RESUMO
PURPOSE: To dissect the genetics of benign familial epilepsies of the first year of life and to assess the extent of the genetic overlap between benign familial neonatal seizures (BFNS), benign familial neonatal-infantile seizures (BFNIS), and benign familial infantile seizures (BFIS). METHODS: Families with at least two first-degree relatives affected by focal seizures starting within the first year of life and normal development before seizure onset were included. Families were classified as BFNS when all family members experienced neonatal seizures, BFNIS when the onset of seizures in family members was between 1 and 4 months of age or showed both neonatal and infantile seizures, and BFIS when the onset of seizures was after 4 months of age in all family members. SCN2A, KCNQ2, KCNQ3, PPRT2 point mutations were analyzed by direct sequencing of amplified genomic DNA. Genomic deletions involving KCNQ2 and KCNQ3 were analyzed by multiple-dependent probe amplification method. KEY FINDINGS: A total of 46 families including 165 affected members were collected. Eight families were classified as BFNS, 9 as BFNIS, and 29 as BFIS. Genetic analysis led to the identification of 41 mutations, 14 affecting KCNQ2, 1 affecting KCNQ3, 5 affecting SCN2A, and 21 affecting PRRT2. The detection rate of mutations in the entire cohort was 89%. In BFNS, mutations specifically involve KCNQ2. In BFNIS two genes are involved (KCNQ2, six families; SCN2A, two families). BFIS families are the most genetically heterogeneous, with all four genes involved, although about 70% of them carry a PRRT2 mutation. SIGNIFICANCE: Our data highlight the important role of KCNQ2 in the entire spectrum of disorders, although progressively decreasing as the age of onset advances. The occurrence of afebrile seizures during follow-up is associated with KCNQ2 mutations and may represent a predictive factor. In addition, we showed that KCNQ3 mutations might be also involved in families with infantile seizures. Taken together our data indicate an important role of K-channel genes beyond the typical neonatal epilepsies. The identification of a novel SCN2A mutation in a family with infantile seizures with onset between 6 and 8 months provides further confirmation that this gene is not specifically associated with BFNIS and is also involved in families with a delayed age of onset. Our data indicate that PRRT2 mutations are clustered in families with BFIS. Paroxysmal kinesigenic dyskinesia emerges as a distinctive feature of PRRT2 families, although uncommon in our series. We showed that the age of onset of seizures is significantly correlated with underlying genetics, as about 90% of the typical BFNS families are linked to KCNQ2 compared to only 3% of the BFIS families, for which PRRT2 represents the major gene.
Assuntos
Epilepsia Neonatal Benigna/diagnóstico , Epilepsia Neonatal Benigna/genética , Testes Genéticos , Canal de Potássio KCNQ2/genética , Canal de Potássio KCNQ3/genética , Proteínas de Membrana/genética , Canal de Sódio Disparado por Voltagem NAV1.2/genética , Proteínas do Tecido Nervoso/genética , Adolescente , Adulto , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Testes Genéticos/métodos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Família Multigênica/genética , Mutação/genética , Valor Preditivo dos Testes , Adulto JovemRESUMO
Gelastic epilepsy are focal seizures manifesting as recurrent brief seizures starting as laughter or grimaces. They are most commonly associated with other types of seizures and can be secondary to infectious, malformative, metabolic, or neoplastic processes involving the central nervous system. We report on an 18-month-old girl who presented since the age of 2 months with multiple, recurrent, unprovoked episodes of stereotypical laughter. Brain magnetic resonance study revealed an hypothalamic hamartoma. Endoscopic tumor disconnection of the hamartoma resulted in rapid resolution of neurological symptomatology.
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Epilepsias Parciais/etiologia , Epilepsias Parciais/cirurgia , Hamartoma/complicações , Hamartoma/cirurgia , Doenças Hipotalâmicas/complicações , Doenças Hipotalâmicas/cirurgia , Epilepsias Parciais/fisiopatologia , Feminino , Hamartoma/diagnóstico , Humanos , Doenças Hipotalâmicas/diagnóstico , Lactente , NeuroendoscopiaRESUMO
BACKGROUND: Familial spinal neurofibromatosis is a form of neurofibromatosis 1 (NF1), consisting of extensive, symmetrical, histologically proven, multiple neurofibromas of the spinal roots at every level and of all major peripheral nerves sometimes associated with typical NF1 stigmata; most cases underlie NF1 gene mutations. OBJECTIVES: The objectives of this study are (1) to report the findings in a set of 16-year-old monozygotic twin girls and a 14-year-old boy and (2) to review the existing literature. METHODS AND RESULTS: In this article, we report the cases of three children who (1) had manifested mildly different symptomatic neuropathy (twins, aged 4 years; and a boy, aged 9 years) associated with massive, symmetrical neurofibromas; (2) had few café-au-lait spots with irregular margins and pale brown pigmentation; (3) were presented with, at brain magnetic resonance imaging (MRI), bilateral, NF1-like high-signal abnormalities in the basal ganglia; (4) yielded missense NF1 gene mutations in exon 39; and (5) had unaffected parents with negative NF1 genetic testing as well as discuss 12 families and 20 sporadic and 5 additional cases that presented spinal neurofibromatosis within classical NF1 families (53 cases) that were reported in the literature. CONCLUSIONS: This article presents the first report on (1) spinal neurofibromatosis in a set of affected monozygotic twins; (2) the earliest onset of the disease; and (3) the occurrence of high signal lesions in the brain at MRI.
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Encéfalo/patologia , Manchas Café com Leite/diagnóstico , Doenças em Gêmeos/diagnóstico , Neurofibromatoses/diagnóstico , Fenótipo , Adolescente , Manchas Café com Leite/complicações , Manchas Café com Leite/genética , Doenças em Gêmeos/genética , Feminino , Testes Genéticos , Humanos , Masculino , Neurofibromatoses/complicações , Neurofibromatoses/genética , Gêmeos Monozigóticos/genéticaRESUMO
PURPOSE: Mutation analysis of the SCN1B, SCN1A and GABRG2 genes in children affected by Genetic (Generalised) Epilepsy with Febrile Seizures plus (GEFS(+)) and their affected and some unaffected family members, coming from a restricted geographic area, was performed. METHODS: Eight GEFS(+) families (58 members) diagnosed according to current GEFS(+) criteria were studied. RESULTS: A heterozygous point mutation A2336G was detected in exon 13 of the SCNA1 gene in three affected members of one family but not in their unaffected relatives; a novel Ile1944Thr mutation was located within the intracellular C-terminal region of the SCNA1 gene in the proband and his healthy father in a second family. In the former family, the proband had dysmorphic features including large forehead, large nasal bridge, pointed nasal tip, triangular nostrils, deep nasolabial folds, thin upper lips with large mouth, congenital gingival hyperplasia with wide gingiva and mental retardation, abnormalities not previously listed in the clinical spectrum of GEFS(+). CONCLUSIONS: Our study confirms that just a few GEFS(+) families have mutations in the five genes classically known and reinforces the genetic and also the phenotypic variability of GEFS(+) featuring clinical manifestations. Question rises whether the cognitive problems seen in two siblings and dysmorphic features in one of them may be related to the channelopathy as it occurs in other well-known ion channel disorders.
Assuntos
Epilepsia Generalizada/genética , Proteínas do Tecido Nervoso/genética , Receptores de GABA-A/genética , Convulsões Febris/genética , Canais de Sódio/genética , Adulto , Criança , Pré-Escolar , Análise Mutacional de DNA , Feminino , Humanos , Lactente , Masculino , Canal de Sódio Disparado por Voltagem NAV1.1 , Linhagem , Mutação Puntual , Subunidade beta-1 do Canal de Sódio Disparado por VoltagemRESUMO
BACKGROUND: Alternating of Childhood (AHC) is an uncommon and complex disorder characterized by age of onset before 18 months with recurrent hemiplegia of one or either sides of the body or quadriplegia. The disorder is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene. In AHC neurological co-morbidities are various and frequently reported including developmental delay, epilepsy, tonic or dystonic spells, nystagmus,autonomic manifestations with intrafamilial variability. CASE PRESENTATION: Clinical and genetic findings of a couple of twins (Family 1: Case 1 and Case 2) and a couple of siblings (Family 2: Case 3 and Case 4) coming from two different Italian families affected by AHC were deeply examined. In twins of Family 1, a pathogenic variant in ATP1A3 gene (c.2318A>G) was detected. In siblings of Family 2, the younger brother showed a novel GRIN2A variant (c.3175 T > A), while the older carried the same GRIN2A variant, and two missense mutations in SCNIB (c.632 > A) and KCNQ2 (1870 G > A) genes. Clinical manifestations of the four affected children were reported along with cases of AHC drawn from the literature. CONCLUSIONS: Hemiplegic episode is only a sign even if the most remarkable of several and various neurological comorbidities in AHC affected individuals. Molecular analysis of the families here reported showed that clinical features of AHC may be also the result of an unexpected genetic heterogeneity.
Assuntos
Hemiplegia , ATPase Trocadora de Sódio-Potássio , Criança , Hemiplegia/diagnóstico , Hemiplegia/epidemiologia , Hemiplegia/genética , Humanos , Lactente , Masculino , Mutação , Mutação de Sentido Incorreto , ATPase Trocadora de Sódio-Potássio/genéticaRESUMO
Currarino syndrome (CS) is a peculiar form of caudal regression syndrome [also known as autosomal dominant sacral agenesis (OMIM no. 176450)] characterised by (1) partial absence of the sacrum with intact first sacral vertebra, (2) a pre-sacral mass and (3) anorectal anomalies (Currarino triad). We studied a 3-year-old girl with Currarino triad who had additional systemic features and performed array comparative genomic hybridisation to look for chromosomal abnormalities. This girl had the typical spectrum of anomalies of the CS including (a) partial sacral agenesis (hemisacrum with remnants of only sacral S1-S2 vertebrae and a residual S3 vertebral body) associated with complete coccygeal agenesis, (b) pre-intrasacral dermoid, (c) intra-dural lipoma, (d) ectopic anus and (e) tethered cord. She had, in addition, pre- and post-natal growth impairment (<3rd percentile), severe microcephaly (<-3 SD) with normal gyration pattern and lack of cortical thickening associated with a hypoplastic inferior vermis, facial dysmorphism, sensorineural deafness and decreased serum levels of IGF-1. A de novo 10.3-Mb duplication of 7q34-q35 and an 8.8-Mb deletion on 7q36 were identified in this patient. The Homeobox HLXB9 (CS) gene is contained within the deletion accounting for the CS phenotype including microcephaly. The spectrums of associated abnormalities in the IGF-1 deficiency growth retardation with sensorineural deafness and mental retardation syndrome (OMIM no. 608747) are discussed. To the best of our knowledge, this is the first reported case of a patient with distal 7q chromosomal imbalance and features of CS triad (including microcephaly) and the first documented case of a patient with normal gyration pattern microcephaly. The spectrum of associated anomalies in this newly recognised phenotype complex consists of growth failure, typical facial anomalies with additional (previously unreported) nervous system abnormalities (e.g. sensorineural deafness) and somatomedin C deficiency.
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Cromossomos Humanos Par 7/genética , Deleção de Genes , Duplicação Gênica , Perda Auditiva Neurossensorial/complicações , Perda Auditiva Neurossensorial/genética , Microcefalia/complicações , Microcefalia/genética , Reto/anormalidades , Sacro/anormalidades , Anormalidades Múltiplas , Pré-Escolar , Feminino , HumanosRESUMO
Alternating Hemiplegia of Childhood (AHC) is a rare disorder characterized by frequent, transient attacks of hemiplegia involving either side of the body or both in association to several other disturbances including dystonic spells, abnormal ocular movements, autonomic manifestations, epileptic seizures and cognitive impairment. The clinical manifestations usually start before the age of 18 months. Two forms of the disorder known as AHC-1 (MIM#104290) and AHC-2 (MIM#614820) depends on mutations in ATP1A2 and ATP1A3 genes respectively, with over 75% of AHC caused by a mutation in the ATP1A3 gene. Herewith, we report serial clinical follow-up data of monozygotic (MZ) twin sisters, who presented in early life bath-induced dystonia, signs of acute encephalopathy at the age of 2 years, hemiplegic spells, and motor dysfunction after the age of 3 years, and in young/adult frequent episodes of headache with drastic reduction of paroxysmal motor attacks. The molecular analysis revealed a known pathogenic variant p.Asn773Ser (rs606231437) in ATP1A3 gene associated with an unusual and moderate AHC-2 phenotype, with mild cognitive impairment and lack of epilepsy. The aim of this study is to analyze the clinical phases of the MZ twins, and to investigate the novel genotype-phenotype correlation.
Assuntos
Hemiplegia/genética , Fenótipo , ATPase Trocadora de Sódio-Potássio/genética , Gêmeos Monozigóticos/genética , Feminino , Genótipo , Hemiplegia/patologia , Humanos , Mutação , Adulto JovemRESUMO
BACKGROUND: Neurotoxicity has been reported in about 5% of children treated with ifosfamide for tumors not involving the central nervous system. The entity of ifosfamide neurotoxicity can be of different degree, from very light and transient to fatal. CASE REPORTS: All cases of ifosfamide neurotoxicity recorded at the Pediatric Hematology and Oncology Unit in the 15-year period between 1989 and 2003 are reported. Five cases of neurotoxicity occurring during or immediately after ifosfamide infusion were recorded in children with both solid tumors or leukemia. The drug was administered in different chemotherapeutic associations and dosages. Concomitant clinical conditions possibly playing a role as risk factors were the administration of other neurotoxic drugs, the presence of cerebral metastasis, a subclinical lysis syndrome, and altered respiratory function. Symptoms were transient in all cases and consisted in all but one of partial or generalized seizures. In four cases the treatment was continued, substituting ifosfamide with cyclophosphamide. CONCLUSIONS: Particularly in patients presenting risk factors, we advise paying attention to the risk of ifosfamide neurotoxicity and rapidly suspending the drug administration to avoid irreparable damage to the central nervous system. Thereafter the treatment can be reassessed. If ifosfamide is considered the best option for the given case, it could be safely readministered in association with methylene blue or thiamine. If encephalopathy reappears, substitution of ifosfamide with cyclophosphamide could offer the same opportunities of cure to the patient.
Assuntos
Antineoplásicos Alquilantes/toxicidade , Ifosfamida/toxicidade , Neoplasias/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/patologia , Adolescente , Criança , Pré-Escolar , Ciclofosfamida/uso terapêutico , Feminino , Humanos , Ifosfamida/uso terapêutico , MasculinoRESUMO
BACKGROUND: There is no agreement on the prevalence, natural history and outcome of infantile spasms (IS) in neurofibromatosis type 1 (NF1). By contrast, its prevalence and outcome are well characterised in the setting of other neurocutaneous disorders (e.g. tuberous sclerosis). MATERIALS AND METHODS: The aim of the present study was to try to establish a genotype-phenotype correlation in IS in the setting of NF1. A retrospective (years 1990-2000) and prospective (years 2000-2006) study in three paediatric centres in Italy were taken as referral populations for: (1) children with NF1 and (2) neurological problems in childhood. RESULTS: Ten NF1 patients have had IS. The calculated population-based: (1) prevalence of IS in NF1 (0.76%) was higher than the reported frequency of IS in the general population (0.02-0.05%) and (2) frequency of NF1 in the IS series in two out of three centres (0.62-0.90%) was lower than the estimated frequencies in the literature (1.5-3.0%). Patients had psychomotor delay preceding the spasms (50%), symmetrical spasms (50%), typical (80%) and modified (20%) hypsarrhythmia and foci of spikes and waves and a good response to corticosteroid treatment (50%). Outcome was good in 30%. Imaging revealed high-signal foci in atypical locations (sub-cortical and central brain regions). Deoxyribonucleic acid analysis revealed three novel NF1 gene mutations without genotype-phenotype correlation. CONCLUSION: Even though the combination of IS and NF1 does not seem to be coincidental, it is certainly an unusual event in NF1--rarer than in other neurocutaneous disorders. Spasms in NF1 are not associated with specific genetic defects.
Assuntos
Neurofibromatose 1/complicações , Espasmos Infantis/etiologia , Adolescente , Criança , Pré-Escolar , Feminino , Genótipo , Humanos , Lactente , Itália/epidemiologia , Masculino , Mutação , Neurofibromatose 1/epidemiologia , Neurofibromatose 1/genética , Neurofibromina 1/genética , Fenótipo , Prevalência , Estudos Prospectivos , Estudos Retrospectivos , Espasmos Infantis/epidemiologiaRESUMO
INTRODUCTION: The prevalence and outcome of the most frequent type of epilepsy in infancy-infantile spasms (IS)-are well characterized in the setting of most neurocutaneous disorders. By contrast, still there is no study describing the natural history of IS in the setting of Sturge-Weber syndrome (SWS). MATERIALS AND METHODS: Two patients with SWS and IS were identified in our series and five in the literature. The aim of study is to evaluate the clinical, electroencephalographic (EEG) and imaging features of our cases and to compare our cases with those described in the literature. IS in the setting of SWS is an uncommon but possible event (2/19 patients seen over 13 years in our institutions). RESULTS: We confirmed the correlation between IS and severity of SWS cutaneous and neural (extension of leptomeningeal capillary malformation) phenotype. IS in SWS seems to be atypical both from a clinical viewpoint (they are asymmetric) and from a laboratory viewpoint (EEG is not classically hypsarrhythmic).
Assuntos
Espasmos Infantis/patologia , Síndrome de Sturge-Weber/patologia , Criança , Pré-Escolar , Eletroencefalografia/métodos , Feminino , Humanos , Lactente , Masculino , Índice de Gravidade de Doença , Espasmos Infantis/etiologia , Espasmos Infantis/fisiopatologia , Síndrome de Sturge-Weber/complicações , Síndrome de Sturge-Weber/fisiopatologiaRESUMO
BACKGROUND: Stroke is a rare disorder in childhood; among its risk factors, C677T mutations in the methylenetetrahydrofolate reductase (MTHFR) gene with secondary hyperhomocysteinemia are considered. PATIENTS AND METHODS: We report on a family in which two brothers had arterial ischemic stroke (AIS). One of these siblings came to our observation at the age of 4 years because of decreased motility of the right arm, mild hypotrophy of the right limbs, and frequent falls: brain magnetic resonance imaging revealed a large left AIS. Family history revealed that his older brother had died at the age of 7 due to AIS. An extensive metabolic investigation revealed a homozygous C677T [G80A-reduced folate carrier 1 (RFC1)] mutation in the MTHFR gene in both the affected siblings and in their healthy older brother and heterozygous mutations in the parents. None of these family members presented hyperhomocysteinemia. CONCLUSIONS: To the best of our knowledge, this is the first family with multiple AIS patients harboring homozygous MTHFR gene C677T (G80A-RFC1) mutations without associated hyperhomocysteinemia (the latter factor is usually considered as effector of vascular damage in patients with MTHFR C677T mutations). The pathogenic hypotheses of stroke in this family are considered.
Assuntos
Isquemia Encefálica/genética , Homozigoto , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Mutação , Irmãos , Acidente Vascular Cerebral/genética , Encéfalo/irrigação sanguínea , Encéfalo/patologia , Encéfalo/fisiopatologia , Isquemia Encefálica/enzimologia , Criança , Pré-Escolar , Família , Genótipo , Humanos , Hiper-Homocisteinemia/enzimologia , Hiper-Homocisteinemia/genética , Imageamento por Ressonância Magnética , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/deficiência , Acidente Vascular Cerebral/enzimologiaRESUMO
OBJECTIVE: To determine the frequency of neurologic manifestations in children with gluten sensitivity (GS) and the frequency of GS in children with neurologic disease. STUDY DESIGN: A total of 835 children with GS (based on positive titers for serum anti-gliadin antibody [AGA], anti-endomysial antibody [EMA], and anti-tissue transglutamine [tTG] antibody and a positive gut biopsy), representing the local childhood GS population in the town of Catania, Italy, were recruited, prospectively followed up, and screened for neurologic and psychiatric disturbances between 1991 and 2004. Serum AGA, EMA, and anti-tTG antibody titers were estimated in a prevalence sample of 630 consecutive children with neurologic disorders of unknown cause despite full investigation, 300 children with known neurologic syndromes, and 300 healthy children who served as controls. Statistical significance was assessed by the chi(2) test and Yates' chi(2) test. RESULTS: Neurologic or psychiatric problems were noted in 15 of 835 children with GS (1.79%) with previously diagnosed GS enteropathy (GSE). In 7 of 630 children (1.1%) with a cryptogenic neurologic disorder, GS was identified based on GS autoantibody screening. These 22 children had febrile seizures, epilepsy, headache, mental retardation, neuropathy, and bipolar disorder; no children had ataxia or cerebellar disturbances. The HLAs were DQ2 (n = 16), DQ8 (n = 4), and DQ2/DQ8 (n = 2). Two of the 300 healthy controls (0.66%) had GS. CONCLUSIONS: Based on our findings, the prevalence of neurologic/psychiatric manifestations in this group of children with GS was low but slightly higher than that in the controls (P = .041). Children with known (P = .772) and cryptogenic (P = 1.0) neurologic disorders did not exhibit a higher prevalence of GS.
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Doença Celíaca/complicações , Doença Celíaca/epidemiologia , Transtornos Mentais/epidemiologia , Doenças do Sistema Nervoso/epidemiologia , Adolescente , Biópsia , Estudos de Casos e Controles , Doença Celíaca/diagnóstico , Doença Celíaca/psicologia , Criança , Pré-Escolar , Feminino , Antígenos HLA/química , Humanos , Lactente , Masculino , Modelos Estatísticos , Fenótipo , Prevalência , Resultado do TratamentoRESUMO
Congenital lymphangiectasia-lymphedema is a rare disorder that presents with edema of the lower half of the body, the face, hands, and scrotum, or with protein-losing enteropathy owing to structural anomalies in the endothelium of the lymphatic system. We describe a biopsy-proven case of severe lymphangiectasia-lymphedema in a 16-year-old boy who was born to consanguineous parents and who, in addition, had mild (20 to 40 dB), early onset, sensorineural deafness and skin abnormalities, consisting of angiokeratomas of the face, hands, and feet, and also a large, localized angiokeratoma of the scrotum and the penis (Fordyce type). Both of the proband's parents had profound (>80 dB), congenital, mixed conductive/sensorineural, nonsyndromic deafness to low-mid frequencies. To the best of our knowledge, this constellation of lymphatic, skin, hearing, and systemic abnormalities seen in the proband has not been previously reported.
Assuntos
Angioceratoma/complicações , Perda Auditiva Neurossensorial/complicações , Linfangiectasia/complicações , Linfedema/complicações , Adolescente , Angioceratoma/patologia , Biópsia , Consanguinidade , Humanos , Linfangiectasia/congênito , Linfedema/congênito , Masculino , Neoplasias Penianas/complicações , Neoplasias Penianas/patologia , Escroto/patologia , Neoplasias Cutâneas/complicações , Neoplasias Cutâneas/patologiaRESUMO
We report on monozygotic twins with neonatal onset of daily reflex seizures triggered by hot water. Video record during the hot water bathing showed clinical signs consistent with a reflex seizure. The numbers of episodes were markedly reduced when the mother began bathing the children with reduced temperature bath water. At the age of 20 months, the twins developed episodes of paroxysmal disturbances including alternating hemiplegia. These two patients are the youngest reported cases of reflex hot water seizures, and the only reported cases in which reflex hot water seizures subsequently manifested episodes of alternating hemiplegia.
Assuntos
Epilepsia Reflexa/fisiopatologia , Hemiplegia/etiologia , Temperatura Alta , Confusão/etiologia , Confusão/psicologia , Eletroencefalografia , Epilepsia Reflexa/complicações , Epilepsia Reflexa/genética , Feminino , Lateralidade Funcional/fisiologia , Hemiplegia/psicologia , Humanos , Recém-Nascido , ATPase Trocadora de Sódio-Potássio/genética , Gêmeos Monozigóticos , ÁguaRESUMO
Polyneuritis cranialis is a rare disorder of multiple cranial nerve palsies without spinal cord involvement. The case reported is of a 10-year-old boy with multiple palsies involving cranial nerves III, IV, V, VI, VII, IX, X, XI, and XII cranial nerves, unilaterally or bilaterally. After initial, unsuccessful treatment, corticosteroids and acyclovir were administered. The patient dramatically improved after two cycles of intravenous immunoglobulins. He was left with a mild residual left VI nerve deficit, which fully remitted after 2 months.
Assuntos
Doenças dos Nervos Cranianos/tratamento farmacológico , Imunoglobulinas Intravenosas/uso terapêutico , Neurite (Inflamação)/tratamento farmacológico , Criança , Humanos , Masculino , Recuperação de Função FisiológicaRESUMO
This study aimed to evaluate the long-term efficacy and safety of topiramate in treating children with drug-resistant epilepsy. A multicentric, retrospective, open-label, add-on study was undertaken of 277 children (mean age 8.4 years; range 12 months to 16 years) affected by drug-resistant epilepsy. The efficacy was rated according to the seizure types and epilepsy syndrome. After a mean period of 27.5 months of treatment (range 24-61 months), 11 patients (4%) were seizure free and 56 (20%) had more than 50% reduction in seizure frequency. The efficacy of topiramate treatment was noted in localization-related epilepsy and in generalized epilepsy. In addition, in a group of 114 patients, we compared the initial efficacy (evaluated after a mean of 9 months of follow-up) and the retention at a mean of 30 months of topiramate with regard to loss of efficacy (defined as the return to the baseline seizure frequency). Fifty-five (48%) of 114 patients were initial responders. The retention at a mean of 30 months was 23 of 114 patients (20%), 4 of whom (3.5%) were still seizure free. A loss of efficacy occurred in 32 of the 55 initial responders (58%). It was prominent in patients with generalized epilepsy, such as symptomatic infantile spasms and Lennox-Gastaut syndrome, as well as in those with Dravet syndrome. By contrast, a well-sustained topiramate efficacy was noted among patients with localization-related epilepsy. Globally, adverse events were observed in 161 patients (58%) and were mainly represented by weight loss, hyperthermia, sedation, and nervousness, which, in most cases, disappeared after slowing titration or reducing the dosage of the drug. In conclusion, the present long-term study confirms that topiramate represents a useful drug effective in a wide range of seizures and epilepsy syndromes. Moreover, preliminary data seem to suggest that the efficacy of topiramate, when evaluated in the long-term perspective, is more sustained in localization-related epilepsy than in generalized epilepsy.
Assuntos
Anticonvulsivantes/efeitos adversos , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Frutose/análogos & derivados , Adolescente , Criança , Pré-Escolar , Relação Dose-Resposta a Droga , Resistência a Medicamentos , Feminino , Seguimentos , Frutose/efeitos adversos , Frutose/uso terapêutico , Humanos , Lactente , Masculino , Estudos Retrospectivos , Topiramato , Resultado do TratamentoRESUMO
PURPOSE: To determine clinical phenotypes, evolution and genetic background of a large family with a combination of two unusual forms of reflex epilepsies. METHOD: Phenotyping was performed in eighteen family members (10 F, 8 M) including standardized EEG recordings with intermittent photic stimulation (IPS). Genetic analyses (linkage scans, Whole Exome Sequencing (WES) and Functional studies) were performed using photoparoxysmal EEG responses (PPRs) as affection status. RESULTS: The proband suffered from speaking induced jaw-jerks and increasing limb jerks evoked by flickering sunlight since about 50 years of age. Three of her family members had the same phenotype. Generalized PPRs were found in seven members (six above 50 years of age) with myoclonus during the PPR. Evolution was typical: Sensitivity to lights with migraine-like complaints around adolescence, followed by jerks evoked by lights and spontaneously with dropping of objects, and strong increase of light sensitivity and onset of talking induced jaw jerks around 50 years. Linkage analysis showed suggestive evidence for linkage to four genomic regions. All photosensitive family members shared a heterozygous R129C mutation in the SCNM1 gene that regulates splicing of voltage gated ion channels. Mutation screening of 134 unrelated PPR patients and 95 healthy controls, did not replicate these findings. CONCLUSION: This family presents a combination of two rare reflex epilepsies. Genetic analysis favors four genomic regions and points to a shared SCNM1 mutation that was not replicated in a general cohort of photosensitive subjects. Further genetic studies in families with similar combination of features are warranted.
Assuntos
Proteínas de Transporte/genética , Epilepsia Reflexa/genética , Epilepsia Reflexa/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Família , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Países Baixos , Linhagem , Fenótipo , Estimulação Luminosa , Fatores de Processamento de RNA , População Branca/genética , Adulto JovemRESUMO
The occurrence of seizures in patients with fragile X syndrome (Fra-X) is reported. Among the 30 patients, six had epilepsy that was particularly severe and two also showed atypical facial dysmorphism that was different from that seen in classical Fra-X. From the study performed in this series of Fra-X patients the authors arrived at the following conclusions. (1) The occurrence of seizures in Fra-X population is around 20%, as reported in the literature. (2) The EEG pattern of benign childhood epilepsy with central-temporal spikes (BCECTS) was found in only three patients (10%). (3) According to the pattern of seizures and EEGs, four groups may be recognizable, the less frequent being the uncommon group characterized by severe epilepsy unresponsive to treatment. (4) In this group atypical facial dysmorphism (although not similar in the two patients and different from the classical facial pattern of Fra-X) was found. The authors maintain that additional genetic factors might influence the clinical course and neurological aspects of Fra-X syndrome.
Assuntos
Epilepsia/fisiopatologia , Síndrome do Cromossomo X Frágil/fisiopatologia , Potenciais de Ação/fisiologia , Adolescente , Córtex Cerebral/fisiopatologia , Criança , Pré-Escolar , Resistência a Medicamentos/fisiologia , Eletroencefalografia , Humanos , MasculinoRESUMO
The objective of this study was to assess brain involvement through the presence of antineuronal antibodies in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcus (PANDAS) and in uncomplicated active Group A streptococcal infection. We compared serum antibrain antibody to human basal ganglia sections assessed by indirect tissue immunofluorescence in two groups: a PANDAS group, comprised of 22 patients (mean age 10.1 years; 20 male, 2 female) who met strict National Institutes of Mental Health diagnostic criteria for PANDAS and had clinically active tics or obsessive-compulsive disorder, or both; and a GABHS control group consisting of 22 patients (mean age 9.1 years; 15 mol/L, 7 female) with clinical evidence of active Group A beta-hemolytic streptococcal (GABHS) infection confirmed by throat culture and elevated antistreptolysin O titers but without history or clinical evidence of tics or obsessive-compulsive disorder. We observed positive anti-basal ganglia staining (defined as detectable staining at 1:10 serum dilution) in 14/22 patients in the PANDAS group (64%) but only 2/22 (9%) in the GABHS control group (P < 0.001, Fisher's exact test). These results suggest that antibrain antibodies are present in children with PANDAS that cannot be explained merely by a history of GABHS infection.