileptic children, with a prevalence of anxious-depressive disorders and attention deficit hyperactivity disorder (ADHD). Specifically, generalized epilepsy, antiepileptic drug intake and more frequent seizures were associated with externalizing problems, while focal epilepsy was linked with anxiety disorders. The follow-up at 18 months revealed that about 90% of patients had achieved a reduction in the frequency and duration of their seizures, but their psychopathological assessment remained virtually unchanged. The patients' psychological issues had warranted psychotherapy in 43% of cases. CONCLUSIONS: When children or adolescents are diagnosed with epilepsy, their psychopathological profile should be investigated and monitored over time. Psychotherapy and/or psychopharmacological treatments should be offered to pediatric patients with epilepsy who suffer from emotional-behavioral disorders.
Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsia/psicologia , Transtornos Mentais/epidemiologia , Qualidade de Vida , Adolescente , Criança , Pré-Escolar , Comorbidade , Epilepsia/tratamento farmacológico , Epilepsia/fisiopatologia , Feminino , Seguimentos , Humanos , Masculino , Transtornos Mentais/fisiopatologia , Transtornos Mentais/terapia , Prevalência , Estudos Prospectivos , PsicometriaRESUMO
The aim of our study was to describe the clinical, electroencephalogram, molecular findings and the diagnostic and therapeutic flow-chart of children with pyridoxine-dependent epilepsies (PDEs). We performed a retrospective observational study on children with PDEs, diagnosed and followed-up in Italian Pediatric Departments. In each centre, the authors collected data from a cohort of children admitted for intractable seizures, responsive to pyridoxine administration and resistant to other anticonvulsant therapies. Data were retrospectively analysed from January 2016 to January 2017. Sixteen patients (13 males, and 3 females) were included. We found that 93.75% of patients underwent conventional anticonvulsant therapy before starting pyridoxine administration and 62.5% had ex-juvantibus diagnosis, as specific serum diagnostic tests had been performed in only 37.5% of patients by alpha-AASA and pipecolic acid blood and urine dosage. The most common type of seizure was generalized tonic-clonic in 7 patients and the most common EEG pattern was characterized by a "burst suppression" pattern. Before pyridoxine administration, other anticonvulsant drugs were used in 93.75% of patients, with consequent onset of drug-resistance. Phenobarbital was the most frequently used drug as first-line treatment. The importance of our study relies on the need of a deeper knowledge of PDEs in terms of early diagnosis, avoiding incorrect treatment and related adverse events, clinical and EEG pathognomonic features, and genetic aspects of the disease.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Piridoxina/farmacologia , Convulsões/tratamento farmacológico , Adolescente , Criança , Pré-Escolar , Estudos de Coortes , Epilepsia/diagnóstico , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Convulsões/diagnóstico , Complexo Vitamínico B/uso terapêuticoRESUMO
BACKGROUND: The aim of this study was to describe the distribution, timing, and risk factors for psychopathology and to further examine the quality of life (QoL) in an Italian sample of children with recent onset epilepsy. Sociodemographic and psychosocial variables, family factors, as well as illness-related factors themselves were examined in order to clarify the relationship among these variables, psychopathology and QoL. METHODS: For this purpose, 49 children and adolescents (4-18 years), consecutively referred to a Neurophysiology Service, were evaluated by a multidisciplinary team using dimensional as well as categorical instruments both self-administered (self-report and proxy-report) and interviewer administered. RESULTS: Forty-five percent of the patients exhibited one or more Axis I disorders (DSM-IV) when evaluated with K-SADS-PL interview. It's worth noting that preadolescent and adolescent patients tend to underestimate their problems compared to their parents'opinion, when answering self-administer questionnaires. Self-reported QoL appeared to be generally satisfactory. Social and family factor, as well as epilepsy related factors appeared to be linked both to the presence of psychopathology and to the QoL. Patients affected by psychiatric disorders exhibited the poorest QoL. CONCLUSIONS: Also after many years from the onset, childhood epilepsy frequently fosters negative consequences in terms of social life, work, psychopathology and life expectancy. The ability of health services and public health measures to prevent and treat psychiatric comorbidity may have a pivotal role in enhancing patients' QoL.
Assuntos
Epilepsia/psicologia , Transtornos Mentais/epidemiologia , Qualidade de Vida , Adolescente , Criança , Pré-Escolar , Epilepsia/epidemiologia , Epilepsia/etiologia , Feminino , Humanos , Itália , Masculino , Pais/psicologia , Equipe de Assistência ao Paciente , Estudos Prospectivos , Fatores de Risco , Autorrelato , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: To describe the clinical, neuropsychological, and psychopathologic features of a cohort of children with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy at time of recruitment and through the first month. The selected population will be followed for 2-5 years after enrollment to investigate the epilepsy course and identify early predictors of drug resistance. METHODS: In this observational, multicenter, nationwide study, children (age 1 month-12.9 years) with a new diagnosis of symptomatic or presumed symptomatic focal epilepsy were consecutively enrolled in 15 Italian tertiary childhood epilepsy centers. Inclusion criteria were as follows: (1) diagnosis of symptomatic focal epilepsy due to acquired and developmental etiologies, and presumed symptomatic focal epilepsy; (2) age at diagnosis older than 1 month and <13 years; and (3) written informed consent. Children were subdivided into three groups: ≤3 years, >3 to 6 years, and >6 years. Clinical, electroencephalography (EEG), neuroimaging, and neuropsychological variables were identified for statistical analyses. RESULTS: Two hundred fifty-nine children were enrolled (116 female and 143 male). Median age: 4.4 years (range 1 month-12.9 years); 46.0% (n = 119) of children were younger than 3 years, 24% (61) from 3 to 6 years of age, and 30% (79) older than 6 years. Neurologic examination findings were normal in 71.8%. Brain magnetic resonance imaging (MRI) was abnormal in 59.9%. Children age ≤3 years experienced the highest seizure frequency in the first month after recruitment (p < 0.0001). Monotherapy in the first month was used in 67.2%. Cognitive tests at baseline revealed abnormal scores in 30%; behavioral problems were present in 21%. At multivariate analysis, higher chances to exhibit more than five seizures in the first month after epilepsy onset was confirmed for younger children and those with temporal lobe epilepsy. SIGNIFICANCE: In this prospective cohort study, an extensive characterization of epilepsy onset in children with symptomatic or presumed symptomatic focal epilepsies is reported in relation to the age group and the localization of the epileptogenic zone.
Assuntos
Encéfalo/diagnóstico por imagem , Transtornos Cognitivos/etiologia , Epilepsias Parciais/complicações , Adolescente , Distribuição por Idade , Criança , Pré-Escolar , Transtornos Cognitivos/diagnóstico , Estudos de Coortes , Eletroencefalografia , Epilepsias Parciais/diagnóstico por imagem , Feminino , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Testes Neuropsicológicos , Estudos ProspectivosAssuntos
Coração , Taquicardia Supraventricular , Encéfalo , Eletrocardiografia , Epilepsias Mioclônicas , Humanos , Estado EpilépticoRESUMO
The KCNT1 gene encodes for subunits contributing to the Na(+)-activated K(+) current (KNa), expressed in many cell types. Mutations in KCNT1 have been found in patients affected with a wide spectrum of early-onset epilepsies, including Malignant Migrating Partial Seizures in Infancy (MMPSI), a severe early-onset epileptic encephalopathy characterized by pharmacoresistant focal seizures migrating from one brain region or hemisphere to another and neurodevelopment arrest or regression, resulting in profound disability. In the present study we report identification by whole exome sequencing (WES) of two de novo, heterozygous KCNT1 mutations (G288S and, not previously reported, M516V) in two unrelated MMPSI probands. Functional studies in a heterologous expression system revealed that channels formed by mutant KCNT1 subunits carried larger currents when compared to wild-type KCNT1 channels, both as homo- and heteromers with these last. Both mutations induced a marked leftward shift in homomeric channel activation gating. Interestingly, the KCNT1 blockers quinidine (3-1000µM) and bepridil (0.03-10µM) inhibited both wild-type and mutant KCNT1 currents in a concentration-dependent manner, with mutant channels showing higher sensitivity to blockade. This latter result suggests two genotype-tailored pharmacological strategies to specifically counteract the dysfunction of KCNT1 activating mutations in MMPSI patients.
Assuntos
Mutação de Sentido Incorreto , Proteínas do Tecido Nervoso/genética , Canais de Potássio/genética , Espasmos Infantis/genética , Animais , Células CHO , Cricetinae , Cricetulus , Exoma , Humanos , Lactente , Ativação do Canal Iônico , Masculino , Proteínas do Tecido Nervoso/antagonistas & inibidores , Proteínas do Tecido Nervoso/metabolismo , Bloqueadores dos Canais de Potássio/farmacologia , Canais de Potássio/metabolismo , Canais de Potássio Ativados por Sódio , Espasmos Infantis/diagnósticoRESUMO
BACKGROUND: The possibility that epileptic seizures and arrhythmias are different clinical manifestations of a common channelopathy is an interesting but unproved hypothesis. Patients with Dravet syndrome show heart rate variability and affected individuals with arrhythmias have also been documented. The possibility that a genetic mutation affecting sodium channel functions may predispose to both Dravet syndrome and arrhythmogenic disorders is an interesting hypothesis. PATIENT PRESENTATION: We describe a 5-month-old girl with Dravet syndrome who presented with paroxysmal supraventricular tachycardia during status epilepticus. She presented to the hospital the first time with afebrile tonic-clonic seizures and then several subsequent times with status epilepticus confirmed with electroencephalography. During two of these episodes she also exhibited paroxysmal supraventricular tachycardia. She received propofol for status epilepticus and adenosine for the arrhythmia. A clinical and genetic (denovo mutation of a sodium channel, SCN1A) diagnosis of Dravet syndrome was made. CONCLUSIONS: Our patient supports the hypothesis that SCN1A mutation might have a role as a common substrate to both epilepsy and cardiac arrhythmia. More studies are needed to better assess genetic, cardiac, respiratory, and autonomic dysfunction in patients with Dravet syndrome.
Assuntos
Encéfalo/fisiopatologia , Epilepsias Mioclônicas/complicações , Coração/fisiopatologia , Estado Epiléptico/etiologia , Taquicardia Supraventricular/etiologia , Eletrocardiografia , Eletroencefalografia , Epilepsias Mioclônicas/genética , Feminino , Humanos , Lactente , Mutação/genética , Canal de Sódio Disparado por Voltagem NAV1.1/genéticaRESUMO
Ring chromosomes are rare abnormalities caused by the fusion of the telomeric regions. Three-ring chromosome syndromes (Cr 20, Cr 17 and Cr 14) cause epilepsy with variable phenotypes. In ring 17 patients with mild phenotype, some authors have shown an epilepsy syndrome similar to that of ring 20. We report the first case of a girl with ring chromosome 17 and a normal neurological and general cognitive profile. She had had, from 9 years old, focal pharmacoresistant epilepsy associated with episodes of non-convulsive status epilepticus with mainly autonomic features. Cytogenetic analysis revealed an abnormal karyotype characterised by the presence of de novo ring chromosome 17 in 19% of metaphases. The array CGH (100 KB) did not show any genetic deletion. The clinical and epilepsy phenotype was, to a certain degree, similar to that of ring 20 syndrome.
Assuntos
Cromossomos Humanos Par 17/genética , Deficiência Intelectual/psicologia , Adolescente , Cognição , Resistência a Medicamentos , Eletroencefalografia , Epilepsia/etiologia , Epilepsia/psicologia , Função Executiva , Feminino , Humanos , Testes Neuropsicológicos , Cromossomos em Anel , SíndromeRESUMO
Convulsive epileptic seizures in children represent a common cause of admission to pediatric emergency department. Data about incidence, etiology, and outcome are still lacking in literature. We retrospectively reviewed medical records of children presenting to our pediatric emergency department with convulsive seizures during a 12-month period and collected their diagnoses over the following year. In all, 182 children met the inclusion criteria, for a total of 214 visits (1.2% of all attendances, n = 24 864). Seizures lasted less than 5 minutes in 76%, 5 to 30 minutes in 20%, 30 to 60 minutes in 2%, and over 60 minutes in 2% visits ("early," "established," "refractory," convulsive status epilepticus, respectively). Incidence of "early" (seizure lasting 5-30 minutes) and "established" (seizure lasting 30-60 minutes) status epilepticus was 52/100 000/year and 7/100 000/year respectively. Most common causes were febrile seizures (56%) and remote symptomatic seizures (19%). Knowing the epidemiology of convulsive seizures in children is important to guide appropriate management and individualized follow-up.
Assuntos
Serviço Hospitalar de Emergência/estatística & dados numéricos , Hospitais Pediátricos , Convulsões/epidemiologia , Distribuição por Idade , Pré-Escolar , Planejamento em Saúde Comunitária , Feminino , Humanos , Lactente , Itália/epidemiologia , Masculino , Estudos Retrospectivos , Convulsões/etiologia , Convulsões/terapiaRESUMO
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.