Hemorrhage rates and outcomes when using up to 100 mg intra-arterial t-PA for thrombolysis in acute ischemic stroke.

This work presents a unique single center experience with intra-arterial delivery of tissue plasminogen activator (t-PA) doses as high as 100mg for thrombolysis. Hemorrhage volumes, hemorrhage rates, clinical outcomes and radiographic outcomes were assessed. Prospectively collected angiographic, clinical and laboratory information on 67 consecutive patients with acute ischemic stroke involving either the m1 segment of the middle cerebral artery, the intracranial internal carotid artery or the basilar artery were retrospectively analyzed. Patients who received more than 50 mg t-PA were compared with those patients receiving 50 mg or less. Outcome measures included: symptomatic hemorrhage, significant hemorrhage volume (greater than 25 ml), hemorrhage rate, change in National Institutes of Health stroke scale score at 24 hours and at hospital discharge, modified Rankin score at 90 days, in-hospital deaths, death within 90 days, reperfusion rate, and infarct volume. Multivariate logistic regression analysis demonstrated that t-PA dose over 50 mg was associated with higher rates of hemorrhage and larger hemorrhages. Poor pial collateral formation, poor reperfusion (less than 50% of the territory involved), and platelet count below 200 K/µL influenced hemorrhage. Limiting t-PA dose to 100mg rather than 50mg improved documented reperfusion rates from 37% to 61%. Restricting intra-arterial t-PA administration to 100mg rather than 50mg, is associated with higher overall reperfusion rates and improves overall outcomes, however, the hemorrhage rate is also elevated. Poor pial collateral formation and platelet count less than 200 K/µL may be reasons to curtail the use of higher t-PA dose to reduce hemorrhage rate.

Predictors of hemorrhage following intra-arterial thrombolysis for acute ischemic stroke: the role of pial collateral formation.

BACKGROUND AND PURPOSE: The extent of pial collateral formation during acute ischemic stroke has been shown to influence outcomes. This study examines whether angiographic assessment of pial collateral formation is predictive of hemorrhagic transformation following intra-arterial thrombolysis (IAT) for acute ischemic stroke. MATERIALS AND METHODS: Rates of any hemorrhage and significant hemorrhage (>25 mL) were reviewed in 104 consecutive patients who underwent IAT following acute ischemic stroke. The influence of the anatomic extent of pial collateral formation on the rates of hemorrhage and significant hemorrhage relative to known predictors for hemorrhagic transformation (presenting systolic blood pressure, blood glucose level, platelet level, and National Institutes of Health Stroke Scale [NIHSS] score, history of diabetes, time to treatment, age, sex, occlusion site, and extent of reperfusion) was analyzed by using logistic regression models. RESULTS: Rates of any hemorrhage and significant hemorrhage were 25.2% (26/104) and 9.7% (10/104), respectively. The rate of significant hemorrhage was 25.0% (8/32) in patients with poor pial collaterals and 2.78% (2/72) in those with good pial collaterals (P = .0004, Pearson correlation). The rate of any hemorrhage was also significantly higher in patients with poor pial collaterals (40.6% versus 18.1%; P = .0142, Pearson correlation). Logistic regression analyses revealed that pial collateral formation (odds ratio [OR] = 3.04), history of diabetes (OR = 4.83), platelets <200,000/microL (OR = 2.95), and time to treatment <3 hours (OR = 12.0) were statistically significant predictors of hemorrhage, whereas pial collateral formation (OR = 13.1) and platelets <200,000/microL (OR = 8.1) were statistically significant predictors of significant hemorrhage. CONCLUSIONS: Poor pial collateral formation is associated with higher incidence and larger size of hemorrhage following IAT.

Arteriographic demonstration of slow antegrade opacification distal to a cerebrovascular thromboembolic occlusion site as a favorable indicator for intra-arterial thrombolysis.

PURPOSE: This study sought to determine whether the angiographic demonstration of slow antegrade contrast opacification of an occluded cerebral artery distal to the thrombus (clot outline sign) on cerebral arteriograms performed immediately before thrombolytic treatment is associated with higher recanalization rates relative to patients without antegrade contrast opacification distal to the occlusion site. METHODS: The angiographic images of 100 consecutive arteriograms performed before thrombolysis in patients eligible for intra-arterial thrombolysis from May 1995 to February 2005 were reviewed. A modified Thrombolysis in Myocardial Infarction flow grade (mTIMI) was adapted to grade recanalization after cerebral thrombolysis. Clot outline sign was defined as slow antegrade contrast opacification distal to the thrombus on the delayed images of the presenting arteriogram. Logistic regression analysis for mTIMI grade included the following potential predictors: presence of outline sign, age, time to treatment, sex, site of occlusion, presenting National Institutes of Health Stroke Scale (NIHSS) score, presenting platelets, presenting systolic blood pressure, presence of pial collaterals, and admitting glucose value. RESULTS: Eighty-seven arteriograms were reviewed. Of these, 19 (22%) displayed the clot outline sign. Thirteen (69%) of 19 had clot outline sign, and 16 of 68 (29%) were not completely recanalized (mTIMI = 3); 95% with clot outline sign and 54% without were associated with either mTIMI 2 or 3 (P = .0055, Pearson correlation). Logistic regression analysis for recanalization relative to other predictors indicates that only the clot outline sign could act as a statistically significant predictor for recanalization (P = .0007). CONCLUSION: Prethrombolysis cerebral arteriograms demonstrating delayed antegrade contrast opacification distal to the occlusion site are associated with higher recanalization rates.

High-dose methylprednisolone treatment in experimental focal cerebral ischemia.

Previous studies using steroids for experimental focal stroke have demonstrated conflicting results, possibly related to dose used or ischemic models employed. In this study we examined high-dose methylprednisolone treatment following permanent and temporary focal cerebral ischemia in the rat. Focal stroke was induced in spontaneously hypertensive rats by permanent right common carotid and either permanent or 3 h of temporary middle cerebral artery (MCA) occlusion. Methylprednisolone (105 mg/kg) was administered intra-arterially. Infarct volume was measured at 24 h after permanent and temporary MCA occlusion. Cerebral edema was determined by measuring right and left hemispheric volumes and water content 24 h after permanent MCA occlusion in one experiment. Methylprednisolone, whether administered in divided doses over 12 h (n = 15 in each group) or a single bolus (n = 9 per group), had no effect on infarct volume after permanent MCA occlusion. Methylprednisolone treatment also had no influence on cerebral edema (n = 9 per group). In two different experiments, methylprednisolone given in divided doses over 12 h (n = 11, n = 25) after temporary MCA occlusion decreased infarct volume (P < 0.05) by 20% compared with saline controls (n = 10, n = 25). High dose methylprednisolone decreased infarct volume following temporary, but not permanent, focal ischemia. The benefit suggests that high dose methylprednisolone may prove useful clinically if reperfusion can be established with thrombolytic agents. Furthermore, the differential treatment effect in the setting of comparable ischemic insults implies that different modifiable biochemical processes may be present during temporary but not permanent focal ischemia, thus providing indirect evidence for reperfusion injury.

Noninfective mitral valve vegetations identified by transesophageal echocardiography as a cause of stroke.

BACKGROUND: Transesophageal echocardiography (TEE) is a useful procedure to evaluate selected stroke patients for cardiac sources of embolism. To date, noninfective valvular vegetations have not been described in large studies using transesophageal echocardiography to detect cardiac sources of embolism. We sought to investigate the frequency of noninfective valvular vegetations in patients with unexplained stroke referred for TEE and to determine the relationship of these vegetations to unrecognized thrombophilic disorders. METHODS: We evaluated 641 consecutive patients referred for TEE as a result of unexplained stroke or transient ischemic attack for the presence of valvular vegetations. Of those with vegetations identified, serial blood cultures were obtained to evaluate for an infectious etiology. Patients also had serum testing for thrombophilic disorders and selected patients underwent cerebral angiography. RESULTS: Thirteen patients (2%) who underwent TEE evaluation for unexplained stroke or transient ischemic attack were found to have noninfective valvular vegetations, all involving the mitral valve; none were identified by transthoracic echocardiography. Antiphospholipid antibodies were identified in 8 of these 13 patients (62%) and a protein C deficiency in 1 patient (8%). CONCLUSIONS: Noninfective valvular vegetations are a potential cardiac source of embolism in patients with unexplained stroke that can be better identified using transesophageal echocardiography. A large percentage of these individuals have a previously unrecognized thrombophilic disorder.

Mitral valve strands in patients with focal cerebral ischemia.

BACKGROUND AND PURPOSE: Filamentous strands attached to the mitral valve are a recently described finding in occasional patients undergoing transesophageal echocardiography (TEE), but the frequency and clinical significance of these strands remain poorly defined. The purpose of the present study was to review the prevalence of mitral valve strands in patients undergoing TEE examination and to explore the relation of these strands to cardioembolic cerebral ischemia. METHODS: All patients with native mitral valves referred for clinically indicated TEE over a 2-year period at our institution were evaluated for the presence of mitral valve strands (defined as highly mobile filamentous masses <1 mm thick attached to the atrial surface of mitral leaflets). RESULTS: Of 968 study patients, mitral valve strands were identified in 22 individuals (2.3%). Mitral valve strands were significantly more common in patients referred for TEE as a result of a recent ischemic cerebrovascular event compared with patients referred for other study indications (6.3% versus 0.3%, respectively; P<.00001). Among patients < or = 50 years of age with likely cardioembolic stroke or transient ischemic attack, 16% were found to have mitral valve strands on TEE examination. In 9% of these young patients, no other TEE finding associated with cardioembolic risk was present. CONCLUSIONS: Filamentous strands attached to the mitral valve appear to represent another risk factor for embolic cerebral ischemia, particularly in patients < or = 50 years of age.

Extracranial plasma cell granuloma presenting as a diffuse meningeal and intraparenchymal mass.

Plasma cell granuloma (PCG) is uncommon, characterized by polyclonal proliferation of mature plasma cells, usually within systemic organs. Only four previous cases have involved the central nervous system (CNS).

Progressive multifocal leukoencephalopathy presenting as multiple enhancing lesions on MRI: case report and literature review.

This report describes an immunocompetent patient with memory loss and motor abnormalities whose magnetic resonance images demonstrated multiple enhancing white matter lesions, including one that was cystic, suggestive of metastatic tumors or abscesses. Neuropathological evaluation at biopsy and subsequent autopsy revealed progressive multifocal leukoencephalopathy. Magnetic resonance evidence of enhancement and cystic changes are rare findings in progressive multifocal leukoencephalopathy, but should be considered in the differential diagnosis, especially in patients without evidence for primary malignancy or infection.

High-performance liquid chromatography separation and quantitation of methylprednisolone from rat brain.

A sensitive, reliable method for the extraction, separation, and quantitation of methylprednisolone from rat brain is reported. The method can accurately quantitate methylprednisolone levels between 9.8 and 2500 ng/injection using a two-step HPLC separation and monitoring absorbance at 254 nm. A 90% extraction recovery of methylprednisolone (interday variation of 9.0% and an intraday variation of 0.0 to 7.7%) from rat cortex was obtained with a double extraction method using low toxicity solvents. These solvents are known to quantitatively extract the neutral lipids and phospholipids from brain. Combined with the ability to separate the neutral lipid and methylprednisolone fractions for further separation, and the ability to separate all phospholipid classes in the first run, this method offers great utility combined with the reliable, high extraction recovery and sensitive quantitation of methylprednisolone.

Hypertension and hyperglycemia in experimental stroke.

Both diabetes mellitus and hypertension are risk factors for stroke and also influence prognosis following stroke. Experimentally, hyperglycemia augments cortical infarct size in stroke models where collateral circulation exists, and infarct size in hypertensive rats is larger than in normotensive strains. Whether the deleterious effect of hyperglycemia is altered in the setting of hypertension has not previously been studied experimentally. The effect of hyperglycemia on infarct size in spontaneously hypertensive rats was examined in this study. Focal neocortical cerebral ischemia was induced by tandem right common carotid and middle cerebral artery occlusion. Preischemic hyperglycemia had no influence on infarct volume whether the duration of postischemic hyperglycemia was transient or prolonged. Although hyperglycemia increases infarct size in cortical stroke models where collateral circulation is available, this study demonstrates the effect can be modified by the presence of underlying hypertension.

The clinical spectrum of necrotizing angiopathy of the peripheral nervous system.

The peripheral neuropathy seen with necrotizing angiopathy is said to begin classically as a mononeuritis multiplex, usually associated with polyarteritis nodosa, rheumatoid arthritis, or systemic lupus erythematosus. Our experience, however, suggests that a large number of these patients do not have a well-defined collagen vascular disease or the typical clinical pattern. In 350 consecutive nerve biopsies (sural or superficial radial), 16 patients showed a necrotizing angiopathy in the epineurial blood vessels. Six of these 16 patients had a distal symmetrical sensorimotor polyneuropathy. The remaining 10 had a mononeuritis multiplex, although in 8 overlapping nerve involvement somewhat obscured the picture of mononeuritis. In 12 patients, no specific underlying collagen vascular disease could be diagnosed by accepted criteria despite extensive clinical, radiological, and serological evaluations. The peripheral neuropathy was the only objective evidence of vasculitis in 7 of these 12 patients. Our findings suggest that patients with a peripheral neuropathy secondary to necrotizing angiopathy often do not have a definable collagen vascular disease. In fact, peripheral neuropathy may be the sole manifestation of vasculitis. Furthermore, the neuropathy was found to be a distal symmetrical sensorimotor neuropathy in a higher proportion of cases than has been documented previously.