Contribution of "Omic" studies to the understanding of CADASIL. A systematic review

Altres ajuts: Generación Project, Maestro Project, INVICTUS+ networkAltres ajuts: Fundació la Marató de TV (Epigenesis Project)CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is a small vessel disease caused by mutations in NOTCH3 that lead to an odd number of cysteines in the epidermal growth factor (EGF)-like repeat domain, causing protein misfolding and aggregation. The main symptoms are migraines, psychiatric disorders, recurrent strokes, and dementia. Omic technologies allow the massive study of different molecules for understanding diseases in a non-biased manner or even for discovering targets and their possible treatments. We analyzed the progress in understanding CADASIL that has been made possible by omics sciences. For this purpose, we included studies that focused on CADASIL and used omics techniques, searching bibliographic resources, such as PubMed. We excluded studies with other phenotypes, such as migraine or leukodystrophies. A total of 18 articles were reviewed. Due to the high prevalence of NOTCH3 mutations considered pathogenic to date in genomic repositories, one can ask whether all of them produce CADASIL, different degrees of the disease, or whether they are just a risk factor for small vessel disease. Besides, proteomics and transcriptomics studies found that the molecules that are significantly altered in CADASIL are mainly related to cell adhesion, the cytoskeleton or extracellular matrix components, misfolding control, autophagia, angiogenesis, or the transforming growth factor β (TGFβ) signaling pathway. The omics studies performed on CADASIL have been useful for understanding the biological mechanisms and could be key factors for finding potential drug targets

Infarction in the territory of the anterior cerebral artery: clinical study of 51 patients

<p>Abstract</p> <p>Background</p> <p>Little is known about clinical features and prognosis of patients with ischaemic stroke caused by infarction in the territory of the anterior cerebral artery (ACA). This single centre, retrospective study was conducted with the following objectives: a) to describe the clinical characteristics and short-term outcome of stroke patients with ACA infarction as compared with that of patients with ischaemic stroke due to middle cerebral artery (MCA) and posterior cerebral artery (PCA) infarctions, and b) to identify predictors of ACA stroke.</p> <p>Methods</p> <p>Fifty-one patients with ACA stroke were included in the "Sagrat Cor Hospital of Barcelona Stroke Registry" during a period of 19 years (1986–2004). Data from stroke patients are entered in the stroke registry following a standardized protocol with 161 items regarding demographics, risk factors, clinical features, laboratory and neuroimaging data, complications and outcome. The characteristics of these 51 patients with ACA stroke were compared with those of the 1355 patients with MCA infarctions and 232 patients with PCA infarctions included in the registry.</p> <p>Results</p> <p>Infarctions of the ACA accounted for 1.3% of all cases of stroke (<it>n </it>= 3808) and 1.8% of cerebral infarctions (<it>n </it>= 2704). Stroke subtypes included cardioembolic infarction in 45.1% of patients, atherothrombotic infarction in 29.4%, lacunar infarct in 11.8%, infarct of unknown cause in 11.8% and infarction of unusual aetiology in 2%. In-hospital mortality was 7.8% (<it>n </it>= 4). Only 5 (9.8%) patients were symptom-free at hospital discharge. Speech disturbances (odds ratio [OR] = 0.48) and altered consciousness (OR = 0.31) were independent variables of ACA stroke in comparison with MCA infarction, whereas limb weakness (OR = 9.11), cardioembolism as stroke mechanism (OR = 2.49) and sensory deficit (OR = 0.35) were independent variables associated with ACA stroke in comparison with PCA infarction.</p> <p>Conclusion</p> <p>Cardioembolism is the main cause of brain infarction in the territory of the ACA. Several clinical features are more frequent in stroke patients with ACA infarction than in patients with ischaemic stroke due to infarction in the MCA and PCA territories.</p

Infarctions in the vascular territory of the posterior cerebral artery: clinical features in 232 patients

<p>Abstract</p> <p>Background</p> <p>Ischemic stroke caused by infarction in the territory of the posterior cerebral artery (PCA) has not been studied as extensively as infarctions in other vascular territories. This single centre, retrospective clinical study was conducted a) to describe salient characteristics of stroke patients with PCA infarction, b) to compare data of these patients with those with ischaemic stroke due to middle cerebral artery (MCA) and anterior cerebral artery (ACA) infarctions, and c) to identify predictors of PCA stroke.</p> <p>Findings</p> <p>A total of 232 patients with PCA stroke were included in the "Sagrat Cor Hospital of Barcelona Stroke Registry" during a period of 19 years (1986-2004). Data from stroke patients are entered in the stroke registry following a standardized protocol with 161 items regarding demographics, risk factors, clinical features, laboratory and neuroimaging data, complications and outcome. The characteristics of these 232 patients with PCA stroke were compared with those of the 1355 patients with MCA infarctions and 51 patients with ACA infarctions included in the registry.</p> <p>Infarctions of the PCA accounted for 6.8% of all cases of stroke (<it>n </it>= 3808) and 9.6% of cerebral infarctions (<it>n </it>= 2704). Lacunar infarction was the most frequent stroke subtype (34.5%) followed by atherothrombotic infarction (29.3%) and cardioembolic infarction (21.6%). In-hospital mortality was 3.9% (<it>n </it>= 9). Forty-five patients (19.4%) were symptom-free at hospital discharge. Hemianopia (odds ratio [OR] = 6.43), lacunar stroke subtype (OR = 2.18), symptom-free at discharge (OR = 1.92), limb weakness (OR = 0.10), speech disorders (OR = 0.33) and cardioembolism (OR = 0.65) were independent variables of PCA stroke in comparison with MCA infarction, whereas sensory deficit (OR = 2.36), limb weakness (OR = 0.11) and cardioembolism as stroke mechanism (OR = 0.43) were independent variables associated with PCA stroke in comparison with ACA infarction.</p> <p>Conclusions</p> <p>Lacunar stroke is the main subtype of infarction occurring in the PCA territory. Several clinical features are more frequent in stroke patients with PCA infarction than in patients with ischaemic stroke due to infarction in the MCA and ACA territories. In-hospital mortality in patients with PCA territory is low.</p

Factors associated with in-hospital mortality following intracerebral hemorrhage: a three-year study in Tehran, Iran

BACKGROUND: Primary intracerebral hemorrhage (ICH) is one of the common vascular insults with a relatively high rate of mortality. The aim of the current study was to determine the mortality rate and to evaluate the influence of various factors on the mortality of patients with intracerebral hemorrhage (ICH). Demographic characteristics along with clinical features and neuroimaging information on 122 patients with primary ICH admitted to Sina Hospital between 1999–2002 were assessed by multivariate analysis. RESULTS: Of 122 patients diagnosed with intracerebral hemorrhage, 70 were men and 52 were women. Sixtynine percent of subjects were between 60 to 80 years of age. A history of hypertension was the primary cause in 67.2% of participants and it was found more frequent compared to other cardiovascular risk factors such as a history of ischemic heart disease (17.2%), diabetes mellitus (18%) and cigarette smoking (13.1%). The overall mortality rate among ICH patients admitted to the hospital was 46.7%. About one third of the deaths occurred within the first two days after brain injury. Factor independently associated with in-hospital mortality were Glasgow Coma Scale (GCS) score (≤ 8), diabetes mellitus disease, volume of hematoma and and intraventricular hematoma. CONCLUSION: Higher rate of mortality were observed during the first two weeks of hospitalization following ICH. Neuroimaging features along with GCS score can help the clinicians in developing their prognosis

Thalamic haemorrhage vs internal capsule-basal ganglia haemorrhage: clinical profile and predictors of in-hospital mortality

Background: There is a paucity of clinical studies focused specifically on intracerebral haemorrhages of subcortical topography, a subject matter of interest to clinicians involved in stroke management. This single centre, retrospective study was conducted with the following objectives: a) to describe the aetiological, clinical and prognostic characteristics of patients with thalamic haemorrhage as compared with that of patients with internal capsule-basal ganglia haemorrhage, and b) to identify predictors of in-hospital mortality in patients with thalamic haemorrhage. Methods: Forty-seven patients with thalamic haemorrhage were included in the '' Sagrat Cor Hospital of Barcelona Stroke Registry '' during a period of 17 years. Data from stroke patients are entered in the stroke registry following a standardized protocol with 161 items regarding demographics, risk factors, clinical features, laboratory and neuroimaging data, complications and outcome. The region of the intracranial haemorrhage was identified on computerized tomographic (CT) scans and/or magnetic resonance imaging (MRI) of the brain. Results: Thalamic haemorrhage accounted for 1.4% of all cases of stroke (n = 3420) and 13% of intracerebral haemorrhage (n = 364). Hypertension (53.2%), vascular malformations (6.4%), haematological conditions (4.3%) and anticoagulation (2.1%) were the main causes of thalamic haemorrhage. In-hospital mortality was 19% (n = 9). Sensory deficit, speech disturbances and lacunar syndrome were significantly associated with thalamic haemorrhage, whereas altered consciousness (odds ratio [OR] = 39.56), intraventricular involvement (OR = 24.74) and age (OR = 1.23), were independent predictors of in-hospital mortality. Conclusion: One in 8 patients with acute intracerebral haemorrhage had a thalamic hematoma. Altered consciousness, intraventricular extension of the hematoma and advanced age were determinants of a poor early outcome

Assessing the magnitude and direction of asymmetry in unilateral jump and change of direction speed tasks in youth female team-sport athletes

The direction of inter-limb asymmetries and the change of direction (COD) deficit are two aspects that have increased in recent years. The main objective of the present study was to assess the magnitude of neuromuscular asymmetries in an elite youth female team-sports sample and determine its directionality. Secondary objectives were to evaluate the relationship between COD deficit, linear speed and COD time performance. Elite female youth basketball and handball players (n = 33, age = 16 ± 1.17 y) performed the Single Leg Countermovement Jump in vertical (SLCJ-V), horizontal (SLCJ-H), and lateral (SLCJ-L) directions, the COD and the 10-m sprint. Results showed statistical differences between limbs in all the neuromuscular tests (p &lt; 0.001). The Kappa coefficient showed poor to fair levels of agreement between tasks (K range = -0.087 to 0.233), indicating that asymmetries rarely favoured the same limb between skills. Additionally, small and non-significant correlations were found between the linear sprint capacity and the COD ability. The findings of the present study highlight the independent directionality of asymmetries across tests. The COD deficit does not appear to be much more advantageous than COD total time to measure asymmetry. Practitioners are encouraged to use a fitness testing battery to detect existing side differences and each ability should be specifically trained with functional tasks

Cerebral infarction in diabetes: Clinical pattern, stroke subtypes, and predictors of in-hospital mortality

BACKGROUND: To compare the characteristics and prognostic features of ischemic stroke in patients with diabetes and without diabetes, and to determine the independent predictors of in-hospital mortality in people with diabetes and ischemic stroke. METHODS: Diabetes was diagnosed in 393 (21.3%) of 1,840 consecutive patients with cerebral infarction included in a prospective stroke registry over a 12-year period. Demographic characteristics, cardiovascular risk factors, clinical events, stroke subtypes, neuroimaging data, and outcome in ischemic stroke patients with and without diabetes were compared. Predictors of in-hospital mortality in diabetic patients with ischemic stroke were assessed by multivariate analysis. RESULTS: People with diabetes compared to people without diabetes presented more frequently atherothrombotic stroke (41.2% vs 27%) and lacunar infarction (35.1% vs 23.9%) (P < 0.01). The in-hospital mortality in ischemic stroke patients with diabetes was 12.5% and 14.6% in those without (P = NS). Ischemic heart disease, hyperlipidemia, subacute onset, 85 years old or more, atherothrombotic and lacunar infarcts, and thalamic topography were independently associated with ischemic stroke in patients with diabetes, whereas predictors of in-hospital mortality included the patient's age, decreased consciousness, chronic nephropathy, congestive heart failure and atrial fibrillation CONCLUSION: Ischemic stroke in people with diabetes showed a different clinical pattern from those without diabetes, with atherothrombotic stroke and lacunar infarcts being more frequent. Clinical factors indicative of the severity of ischemic stroke available at onset have a predominant influence upon in-hospital mortality and may help clinicians to assess prognosis more accurately

Cerebral infarction in diabetes: Clinical pattern, stroke subtypes, and predictors of in-hospital mortality

BACKGROUND: To compare the characteristics and prognostic features of ischemic stroke in patients with diabetes and without diabetes, and to determine the independent predictors of in-hospital mortality in people with diabetes and ischemic stroke. METHODS: Diabetes was diagnosed in 393 (21.3%) of 1,840 consecutive patients with cerebral infarction included in a prospective stroke registry over a 12-year period. Demographic characteristics, cardiovascular risk factors, clinical events, stroke subtypes, neuroimaging data, and outcome in ischemic stroke patients with and without diabetes were compared. Predictors of in-hospital mortality in diabetic patients with ischemic stroke were assessed by multivariate analysis. RESULTS: People with diabetes compared to people without diabetes presented more frequently atherothrombotic stroke (41.2% vs 27%) and lacunar infarction (35.1% vs 23.9%) (P < 0.01). The in-hospital mortality in ischemic stroke patients with diabetes was 12.5% and 14.6% in those without (P = NS). Ischemic heart disease, hyperlipidemia, subacute onset, 85 years old or more, atherothrombotic and lacunar infarcts, and thalamic topography were independently associated with ischemic stroke in patients with diabetes, whereas predictors of in-hospital mortality included the patient's age, decreased consciousness, chronic nephropathy, congestive heart failure and atrial fibrillation CONCLUSION: Ischemic stroke in people with diabetes showed a different clinical pattern from those without diabetes, with atherothrombotic stroke and lacunar infarcts being more frequent. Clinical factors indicative of the severity of ischemic stroke available at onset have a predominant influence upon in-hospital mortality and may help clinicians to assess prognosis more accurately