Autosomal recessive spinocerebellar ataxia SCAR8/ARCA1: first families detected in Spain.

INTRODUCTION: Autosomal recessive spinocerebellar ataxia type 8 (ARCA1/SCAR8) is caused by mutations of the SYNE1 gene. The disease was initially described in families from Quebec (Canada) with a phenotype of pure cerebellar syndrome, but in recent years has been reported with a more variable clinical phenotype in other countries. Cases have recently been described of muscular dystrophy, arthrogryposis, and cardiomyopathy due to SYNE1 mutations. OBJECTIVE: To describe clinical and molecular findings from 4 patients (3 men and one woman) diagnosed with ARCA1/SCAR8 from 3 Spanish families from different regions. MATERIAL AND METHODS: We describe the clinical, paraclinical, and genetic results from 4 patients diagnosed with ARCA1/SCAR8 at different Spanish neurology departments. RESULTS: Onset occurred in the third or fourth decade of life in all patients. After 15 years of progression, 3 patients presented pure cerebellar syndrome, similar to the Canadian patients; the fourth patient, with over 30 years' progression, presented vertical gaze palsy, pyramidal signs, and moderate cognitive impairment. In all patients, MRI studies showed cerebellar atrophy. The genetic study revealed distinct pathogenic SYNE1 mutations in each family. CONCLUSIONS: ARCA1/SCAR8 can be found worldwide and may be caused by many distinct mutations in the SYNE1 gene. The disease may manifest with a complex phenotype of varying severity.

Exploratory dietary patterns and cognitive function in the "Seguimiento Universidad de Navarra" (SUN) Prospective Cohort.

BACKGROUND: Dementia is projected to affect 135 million by 2050. Diet is a pertinent target for primary prevention, but firm recommendations for dementia prevention are not available yet. Our aim was to address the association between exploratory (empirically derived) dietary patterns (DP) and changes in the Spanish Telephone Interview for Cognitive Status (STICS-m, maximum score = 41 points) over 6 years. METHOD: Information on diet was collected with a validated 136-item food-frequency questionnaire from 803 participants in the Mediterranean cohort "Seguimiento Universidad de Navarra." We used principal component analysis to derive exploratory DP. The derived DP were associated with change in STICS-m scores over 6 years, through adjusted multiple linear regression models. RESULTS: Two main DP were identified. The first DP resembled a Western dietary pattern (WDP)-high in sugar, fat, processed foods, and red meat-and the second DP resembled a Mediterranean dietary pattern (MDP)-high in vegetables, fruits, nuts, fish, and olive oil. Adherence to the WDP (tertile 3 vs tertile 1) was significantly associated with negative STICS-m changes after 6 years (between-tertile difference in changes: -0.80 points; 95% confidence interval [CI] -1.51, -0.08, p value = 0.03). Meanwhile, the MDP showed a positive +0.71 point (95% CI 0.15, 1.26, p value = 0.01) between-tertile difference in changes in the STICS-m score. CONCLUSIONS: A healthy, prudent, MDP was associated with less decline in cognitive function and, thus, could help to lower dementia incidence. Western-type diets were associated with a greater decline in cognitive performance and could increase dementia incidence.

Autosomal recessive spinocerebellar ataxia SCAR8/ARCA1: First families detected in Spain. / Heredoataxia cerebelosa recesiva ARCA1/SCAR8: primeras familias detectadas en España.

INTRODUCTION: Autosomal recessive spinocerebellar ataxia type 8 (ARCA1/SCAR8) is caused by mutations of the SYNE1 gene. The disease was initially described in families from Quebec (Canada) with a phenotype of pure cerebellar syndrome, but in recent years has been reported with a more variable clinical phenotype in other countries. Cases have recently been described of muscular dystrophy, arthrogryposis, and cardiomyopathy due to SYNE1 mutations. OBJECTIVE: To describe clinical and molecular findings from 4 patients (3 men and one woman) diagnosed with ARCA1/SCAR8 from 3 Spanish families from different regions. MATERIAL AND METHODS: We describe the clinical, paraclinical, and genetic results from 4 patients diagnosed with ARCA1/SCAR8 at different Spanish neurology departments. RESULTS: Onset occurred in the third or fourth decade of live in all patients. After 15 years of progression, 3 patients presented pure cerebellar syndrome, similar to the Canadian patients; the fourth patient, with over 30 years' progression, presented vertical gaze palsy, pyramidal signs, and moderate cognitive impairment. In all patients, MRI studies showed cerebellar atrophy. The genetic study revealed distinct pathogenic SYNE1 mutations in each family. CONCLUSIONS: ARCA1/SCAR8 can be found worldwide and may be caused by many distinct mutations in the SYNE1 gene. The disease may manifest with a complex phenotype of varying severity.

Demencia frontotemporal variante conductual: biomarcadores, una aproximación a la enfermedad / Biomarkers: A new approach to behavioural variant frontotemporal dementia

Introducción: Las degeneraciones lobares frontotemporales (DLFT) son un grupo de patologías moleculares que se definen en función de la proteína acumulada en el sistema nervioso central. La demencia frontotemporal variante conductual (DFT vc) es el síndrome clínico de presentación más frecuente. Los avances realizados en los últimos anos han contribuido a un mayor conocimiento de esta entidad, que puede ser el modo de presentación de diferentes enfermedades neurodegenerativas. Desarrollo: Se revisa la correlación entre clínica, patología y genética de las DLFT, en especial de la DFT vc, así como los principales biomarcadores de la enfermedad. La anatomía patológica de la DFT vc es muy variada, sin mostrar asociación significativa con ningún subtipo histopatológico concreto. Entre los biomarcadores disponibles, destacan la neuroimagen anatómica y funcional, los biomarcadores analíticos y la genética. Se están disenando fármacos dirigidos contra dianas moleculares concretas implicadas en la patogenia de las DLFT. Conclusiones: La DFT vc es una causa frecuente de demencia. De entre todas las variantes clínicas de las DLFT, es en la que resulta más difícil establecer una relación clínico-patológica. El uso de biomarcadores puede ayudar a predecir la anatomía patológica subyacente, lo que junto al desarrollo de fármacos ligando-específicos ofrece nuevas posibilidades terapéuticas

Introduction: Lobar frontotemporal degeneration (FTLD) encompasses a group of molecular disease defined by the deposition of an abnormal protein in the central nervous system. Behavioural variant frontotemporal dementia (bvFTD) is the most frequent clinical presentation of FTLD. The past two decades of research have contributed to a better understanding of this entity, which may be the first manifestation in many different neurodegenerative disorders. Development: We reviewed correlations between clinical, pathological, and genetic findings and the main disease biomarkers of FTLD, with particular interest in bvFTD. Anatomical pathology findings in FTLD are heterogeneous and the syndrome is not associated with any one specific histopathological type. Promising available biomarkers include structural and functional neuroimaging techniques and biochemical and genetic biomarkers. Disease-modifying drugs designed for specific molecular targets that are implicated in FTLD pathogenesis are being developed. Conclusions: BvFTD is a frequent cause of dementia. Of all the clinical variants of FTLD, behavioural variant is the one in which establishing a correlation between clinical and pathological signs is the most problematic. A biomarker evaluation may help predict the underlying pathology; this approach, in conjunction with the development of disease-modifying drugs, offers new therapeutic possibilities

Biomarkers: a new approach to behavioural variant frontotemporal dementia.

INTRODUCTION: Lobar frontotemporal degeneration (FTLD) encompasses a group of molecular disease defined by the deposition of an abnormal protein in the central nervous system. Behavioural variant frontotemporal dementia (bvFTD) is the most frequent clinical presentation of FTLD. The past two decades of research have contributed to a better understanding of this entity, which may be the first manifestation in many different neurodegenerative disorders. DEVELOPMENT: We reviewed correlations between clinical, pathological, and genetic findings and the main disease biomarkers of FTLD, with particular interest in bvFTD. Anatomical pathology findings in FTLD are heterogeneous and the syndrome is not associated with any one specific histopathological type. Promising available biomarkers include structural and functional neuroimaging techniques and biochemical and genetic biomarkers. Disease-modifying drugs designed for specific molecular targets that are implicated in FTLD pathogenesis are being developed. CONCLUSIONS: BvFTD is a frequent cause of dementia. Of all the clinical variants of FTLD, behavioural variant is the one in which establishing a correlation between clinical and pathological signs is the most problematic. A biomarker evaluation may help predict the underlying pathology; this approach, in conjunction with the development of disease-modifying drugs, offers new therapeutic possibilities.

Demencia frontotemporal variante conductual: aproximación clínica y terapéutica / Behavioural variant frontotemporal dementia: Clinical and therapeutic approaches

Introducción: La variante conductual de la demencia frontotemporal (DFT vc) es el síndrome clínico más frecuente de las demencias frontotemporales (DFT) y se caracteriza por una alteración progresiva de la personalidad y la conducta. En las últimas 2 décadas, los avances en biología molecular y genética han contribuido a un mayor conocimiento de esta entidad, que puede ser el modo de presentación de diferentes enfermedades neurodegenerativas. Desarrollo: Se revisan los principales aspectos epidemiológicos, clínicos, diagnósticos y terapéuticos de la DFT vc. La mayoría de los casos son esporádicos, iniciándose en torno a los 58 años de media. Los criterios diagnósticos vigentes establecen 3 niveles de certeza diagnóstica: posible, probable y definitivo. El diagnóstico clínico se basa en la anamnesis detallada de familiares, complementada con la realización de test neuropsicológicos dirigidos. Hasta la fecha, los tratamientos empleados son solo sintomáticos y de eficacia controvertida. Se están diseñando fármacos dirigidos contra dianas moleculares específicas implicadas en la patogenia de las degeneraciones lobares frontotemporales. Conclusiones: La DFT vc es una causa frecuente de demencia. Se trata de un síndrome amplio, heterogéneo desde el punto de vista histopatológico y biomolecular. La definición de subtipos clínicos y la identificación de biomarcadores podrían ayudar a predecir la afección subyacente,lo que junto con el desarrollo de fármacos dirigidos contra dianas moleculares ofrece nuevas posibilidades terapéuticas

Introduction: Behavioural variant frontotemporal dementia (bvFTD) is the most frequent presentation in the clinical spectrum of frontotemporal dementia (FTD) and it is characterised by progressive changes in personality and conduct. Major breakthroughs in molecular biology and genetics made during the last two decades have lent us a better understanding of this syndrome, which may be the first manifestation in many different neurodegenerative diseases. Development: We reviewed the main epidemiological, clinical, diagnostic and therapeutic aspects of bvFTD. Most cases manifest sporadically and the average age of onset is 58 years. Current criteria for bvFTD propose three levels of diagnostic certainty: possible, probable, and definite. Clinical diagnosis is based on a detailed medical history provided by family members and caregivers, in conjunction with neuropsychological testing. Treatments which have been used in bvFDT to date are all symptomatic and their effectiveness is debatable. New drugs designed for specific molecular targets that are implicated in frontotemporal lobar degeneration are being developed. Conclusions: BvFDT is a frequent cause of dementia. It is a non-specific syndrome associated with heterogeneous histopathological and biomolecular findings. The definition of clinical subtypes complemented by biomarker identification may help predict the underlying pathology. This knowledge, along with the development of drugs designed for molecular targets, will offer new treatment possibilities

Oclusión arterial de gran vaso diagnosticada por angiografía portomografía computarizada en el ictus isquémico agudo: frecuencia, factores predictores y seguridad / Large artery occlusion diagnosed by computed tomography angiography in acute ischaemic stroke: frequency, predictive factors, and safety

Introducción: Con la creciente disponibilidad de las terapias endovasculares, la demostración de oclusión arterial en el ictus isquémico agudo ha cobrado mayor relevancia. Este estudio evalúa la frecuencia de oclusión arterial y los factores asociados a la misma, así como las complicaciones derivadas del uso de angio-TC en el ictus agudo. Métodos: Se analizan retrospectivamente a los pacientes con ictus isquémico entre el 1 de julio y el 31 de diciembre del 2011. Resultados: Ciento cincuenta y siete pacientes (edad media de 74±11 años, NIHSS 5 [2-13]). Un 56,7% llegó al hospital con menos de 8 h de evolución. Se realizó angio-TC en 71 casos (45,2%), detectando oclusión de gran vaso en 37 (52,1%). La localización más frecuente fue M1 (40%). En el análisis univariante se halló asociación de la escala NIHSS (17 vs. 7, p < 0,001) y la fibrilación auricular (64% vs. 32%, p = 0,006) con la presencia de oclusión arterial. Posteriormente, se realizó una regresión logística, confirmando dicha asociación. No se observó ningún caso de nefropatía por contraste. El tiempo puerta-aguja para fibrinólisis intravenosa fue de 61,2 ± 24,5 min en los pacientes en que se realizó angio-TC y 53,5 ± 34,3 en los que no se realizó (p = 0,495). Conclusiones: La oclusión de gran vaso se detecta en el 23,6% de la muestra, especialmente en los pacientes traídos en las primeras horas. La escala NIHSS es un buen factor predictor

Introduction: Demonstrating artery occlusion in ischaemic stroke has gained importance due to the increasing availability of endovascular therapies. This study evaluates the frequency of artery occlusion, its associated factors, and complications following the use of CT-angiography in acute stroke. Methods: We retrospectively analysed a cohort of patients who suffered acute ischaemic stroke between July and-December 2011. Results: We included 157 patients (mean age, 74 ± 11; mean NIHSS score, 5 [2-13]). Of that total, 56.7% of the patients were admitted to hospital during the first 8 hours. CT-angiography was performed in 71 cases (45.2%); arterial large-vessel occlusion was detected in 37 (52.1%) of these cases, and the most frequent site was M1 (40%). Univariate analysis showed that the NIHSS score (17 vs 7, P < .001) and atrial fibrillation (64% vs 32%, P = .006) were associated with artery occlusion. A logistic regression analysis was performed subsequently, confirming theseassociations. There were no cases of contrast-induced nephropathy. Door-to-needle time for intravenous thrombolysis was 61.2 ± 24.5 minutes in patients who underwent CT-angiography, and 53.5±34.3 minutes in those who did not (P = .495). Conclusions: Arterial occlusions are seen in 23.6% of patients, especially in those who are admitted during the first few hours. NIHSS score serves as a useful predictive factor

Large artery occlusion diagnosed by computed tomography angiography in acute ischaemic stroke: frequency, predictive factors, and safety.

INTRODUCTION: Demonstrating artery occlusion in ischaemic stroke has gained importance due to the increasing availability of endovascular therapies. This study evaluates the frequency of artery occlusion, its associated factors, and complications following the use of CT-angiography in acute stroke. METHODS: We retrospectively analysed a cohort of patients who suffered acute ischaemic stroke between July and-December 2011. RESULTS: We included 157 patients (mean age, 74±11; mean NIHSS score, 5 [2-13]). Of that total, 56.7% of the patients were admitted to hospital during the first 8hours. CT-angiography was performed in 71 cases (45.2%); arterial large-vessel occlusion was detected in 37 (52.1%) of these cases, and the most frequent site was M1 (40%). Univariate analysis showed that the NIHSS score (17 vs 7, P<.001) and atrial fibrillation (64% vs 32%, P=.006) were associated with artery occlusion. A logistic regression analysis was performed subsequently, confirming these associations. There were no cases of contrast-induced nephropathy. Door-to-needle time for intravenous thrombolysis was 61.2±24.5minutes in patients who underwent CT-angiography, and 53.5±34.3minutes in those who did not (P=.495). CONCLUSIONS: Arterial occlusions are seen in 23.6% of patients, especially in those who are admitted during the first few hours. NIHSS score serves as a useful predictive factor.

Behavioural variant frontotemporal dementia: clinical and therapeutic approaches.

INTRODUCTION: Behavioural variant frontotemporal dementia (bvFTD) is the most frequent presentation in the clinical spectrum of frontotemporal dementia (FTD) and it is characterised by progressive changes in personality and conduct. Major breakthroughs in molecular biology and genetics made during the last two decades have lent us a better understanding of this syndrome, which may be the first manifestation in many different neurodegenerative diseases. DEVELOPMENT: We reviewed the main epidemiological, clinical, diagnostic and therapeutic aspects of bvFTD. Most cases manifest sporadically and the average age of onset is 58 years. Current criteria for bvFTD propose three levels of diagnostic certainty: possible, probable, and definite. Clinical diagnosis is based on a detailed medical history provided by family members and caregivers, in conjunction with neuropsychological testing. Treatments which have been used in bvFDT to date are all symptomatic and their effectiveness is debatable. New drugs designed for specific molecular targets that are implicated in frontotemporal lobar degeneration are being developed. CONCLUSIONS: BvFDT is a frequent cause of dementia. It is a non-specific syndrome associated with heterogeneous histopathological and biomolecular findings. The definition of clinical subtypes complemented by biomarker identification may help predict the underlying pathology. This knowledge, along with the development of drugs designed for molecular targets, will offer new treatment possibilities.