PREvention of VENous Thromboembolism in Hemorrhagic Stroke Patients - PREVENTIHS Study: A Randomized Controlled Trial and a Systematic Review and Meta-Analysis.

BACKGROUND: In this randomized trial, currently utilized standard treatments were compared with enoxaparin for the prevention of venous thromboembolism (VTE) in patients with intracerebral hemorrhage (ICH). METHODS: Enoxaparin (0.4 mg daily for 10 days) was started after 72 h from the onset of ICH. The primary outcome was symptomatic or asymptomatic deep venous thrombosis as assessed by ultrasound at the end of study treatment. The safety of enoxaparin was also assessed. We included the results of this study in a meta-analysis of all relevant studies comparing anticoagulants with standard treatments or placebo. RESULTS: PREVENTIHS was prematurely stopped after the randomization of 73 patients, due to the low recruitment rate. The prevalence of any VTE at 10 days was 15.8% in the enoxaparin group and 20.0% in the control group (RR 0.79 [95% CI 0.29-2.12]); 2.6% of enoxaparin and 8.6% of standard therapy patients had severe bleedings (RR 0.31 [95% CI 0.03-2.82]). When these results were meta-analyzed with the results of the selected studies (4,609 patients; 194 from randomized trials), anticoagulants were associated with a nonsignificant reduction in any VTE (OR 0.81; 95% CI 0.43-1.51), in pulmonary embolism (OR 0.53; 95% CI, 0.17-1.60), and in mortality (OR 0.85; 95% CI 0.64-1.12) without increase in hematoma enlargement (OR 0.97; 95% CI, 0.31-3.04). CONCLUSIONS: In patients with acute ICH, the use of anticoagulants to prevent VTE was safe but the overall level of evidence was low due to the low number of patients included in randomized clinical trials.

Formant Space Reconstruction From Brain Activity in Frontal and Temporal Regions Coding for Heard Vowels.

Classical studies have isolated a distributed network of temporal and frontal areas engaged in the neural representation of speech perception and production. With modern literature arguing against unique roles for these cortical regions, different theories have favored either neural code-sharing or cortical space-sharing, thus trying to explain the intertwined spatial and functional organization of motor and acoustic components across the fronto-temporal cortical network. In this context, the focus of attention has recently shifted toward specific model fitting, aimed at motor and/or acoustic space reconstruction in brain activity within the language network. Here, we tested a model based on acoustic properties (formants), and one based on motor properties (articulation parameters), where model-free decoding of evoked fMRI activity during perception, imagery, and production of vowels had been successful. Results revealed that phonological information organizes around formant structure during the perception of vowels; interestingly, such a model was reconstructed in a broad temporal region, outside of the primary auditory cortex, but also in the pars triangularis of the left inferior frontal gyrus. Conversely, articulatory features were not associated with brain activity in these regions. Overall, our results call for a degree of interdependence based on acoustic information, between the frontal and temporal ends of the language network.

Functional and spatial segregation within the inferior frontal and superior temporal cortices during listening, articulation imagery, and production of vowels.

Classical models of language localize speech perception in the left superior temporal and production in the inferior frontal cortex. Nonetheless, neuropsychological, structural and functional studies have questioned such subdivision, suggesting an interwoven organization of the speech function within these cortices. We tested whether sub-regions within frontal and temporal speech-related areas retain specific phonological representations during both perception and production. Using functional magnetic resonance imaging and multivoxel pattern analysis, we showed functional and spatial segregation across the left fronto-temporal cortex during listening, imagery and production of vowels. In accordance with classical models of language and evidence from functional studies, the inferior frontal and superior temporal cortices discriminated among perceived and produced vowels respectively, also engaging in the non-classical, alternative function - i.e. perception in the inferior frontal and production in the superior temporal cortex. Crucially, though, contiguous and non-overlapping sub-regions within these hubs performed either the classical or non-classical function, the latter also representing non-linguistic sounds (i.e., pure tones). Extending previous results and in line with integration theories, our findings not only demonstrate that sensitivity to speech listening exists in production-related regions and vice versa, but they also suggest that the nature of such interwoven organisation is built upon low-level perception.

Modality-independent encoding of individual concepts in the left parietal cortex.

The organization of semantic information in the brain has been mainly explored through category-based models, on the assumption that categories broadly reflect the organization of conceptual knowledge. However, the analysis of concepts as individual entities, rather than as items belonging to distinct superordinate categories, may represent a significant advancement in the comprehension of how conceptual knowledge is encoded in the human brain. Here, we studied the individual representation of thirty concrete nouns from six different categories, across different sensory modalities (i.e., auditory and visual) and groups (i.e., sighted and congenitally blind individuals) in a core hub of the semantic network, the left angular gyrus, and in its neighboring regions within the lateral parietal cortex. Four models based on either perceptual or semantic features at different levels of complexity (i.e., low- or high-level) were used to predict fMRI brain activity using representational similarity encoding analysis. When controlling for the superordinate component, high-level models based on semantic and shape information led to significant encoding accuracies in the intraparietal sulcus only. This region is involved in feature binding and combination of concepts across multiple sensory modalities, suggesting its role in high-level representation of conceptual knowledge. Moreover, when the information regarding superordinate categories is retained, a large extent of parietal cortex is engaged. This result indicates the need to control for the coarse-level categorial organization when performing studies on higher-level processes related to the retrieval of semantic information.

How concepts are encoded in the human brain: A modality independent, category-based cortical organization of semantic knowledge.

How conceptual knowledge is represented in the human brain remains to be determined. To address the differential role of low-level sensory-based and high-level abstract features in semantic processing, we combined behavioral studies of linguistic production and brain activity measures by functional magnetic resonance imaging in sighted and congenitally blind individuals while they performed a property-generation task with concrete nouns from eight categories, presented through visual and/or auditory modalities. Patterns of neural activity within a large semantic cortical network that comprised parahippocampal, lateral occipital, temporo-parieto-occipital and inferior parietal cortices correlated with linguistic production and were independent both from the modality of stimulus presentation (either visual or auditory) and the (lack of) visual experience. In contrast, selected modality-dependent differences were observed only when the analysis was limited to the individual regions within the semantic cortical network. We conclude that conceptual knowledge in the human brain relies on a distributed, modality-independent cortical representation that integrates the partial category and modality specific information retained at a regional level.

Arterial stiffness in patients with deep and lobar intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) accounts for approximately 10% of stroke cases. Hypertension may play a role in the pathogenesis of ICH that occurs in the basal ganglia, thalamus, pons, and cerebellum, but not in that of lobar ICH. Hypertension contributes to decreased elasticity of arteries, thereby increasing the likelihood of rupture in response to acute elevation in intravascular pressure. This study aimed to evaluate arterial stiffness (using the arterial stiffness index [ASI]) in patients with deep (putaminal and thalamic) ICH in comparison with patients with lobar ICH. METHODS: We enrolled 64 patients (mean±SD age: 69.3±10.7 years; 47 men and 17 women) among 73 who referred consecutively to our department for intraparenchymal hemorrhage and underwent brain computed tomography (CT) and cerebral angio-CT. In all the subjects, 24-hour heart rates and blood pressures were monitored. The linear regression slope of diastolic on systolic blood pressure was assumed as a global measure of arterial compliance, and its complement (1 minus the slope), ASI, has been considered as a measure of arterial stiffness. RESULTS: In the patients with deep ICH, ASI was significantly higher than in the patients with lobar ICH (0.64±0.19 vs. 0.53±0.17, P=0.04). CONCLUSIONS: Our results suggest that in deep ICH, arterial stiffening represents a possible pathogenetic factor that modifies arterial wall properties and contributes to vascular rupture in response to intravascular pressure acute elevation. Therapeutic strategies that reduce arterial stiffness may potentially lower the incidence of deep hemorrhagic stroke.

Thrombolytic treatment of cardiac myxoma-induced ischemic stroke: a review.

Primary cardiac tumors are uncommon, with an autopsy frequency of 0.001%-0.28%: 75% of them are benign, and 50-75% of these are myxomas. Often the first neurological manifestations of a cardiac myxoma include transient ischemic attacks and ischemic strokes. Although thrombolytic therapy represents the gold standard for acute ischemic stroke treatment, its safety and effectiveness in stroke patients with myxoma is unknown. From the analysis of the literature on thrombolysis in ischemic stroke patients with myxoma we report clinical evidence supporting the use of thrombolytics, and the application of thrombolysis in this setting of patients. 23 previous reports presented patients with acute ischemic stroke and associated cardiac myxoma treated with thrombolytic therapy: 16 patients were treated with intravenous thrombolysis, 4 patients with intra-arterial thrombolysis and 3 patients were treated with bridging therapy (intravenous alteplase followed by local mechanical thrombolysis). Our review showed that the possible risk of major bleeding in these patients resulted in limited and small hemorrhages; furthermore patients who developed cerebral hemorrhage did not deteriorate clinically: waiting for further confirmation and additional data from a future register, these observations may suggest that, notwithstanding a possible publication bias, i.v. thrombolytic therapy may be a safe treatment in these patients.

Stroke warning syndrome: 18 new cases.

BACKGROUND: Stroke warning syndrome (SWS) is a rare cause of stroke characterized by recurrent and short-lasting episodes of transient focal neurological deficits leading up to infarction. On the basis of clinical findings and neuroimaging, it can be capsular, pontine, or callosal. The aim of this study is to evaluate the prevalence of SWS in patients admitted to our Stroke Unit for an ischemic stroke and to look for the difference in outcome between patients treated or not with systemic thrombolysis by intravenous recombinant tissue plasminogen activator (IV-rtPA). METHODS: Among the 967 patients admitted to our Stroke Unit between April 2008 and January 2013 for ischemic stroke, we identified 18 patients with SWS. Nine patients underwent IV-rtPA (IV Group) and the other 9 (No IV Group) other therapies. RESULTS: The prevalence of SWS in our population was 1.8%. The most common risk factors were hypertension and dyslipidemia in both groups. A good outcome at 3-month follow-up (modified Rankin Scale 0-2) was found in 3 patients (33%) in IV Group and in 5 patients (55%) in No IV Group. CONCLUSION: SWS is an under-recognized syndrome. Intravenous rt-PA treatment seems to have lower efficacy than in other subtypes of strokes, but none of the patients with SWS undergoing treatment presented haemorrhagic transformation or other complications.

BLIND: a set of semantic feature norms from the congenitally blind.

Feature-based descriptions of concepts produced by subjects in a property generation task are widely used in cognitive science to develop empirically grounded concept representations and to study systematic trends in such representations. This article introduces BLIND, a collection of parallel semantic norms collected from a group of congenitally blind Italian subjects and comparable sighted subjects. The BLIND norms comprise descriptions of 50 nouns and 20 verbs. All the materials have been semantically annotated and translated into English, to make them easily accessible to the scientific community. The article also presents a preliminary analysis of the BLIND data that highlights both the large degree of overlap between the groups and interesting differences. The complete BLIND norms are freely available and can be downloaded from http://sesia.humnet.unipi.it/blind_data .

Autonomic activity and baroreflex sensitivity in patients submitted to carotid stenting.

Arterial baroreflex and cardiac autonomic control play important roles in hemodynamic instability after carotid artery stenting (CAS). Spontaneous baroreflex sensitivity (BRS), heart rate variability (HRV) and blood pressure variability (BPV) are established tools for the assessment of arterial baroreflex and cardiac autonomic activity. Aim of the study was to evaluate cardiac autonomic activity (by means of HRV, BPV and BRS) after CAS and to explore the impact of internal carotid artery stenosis on BRS changes after CAS. 37 patients (68±10.45 years) with internal carotid stenosis underwent CAS. HRV, BPV and BRS were measured in all subjects before and at 1 and 72h after CAS. ANOVA was performed to compare BRS, HRV and BPV parameters before and after CAS. Spearman analysis was performed to determine a possible correlation between carotid stenosis degree (or carotid plaque diameter) and BRS changes (ΔBRS). LF/HF (index of sympatho-vagal balance) decreased during postoperative period, in comparison with baseline (2.32±1.70 vs 1.65±1.40, p<0.05). There was a significant negative correlation between carotid stenosis degree and ΔBRS (r=-0.35, p=0.03) and between carotid plaques thickness and ΔBRS (r=-0.36, p=0.02). CAS procedure may cause an alteration of carotid wall mechanical properties, increasing baroreflex sensitivity. BRS does not increase in all the patients, because arterial wall damage and nerve destruction determined by atherosclerotic plaque may reduce ΔBRS.

Safety of intravenous thrombolysis in ischemic stroke caused by left atrial myxoma.

Intravenous thrombolytic treatment represents the gold standard for acute ischemic stroke treatment. However there is some concern to perform this treatment in patients with known cardiac myxomas for the risk of haemorragic complications. Here we described a 63-year-old patient with ischemic stroke due to embolization of atrial myxoma and treated with intravenous recombinant tissue plasminogen activator alteplase. The patient did not show improvement after treatment; 25 days later a brain CT showed an asymptomatic small hemorrhagic infarction, probably due to the large size of ischemic lesion. The lack of response might be explained by the embolization of a large tumor fragment. One-year after cardiac surgery clinical follow-up did not reveal new neurological signs nor symptoms. This case report suggests that systemic thrombolysis is a safe procedure also in patient with atrial myxoma. The efficacy of therapy seems to be related to embolus composition.

[Acquired factor VIII hemophilia in a geriatric patient]. / Emofilia A acquisita: descrizione di un caso clinico in età geriatrica.

Acquired hemophilia is a rare coagulopathy in adults, associated with bleeding complications. Although the etiology of this disorder remains obscure, an autoimmune mechanism produces the development of autoantibodies against factor VIII. About half of cases are associated with other conditions, mainly post-partum, underlying cancer, autoimmune disease. An 81-year-old male was admitted to the hospital with extensive hematomas (neck, chest, arms and lower limbs). There was no family or personal history of congenital bleeding diathesis. He had chronic bronchitis and cerebrovascular disease; no drugs had been used during the month prior to noted symptoms. Laboratory parameters revealed: hemoglobin 10.9 g%, normal platelet count and white blood cells, prolonged activated partial thromboplastin time (98 s), with normal prothrombin time and fibrinogen concentration. An activated partial thromboplastin time mixing study did not show any correction, suggesting a coagulation inhibitor. Lupus anticoagulant and anticardiolipin antibodies were negative. Biochemical, immunological tests and tumor markers were normal. Thoracic and abdominal computed tomographic scan did not reveal pathological images or hematomas. Analysis of clotting factors revealed decreased factor VIII (< 2%) and elevated factor VIII inhibitor (55 Bethesda units). Idiopathic acquired hemophilia diagnosis was made. Red blood cell transfusion and human factor VIII (2000 U/day for 7 days) infusion were initiated, intravenously with methylprednisolone. A progressive improvement in clinical conditions and laboratory parameters was observed. After 18 days the patient was discharged and treated with prednisone. At follow-up control the clinical conditions and laboratory parameters were normal.