Awareness of Stroke Risk after TIA in Swiss General Practitioners and Hospital Physicians.

BACKGROUND Transient ischemic attacks (TIA) are stroke warning signs and emergency situations, and, if immediately investigated, doctors can intervene to prevent strokes. Nevertheless, many patients delay going to the doctor, and doctors might delay urgently needed investigations and preventative treatments. We set out to determine how much general practitioners (GPs) and hospital physicians (HPs) knew about stroke risk after TIA, and to measure their referral rates. METHODS We used a structured questionnaire to ask GPs and HPs in the catchment area of the University Hospital of Bern to estimate a patient's risk of stroke after TIA. We also assessed their referral behavior. We then statistically analysed their reasons for deciding not to immediately refer patients. RESULTS Of the 1545 physicians, 40% (614) returned the survey. Of these, 75% (457) overestimated stroke risk within 24 hours, and 40% (245) overestimated risk within 3 months after TIA. Only 9% (53) underestimated stroke risk within 24 hours and 26% (158) underestimated risk within 3 months; 78% (473) of physicians overestimated the amount that carotid endarterectomy reduces stroke risk; 93% (543) would rigorously investigate the cause of a TIA, but only 38% (229) would refer TIA patients for urgent investigations "very often". Physicians most commonly gave these reasons for not making emergency referrals: patient's advanced age; patient's preference; patient was multimorbid; and, patient needed long-term care. CONCLUSIONS Although physicians overestimate stroke risk after TIA, their rate of emergency referral is modest, mainly because they tend not to refer multimorbid and elderly patients at the appropriate rate. Since old and frail patients benefit from urgent investigations and treatment after TIA as much as younger patients, future educational campaigns should focus on the importance of emergency evaluations for all TIA patients.

Identification of Sleep-Modulated Pathways Involved in Neuroprotection from Stroke.

STUDY OBJECTIVES Sleep deprivation (SDp) performed before stroke induces an ischemic tolerance state as observed in other forms of preconditioning. As the mechanisms underlying this effect are not well understood, we used DNA oligonucleotide microarray analysis to identify the genes and the gene-pathways underlying SDp preconditioning effects. DESIGN Gene expression was analyzed 3 days after stroke in 4 experimental groups: (i) SDp performed before focal cerebral ischemia (IS) induction; (ii) SDp performed before sham surgery; (iii) IS without SDp; and (iv) sham surgery without SDp. SDp was performed by gentle handling during the last 6 h of the light period, and ischemia was induced immediately after. SETTINGS Basic sleep research laboratory. MEASUREMENTS AND RESULTS Stroke induced a massive alteration in gene expression both in sleep deprived and non-sleep deprived animals. However, compared to animals that underwent ischemia alone, SDp induced a general reduction in transcriptional changes with a reduction in the upregulation of genes involved in cell cycle regulation and immune response. Moreover, an upregulation of a new neuroendocrine pathway which included melanin concentrating hormone, glycoprotein hormones-α-polypeptide and hypocretin was observed exclusively in rats sleep deprived before stroke. CONCLUSION Our data indicate that sleep deprivation before stroke reprogrammed the signaling response to injury. The inhibition of cell cycle regulation and inflammation are neuroprotective mechanisms reported also for other forms of preconditioning treatment, whereas the implication of the neuroendocrine function is novel and has never been described before. These results therefore provide new insights into neuroprotective mechanisms involved in ischemic tolerance mechanisms.

Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke

Each year about 650,000 Europeans die from stroke and a similar number lives with the sequelae of multiple sclerosis (MS). Stroke and MS differ in their etiology. Although cause and likewise clinical presentation set the two diseases apart, they share common downstream mechanisms that lead to damage and recovery. Demyelination and axonal injury are characteristics of MS but are also observed in stroke. Conversely, hallmarks of stroke, such as vascular impairment and neurodegeneration, are found in MS. However, the most conspicuous common feature is the marked neuroinflammatory response, marked by glia cell activation and immune cell influx. In MS and stroke the blood-brain barrier is disrupted allowing bone marrow-derived macrophages to invade the brain in support of the resident microglia. In addition, there is a massive invasion of auto-reactive T-cells into the brain of patients with MS. Though less pronounced a similar phenomenon is also found in ischemic lesions. Not surprisingly, the two diseases also resemble each other at the level of gene expression and the biosynthesis of other proinflammatory mediators. While MS has traditionally been considered to be an autoimmune neuroinflammatory disorder, the role of inflammation for cerebral ischemia has only been recognized later. In the case of MS the long track record as neuroinflammatory disease has paid off with respect to treatment options. There are now about a dozen of approved drugs for the treatment of MS that specifically target neuroinflammation by modulating the immune system. Interestingly, experimental work demonstrated that drugs that are in routine use to mitigate neuroinflammation in MS may also work in stroke models. Examples include Fingolimod, glatiramer acetate, and antibodies blocking the leukocyte integrin VLA-4. Moreover, therapeutic strategies that were discovered in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, turned out to be also effective in experimental stroke models. This suggests that previous achievements in MS research may be relevant for stroke. Interestingly, the converse is equally true. Concepts on the neurovascular unit that were developed in a stroke context turned out to be applicable to neuroinflammatory research in MS. Examples include work on the important role of the vascular basement membrane and the BBB for the invasion of immune cells into the brain. Furthermore, tissue plasminogen activator (tPA), the only established drug treatment in acute stroke, modulates the pathogenesis of MS. Endogenous tPA is released from endothelium and astroglia and acts on the BBB, microglia and other neuroinflammatory cells. Thus, the vascular perspective of stroke research provides important input into the mechanisms on how endothelial cells and the BBB regulate inflammation in MS, particularly the invasion of immune cells into the CNS. In the current review we will first discuss pathogenesis of both diseases and current treatment regimens and will provide a detailed overview on pathways of immune cell migration across the barriers of the CNS and the role of activated astrocytes in this process. This article is part of a Special Issue entitled: Neuro inflammation: A common denominator for stroke, multiple sclerosis and Alzheimer's disease, guest edited by Helga de Vries and Markus Swaninger.

Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage

Thioredoxin (TRX) plays important biological roles both in intra- and extracellular compartments, including in regulation of various intracellular molecules via thiol redox control. We produced TRX overexpressing mice and confirmed that there were no anatomical and physiological differences between wild-type (WT) mice and TRX transgenic (Tg) mice. In the present study we subjected mice to focal brain ischemia to shed light on the role of TRX in brain ischemic injury. At 24 hr after middle cerebral artery occlusion, infarct areas and volume were significantly smaller in Tg mice than in WT mice. Moreover neurological deficit was ameliorated in Tg mice compared with WT mice. Protein carbonyl content, a marker of cellular protein oxidation, in Tg mice showed less increase than did that of WT mice after the ischemic insult. Furthermore, c-fos expression in Tg mice was stronger than in WT mice 1 hr after ischemia. Our results suggest that transgene expression of TRX decreased ischemic neuronal injury and that TRX and the redox state modified by TRX play a crucial role in brain damage during stroke.

Immunologic tolerance to myelin basic protein decreases stroke size after transient focal cerebral ischemia

Immune mechanisms contribute to cerebral ischemic injury. Therapeutic immunosuppressive options are limited due to systemic side effects. We attempted to achieve immunosuppression in the brain through oral tolerance to myelin basic protein (MBP). Lewis rats were fed low-dose bovine MBP or ovalbumin (1 mg, five times) before 3 h of middle cerebral artery occlusion (MCAO). A third group of animals was sensitized to MBP but did not survive the post-stroke period. Infarct size at 24 and 96 h after ischemia was significantly less in tolerized animals. Tolerance to MBP was confirmed in vivo by a decrease in delayed-type hypersensitivity to MBP. Systemic immune responses, characterized in vitro by spleen cell proliferation to Con A, lipopolysaccharide, and MBP, again confirmed antigen-specific immunologic tolerance. Immunohistochemistry revealed transforming growth factor β1 production by T cells in the brains of tolerized but not control animals. Systemic transforming growth factor β1 levels were equivalent in both groups. Corticosterone levels 24 h after surgery were elevated in all sham-operated animals and ischemic control animals but not in ischemic tolerized animals. These results demonstrate that antigen-specific modulation of the immune response decreases infarct size after focal cerebral ischemia and that sensitization to the same antigen may actually worsen outcome.

Discovery of adrenomedullin in rat ischemic cortex and evidence for its role in exacerbating focal brain ischemic damage.

Focal brain ischemia is the most common event leading to stroke in humans. To understand the molecular mechanisms associated with brain ischemia, we applied the technique of mRNA differential display and isolated a gene that encodes a recently discovered peptide, adrenomedullin (AM), which is a member of the calcitonin gene-related peptide (CGRP) family. Using the rat focal stroke model of middle cerebral artery occlusion (MCAO), we determined that AM mRNA expression was significantly increased in the ischemic cortex up to 17.4-fold at 3 h post-MCAO (P < 0.05) and 21.7-fold at 6 h post-MCAO (P < 0.05) and remained elevated for up to 15 days (9.6-fold increase; P < 0.05). Immunohistochemical studies localized AM to ischemic neuronal processes, and radioligand (125I-labeled CGRP) displacement revealed high-affinity (IC50 = 80.3 nmol) binding of AM to CGRP receptors in brain cortex. The cerebrovascular function of AM was studied using synthetic AM microinjected onto rat pial vessels using a cranial window or applied to canine basilar arteries in vitro. AM, applied abluminally, produced dose-dependent relaxation of preconstricted pial vessels (P < 0.05). Intracerebroventricular (but not systemic) AM administration at a high dose (8 nmol), prior to and after MCAO, increased the degree of focal ischemic injury (P < 0.05). The ischemia-induced expression of both AM mRNA and peptide in ischemic cortical neurons, the demonstration of the direct vasodilating effects of the peptide on cerebral vessels, and the ability of AM to exacerbate ischemic brain damage suggests that AM plays a significant role in focal ischemic brain injury.

Is ultrasound perfusion imaging capable of detecting mismatch? A proof-of-concept study in acute stroke patients.

In this study, we compared contrast-enhanced ultrasound perfusion imaging with magnetic resonance perfusion-weighted imaging or perfusion computed tomography for detecting normo-, hypo-, and nonperfused brain areas in acute middle cerebral artery stroke. We performed high mechanical index contrast-enhanced ultrasound perfusion imaging in 30 patients. Time-to-peak intensity of 10 ischemic regions of interests was compared to four standardized nonischemic regions of interests of the same patient. A time-to-peak >3 s (ultrasound perfusion imaging) or >4 s (perfusion computed tomography and magnetic resonance perfusion) defined hypoperfusion. In 16 patients, 98 of 160 ultrasound perfusion imaging regions of interests of the ischemic hemisphere were classified as normal, and 52 as hypoperfused or nonperfused. Ten regions of interests were excluded due to artifacts. There was a significant correlation of the ultrasound perfusion imaging and magnetic resonance perfusion or perfusion computed tomography (Pearson`s chi-squared test 79.119, p < 0.001) (OR 0.1065, 95% CI 0.06-0.18). No perfusion in ultrasound perfusion imaging (18 regions of interests) correlated highly with diffusion restriction on magnetic resonance imaging (Pearson's chi-squared test 42.307, p < 0.001). Analysis of receiver operating characteristics proved a high sensitivity of ultrasound perfusion imaging in the diagnosis of hypoperfused area under the curve, (AUC = 0.917; p < 0.001) and nonperfused (AUC = 0.830; p < 0.001) tissue in comparison with perfusion computed tomography and magnetic resonance perfusion. We present a proof of concept in determining normo-, hypo-, and nonperfused tissue in acute stroke by advanced contrast-enhanced ultrasound perfusion imaging.

The Virtual International Stroke Trials Archive

Background and Purpose - Stroke has global importance and it causes an increasing amount of human suffering and economic burden, but its management is far from optimal. The unsuccessful outcome of several research programs highlights the need for reliable data on which to plan future clinical trials. The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses. Methods - Data were contributed by the principal investigators of numerous trials from the past 16 years. These data have been centrally collated and are available for anonymized analysis and hypothesis testing. Results - ”Currently, the Virtual International Stroke Trials Archive contains 21 trials. There are data on 15 000 patients with both ischemic and hemorrhagic stroke. Ages range between 18 and 103 years, with a mean age of 6912 years. Outcome measures include the Barthel Index, Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin Scale. Medical history and onset-to-treatment time are readily available, and computed tomography lesion data are available for selected trials. Conclusions - This resource has the potential to influence clinical trial design and implementation through data analyses that inform planning. (Stroke. 2007;38:1905-1910.)

Malignant Otitis Externa and Stroke

Malignant otitis externa (MOE) is an aggressive but benign entity which evolves into skull base osteomyelitis. An 81-year-old female patient was admitted for left hemiparesis and homonymous hemianopia. She complained of headache radiating to the right cervical area. A recent history of recurrent otitis media was present. Head and neck imaging showed an ischemic infarction (right temporo-occipital) and a parapharyngeal soft tissue mass originating in an external and medial ear infection. Culture samples revealed Pseudomonas aeruginosa infection leading to the diagnosis of Malignant otitis externa (MOE). Parenteral antibacterial therapy and hyperbaric oxygen therapy resulted in improvement.

Central Auditory Processing Outcome After Stroke In Children.

To investigate central auditory processing in children with unilateral stroke and to verify whether the hemisphere affected by the lesion influenced auditory competence. 23 children (13 male) between 7 and 16 years old were evaluated through speech-in-noise tests (auditory closure); dichotic digit test and staggered spondaic word test (selective attention); pitch pattern and duration pattern sequence tests (temporal processing) and their results were compared with control children. Auditory competence was established according to the performance in auditory analysis ability. Was verified similar performance between groups in auditory closure ability and pronounced deficits in selective attention and temporal processing abilities. Most children with stroke showed an impaired auditory ability in a moderate degree. Children with stroke showed deficits in auditory processing and the degree of impairment was not related to the hemisphere affected by the lesion.

Atividade fisica e a relação com a qualidade de vida, ansiedade e depressão em pessoas com sequelas de acidente vascular cerebral isquemico (AVCI)/ c Alberto Martins da Costa

Universidade Estadual de Campinas . Faculdade de Educação Física

Balance control in hemiparetic stroke patients: Main tools for evaluation

Balance problems in hemiparetic patients after stroke can be caused by different impairments in the physiological systems involved in Postural control, including sensory afferents, movement strategies, biomechanical constraints, cognitive processing, and perception of verticality. Balance impairments and disabilities must be appropriately addressed. This article reviews the most common balance abnormalities in hemiparetic patients with stroke and the main tools used to diagnose them.

An evaluation of the time dependence of the anisotropy of the water diffusion tensor in acute human ischemia

We have performed MRI examinations to determine the water diffusion tensor in the brain of six patients who were admitted to the hospital within 12 h after the onset of cerebral ischemic symptoms. The examinations have been carried out immediately after admission, and thereafter at varying intervals up to 90 days post admission. Maps of the trace of the diffusion tensor, the fractional anisotropy and the lattice index, as well as maps of cerebral blood perfusion parameters, were generated to quantitatively assess the character of the water diffusion tensor in the infarcted area. In patients with significant perfusion deficits and substantial lesion volume changes, four of six cases, our measurements show a monotonic and significant decrease in the diffusion anisotropy within the ischemic lesion as a function of time. We propose that retrospective analysis of this quantity, in combination with brain tissue segmentation and cerebral perfusion maps, may be used in future studies to assess the severity of the ischemic event. (C) 1999 Elsevier Science Inc.

Further validation of "timed up and go" in stroke patients

Objective: To compare the Barthel Index (BI), a well-known and accepted measure of functional disability, with Timed Up and Go (TUG). Method: Thirty-three stroke patients had their BI and TUG assessed by independent blinded observers. Results: There was good agreement between BI and TUG, with good repeatability. Conclusion: Thus TUG is a good measure of function pre-discharge but needs to be further validated on more disabled patients.

Trends in the incidence, severity, and short-term outcome of stroke in Perth, Western Australia

Background and Purpose-This report describes trends in the key indices of cerebrovascular disease over 6 years from the end of the 1980s in a geographically defined segment of the city of Perth, Western Australia. Methods-Identical methods were used to find and assess all cases of suspected stroke in a population of approximately 134 000 residents in a triangular area of the northern suburbs of Perth. Case fatality was measured as vital status at 28 days after the onset of symptoms. Data for first-ever strokes and for all strokes for equivalent periods of 12 months in 1989-1990 and 1995-1996 were compared by age-standardized rates and proportions and Poisson regression. Results-There were 355 strokes in 328 patients and 251 first-ever strokes (71%) for 1989-1990 and 290 events in 281 patients and 213 first-ever strokes (73%) for 1995-1996. In Poisson models including age and period, overall trends in the incidence of both first-ever strokes (rate ratio = 0.75; 95% confidence limits, 0.63, 0.90) and all strokes (rate ratio = 0.73; 95% confidence limits, 0.62, 0.85) were obviously significant, but only the changes in men were independently significant. Case fatality did not change, and the balance between hemorrhagic and occlusive strokes in 1995-1996 was almost indistinguishable from that observed in 1989-1990. Conclusions-Our results, which are the only longitudinal population-based data available for Australia for key indices of stroke, suggest that it is a change in the frequency of stroke, rather than its outcome, that is chiefly responsible nationally for the fall in mortality from cerebrovascular disease.