Risk of acute brain injury related to cerebral microembolism during cardiac catheterization performed by right upper limb arterial access.

BACKGROUND AND PURPOSE: The primary objective of this study was to assess the incidence of new cerebral infarcts related to cardiac catheterization in patients explored through the right transradial approach. METHODS: This prospective study involved 41 consecutive patients with severe aortic valve stenosis. To assess the incidence of cerebral infarction, all patients underwent cerebral diffusion-weighted MRI before and after cardiac catheterization through the right transradial approach. RESULTS: We detected only two patients (4.9%) with new, small, isolated acute cerebral diffusion abnormalities postcatheterization. All patients remained asymptomatic. CONCLUSIONS: New cerebral lesions on diffusion-weighted MRI are infrequent in patients explored through the right transradial approach. Randomized studies are warranted to confirm for potential advantages of transradial approach versus the femoral approach in cardiac catheterization.

Analysis of thrombi retrieved from cerebral arteries of patients with acute ischemic stroke.

BACKGROUND AND PURPOSE: Information regarding the histological structure of thromboemboli that cause acute stroke provides insight into pathogenesis and clinical management. METHODS: This report describes the histological analysis of thromboemboli retrieved by endovascular mechanical extraction from the middle cerebral artery (MCA) and intracranial carotid artery (ICA) of 25 patients with acute ischemic stroke. RESULTS: The large majority (75%) of thromboemboli shared architectural features of random fibrin:platelet deposits interspersed with linear collections of nucleated cells (monocytes and neutrophils) and confined erythrocyte-rich regions. This histology was prevalent with both cardioembolic and atherosclerotic sources of embolism. "Red" clots composed uniquely of erythrocytes were uncommon and observed only with incomplete extractions, and cholesterol crystals were notably absent. The histology of thromboemboli that could not be retrieved from 29 concurrent patients may be different. No thrombus >3 mm wide caused stroke limited to the MCA, and no thrombus >5 mm wide was removed from the ICA. A mycotic embolus was successfully removed in 1 case, and a small atheroma and attached intima were removed without clinical consequence from another. CONCLUSIONS: Thromboemboli retrieved from the MCA or intracranial ICA of patients with acute ischemic stroke have similar histological components, whether derived from cardiac or arterial sources. Embolus size determines ultimate destination, those >5 mm wide likely bypassing the cerebral vessels entirely. The fibrin:platelet pattern that dominates thromboembolic structure provides a foundation for both antiplatelet and anticoagulant treatment strategies in stroke prevention.

Stroke attributable to a calcific embolus from the brachiocephalic trunk.

BACKGROUND AND PURPOSE: Calcific brain embolization is a rare event that is usually secondary to cardiac valve calcification. We present a case of stroke caused by embolization of calcific material from the brachiocephalic trunk, probably induced by radiotherapy. SUMMARY OF CASE: A 56-year-old right-handed female developed left-sided hemiparesis, hemihypesthesia, and sensory inattention. She had a history of right breast carcinoma that was excised 8 years previously followed by radiotherapy. She had no other history of note. Computed tomography of the head and magnetic resonance imaging confirmed a calcific embolus in right middle cerebral artery and an acute infarction in the corresponding territory. Plain chest radiography, carotid ultrasonography, transthoracic and transoesophageal echocardiography failed to demonstrate the source of calcific embolism. Computed tomography of the thorax revealed heavy calcification of the brachiocephalic trunk and the origin of the right common carotid artery. CONCLUSIONS: Undertaking a vigilant systematic search for the source in cases of calcific embolization is necessary. The aorta and its main branches are possible, yet unusual, sources of calcific emboli that merit investigation.

Absence of microemboli on transcranial Doppler identifies low-risk patients with asymptomatic carotid stenosis.

BACKGROUND AND PURPOSE: Carotid endarterectomy clearly benefits patients with symptomatic severe stenosis (SCS), but the risk of stroke is so low for asymptomatic patients (ACS) that the number needed to treat is very high. We studied transcranial Doppler (TCD) embolus detection as a method for identifying patients at higher risk who would have a lower number needed to treat. METHODS: Patients with carotid stenosis of > or =60% by Doppler ultrasound who had never been symptomatic (81%) or had been asymptomatic for at least 18 months (19%) were studied with TCD embolus detection for up to 1 hour on 2 occasions a week apart; patients were followed for 2 years. RESULTS: 319 patients were studied, age (standard deviation) 69.68 (9.12) years; 32 (10%) had microemboli at baseline (TCD+). Events were more likely to occur in the first year. Patients with microemboli were much more likely to have microemboli 1 year later (34.4 versus 1.4%; P<0.0001) and were more likely to have a stroke during the first year of follow-up (15.6%, 95% CI, 4.1 to 79; versus 1%, 95% CI, 1.01 to 1.36; P<0.0001). CONCLUSIONS: Our findings indicate that TCD- ACS will not benefit from endarterectomy or stenting unless it can be done with a risk <1%; TCD+ may benefit as much as SCS if their surgical risk is not higher. These findings suggest that ACS should be managed medically with delay of surgery or stenting until the occurrence of symptoms or emboli.

Can transcranial Doppler discriminate between solid and gaseous microemboli? Assessment of a dual-frequency transducer system.

BACKGROUND AND PURPOSE: Transcranial Doppler ultrasound can reliably detect both gaseous and solid cerebral emboli. However, conventional equipment is unable to discriminate between gaseous and solid emboli. This is a major limitation in situations in which the 2 coexist, because they may have very different clinical relevance. Recently, a novel Embo-Dop system, using insonation at 2 ultrasound transducer frequencies, has been developed. An initial study with a small sample size suggested it provided excellent discrimination. We performed a validation study in subjects with embolic signals of known nature. METHODS: Gaseous embolic signals were obtained in 7 patients with known patient foramen ovale by intravenous injection of agitated saline injections. Solid embolic signals were obtained in patients with symptomatic carotid stenosis (N=23). Discrimination of the 2 using the Embo-Dop system dual-frequency system was assessed. It was compared with discrimination using embolic signal maximum intensity with an intensity threshold. RESULTS: One hundred forty-five solid embolic signals were recorded from carotid stenosis patients. Seventy-three were classified as solid and 72 as gaseous by the Embo-Dop system. Six hundred forty-eight gaseous embolic signals were recorded from 7 patients with patent foramen ovale. Six hundred twenty-five were classified as gaseous and 23 as solid. This gave a sensitivity of 50.3% and specificity of 96.5% for detecting solid embolic signals. Discrimination was better than using a simple intensity threshold. CONCLUSIONS: The Embo-Dop dual-frequency system allows better discrimination than a simple intensity threshold but it is not accurate enough for use in clinical or research studies. Further work is needed to develop reliable clinical systems for discrimination of emboli.

Map-ISODATA demarcates regional response to combination rt-PA and 7E3 F(ab')2 treatment of embolic stroke in the rat.

PURPOSE: To investigate the ability of map-ISODATA (Iterative Self-Organizing Data Analysis Technique) to classify the different categories of ischemic damage in the lesion and to evaluate a combined (thrombolysis plus antiplatelet) treatment efficacy in an embolic stroke of rat. MATERIALS AND METHODS: Rats subjected to embolic stroke with (N=12) and without (N=10) rt-PA and 7E3 F(ab')2 treatment (4 hours after embolization) were followed (at 2, 24, and 48 hours post-MCAO) with magnetic resonance imaging (MRI) using T1, T2, and apparent diffusion coefficient of water (ADCw). ISODATA was computed from T1, T2, and ADCw maps. The signatures characterized by the map-ISODATA were compared with histological quantitative evaluation and were employed to demarcate the specific regions in the lesion. RESULTS: The signature described by map-ISODATA is highly correlated with the degree of tissue damage in the lesion and can distinguish the severity of ischemic tissue injury. Based upon map-ISODATA, ischemic lesion area can be divided into three specific regions, each characterized by a distinct evolution of injury and treatment response. The combined treatment significantly reduces the lesion size between 24 and 48 hours and improves the outcome 48 hours post-MCAO compared with the control group. CONCLUSION: Map-ISODATA provides an accurate means to identify lesion area, to distinguish ischemic damage, and to detect treatment response. 7E3 F(ab')2 extends the rt-PA treatment window to at least four hours after the onset of embolic stroke of rat.

Long-term effects of sequential cortical infarcts on scar size, brain volume and cognitive function.

Focal ischemia induces long-term pathophysiological consequences in widespread brain areas. Here we analyzed long-term effects of sequential cortical lesions on brain volume and cognitive function. Rats received either single photothrombotic lesions in the forelimb sensorimotor cortex (SL) or two lesions in sequence either immediately (DL0), 2 days (DL2), 7 days (DL7), or 10 days (DL10) after the first surgery in the homotopic contralateral area. Infarct and global brain volume were measured 7 days (SL and DL2 groups) and one month (all groups) after the last period of ischemia. In the weeks following a stroke, the single lesion shrank considerably. This shrinkage was accentuated by a further lesion received either earlier or later. Thirty-one days after obtaining the second lesion, the lesion scars on both sides had a mean volume of 5.8 +/- 2.3 mm3 in DL2 as compared to 8.5 +/- 3.5 mm3 in SL-animals. In addition, there was a super-additive loss of residual brain volume by 2.2-8.0% in each hemisphere in animals with sequential lesions. In the watermaze, this loss of brain volume corresponded to a slight but significant impairment in performance. The present study revealed a complex interaction of lesions in animals with sequential strokes associated with global reduction of brain volume and cognitive impairment indicating degenerative processes beyond the lesions itself.

Analysis of combined treatment of embolic stroke in rat with r-tPA and a GPIIb/IIIa inhibitor.

Suppression of platelet activation improves the efficacy of thrombolytic therapy for stroke. Thus, combination treatment with recombinant tissue plasminogen activator (r-tPA) and 7E3 F(ab')2, a GPIIb/IIIa inhibitor that binds the platelet to fibrin, may improve the efficacy of thrombolytic therapy in embolic stroke. Magnetic resonance imaging (MRI) was used to monitor treatment response in rats subjected to embolic middle cerebral artery (MCA) occlusion (MCAo). Animals were randomized into treated (n=12) and control (n=10) groups and received intravenous combination therapy or saline, respectively, 4 hours after MCAo. Magnetic resonance imaging (MRI) measurements performed 1 hour after MCAo showed no difference between groups. However, an increased incidence (50%) of MCA recanalization was found in the treated group at 24 hours compared with 20% in the control group. The area of low cerebral blood flow at 24 and 48 hours was significantly smaller in the combination treatment group, and the lesion size, as indicated from the T2 and T1 maps, differed significantly between groups. Fluorescence microscopy measurements of cerebral microvessels perfused with fluorescein isothiocyanate-dextran and measurements of infarct volume revealed that the combination treatment significantly increased microvascular patency and reduced infarct volume, respectively, compared with the control rats. The efficacy of combination treatment 4 hours after ischemia is reflected by MRI indices of tissue perfusion, MCA recanalization, and reduction of lesion volume. The treatment also reduced secondary microvascular perfusion deficits.

[Does the result of thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) in rabbits depend on the erythrocyte- and fibrin-content of a thrombus?]. / Hängt das Ergebnis einer Thrombolyse mit rekombinantem Gewebe-Plasminogenaktivator (rt-PA) beim Kaninchen vom Erythrozyten- und Fibringehalt eines Thrombus ab?

PURPOSE: It is known from autopsy studies that thromboembolic stroke can be caused by red, white and mixed clots. We therefore examined whether the efficacy of thrombolysis with recombinant tissue-type plasminogen activator (rt-PA) depends on the proportions of fibrin and erythrocytes within thromboembolic material. METHODS: In 23 rabbits intraarterial thrombolysis with 3 mg rt-PA/kg body weight was started 30 minutes after middle cerebral artery occlusion with either red or white autologous emboli 20 hours old. 20 rabbits served as control. Cerebral perfusion was monitored by MRI. RESULTS: rt-PA enhanced lysis of red but not of white emboli and decreased the infarct volume only if vascular occlusion was due to red emboli (p <.01). Cerebral perfusion improved only in the red treatment group where the normalized first moment (NFM) decreased (p <.05) and the relative regional cerebral blood volume (rrCBV) reached normal values (p <.05). CONCLUSION: We suggest that in our animal model the efficacy of thrombolysis increases with the proportion of erythrocytes within thromboembolic material and decreases with its content of fibrin. lf these findings would also be applicable to patients, pretherapeutic estimation of the efficacy of thrombolysis might become feasible because the CT values of red and white thrombi differ.

Obesity does not induce abnormal CSF pressure in subjects with normal cerebral MR venography.

Obesity has been shown to increase lumbar CSF pressure in healthy subjects. The authors studied lumbar CSF opening pressure in 18 obese, 33 overweight, and 49 nonoverweight subjects with normal MRI and MR venography (MRV) of the brain. No subject had a CSF pressure above 200 mm H2O. Obesity does not cause abnormal CSF pressure in subjects with normal MRV. Individuals with a CSF pressure higher than 200 mm H2O should undergo MRV to exclude cerebral venous thrombosis.

Interferon-beta administration confers a beneficial outcome in a rabbit model of thromboembolic cerebral ischemia.

We demonstrate that treatment with the cytokine human interferon-beta (IFN-beta) resulted in a beneficial outcome in a rabbit model of thromboembolic cerebral ischemia. Rabbits administered subcutaneously with IFN-beta prior to (pre-treatment) or after (post-treatment) the introduction of an autologous blood clot into the middle cerebral artery have consistently smaller subcortical infarct volumes compared to control (untreated) counterparts. The average subcortical infarct volume of pre-treatment rabbits is 46.3+/-9.3 mm(3) (n=4), and that of post-treatment rabbit is 40.0+/-23.1 mm(3) (n=4). Both are significantly lower (P=0.003 and P=0.004, respectively) than the average subcortical infarct volume of control rabbits (121.6+/-32.9 mm(3), n=5). Although the precise mechanism responsible for the beneficial effect of IFN-beta on stroke is not yet clear, our results are in line with the known anti-inflammatory potential and anti-apoptotic function of IFN-beta.

Impairment of adenylyl cyclase and of spatial memory function after microsphere embolism in rats.

The purpose of the present study was to characterize alterations in the adenylyl cyclase (AC), cyclic adenosine 3',5'-monophosphate (cAMP), and spatial memory function after sustained cerebral ischemia. Sustained cerebral ischemia was induced by injection of 900 microspheres (48 microm in diameter) into the right (ipsilateral) hemisphere of rats. Alterations in the AC and cAMP in the cerebral cortex and hippocampus were examined up to 7 days after the embolism. A decrease in the cAMP content was seen in the ipsilateral hemisphere throughout the experiment. Microsphere embolism (ME) decreased the activity of Ca(2+)/calmodulin (CaM)-sensitive AC in the ipsilateral hemisphere throughout the experiment, whereas the basal and 5'-guanylyl imidodiphosphate (Gpp(NH)p)-sensitive AC activities were not altered. Immunoblotting analysis of AC subtypes with specific antibodies showed a decrease in the immunoreactivity of AC-I in the ipsilateral hemisphere during these periods. No significant differences in the immunoreactivity of AC-V/VI and AC-VIII were observed after ME. The levels of GTP-binding proteins Galpha(s), Galpha(i), and Gbetawere unchanged. Furthermore, microsphere-embolized rats showed prolongation of the escape latency in the water maze task determined on the seventh to ninth day after the operation. These results suggest that sustained cerebral ischemia may induce the impairment of the AC, particularly a selective reduction in the AC-I level and activity, coupled with the decrease in cAMP content. This reduction may play an appreciable role in the disturbance in cAMP-mediated signal transduction system, possibly leading to learning and memory dysfunction.

Time course of cerebral infarction in the middle cerebral arterial territory: deep watershed versus territorial subtypes on diffusion-weighted MR images.

PURPOSE: To examine possible differences between the evolution of cerebral watershed infarction (WI) and that of territorial thromboembolic infarction (TI) by using diffusion-weighted (DW) and T2-weighted magnetic resonance (MR) images and apparent diffusion coefficient (ADC) maps. MATERIALS AND METHODS: Fourteen patients with TI and nine with WI underwent MR imaging from the acute to chronic infarction stages. ADC maps were derived from DW images. Lesion-to-normal tissue signal intensity ratios on ADC maps (rADC), echo-planar T2-weighted images, and DW images were calculated. Lesion volumes at acute or early subacute infarction stages were measured on DW images, and final lesion volumes were estimated on fluid-attenuated inversion-recovery images. RESULTS: Analysis of variance revealed a significant difference in temporal evolution patterns of rADC between WI and TI (P <.001). rADC pseudonormalization following TI began about 10 days after symptom onset, but that following WI did not occur until about 1 month after symptom onset. The Pearson correlation coefficient between final and initial infarct volumes was 0.9899 for both infarction subtypes, indicating that the initial ischemic injury volume measured at the acute or early subacute stage predicted the final lesion volume fairly well. CONCLUSION: The evolution time of ADC is faster for TI than for WI. This difference, which likely originates from the different pathophysiologic and hemodynamic features of the two infarction types, might account for the relatively large range of ADC values reported for the time course of ischemic strokes.

Massive haemorrhagic transformation in cardioembolic stroke: the role of arterial wall trauma and dissection.

The pathogenesis of massive haemorrhagic transformation is not well established. Fatal haemorrhagic transformation associated with in situ dissection after acute middle cerebral artery (MCA) occlusion in a patient with atrial fibrillation is reported. An 80 year old woman with atrial fibrillation developed mild hemiparesis and aphasia. Brain CT and MRI at 4 and 5 hours, respectively, of symptom onset showed proximal MCA trunk occlusion with developing striatocapsular infarct and hypoperfusion in the superficial MCA territory. A few hours later, she developed massive bleeding into the ischaemic area and died. Pathological examination showed MCA trunk dissection, surrounded by a subarachnoid clot which communicated with the cerebral haematoma. It is suggested that direct arterial wall trauma as a result of cardioembolic MCA occlusion caused bleeding into the infarct. Secondary in situ dissection may be an overlooked mechanism of haemorrhagic transformation.