RESUMO
We report a 4-year-old girl presenting with sudden severe bilateral visual loss. Ophthalmological examination revealed optic disc pallor. Further neurological examination was normal. Brain magnetic resonance imaging (MRI) suggested chiasmal optic neuritis, and further etiological investigations were negative. We review the literature on the incidence and underlying etiology of chiasmal optic neuritis in childhood.
Assuntos
Quiasma Óptico/patologia , Neurite Óptica/diagnóstico , Pré-Escolar , Feminino , Humanos , Imageamento por Ressonância Magnética , Neurite Óptica/complicações , Transtornos da Visão/etiologiaRESUMO
OBJECTIVE: We have recently shown that de novo mutations in the TUBA1A gene are responsible for a wide spectrum of neuronal migration disorders. To better define the range of these abnormalities, we searched for additional mutations in a cohort of 100 patients with lissencephaly spectrum for whom no mutation was identified in DCX, LIS1 and ARX genes and compared these data to five previously described patients with TUBA1A mutations. RESULTS: We detected de novo TUBA1A mutations in six patients and highlight the existence of a prominent form of TUBA1A related lissencephaly. In four patients, the mutations identified, c.1190T>C (p.L397P), c.1265G>A (p.R422H), c.1264C>T (p.R422C), c.1306G>T (p.G436R), have not been reported before and in two others, the mutation corresponds to a recurrent missense mutation, c.790C>T (p.R264C), likely to be a hot spot of mutation. All together, it emerges that the TUBA1A related lissencephaly spectrum ranges from perisylvian pachygyria, in the less severe form, to posteriorly predominant pachygyria in the most severe, associated with dysgenesis of the anterior limb of the internal capsule and mild to severe cerebellar hypoplasia. When compared with a large series of lissencephaly of other origins (ILS17, ILSX or unknown origin), these features appear to be specific to TUBA1A related lissencephaly. In addition, TUBA1A mutated patients share a common clinical phenotype that consists of congenital microcephaly, mental retardation and diplegia/tetraplegia. CONCLUSIONS: Our data highlight the presence of consistent and specific abnormalities that should allow the differentiation of TUBA1A related lissencephalies from those related to LIS1, DCX and ARX genes.
Assuntos
Lisencefalia/genética , Tubulina (Proteína)/genética , Criança , Pré-Escolar , Feminino , Heterozigoto , Humanos , Lactente , Lisencefalia/patologia , Imageamento por Ressonância Magnética , Masculino , Mutação de Sentido Incorreto , Fenótipo , Tubulina (Proteína)/químicaRESUMO
We examined the efficacy, optimum dosage and adverse effects of levetiracetam in two prospective trials in children with epilepsy. In the add-on trial, 67 children between 6 months and 16 years were included. In the mono-therapy trial, 10 children between 4 years and 16 years were included. Levetiracetam was titrated up to an optimal dosage for every individual patient, depending on efficacy and tolerability, and reflecting clinical practice. The range of dosages used was between 12 and 62 mg/kg/day, with a median of 33 mg/kg/day. Overall, 20 weeks after the start of levetiracetam, there was a median seizure reduction of 60% (add-on trial 50%; mono-therapy trial 81%). Levetiracetam was equally effective for partial and generalized seizures. Side effects were less common in the mono-therapy trial. Tiredness (7.8%) and aggressiveness (5%) were the most common side effects, and were dose-related, but were no reason to discontinue levetiracetam. In 25% of the children, a positive effect was seen on behaviour and/or alertness. This could not be related directly to seizure control. Overall, these two clinical trials confirm that levetiracetam is a broad spectrum anti-epileptic drug with a favourable safety profile. The positive effect on behaviour needs further quantitative study.
Assuntos
Anticonvulsivantes/administração & dosagem , Epilepsias Parciais/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Piracetam/análogos & derivados , Piracetam/administração & dosagem , Adolescente , Anticonvulsivantes/efeitos adversos , Criança , Pré-Escolar , Estudos de Coortes , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Eletroencefalografia/efeitos dos fármacos , Epilepsias Mioclônicas/tratamento farmacológico , Epilepsias Parciais/induzido quimicamente , Epilepsia Tipo Ausência/tratamento farmacológico , Epilepsia Generalizada/induzido quimicamente , Feminino , Humanos , Lactente , Levetiracetam , Masculino , Piracetam/efeitos adversos , Estudos Prospectivos , Síndrome , Resultado do TratamentoRESUMO
It has been proposed that the pI(Cln) protein forms a nucleotide-sensitive plasma membrane anion channel with a GXGXG motif being an essential component of the extracellular nucleotide-binding site. To evaluate this hypothesis, we have performed voltage-clamp experiments on Xenopus laevis oocytes injected with RNA encoding a rat mutant pI(Cln) in which the three glycines of the putative nucleotide-binding site have been changed into alanines (G54A; G56A; G58A). The injected oocytes displayed outwardly rectifying anion currents, which were voltage-dependently blocked by extracellular cAMP, but which were not affected by removal of extracellular Ca2+. Furthermore, the mutation did not affect the voltage-dependent inactivation. We therefore conclude that there is no evidence in favour of an extracellular nucleotide-binding site in pI(Cln).
Assuntos
Canais de Cloreto/química , Canais Iônicos , Animais , Cálcio/fisiologia , Canais de Cloreto/fisiologia , AMP Cíclico/farmacologia , Condutividade Elétrica , Espaço Extracelular , Ativação do Canal Iônico , Potenciais da Membrana , Mutagênese Sítio-Dirigida , Oócitos , Ratos , Relação Estrutura-Atividade , Proteínas de Xenopus , Xenopus laevisRESUMO
Possible heteromultimer formation between Kv- and Kir-type K+ channels was investigated, in connection with the known functional diversity of K+ channels in vivo. Voltage-clamp experiments were performed on Xenopus oocytes, either injected with concatenated Kir2.1-Kv1.1 mRNA, or co-injected with Kv1.1 and Kir2.1 mRNA. K+ currents could be approximated by the algebraic sum of the 2 K+ current types alone. The tandem construct did not show functional expression, although it could be detected by Western blotting. We conclude that Kv1.1 and Kir2.1 alpha-subunit proteins fail to assemble and do not contribute functional diversity to K+ channels.
Assuntos
Ativação do Canal Iônico/fisiologia , Canais de Potássio Corretores do Fluxo de Internalização , Canais de Potássio/metabolismo , Animais , Western Blotting , Clonagem Molecular , Expressão Gênica , Oócitos , Técnicas de Patch-Clamp , Canais de Potássio/química , Canais de Potássio/genética , Conformação Proteica , RNA Mensageiro/metabolismo , Xenopus laevisRESUMO
Desmoplastic infantile ganglioglioma is a rare intracranial tumor of early childhood with a usually excellent prognosis despite malignant features both radiologically and histologically. We present the case of a desmoplastic infantile ganglioglioma with histologically highly anaplastic features and both intracerebral and pial metastases. After partial resection the tumor was rapidly progressive and new metastases appeared. A combination of vincristine and carboplatinum was used according to the Low Grade Glioma Protocol of the International Society of Pediatric Oncology, with a temporary good response. When histologically characterized by highly anaplastic features, it seems the biologic behavior of this tumor remains uncertain. The aggressive behavior and the responsiveness to chemotherapy in this case may challenge the belief in the benign nature of these rare tumors.
Assuntos
Neoplasias Encefálicas/patologia , Ganglioglioma/secundário , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/análise , Encéfalo/patologia , Neoplasias Encefálicas/química , Neoplasias Encefálicas/terapia , Carboplatina/administração & dosagem , Pré-Escolar , Desmina , Evolução Fatal , Feminino , Ganglioglioma/química , Ganglioglioma/terapia , Humanos , Imuno-Histoquímica , Imageamento por Ressonância Magnética , Proteínas de Neoplasias/análise , Vincristina/administração & dosagemRESUMO
In this open-label add-on study of levetiracetam in refractory childhood epilepsy syndromes, we studied the effect of a rapid introduction of levetiracetam on the total seizure frequency in 21 children, known to have partial and generalized seizures. Starting dosage was 10 mg/kg/day, increased every 4th day by 10 mg/kg up to a maximum of 60 mg/kg/day, depending on efficacy and tolerability. In this highly refractory population, 47% showed a seizure frequency reduction of more than 50%. Levetiracetam was effective both in partial and generalized seizures, with a significant effect on myoclonic seizures. Only mild side-effects were observed in four of 21 children, at a dosage of more than 40 mg/kg/day.
Assuntos
Anticonvulsivantes/uso terapêutico , Epilepsias Parciais/tratamento farmacológico , Epilepsia Generalizada/tratamento farmacológico , Piracetam/análogos & derivados , Piracetam/uso terapêutico , Adolescente , Anticonvulsivantes/administração & dosagem , Criança , Pré-Escolar , Esquema de Medicação , Feminino , Humanos , Lactente , Levetiracetam , Masculino , Piracetam/administração & dosagem , SíndromeRESUMO
In recent years, different research lines have examined the epileptogenic process in order to understand the different stages in this process, and with the hope that early recognition and intervention could prevent chronic epilepsy in patients with epileptic seizures. In animals, acquired epilepsy is studied most commonly with kindling models, status epilepticus models and traumatic brain injury models. Molecular genetic studies substantially help to understand age-specific channel and receptor abnormalities. Major progress has been made in recent years and we are now waiting for the first large scale multi-center clinical trials that test the possible anti-epileptogenic properties of anti-epileptic drugs or other compounds in well defined patient groups. In clinical practice, a structured diagnostic work-up in all patients with recurrent seizures is a first and necessary step in the recognition of patients at risk for developing chronic and refractory epilepsy.
Assuntos
Epilepsia/etiologia , Epilepsia/fisiopatologia , Animais , Anticonvulsivantes/farmacologia , Epilepsia/tratamento farmacológico , Humanos , Excitação Neurológica , Modelos AnimaisRESUMO
Clean intermittent (self)catheterisation (CIC) in combination with oral anticholinergic drugs (oxybutynin hydrochloride [OH] is the present standard therapy for neurogenic bladder dysfunction (NBD) with detrusor hyperactivity. However, complete suppression of detrusor contractions and complete urinary continence is not always obtained despite maximal dosage, and the high incidence of severe systemic anticholinergic side-effects often impairs therapeutic compliance, resulting in dose reduction or even discontinuation of therapy. The intravesical administration of OH has been shown recently to be an effective alternative for treating persistent detrusor hyperactivity, and occurrence and severity of systemic side-effects appeared to be significantly decreased. However, available data are limited from a paediatric view. Furthermore, it is our belief that the use of crushed OH tablets with consequent problems of impracticability accounts for the variable long-term patient compliance reported to be the only disadvantage to intravesical OH. Using an optimized drug preparation we demonstrate the superiority of intravesical OH for treatment of NBD in 15 children (range 0.6-13.75 years, mean 6.1) with incomplete detrusor activity suppression and/or intolerable systemic side-effects on oral OH therapy. Since the previous reported problems of impracticability and variable long-term patient compliance can be resolved by optimized drug preparation, we therefore conclude that the era of crushing OH tablets should be over in order to allow the intravesical OH therapy on a long-lasting and large-scale basis.
Assuntos
Antagonistas Colinérgicos/administração & dosagem , Ácidos Mandélicos/administração & dosagem , Disrafismo Espinal/complicações , Bexiga Urinaria Neurogênica/terapia , Cateterismo Urinário , Administração Intravesical , Adolescente , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Lactente , Masculino , Resultado do Tratamento , Bexiga Urinaria Neurogênica/etiologiaRESUMO
An infant with frequent upper airways infections presented syncopes during meals and weeping since the age of eleven months. Cardiac examination was always normal. At 14 months of age, an echocardiogram with colour Doppler demonstrated a severely stenotic isolated supramitral membrane with severe pulmonary hypertension. The membrane was immediately excised curing the malformation and suppressing definitively the syncopes, probably due to decreased cerebral blood flow during exertion. An echocardiogram should always be performed when syncopes remain unexplained in small children. It allows early diagnosis and treatment of congenital heart defects which do not have auscultatory findings especially those resulting in severe pulmonary venous obstruction.
Assuntos
Estenose da Valva Mitral/complicações , Síncope/etiologia , Ecocardiografia , Humanos , Hipertensão Pulmonar/etiologia , Hipertrofia Ventricular Direita/etiologia , Lactente , Masculino , Estenose da Valva Mitral/congênito , Estenose da Valva Mitral/diagnóstico , Estenose da Valva Mitral/cirurgia , Esforço FísicoRESUMO
This rare case of brain stem tethering presented with chronic and progressive geniculate neuralgia. In view of the fact that an occipital subcutaneous lipoma had been resected in childhood, it probably concerned a primary tethering, fitting in with an occult occipital dysraphism. Magnetic resonance imaging (MRI) clearly demonstrated an underlying tethering, causing a distortion of the brain stem. Consequently, this led to the hypothesis that the geniculate neuralgia could be explained by traction on the lower cranial nerves secondary to the brain stem displacement. Untethering resulted in a considerable decrease of the neuralgia. MRI proved to be essential in the diagnosis and treatment of this unusual case.
Assuntos
Tronco Encefálico/anormalidades , Doenças do Nervo Facial/etiologia , Adulto , Tronco Encefálico/patologia , Tronco Encefálico/cirurgia , Doenças do Nervo Facial/patologia , Doenças do Nervo Facial/cirurgia , Feminino , Humanos , Imageamento por Ressonância MagnéticaAssuntos
Soros Imunes , Bainha de Mielina/imunologia , Polirradiculopatia/imunologia , Animais , Axônios , Proteínas do Sistema Complemento , Técnicas de Cultura , Doenças Desmielinizantes/patologia , Feto , Gânglios Espinais/citologia , Humanos , Microscopia Eletrônica , Polirradiculopatia/sangue , Polirradiculopatia/líquido cefalorraquidiano , Roedores , Células de SchwannAssuntos
Tronco Encefálico , Encefalite , Autopsia , Peso Corporal , Encefalite/patologia , Humanos , Masculino , Pessoa de Meia-Idade , RecidivaRESUMO
BACKGROUND: Lissencephaly is a neuronal migration disorder leading to absent or reduced gyration and a broadened but poorly organized cortex. The most common form of lissencephaly is isolated, referred as classic or type 1 lissencephaly. Type 1 lissencephaly is mostly associated with a heterozygous deletion of the entire LIS1 gene, whereas intragenic heterozygous LIS1 mutations or hemizygous DCX mutations in males are less common. METHODS: Eighteen unrelated patients with type 1 lissencephaly were clinically and genetically assessed. In addition, patients with subcortical band heterotopia (n = 1) or lissencephaly with cerebellar hypoplasia (n = 2) were included. RESULTS: Fourteen new and seven previously described LIS1 mutations were identified. We observed nine truncating mutations (nonsense, n = 2; frameshift, n = 7), six splice site mutations, five missense mutations, and one in-frame deletion. Somatic mosaicism was assumed in three patients with partial subcortical band heterotopia in the occipital-parietal lobes or mild pachygyria. We report three mutations in exon 11, including a frameshift which extends the LIS1 protein, leading to type 1 lissencephaly and illustrating the functional importance of the WD domains at the C terminus. Furthermore, we present two patients with novel LIS1 mutations in exon 10 associated with lissencephaly with cerebellar hypoplasia type a. CONCLUSION: In contrast to previous reports, our data suggest that neither type nor position of intragenic mutations in the LIS1 gene allows an unambiguous prediction of the phenotypic severity. Furthermore, patients presenting with mild cerebral malformations such as subcortical band heterotopia or cerebellar hypoplasia should be considered for genetic analysis of the LIS1 gene.
Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Córtex Cerebral/anormalidades , Predisposição Genética para Doença/genética , Proteínas Associadas aos Microtúbulos/genética , Mutação/genética , Malformações do Sistema Nervoso/genética , Adolescente , Adulto , Movimento Celular/genética , Cerebelo/anormalidades , Córtex Cerebral/metabolismo , Córtex Cerebral/fisiopatologia , Criança , Pré-Escolar , Coristoma/genética , Coristoma/metabolismo , Análise Mutacional de DNA , Feminino , Marcadores Genéticos/genética , Testes Genéticos , Genótipo , Humanos , Lactente , Masculino , Malformações do Sistema Nervoso/metabolismo , Malformações do Sistema Nervoso/fisiopatologia , Penetrância , FenótipoRESUMO
Hereditary sensory and autonomic neuropathy type II (HSAN-II) is caused by recessive mutations in the HSN2 gene assigned to chromosome 12p13.33. The authors report three unrelated HSAN-II families with homozygous or compound heterozygous mutations resulting in the truncation of the HSN2 protein. Genotype-phenotype correlations indicated that HSN2 mutations are associated with an early childhood onset of a predominantly sensory neuropathy, complicated by acromutilations in both upper and lower limbs.
Assuntos
Cromossomos Humanos Par 12 , Neuropatias Hereditárias Sensoriais e Autônomas/genética , Mutação , Proteínas do Tecido Nervoso/genética , Adulto , Sequência de Bases , Mapeamento Cromossômico , Éxons , Feminino , Triagem de Portadores Genéticos , Genótipo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Íntrons , Masculino , Pessoa de Meia-Idade , Antígenos de Histocompatibilidade Menor , Linhagem , Fenótipo , Proteínas Serina-Treonina Quinases , Deleção de Sequência , Proteína Quinase 1 Deficiente de Lisina WNKRESUMO
Fibrodysplasia ossificans progressiva (FOP), a rare autosomal dominant disorder, is characterized by symmetrical congenital skeletal abnormalities and progressive heterotopic ossification of the connective tissues. At present, more than 300 years after the first report by Patin in 1648 in which he described the woman who "turned to wood", its pathogenesis remains largely unknown and its therapy is limited to symptom-modifying trials. However, significant progress has been recently made and new data on the molecular organization and regulation of normal and disordered bone induction are likely to lead to a more specific therapy. FOP is believed to be a genetic disorder characterized by a disturbed expression of the endochondral osteogenesis programme, and the remarkable "clues from the fly" reported by Kaplan et al. [8] in 1990 suggest a gain-of-function mutation in the genetic regulation of bone morphogenetic proteins.
Assuntos
Miosite Ossificante , Proteínas Morfogenéticas Ósseas , Criança , Diagnóstico Diferencial , Ácido Etidrônico/uso terapêutico , Substâncias de Crescimento/fisiologia , Humanos , Miosite Ossificante/diagnóstico , Miosite Ossificante/fisiopatologia , Miosite Ossificante/terapia , Proteínas/fisiologiaRESUMO
PURPOSE: To improve patient compliance with and acceptance of intravesical oxybutynin therapy for neurogenic bladder dysfunction we developed a stable oxybutynin solution that eliminates the complicated crushing procedure. MATERIALS AND METHODS: From January 1995 to January 1997 we prospectively evaluated 15 children with a mean age of 6.1 years with persistent detrusor hyperactivity or significant side effects on oral oxybutynin therapy who received intravesically 0.2 mg./kg. (maximum 5 mg.) of a stable oxybutynin solution (5 mg./5 ml., pH 5.85) twice daily. RESULTS: The oxybutynin solution remained stable up to 24 months. In 13 of the 15 children therapeutic compliance was excellent. Detrusor hyperactivity decreased and systemic side effects were absent or minimal. After 4 and 24 months mean cystometric bladder capacity plus or minus standard error of mean increased from 114+/-15.2 to 161+/-26.6 and 214+/-21.7 ml. (p <0.01), mean ratio of cystometric-to-expected bladder capacity increased from 0.88+/-0.12 to 1.18+/-0.14 and 1.24+/-0.16 (p <0.01), and end filling bladder pressure decreased from 57.0+/-7.1 to 25.6+/-4.4 and 30.8+/-4.4 cm. water (p <0.01), respectively. CONCLUSIONS: Intravesical instillation of a specially prepared oxybutynin solution is safe and reliable in children with persistent detrusor hyperactivity or side effects on oral oxybutynin therapy. Eliminating the complex crushing preparation of the solution by the child or parent has made this therapy easy to use and acceptable in the long term.
Assuntos
Antagonistas Colinérgicos/administração & dosagem , Ácidos Mandélicos/administração & dosagem , Cooperação do Paciente , Bexiga Urinaria Neurogênica/tratamento farmacológico , Administração Intravesical , Adolescente , Criança , Pré-Escolar , Estabilidade de Medicamentos , Feminino , Humanos , Lactente , Masculino , Estudos Prospectivos , SoluçõesRESUMO
Parental telephone calls and visits are analysed during the entire stay of the premature infant in the neonatal special care unit in Leuven, Belgium. It is concluded that the summation of parental visits and telephone calls is a better measure of parental contact than parental visits or parental telephone calls separately. This measure is significantly related to parental profession. It is not significantly related to the distance between the family home and the hospital, to the presence of a car or a telephone at home or to the presence of siblings. Parental contacts remain stable during the entire stay of the baby in the neonatal special care unit.
Assuntos
Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Pais , Feminino , Humanos , Recém-Nascido , Masculino , Ocupações , Relações Pais-Filho , TelefoneRESUMO
We present a patient with juvenile neuronal ceroid lipofuscinosis who developed a neuroleptic malignant syndrome when treated for hallucinations with a very low dose of risperidone, an atypical neuroleptic medication with usually few extrapyramidal side-effects. The loss of dopaminergic neurons in this condition may make these patients more vulnerable to this severe adverse effect.