Role of the nigrosome 1 absence as a biomarker in amyotrophic lateral sclerosis.

INTRODUCTION: The absence of nigrosome 1 on brain MRI and the hyperechogenicity of substantia nigra (SNh) by transcranial sonography are two useful biomarkers in the diagnosis of parkinsonisms. We aimed to evaluate the absence of nigrosome 1 in amyotrophic lateral sclerosis (ALS) and to address its meaning. METHODS: 136 ALS patients were recruited, including 16 progressive muscular atrophy (PMA) and 22 primary lateral sclerosis (PLS) patients. The SNh area was measured planimetrically by standard protocols. The nigrosome 1 status was qualitatively assessed by two blind evaluators in susceptibility weight images of 3T MRI. Demographic and clinical data were collected and the C9ORF72 expansion was tested in all patients. RESULTS: Nigrosome 1 was absent in 30% of ALS patients (36% of PLS, 29% of classical ALS and 19% of PMA patients). There was no relationship between radiological and clinical laterality, nor between nigrosome 1 and SNh area. Male sex (OR = 3.63 [1.51, 9.38], p = 0.005) and a higher upper motor neuron (UMN) score (OR = 1.10 [1.02, 1.2], p = 0.022) were independently associated to nigrosome 1 absence, which also was an independent marker of poor survival (HR = 1.79 [1.3, 2.8], p = 0.013). CONCLUSION: In ALS patients, the absence of nigrosome 1 is associated with male sex, UMN impairment and shorter survival. This suggests that constitutional factors and the degree of pyramidal involvement are related to the substantia nigra involvement in ALS. Thus, nigrosome 1 could be a marker of a multisystem degeneration, which in turn associates to poor prognosis.

Clot Composition Analysis as a Diagnostic Tool to Gain Insight into Ischemic Stroke Etiology: A Systematic Review.

Mechanical thrombectomy renders the occluding clot available for analysis. Insights into thrombus composition could help establish the stroke cause. We aimed to investigate the value of clot composition analysis as a complementary diagnostic tool in determining the etiology of large vessel occlusion (LVO) ischemic strokes (International Prospective Register of Systematic Reviews [PROSPERO] registration # CRD42020199436). Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we ran searches on Medline (using the PubMed interface) and Web of Science for studies reporting analyses of thrombi retrieved from LVO stroke patients subjected to mechanical thrombectomy (January 1, 2006 to September 21, 2020). The PubMed search was updated weekly up to February 22, 2021. Reference lists of included studies and relevant reviews were hand-searched. From 1,714 identified studies, 134 eligible studies (97 cohort studies, 31 case reports, and six case series) were included in the qualitative synthesis. Physical, histopathological, biological, and microbiological analyses provided information about the gross appearance, mechanical properties, structure, and composition of the thrombi. There were non-unanimous associations of thrombus size, structure, and composition (mainly proportions of fibrin and blood formed elements) with the Trial of Org 10172 in Acute Stroke Treatment (TOAST) etiology and underlying pathologies, and similarities between cryptogenic thrombi and those of known TOAST etiology. Individual thrombus analysis contributed to the diagnosis, mainly in atypical cases. Although cohort studies report an abundance of quantitative rates of main thrombus components, a definite clot signature for accurate diagnosis of stroke etiology is still lacking. Nevertheless, the qualitative examination of the embolus remains an invaluable tool for diagnosing individual cases, particularly regarding atypical stroke causes.

The width of the third ventricle associates with cognition and behaviour in motor neuron disease.

OBJECTIVES: An enlarged width of the third ventricle (WTV) has been described in amyotrophic lateral sclerosis (ALS) patients, although its clinical meaning is unknown. The aims of this study were to evaluate the contribution of demographical, clinical and genetic factors to the WTV in different motor neuron disease (MND) phenotypes and to assess its brain structural correlates. MATERIALS AND METHODS: The WTV was measured by transcranial ultrasound in 107 MND patients (82 diagnosed with classical ALS, 16 with progressive muscular atrophy and 9 with primary lateral sclerosis) and 25 controls. Genetic analysis, and neurological and neuropsychological examinations were performed in patients. Brain volumetric analysis of MR images was obtained in 85 patients. The association of WTV with demographical, clinical, genetic and neuropsychological variables as well as with brain volumes was assessed by multivariable models. RESULTS: Eighteen patients were diagnosed with genetic MND and 42.3% of patients showed executive or behavioural impairment (EBI). MND patients showed larger WTV than controls. The WTV was significantly associated with age, spinal onset and the presence of EBI, but not with the genetic background, the phenotype or disability. Greater WTV was also associated with reduced subcortical grey matter volume, but not with the cortical or the white matter volume. CONCLUSIONS: The enlargement of the WTV found in the different MND phenotypes is attributable to the subcortical grey matter atrophy and is associated with cognitive and behavioural impairment. Larger longitudinal studies are needed to determine its role as biomarker in MND patients with frontotemporal dementia.

Genetic and constitutional factors are major contributors to substantia nigra hyperechogenicity.

Hyperechogenicity of substantia nigra (SNh) is a frequent finding in amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD) and other movement disorders (MD) patients, but its meaning is unclear. To ascertain the contribution of different factors to SNh area, we measured it in 108 ALS, 102 PD, 91 other MD patients and 91 healthy controls. Demographical data were collected in all patients and controls. In ALS patients, we also recorded clinical variables, performed genetic analysis and measured baseline levels of ferritin. After family history and genetic testing, ALS patients were classified as familial (15) or sporadic (93). ALS, PD and other MD patients had a larger SNh area than controls. Left SNh and male gender, but not age, associated with larger SNh area in both patients and controls. Familial ALS patients showed larger SNh area than sporadic ones and familial ALS was the only clinical variable in the multivariate analysis to be associated with larger SNh area in ALS patients. Our results suggest that SNh associates with genetic and constitutional factors (male gender, handedness), some of which predispose to certain neurodegenerative diseases. This evidence supports the idea of SNh as an inborn marker of unspecific neuronal vulnerability.

Neutrophil extracellular traps are increased in patients with acute ischemic stroke: prognostic significance.

Neutrophil extracellular traps (NETs) are networks of DNA, histones, and proteolytic enzymes produced by activated neutrophils through different mechanisms. NET formation is promoted by activated platelets and can in turn activate platelets, thus favoring thrombotic processes. NETs have been detected in venous and arterial thrombosis, but data in stroke are scarce. The aim of this study was to evaluate NETs in the plasma of patients with acute ischemic stroke and their potential association with baseline clinical characteristics, stroke severity, and one-year clinical outcomes. The study included 243 patients with acute ischemic stroke. Clinical and demographic data and scores of stroke severity (NIHSS and mRs) at onset and discharge were recorded. Markers of NETs (cell-free DNA, nucleosomes, and citrullinated histone 3 (citH3)), were determined in plasma. Patients were followed-up for 12 months after the ischemic event. NETs were significantly elevated in the plasma of patients with acute ischemic stroke when compared to healthy subjects. NETs were increased in patients who were over 65 years of age and in those with a history of atrial fibrillation (AF), cardioembolic stroke, high glucose levels, and severe stroke scores at admission and discharge. In multivariate analysis, elevated levels of citH3, the most specific marker of NETs, at onset were independently associated with AF and all-cause mortality at one-year follow-up. NETs play a role in the pathophysiology of stroke and are associated with severity and mortality. In conclusion, citH3 may constitute a useful prognostic marker and therapeutic target in patients with acute stroke.

Fibrinólisis sistémica exitosa en un paciente con endocarditis bacteriana / Successful endovenous fibrinolysis in a patient with bacterial endocarditis

No disponible

Atención urgente al ictus en hospitales con unidad de ictus. Proyecto Quick / Urgent stroke care in hospitals with a stroke unit. Quick Project

Introducción. El ictus es una emergencia médica dependiente del tiempo. La rapidez en su reconocimiento y en la atención que reciben los pacientes es clave en el pronóstico. Objetivos. Analizar los tiempos de actuación médica, evaluar posibles áreas de mejora y estudiar la dotación de recursos de los centros. Pacientes y métodos. Registro prospectivo de pacientes atendidos en ocho unidades de ictus experimentadas españolas con sospecha de ictus y activación del código ictus. Se recogieron los tiempos inicio-puerta, puerta-tomografía computarizada (TC), puerta-aguja, TC-aguja e inicio-aguja. También se recogieron el método de trasporte al hospital, el tipo de ictus y las terapias de reperfusión. En cuanto a la dotación estructural de los centros, se recogieron la ratio de enfermería, la monitorización de camas, la disponibilidad de TC multimodal y resonancia magnética, y la realización de cursos de información o formación. Resultados. Se incluyeron 197 pacientes, de los cuales fueron válidos 181 (151 infartos y 30 hemorragias cerebrales). Las medianas (p25-p75) en minutos fueron: inicio-puerta, 104 (70-188); puerta-TC, 27 (19-41); TC-aguja, 30 (21-43); puertaaguja, 64 (49-83); e inicio-aguja, 156 (129-202). Se aplicaron terapias de reperfusión en 68 pacientes (el 45% de los infartos cerebrales), de los cuales el 81% fueron trombólisis intravenosas; el 7%, tratamientos endovasculares; y el 12%, una combinación de ambos. Los recursos de los centros estuvieron de acuerdo con lo recomendado por las guías clínicas. Hubo un bajo porcentaje de pacientes estudiados con resonancia magnética. Conclusión. El porcentaje de pacientes tratados con trombólisis fue muy elevado y los tiempos de los circuitos intrahospitalarios, aunque buenos, tienen margen de mejora (AU)

Introduction. A stroke is a time-dependent medical emergency. Swiftness in its recognition and in the care received by the patients plays a key role in the prognosis. Aims. To analyse the medical intervention times, to evaluate possible areas where improvements can be made and to examine the allocation of resources in the centres. Patients and methods. The study was based on a prospective register of patients with suspected stroke and stroke code activation treated in eight experienced Spanish stroke units. Onset-to-door, door-to-computed tomography (CT), door-toneedle, CT-to-needle and onset-to-needle times were collected. Information about the means of transport used to get to the hospital, the type of stroke and reperfusion therapies was also collected. With regard to the structural resources of the centres, data were gathered about the nurse-to-patient ratio, bed monitoring, availability of multimodal CT and magnetic resonance, and doing information or training courses. Results. Altogether 197 patients were included, of whom 181 (151 infarctions and 30 brain haemorrhages) were valid. The medians (p25-p75) in minutes were: onset-to-door, 104 (70-188); door-to-CT, 27 (19-41); CT-to-needle, 30 (21-43); doorto-needle, 64 (49-83); and onset-to-needle, 156 (129-202). Reperfusion therapies were applied in 68 patients (45% of the cerebral infarctions), of which 81% were intravenous thrombolyses; 7%, endovascular treatments; and 12%, a combination of the two. The resources available in the centres were in accordance with those recommended by the clinical guidelines. There was a low percentage of patients who were studied by means of magnetic resonance. Conclusion. The percentage of patients treated with thrombolysis was very high and although the times of the in-hospital circuits were good, there is still room for further improvement (AU)

[Urgent stroke care in hospitals with a stroke unit. Quick Project]. / Atención urgente al ictus en hospitales con unidad de ictus. Proyecto Quick.

INTRODUCTION: A stroke is a time-dependent medical emergency. Swiftness in its recognition and in the care received by the patients plays a key role in the prognosis. AIMS: To analyse the medical intervention times, to evaluate possible areas where improvements can be made and to examine the allocation of resources in the centres. PATIENTS AND METHODS: The study was based on a prospective register of patients with suspected stroke and stroke code activation treated in eight experienced Spanish stroke units. Onset-to-door, door-to-computed tomography (CT), door-to-needle, CT-to-needle and onset-to-needle times were collected. Information about the means of transport used to get to the hospital, the type of stroke and reperfusion therapies was also collected. With regard to the structural resources of the centres, data were gathered about the nurse-to-patient ratio, bed monitoring, availability of multimodal CT and magnetic resonance, and doing information or training courses. RESULTS: Altogether 197 patients were included, of whom 181 (151 infarctions and 30 brain haemorrhages) were valid. The medians (p25-p75) in minutes were: onset-to-door, 104 (70-188); door-to-CT, 27 (19-41); CT-to-needle, 30 (21-43); door-to-needle, 64 (49-83); and onset-to-needle, 156 (129-202). Reperfusion therapies were applied in 68 patients (45% of the cerebral infarctions), of which 81% were intravenous thrombolyses; 7%, endovascular treatments; and 12%, a combination of the two. The resources available in the centres were in accordance with those recommended by the clinical guidelines. There was a low percentage of patients who were studied by means of magnetic resonance. CONCLUSION: The percentage of patients treated with thrombolysis was very high and although the times of the in-hospital circuits were good, there is still room for further improvement.

TITLE: Atencion urgente al ictus en hospitales con unidad de ictus. Proyecto Quick.Introduccion. El ictus es una emergencia medica dependiente del tiempo. La rapidez en su reconocimiento y en la atencion que reciben los pacientes es clave en el pronostico. Objetivos. Analizar los tiempos de actuacion medica, evaluar posibles areas de mejora y estudiar la dotacion de recursos de los centros. Pacientes y metodos. Registro prospectivo de pacientes atendidos en ocho unidades de ictus experimentadas españolas con sospecha de ictus y activacion del codigo ictus. Se recogieron los tiempos inicio-puerta, puerta-tomografia computarizada (TC), puerta-aguja, TC-aguja e inicio-aguja. Tambien se recogieron el metodo de trasporte al hospital, el tipo de ictus y las terapias de reperfusion. En cuanto a la dotacion estructural de los centros, se recogieron la ratio de enfermeria, la monitorizacion de camas, la disponibilidad de TC multimodal y resonancia magnetica, y la realizacion de cursos de informacion o formacion. Resultados. Se incluyeron 197 pacientes, de los cuales fueron validos 181 (151 infartos y 30 hemorragias cerebrales). Las medianas (p25-p75) en minutos fueron: inicio-puerta, 104 (70-188); puerta-TC, 27 (19-41); TC-aguja, 30 (21-43); puerta-aguja, 64 (49-83); e inicio-aguja, 156 (129-202). Se aplicaron terapias de reperfusion en 68 pacientes (el 45% de los infartos cerebrales), de los cuales el 81% fueron trombolisis intravenosas; el 7%, tratamientos endovasculares; y el 12%, una combinacion de ambos. Los recursos de los centros estuvieron de acuerdo con lo recomendado por las guias clinicas. Hubo un bajo porcentaje de pacientes estudiados con resonancia magnetica. Conclusion. El porcentaje de pacientes tratados con trombolisis fue muy elevado y los tiempos de los circuitos intrahospitalarios, aunque buenos, tienen margen de mejora.

[Long-term development of carotid stenosis treated by endovascular means: a prospective study in a neurovascular unit]. / Evolución a largo plazo de la estenosis carotídea tratada endovascularmente: estudio prospectivo en una unidad neurovascular.

AIMS: Even today, unlike endarterectomy, long-term development in carotid angioplasty has still not been well defined. The aim of this study is to describe both the short- and long-term development and the rate of restenosis in a consecutive series of patients with carotid stenosis who underwent endovascular treatment at the Hospital Universitario La Fe; a distinction is made between patients with and without symptoms. PATIENTS AND METHODS: From 1999 to 2010, 426 patients were submitted to a carotid angioplasty (25.5% were asymptomatic patients). Clinical follow-ups were conducted in the case of 374 patients. They had annual check-ups and every year a neurosonological study was performed. The aim was to determine what complications occurred during the first 30 days, as well as the long-term complications, to establish the rate of restenosis and to evaluate possible differences between patients with and without symptoms. RESULTS: The morbidity and mortality rate in the first month was 4.2% (4.4% in symptomatic patients and 3.8% in asymptomatic patients). The mean follow-up time was 55 months: 8% of patients presented strokes, 11% suffered from myocardial infarct and 24.3% died, with no significant differences between patients with or without symptoms. The rate of restenosis was 17.3% at five years, 7.5% equal to or above 50% and, of those, 1.1% were symptomatic. Five patients with significant restenosis were successfully treated with endovascular techniques. CONCLUSIONS: Carotid angioplasty is an effective, safe technique in the hands of an experienced professional; our findings are good, both in the short and the long term, with a low rate of restenosis. If this latter condition occurs, vascular intervention techniques are safe and efficient.

Recommendations for the use of transcranial Doppler ultrasonography to determine the existence of cerebral circulatory arrest as diagnostic support for brain death.

INTRODUCTION: The clinical criteria for brain death consist of the demonstration of the absence of any clinical sign of encephalic activity. Confirmatory testing is usually not required for the diagnosis of brain death, except in some special situations that Spanish law details. In these situations demonstrating cerebral circulatory arrest (CCA) by cerebral flow studies is necessary to support the diagnosis of brain death. AIM: To review the use of transcranial Doppler ultrasonography (TCD) for confirming brain death and to establish uniform criteria for the routine use of TCD as a confirmatory test. METHODS: Based on literature analysis, the authors developed guidelines for performance and interpretation of TCD in clinically brain-dead patients, in order to confirm the diagnosis. The active members of the Spanish Neurosonology Society (SONES) reviewed an initial draft, until a consensus was reached. RESULTS: In a clinically brain-dead patient, specific intracranial flow patterns indicating CCA can be visualized by TCD. The specific flow patterns are the presence of reverberating flow and/or systolic spikes, and should be detected in both middle cerebral arteries and also in the basilar artery. We recommend repeating the examination within 30 minutes to confirm the findings. CONCLUSIONS: TCD is a useful method for detecting CCA and therefore can be used to confirm brain death in a clinically brain-dead patient. The presence of reverberating flow, systolic spikes or absence of flow in the basilar and both middle cerebral arteries observed in two examinations is highly specific for the prediction of CCA and brain death in all patients.