RESUMEN
OBJECTIVE: Mutations in the CDKL5 gene cause an early-onset epileptic encephalopathy. To date, little is known about effective antiepileptic treatment in this disorder. METHOD: Accordingly, the aim of this retrospective study was to explore the role of different antiepileptic drugs (AEDs) and the ketogenic diet (KD) in the treatment of this rare genetic disorder. We evaluated the efficacy in 39 patients with CDKL5 mutations at 3, 6 and 12 months after the introduction of each treatment. One patient was lost to follow-up after 6 and 12 months. RESULTS: The responder rate (>50% reduction in seizure frequency) to at least one AED or KD was 69% (27/39) after 3 months, 45% (17/38) after 6 months and 24% (9/38) after 12 months. The highest rate of seizure reduction after 3 months was reported for FBM (3/3), VGB (8/25), CLB (4/17), VPA (7/34), steroids (5/26), LTG (5/23) and ZNS (2/11). Twelve patients (31%) experienced a seizure aggravation to at least one AED. Most patients showed some but only initial response to various AEDs with different modes of actions. SIGNIFICANCE: Considering both age-related and spontaneous fluctuation in seizure frequency and the unknown impact of many AEDs or KD on cognition, our data may help defining realistic treatment goals and avoiding overtreatment in patients with CDKL5 mutations. There is a strong need to develop new treatment strategies for patients with this rare mutation.
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Anticonvulsivantes/uso terapéutico , Dieta Cetogénica , Epilepsia/dietoterapia , Epilepsia/tratamiento farmacológico , Adulto , Epilepsia/genética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Proteínas Serina-Treonina Quinasas/genética , Estudios Retrospectivos , Convulsiones/prevención & control , Resultado del Tratamiento , Adulto JovenRESUMEN
Congenital disorders of glycosylation (CDG) are a group of hereditary metabolic diseases characterized by abnormal glycosylation of proteins and lipids. Often, multisystem disorders with central nervous system involvement and a large variety of clinical symptoms occur. The main characteristics are developmental delay, seizures, and ataxia. In this paper we report the clinical and biochemical characteristics of a 5-year-old girl with a defective galactosylation of N-glycans, resulting in developmental delay, muscular hypotonia, epileptic seizures, inverted nipples, and visual impairment. Next generation sequencing revealed a de novo mutation (c.797G > T, p.G266V) in the X-chromosomal gene SLC35A2 (solute carrier family 35, UDP-galactose transporter, member A2; MIM 300896). While this mutation was found heterozygous, random X-inactivation of the normal allele will lead to loss of normal SLC35A2 activity in respective cells. The functional relevance of the mutation was demonstrated by complementation of UGT-deficient MDCK-RCA(r) and CHO-Lec8 cells by normal UGT-expression construct but not by the mutant version. The effect of dietary galactose supplementation on glycosylation was investigated, showing a nearly complete normalization of transferrin glycosylation.
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Trastornos Congénitos de Glicosilación/genética , Trastornos Congénitos de Glicosilación/terapia , Proteínas de Transporte de Monosacáridos/genética , Animales , Células CHO , Preescolar , Cricetinae , Cricetulus , Análisis Mutacional de ADN , Perros , Femenino , Galactosa/uso terapéutico , Humanos , Células de Riñón Canino Madin Darby , Proteínas de Transporte de Monosacáridos/deficiencia , FenotipoRESUMEN
OBJECTIVE: Limbic encephalitis is rare in people <18 years of age and rarely given a formal diagnosis. DESIGN: Retrospective study on presentation and outcome of children and adolescents with the clinico-radiological syndrome of limbic encephalitis tested for specific neuronal autoantibodies (Abs) over 3.5 years. SETTING: Assessment, diagnosis, treatment and follow-up at 12 neuropaediatric and neurological departments in Europe, with Abs determined in Bonn, Germany and Oxford, UK. PATIENTS: Ten patients <18 years of age who presented with a disorder mainly affecting the limbic areas of <5 years' duration with MRI evidence of mediotemporal encephalitis (hyperintense T2/FLAIR signal, resolving over time). RESULTS: Median age at disease onset was 14 years (range 3-17). Eight patients had defined Abs: one each with Hu or Ma1/2 Abs, four with high titre glutamic acid decarboxylase (GAD) Abs, two of whom had low voltage-gated potassium channel (VGKC) Abs and two with only low titre VGKC Abs. A tumour was only found in the patient with Hu Abs (a neuroblastoma). After a median follow-up of 15 months with corticosteroid or intravenous immunoglobulin treatment, starting after a median of 4 months, two patients recovered, eight remained impaired and one died. CONCLUSIONS: Limbic encephalitis is a disease that can occur in childhood or adolescence with many of the hallmarks of the adult disorder, suggesting that both result from similar pathogenic processes. Since most of the cases were non-paraneoplastic, as now also recognised in adults, more systematic and aggressive immunotherapies should be evaluated in order to improve outcomes.
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Encefalitis Límbica/diagnóstico , Adolescente , Autoanticuerpos/sangre , Encéfalo/patología , Niño , Preescolar , Femenino , Estudios de Seguimiento , Glucocorticoides/uso terapéutico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Encefalitis Límbica/tratamiento farmacológico , Encefalitis Límbica/inmunología , Imagen por Resonancia Magnética , Masculino , Neuroblastoma/diagnóstico , Neuroblastoma/tratamiento farmacológico , Neuroblastoma/inmunología , Neuronas/inmunología , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/tratamiento farmacológico , Síndromes Paraneoplásicos/inmunología , Pronóstico , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
OBJECTIVE: Prospective memory (PM) describes the ability to fulfill previously planned intentions and is highly dependent on executive functions. Previous studies have shown deficits in executive functions in patients with juvenile myoclonic epilepsy (JME) and in their unaffected siblings. JME has a strong genetic predisposition and it is hypothesized that cognitive deficits are also genetically determined. The present study aimed at investigating potential differences in PM between patients with JME, their siblings, and healthy controls. METHODS: Nineteen patients with JME, 21 siblings, and 21 healthy controls were examined with a complex PM paradigm allowing us to evaluate the different phases of PM (i.e., intention formation, intention retention, intention initiation, intention execution). RESULTS: Patients with JME and siblings showed specific deficits during intention formation and intention execution of PM. Patients with JME were more impaired than both siblings and healthy controls. Correlation analysis revealed an influence of planning on prospective memory abilities in patients with JME. CONCLUSION: The results of this study support the hypothesis of frontal dysfunctions being part of the epileptic syndrome and therefore genetically determined. As in this study patients with JME are more severely cognitively impaired than their siblings, additional influencing factors, such as side effects of anticonvulsants or cognitive effects of subclinical epileptic discharges, might contribute to patients' performance.
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Cognición , Función Ejecutiva , Memoria , Epilepsia Mioclónica Juvenil/psicología , Hermanos/psicología , Adolescente , Adulto , Estudios de Casos y Controles , Electroencefalografía , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Epilepsia Mioclónica Juvenil/genética , Epilepsia Mioclónica Juvenil/fisiopatología , Pruebas Neuropsicológicas , Retención en Psicología , Adulto JovenRESUMEN
This 12-week open label study explored cognitive and seizure outcomes of 53 children treated with topiramate (TPM). The digit symbol test and verbal learning memory test were administered at baseline and study endpoint. Topiramate was started either in monotherapy or add-on therapy. Overall, 57% of children experienced a ≥50% seizure reduction, 36% became seizure free and cognitive testing revealed no significant changes during TPM therapy. Due to the heterogeneity of the study population, post hoc analyses were added to compare patients in initial or conversion to TPM monotherapy as well as patients who continued add-on therapy. Verbal learning memory test parameters showed neither significant differences within any subgroup comparing baseline with endpoint nor significant differences between described subgroups except for one finding. The digit symbol test revealed no differences between each subgroup between baseline and endpoint. Comparing pre-post differences, TPM monotherapy was associated with better cognitive outcomes than treatment in add-on therapy. These results have to be interpreted with caution given the short study duration and the heterogeneity of the study population. Despite these limitations, our overall results suggest that treatment with topiramate is associated with improved seizure control without significant changes in cognitive functions at the low doses tested.
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Anticonvulsivantes/uso terapéutico , Trastornos del Conocimiento/tratamiento farmacológico , Epilepsia/tratamiento farmacológico , Fructosa/análogos & derivados , Convulsiones/tratamiento farmacológico , Adolescente , Anticonvulsivantes/farmacología , Peso Corporal/efectos de los fármacos , Niño , Trastornos del Conocimiento/etiología , Relación Dosis-Respuesta a Droga , Epilepsia/complicaciones , Femenino , Fructosa/farmacología , Fructosa/uso terapéutico , Humanos , Masculino , Trastornos de la Memoria/tratamiento farmacológico , Trastornos de la Memoria/etiología , Pruebas Neuropsicológicas , Estudios Prospectivos , Escalas de Valoración Psiquiátrica , Convulsiones/etiología , Índice de Severidad de la Enfermedad , Método Simple Ciego , Factores de Tiempo , Topiramato , Aprendizaje Verbal/efectos de los fármacosRESUMEN
OBJECTIVE: Maximum seizure control, preservation of cognition, and prevention of developmental hindrance are major aims of the pharmacological treatment of children and adolescents with epilepsy. Herewith we introduce the junior version of EpiTrack, a 12- to 15-minute screening test for monitoring the cognitive effects of antiepileptic drug treatment in children and adolescents aged 6 to 18. METHODS: The test, which comprises six subtests (Speed, Flexibility, Planning, Response Inhibition, Word Fluency, Working Memory), was administered to 277 children and adolescents aged 6-18 years, 111 of whom were retested after an interval of 3 months. For the first clinical validation, 155 patients (46% idiopathic/benign, 62% seizure free) were evaluated. RESULTS: Standardization and correction for age resulted in a mean score of 33 ± 2 points, which was no longer correlated with age (r=0.005). The retest practice effect was 0.7 ± 2 points, and the reliability r(tt)=0.78. Factor analysis indicated one executive factor in controls and patients. In the epilepsy group, 50% of the patients were impaired (controls 14%). Number of antiepileptic drugs, use/no use of individual drugs, type of epilepsy, earlier age at onset, generalized tonic-clonic seizures, and history of febrile seizures made a difference in test performance. For patients and controls, EpiTrack scores reflected parents' performance ratings and the children's needs for extra education. CONCLUSION: The junior version of EpiTrack appears to be a valid and reliable screening tool for the assessment of executive functions in children and adolescents. Future studies with a repeated measurement design must show how well this tool is suited for the tracking of cognitive effects of antiepileptic drug treatment.
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Anticonvulsivantes/efectos adversos , Anticonvulsivantes/farmacología , Atención/efectos de los fármacos , Trastornos del Conocimiento/inducido químicamente , Trastornos del Conocimiento/diagnóstico , Función Ejecutiva/efectos de los fármacos , Pruebas Neuropsicológicas , Adolescente , Factores de Edad , Análisis de Varianza , Anticonvulsivantes/uso terapéutico , Niño , Epilepsia/tratamiento farmacológico , Epilepsia/fisiopatología , Femenino , Humanos , Masculino , Análisis de Regresión , Reproducibilidad de los ResultadosRESUMEN
Neurodegeneration with brain iron accumulation encompasses a heterogeneous group of rare neurodegenerative disorders that are characterized by iron accumulation in the brain. Severe generalized dystonia is frequently a prominent symptom and can be very disabling, causing gait impairment, difficulty with speech and swallowing, pain and respiratory distress. Several case reports and one case series have been published concerning therapeutic outcome of pallidal deep brain stimulation in dystonia caused by neurodegeneration with brain iron degeneration, reporting mostly favourable outcomes. However, with case studies, there may be a reporting bias towards favourable outcome. Thus, we undertook this multi-centre retrospective study to gather worldwide experiences with bilateral pallidal deep brain stimulation in patients with neurodegeneration with brain iron accumulation. A total of 16 centres contributed 23 patients with confirmed neurodegeneration with brain iron accumulation and bilateral pallidal deep brain stimulation. Patient details including gender, age at onset, age at operation, genetic status, magnetic resonance imaging status, history and clinical findings were requested. Data on severity of dystonia (Burke Fahn Marsden Dystonia Rating Scale-Motor Scale, Barry Albright Dystonia Scale), disability (Burke Fahn Marsden Dystonia Rating Scale-Disability Scale), quality of life (subjective global rating from 1 to 10 obtained retrospectively from patient and caregiver) as well as data on supportive therapy, concurrent pharmacotherapy, stimulation settings, adverse events and side effects were collected. Data were collected once preoperatively and at 2-6 and 9-15 months postoperatively. The primary outcome measure was change in severity of dystonia. The mean improvement in severity of dystonia was 28.5% at 2-6 months and 25.7% at 9-15 months. At 9-15 months postoperatively, 66.7% of patients showed an improvement of 20% or more in severity of dystonia, and 31.3% showed an improvement of 20% or more in disability. Global quality of life ratings showed a median improvement of 83.3% at 9-15 months. Severity of dystonia preoperatively and disease duration predicted improvement in severity of dystonia at 2-6 months; this failed to reach significance at 9-15 months. The study confirms that dystonia in neurodegeneration with brain iron accumulation improves with bilateral pallidal deep brain stimulation, although this improvement is not as great as the benefit reported in patients with primary generalized dystonias or some other secondary dystonias. The patients with more severe dystonia seem to benefit more. A well-controlled, multi-centre prospective study is necessary to enable evidence-based therapeutic decisions and better predict therapeutic outcomes.
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Encefalopatías/terapia , Encéfalo/fisiopatología , Estimulación Encefálica Profunda/métodos , Distonía/terapia , Hierro/metabolismo , Enfermedades Neurodegenerativas/terapia , Adolescente , Adulto , Encefalopatías/fisiopatología , Niño , Preescolar , Estimulación Encefálica Profunda/efectos adversos , Distonía/fisiopatología , Femenino , Lateralidad Funcional , Globo Pálido/fisiopatología , Humanos , Lactante , Masculino , Enfermedades Neurodegenerativas/fisiopatología , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: To explore the involvement of M-type potassium channels KCNQ2, Q3, and Q5 in the pathogenesis of common idiopathic epilepsies. METHODS: Sequence analysis of the KCNQ2, Q3, and Q5 coding regions was performed in a screening sample consisting of 58 nuclear families with rolandic epilepsy. Subsequently, an association study was conducted for all discovered variants in a case-control sample comprising 459 German patients with idiopathic generalized epilepsy (IGE) and 462 population controls. RESULTS: An in-frame deletion of codon 116 in KCNQ2 (p.Lys116del) and a missense mutation in KCNQ3 (p.Glu299Lys) were detected in two index cases exhibiting rolandic epilepsy and benign neonatal convulsions. Both mutations resulted in reduced potassium current amplitude in Xenopus oocytes. Mutation analysis of families with rolandic epilepsy without neonatal seizures discovered three novel missense variations (KCNQ2 p.Ile592Met, KCNQ3 p.Ala381Val, KCNQ3 p.Pro574Ser). The KCNQ2 p.Ile592Met variant displayed a significant reduction of potassium current amplitude in Xenopus oocytes and was present only once in 552 controls. Both missense variants identified in KCNQ3 (p.Ala381Val and p.Pro574Ser) were present in all affected family members and did not occur in controls, but did not show obvious functional abnormalities. The KCNQ3 missense variant p.Pro574Ser was also detected in 8 of 455 IGE patients but not in 454 controls (p = 0.008). In KCNQ2, a silent single nucleotide polymorphism (rs1801545) was found overrepresented in both epilepsy samples (IGE, p = 0.004). CONCLUSION: Sequence variations of the KCNQ2 and KCNQ3 genes may contribute to the etiology of common idiopathic epilepsy syndromes.
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Epilepsia/clasificación , Epilepsia/genética , Canal de Potasio KCNQ2/genética , Canal de Potasio KCNQ3/genética , Mutación , Adolescente , Adulto , Animales , Estudios de Casos y Controles , Preescolar , Análisis Mutacional de ADN , Epilepsia/patología , Femenino , Humanos , Recién Nacido , Masculino , Mutación Missense , Linaje , Síndrome , Xenopus laevisRESUMEN
Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder selectively affecting axons of spinal cord motoneurons. Classical mutations in the most frequent HSP gene SPAST (spastin protein) act through haploinsufficiency by abolishing the activity of a C-terminal ATPase domain or by interfering with expression from the affected allele. N-terminal missense variants have been suggested to represent rare polymorphisms, to cause unusually mild phenotypes, and to aggravate the effect of a classical mutation. We confirm these associations for p.S44L but do not detect two other variants (p.E43Q; p.P45Q) in HSP patients and controls. We show that neither of several disease mechanisms associated with classical SPAST mutations applies to the N-terminal variants. Instead, all three alterations enhance the stability of one of two alternative spastin isoforms. Their phenotypic effect may thus not be mediated by haploinsufficiency but by increasing isoform competition for interacting proteins, substrates or oligomerization partners.
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Adenosina Trifosfatasas/genética , Predisposición Genética a la Enfermedad/genética , Mutación Missense/genética , Paraplejía Espástica Hereditaria/genética , Paraplejía Espástica Hereditaria/metabolismo , Adolescente , Adulto , Edad de Inicio , Empalme Alternativo , Niño , Preescolar , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Pruebas Genéticas , Variación Genética , Genotipo , Haplotipos , Humanos , Masculino , Linaje , Fenotipo , Polimorfismo Genético , Isoformas de Proteínas/genética , Estructura Terciaria de Proteína/genética , Paraplejía Espástica Hereditaria/fisiopatología , EspastinaRESUMEN
The authors conducted a double-blind, placebo-controlled, crossover study to investigate the efficacy of oral zolmitriptan in the treatment of migraine in children and adolescents. Patients (n = 32) received placebo, zolmitriptan 2.5 mg, and ibuprofen 200 to 400 mg to treat three consecutive migraine attacks. Pain relief rates after 2 hours were 28% for placebo, 62% for zolmitriptan, and 69% for ibuprofen (p < 0.05). Both drugs are well tolerated with only mild side effects.
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Ibuprofeno/uso terapéutico , Trastornos Migrañosos/tratamiento farmacológico , Oxazolidinonas/uso terapéutico , Triptaminas/uso terapéutico , Administración Oral , Adolescente , Antiinflamatorios no Esteroideos/administración & dosificación , Antiinflamatorios no Esteroideos/uso terapéutico , Niño , Método Doble Ciego , Femenino , Humanos , Ibuprofeno/efectos adversos , Oxazolidinonas/efectos adversos , Agonistas de Receptores de Serotonina/administración & dosificación , Agonistas de Receptores de Serotonina/uso terapéutico , Triptaminas/efectos adversosRESUMEN
PURPOSE: To evaluate single photon emission computed tomography (SPECT) using the amino acid l-3-[123I]-alpha-methyl tyrosine (IMT) and contrast enhanced magnetic resonance imaging (MRI) as diagnostic tools in primary paediatric brain tumours in respect of non-invasive tumour grading. Patients, materials, methods: 45 children with primary brain tumours were retrospectively evaluated. IMT uptake was quantified as tumour/nontumour-ratio, a 4-value-scale was used to measure gadolinium enhancement on contrast enhanced MRI. Statistical analyses were performed to evaluate IMT uptake and gadolinium enhancement in low (WHO I/II) and high (WHO III/IV) grade tumours and to disclose a potential relationship of IMT uptake to disruption of blood brain barrier as measured in corresponding MRI scans. RESULTS: IMT uptake above background level was observed in 35 of 45 patients. IMT uptake was slightly higher in high grade tumours but the difference failed to attain statistical significance. Grading of individual tumours was neither possible by IMT SPECT nor by gadolinium enhanced MRI. CONCLUSION: IMT is accumulated in most brain tumours in children. Tumour grading was not possible using IMT or contrast enhancement as determined by MRI. Neither morphological nor functional imaging can replace histology in paediatric brain tumours.
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Aminoácidos , Neoplasias Encefálicas/diagnóstico , Imagen por Resonancia Magnética/métodos , Tomografía de Emisión de Positrones , Adolescente , Neoplasias Encefálicas/clasificación , Neoplasias Encefálicas/diagnóstico por imagen , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Lamotrigine is a broadly effective antiepileptic drug in mono- and add-on therapy for children and adolescents with focal and generalized epilepsies. Some epileptologists consider lamotrigine as the drug of primary choice in older school children and adolescents because of its good tolerability (no increase of body weight, no impairment of cognitive functions, due to new data probably no teratogenic properties). Lamotrigine can be used with good efficacy in numerable epilepsy diseases, such as tuberous sclerosis, juvenile neuronal lipofuscinosis and Rett syndrome. The first studies show that lamotrigine is also effective in children under 2 years of age. For therapy of difficult-to-treat epilepsies the combination of lamotrigine with valproate has proved as especially useful. This clinical observation is supported by new results of animal experiments. The dose-dependant and typical CNS side effects vertigo, ataxia, nausea, tremor and diplopia are found most frequently. The rate of allergic skin rashes which was very high before 1998 has decreased markedly by new dosage guidelines and is now as low as in older antiepileptic drugs. Lamotrigine does not impair cognitive functions, especially not memory and language. It has mood-stabilizing features and may improve quality of life. In animal experiments lamotrigine shows antiepileptogenic and neuroprotective effects.
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Anticonvulsivantes/administración & dosificación , Epilepsias Parciales/tratamiento farmacológico , Epilepsia Generalizada/tratamiento farmacológico , Triazinas/administración & dosificación , Adolescente , Animales , Anticonvulsivantes/efectos adversos , Encéfalo/efectos de los fármacos , Niño , Preescolar , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Humanos , Lactante , Lamotrigina , Resultado del Tratamiento , Triazinas/efectos adversosRESUMEN
Severe myoclonic epilepsy in infancy (SMEI), severe idiopathic generalized epilepsy of infancy (SIGEI) with generalized tonic clonic seizures (GTCS), and myoclonic astatic epilepsy (MAE) may show semiological overlaps. In GEFS+ families, all three phenotypes were found associated with mutations in the SCN1A gene. We analyzed the SCN1A gene in 20 patients with non-familial myoclonic astatic epilepsy -- including 12 probands of the original cohort used by Doose et al. in 1970 to delineate MAE. In addition, 18 patients with sporadic SIGEI -- mostly without myoclonic-astatic seizures -- were analyzed. Novel SCN1A mutations were found in 3 individuals. A frame shift resulting in an early premature stop codon in a now 35-year-old woman with a borderline phenotype of MAE and SIGEI (L433fsX449) was identified. A splice site variant (IVS18 + 5 G --> C) and a missense mutation in the conserved pore region (40736 C --> A; R946 S) were detected each in a child with SIGEI. We conclude that, independent of precise syndromic delineation, myoclonic-astatic seizures are not predictive of SCN1A mutations in sporadic myoclonic epilepsies of infancy and early childhood.
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Epilepsias Mioclónicas/genética , Epilepsia Tónico-Clónica/genética , Proteínas del Tejido Nervioso/genética , Canales de Sodio/genética , Niño , Desarrollo Infantil , Análisis Mutacional de ADN , Epilepsias Mioclónicas/fisiopatología , Epilepsias Mioclónicas/psicología , Epilepsia Tónico-Clónica/fisiopatología , Epilepsia Tónico-Clónica/psicología , Femenino , Estudios de Seguimiento , Humanos , Lactante , Masculino , Canal de Sodio Activado por Voltaje NAV1.1RESUMEN
PURPOSE: The aim of this study was to evaluate the differential uptake of O-(2-[18F]fluorethyl)-L-tyrosine (FET) in suspected primary brain tumours. METHODS: Positron emission tomography (PET) was performed in 44 patients referred for the evaluation of a suspected brain tumour. Acquisition consisted of four 10-min frames starting upon i.v. injection of FET. Tumour uptake was calculated as the ratio of maximal tumour intensity to mean activity within a reference region (FETmax). RESULTS: FET uptake above the cortical level was observed in 35/44 lesions. All histologically confirmed gliomas and many other lesions showed FET uptake to a variable extent. No uptake was observed in nine lesions (one inflammatory lesion, one dysembryoplastic neuroepithelial tumour, one mature teratoma, six lesions without histological confirmation). An analysis of uptake dynamics was done in the patients with increased FET uptake (22 gliomas, three lymphomas, three non-neoplastic lesions, three lesions with unknown histology and four other primaries). Upon classification of tumours into low (i.e. WHO I and II) and high grade (i.e. WHO III and IV), a significant difference in FETmax between the two categories was observed only in the first image frame (0-10 min p.i.), with FETmax=2.0 in low-grade and 3.2 in high-grade tumours (p<0.05); no significant differences were found in frame 4 (30-40 min p.i.), with FETmax=2.4 vs 2.7. Similar results were obtained when the analysis was applied only to astrocytic tumours (2.0 vs 3.1 in the first frame; 2.4 vs 2.6 in the fourth frame). CONCLUSION: These initial results indicate that FET PET is a useful method to identify malignant brain lesions. It appears that high- and low-grade brain tumours exhibit a different uptake kinetics of FET. A kinetic analysis of FET PET may provide additional information in the differentiation of suspected brain lesions.
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Neoplasias Encefálicas/diagnóstico por imagen , Neoplasias Encefálicas/metabolismo , Radioisótopos de Flúor/farmacocinética , Tomografía de Emisión de Positrones/métodos , Tirosina/análogos & derivados , Tirosina/farmacocinética , Adolescente , Adulto , Anciano , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Radiofármacos/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadAsunto(s)
Luz/efectos adversos , Trastornos por Fotosensibilidad/genética , Adolescente , Adulto , Mapeo Encefálico , Niño , Electroencefalografía/métodos , Epilepsia Refleja/etiología , Epilepsia Refleja/genética , Salud de la Familia , Femenino , Humanos , Escala de Lod , Masculino , Biología Molecular/métodos , Linaje , Estimulación Luminosa/métodos , Trastornos por Fotosensibilidad/diagnóstico , Trastornos por Fotosensibilidad/fisiopatología , Polimorfismo Genético , Proteínas Tirosina Fosfatasas/genética , Proteínas Tirosina Fosfatasas no Receptoras , Receptores Dopaminérgicos/genéticaAsunto(s)
Neoplasias Encefálicas/diagnóstico , Neoplasias Neuroepiteliales/diagnóstico , Lóbulo Occipital/patología , Adulto , Factores de Edad , Neoplasias Encefálicas/patología , Neoplasias Encefálicas/cirugía , Preescolar , Padre , Femenino , Predisposición Genética a la Enfermedad , Hemianopsia/etiología , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias Neuroepiteliales/patología , Neoplasias Neuroepiteliales/cirugía , Núcleo Familiar , Lóbulo Occipital/cirugía , Convulsiones/etiologíaRESUMEN
BACKGROUND: Mutations in various genes of the neuromuscular junction may cause congenital myasthenic syndromes (CMS). Most mutations identified to date affect the epsilon-subunit gene of the acetylcholine receptor (AChR), leading to end-plate AChR deficiency. Recently, three different mutations in the RAPSN gene have been identified in four CMS patients with AChR deficiency. OBJECTIVE: To perform mutation analysis of the RAPSN gene in patients with sporadic or autosomal recessive CMS. METHODS: One hundred twenty CMS patients from 110 unrelated families were analyzed for the RAPSN mutation N88K by restriction fragment length polymorphism and sequence analysis. RESULTS: In 12 CMS patients from 10 independent families, RAPSN N88K was identified either homozygous or heteroallelic to another missense mutation. Symptoms usually started perinatally or in the first years of life. However, one patient did not show any myasthenic symptoms before the third decade. Clinical symptoms typically included bilateral ptosis, weakness of facial, bulbar, and limb muscles, and a favorable response to anticholinesterase treatment. Crisis-like exacerbations with respiratory insufficiency provoked by stress, fever, or infections in early childhood were frequent. All RAPSN N88K families originate from Central or Western European countries. Genotype analysis indicated that they derive from a common ancestor (founder). CONCLUSIONS: The RAPSN mutation N88K is a frequent cause of rapsyn-related CMS in European patients. In general, patients (RAPSN N88K) were characterized by mild to moderate myasthenic symptoms with favorable response to anticholinesterase treatment. However, severity and onset of symptoms may vary to a great extent.
Asunto(s)
Predisposición Genética a la Enfermedad , Proteínas Musculares/genética , Mutación Missense , Síndromes Miasténicos Congénitos/genética , Adolescente , Adulto , Secuencia de Aminoácidos , Niño , Preescolar , Análisis Mutacional de ADN , Europa (Continente) , Femenino , Frecuencia de los Genes , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Síndromes Miasténicos Congénitos/diagnóstico , Linaje , Fenotipo , Alineación de SecuenciaRESUMEN
Giant axonal neuropathy (GAN) is a severe early onset neurodegenerative disorder affecting both the peripheral nerves and the central nervous system. The diagnosis is based on the presence of characteristic giant axons on nerve biopsy. In GAN, the integrity of the intermediate filament network is altered. Indeed, abnormal accumulation of the intermediate filaments has been reported in different cell types, including in the swollen axons, which are filled with neurofilaments. We identified the defective protein, gigaxonin, of unknown function, and reported fourteen distinct mutations in twelve families of various origins. Two additional mutations have been recently reported. In the present study, we analysed the GAN gene in 6 families, and identified seven novel mutations: three nonsense and two missense mutations and two deletions. In addition, the molecular result for an already reported family was re-evaluated. In this family, the R269Q "polymorphism" is in fact the pathogenic mutation.
Asunto(s)
Proteínas del Citoesqueleto/genética , Mutación , Edad de Inicio , Sustitución de Aminoácidos/genética , Preescolar , Exones/genética , Femenino , Ligamiento Genético/genética , Haplotipos/genética , Humanos , Masculino , Linaje , FenotipoRESUMEN
BACKGROUND AND PURPOSE: Ischemic symptoms in children with Moyamoya syndrome are typically provoked by hyperventilation (HV) and are accompanied by the "re-build-up" phenomenon in EEG. The value of scintigraphic detection of HV-provoked perfusion deficits remains to be elucidated. PATIENTS AND METHODS: In seven children with Moyamoya syndrome regional cerebral blood flow was assessed by 99mTc-ethyl-cysteine-dimer (ECD) single photon emission computed tomography (SPECT) after HV and under baseline conditions to identify ischemia prone regions. RESULTS: Regional marked hypoperfusion after HV was found in all patients. Predominant perfusion deficits were detected in the frontal lobes. CONCLUSION: ECD SPECT is a potential tool for the preoperative evaluation of cerebral hemodynamics and for monitoring angiosurgical therapies in Moyamoya disease.
Asunto(s)
Cisteína/análogos & derivados , Electroencefalografía , Hiperventilación/fisiopatología , Enfermedad de Moyamoya/diagnóstico por imagen , Enfermedad de Moyamoya/fisiopatología , Compuestos de Organotecnecio , Tomografía Computarizada de Emisión de Fotón Único , Adolescente , Edad de Inicio , Encéfalo/diagnóstico por imagen , Niño , Hemodinámica , Humanos , Hiperventilación/diagnóstico por imagen , RadiofármacosRESUMEN
We report on a preterm infant born at 30+5/7 gestational weeks who developed severe cystic cerebral lesions after exposure to a car accident one day before delivery. The literature on car accidents during pregnancy is reviewed with specific focus on neonatal neurological outcome.