RESUMO
OBJECTIVE: To study the long-term neurocognitive changes of a right-handed girl with intractable epilepsy after late right hemispherectomy and compare them with data in the literature. METHOD: The girl was affected by an epileptic encephalopathy associated with right fronto-temporo-parietal polymicrogyria; she was submitted to right hemispherectomy at the age of 5 and examined with cognitive and neuropsychological tests at the age of 17 years. The girl took advantage of neurocognitive rehabilitation for several years; she is currently seizure-free and off therapy. RESULTS: At the end of the follow-up, the full-scale IQ is stable and within the normal range (p = 88). As the discrepancy between verbal IQ (pp = 120) and performance IQ (pp = 71) is significantly high, the girl was subjected to neurocognitive evaluation with the following results: verbal problem solving, verbal short- and long-term memory, and executive functions are within normal range. The most fragile functional areas are visual and spatial reasoning, verbal working memory, short-term visuospatial memory, visual attention, and processing speed, all > 2 SD. The spatial tests, such as coding, matrix reasoning, picture concepts, and arithmetic reasoning (which are favored by other functions such as associative memory and learning ability), are less severely impaired. CONCLUSIONS: These findings show that good conceptual skills and verbal reasoning can compensate for some deficits in visual-perceptual and visuospatial functions.
Assuntos
Remediação Cognitiva/tendências , Epilepsia Resistente a Medicamentos/cirurgia , Hemisferectomia/tendências , Transtornos Neurocognitivos/cirurgia , Adolescente , Epilepsia Resistente a Medicamentos/complicações , Epilepsia Resistente a Medicamentos/psicologia , Feminino , Hemisferectomia/psicologia , Humanos , Testes de Estado Mental e Demência , Transtornos Neurocognitivos/complicações , Transtornos Neurocognitivos/psicologia , Fatores de Tempo , Resultado do TratamentoRESUMO
Mutations in SCN8A gene have been described in relation to infantile onset epilepsy with movement disorders and developmental delay. Recently various authors have reported patients carrying autosomal dominant heterozygous SCN8A mutations and a milder phenotype expression. We discuss the case of a 6-year-old girl with a positive family history for epilepsy, early benign focal epilepsy, well controlled by Carbamazepine, upper limb tremor since birth, ataxia, slight motor delay and normal cognitive development. Neuroradiological study is normal, waking EEGs are normal, while epileptiform abnormalities on the vertex appear during sleep. The girl carries a de novo mutation of the SCN8A gene with nucleotide substitution of c.3943Gâ¯>â¯A (p.Val 1315 Met), located in the domain III S4/S5 intracellular linker. In literature two other cases with the same mutation have been reported, both patients have an epileptic encephalopathy. Our patient's milder phenotype could be caused by a modifier effect, possibly a mutation in another gene or a mosaicism. The detailed description of our case should contribute to enlarging the description of the clinical features of SCN8A mutations and to recommending the deepening of genetic investigations to.
Assuntos
Epilepsia/genética , Epilepsia/fisiopatologia , Mutação/genética , Canal de Sódio Disparado por Voltagem NAV1.6/genética , Ondas Encefálicas/genética , Criança , Eletroencefalografia , Feminino , Humanos , FenótipoRESUMO
UNLABELLED: Children with ADHD may present with sleep disturbances that add to the impairment of the disorder. The long-term sleep effects of the first-line pharmacological treatment for ADHD, i.e., psychostimulants, are unclear. In this pilot study, we compared polysomnographic variables in children with ADHD (n = 11, aged 6-15 years), before pharmacological treatment, and in children without ADHD (n = 22, aged 5-14 years); we also assessed polysomnographic changes in children with ADHD (n = 7) after a 6-month treatment with methylphenidate immediate-release (once or twice daily). Compared to children without ADHD, those with ADHD at baseline presented with significantly increased duration of awakenings (p = 0.02), reduction in sleep efficiency (p = 0.03), and increase in stage I (N1) (p < 0.01) and reduction in stage II (N2) (p = 0.02) and stage III-IV (N3) percentages. Methylphenidate treatment did not significantly change any parameter of sleep architecture. CONCLUSION: Preliminary evidence from this pilot study shows that, compared to children without ADHD, those with ADHD presented a more fragmented and less effective sleep at baseline and that the 6-month methylphenidate treatment did not further negatively impact on sleep architecture. WHAT IS KNOWN: ⢠Children with ADHD may present with subjectively reported and/or objectively confirmed disturbances of sleep. ⢠The long-term effects on sleep of the first-line pharmacological treatment for ADHD, i.e., psychostimulants, are not clear. What is new: ⢠Our study showed that the 6-month continuous treatment with methylphenidate did not further negatively impact on sleep architecture in children with ADHD.
Assuntos
Transtornos de Deficit da Atenção e do Comportamento Disruptivo/tratamento farmacológico , Metilfenidato/uso terapêutico , Sono/fisiologia , Adolescente , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/fisiopatologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Masculino , Projetos Piloto , Polissonografia , Estudos Retrospectivos , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
15q.13.3 microdeletion has been described in a variety of neurodevelopmental disorders. Epilepsy appears to be a common feature and, specifically, the 15q13.3 microdeletion is found in about 1% of patients with idiopathic generalized epilepsy. Recently, absence seizures with intellectual disability (ID) have been reported in patients carrying this mutation. We describe two families in which several affected members carry a 15q13.3 microdeletion in a pattern suggestive of autosomal dominant inheritance. Their phenotype includes mainly absence epilepsy and mild ID, suggesting only similarities with genetic/idiopathic generalized epilepsies but not typical features. The importance of studying such families is crucial to broaden the phenotype and understand the long-term outcome of patients with this condition.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 15/genética , Epilepsia Generalizada/genética , Predisposição Genética para Doença , Adolescente , Adulto , Eletroencefalografia , Epilepsia Generalizada/patologia , Saúde da Família , Feminino , Humanos , Inteligência , Itália , Imageamento por Ressonância Magnética , Masculino , MutaçãoRESUMO
The KCNAB1 gene is a candidate susceptibility factor for lateral temporal epilepsy (LTE) because of its functional interaction with LGI1, the gene responsible for the autosomal dominant form of LTE. We investigated association between polymorphic variants across the KCNAB1 gene and LTE. The allele and genotype frequencies of 14 KCNAB1 intronic SNPs were determined in 142 Italian LTE patients and 104 healthy controls and statistically evaluated. Single SNP analysis revealed one SNP (rs992353) located near the 3'end of KCNAB1 slightly associated with LTE after multiple testing correction (odds ratio=2.25; 95% confidence interval 1.26-4.04; P=0.0058). Haplotype analysis revealed two haplotypes with frequencies higher in cases than in controls, and these differences were statistically significant after permutation tests (Psim=0.047 and 0.034). One of these haplotypes was shown to confer a high risk for the syndrome (odds ratio=12.24; 95% confidence interval 1.32-113.05) by logistic regression analysis. These results support KCNAB1 as a susceptibility gene for LTE, in agreement with previous studies showing that this gene may alter susceptibility to focal epilepsy.
Assuntos
Epilepsia do Lobo Temporal/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Íntrons/genética , Canal de Potássio Kv1.3/genética , Polimorfismo de Nucleotídeo Único/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Desequilíbrio de Ligação , Modelos Logísticos , Masculino , Proteínas/genética , Proteínas/metabolismoRESUMO
Since the age of three years the patient suffered from early drug-resistant partial epilepsy with electric status during slow sleep, owing to a micropolygyric malformation of the right fronto-temporo-parietal lobes. The hemispherotomy (when five years of age) was followed by immediate and persistent disappearance of the seizures and withdrawal of the treatment. The transfer of right hemispheric functions to the left hemisphere occurred very early; the child's development was examined in relation to the restoration of these functions and the age at surgery. The early surgical intervention and the plasticity of the brain - along with an intensive cognitive rehabilitation - seem to be important in determining the favorable global cognitive outcome. Visuo-spatial abilities and multi-modal integration of these functions with memory, attention and language have been the most critical domains and are recently in progress. The rapidity of processing complex tasks is particularly lacking. This seems to be the expression of the defective development of the Central Executive System.
Assuntos
Cérebro/cirurgia , Cognição/fisiologia , Epilepsias Parciais , Cérebro/anormalidades , Cérebro/fisiologia , Cérebro/fisiopatologia , Criança , Pré-Escolar , Eletroencefalografia , Epilepsias Parciais/patologia , Epilepsias Parciais/fisiopatologia , Epilepsias Parciais/cirurgia , Feminino , Humanos , Idioma , Testes Neuropsicológicos , Percepção Visual/fisiologiaRESUMO
Merosin-deficient congenital muscular dystrophy (MD) type 1A (MDC1A) is one of the most frequent forms of CMD in Western countries. The classical form, characterized by a total lack of laminin alpha2 chain expression, usually shows severe clinical features; cases with complete laminin alpha2 deficiency and mild phenotype have also been reported, although the mechanisms underlying the lack of genotype-phenotype correlation have not been elucidated. Epilepsy and focal cortical dysplasia-in addition to the classical diffuse white matter abnormalities-have been described in some of these patients associated with cognitive deterioration. We report on a patient with total laminin alpha2 deficiency due to a homozygous stop-codon mutation in the LAMA2 gene, with mild evolution. When 6.9 years old, she developed focal occipital seizures and absence-like status when awake, with probable relation to an extensive bilateral occipital micropolygyria. Soon afterwards she lost ambulation and developed cognitive deterioration. Our case confirms that the clinical spectrum of MDC1A is more heterogeneous than previously thought.
Assuntos
Códon sem Sentido , Laminina/genética , Distrofias Musculares/genética , Criança , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/fisiopatologia , Epilepsia/etiologia , Epilepsia/fisiopatologia , Feminino , Genótipo , Humanos , Laminina/deficiência , Imageamento por Ressonância Magnética/métodos , Malformações do Desenvolvimento Cortical/etiologia , Malformações do Desenvolvimento Cortical/fisiopatologia , Distrofias Musculares/complicações , Distrofias Musculares/fisiopatologia , Lobo Occipital/patologia , Lobo Occipital/fisiopatologia , Fenótipo , Convulsões/etiologia , Convulsões/fisiopatologiaRESUMO
OBJECTIVES: Mutations in the EFHC1 gene have been reported in six juvenile myoclonic epilepsy (JME) families from Mexico and Belize. In this study, we screened 27 unrelated JME Italian families for mutations in the EFHC1 gene. MATERIALS AND METHODS: Twenty-seven families (86 affected individuals, 52 women) with at least two affected members with JME were selected. DNA was isolated from peripheral blood lymphocytes by standard methods and each exon of the EFHC1 gene was amplified and sequenced using intronic primers. RESULTS: Two heterozygous mutations were identified in three unrelated families. One (R353 W) was a novel missense mutation, while the F229 L mutation was previously described (say which on of the two occurred in two families). Both mutations cosegregated with the disease. In a fourth family, the variant 545G-->A (resulting in the amino acid substitution R182 H) cosegregated with JME. CONCLUSIONS: The results of our study extend the distribution of EFHC1 mutations to the white population and confirm the high level of genetic heterogeneity associated with JME.
Assuntos
Proteínas de Ligação ao Cálcio/genética , Análise Mutacional de DNA , Família , Mutação/genética , Epilepsia Mioclônica Juvenil/genética , Adulto , Mapeamento Cromossômico , Feminino , Heterogeneidade Genética , Testes Genéticos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto/genética , Epilepsia Mioclônica Juvenil/epidemiologia , Epilepsia Mioclônica Juvenil/etnologia , Linhagem , Fenótipo , População Branca/genéticaRESUMO
Severe myoclonic epilepsy of infancy (SMEI) has been long suspected to have a genetic origin. Recently mutations in the gene encoding a voltage-gated alpha-1 sodium channel subunit-SCN1A-have been identified as a common cause of SMEI. Moreover, a mutation in the gene encoding the gamma2 subunit of the GABA(A) receptor-GABRG2-has been described in a GEFS+ family with a member affected by SMEI. In order to further investigate the role of GABRG2 in the pathogenesis of SMEI, we have screened for mutations 53 SMEI patients who resulted negative for SCN1A mutations. Mutational screening of GABRG2 genes was performed by denaturing high performance liquid chromatography (DHPLC) and direct sequencing of DNA fragments showing a variant chromatogram. Twenty-nine variant chromatograms were identified corresponding to seven different nucleotide variants. None of them leads to an amino acid change or obvious protein dysfunction. No difference in allele frequency was observed for the SMEI patients compared to a control population indicating that these variants are not involved in SMEI. Our study demonstrates that GABRG2 is not a commonly involved in the etiology of SMEI and suggests that other and yet unidentified genes are involved in the syndrome
Assuntos
Epilepsias Mioclônicas/genética , Epilepsias Mioclônicas/fisiopatologia , Mutação , Receptores de GABA-A/genética , Alelos , Sequência de Aminoácidos/genética , Pré-Escolar , Cromatografia Líquida de Alta Pressão , Análise Mutacional de DNA , Feminino , Frequência do Gene , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético/genética , Índice de Gravidade de DoençaRESUMO
In the literature, several malformations of cortical development have been described as additional lesions in tuberous sclerosis complex. Among these lesions, a very large focal cortical dysplasia has peculiar magnetic resonance imaging features: a signal abnormality that extends radially inward toward the lateral ventricle from the pachygyric cortical surface plus a homogeneous clinical picture. Affected patients have early-onset drug-resistant epilepsy and severe developmental delay. We describe the clinical, genetic, neurophysiologic, and neuroradiologic characteristics of four patients affected by tuberous sclerosis and this type of cortical dysplasia these patients are of special interest because they have been operated on for their dysplastic lesions. Total control of seizures has been achieved in the three children who underwent a complete lesionectomy. This result cannot be permanent, however, because of the presence of other cortical tubers which could become epileptogenic. All things considered, our choice was to give these children at least temporary relief from severe epilepsy and possibly support for developmental progression.