Corrado Argentino

Clinical and instrumental evaluation of patients with ischemic stroke within the first six hours

The development of fibrinolytic agents such as streptokinase and recombinant tissue type plasminogen activator (r-TPA) and other modalities of treatment in acute ischemic stroke, has raised the need for a more precise knowledge of the pathophysiology of the acute phases of ischemic stroke as it pertains to prediction of clinical outcome. In a prospective analysis, 80 patients were studied within less than 6 h from the onset of symptoms by means of a detailed protocol including clinical evaluation, cerebral computed tomography, digital angiography and ultrasound transcranial Doppler sonography. Early angiography revealed a complete arterial occlusion in 76% of cases, the majority of which were intracranial (66%). Seventy percent of the occlusions that were retested were removed within 1 week. Potential embolic sources were found in more than 80% of cases. Patients with documented intracranial occlusion and scarce or absent collateral filling at early angiography, had the worst clinical outcome (P less than 0.05), based on mortality data and the Canadian Neurological Scale. The 30-day mortality rate was 25%. Survival was significantly better (P less than 0.01) in patients with a Canadian Neurological Score on entry of greater than or equal to 6.5 than in patients with a less than 6.5 value. Our data indicate that early pathophysiological studies augment the clinical information and should be taken into account in the design and analysis of therapeutic trials of acute ischemic stroke.

Comparison of cerebral angiography and transcranial Doppler sonography in acute stroke.

We compared digital intra-arterial angiography and transcranial Doppler sonography in acute cerebral ischemia as part of a wider study on a continuous series of 48 patients with acute focal cerebral ischemia in the carotid territory, observed within 4 hours of the onset of symptoms. The most significant Doppler findings of the middle cerebral artery included no detection of the artery when occlusion of the carotid siphon or the middle cerebral artery at its origin was shown by angiography and reduced flow velocities and asymmetry (symptomatic less than asymptomatic) when the occlusion was located in the terminal tract of the middle cerebral artery mainstem or in numerous terminal branches. Higher flow velocities in the anterior cerebral artery or posterior cerebral artery, mostly in the symptomatic hemisphere, often accompanied middle cerebral artery pathology, probably indicating collateral compensatory pathways.

Hemorrhagic transformation of brain infarct Predictability in the first 5 hours from stroke onset and influence on clinical outcome

Objective: To identify, in the first 5 hours of acute brain infarct, clinical and radiologic predictors of subsequent hemorrhagic transformation (HT), and to evaluate its influence on the clinical course. Background: The identification of early predictors of HT might be important to plan antithrombotic or thrombolytic treatments. Patients: One hundred fifty consecutive patients with cerebral anterior circulation infarct systematically underwent a first CT within 5 hours of onset. During the first week after stroke, we performed a repeat CT or autopsy to look for HT. Outcome measures were early neurologic deterioration within the first week of onset and 30-day case fatality rate and disability. Results: HT was observed in 65 patients (43%): 58 (89%) had a petechial HT and seven (11%) a hematoma. Among initial clinical and CT findings, the only independent predictor of HT was early focal hypodensity. Its presence was associated with subsequent HT in 77% of cases (95% CI, 68 to 86%), whereas its absence predicted the absence of subsequent HT in 94% of cases (95% CI, 89 to 99%). No baseline clinical or CT characteristic differentiated patients with petechial HT from those with hematoma. Antithrombotic and antiplatelet agents did not influence the occurrence of either type of HT. The frequency of early neurologic deterioration and of 30-day death or disability in HT patients was twice as high as in those without HT. However, a large-sized infarct and the presence of mass effect at the repeat CT or autopsy were the only factors independently linked to both the outcome events, irrespective of the development of HT. Clinical evolution of HT patients given antithrombotics was comparable with that of HT patients not receiving these drugs. Conclusions: HT of a brain infarct is a common event that occurs independently of anticoagulation and can be reliably predicted as early as 5 hours from stroke onset by the presence of focal hypodensity at CT. Apart from the infrequent cases of massive hematoma, HT does not influence prognosis, whereas a poor outcome in HT patients is correlated with a higher frequency of large edematous infarcts in this subgroup. The clinical course and final outcome of HT in anticoagulated patients does not differ from that of non-anticoagulated HT patients. NEUROLOGY 1966;46: 341-345

Circadian variation in the frequency of ischemic stroke.

The frequency of myocardial infarction and sudden death is increased between 6 AM and noon. To determine whether the same is true for the onset of ischemic stroke, we studied 426 consecutive patients within 12 hours after the onset of their first hemispheric stroke. The frequency of onset of hemispheric stroke was significantly (p = 0.0001) higher from 6:01 AM to noon (56.1%) than from 12:01 PM to 6 PM (20.2%), from 6:01 PM to midnight (8.2%), and from 12:01 AM to 6 AM (15.5%). The identification of periods of high risk for vascular events may have important therapeutic implications, such as matching drug effects with vulnerability.

Early Spontaneous Improvement and Deterioration of Ischemic Stroke Patients A Serial Study With Transcranial Doppler Ultrasonography

BACKGROUND AND PURPOSE The purpose of our study was to investigate whether emergency transcranial Doppler (TCD) findings and their modifications over the first 48 hours are related to early neurological changes in acute ischemic stroke patients. METHODS Ninety-three patients underwent CT scan within 5 hours of a first-ever ischemic hemispheric stroke, and TCD serial examinations at 6, 24, and 48 hours after stroke onset. We classified TCD findings as follows: normal; middle cerebral artery (MCA) asymmetry (asymmetry index between affected and contralateral MCAs below -21%); and MCA no-flow (absence of flow signal from the affected MCA in the presence of ipsilateral anterior and posterior cerebral artery signals through the same acoustic window). We considered early deterioration and early improvement to be a decrease or an increase of 1 or more points, respectively, in the Canadian Neurological Scale score over the same period. RESULTS At 6-hour TCD examination, MCA asymmetry and MCA no-flow were present in 6 (22%) and 2 (7%), respectively, of 27 improving patients; in 20 (43%) and 10 (22%) of 46 stable patients, and in 9 (45%) and 8 (40%) of 20 deteriorating patients. TCD findings were normal in the remaining patients (P = 0.001). At serial TCD, we detected early (within 24 hours) recanalization (from no-flow to asymmetry or normal and from asymmetry to normal) in 2 (25%) improving patients, in 7 (23%) stable patients, and in 5 (29%) deteriorating patients and late (between 24 and 48 hours) recanalization in 4 (50%) improving patients, in 6 (20%) stable patients, and in none of the deteriorating patients (P = 0.03, chi 2 for trend, improving versus nonimproving irrespective of the timing of recanalization). One deteriorating patient (5%) developed a non-flow from an initial MCA asymmetry. Logistic regression selected normal TCD (odds ratio [OR], 0.17; 95% confidence interval [CI], 0.06 to 0.46) as an independent predictor of early improvement and abnormal TCD (asymmetry plus no-flow) (OR, 5.02; 95% CI, 1.31 to 19.3) as an independent predictor of early deterioration. CONCLUSIONS TCD examination within 6 hours after stroke can help to predict both early deterioration and early improvement. Serial TCD shows that propagation of arterial occlusion is rarely related to early deterioration, whereas the fact that it can detect early recanalization (within 24 hours) in deteriorating patients and both early and late recanalization (after 24 hours) in improving patients suggests the existence of individual time frames for tissue recovery.

Predictive value of brain perfusion single-photon emission computed tomography in acute ischemic stroke.

We investigated 32 patients with completed ischemic stroke less than or equal to 6 hours after the onset of symptoms by means of computed tomography, cerebral angiography, and technetium-99m-labeled hexamethylpropyleneamine oxime single-photon emission computed tomography to study cerebral blood flow. Follow-up computed tomography and cerebral blood flow studies were performed 1 week and 1 month after admission. Poor outcome at 1 month was evident in 18 (78%) of the 23 patients with severe neurologic deficit on admission and in 11 (92%) of the 12 patients with severe hypoperfusion in the affected hemisphere on admission. All 10 patients with severe impairment of both neurologic status and cerebral blood flow had a poor outcome at 1 month. We detected severe hypoperfusion in patients with large lesions on computed tomograms or cerebral artery occlusions on angiograms. Cerebral blood flow had increased at the 1-week follow-up despite different clinical outcomes. Our data provide evidence that early evaluation of cerebral blood flow with single-photon emission computed tomography is useful to detect subgroups of patients with different clinical outcomes during the acute phase of ischemic stroke.

Imaging of leukocytic infiltration in human cerebral infarcts.

The circulating white blood cells of patients with brain infarction were labelled in vitro with Indium-111 tropolonate; the cells were reinjected to study the inflammatory process by gamma camera imaging. Eight patients with acute cerebral ischemic infarct were studied during the first two weeks after the onset of neurological symptoms. In seven cases a well defined area of increased radioactivity was revealed in the infarcted hemisphere indicating active migration and tracking of labelled leukocytes in cerebral infarct. This method allows monitoring of the cellular inflammatory response in human cerebral infarcts and adds another imaging technique.

Prognostic significance of admission levels of troponin I in patients with acute ischaemic stroke

Objectives: Successful prediction of cardiac complications early in the course of acute ischaemic stroke could have an impact on the clinical management. Markers of myocardial injury on admission deserve investigation as potential predictors of poor outcome from stroke. Methods: We prospectively investigated 330 consecutive patients with acute ischaemic stroke admitted to our emergency department based stroke unit. We analysed the association of baseline levels of cardiac troponin I (cTnI) with (a) all-cause mortality over a six month follow up, and (b) inhospital death or major non-fatal cardiac event (angina, myocardial infarction, or heart failure). Results: cTnI levels on admission were normal (lower than 0.10 ng/ml) in 277 patients (83.9%), low positive (0.10–0.39 ng/ml) in 35 (10.6%), and high positive (0.40 ng/ml or higher) in 18 (5.5%). Six month survival decreased significantly across the three groups (p<0.0001, log rank test for trend). On multivariate analysis, cTnI level was an independent predictor of mortality (low positive cTnI, hazard ratio (HR) 2.14; 95% CI 1.13 to 4.05; p = 0.01; and high positive cTnI, HR 2.47; 95% CI 1.22 to 5.02; p = 0.01), together with age and stroke severity. cTnI also predicted a higher risk of the combined endpoint “inhospital death or non-fatal cardiac event”. Neither the adjustment for other potential confounders nor the adjustment for ECG changes and levels of CK-MB and myoglobin on admission altered these results. Conclusions: cTnI positivity on admission is an independent prognostic predictor in acute ischaemic stroke. Whether further evaluation and treatment of cTnI positive patients can reduce cardiac morbidity and mortality should be the focus of future research.

Changing prognosis of primary intracerebral hemorrhage: results of a clinical and computed tomographic follow-up study of 104 patients.

One hundred four consecutive cases of primary intracerebral hemorrhage hospitalized at the time of stroke were followed until death or for 1 year. All were treated nonsurgically. The 30-day mortality rate was 30%. Good clinical outcome and complete resolution of the lesion on computed tomography were observed in 49 and 13% of patients, respectively. Age, state of consciousness, and size of the hemorrhage on computed tomography scan were reliable prognostic indicators. The long-term survival rate, 66%, was higher than that previously reported and should be considered in future trials evaluating medical and surgical treatment of intracerebral hemorrhage.

Acute Ischemic Strokes Improving During the First 48 Hours of Onset: Predictability, Outcome, and Possible Mechanisms A Comparison With Early Deteriorating Strokes

BACKGROUND AND PURPOSE Our aims were to identify predictors of early neurological improvement in acute ischemic stroke patients, to evaluate its impact on clinical outcome, and to investigate possible mechanisms. METHODS A consecutive series of 152 first-ever ischemic hemispheric stroke patients hospitalized within 5 hours of onset underwent a first CT scan within 1 hour of hospitalization, and the initial subset of 80 patients also underwent angiography. During the first 48 hours of hospital stay, an increase or a decrease of 1 or more points in the admission Canadian Neurological Scale (CNS) score was defined as early improvement or early deterioration, respectively. Repeated CT scan or autopsy was performed 5 to 9 days after stroke. RESULTS Thirty-four patients (22%) improved, 84 (56%) remained stable, and 34 (22%) deteriorated. Logistic regression, which took into account vascular risk factors, baseline clinical and CT data, and therapies administered, selected younger age, lower admission CNS score, and absence of early hypodensity at first CT as independent predictors of early improvement. Among the patients who underwent angiography, logistic regression selected arterial patency and presence of collateral blood supply as independent predictors of early improvement. At the repeated CT scan or autopsy, improving patients presented the highest frequency of small infarcts. Thirty-day case-fatality rate and disability were lower in improving patients. Variables independently associated with outcome at logistic regression were admission CNS score, early deterioration, and early improvement. CONCLUSIONS Early improvement can be predicted by the absence of early CT hypodensity and is highly predictive of good outcome. Presence of collateral blood supply and presumably early spontaneous recanalization are likely to be the mechanisms underlying early improvement.