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Treatment of embolic stroke as a medical emergency. Implications in a managed care environment.

Encouraging innovations should be a concern of the providers/gatekeepers of health-care if lower health-care costs are to become a reality. Controlled prices and improper incentives will dramatically slow innovation in American medicine. For the vertically integrated health-care system providing capitated coverage, the aggressive treatment of stroke is a sound financial decision.

Cerebrovascular Disorders↗

Embolic stroke after "cured" prosthetic aortic valve endocarditis.

The authors report on the case of a patient with infective endocarditis of a prosthetic valve in the aortic position, after receiving percutaneous transluminal coronary angioplasty. Transesophageal echocardiography provided valuable information about the existence and size of vegetations at the time of initial diagnosis and during followup. Despite successful treatment resulting in good control of the infection and a significant reduction of vegetation size, the patient still suffered a major cerebral embolic event early after hospital discharge.

Aged↗

Selective MCA occlusion: a precise embolic stroke model.

The present study describes a method for improving the precision and accuracy of clot placement within the middle cerebral artery (MCA) of rats, utilizing a micro-catheter and laser Doppler flowmetry. This technique reduces the size of clot needed to achieve stable occlusion with no failed embolizations and a low percentage of early recanalizations. Infarctions were consistent in both size and distribution within the MCA perfusion territory. Selective embolization in aged animals (n = 10) resulted in substantially larger infarctions than those seen in aged animals (n = 10) following non-selective embolization (P < 0.05), or young animals (n = 10) subjected to filamentous occlusion (P < 0.001). Clots were localized to the MCA by direct examination at 0, 60 and 120 min post-embolization (n = 14). All aged animals surviving 24h exhibited moderate to severe functional deficits, with selectively occluded animals having a higher mean score on the modified neurologic severity scale (P = 0.002). This model provides a highly reproducible method for embolization of the MCA and reliable reperfusion with rt-PA.

Aging↗

Prediction of acute embolic stroke outcome after local intraarterial thrombolysis: value of pretreatment and posttreatment 99mTc-ethyl cysteinate dimer single photon emission computed tomography.

The aim of this study was to investigate the efficacy of pre- and posttreatment 99mTc-ethyl cysteinate dimer (99mTc-ECD) single photon emission computed tomography (SPECT) for predicting the ischemic outcome of embolic middle cerebral artery occlusion after treatment with local intraarterial thrombolysis. The authors examined 28 patients with a moderately ischemic area (ratio of affected regional activity to cerebellar activity (A/C ratio) of 0.4 to 0.7) determined using pretreatment SPECT, and with complete recanalization within 6 hours. Posttreatment dynamic and static SPECT studies were performed immediately after thrombolysis. The extent of the affected area outlined on pretreatment SPECT was used for the posttreatment SPECT images, and A/C ratios were calculated. The relative retention ratio of 99mTc-ECD in the affected area was also analyzed using posttreatment dynamic SPECT. Fourteen patients either without infarction or with small subcortical and basal ganglial infarction, 11 patients with medium or large cortical infarction, and 3 patients with hemorrhage were identified by follow-up computed tomography. Ischemic outcome correlated with the relative retention ratio of 99mTc-ECD more closely than either the pre- or posttreatment A/C ratios. In particular, a threshold value for the development of hemorrhage was distinct only in the relative retention ratio of 99mTc-ECD. Pretreatment 99mTc-ECD SPECT did not always predict the occurrence of hemorrhagic transformation, whereas dynamic 99mTc-ECD SPECT performed immediately after thrombolysis allowed clear identification of patients at risk for hemorrhagic transformation.

Adult↗

Treatment of embolic stroke in rats with bortezomib and recombinant human tissue plasminogen activator.

Stroke elicits a progressive vascular dysfunction, which contributes to the evolution of brain injury. Thrombolysis with tissue plasminogen activator (tPA) promotes adverse vascular events that limit the therapeutic window of stroke to three hours. Proteasome inhibitors reduce vascular thrombotic and inflammatory events, and consequently protect vascular function. The present study evaluated the neuroprotective effect of bortezomib, a potent and selective inhibitor of the proteasome, alone and in combination with delayed thrombolytic therapy on a rat model of embolic focal cerebral ischemia. Treatment with bortezomib reduces adverse cerebrovascular events including secondary thrombosis, inflammatory responses, and blood brain barrier (BBB) disruption, and hence reduces infarct volume and neurological functional deficit when administrated within 4 h after stroke onset. Combination of bortezomib and tPA extends the thrombolytic window for stroke to 6 h, which is associated with the improvement of vascular patency and integrity. Real time RT-PCR of endothelial cells isolated by laser-capture microdissection from brain tissue and Western blot analysis showed that bortezomib upregulates endothelial nitric oxide synthase (eNOS) expression and blocks NF-kappaB activation. These results demonstrate that bortezomib promotes eNOS dependent vascular protection, and reduces NF-kappaB dependent vascular disruption, all of which may contribute to neuroprotection after stroke.

Animals↗

[Risk of recurrent cerebral embolism in isolated and combined cardial pathology in patients with cardio-embolic stroke].

To study cerebral microembolism and focal impairment of the brain in patients with isolated and combined cardiac affection, we examined 84 patients who had survived cardioembolic stroke (CES). The examination included computed tomography of the head, echocardiography and transcranialdopplerographic monitoring of microembolic signals (MES). Group 1 consisted of 53 (63.1%) patients with one source of cardiocerebral embolism, group 2-31 (36.9%) patients with two potential causes of cardial embolic complications. In group 2 average number of documented MES (3[1;5]) and average number of cerebral ischemic foci (2[1;2]) were greater than those of group 1-2[1;4] and 1[1;1], respectively. As to the size of the lesion, it was found that small, middle-size and large foci were also visualized in group 2 more frequently. Thus, combination of two sources of cerebral embolism observed in 1/3 of CES enhances cardiogenic embologenic potential and probability of microembolism transformation into cerebral focal lesion as a result of potentiation of different ways of thrombogenesis.

Adolescent↗

Papillary fibroelastoma of the cardiac valves: a rare cause of embolic stroke.

Papillary fibroelastomas are rare, primary, benign cardiac tumours most frequently located in the heart valves. They are a potential cause of systemic emboli, stroke, myocardial infarction and sudden death. We present two cases of papillary fibroelastomas located in the mitral and aortic valves of patients who had suffered multiple strokes. The fibroelastomas were diagnosed using transoesophageal echocardiography and the patients were treated surgically, with broad excision of the tumours and preservation of the valves. The echocardiographic and microscopic characteristics of the fibroelastomas are analysed and methods for their differential diagnosis from other cardiac tumours are discussed in the context of the available literature.

Aortic Valve↗

D-amphetamine improves cognitive deficits and physical therapy promotes fine motor rehabilitation in a rat embolic stroke model.

BACKGROUND AND PURPOSE: The purpose of this study was to examine the effects of D-amphetamine (D-amph) and physical therapy separately or combined on fine motor performance, gross motor performance and cognition after middle cerebral artery thromboembolization in rats. METHODS: Seventy-four rats were trained in appropriate cognitive and motor behaviours. Thirteen animals were sham-operated and fifty-nine animals were embolized in the right carotid territory. Animals were randomly assigned to five groups: 1) SHAM (non-embolized, saline), 2) CONTROL (embolized, saline), 3) D-AMPH (embolized, D-amph), 4) THERAPY (embolized, saline + physical therapy) and 5) D-AMPH + THERAPY (embolized, D-amph + physical therapy). Rats of the groups 4-5 underwent d-amph or saline treatment on days 1, 3, 5 and 7 after surgery and were re-trained for 1 h starting 60 min after each treatment. During this time, rats were allowed to voluntarily engage in suitable cognitive or motor behaviours in order to obtain food. Animals from all groups were re-tested during days 21-28 after surgery. RESULTS: No differences in infarct volumes were observed between the groups of embolized animals. When evaluating performances on days 21-28 after surgery, rats of the SHAM and THERAPY groups had better fine motor performance than those of the CONTROL (P < 0.05), whereas rats of SHAM and D-AMPH groups achieved better cognitive performance than CONTROL rats (P < 0.05). No significant differences were observed between any groups regarding gross motor performance. CONCLUSIONS: After embolization, physical therapy improved fine motor performance and D-amph accelerated rehabilitation of cognitive performance as observed in the rats of the THERAPY and D-AMPH groups. As a result of the administration of a high dose of D-amph, the rats of the D-AMPH + THERAPY combination group failed to engage in physical therapy during D-amph intoxication, thereby limiting any promotion of rehabilitation by combining physical therapy and D-amph.

Animals↗

Hydroxyethyl starch 200/0.5 reduces infarct volume after embolic stroke in rats.

BACKGROUND AND PURPOSE: We evaluated isovolumic hemodilution with hydroxyethyl starch 200/0.5 in a rat model of focal cerebral ischemia. This compound avoids the unfavorable viscosity and erythrocyte aggregation abnormalities of low molecular weight dextran during administration over a period of several days. METHODS: Sprague-Dawley rats, anesthetized with 0.5-1% halothane and 70% N2O, were subjected to silicon cylinder (treated and control groups) or sham (sham group) embolization of the cerebral circulation. Thirty minutes after embolization, the treated group (n = 5) was infused with 11 ml/kg of 10% hydroxyethyl starch 200/0.5, and the control (n = 5) and sham (n = 4) groups were infused with saline for 1 hour. In the treated group, 7.1 ml/kg of blood was withdrawn. After 24 hours, the animals were reanesthetized, and cerebral blood flow was determined with [14C]iodoantipyrine. Alternative brain slices were either incubated with 2,3,5-triphenyltetrazolium chloride for infarct volume determination or frozen for ischemic volume and cerebral blood flow determination using autoradiography. RESULTS: The hematocrit in the treated group was reduced from (mean +/- SEM) 46 +/- 1% to 35 +/- 2% at 1.5 hours (p < 0.01). Cortical blood flow was within the normal range of 115-185 ml/min/100 g, except for the ischemic cortex in the embolized groups, treated and control. The ischemic and infarct volume of the treated group was reduced by 74% (p < 0.05) and 89% (p < 0.05), respectively, from the control group. The treated and sham ischemic and infarct volumes were not statistically different. CONCLUSIONS: These data suggest that hydroxyethyl starch 200/0.5 could be an effective treatment for ischemic stroke when administered early, because it reduces infarct and ischemic volumes from control values to levels indistinguishable from those of the sham group.

Animals↗

Haemodynamic changes in pre and post ischaemia following simulated embolic stroke of middle cerebral artery occlusion.

The effects of middle cerebral artery (MCA) occlusion (15, 30, 60 min) and recirculation of cerebral blood flow (CBF) were studied in 18 rabbits. The change of cortical oxygen tension (CoPo2) accompanying MCA occlusion was also recorded in 12 rabbits and was compared with the results of CBF recording. CBF and CoPo2 immediately decreased to a minimal level following MCA occlusion and partially improved in the first 5 min of occlusion. CBF and CoPo2 values in the first 5 min following occlusion were significantly higher than the minimal values. The degree of CBF and CoPo2 recovery in the first 5 min of occlusion had a statistically significant correlation with the minimal values. It was postulated that local tissue acidosis due to ischaemia was responsible for this recovery in the early occlusive phase. CBF and CoPo2 became relatively stable after 5 min of occlusion. The results suggest that following embolic occlusion, the degree of recovery of CBF following its initial depression is one of the pathophysiological mechanisms that differentiate between TIAs and stroke. Postischaemic hyperperfusion was observed in all cases after 15 to 60 min of occlusion. The duration of postischaemic hyperperfusion did not correlate with the CBF value just before reperfusion. However, the magnitude of postischaemic hyperperfusion had a significant correlation with the depression of the CBF value just before reperfusion. It could be concluded from our results that the magnitude of postischaemic hyperperfusion represented the severity of ischaemia, at least up to 60 min of occlusion.

Animals↗