Neuronal Ceroid Lipofuscinosis Type 6 (CLN6) clinical findings and molecular diagnosis: Costa Rica's experience.

BACKGROUND: Commonly known as Batten disease, the neuronal ceroid lipofuscinoses (NCLs) are a genetically heterogeneous group of rare pediatric lysosomal storage disorders characterized by the intracellular accumulation of autofluorescent material (known as lipofuscin), progressive neurodegeneration, and neurological symptoms. In 2002, a disease-causing NCL mutation in the CLN6 gene was identified (c.214G > T) in the Costa Rican population, but the frequency of this mutation among local Batten disease patients remains incompletely characterized, as do clinical and demographic attributes for this rare patient population. OBJECTIVE: To describe the main sociodemographic and clinical characteristics of patients with a clinical diagnosis for Batten Disease treated at the National Children's Hospital in Costa Rica and to characterize via molecular testing their causative mutations. METHODS: DNA extracted from buccal swabs was used for CLN6 gene sequencing. Participants' sociodemographic and clinical characteristics were also obtained from their medical records. RESULTS: Nine patients with a clinical diagnosis of Batten disease were identified. Genetic sequencing determined the presence of the previously described Costa Rican homozygous mutation in 8 of 9 cases. One patient did not have mutations in the CLN6 gene. In all cases where the Costa Rican CLN6 mutation was present, it was accompanied by a substitution in intron 2. Patients were born in 4 of the 7 Costa Rican provinces, with an average onset of symptoms close to 4 years of age. No parental consanguinity was present in pedigrees. Initial clinical manifestations varied between patients but generally included: gait disturbances, language problems, visual impairment, seizures and psychomotor regression. Cortical and cerebellar atrophy was a constant finding when neuroimaging was performed. Seizure medication was a common element of treatment regimens. CONCLUSIONS: This investigation supports that the previously characterized c.214G > T mutation is the most common causative NCL mutation in the Costa Rican population. This mutation is geographically widespread among Costa Rican NCL patients and yields a clinical presentation similar to that observed for CLN6 NCL patients in other geographies.

[X-linked adrenoleukodystrophy with an atypical radiological pattern]. / Adrenoleucodistrofia ligada al X con patron radiologico atipico.

INTRODUCTION: X-linked adrenoleukodystrophy (X-ALD) is the most frequent peroxisomal disease. It is due to a mutation in the ABCD1 gene. The loss of functioning of ABCD1 triggers ineffective beta oxidation of very long-chain fatty acids, which gives rise to an accumulation of these fatty acids. The typical alteration revealed in neuroimaging scans in the cerebral form is symmetrical periventricular demyelination with posterior location. CASE REPORT: We report the case of a 10-year-old boy with right spastic hemiparesis and subacute cognitive impairment. Magnetic resonance imaging of the brain showed symmetrical involvement of the white matter in the left frontoparietotemporal region, and calcifications were observed in the computerised axial tomography scan. X-ALD was confirmed by means of the elevated levels of very long-chain fatty acids, and a pathogenic variant was found in the ABCD1 gene. CONCLUSIONS: Symmetrical demyelination with calcifications has rarely been reported in X-ALD, and these findings could delay diagnosis. This exceptional presentation should always be taken into consideration in children with subacute onset of motor symptoms and cognitive or behavioural regression.

TITLE: Adrenoleucodistrofia ligada al X con patron radiologico atipico.Introduccion. La adrenoleucodistrofia ligada al X (ALD-X) es la enfermedad peroxisomica mas frecuente. Se debe a una mutacion en el gen ABCD1. La perdida de la funcion de ABCD1 provoca una betaoxidacion inefectiva de los acidos grasos de cadena muy larga, lo que provoca la acumulacion de estos acidos grasos. La alteracion tipica en la neuroimagen en la forma cerebral es la desmielinizacion periventricular simetrica y de localizacion posterior. Caso clinico. Niño de 10 anos, con hemiparesia espastica derecha y deterioro cognitivo subagudo. La resonancia magnetica cerebral mostro afectacion asimetrica de la sustancia blanca en la region frontoparietotemporal izquierda, y en la tomografia axial computarizada se visualizaban calcificaciones. Se confirmo ALD-X mediante la elevacion de los niveles de acidos grasos de cadena muy larga, y se encontro una variante patogenica en el gen ABCD1. Conclusiones. La desmielinizacion asimetrica con calcificaciones raramente se ha descrito en la ALD-X, y estos hallazgos podrian retrasar el diagnostico. Esta presentacion excepcional se deberia considerar siempre en niños con inicio subagudo de sintomas motores y regresion cognitiva o del comportamiento.

Diagnóstico diferencial de parálisis flácida en pediatría / Differential diagnosis of flaccid paralysis in paediatric medicine

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Automated seizure detection systems and their effectiveness for each type of seizure.

Epilepsy affects almost 1% of the population and most of the approximately 20-30% of patients with refractory epilepsy have one or more seizures per month. Seizure detection devices allow an objective assessment of seizure frequency and a treatment tailored to the individual patient. A rapid recognition and treatment of seizures through closed-loop systems could potentially decrease morbidity and mortality in epilepsy. However, no single detection device can detect all seizure types. Therefore, the choice of a seizure detection device should consider the patient-specific seizure semiologies. This review of the literature evaluates seizure detection devices and their effectiveness for different seizure types. Our aim is to summarize current evidence, offer suggestions on how to select the most suitable seizure detection device for each patient and provide guidance to physicians, families and researchers when choosing or designing seizure detection devices. Further, this review will guide future prospective validation studies.

Resultados de la colocación del estimulador del nervio vago en epilepsia y calidad de vida en un hospital pediátrico / Vagus nerve stimulator implantation for epilepsy in a paediatric hospital: outcomes and effect on quality of life

Introducción: La epilepsia es uno de los trastornos neurológicos más frecuentes de la infancia, presentándose en un 0,5-1%. Aproximadamente un 20-30% de los pacientes son farmacorresistentes. El objetivo de este trabajo es describir en 30 pacientes el impacto sobre las crisis y la calidad de vida del estimulador del nervio vago (ENV). Métodos: Se trata de un estudio descriptivo, retrospectivo, mediante revisión de las historias clínicas de todos los pacientes a quienes se les colocó el ENV entre el 2008 y 2013 en nuestro centro. La calidad de vida fue valorada mediante la escala de calidad de vida en el niño con epilepsia (CAVE), obtenida por medio de una entrevista telefónica. Resultados: Se incluyeron 19 niños (64%) y 11 niñas (36%) con una mediana de comienzo de las crisis de 21 meses (1-144 meses). La edad promedio de colocación del ENV fue de 11,89 años. El tiempo de seguimiento fue de 6-36 meses. A los 6 meses la reducción de las crisis en promedio fue del 38%, a los 12 meses del 43%, a los 24 meses del 42% y a los 36 meses del 54%. De todos los pacientes evaluados al menos un 50% se catalogaron como respondedores. Según la CAVE un 54% de las familias encontró el efecto del ENV como bueno o muy bueno y un 39% como regular. Conclusiones: El ENV es un tratamiento paliativo, generalmente bien tolerado, parcialmente efectivo para el control de la epilepsia refractaria en pediatría y con repercusiones positivas sobre la calidad de vida

Introduction: Epilepsy, which is present in 0.5% to 1% of the paediatric population, is one of the most frequent childhood neurological disorders. Approximately 20% to 30% of these cases will be drug-resistant. The objective of this study is to describe the impact of vagal nerve stimulation (VNS) on seizures and quality of life in a sample of 30 patients. Methods: Descriptive, retrospective study of all patients with a VNS device implanted between 2008 and 2013 in a single paediatric hospital, based on patients’ medical records. Quality of life was assessed using the Spanish scale for quality of life in children with epilepsy, completed by means of a telephone interview. Results: We describe a population of 19 boys (64%) and 11 girls (36%) with a mean age at seizure onset of 21 months (1-144 months). The mean age of VNS implantation was 11.89 years. Follow-up periods ranged from 6 to 36 months. Mean reduction in seizures at 6 months was 38%, with a reduction of 43% at 12 months, 42% at 24 months, and 54% at 36 months. At least half of all patients were classified as responders. According to the quality of life scale, 54% of the families rated the effect of VNS as either very good or good while 39% rated it as fair. Conclusions: VNS is a safe palliative treatment that is generally well tolerated. It is partially effective for controlling drug-resistant epilepsy and exerts a positive effect on quality of life

Vagus nerve stimulator implantation for epilepsy in a paediatric hospital: outcomes and effect on quality of life.

INTRODUCTION: Epilepsy, which is present in 0.5% to 1% of the paediatric population, is one of the most frequent childhood neurological disorders. Approximately 20% to 30% of these cases will be drug-resistant. The objective of this study is to describe the impact of vagal nerve stimulation (VNS) on seizures and quality of life in a sample of 30 patients. METHODS: Descriptive, retrospective study of all patients with a VNS device implanted between 2008 and 2013 in a single paediatric hospital, based on patients' medical records. Quality of life was assessed using the Spanish scale for quality of life in children with epilepsy, completed by means of a telephone interview. RESULTS: We describe a population of 19 boys (64%) and 11 girls (36%) with a mean age at seizure onset of 21 months (1-144 months). The mean age of VNS implantation was 11.89 years. Follow-up periods ranged from 6 to 36 months. Mean reduction in seizures at 6 months was 38%, with a reduction of 43% at 12 months, 42% at 24 months, and 54% at 36 months. At least half of all patients were classified as responders. According to the quality of life scale, 54% of the families rated the effect of VNS as either very good or good while 39% rated it as fair. CONCLUSIONS: VNS is a safe palliative treatment that is generally well tolerated. It is partially effective for controlling drug-resistant epilepsy and exerts a positive effect on quality of life.

Síndrome de Down y epilepsia / Down’s syndrome and epilepsy

El síndrome de Down (SD) es la primera causa genética de retraso mental: afecta aproximadamente a uno de cada 660 nacimientos. Se asocia con numerosas complicaciones eurológicas, como la demencia de inicio precoz (similar a la enfermedad de Alzheimer), a enfermedad de moyamoya, la laxitud de ligamentos espinales y la epilepsia. La prevalencia de epilepsia en individuos con SD es mayor que en la población en general, con tasas que varían entre el 1% y el 13% y una media del 5,5%. La mayor propensión de estos pacientes a desarrollar epilepsia está relacionada con anomalías estructurales y moleculares del cerebro y con complicaciones secundarias. También se sabe que poseen menos células que contienen gránulos de ácido γ-aminobutírico y una concentración mayor de glutamato que favorece un estado hiperexcitatorio. El síndrome de West, con espasmos infantiles (EI), es el síndrome epiléptico más común en los niños con SD. Hay muchas anomalías en el electroencefalograma (EEG) asociadas con el SD, pero sin que se haya establecido ningún patrón específico. El esquema terapéutico de elección para los EI suele incluir hormona adrenocorticotropa, valproato y vigabatrina, pero no se ha demostrado que exista una diferencia significativa entre los distintos esquemas terapéuticos. Diversos estudios ponen de manifiesto que la población infantil con SD tiene un mejor control de la epilepsia cuando se compara con la de niños con EI asociados a otras causas. En adultos con SD se han descrito convulsiones focales, crisis reflejas y epilepsia mioclónica de inicio tardío asociada con demencia. En este artículo se presenta una revisión de la epilepsia en el SD (AU)

Down syndrome (DS) is the most common genetic cause of mental retardation affecting approximately one in 660 births. DS is associated with many neurological complications, including early-onset dementia that resembles Alzheimer’s disease, Moyamoya disease, strokes, spinal ligamentous laxity and epilepsy. The prevalence of epilepsy in individuals with DS is higher than in the general population, with rates ranging from 1 to 13%, with a media of 5.5%. The increased seizure susceptibility in DS has been attributed to inherent structural and molecular anomalies of the brain and to secondary complications. Among other facts patients with DS have less inhibitory γ-aminobutiric acid containing granule cells and an increased level of glutamate, which favours a hyperexcitable state. West syndrome, with infantile spasms, is the most common epilepsy syndrome in children with DS. There are many electroencephalographic (EEG) anomalies associated with DS but no specific pattern has been established. The primary drug choices for infantile spasms are adrenocorticotropic hormone, valproate and vigabatrine, but no significant difference has been demonstrated with different treatment options. Studies have shown that children with DS have better seizure control compared to other children with symptomatic infantile spasms. Other seizure types have been described in adult patients with DS including focal crisis, reflex seizures, and late-onset myoclonic epilepsy associated with dementia. This article provides an overview of epilepsy in DS (AU)