Enfermedad de Huntington de inicio en la infancia. Una presentación poco frecuente / Childhood-onset Huntignton´s disease. A rare presentation

Introducción La enfermedad de Huntington (EH) es una enfermedad de herencia autosómica dominante caracterizada por la expansión de tripletes de citosina-adenina-guanina (CAG) en el gen que codifica la huntingtina. Los síntomas en la descendencia suelen ser más tempranos por el fenómeno de anticipación. La clínica de inicio en la infancia, antes de los 10 años, difiere de la observada en la adultez. Se manifiesta por afectación motora, dificultades conductuales y retraso o regresión del desarrollo. La corea es infrecuente. El objetivo del caso es describir aspectos clínicos de una paciente con EH de inicio infantil. Caso clínico Niña de 5 años con antecedentes familiares de EH y desarrollo típico hasta los 3 años. Presentó progresivamente afectación del lenguaje con habilidades descendidas para su edad en aspectos expresivos y comprensivos, sin afectación en las habilidades pragmáticas y sociales. En cuanto a la motricidad, la marcha y la bipedestación eran inestables, y mostraba rigidez, distonía y movimientos coreicos. Presentó atrofia de los núcleos lenticulares y caudados en la resonancia magnética, y posteriormente se realizó el diagnóstico molecular con la expansión de tripletes CAG (51 copias). Conclusión La EH de inicio en la infancia presenta manifestaciones clínicas distintas a la forma del adulto. Debe considerarse en pacientes con afectación motora y cognitiva progresiva. Por la herencia familiar, es importante interrogar cuidadosamente sobre los antecedentes familiares y tenerla en cuenta aun sin familiares afectados por el fenómeno de anticipación. (AU)

INTRODUCTIO NHuntington’s disease (HD) is a rare autosomal dominant disease caused by the expansion of CAG triplets in the gene that encodes huntingtin. There are earlier symptoms’ onset in offspring due to the phenomenon of anticipation. The clinical features of childhood-onset HD, before age 10 years, differs from adult-onset form. It is characterized by motor impairment, behavioral difficulties and delay or regression in areas of development; while chorea is rarely seen. In this case we describe clinical aspects of a patient with childhood-onset Huntington’s disease. CASE REPORT A 5-year-old girl with a family history of HD and typical development up to 3 years of age. She progressively acquired language impairment with skills that were below her age in expressive and receptive areas, without deficits in pragmatic and social skills. Regarding motor skills, she manifested instability at walking and standing, with rigidity, dystonia and choreic movements. Atrophy of the basal ganglia was evident on MRI, EEG was normal, and molecular confirmation of CAG triplet revealed repeat length of 51 copies. CONCLUSION. Childhood-onset HD differs from adult-form´s clinical manifestations. It should be considered in patients with progressive motor and cognitive impairment. Due to family inheritance, it is important to carefully examine family history and take it into account even without relatives affected, considering the anticipation phenomenon. (AU)

Carga del cuidador y calidad de vida referida en pacientes neurológicos portadores de sonda de gastrostomía / Caregiver burden and reported quality of life in neurological patients with gastrostomy tubes

Objetivo: el objetivo del estudio es determinar si el uso de nutrición enteral domiciliaria (NED) por gastrostomía endoscópica percutánea (PEG) reduce la carga del cuidador y mejora la calidad de vida de los pacientes referida por los cuidadores. Material y métodos: se llevó a cabo un estudio observacional, descriptivo, prospectivo de una cohorte única de 30 pacientes. Resultados: los resultados mostraron una mejoría del estado nutricional y parámetros analíticos. Se observaron reducción de los ingresos (1,50 ± 0,90 vs 0,17 ± 0,38; p < 0,001) y estancia hospitalaria tras la colocación de la PEG a los 3 meses (10,2 ± 8,02 días vs 0,27 ± 0,69 días; p < 0,001). Los minutos que le dedicaban los cuidadores a la administración de NED disminuyeron tras la colocación de la PEG en 28,5 minutos por toma, lo que supone a lo largo de un día y 5 tomas diarias casi 150 minutos. Hubo una reducción de la percepción de sobrecarga de 13,5 puntos según el test de Zarit. El 56,6 % de los cuidadores refirieron que la calidad de vida había mejorado “bastante”, frente al 6,7 % que respondieron poca mejoría y el 36,7 % que contestaron mucha mejoría. Asimismo, se obtuvo una puntuación de 3,40 puntos superior en la escala QoL-AD tras la colocación de la PEG. Conclusiones: El uso de NED por sonda PEG reduce el tiempo que el cuidador le dedica a la administración de NE, dando lugar a una reducción de la carga. Además, mejora la calidad de vida de los pacientes referida por los cuidadores. (AU)

Objective: the aim of the study is to determine if the use of home enteral nutrition (HEN) by percutaneous endoscopic gastrostomy (PEG) reduces the burden on the caregiver and improves the patients' quality of life reported by the caregivers. Material and methods: a prospective, cross-sectional, descriptive, and observational study of a single cohort of 30 patients was conducted. Results: the results showed an improvement in nutritional status and analytical parameters. Fewer admissions (1.50 ± 0.90 vs 0.17 ± 0.38; p < 0.001) and hospital stays were reported at 3 months after gastrostomy (10.2 ± 8.02 days vs 0.27 ± 0.69 days; p < 0.001). The minutes spent by caregivers administering NEDs decreased after PEG placement by 28.5 minutes per feeding, which amounts to almost 150 minutes over a day and 5 feedings per day. In the Zarit questionnaire, there was a reduction of 13.5 points in the perception of overload. A total of 56.6 % of caregivers reported that quality of life had improved "quite a lot", compared to 6.7 % who reported little improvement, and 36.7 % who reported a lot of improvement. In the QoL-AD questionnaire, a higher score of 3.40 points was obtained. Conclusion: the use of HEN by PEG tube reduces the time spent by the caregiver administering EN, which results in a reduced burden. In addition, the quality of life of patients reported by caregivers improved. (AU)

[Caregiver burden and reported quality of life in neurological patients with gastrostomy tubes.] / Carga del cuidador y calidad de vida referida en pacientes neurológicos portadores de sonda de gastrostomía.

Introduction: Objective: the aim of the study is to determine if the use of home enteral nutrition (HEN) by percutaneous endoscopic gastrostomy (PEG) reduces the burden on the caregiver and improves the patients' quality of life reported by the caregivers. Material and methods: a prospective, cross-sectional, descriptive, and observational study of a single cohort of 30 patients was conducted. Results: the results showed an improvement in nutritional status and analytical parameters. Fewer admissions (1.50 ± 0.90 vs 0.17 ± 0.38; p < 0.001) and hospital stays were reported at 3 months after gastrostomy (10.2 ± 8.02 days vs 0.27 ± 0.69 days; p < 0.001). The minutes spent by caregivers administering NEDs decreased after PEG placement by 28.5 minutes per feeding, which amounts to almost 150 minutes over a day and 5 feedings per day. In the Zarit questionnaire, there was a reduction of 13.5 points in the perception of overload. A total of 56.6 % of caregivers reported that quality of life had improved "quite a lot", compared to 6.7 % who reported little improvement, and 36.7 % who reported a lot of improvement. In the QoL-AD questionnaire, a higher score of 3.40 points was obtained. Conclusion: the use of HEN by PEG tube reduces the time spent by the caregiver administering EN, which results in a reduced burden. In addition, the quality of life of patients reported by caregivers improved.

Introducción: Objetivo: el objetivo del estudio es determinar si el uso de nutrición enteral domiciliaria (NED) por gastrostomía endoscópica percutánea (PEG) reduce la carga del cuidador y mejora la calidad de vida de los pacientes referida por los cuidadores. Material y métodos: se llevó a cabo un estudio observacional, descriptivo, prospectivo de una cohorte única de 30 pacientes. Resultados: los resultados mostraron una mejoría del estado nutricional y parámetros analíticos. Se observaron reducción de los ingresos (1,50 ± 0,90 vs 0,17 ± 0,38; p < 0,001) y estancia hospitalaria tras la colocación de la PEG a los 3 meses (10,2 ± 8,02 días vs 0,27 ± 0,69 días; p < 0,001). Los minutos que le dedicaban los cuidadores a la administración de NED disminuyeron tras la colocación de la PEG en 28,5 minutos por toma, lo que supone a lo largo de un día y 5 tomas diarias casi 150 minutos. Hubo una reducción de la percepción de sobrecarga de 13,5 puntos según el test de Zarit. El 56,6 % de los cuidadores refirieron que la calidad de vida había mejorado "bastante", frente al 6,7 % que respondieron poca mejoría y el 36,7 % que contestaron mucha mejoría. Asimismo, se obtuvo una puntuación de 3,40 puntos superior en la escala QoL-AD tras la colocación de la PEG. Conclusiones: El uso de NED por sonda PEG reduce el tiempo que el cuidador le dedica a la administración de NE, dando lugar a una reducción de la carga. Además, mejora la calidad de vida de los pacientes referida por los cuidadores.

Resultados estandarizados del Montreal Cognitive Assessment (MoCA) para cribado neurocognitivo en población chilena / Standardized results of the Montreal Cognitive Assessment (MoCA) for neurocognitive screening in a Chilean population

Introducción: El envejecimiento poblacional implica un desafío para los países respecto a prevenir y detectar trastornos neurodegenerativos. El Montreal Cognitive Assessment (MoCA), test de cribado breve, de simple aplicación, válido y confiable, evalúa el estado cognitivo general, siendo útil en contextos de salud pública. El estudio busca normalizar y estandarizar el test MoCA para población chilena. Método: Se presenta estudio de validación para prueba diagnóstica de tipo descriptivo y correlacional, se evaluó a 526 sujetos, hombres y mujeres, de entre 18 y 90 años, sanos, del norte, centro y sur de Chile, analizando: el efecto de la edad, nivel educativo y sexo, para rendimiento de MoCA. Resultados: Se demuestra un efecto significativo de la edad y el nivel educativo sobre el rendimiento cognitivo general según MoCA. La edad, educación y sexo explican 1-7% de la varianza. El rendimiento cognitivo medio del total de la muestra fue de 24,04 ± 3,22, para un rango definido originalmente por el instrumento de 26 puntos sobre 30. Los adultos mayores con menor educación formal presentaron bajos resultados y menor rendimiento cognitivo. Se propone protocolo de evaluación de resultados en percentiles y puntuaciones por rango de edad y puntuación escalar normalizada individual. Discusión: Se presentan datos normativos de MoCA según las características sociodemográficas chilenas y puntos de corte propuestos para discriminar el rendimiento cognitivo normal de trastornos neurocognitivos según rangos de edad, ajustando los resultados al nivel educacional, la propuesta permitiría facilitar el uso del instrumento y disminuir la aparición de falsos positivos.(AU)

Introduction: Population ageing poses a challenge for countries in preventing and detecting neurodegenerative disorders. The Montreal Cognitive Assessment (MoCA), a short, simple, valid, and reliable screening test, assesses general cognitive status, and is useful in public health contexts. This study aims to normalise and standardise the MoCA test for the Chilean population. Method: We performed a descriptive, correlational validation study of the MoCA test, using a sample including 526 healthy individuals of both sexes, aged between 18 and 90 years, from the north, centre, and south of Chile. We analysed the effects of age, education level, and sex on MoCA performance. Results: Age and education level had a significant impact on general cognitive performance, as determined by MoCA score. Age, education, and sex account for 1-7% of variance. The mean (standard deviation) score for the total sample was 24.04 (3.22), whereas the normal range originally defined for the instrument is 26-30 points. Older adults with less formal education presented poorer results and lower cognitive performance. We propose a protocol for evaluating results by percentiles and scores for different age ranges, and an individual normalised scalar score. Discussion: We present normative data for the MoCA test in the Chilean population, and propose cut-off points for different age ranges to discriminate normal cognitive performance from neurocognitive disorders; results are adjusted for education level. This proposal would assist in the use of the test and reduce the rate of false positives.(AU)

Standardised results of the Montreal Cognitive Assessment (MoCA) for neurocognitive screening in a Chilean population.

INTRODUCTION: Population ageing poses a challenge for countries in preventing and detecting neurodegenerative disorders. The Montreal Cognitive Assessment (MoCA), a short, simple, valid, and reliable screening test, assesses general cognitive status, and is useful in public health contexts. This study aims to normalise and standardise the MoCA test for the Chilean population. METHOD: We performed a descriptive, correlational validation study of the MoCA test, using a sample including 526 healthy individuals of both sexes, aged between 18 and 90 years, from the north, centre, and south of Chile. We analysed the effects of age, education level, and sex on MoCA performance. RESULTS: Age and education level had a significant impact on general cognitive performance, as determined by MoCA score. Age, education, and sex account for 1%-7% of variance. The mean (standard deviation) score for the total sample was 24.04 (3.22), whereas the normal range originally defined for the instrument is 26-30 points. Older adults with less formal education presented poorer results and lower cognitive performance. We propose a protocol for evaluating results by percentiles and scores for different age ranges, and an individual normalised scalar score. DISCUSSION: We present normative data for the MoCA test in the Chilean population, and propose cut-off points for different age ranges to discriminate normal cognitive performance from neurocognitive disorders; results are adjusted for education level. This proposal would assist in the use of the test and reduce the rate of false positives.

Experiencia con cuatro casos clínicos, ¿puede la encefalopatía traumática crónica estar asociada a un traumatismo craneoencefálico único? / Experience with 4 clinical cases. Traumatic encephalopathy may be associated with a single traumatic brain injury?

La encefalopatía traumática crónica (ETC) es una enfermedad neurodegenerativa que afecta a personas que han padecido traumatismos craneales repetitivos. No obstante, también durante el seguimiento de los pacientes con traumatismo craneoencefálico (TCE) único se pueden observar cambios respecto de su situación previa. Presentamos cuatro casos clínicos de pacientes visitados en la consulta externa del Instituto Guttmann entre 2017 y 2019, afectos de secuelas leves de TCE grave y único que han desarrollado posteriormente una enfermedad neurodegenerativa sin un diagnóstico concreto y que pudiesen cumplir criterios clínicos de síndrome de encefalopatía traumática crónica. Los médicos rehabilitadores son los profesionales con mayor posibilidad de identificar estos pacientes, indicando las exploraciones complementarias necesarias y estableciendo nuevos objetivos de rehabilitación.(AU)

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that affects people who had repetitive head trauma. Also, in single traumatic brain injury (TBI), changes may be found during the follow-up visits.We present four clinical cases of patients visited at the Institut Guttmann clinic between 2017 and 2019. They were affected by mild sequelae of severe and unique TBI who have subsequently developed a neurodegenerative disease without a specific diagnosis, and who could meet clinical criteria for chronic traumatic encephalopathy syndrome. Rehabilitation doctors are the professionals with the greatest possibility of identifying a suggestive clinic of this pathology, they can order the appropriate studies and indicate the new rehabilitation goals according to the new neurological situation.(AU)

[Experience with 4 clinical cases. Traumatic encephalopathy may be associated with a single traumatic brain injury?] / Experiencia con cuatro casos clínicos, ¿puede la encefalopatía traumática crónica estar asociada a un traumatismo craneoencefálico único?

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease that affects people who had repetitive head trauma. Also, in single traumatic brain injury (TBI), changes may be found during the follow-up visits. We present four clinical cases of patients visited at the Institut Guttmann clinic between 2017 and 2019. They were affected by mild sequelae of severe and unique TBI who have subsequently developed a neurodegenerative disease without a specific diagnosis, and who could meet clinical criteria for chronic traumatic encephalopathy syndrome. Rehabilitation doctors are the professionals with the greatest possibility of identifying a suggestive clinic of this pathology, they can order the appropriate studies and indicate the new rehabilitation goals according to the new neurological situation.

SARS-CoV-2 en el adulto mayor con enfermedad neurodegenerativa / SARS-CoV-2 in older adult with neurodegenerative disease

Resumen A pesar de la gran cantidad de complicaciones neurológicas relacionadas con la infección por SARS-CoV-2, aún no está claro si estos síntomas son el resultado de una lesión neural directa o se deben a alguna otra razón. Actualmente, parece que la mayoría de los síntomas neurológicos del COVID-19 son inespecíficos y secundarios a la enfermedad sistémica. Hasta la fecha no se cuenta con suficiente evidencia científica que confirme que el virus del SARS-CoV-2 afecta de forma directa al sistema nervioso central o periférico en los seres humanos. En el presente artículo corto se presentan las implicaciones de SARS-CoV-2 en el adulto mayor con enfermedad neurodegenerativa, así como los mecanismos de acción relacionados en sistema nervioso.

Abstract Despite the many neurological complications associated with SARS-CoV-2 infection, it isn´t still clear whether these symptoms are the result of direct neural injury or due to some other reason. Currently, it appears that most of the neurological symptoms of COVID-19 are nonspecific and secondary to systemic disease. To date, there is not enough scientific evidence to confirm that SARS-CoV-2 virus directly affects the central or peripheral nervous system in humans. This short article presents the implications of SARS-CoV-2 in the elderly with neurodegenerative disease, as well as the related mechanisms of action in the nervous system.

Standardized results of the Montreal Cognitive Assessment (MoCA) for neurocognitive screening in a Chilean population. / Resultados estandarizados del Montreal Cognitive Assessment (MoCA) para cribado neurocognitivo en población chilena.

INTRODUCTION: Population ageing poses a challenge for countries in preventing and detecting neurodegenerative disorders. The Montreal Cognitive Assessment (MoCA), a short, simple, valid, and reliable screening test, assesses general cognitive status, and is useful in public health contexts. This study aims to normalise and standardise the MoCA test for the Chilean population. METHOD: We performed a descriptive, correlational validation study of the MoCA test, using a sample including 526 healthy individuals of both sexes, aged between 18 and 90 years, from the north, centre, and south of Chile. We analysed the effects of age, education level, and sex on MoCA performance. RESULTS: Age and education level had a significant impact on general cognitive performance, as determined by MoCA score. Age, education, and sex account for 1-7% of variance. The mean (standard deviation) score for the total sample was 24.04 (3.22), whereas the normal range originally defined for the instrument is 26-30 points. Older adults with less formal education presented poorer results and lower cognitive performance. We propose a protocol for evaluating results by percentiles and scores for different age ranges, and an individual normalised scalar score. DISCUSSION: We present normative data for the MoCA test in the Chilean population, and propose cut-off points for different age ranges to discriminate normal cognitive performance from neurocognitive disorders; results are adjusted for education level. This proposal would assist in the use of the test and reduce the rate of false positives.

Diagnóstico clínico y bioquímico del síndrome de leigh en cinco pacientes colombianos / Clinical and biochemical diagnosis of leigh syndrome in five colombian patients / Diagnóstico clínico e bioquímico da síndrome de leigh em cinco pacientes colombianos

Resumen El síndrome de Leigh (SL) es una enfermedad neurodegenerativa, descrita como una encefalomielopatía necrotizante subaguda, y es una de las enfermedades de origen mitocondrial más frecuentes. El SL es causado por el déficit en la producción de energía, originada en defectos en los genes que codifican alguno de los complejos mitocondriales; el gen afectado puede ser de codificación tanto nuclear como mitocondrial, lo que explica que se encuentren diferentes mecanismos de herencia, incluyendo autosómica recesiva y herencia materna, lo que, a su vez, hace más difícil su diagnóstico molecular. Clínicamente se presenta con regresión del desarrollo cognitivo y pérdida de habilidades motoras con trastorno de movimiento, de rápida progresión. El diagnóstico se basa en la demostración bioquímica de la elevación del ácido láctico y de la relación lactato/piruvato, así como hallazgos en las neuroimágenes por resonancia magnética que muestran lesiones focales, bilaterales y simétricas en ganglios basales o tallo cerebral asociadas a leucoencefalopatía y atrofia cerebral. Se reportan cinco casos con diagnóstico clínico y bioquímico del SL que ejemplifican la variabilidad clínica y gravedad encontrada en este grupo de pacientes.

Summary Leigh syndrome (LS) is a neurodegenerative disease, described as a subacute necrotizing encephalomyelopathy and is one of the most frequent diseases of mitochondrial origin. LS is caused by a deficit in the energy production due to defects in the genes that encode some of the mitochondrial complexes. The affected gene can be due to either nuclear and/or mitochondrial coding, which explains why there are different ways of inheriting the disease, including autosomal recessive and maternal inheritance, which makes its molecular diagnosis even more difficult. Clinically, LS is characterized by regression in cognitive development and motor abilities, as well as movement disorders of rapid progression. Its diagnosis is based on the biochemical demonstration of an increase in lactic acid and lactate / pyruvate ratio, as well as magnetic resonance neuroimaging findings showing focal, bilateral and symmetric lesions in basal ganglia or brainstem associated with leukoencephalopathy and cerebral atrophy. Five cases are reported with clinical and biochemical diagnosis of LS that exemplify the clinical variability and severity found in this group of patients.

Resumo A síndrome de Leigh (SL) é uma doença neurodegenerativa, descrita como uma encefalomielopatia necrotizante subaguda e é uma das doenças de origem mitocondrial mais frequente. A SL é causada pelo déficit na produção de energia originada em defeitos nos genes que codificam algum dos complexos mitocondriais; o gene afetado pode ser de codificação tanto nuclear como mitocondrial, o que explica que se encontrem diferentes mecanismos de herança, incluindo autossômica recessiva e herança materna, o que torna mais difícil seu diagnóstico molecular. Clinicamente se apresenta com regressão do desenvolvimento do desenvolvimento cognitivo e perda de habilidades motoras com transtorno de movimento, de rápida progressão. O diagnóstico se baseia na demonstração bioquímica da elevação do ácido láctico e da relação lactato/piruvato, assim como descobertas nas neuro imagens por ressonância magnética que mostram lesões focais, bilaterais e simétricas em gânglios basais ou talo cerebral associadas a leucoencefalopatia e atrofia cerebral. Reportam-se cinco casos com diagnóstico clínico e bioquímico da SL que exemplificam a variabilidade clínica e gravidade encontrada neste grupo de pacientes.

Medicinal plants used in Brazil Public Health System with neuroprotective potential: a systematic review / Plantas medicinales utilizadas en el Sistema de Salud Pública de Brasil con potencial neuroprotector: una revisión sistemática

Current pharmacological therapies to treat neurological diseases are at best palliative and manage only the symptoms. Unfortunately, few therapies can affect diseases outcomes and alternative strategies such as stem cell therapy, neurotransplantation and deep brain stimulation are still in progress. Diseases such as Alzheimer's and Parkinson's disease become major public health challenge worldwide. In this way, the interest in the development of neuroprotective drugs of natural origin grows. Hence, this systematic review has quantified the studies that refer neuroprotective potential of plants listed in the Brazilian National List of Medicinal Plants of Interest to the Unified Health System (RENISUS). Searches were performed in two scientific databases (PubMed and Science Direct) from 2010 to 2016. A total of 4.532 articles met the inclusion criteria. 445 studies were considered eligible and were reviewed as full text. Following full analysis, 63 studies were included in this review. The studies covered 12 of the 71 plants belonging to RENISUS. In addition, two species are currently available in the Brazilian public health system as herbal medicine. This review may encourage and contribute to the proper use of medicinal plants in public health system.

Las terapias farmacológicas actuales para tratar enfermedades neurológicas son, en el mejor de los casos, paliativas y sólo controlan los síntomas. Desafortunadamente, pocas terapias pueden afectar los avances de las enfermedades y las estrategias alternativas tales como terapia con células madre, neurotransplantate y la estimulación profunda del cerebro están todavía en curso. Enfermedades como el Alzheimer y la enfermedad de Parkinson se convierten en un reto importante para la salud pública en todo el mundo. De esta manera, crece el interés en el desarrollo de fármacos neuroprotectores de origen natural. Por lo tanto, esta revisión sistemática ha cuantificado los estudios que hacen referencia al potencial neuroprotector de las plantas incluidas en la Lista Nacional Brasileña de Plantas Medicinales de Interés para el Sistema Único de Salud (RENISUS). Las búsquedas se realizaron en dos bases de datos científicas (PubMed y Science Direct) de 2010 a 2016. Un total de 4,532 artículos cumplieron los criterios de inclusión. 445 estudios se consideraron elegibles y se revisaron como texto completo. Después del análisis completo, se incluyeron 63 estudios en esta revisión. Los estudios abarcaron 12 de las 71 plantas pertenecientes a RENISUS. Además, actualmente hay dos especies disponibles en el sistema de salud pública brasileño como medicina herbaria. Esta revisión puede alentar y contribuir al uso adecuado de las plantas medicinales en el sistema de salud pública.

Nueva mutación en el gen ATM en paciente con ataxis telangiectasia: Caso clínico / New mutation in ATM gen in patient whith Ataxia Telangiectasia: Clinical case

Introducción: El síndrome de ataxia telangiectasia (AT) es una enfermedad genética autosómica recesiva de compromiso multisistémico, con un espectro clínico amplio, ocasionada por la mutación del gen ATM, lo que causa la disminución o ausencia de la proteinkinasa ATM, por lo que se alteran procesos del ciclo celular, reparación del ADN y apoptosis. El objetivo de este artículo es el de reportar el caso de una paciente con síndrome de AT causada por una mutación no reportada previamente en la literatura. Caso clínico: Paciente originaria de Colombia, de 14 años de edad, con manifestaciones clínicas y fenotípicas clásicas del síndrome de AT a partir de los 6 años de edad, con alteración pondoestatural, infecciones respiratorias a repetición, telangiectasias oculocutáneas y compromiso neurológico progresivo, caracterizado por regresión en su desarrollo psicomotor, ataxia y apraxia oculomotora. Se realizó secuenciación del gen ATM que demostró mutación en homocigosis no reportada previamente en la literatura. Discusión: En Latinoamérica son escasos los reportes de pacientes con AT y pocos aquellos en donde se describen los hallazgos moleculares. Los estudios moleculares son una herramienta que facilita el diagnóstico y permite orientar mejor el manejo y pronóstico de pacientes con enfermedades neurodegenerativas. El reporte de variantes moleculares no descritas es de gran importancia para establecer la causa etiológica de este tipo de patologías en grupos poblacionales diversos, como lo son los países de Latinoamérica.

Introduction: The ataxia telangiectasia syndrome (AT) is a genetic disease with an autosomal recessive inheritance pattern, with multisystem involvement and a broad clinical spectrum. It is caused by the mutation of the ATM gene, causing reduction or absence of the ATM proteinkinase, altering processes in the cell cycle, DNA repair and apoptosis. The objective of this article is to report the case of a patient with ataxia telangiectasia syndrome, caused by a mutation not previously reported in the literature. Case report: A 14 year-old patient native to Colombia, with classic clinical and phenotypical manifestations of AT syndrome, which started at 6 years of age with pondostatural alteration, recurrent respiratory infections, oculocutaneus telangiectasias and progressive neurological disorder that included: regression in her psychomotor development, ataxia and oculomotor apraxia. ATM gene sequencing is performed evidencing a homozygous mutation not reported in literature. Discussion: In Latin America are sparse the number of reports of patients with ataxia telangiectasia and only few of these describe their molecular findings. Molecular studies allow the diagnosis and a better orientation in the management and prognosis of patients with neurodegenerative diseases. The report of undescribed molecular variants is of great importance to establish the etiology of such diseases in diverse population groups, such as the countries of Latin America.

Presentación atípica de la enfermedad de Alexander infantil sin macrocefalia / An atypical presentation of Infantile Alexander disease lacking macrocephaly

Resumen: Introducción: La enfermedad de Alexander consiste en una forma de leucodistrofia poco frecuente que afecta principalmente a los astrocitos; tiene un patrón de herencia autosómica recesiva y es causada por mutaciones en el gen GFAP, localizado en el cromosoma 17q21. Puede presentarse a cualquier edad y la forma infantil se caracteriza por macrocefalia, crisis convulsivas, retraso motor y cognitivo grave y espasticidad o ataxia progresivas. Caso clínico: Paciente de sexo femenino de 8 meses evaluada por retraso psicomotor y crisis convulsivas motoras focales no provocadas. En la exploración física, con perímetro cefálico normal, respuesta motora incrementada ante estímulos táctiles y al ruido, signos piramidales y ausencia de visceromegalias. Se observó hipodensidad generalizada de la sustancia blanca en la resonancia magnética y punción lumbar con hiperproteinorraquia. Se descartó enfermedad de Krabbe mediante ensayo enzimático y secuenciación del gen GALC. En la reevaluación del caso, las alteraciones en la neuroimagen hicieron sospechar de enfermedad de Alexander, y la secuenciación del gen GFAP reportó una mutación en el exón 4 c.716G > A, lo que ocasionó un cambio de arginina por histidina en la posición 239 de la proteína (p.Arg239His). Conclusiones: Los signos radiológicos en la resonancia fueron determinantes para el diagnóstico, que posteriormente se confirmó con estudio molecular. Es importante considerar que ciertas mutaciones no se asocian con macrocefalia, lo cual puede ocasionar retraso en el diagnóstico.

Abstract: Background: Alexander disease is a rare form of leukodystrophy that involves mainly astrocytes; it is inherited in an autosomal recessive manner and occurs by mutations in the GFAP gene, located on chromosome 17q21. It can occur at any age and its infantile form is characterized by macrocephaly, seizures, severe motor and cognitive delay, and progressive spasticity or ataxia. Case report: An 8-month-old female was evaluated with a history of neurodevelopmental delay and unprovoked focal motor seizures. Physical examination showed normal head circumference, increased motor responses to tactile and noise stimuli, pyramidal signs and no visceromegalies. Widespread hypodense white matter was found on magnetic resonance and lumbar puncture showed hyperproteinorrachia. Krabbe disease was ruled out by enzymatic assay and gene sequencing of GALC. In the reassessment of the case, abnormalities in neuroimaging lead to suspicion of Alexander disease, and GFAP gene sequencing reported a pathogenic mutation in exon 4 c.716G > A, which caused a change of arginine to histidine at position 239 of the protein (p.Arg239His). Conclusions: The radiographic signs observed in the resonance were decisive for the diagnosis, later confirmed by molecular study. It is important to consider that certain mutations are not associated with macrocephaly, which may cause delay in diagnosis.

[An atypical presentation of Infantile Alexander disease lacking macrocephaly]. / Presentación atípica de la enfermedad de Alexander infantil sin macrocefalia.

BACKGROUND: Alexander disease is a rare form of leukodystrophy that involves mainly astrocytes; it is inherited in an autosomal recessive manner and occurs by mutations in the GFAP gene, located on chromosome 17q21. It can occur at any age and its infantile form is characterized by macrocephaly, seizures, severe motor and cognitive delay, and progressive spasticity or ataxia. CASE REPORT: An 8-month-old female was evaluated with a history of neurodevelopmental delay and unprovoked focal motor seizures. Physical examination showed normal head circumference, increased motor responses to tactile and noise stimuli, pyramidal signs and no visceromegalies. Widespread hypodense white matter was found on magnetic resonance and lumbar puncture showed hyperproteinorrachia. Krabbe disease was ruled out by enzymatic assay and gene sequencing of GALC. In the reassessment of the case, abnormalities in neuroimaging lead to suspicion of Alexander disease, and GFAP gene sequencing reported a pathogenic mutation in exon 4 c.716G>A, which caused a change of arginine to histidine at position 239 of the protein (p.Arg239His). CONCLUSIONS: The radiographic signs observed in the resonance were decisive for the diagnosis, later confirmed by molecular study. It is important to consider that certain mutations are not associated with macrocephaly, which may cause delay in diagnosis.

Enfermedad de Tay-Sachs / Tay-Sachs disease

La enfermedad de Tay-Sachs es un trastorno neurodegenerativo progresivo de herencia autosómica recesiva. Se debe a la deficiencia de la enzima β-hexosaminidasa A, que provoca una acumulación de gangliósidos GM2 en los lisosomas. Se incluye dentro de las esfingolipidosis. De las esfingolipidosis que presentan mancha rojo cereza en la mácula, la enfermedad de Tay-Sachs es la única en la que no se evidencia hepatoesplenomegalia. La variante más frecuente se inicia en la lactancia. Se presenta un lactante del sexo masculino al que se le realizó el diagnóstico de esta entidad a los 8 meses de edad. A partir de los 4 meses comenzó a presentar una reacción de sobresalto. A los 6 meses comenzó a perder habilidades previamente adquiridas y crisis epilépticas mioclónicas. Se constató una disminución de la actividad específica de la enzima hexosaminidasa A en leucocitos.

Tay-Sachs disease is a progressive autosomal recessive inherited neurodegenerative disorder caused by Beta-hexosaminidase A enzyme deficiency that in turn provokes GM2 ganglioside accumulation in the lysosomes. It is included in the sphyngolipidoses classification. Among the sphyngolipidoses that present with cherry-red spot in the macula, Tay-Sachs disease is the only one that does not show hepatosplenomegaly. The most frequent variant begins at the breast-feeding phase. This report presented a male nursling who was diagnosed with Tay-Sachs disease at the age of 8 months. At 4 months of age, he had begun getting some fright reactions. At 6 months-old, he began losing his previously acquired skills and suffering myoclonic seizures. The cause was the reduced specific activity of the hexosaminidase A enzyme in leukocytes.

Enfermedad de Tay-Sachs / Tay-Sachs disease

La enfermedad de Tay-Sachs es un trastorno neurodegenerativo progresivo de herencia autosómica recesiva. Se debe a la deficiencia de la enzima β-hexosaminidasa A, que provoca una acumulación de gangliósidos GM2 en los lisosomas. Se incluye dentro de las esfingolipidosis. De las esfingolipidosis que presentan mancha rojo cereza en la mácula, la enfermedad de Tay-Sachs es la única en la que no se evidencia hepatoesplenomegalia. La variante más frecuente se inicia en la lactancia. Se presenta un lactante del sexo masculino al que se le realizó el diagnóstico de esta entidad a los 8 meses de edad. A partir de los 4 meses comenzó a presentar una reacción de sobresalto. A los 6 meses comenzó a perder habilidades previamente adquiridas y crisis epilépticas mioclónicas. Se constató una disminución de la actividad específica de la enzima hexosaminidasa A en leucocitos(AU)

Tay-Sachs disease is a progressive autosomal recessive inherited neurodegenerative disorder caused by Beta-hexosaminidase A enzyme deficiency that in turn provokes GM2 ganglioside accumulation in the lysosomes. It is included in the sphyngolipidoses classification. Among the sphyngolipidoses that present with cherry-red spot in the macula, Tay-Sachs disease is the only one that does not show hepatosplenomegaly. The most frequent variant begins at the breast-feeding phase. This report presented a male nursling who was diagnosed with Tay-Sachs disease at the age of 8 months. At 4 months of age, he had begun getting some fright reactions. At 6 months-old, he began losing his previously acquired skills and suffering myoclonic seizures. The cause was the reduced specific activity of the hexosaminidase A enzyme in leukocytes(AU)

Promotion of cardiovascular health at three stages of life: never too soon, never too late.

Cardiovascular disease is the leading cause of death worldwide, with an especially devastating impact in low-to-medium income countries. Cardiovascular disease has been elevated to this position by a combination of factors that include urbanization and its attendant effects, such as obesity, a sedentary lifestyle, changes in dietary habits, and smoking. Given the enormous extent of the problem and the complexity of its causes, which include cultural, social, political, and health care factors, an equally sophisticated and comprehensive strategy is required to combat cardiovascular disease on a global scale. Because exposure to cardiovascular risk factors occurs from early ages, this strategy must be expanded and adjusted throughout the life of an individual. Thus, our efforts should be concentrated not only on cardiovascular disease treatment and prevention, but also on health promotion and primordial prevention. In this review, we present different strategies yielding encouraging results at the population level, from childhood until old age, that aim to protect against the challenges facing the scientific community when combating cardiovascular disease.

Comportamiento de la mortalidad por la Enfermedad de Parkinson en Chile en el periodo 1990-2009 / Mortality behavior of Parkinson's disease in Chile 1990-2009

Introducción. La Enfermedad de Parkinson ocupa el cuarto lugar dentro de las enfermedades neurodegenerativas en el mundo. Objetivo. Describir el comportamiento de las tasas de mortalidad por la Enfermedad de Parkinson en el periodo de 20 años (1990 a 2009) en Chile. Materiales y Métodos. Los datos de mortalidad fueron obtenidos del Departamento de Estadísticas e Información de Salud del Ministerio de Salud de Chile. Se seleccionaron muertes según la Clasificación Internacional de Enfermedades versiones 9 y 10. Se ajustaron las tasas mediante el método de estandarización directo. Para el análisis de tendencia de tasas de mortalidad se utilizaron modelos de regresión de joinpoint. Resultados. Entre 1990 y 2009 hubo 4910 muertes por la Enfermedad de Parkinson (2565 hombres y 2345 mujeres). En este periodo la tasa de mortalidad ajustada aumentó de 0,94 a 2,0 por 100.000 habitantes. La mayor mortalidad ocurrió en hombres (1,19 a 2,54 por 100.000 habitantes versus mujeres 0,75 a 1,62 por 100.000 habitante). El mayor aumento de la mortalidad ocurrió en el periodo 1999-2002 (47,8%), mientras que entre los años 2002 y 2009 el aumento sólo fue de 2,5%. Similar comportamiento se evidenció en mujeres (45,3% y 2,4% respectivamente). Discusión y Conclusión. La tasa de mortalidad por la Enfermedad de Parkinson se ha duplicado en el curso de dos décadas en Chile. Este efecto podría deberse a mayor capacidad diagnóstica o a un aumento genuino en la mortalidad. Se deben investigar las causas de este comportamiento.

Introduction. Parkinson's disease is the fourth in neurodegenerative diseases in the world. Objective. To describe the behavior of mortality rates of Parkinson's disease in a span of 20 years (1990 to 2009) in Chile. Materials and Methods. Mortality data were obtained from the Department of Health Information and Statistics of the Ministry of Health of Chile. Deaths according to the International Classification of Diseases versions 9 and 10 were selected. Rates were adjusted by the method of direct standardization. For trend analysis of mortality rates Joinpoint Regression models were used. Results. Between 1990 and 2009 there were 4910 deaths by Parkinson's disease (2565 men and 2345 women). The adjusted mortality rate increased from 0.94 to 2.0 per 100,000 populations between 1990 and 2009. The Parkinson's disease mortality rate doubled during the study period with sex differences, being higher in men (1.19 to 2.54 per 100,000 in men versus 0.75 to 1.62 per 100,000 in women) between 1990 and 2009. Conclusion. The mortality rate for Parkinson's disease has doubled in the course of two decades. This effect could be due to greater diagnostic capacity or to a genuine increase in mortality. It is necessary to investigate the causes of such increase and of gender differences.

Cycads and their association with certain neurodegenerative diseases.

INTRODUCTION: Cycads are ornamental plants that in some parts of the world are used as fresh food or raw material for producing flour with a high nutritional value. However, they also contain active compounds, including methylazoxymethanol, ß-methylamino-L-alanine, ß-alanine-L-oxalylamino and cycasin, which may produce neurotoxic effects. Some studies have associated consuming cycads and their derivatives with neurodegenerative diseases such as amyotrophic lateral sclerosis/Parkinsonism dementia complex, and other diseases characterised by motor impairment. Therefore, we must not forget that any product, no matter how natural, may present health risks or benefits depending on the chemical compounds it contains and the susceptibility of those who consume it. DEVELOPMENT: We completed a literature analysis to evaluate the neurotoxic properties of cycads and their association with neurological diseases in order to provide structured scientific information that may contribute to preventing health problems in people who use these plants. CONCLUSION: Cycads contain neurotoxic compounds that may contribute to the development of neurological diseases when ingested improperly. We must be mindful of the fact that while some plants have a high nutritional value and may fill the food gap for vulnerable populations, they can also be toxic and have a negative impact on health.

Actualización sobre la Enfermedad de Alzheimer / Alzheimers Disease Updating

La enfermedad de Alzheimer es un padecimiento neurodegenerativo progresivo, que afecta la memoria, el pensamiento, la conducta y la capacidad de realizar actividades diarias; constituyendo un creciente problema de salud en el orden médico, económico, social y humano. Pese a décadas de investigaciones, los médicos tienen pocos tratamientos para este tipo de demencia. Identificar a los pacientes que corren riesgo de sufrir la enfermedad ayudaría a tomar las medidas necesarias para prevenir o retrasar su aparición. Por tanto, es una necesidad urgente que se realicen investigaciones dirigidas a estimar la prevalencia e incidencia de la enfermedad, así como sus elementos epidemiológicos. Es por ello que en la presente revisión se abordan los aspectos relacionados con la epidemiología, los factores de riesgo, el diagnóstico y las estrategias actuales de tratamiento de esta patología (AU)

Alzheimer's disease is a progressive neurodegenerative disease that affects memory, thought, behavior and the capacity of carrying out daily activities, constituting a growing health problem in the medical, economic, social and human order. In spite of decades of investigations, doctors have few treatments for this type of dementia. To identify the patients at risk of suffering this illness would help to take the necessary measures to prevent or to delay its appearance. Therefore, there is an urgent necessity to do research directed to estimate the prevalence and incidence of the disease, as well as its epidemic elements. That is why the aspects related to the epidemiology, risk factors, diagnosis and current strategies of treatment for this pathology are dealt with in the present revision (AU)