Beneficios en la calidad de vida de un programa de cribado y tratamiento de apnea obstructiva del sueño en pacientes con ictus isquémico agudo

[Introducción] La apnea obstructiva del sueño (AOS) se ha propuesto como un factor de mal pronóstico en el ictus. Pretendemos determinar si una intervención sobre la AOS puede mejorar las escalas de calidad de vida (primer objetivo) y de discapacidad (segundo objetivo).[Pacientes y métodos] El grupo de intervención de este estudio cuasi experimental incluye a pacientes con ictus isquémico agudo < 72 horas de evolución a quienes se les realizó poligrafía, así como presión positiva continua en las vías aéreas (CPAP) y medidas higienicodietéticas si se requerían. En el grupo de control se siguió la práctica clínica habitual. Se aplicaron las escalas Short Form 36 Health Survey (SF-36) y modified Rankin Score (mRS) en el sexto mes del ictus en ambos grupos.[Resultados] Se incluyó a 55 y a 62 pacientes en el grupo de intervención y en el de control, respectivamente. En el grupo de intervención, el 64,71% de los pacientes aceptó la CPAP indicada (16 casos con buena adhesión). Se detectó una mejoría en los ítems de la escala SF-36 en el grupo de intervención: funcionamiento físico (p = 0,008), rol físico (p = 0,002), dolor corporal (p = 0,008), salud general (p < 0,001), vitalidad (p = 0,001) y rol emocional (p = 0,015). En un análisis por protocolo, todas estas mejorías se comprobaron en el grupo de pacientes tratados con CPAP con buena adhesión (p < 0,05 en todos los ítems de la SF-36). El porcentaje de pacientes con el sumatorio del componente físico = 50 fue más alto en el grupo de intervención (p = 0,003). No había diferencias en la mediana de la mRS (p = 0,262).[Conclusiones] Aunque se necesitan más evidencias, nuestro estudio sugiere una mejoría significativa de la calidad de vida tras nuestra intervención en la AOS, especialmente en pacientes con buena adhesión a la CPAP.Peer reviewe

High prevalence of obstructive sleep apnea syndrome in Spain’s Stroke Belt

[Objective] Spain’s so-called Stroke Belt is an area with high prevalence of vascular disease. We aimed to determine the prevalence of undetected obstructive sleep apnea–hypopnea syndrome (OSAHS) among patients with acute ischemic stroke (AIS) in southern Spain.[Methods] We conducted a cross-sectional study at the Virgen Macarena University Hospital Stroke Unit during 2018 to 2019. We included patients <72 hours after AIS with a neuroimaging lesion and performed sleep tests.[Results] Seventy-two patients were included. The median participant age was 72 years. Mean body mass index was 27.07 kg/m2, and 40.28% were daily alcohol drinkers. Hypertension, atrial fibrillation, ischemic cardiomyopathy, and previous stroke were detected in 63.9%, 11.1%, 15.3%, and 17.6% of patients, respectively. Polygraphy was feasible in 91.38% of patients. The prevalence of OSAHS was 84.72% (apnea–hypopnea index ≥5). Patients with moderate and severe OSAHS were more likely to be obese and to have a larger neck circumference and facial palsy. The diagnostic criteria of central sleep apnea syndrome were met in only 1.38% of patients.[Conclusions] The high prevalence of OSAHS found in the Spanish Stroke Belt justifies further investigation and development of a screening program as a strategy to identify patients with undetected OSAHS.The authors disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported by the Neurovascular Research Group, part of the Cooperative Cerebrovascular Disease Research Network (INVICTUS+) (RD16/0019/0015).Peer reviewe

Genome-wide association analysis of dementia and its clinical endophenotypes reveal novel loci associated with Alzheimer's disease and three causality networks : The GR@ACE project

Introduction: Large variability among Alzheimer's disease (AD) cases might impact genetic discoveries and complicate dissection of underlying biological pathways. Methods: Genome Research at Fundacio ACE (GR@ACE) is a genome-wide study of dementia and its clinical endophenotypes, defined based on AD's clinical certainty and vascular burden. We assessed the impact of known AD loci across endophenotypes to generate loci categories. We incorporated gene coexpression data and conducted pathway analysis per category. Finally, to evaluate the effect of heterogeneity in genetic studies, GR@ACE series were meta-analyzed with additional genome-wide association study data sets. Results: We classified known AD loci into three categories, which might reflect the disease clinical heterogeneity. Vascular processes were only detected as a causal mechanism in probable AD. The meta-analysis strategy revealed the ANKRD31-rs4704171 and NDUFAF6-rs10098778 and confirmed SCIMP-rs7225151 and CD33-rs3865444. Discussion: The regulation of vasculature is a prominent causal component of probable AD. GR@ACE meta-analysis revealed novel AD genetic signals, strongly driven by the presence of clinical heterogeneity in the AD series

Multiancestry analysis of the HLA locus in Alzheimer’s and Parkinson’s diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes

Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinson’s disease (PD) and Alzheimer’s disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased Aβ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues

Cervical dissection diagnoses increase following endovascular treatments

[Objectives] The detection of cervical arterial dissection (CAD) has been rising in recent years owing to advanced imaging techniques. The aim of this study was to explore whether wide implementation of endovascular treatment for ischemic stroke has an impact on the diagnosis of CAD.[Methods] We included all patients with CAD diagnosed at two university hospitals in Seville, Spain from January 2015 to December 2017. We collected clinical variables and information on imaging techniques used for the diagnosis. Implementation of 24 hour/365 day mechanical thrombectomy began in Seville on 15 August 2016. We compared diagnosis rates of CAD performed before and after this date.[Results] We identified 41 patients with CAD. We found 13 patients diagnosed before (1.1% of all ischemic strokes) and 28 (2.2%) after implementation of neurointerventional therapy. In 17 patients, diagnosis was made in the acute phase. Dissection was not suspected according to computed tomography angiography in 11 patients owing to small dissections (n = 2) or total occlusion (n = 9).[Conclusions] CAD diagnoses have been rising in recent years, essentially owing to continuous improvement in imaging techniques. Rapid access to arteriography for thrombectomy is increasing the diagnoses of CAD, even in patients with a low suspicion of dissection

Circulating microRNA after autologous bone marrow mononuclear cell (BM-MNC) injection in patients with ischemic stroke

Previous studies have shown the potential of microRNAs (miRNA) in the pathological process of stroke and functional recovery. Bone marrow mononuclear cell (BM-MNC) transplantation improves recovery in experimental models of ischemic stroke that might be related with miRNA modifications. However, its effect on circulating miRNA has not been described in patients with stroke. We aimed to evaluate the circulating levels of miRNAs after autologous BM-MNC transplantation in patients with stroke. We investigate the pattern of miRNA-133b and miRNA-34a expression in patients with ischemic stroke included in a multicenter randomized controlled phase IIb trial (http://www.clinicaltrials.gov; unique identifier: NCT02178657). Patients were randomized to 2 different doses of autologous intra-arterial BM-MNC injection (2×106/kg or 5×106/kg) or control group within the first 7 days after stroke onset. We evaluate plasma concentration of miRNA-113b and miRNA-34a at inclusion and 4, 7, and 90 days after treatment. Thirteen cases (8 with 2×106/kg BM-MNC dose and 5 with 5×106/kg dose) and 11 controls (BM-MNC non-treated) were consecutively included. Mean age was 64.1±12.3 with a mean National Institutes of Health Stroke Scale score at inclusion of 14.5. Basal levels of miRNA were similar in both groups. miR-34a-5p and miR-133b showed different expression patterns. There was a significant dose-dependent increase of miRNA-34a levels 4 days after BM-MNC injection (fold change 3.7, p<0.001), whereas miRNA-133b showed a significant increase in the low-dose BM-MNC group at 90 days. Intra-arterial BM-MNC transplantation in patients with ischemic stroke seems to modulate early circulating miRNA-34a levels, which have been related to precursor cell migration in stroke and smaller infarct volumes.This work has been supported by the grants PI15/01197, PI18/01414 and RD16/0019/0015 (INVICTUS+) from the Spanish Ministry of Economy and Competitiveness, cofunded by ISCIII and FEDER funds; Mutua Madrileña grant. FMa is supported by a Rio Hortega contract (CM16/00015). Andalusian Initiative for Advanced Therapies (IATA) is the sponsor of the trial