RESUMEN

BACKGROUND: Colorectal cancer liver metastases respond to chemotherapy and targeted agents not only by shrinking, but also by morphologic and metabolic changes. The aim of this study was to evaluate the value of advanced magnetic resonance imaging (MRI) methods in predicting treatment response and survival. PATIENTS AND METHODS: We investigated contrast-enhanced MRI, apparent diffusion coefficient (ADC) in diffusion-weighted imaging and 1H-magnetic resonance spectroscopy (1H-MRS) in detecting early morphologic and metabolic changes in borderline or resectable liver metastases, as a response to first-line neoadjuvant or conversion therapy in a prospective substudy of the RAXO trial (NCT01531621, EudraCT2011-003158-24). MRI findings were compared with histology of resected liver metastases and Kaplan-Meier estimates of overall survival (OS). RESULTS: In 2012-2018, 52 patients at four Finnish university hospitals were recruited. Forty-seven patients received neoadjuvant or conversion chemotherapy and 40 liver resections were carried out. Low ADC values (below median) of the representative liver metastases, at baseline and after systemic therapy, were associated with partial response according to RECIST criteria, but not with morphologic MRI changes or histology. Decreasing ADC values following systemic therapy were associated with improved OS compared to unchanged or increasing ADC, both in the liver resected subgroup (5-year OS rate 100% and 34%, respectively, P = 0.022) and systemic therapy subgroup (5-year OS rate 62% and 23%, P = 0.049). 1H-MRS revealed steatohepatosis induced by systemic therapy. CONCLUSIONS: Low ADC values at baseline or during systemic therapy were associated with treatment response by RECIST but not with histology, morphologic or detectable metabolic changes. A decreasing ADC during systemic therapy is associated with improved OS both in all patients receiving systemic therapy and in the resected subgroup.

Asunto(s)

Neoplasias Colorrectales , Neoplasias Hepáticas , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/tratamiento farmacológico , Imagen de Difusión por Resonancia Magnética , Estudios de Seguimiento , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/tratamiento farmacológico , Espectroscopía de Resonancia Magnética , Terapia Neoadyuvante , Estudios Prospectivos

RESUMEN

INTRODUCTION: Adverse events in radiology are quite rare, but they do occur. Radiation safety regulations and the law obligate organizations to report certain adverse events, harm and near misses, especially events related to patients' health and safety. The aim of this study was to describe and analyse incidents related to radiation safety issues reported in Finland. METHODS: The data were collected from incident reports documented by radiology personnel concerning notifications of abnormal events in medical imaging made to the Radiation and Nuclear Safety Authority between 2010 and 2017. During these eight years, 312 reports were submitted. Only events reported from radiology departments were included; nuclear medicine, radiotherapy and animal radiology cases were excluded. The final number of reports was 293 (94%). RESULTS: The majority of the 293 approved reports were related to computed tomography (CT, 68.3%) and to X-ray examinations (27.6%). Altogether 82.9% of those irradiated were adults, most of whom were exposed to unnecessary radiation through CT (86.5%), 5.5% were children, and 4.4% pregnant women. The most common effective dose of unnecessary radiation was 1 mSv or less (89.7% of all examinations). The highest effective doses were reported in CT (from under 1 mSv-20 mSv and above). The reasons for the adverse events were incorrect identification (32%), incorrect procedure, site or side (30%); and human errors or errors of knowledge (20%). CONCLUSION: Adverse events occurred especially in CT examinations. It is important to collect and analyse incident data, assess the harmful events, learn from them and aim to reduce adverse events. IMPLICATIONS FOR PRACTICE: This study emphasizes the need for radiological personnel to obtain evidence-based information on adverse events and focus on training to improve patient safety.

Asunto(s)

Medicina Nuclear , Exposición a la Radiación , Femenino , Finlandia , Humanos , Embarazo , Radiografía , Gestión de Riesgos

RESUMEN

OBJECTIVES: To compare observer performance in the detection of anatomical structures and pathology in panoramic radiographs using consumer grade with and without digital imaging and communication in medicine (DICOM)-calibration and 6-megapixel (6-MP) displays under different lighting conditions. METHODS: 30 panoramic radiographs were randomly evaluated on three displays under bright (510 lx) and dim (16 lx) ambient lighting by two observers with different years of experience. Dentinoenamel junction, dentinal caries and periapical inflammatory lesions, visibility of cortical border of the floor and pathological lesions in maxillary sinus were evaluated. Consensus between the observers was considered as reference. Intraobserver agreement was determined. Proportion of equivalent ratings and weighted kappa were used to assess reliability. The level of significance was set to p < 0.05. RESULTS: The proportion of equivalent ratings with consensus differed between uncalibrated and DICOM-calibrated consumer grade displays in dentinal caries in the lower molar in dim lighting (p = 0.021) and between DICOM-calibrated consumer grade and 6-MP display in bright lighting (p = 0.038) for an experienced observer. Significant differences were found between uncalibrated and DICOM-calibrated consumer grade displays in dentinal caries in bright lighting (p = 0.044) and periapical lesions in the upper molar in dim lighting (p = 0.008) for a less experienced observer. Intraobserver reliability was better at detecting dentinal caries than at detecting periapical and maxillary sinus pathology. CONCLUSIONS: DICOM calibration may improve observer performance in panoramic radiography in different lighting conditions. Therefore, a DICOM-calibrated consumer grade display can be used instead of a medical display in dental practice without compromising the diagnostic quality.

Asunto(s)

Presentación de Datos/normas , Iluminación , Radiografía Dental Digital , Radiografía Panorámica , Calibración , Humanos , Reproducibilidad de los Resultados

RESUMEN

OBJECTIVE: To define the optimal analysis protocol for semiautomatic quantification of spike index (SI) in continuous spikes and waves in sleep (CSWS). METHODS: Ten overnight EEGs (nine patients) with abundant spiking were used to quantify SI with a previously published semiautomatic quantification based on spike detection with BESA software. We studied (i) dependency of SI on maximal interspike interval (maxISI) defining the continuous discharge, (ii) sensitivity of SI to variations in the spike search protocol, and (iii) stability of SI over time. Finally, the semiautomatic method was compared with the quantification based on visual scoring by two neurophysiologists. RESULTS: MaxISI of 3s appeared to yield the best combination of sensitivity and stability in SI quantification. The SI of the first hour of sleep did not differ significantly from the SI of the whole night. Mean error of the semiautomatic method compared to visual scoring was only seven percentage units. CONCLUSIONS: Semiautomatic quantification of SI functions well with maxISI of 3s, and the first hour of sleep represents the whole night SI with a clinically relevant accuracy. SIGNIFICANCE: This method opens a possibility for objective quantification of near-continuous epileptiform spiking during sleep, and it supports the use of shorter epochs for quantitative assessment of CSWS.

Asunto(s)

Potenciales de Acción/fisiología , Electroencefalografía/métodos , Epilepsia/patología , Epilepsia/fisiopatología , Sueño/fisiología , Encéfalo/patología , Encéfalo/fisiopatología , Niño , Preescolar , Humanos , Imagen por Resonancia Magnética , Modelos Neurológicos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Programas Informáticos

RESUMEN

OBJECTIVE: Mitochondrial DNA polymerase γ (POLG1) mutations in children often manifest as Alpers syndrome, whereas in adults, a common manifestation is mitochondrial recessive ataxia syndrome (MIRAS) with severe epilepsy. Because some patients with MIRAS have presented with ataxia or epilepsy already in childhood, we searched for POLG1 mutations in neurologic manifestations in childhood. METHODS: We investigated POLG1 in 136 children, all clinically suspected to have mitochondrial disease, with one or more of the following: ataxia, axonal neuropathy, severe epilepsy without known epilepsy syndrome, epileptic encephalopathy, encephalohepatopathy, or neuropathologically verified Alpers syndrome. RESULTS: Seven patients had POLG1 mutations, and all of them had severe encephalopathy with intractable epilepsy. Four patients had died after exposure to sodium valproate. Brain MRI showed parieto-occipital or thalamic hyperintense lesions, white matter abnormality, and atrophy. Muscle histology and mitochondrial biochemistry results were normal in all. CONCLUSIONS: POLG1 analysis should belong to the first-line DNA diagnostic tests for children with an encephalitis-like presentation evolving into epileptic encephalopathy with liver involvement (Alpers syndrome), even if brain MRI and morphology, respiratory chain activities, and the amount of mitochondrial DNA in the skeletal muscle are normal. POLG1 analysis should precede valproate therapy in pediatric patients with a typical phenotype. However, POLG1 is not a common cause of isolated epilepsy or ataxia in childhood.

Asunto(s)

ADN Polimerasa Dirigida por ADN/genética , Esclerosis Cerebral Difusa de Schilder/genética , Mutación/genética , Adolescente , Factores de Edad , Secuencia de Aminoácidos , Niño , Preescolar , ADN Polimerasa gamma , Esclerosis Cerebral Difusa de Schilder/diagnóstico , Humanos , Lactante , Discapacidad Intelectual/diagnóstico , Discapacidad Intelectual/genética , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/genética , Datos de Secuencia Molecular , Adulto Joven

RESUMEN

BACKGROUND: Inherited and de novo mutations in sodium channel genes underlie a variety of channelopathies. Mutations in SCN2A, encoding the brain sodium channel Na(V)1.2, have previously been reported to be associated with benign familial neonatal infantile seizures, febrile seizures plus, and intractable epilepsy of infancy. METHODS: We evaluated the clinical characteristics in a patient with a neonatal-onset complex episodic neurologic phenotype. We screened SCN2A for mutations and carried out in vitro electrophysiologic analyses to study the consequences of the identified mutation. We studied the developmental expression of Na(V)1.2 in cerebellum by immunohistochemical analysis. RESULTS: The patient presented with neonatal-onset seizures and variable episodes of ataxia, myoclonia, headache, and back pain after 18 months of age. The patient carries a de novo missense mutation (p.Ala263Val) in SCN2A, which leads to a pronounced gain-of-function, in particular an increased persistent Na(+) current. Immunohistochemical studies suggest a developmentally increasing expression of Na(V)1.2 in granule cell axons projecting to Purkinje neurons. CONCLUSIONS: These results can explain a neuronal hyperexcitability resulting in seizures and other episodic symptoms extending the spectrum of SCN2A-associated phenotypes. The developmentally increasing expression of Na(V)1.2 in cerebellum may be responsible for the later onset of episodic ataxia.

Asunto(s)

Ataxia/genética , Epilepsia/genética , Mutación/genética , Mioclonía/genética , Proteínas del Tejido Nervioso/genética , Dolor/genética , Canales de Sodio/genética , Factores de Edad , Animales , Animales Recién Nacidos , Ataxia/complicaciones , Línea Celular Transformada , Cerebelo/crecimiento & desarrollo , Cerebelo/metabolismo , Cerebelo/patología , Niño , Progresión de la Enfermedad , Electroencefalografía/métodos , Epilepsia/complicaciones , Regulación del Desarrollo de la Expresión Génica , Estudio de Asociación del Genoma Completo/métodos , Humanos , Imagen por Resonancia Magnética , Potenciales de la Membrana/genética , Ratones , Mioclonía/complicaciones , Canal de Sodio Activado por Voltaje NAV1.2 , Proteínas del Tejido Nervioso/metabolismo , Neuronas/metabolismo , Dolor/complicaciones , Técnicas de Placa-Clamp/métodos , Canales de Sodio/metabolismo , Transfección/métodos , Grabación en Video/métodos

RESUMEN

Familial hemiplegic migraine (FHM), a rare autosomal dominant subtype of migraine with aura, has been linked to two chromosomal loci, 19p13 and 1q23. Mutations in the Na+K+-ATPase alpha2 subunit gene, ATP1A2, on 1q23 have recently been shown to cause familial hemiplegic migraine type 2 (FHM2). We sequenced the coding regions of this gene in a Finnish chromosome 1q23-linked FHM family with associated symptoms such as coma and identified a novel A1033G mutation in exon 9. This mutation results in a threonine-to-alanine substitution at codon 345. This residue is located in a highly conserved N-terminal region of the M4-5 loop of the Na+,K+-ATPase. Furthermore, the T345A mutation co-segregated with the disorder in our family and was not present in 132 healthy Finnish control individuals. For these reasons it is most likely the FHM-causing mutation in this family.

Asunto(s)

Cromosomas Humanos Par 1 , Ligamiento Genético , Hemiplejía/genética , Trastornos Migrañosos/genética , Mutación Missense , ATPasa Intercambiadora de Sodio-Potasio/genética , Secuencia de Aminoácidos , Salud de la Familia , Femenino , Finlandia , Frecuencia de los Genes , Haplotipos , Humanos , Masculino , Datos de Secuencia Molecular , Linaje

RESUMEN

OBJECTIVE: To evaluate the occurrence and prognostic importance of focal defects in cerebral cortical glucose metabolism in infants with newly diagnosed symptomatic and cryptogenic infantile spasms. PATIENTS AND METHODS: Ten children with symptomatic and seven with cryptogenic infantile spasms underwent MRI, video-EEG, and PET using fluorodeoxyglucose as a tracer within 2 weeks of diagnosis. PET was repeated at 1 year of age in 12 patients. RESULTS: Cortical hypometabolic foci were found in 13 children (77%) with newly diagnosed spasms (six cryptogenic and seven symptomatic). The hypometabolic foci disappeared in seven of nine reexamined at age 1. The occipital foci disappeared in all (n = 6). Focal findings on PET correlated well with focal findings on video-EEG. There was no difference in quantitative cortical or subcortical glucose metabolic rate at the onset of infantile spasms between children with cryptogenic and symptomatic etiology of spasms. The glucose metabolic rate at the onset of spasms or focal lesions in glucose metabolism did not have prognostic value for seizure outcome. CONCLUSIONS: Infantile spasms are often associated with transient cortical, especially occipital, hypometabolic foci that are not necessarily associated with structural lesions and do not indicate a poor prognosis.

Asunto(s)

Corteza Cerebral/metabolismo , Espasmos Infantiles/diagnóstico por imagen , Espasmos Infantiles/metabolismo , Tomografía Computarizada de Emisión , Corteza Cerebral/diagnóstico por imagen , Femenino , Glucosa/metabolismo , Humanos , Lactante , Masculino , Valor Predictivo de las Pruebas

RESUMEN

The purpose of this study was to investigate early electroclinical manifestations and evaluate treatment responses by video-EEG in infants with newly diagnosed spasms. Spasms were recorded in 44 infants (27 males, 17 females) before adequate treatment. Mean ages at onset of spasms and at first video-EEG were 5.3 months (range 0.9 to 9 months) and 5.9 months (range 2.4 to 11.5 months) respectively. Thirteen infants had cryptogenic and 31 had symptomatic aetiology. First treatment was vigabatrin in 36 infants. All infants were followed until 12 months of age or death. Treatment response in the first months of therapy was assessed by repeated video-EEG studies in 23 infants. On the first video-EEG, 34 infants had typical symmetric motor spasms, three infants showed asymmetric or asynchronous behaviour, and seven infants had only subtle spasms. Interictal EEG showed hypsarrhythmia in 27 infants and multifocal spikes with normal or nearly normal background in 17 infants. Subtle spasms, asymmetric or asynchronous spasms, and asymmetric ictal or interictal EEG abnormalities were associated with symptomatic aetiology and poor cognitive and seizure outcome at 12 months. Serial video-EEG recordings showed a transition from motor to subtle spasms during the first 2 weeks of vigabatrin therapy in four infants and only subtle spasms in two therapy-resistant infants at 12 months. Cessation of spasms usually preceded disappearance of hypsarrhythmia or multifocal spikes, but persistence of multifocal spikes over several weeks was always associated with existing spasms. Transition of hypsarrhythmia into multifocal spikes was observed during vigabatrin therapy even in infants with intractable spasms. Initial diagnosis of infantile spasms requires video-EEG studies especially in infants with symptomatic aetiology who may show only subtle spasms. Video-EEG is the only reliable method for assessing treatment response as spasms and interictal EEG abnormalities are modified by treatment and may become subtle.

Asunto(s)

Anticonvulsivantes/uso terapéutico , Benzodiazepinas , Carbamazepina/análogos & derivados , Electroencefalografía , Espasmos Infantiles/tratamiento farmacológico , Espasmos Infantiles/fisiopatología , Grabación en Video , Ansiolíticos/uso terapéutico , Encéfalo/fisiopatología , Carbamazepina/uso terapéutico , Clobazam , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Oxcarbazepina , Fenobarbital/uso terapéutico , Valor Predictivo de las Pruebas , Piridoxina/uso terapéutico , Resultado del Tratamiento , Vigabatrin/uso terapéutico

RESUMEN

PURPOSE: Proton magnetic resonance spectroscopic imaging (1H MRSI) can lateralize the epileptogenic frontal lobe by detecting metabolic ratio abnormalities in frontal lobe epilepsy (FLE). We used 1H MRS to lateralize and localize the epileptogenic focus, and we also sought to characterize further the metabolic abnormality in FLE. METHODS: We measured signals from N-acetyl aspartate (NAA), choline-containing compounds (Cho), and creatine + phosphocreatine (Cr) in the supraventricular brain of 14 patients with frontal or frontoparietal epilepsy and their matched controls. The supratentorial brain also was segmented into gray matter, white matter, and cerebrospinal fluid classes. Regional metabolite alterations were compared with localizing and lateralizing results from other examination modalities and with histology from three patients. RESULTS: Spectroscopy lateralized the epileptogenic focus in 10 patients in agreement with video-EEG and functional imaging. In four patients, spectroscopy showed bilateral, focal metabolic abnormality, whereas video-EEG suggested unilateral or midline abnormality. In the epileptogenic focus, Cho and Cr were increased by 23% and 14%, respectively, and NAA was decreased by 11%, suggesting metabolic disturbances both in the glial and in the neuronal cell pools. Two Taylor dysplasia lesions confirmed by histology and one with radiologic diagnosis showed high Cho and low or normal NAA, whereas two dysembryoplastic neurogenic tumors had normal Cho and low NAA. Contralateral hemisphere NAA/(Cho + Cr) was decreased in FLE, indicating diffusely altered brain metabolism. Segmentation of brain tissue did not reveal atrophic changes in FLE. CONCLUSIONS: Spectroscopy is useful in lateralizing frontoparietal epilepsy and shows promise as a "noninvasive biopsy" in epileptogenic lesions.

Asunto(s)

Ácido Aspártico/análogos & derivados , Encéfalo/metabolismo , Epilepsia del Lóbulo Frontal/diagnóstico , Espectroscopía de Resonancia Magnética/estadística & datos numéricos , Adolescente , Adulto , Ácido Aspártico/metabolismo , Encéfalo/citología , Niño , Preescolar , Enfermedad Crónica , Creatina/metabolismo , Electroencefalografía/métodos , Electroencefalografía/estadística & datos numéricos , Epilepsia del Lóbulo Frontal/metabolismo , Femenino , Lóbulo Frontal/citología , Lóbulo Frontal/metabolismo , Lateralidad Funcional/fisiología , Humanos , Imagen por Resonancia Magnética , Masculino , Monitoreo Fisiológico , Neuroglía/metabolismo , Neuronas/metabolismo , Lóbulo Parietal/metabolismo , Fosfocreatina/metabolismo , Grabación de Cinta de Video

RESUMEN

Between 1989 and 1994, 18 children with cryptogenic infantile spasms-defined by normal development before onset of spasms, symmetrical hypsarrhythmia or multifocal spikes, and typical spasms on presentation, and no abnormal findings on aetiological studies including neuroradiology-were diagnosed and treated. To assess the risk of cognitive impairment later in life, 15 of these 18 children whose spasms completely resolved within the first year of life were studied. Age at onset of spasms varied between 4.4 and 9.8 months (mean 6.5 months). Children were effectively treated with adrenocorticotrophic hormone (10 children), pyridoxine (three), vigabatrin (one), or sodium valproate (one). Spasms lasted between 11 and 138 days (mean 50 days) and stopped between the age of 6.3 and 10.2 months(mean 8.1 months). EEGs normalized between the age of 7.1 and 13.2 months (mean 9.4 months). Early development was assessed on presentation and within a few months after spasms had stopped. A detailed neuropsychological assessment was performed between the age of 4.0 and 5.9 years. Twelve children had normal intelligence; specific cognitive deficits were found in five. Three children had mild learning disability. Abnormal developmental status at age 8 to 15 months after complete resolution of spasms and EEG abnormalities was associated with cognitive deficits at age 4 to 6 years.

Asunto(s)

Trastornos del Conocimiento/etiología , Espasmos Infantiles/complicaciones , Anticonvulsivantes/uso terapéutico , Niño , Desarrollo Infantil , Preescolar , Electroencefalografía , Femenino , Estudios de Seguimiento , Humanos , Lactante , Recién Nacido , Masculino

RESUMEN

PURPOSE: The efficacy of a protocol consisting of vigabatrin (VGB) as the first and adrenocorticotropic hormone (ACTH) or valproate (VPA) as the second drug was studied in the treatment of newly diagnosed infantile spasms (IS) during 1994 to 1997 in a population-based design. METHODS: Only total disappearance of the spasms with a minimal duration of 1 month was accepted as a response. The treatment response was confirmed by video-EEG study. All infants were studied by magnetic resonance imaging (MRI) or computed tomography (CT) for etiology. RESULTS: Altogether 42 infants, 10 with cryptogenic and 32 with symptomatic etiology, were treated. Eleven (26%) responded to VGB, five (50%) with cryptogenic, and six (19%) with symptomatic etiology; 91% of infants responded to a dose of 50-100 mg/kg/day, and 82% of them within 1 week. ACTH was offered in combination with VGB to 22 and VPA to four infants for whom VGB failed. Eleven responded to ACTH and one to VPA. In total, 26 (62%) infants responded to the treatment protocol; all (100%) with cryptogenic etiology and 16 (50%) with symptomatic etiology. ACTH treatment was associated with more severe side effects than VGB or VPA. Only one infant relapsed after a spasm-free period with VGB of >4 months, but none after ACTH was combined with VGB. CONCLUSIONS: We suggest VGB as a first drug to all infants with IS. After a treatment trial of 10-14 days with increasing dose from 50 to 150 mg/kg, ACTH should be considered.

Asunto(s)

Anticonvulsivantes/uso terapéutico , Espasmos Infantiles/tratamiento farmacológico , Ácido gamma-Aminobutírico/análogos & derivados , 4-Aminobutirato Transaminasa/antagonistas & inhibidores , Hormona Adrenocorticotrópica/uso terapéutico , Encefalopatías/diagnóstico , Niño , Protocolos Clínicos , Esquema de Medicación , Quimioterapia Combinada , Electroencefalografía/estadística & datos numéricos , Finlandia/epidemiología , Humanos , Incidencia , Imagen por Resonancia Magnética , Espasmos Infantiles/diagnóstico , Espasmos Infantiles/epidemiología , Tomografía Computarizada por Rayos X , Resultado del Tratamiento , Ácido Valproico/uso terapéutico , Grabación de Cinta de Video , Vigabatrin , Ácido gamma-Aminobutírico/uso terapéutico

RESUMEN

PURPOSE: Our aim was (a) to localize the primary epileptogenic cortex for possible multiple subpial transsection in four children with the Landau-Kleffner syndrome (LKS), and (b) to evaluate the impact of magnetoencephalography (MEG) in the localizing process. METHODS: We used EEG to detect the overall epileptiform activity and MEG for selective recording of fissural spikes. The cortical generators of MEG spikes were modeled with dipoles, and their activation order was determined. The voltage distribution, consistent with the earliest MEG sources, was then identified during the course of the patient's EEG spikes to determine the relative timing between stereotypic EEG and MEG spikes and to distinguish the earliest (primary) source area among the secondary ones. RESULTS: In all patients, the earliest spike activity originated in the intrasylvian cortex, spreading in one subject to the contralateral sylvian cortex within 20 ms. Secondary spikes occurred within 10-60 ms in ipsilateral perisylvian, temporooccipital, and parietooccipital areas. A single intrasylvian pacemaker initiated all epileptic activity in two patients, whereas the other two had independent left- and right-hemisphere circuits or focal spikes. MEG source dynamics predicted the results of the methohexital suppression test in two patients and was confirmed by surgery outcome in one patient, in whom all epileptic activity ceased after a small transsection of the sylvian pacemaker. CONCLUSIONS: (a) The intrasylvian cortex is a likely pacemaker of epileptic discharges in LKS, and (b) MEG provides useful presurgical information of the cortical spike dynamics in LKS patients.

Asunto(s)

Corteza Cerebral/fisiopatología , Síndrome de Landau-Kleffner/diagnóstico , Magnetoencefalografía , Corteza Auditiva/efectos de los fármacos , Corteza Auditiva/fisiopatología , Corteza Cerebral/efectos de los fármacos , Niño , Electroencefalografía/efectos de los fármacos , Electroencefalografía/estadística & datos numéricos , Femenino , Lateralidad Funcional/efectos de los fármacos , Humanos , Síndrome de Landau-Kleffner/fisiopatología , Síndrome de Landau-Kleffner/cirugía , Masculino , Metohexital/farmacología , Transmisión Sináptica/efectos de los fármacos , Grabación de Cinta de Video

RESUMEN

This study comprised two patients with aspartylglucosaminuria (AGU), who were followed up for 4 and 7 years. The patients underwent allogeneic bone marrow transplantation (BMT) at the ages of 2 and 2.6 years. Both patients had abnormal speech development and gross motor clumsiness. At the time of the BMT, they were mentally retarded. We report on follow-up data of these patients obtained by MRI, in addition to the histopathological, biochemical and clinical investigations. MR images of six non-transplanted patients and seven healthy children served as controls. In the non-transplanted patients, MRI revealed evident delay of myelination in contrast to the two transplanted patients showing fair or evident grey- vs. white matter differentiation on T2-weighted images. The aspartylglucosaminidase (AGA) activity in blood leukocytes reached a heterozygous level. Urinary excretion of aspartylglucosamine and glycoasparagines slowly decreased but remained about a third of the pre-BMT level 5 years after BMT. Storage lysosomes in electron microscopic investigations were not decreased 6 months after BMT, but after 1.5-2 years, rectal mucosa samples showed a decrease in the storage vacuoles of different cells. Three years after BMT, no cells with storage vacuoles were present. Allogeneic BMT slowly normalises the pathological, biochemical and MRI findings in patients with AGU.

Asunto(s)

Aspartilglucosaminuria , Aspartilglucosilaminasa/metabolismo , Trasplante de Médula Ósea , Aspartilglucosilaminasa/orina , Biopsia , Trasplante de Médula Ósea/métodos , Encéfalo/patología , Estudios de Casos y Controles , Niño , Preescolar , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Errores Innatos del Metabolismo/patología , Errores Innatos del Metabolismo/terapia , Músculo Liso/patología

Asunto(s)

Cuerpo Calloso/cirugía , Epilepsia/cirugía , Adolescente , Niño , Preescolar , Electroencefalografía , Epilepsia/fisiopatología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Procedimientos Neuroquirúrgicos/métodos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento

RESUMEN

Oxcarbazepine is similar to carbamazepine in its mechanisms of action and antiepileptic efficacy, but has better tolerability and fewer interactions with other drugs. Very few data are available on the usefulness of oxcarbazepine in patients with intellectual disability and epilepsy. From January 1991 until October 1994, the present authors treated 40 patients with intellectual disability and epilepsy under the age of 18 years with oxcarbazepine. The mean age at onset of epilepsy was 12 months (range = 0-132 months). All patients had previously been intractable to antiepileptic drugs (including carbamazepine in 29 patients). The age at onset of oxcarbazepine therapy ranged from 0.8 to 17.1 years (mean = 6.2 years). Thirty-one patients (78%) received other antiepileptic drugs simultaneously with oxcarbazepine. The mean follow-up with oxcarbazepine treatment was 18.8 months. The mean maximum oxcarbazepine dose was 49 mg kg(-1) day(-1) (range = 21-86 mg kg(-1) day(-1). A reduction in seizures of at least 50% during oxcarbazepine treatment was observed in 14 out of 28 (50%) patients with localization-related epilepsy and in 5 out of 12 (42%) patients with generalized epilepsy. Efficacy was transient in three patients. An increase of atypical absences was observed in one child and an emergence of drop attacks in another. Side-effects were observed in 16 (40%) patients; in eight (20%), these lead to dose reduction or discontinuation. Oxcarbazepine appears to be an effective and well-tolerated drug for children and adolescents with intellectual disability and epilepsy.

Asunto(s)

Anticonvulsivantes/uso terapéutico , Carbamazepina/análogos & derivados , Epilepsia/complicaciones , Epilepsia/tratamiento farmacológico , Discapacidad Intelectual/complicaciones , Adolescente , Carbamazepina/uso terapéutico , Niño , Preescolar , Estudios de Seguimiento , Humanos , Lactante , Oxcarbazepina , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

The Landau-Kleffner Syndrome (LKS) is characterized by acquired receptive aphasia and EEG abnormality with onset between the ages of 3 and 8 years. This study presents neuropsychological assessments in 5 children with LKS. The aims were (1) to specify the neuropsychological deficits characteristic of these children; and (2) to clarify the nature of the receptive aphasia by comparing nonverbal and verbal auditory discrimination. Receptive aphasia was present in all children. Retardation, poor motor coordination, hyperkinesia, and conduct problems were frequent but variable. All children exhibited a dissociation between the discrimination of environmental sounds and phonological auditory discrimination, the latter being more impaired than the former. This suggests that the primary deficit of the receptive aphasia is an impairment of auditory phonological discrimination rather than a generalized auditory agnosia.

Asunto(s)

Agnosia/diagnóstico , Afasia/diagnóstico , Síndrome de Landau-Kleffner/diagnóstico , Percepción del Habla/fisiología , Niño , Preescolar , Electroencefalografía , Epilepsia/diagnóstico , Femenino , Humanos , Masculino , Pruebas Neuropsicológicas , Fonética , Índice de Severidad de la Enfermedad , Sueño/fisiología

RESUMEN

Very little data are available on the usefulness of oxcarbazepine in young children with epilepsy. From January 1991 through October 1994, we treated 53 children under age 7 years with oxcarbazepine. The mean follow-up with oxcarbazepine treatment was 13 months. Etiology was symptomatic in 39, cryptogenic in 12, and idiopathic in 2 children. Forty-three children had previously been intractable to one or more antiepileptic drugs (including carbamazepine in 30 patients) and two had carbamazepine hypersensitivity. The age at onset of oxcarbazepine therapy ranged from 0.6 to 6.9 years (mean, 3.9 yr). The mean maximum oxcarbazepine dose was 50 mg/kg/day (range, 21-86 mg/kg/day). Of the children with localization-related epilepsy, 12 of 44 (27%) became seizure free and an additional 16 of 44 (36%) had an at least 50% reduction of seizures. Five of nine children with generalized epilepsy also had some benefit but none became seizure free. In the 33 children with at least 50% seizure reduction, the mean effective dose and trough serum level of the active metabolite monohydroxycarbazepine were 47 mg/kg/day (range, 21-75 mg/kg/day) and 91 micromol/L (range, 42-130 micromol/L), respectively. Efficacy was transient in 4 children; side effects were observed in 17 children (32%); in 9 (17%) of whom, they led to dose reduction or discontinuation. Oxcarbazepine appears to be an effective and well-tolerated drug for localization-related early childhood epilepsy. Young children need a higher dose per body weight than adults.

Asunto(s)

Anticonvulsivantes/uso terapéutico , Carbamazepina/análogos & derivados , Epilepsia/tratamiento farmacológico , Carbamazepina/uso terapéutico , Niño , Preescolar , Resistencia a Medicamentos , Quimioterapia Combinada , Humanos , Lactante , Estudios Longitudinales , Oxcarbazepina , Vigilancia de Productos Comercializados , Estudios Retrospectivos , Resultado del Tratamiento , Ácido Valproico/uso terapéutico