RESUMO
PURPOSE: This was a phase-II, randomized, double-blind (DB), placebo-controlled study aimed to evaluate neurocognitive effects of eslicarbazepine acetate (ESL) as adjunctive therapy in pediatric patients with refractory focal-onset seizures (FOS). METHODS: Children (6-16years old) with FOS were randomized (2:1) to ESL or placebo. Treatment started at 10mg/kg/day, was up-titrated up to 30mg/kg/day (target dose), and maintained for 8weeks, followed by one-year open-label follow-up. The primary endpoint was change from baseline to the end of maintenance period in the composite Power of Attention assessed with the Cognitive Drug Research (CDR) system. Behavioral and emotional functioning and quality of life (QOL), secondary endpoints, were assessed with Child Health Questionnaire-Parent Form 50 (CHQ-PF50), Child Behavior Checklist (CBCL), and Raven's Standard Progressive Matrices (SPM). Efficacy was evaluated through changes in standardized seizure frequency (SF), responder rate, and proportion of seizure-free patients. Safety was evaluated by the incidence of treatment-emergent adverse events (TEAEs). RESULTS: One hundred and twenty-three patients were randomized. A noninferiority analysis failed to reject the null hypothesis that the change from baseline in the Power of Attention score in the ESL group was at least 121ms inferior to the placebo group for all age groups. The CDR scores showed no differences between placebo and ESL in Power of Attention (1868.0 vs 1759.5), Continuity of Attention (1.136 vs -1.786), Quality of Working Memory (-0.023 vs -0.024), and Speed of Memory (-263.4 vs -249.6). Nonsignificant differences between placebo and ESL were seen for CHQ-PF50, CBCL scores, and Raven's SPM. Episodic Memory Index showed significant negative effect on ESL. Efficacy results favored the ESL group (SF least square [LS] means 1.98 vs 4.29). The TEAEs had a similar incidence between treatment groups (41.0% vs 47.5%). CONCLUSIONS: Overall ESL did not produce statistically significant effects on neurocognitive and behavioral functioning in patients with epilepsy aged 6 to 16years. Additionally, ESL was effective in reducing seizure frequency and was well-tolerated.
Assuntos
Anticonvulsivantes/uso terapêutico , Dibenzazepinas/uso terapêutico , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Adolescente , Atenção/fisiologia , Criança , Cognição/fisiologia , Terapia Combinada , Método Duplo-Cego , Epilepsia/fisiopatologia , Feminino , Humanos , Masculino , Memória/fisiologia , Qualidade de Vida , Convulsões/fisiopatologia , Resultado do TratamentoRESUMO
OBJECTIVE: To delineate the genetic, neurodevelopmental and epileptic spectrum associated with GRIN2A alterations with emphasis on epilepsy treatment. METHODS: Retrospective study of 19 patients (7 females; age: 1-38 years; mean 10.1 years) with epilepsy and GRIN2A alteration. Genetic variants were classified according to the guidelines and recommendations of the American College of Medical Genetics (ACMG). Clinical findings including epilepsy classification, treatment, EEG findings, early childhood development and neurodevelopmental outcome were collected with an electronic questionnaire. RESULTS: 7 out of 19 patients fulfilled the ACMG-criteria of carrying "pathogenic" or "likely pathogenic variants", in twelve patients the alterations were classified as variants of unknown significance. The spectrum of pathogenic/likely pathogenic mutations was as follows: nonsense n = 3, missense n = 2, duplications/deletions n = 1 and splice site n = 1. First seizures occurred at a mean age of 2.4 years with heterogeneous seizure types. Patients were treated with a mean of 5.6 AED. 4/5 patients with VPA had an improved seizure frequency (n = 3 with a truncation: n = 1 missense). 3/5 patients with STM reported an improvement of seizures (n = 2 truncation, n = 1 splicing). 3/5 CLB patients showed an improvement (n = 2: truncation; n = 1 splicing). Steroids were reported to have a positive effect on seizure frequency in 3/5 patients (n = 1 each truncation, splicing or deletion). CONCLUSIONS: Our data indicate that children with epilepsy due to pathogenic GRIN2A mutations present with different clinical phenotypes and a spectrum of seizure types in the context of a pharmacoresistant epilepsy providing information for clinicians treating children with this form of genetically determined epileptic syndrome.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Epilepsia/genética , Receptores de N-Metil-D-Aspartato/genética , Adolescente , Adulto , Criança , Pré-Escolar , Resistência a Medicamentos/genética , Feminino , Humanos , Lactente , Masculino , Mutação , Fenótipo , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Glucose transporter type 1 deficiency syndrome is a genetically determined, treatable, neurologic disorder that is caused by an insufficient transport of glucose into the brain. It is caused by a mutation in the SCL2A1 gene, which is so far the only known to be associated with this condition. Glucose transporter type 1 deficiency syndrome consists of a wide clinical spectrum that usually presents with cognitive impairment, epilepsy, paroxysmal exercise-induced dyskinesia, acquired microcephaly, hemolytic anemia, gait disturbance, and dyspraxia in different combinations. However, there are other clinical manifestations that we consider equally peculiar but that have so far been poorly described in literature. In this review, supported by a video contribution, we will accurately describe this type of clinical manifestation such as oculogyric crises, weakness, paroxysmal kinesigenic and nonkinesigenic dyskinesia in order to provide an additional instrument for a correct, rapid diagnosis.
Assuntos
Erros Inatos do Metabolismo dos Carboidratos/diagnóstico , Erros Inatos do Metabolismo dos Carboidratos/fisiopatologia , Proteínas de Transporte de Monossacarídeos/deficiência , Adolescente , Erros Inatos do Metabolismo dos Carboidratos/genética , Criança , Pré-Escolar , Diagnóstico Diferencial , Progressão da Doença , Feminino , Transportador de Glucose Tipo 1/genética , Humanos , Lactente , Masculino , Proteínas de Transporte de Monossacarídeos/genética , Mutação , Fenótipo , Estudos Retrospectivos , Gravação em Vídeo , Adulto JovemRESUMO
OBJECTIVE: To investigate visual habituation - a measure of visual cortical excitability - in photosensitive patients in pediatric age and compare the findings with a matched sample with idiopathic generalized epilepsies without photosensitivity and with normally developing children. METHODS: We presented a full-field black-and-white checkerboard pattern, at 3 reversal/s with 100% contrast binocularly for 600 consecutive trials and measured the N75-P100 and P100-N145 pattern-reversal visual evoked potential inter-peak amplitudes and N75, P100, N145 latencies for the six blocks of 100 responses. As a measure of habituation we used the slope of the linear regression line of the N75-P100 and P100-N145 peak-to-peak amplitudes. The slope of the linear regression line of the N75-P100 and P100-N145 latencies was also analyzed. RESULTS: Statistical analysis revealed significant differences between the three groups in the slope index of N75-P100 PR-VEP amplitude, with increased or constant amplitude in the PS group compare to the IGE and ND across the six blocks. CONCLUSIONS: Our results support the notion that photosensitivity is associated with altered control of excitatory and inhibitory cortical processes. The causal relationship between habituation deficit and photo-paroxysmal response needs to be further investigated with longitudinal studies. SIGNIFICANCE: This study supports the hypothesis that suppression of PR-VEP is a sensitive intermediate phenotype, which discriminates patients with photosensitivity from those with generalized epilepsies in pediatric age.
Assuntos
Epilepsia Reflexa/diagnóstico , Epilepsia Reflexa/fisiopatologia , Habituação Psicofisiológica/fisiologia , Córtex Visual/fisiopatologia , Percepção Visual/fisiologia , Adolescente , Ondas Encefálicas/fisiologia , Criança , Eletroencefalografia/métodos , Feminino , Humanos , Masculino , Estimulação Luminosa/métodosRESUMO
BACKGROUND: To report on the first multicenter Italian experience with rufinamide as adjunctive drug in children, adolescents and young adults with refractory childhood-onset epileptic encephalopathies other than Lennox-Gastaut syndrome. METHODS: Thirty-eight patients (19 males, 19 females), aged between 4 and 34 (mean 13.7 ± 8.3, median 12.5), all affected by different types of childhood-onset refractory epileptic encephalopathies other than Lennox-Gastaut syndrome, were treated with rufinamide as adjunctive drug for a mean period of 11.4 months (range 3-26 months). RESULTS: Fifteen of 38 patients (39.5%) had a ≥ 50% seizure reduction in countable seizures. Complete seizure freedom was achieved in one of these patients (2.6%). Three patients (7.9%) had a 25-49% seizure reduction, whilst seizure frequency remained unchanged in 15 (39.5%) and increased in five patients (13.1%). Eleven patients (28.9%) reported adverse side effects. Vomiting was reported in five patients (13.1%); drowsiness, decreased appetite and irritability with migraine manifested in other four patients. They were transient and mild in all cases. CONCLUSION: Rufinamide may be an effective and well-tolerated adjunctive drug for the treatment of refractory childhood-onset epileptic encephalopathies other than Lennox-Gastaut syndrome. Rufinamide was most effective in patients with drop-attacks and (bi)frontal spike-wave discharges.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Triazóis/uso terapêutico , Adolescente , Adulto , Encefalopatias/complicações , Encefalopatias/tratamento farmacológico , Criança , Pré-Escolar , Epilepsia/etiologia , Feminino , Humanos , Masculino , Adulto JovemRESUMO
PURPOSE: To try to prove in patients with refractory symptomatic epilepsy due to early brain injury involving thalamus and complicated by CSWS the effects of the isolation of the injured hemisphere, performed with functional hemisperectomy, on epilepsy, namely on CSWS. METHODS: Full clinical follow-up before and after surgery of two cases with CSWS onset at four years in whom functional hemispherecomy was performed with resection of inter-hemispheric connections. RESULTS: An immediate effectiveness of the surgical treatment was observed on both epileptic evolution (no more seizures) and EEG abnormalities. In particular, CSWS completely disappeared, together with a concurrent progressive improving of the cognitive and behavioural disorders. DISCUSSION: The isolation of the injured hemisphere through the section of inter-hemispheric cortico-cortical connections could prevent the contralateral diffusion of discharges coming from the injured cortex and cortico-thalamic network, favouring a normal function of thalamo-cortico-thalamic circuitries in the healthy hemisphere. That could explain the disappearance of CSWS after surgery in our patients and the consequent improvement of cognitive abilities and behaviour.
Assuntos
Lesões Encefálicas/complicações , Epilepsias Parciais/cirurgia , Transtornos do Sono-Vigília/cirurgia , Tálamo/lesões , Idade de Início , Lesões Encefálicas/fisiopatologia , Lesões Encefálicas/cirurgia , Córtex Cerebral/fisiopatologia , Córtex Cerebral/cirurgia , Criança , Pré-Escolar , Transtornos Cognitivos/complicações , Transtornos Cognitivos/fisiopatologia , Transtornos Cognitivos/cirurgia , Progressão da Doença , Intervalo Livre de Doença , Eletroencefalografia , Epilepsias Parciais/complicações , Epilepsias Parciais/fisiopatologia , Feminino , Hemisferectomia , Humanos , Imageamento por Ressonância Magnética , Testes Neuropsicológicos , Qualidade de Vida , Transtornos do Sono-Vigília/complicações , Transtornos do Sono-Vigília/fisiopatologia , Inquéritos e Questionários , Tálamo/fisiopatologia , Tálamo/cirurgia , Resultado do TratamentoRESUMO
AIM: The aim of the study was to evaluate the surgical treatment of epilepsy and detection of possible early surgery predictive elements in patients with tuberous sclerosis complex (TSC). MATERIALS AND METHODS: Forty-two TSC patients with epilepsy were selected and divided into two main groups: definite and fruste forms. Definite forms were divided into different groups: patients with pharmacologically controlled epilepsy, patients with pharmacoresistant epilepsy excluded from surgery after an extensive presurgical assessment, and patients with a pharmacoresistant epilepsy who underwent surgery. We compared the definite TSC groups to identify elements that predict surgical candidacy. Second, we compared all operated patients to assess surgical outcome. CONCLUSION: We found several factors that could predict a surgical intervention even if identification of patients with refractory epilepsy who can benefit from surgery is an evolving process. Also, several positive factors for good surgical outcome were identified. Patients with the fruste form had excellent surgical outcome.
Assuntos
Epilepsia/cirurgia , Esclerose Tuberosa/complicações , Adolescente , Adulto , Criança , Pré-Escolar , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Feminino , Humanos , Masculino , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: We used voxel-based morphometry (VBM) to assess the pattern of regional gray matter (GM) loss in patients with pediatric multiple sclerosis (MS) and its relation with the Expanded Disability Status Scale (EDSS) score, disease duration, and the extent of T2 lesion load (LL). METHODS: From 28 patients with pediatric relapsing-remitting MS (16 girls; mean age = 14.4 years, range = 7 to 16 years) and 21 matched controls, dual-echo and three-dimensional T1-weighted magnetization prepared rapid acquisition gradient echo sequences were acquired. T2 LL was measured using a local thresholding segmentation technique. Data were analyzed using an optimized VBM analysis and statistical parametric mapping. RESULTS: In pediatric patients with MS, mean brain T2 LL was 7.8 mL +/- 11.3. Intracranial volume did not differ between patients and controls. Compared to controls, patients with pediatric MS had significant GM loss in the thalamus, bilaterally, which was significantly correlated with T2 LL (r = -0.80 for the right thalamus, r = -0.74 for the left thalamus, p < 0.05, corrected for multiple comparisons). No correlation was found between thalamic GM loss, disease duration, and disability. CONCLUSIONS: In patients with pediatric multiple sclerosis (MS), differently from what happens in adult-onset MS, gray matter (GM) atrophy seems to involve the thalamus only, with sparing of the cortex and other deep GM nuclei. The correlation found between atrophy and T2 lesion load suggests transsynaptic and Wallerian degenerations as the most likely substrate of tissue loss in the thalamus of these patients.
Assuntos
Atrofia/patologia , Esclerose Múltipla/patologia , Degeneração Neural/patologia , Tálamo/patologia , Adolescente , Fatores Etários , Idade de Início , Atrofia/etiologia , Atrofia/fisiopatologia , Criança , Avaliação da Deficiência , Progressão da Doença , Diagnóstico Precoce , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Esclerose Múltipla/fisiopatologia , Degeneração Neural/etiologia , Degeneração Neural/fisiopatologia , Valor Preditivo dos Testes , Prognóstico , Índice de Gravidade de Doença , Tálamo/fisiopatologia , Degeneração Walleriana/etiologia , Degeneração Walleriana/patologia , Degeneração Walleriana/fisiopatologiaRESUMO
Periventricular heterotopia (PH) occurs when collections of neurons lay along the lateral ventricles or just beneath. Human Filamin A gene (FLNA) mutations are associated with classical X-linked bilateral periventricular nodular heterotopia (PNH), featuring contiguous heterotopic nodules, mega cisterna magna, cardiovascular malformations and epilepsy. FLNA encodes an F-actin-binding cytoplasmic phosphoprotein and is involved in early brain neurogenesis and neuronal migration. A rare, recessive form of bilateral PNH with microcephaly and severe delay is associated with mutations of the ADP-ribosylation factor guanine nucleotide-exchange factor-2 (ARFGEF2) gene, required for vesicle and membrane trafficking from the trans-Golgi. However, PH is a heterogeneous disorder. We studied clinical and brain MRI of 182 patients with PH and, based on its anatomic distribution and associated birth defects, identified 15 subtypes. Classical bilateral PNH represented the largest group (98 patients: 54%). The 14 additional phenotypes (84 patients: 46%) included PNH with Ehlers-Danlos syndrome (EDS), temporo-occipital PNH with hippocampal malformation and cerebellar hypoplasia, PNH with fronto-perisylvian or temporo-occipital polymicrogyria, posterior PNH with hydrocephalus, PNH with microcephaly, PNH with frontonasal dysplasia, PNH with limb abnormalities, PNH with fragile-X syndrome, PNH with ambiguous genitalia, micronodular PH, unilateral PNH, laminar ribbon-like and linear PH. We performed mutation analysis of FLNA in 120 patients, of whom 72 (60%) had classical bilateral PNH and 48 (40%) other PH phenotypes, and identified 25 mutations in 40 individuals. Sixteen mutations had not been reported previously. Mutations were found in 35 patients with classical bilateral PNH, in three with PNH with EDS and in two with unilateral PNH. Twenty one mutations were nonsense and frame-shift and four missense. The high prevalence of mutations causing protein truncations confirms that loss of function is the major cause of the disorder. FLNA mutations were found in 100% of familial cases with X-linked PNH (10 families: 8 with classical bilateral PNH, 1 with EDS and 1 with unilateral PH) and in 26% of sporadic patients with classical bilateral PNH. Overall, mutations occurred in 49% of individuals with classical bilateral PNH irrespective of their being familial or sporadic. However, the chances of finding a mutation were exceedingly gender biased with 93% of mutations occurring in females and 7% in males. The probability of finding FLNA mutations in other phenotypes was 4% but was limited to the minor variants of PNH with EDS and unilateral PNH. Statistical analysis considering all 42 mutations described so far identifies a hotspot region for PNH in the actin-binding domain (P < 0.05).
Assuntos
Encéfalo/anormalidades , Proteínas Contráteis/genética , Doenças Genéticas Ligadas ao Cromossomo X/genética , Proteínas dos Microfilamentos/genética , Mutação , Anormalidades Múltiplas/genética , Adolescente , Adulto , Criança , Pré-Escolar , Síndrome de Ehlers-Danlos/genética , Feminino , Filaminas , Síndrome do Cromossomo X Frágil/genética , Genótipo , Humanos , Hidrocefalia/genética , Deformidades Congênitas dos Membros/genética , Imageamento por Ressonância Magnética/métodos , Masculino , Microcefalia/genética , Pessoa de Meia-Idade , Linhagem , FenótipoRESUMO
BACKGROUND: children affected by refractory epilepsy could be at risk of malnutrition because of feeding difficulties (anorexia, chewing, swallowing difficulties or vomiting) and chronic use of anticonvulsants, which may affect food intake and energy metabolism. Moreover, their energy requirement may be changed as their disabilities would impede normal daily activities. The aim of the present study was to evaluate nutritional status, energy metabolism and food intake in children with refractory epilepsy. METHODS: 17 children with refractory epilepsy (13 boys and 4 girls; mean age 9 +/- 3,2 years; Body Mass Index 15,7 +/- 3,6) underwent an anthropometric assessment, body composition evaluation by dual-energy X-ray absorptiometry, detailed dietetic survey and measurement of resting energy expenditure by indirect calorimetry. Weight-for-age, height-for-age (stunting) and weight-for-height (wasting) were estimated compared to those of a reference population of the same age. RESULTS: 40% of children were malnourished and 24% were wasted. The nutritional status was worse in the more disabled children. Dietary intake resulted unbalanced (18%, 39%, 43% of total daily energy intake derived respectively from protein, lipid and carbohydrate). Adequacy index [nutrient daily intake/recommended allowance (RDA) x 100] was < 60% for calcium iron and zinc. CONCLUSION: many children with refractory epilepsy would benefit from individual nutritional assessment and management as part of their overall care.
Assuntos
Epilepsia/fisiopatologia , Estado Nutricional , Absorciometria de Fóton , Tecido Adiposo , Antropometria , Composição Corporal , Estatura , Índice de Massa Corporal , Peso Corporal , Densidade Óssea , Calorimetria Indireta , Criança , Registros de Dieta , Resistência a Medicamentos , Ingestão de Alimentos , Ingestão de Energia , Metabolismo Energético , Epilepsia/complicações , Epilepsia/tratamento farmacológico , Feminino , Humanos , Deficiência Intelectual/complicações , Masculino , Desnutrição/complicações , Desnutrição/epidemiologia , Minerais/administração & dosagem , Avaliação Nutricional , Necessidades Nutricionais , Descanso , Dobras Cutâneas , Síndrome de Emaciação/complicaçõesRESUMO
At the onset of West syndrome a specific impairment of visual function has been clearly demonstrated, while other aspects of sensorial development, and in particular of the auditory function, have been less studied. The aim of this study was to evaluate auditory function and orienting responses at the onset of West syndrome, and to relate the results with EEG patterns, visual function and neurodevelopmental competence. A prospective multicentric study was performed on 25 successively enrolled infants with West syndrome; all the patients underwent a full clinical assessment, including MRI and video-EEG, visual function and auditory orienting responses (AORs) as well as Griffiths' developmental scales. The whole assessment performed at the onset of spasms (T0) was repeated after two months (T1). AORs resulted significantly impaired both at T0 and T1. At the onset of spasms a highly significant relationship of auditory attention with visual function and neurodevelopmental competence was shown in both cryptogenic and symptomatic forms, but it was no longer present after two months. Our results may suggest a possible pervasive effect of the epileptic disorder on sensory processing, associated to a deficit of neurodevelopment. Although we failed to show a significant correlation between auditory orienting responses and EEG patterns, some evidence seems to support at least partially an influence of the epileptic disorder per se on the genesis of the sensorial impairment. A longer follow up and a larger cohort will be useful for a better clarification of these findings.
Assuntos
Atenção/fisiologia , Eletroencefalografia , Audição/fisiologia , Espasmos Infantis/fisiopatologia , Visão Ocular/fisiologia , Estimulação Acústica/métodos , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética/métodos , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: To define the clinical, radiologic, and genetic features of periventricular heterotopia (PH) with Ehlers-Danlos syndrome (EDS). METHODS: Exonic sequencing and single stranded conformational polymorphism (SSCP) analysis was performed on affected individuals. Linkage analysis using microsatellite markers on the X-chromosome was performed on a single pedigree. Western blotting evaluated for loss of filamin A (FLNA) protein and Southern blotting assessed for any potential chromosome rearrangement in this region. RESULTS: The authors report two familial cases and nine additional sporadic cases of the EDS-variant form of PH, which is characterized by nodular brain heterotopia, joint hypermobility, and development of aortic dilatation in early adulthood. MRI typically demonstrated bilateral nodular PH, indistinguishable from PH due to FLNA mutations. Exonic sequencing or SSCP analyses of FLNA revealed a 2762 delG single base pair deletion in one affected female. Another affected female harbored a C116 single point mutation, resulting in an A39G change. A third affected female had a 4147 delG single base pair deletion. One pedigree with no detectable exonic mutation demonstrated positive linkage to the FLNA locus Xq28, an affected individual in this family also had no detectable FLNA protein, but no chromosomal rearrangement was detected. CONCLUSION: These results suggest that the Ehlers-Danlos variant of periventricular heterotopia (PH), in part, represents an overlapping syndrome with X-linked dominant PH due to filamin A mutations.
Assuntos
Encéfalo/anormalidades , Proteínas Contráteis/deficiência , Síndrome de Ehlers-Danlos/genética , Proteínas dos Microfilamentos/deficiência , Mutação Puntual , Deleção de Sequência , Adolescente , Adulto , Substituição de Aminoácidos , Criança , Cromossomos Humanos X/genética , Proteínas Contráteis/genética , Proteínas Contráteis/fisiologia , Análise Mutacional de DNA , Síndrome de Ehlers-Danlos/patologia , Epilepsia/etiologia , Éxons/genética , Feminino , Filaminas , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/fisiologia , Repetições de Microssatélites , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Fenótipo , Polimorfismo Conformacional de Fita SimplesRESUMO
OBJECTIVES: SCN1A mutations were recently reported in several patients with severe myoclonic epilepsy in infancy (SMEI). The authors analyzed SCN1A mutations in 93 patients with SMEI and made genotype-phenotype correlation to clarify the role of this gene in the etiology of SMEI. METHODS: All patients fulfilled the criteria for SMEI. The authors analyzed all patients for SCN1A mutations using denaturing high performance liquid chromatography. If a patient's chromatogram was abnormal, the authors sequenced the gene in the patient and both parents. RESULTS: SCN1A mutations were identified in 33 patients (35%). Most mutations were de novo, but were inherited in three patients. Parents carrying the inherited mutations had either no symptoms or a milder form of epilepsy. A greater frequency of unilateral motor seizures was the only clinical difference between patients with SCN1A mutations and those without. Truncating mutations were more frequently associated with such seizures than were missense mutations. The percentage of cases with family history of epilepsy was significantly higher in patients with SCN1A mutations. CONCLUSIONS: Unilateral motor seizures may be a specific clinical characteristic of SMEI caused by SCN1A mutations. Ten percent of SCN1A mutations are inherited from an asymptomatic or mildly affected parent, suggesting that SMEI is genetically heterogeneous. The increased frequency of familial epilepsy indicates that other genetic factors may contribute to this disorder.
Assuntos
Epilepsia Mioclônica Juvenil/genética , Proteínas do Tecido Nervoso/genética , Canais de Sódio/genética , Adulto , Idade de Início , Cromatografia Líquida de Alta Pressão , Análise Mutacional de DNA , Epilepsia Tipo Ausência/genética , Etnicidade/genética , Feminino , França/epidemiologia , Heterogeneidade Genética , Predisposição Genética para Doença , Genótipo , Humanos , Lactente , Deficiência Intelectual/genética , Itália/epidemiologia , Masculino , Epilepsia Mioclônica Juvenil/epidemiologia , Canal de Sódio Disparado por Voltagem NAV1.1 , FenótipoRESUMO
PURPOSE: To measure anti-cardiolipin (aCL), anti-beta2 glycoprotein I (anti-beta2GPI), and anti-prothrombin (aPT) antibodies in young patients with epilepsy, and to correlate their presence with demographic data, clinical diagnoses, laboratory and neuroradiologic findings, and antiepileptic drugs (AEDs). METHODS: Sera from one hundred forty-two consecutive patients with epilepsy with a median age of 10 years were tested for aCL and anti-beta2GPI autoantibodies by solid-phase assays. aPT antibodies also were assayed in sera from 90 patients. Positive results were confirmed after a minimum of 6 weeks. Antinuclear antibodies (ANAs) and antibodies against extractable nuclear antigens (ENAs) also were tested. RESULTS: An overall positivity of 41 (28.8%) of 142 sera was found. Fifteen patients were positive for aCL, 25 for anti-beta2GPI, and 18 for aPT antibodies. Several patients (12%) displayed more than one specificity in their serum. Only one of these patients had a concurrent positivity for ANAs and ENAs. A predominance of younger patients was found in the antibody-positive group. All types of epilepsy were represented in the positive group. No relation between antibody positivity and AEDs was found. Diffuse ischemic lesions at computed tomography (CT)/magnetic resonance imaging (MRI) scans were present in higher percentages in patients who were antibody positive. No positive patient had a history of previous thrombosis or other features related to systemic lupus erythematosus (SLE), and no patient was born of a mother with SLE. CONCLUSIONS: Our study suggests a relation between epilepsy and aPL in young patients. A pathogenetic role for these autoantibodies cannot be excluded, and their determination might prove useful even from a therapeutic point of view.
Assuntos
Anticorpos Anticardiolipina/sangue , Epilepsia/epidemiologia , Epilepsia/imunologia , Glicoproteínas/imunologia , Protrombina/imunologia , Adolescente , Adulto , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Epilepsia/tratamento farmacológico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Soroepidemiológicos , beta 2-Glicoproteína IRESUMO
OBJECTIVE: To examine the clinical and MRI associations in bilateral periventricular nodular heterotopia (BPNH) (MIM # 300049) in two families segregating a missense mutation and a C-terminal deletion of the filamin 1(FLN1) gene. BACKGROUND: Classical familial BPNH, an X-linked dominant disorder, has been associated with protein truncations or splicing mutations, which tend to cluster at the N-terminal of the FLN1 protein, causing severe predicted loss of the protein function. The clinical syndrome includes symmetrical contiguous nodular heterotopia lining the lateral ventricles, epilepsy, mild retardation to normal cognitive level in affected females, and prenatal lethality in hemizygous boys. METHODS: Clinical examination, cognitive testing, MRI, mutation analysis (direct sequencing, single-strand conformation polymorphism) in seven patients from two families with BPNH. RESULTS: In Family 1, harboring an A > T change in exon 2 (E82V), heterotopic nodules were few, asymmetric, and noncontiguous. Five boys born from affected females had died unexpectedly early in life. In Family 2, harboring an 8 base pair deletion in exon 47 (7627_7634del TGTGCCCC), heterotopic nodules were thick and contiguous. Affected females in both families showed normal to borderline IQ and epilepsy. CONCLUSION: Missense mutations and distal truncations consistent with partial loss of FLN1 function cause familial BPNH with the classical clinical phenotype including epilepsy and mild mental retardation, if any. However, missense mutations have milder anatomic consequences in affected females and are possibly compatible with live birth but short survival of boys.
Assuntos
Córtex Cerebral , Coristoma/genética , Coristoma/patologia , Proteínas Contráteis/genética , Ventrículos Laterais/patologia , Proteínas dos Microfilamentos/genética , Mutação de Sentido Incorreto/genética , Aborto Espontâneo/genética , Aborto Espontâneo/patologia , Adolescente , Adulto , Sequência de Aminoácidos , Epilepsia/genética , Epilepsia/patologia , Feminino , Filaminas , Deleção de Genes , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , LinhagemRESUMO
PURPOSE: To determine the direct costs of epilepsy in a child neurology referral population, stratified by disease, duration, and severity, comparing three different health care settings [i.e., teaching or clinical research (CR) hospitals, general hospitals, and outpatient services]. METHODS: Patients were accepted if they had confirmed epilepsy and were resident in the center catchment area. Eligible subjects were grouped in the following categories: (a) newly diagnosed patients; (b) patients with epilepsy in remission; (c) patients with active non-drug-resistant epilepsy; and (d) those with drug-resistant epilepsy. Over a 12-month period, data regarding the consuming of all resources (i.e., consultations, tests, hospital admissions, drugs), were collected for each patient. Using the Italian National Health Service tariffs, the unit cost of each resource was calculated and indicated in Euros, the European currency. RESULTS: A total of 189 patients was enrolled by two teaching-CR hospitals, two general hospitals, and two outpatient services. The patients were evenly distributed across the four categories of epilepsy. The mean annual cost per person with epilepsy was 1,767 Euros. Drug-resistant epilepsy was the most expensive category (3,268 Euros) followed by newly diagnosed epilepsy (1,907 Euros), active non-drug-resistant epilepsy (1,112 Euros), and epilepsy in remission (844 Euros). Costs were generally highest in teaching-CR hospitals and lowest in outpatient services. Hospital services were the major cost in all epilepsy groups, followed by drugs. CONCLUSIONS: The cost of epilepsy in children and adolescents in Italy tends to vary significantly depending on the severity and duration of the disease Hospitals services and drugs are the major sources of costs. The setting of health care plays a significant role in the variation of the costs, even for patients in the same category of epilepsy.
Assuntos
Epilepsia/economia , Custos de Cuidados de Saúde/estatística & dados numéricos , Serviços de Saúde/economia , Adolescente , Fatores Etários , Assistência Ambulatorial/economia , Assistência Ambulatorial/estatística & dados numéricos , Anticonvulsivantes/economia , Anticonvulsivantes/uso terapêutico , Criança , Pré-Escolar , Custos de Medicamentos/estatística & dados numéricos , Epilepsia/diagnóstico , Epilepsia/tratamento farmacológico , Feminino , Gastos em Saúde/estatística & dados numéricos , Pesquisa sobre Serviços de Saúde , Custos Hospitalares/estatística & dados numéricos , Hospitalização/economia , Hospitais de Ensino/economia , Hospitais de Ensino/estatística & dados numéricos , Humanos , Itália , Masculino , Qualidade da Assistência à Saúde , Índice de Gravidade de DoençaRESUMO
In 1997, a locus for benign familial infantile convulsions (BFIC) was mapped to chromosome 19q. Further data suggested that this locus is not involved in all families with BFIC. In the present report, we studied eight Italian families and mapped a novel BFIC locus within a 0.7-cM interval of chromosome 2q24, between markers D2S399 and D2S2330. A maximum multipoint HLOD score of 6.29 was obtained under the hypothesis of genetic heterogeneity. Furthermore, the clustering of chromosome 2q24-linked families in southern Italy may indicate a recent founder effect. In our series, 40% of the families are linked to neither chromosome 19q or 2q loci, suggesting that at least three loci are involved in BFIC. This finding is consistent with other autosomal dominant idiopathic epilepsies in which different genes were found to be implicated.
Assuntos
Cromossomos Humanos Par 2/genética , Epilepsia Neonatal Benigna/genética , Heterogeneidade Genética , Mapeamento Cromossômico , Cromossomos Humanos Par 19/genética , Feminino , Efeito Fundador , Genes Dominantes/genética , Marcadores Genéticos/genética , Humanos , Lactente , Recém-Nascido , Itália , Funções Verossimilhança , Escore Lod , Masculino , Dados de Sequência Molecular , LinhagemRESUMO
"Generalized epilepsy with febrile seizures plus" (GEFS+) syndrome has been recently described. This term defines a heterogeneous group of generalized epilepsies observed in several members of large pedigree studies. The syndrome spectrum has been widened by including others forms of generalized epilepsy. We report two Italian families in which the fathers showed febrile seizure plus (FS+), and two sons had severe myoclonic epilepsy of infancy (SMEI). The clinical setting of each epileptic member of the family will be discussed, focusing on the relationship with the GEFS+ group, confirming its wide clinical spectrum. In fact, GEFS+ is different from most other epilepsy syndromes as it is defined not by a set of associated symptoms but by the genetic transmission of a predisposition to febrile convulsions and other seizures, with a variable expression in several members of the same pedigree, perhaps due to ionic channel dysfunction. SMEI could represent the most severe end of the spectrum.
Assuntos
Epilepsias Mioclônicas/diagnóstico , Epilepsia Generalizada/diagnóstico , Convulsões Febris/diagnóstico , Adulto , Idoso , Criança , Pré-Escolar , Cromossomos Humanos Par 19/genética , Cromossomos Humanos Par 2/genética , Epilepsias Mioclônicas/genética , Epilepsia Generalizada/genética , Humanos , Lactente , Itália , Linhagem , Convulsões Febris/genéticaRESUMO
Continuous spikes and waves during slow sleep (CSWS) are a well-known EEG pattern that can be associated with cognitive and behavioural deterioration. We present the long-term clinical, neuropsychological and EEG follow-up of two patients who developed CSWS during childhood. In both the CSWS onset was followed immediately by rapid cognitive and behavioural deterioration. Later the CSWS fragmented or fluctuated and the spike-wave discharges diminished and this was associated with progressive clinical improvement. At the same time bilateral frontal EEG abnormalities appeared awake and in sleep. After the initial period of rapid cognitive and linguistic improvement both patients stabilised. The latest neuropsychological assessment showed a frontal syndrome. The presence of frontal EEG abnormalities superimposed on CSWS, their persistence after CSWS resolution and, in addition, the finding of subtle frontal-type neuropsychological alterations early in recovery may indicate poor long-term outcome.