Thrombolysis with recombinant tissue plasminogen activator in acute ischemic stroke: evaluation with rCBF-SPECT

Background and PurposeWe used Tc-hexamethylpropyleneamine oxime single-photon emission computed tomography (SPECT) to study cerebral perfusion in patients treated with streptokinase for acute ischemic stroke in an open and prospective study. Our primary aims were (1) to compare the extent of reperfusion between patients who had received thrombolytic therapy and a control group studied during the same period who were ineligible to receive such therapy and (2) to determine if, among all patients, reperfusion led to improved outcome.Methods Fifty-seven patients (22 treated with streptokinase) had two SPECT studies performed, the first before streptokinase administration and the second 24 hours later.Results On the first SPECT study hypoperfusion was present in the middle cerebral artery or anterior cerebral artery territories in 40 patients (17 treated with streptokinase). Patients in the treatment and control groups with initial hypoperfusion on SPECT were well matched for the volume of the perfusion defect and the severity of neurological deficit. A greater number of patients who received streptokinase devel-

Section: Discussionmentioning

confidence: 99%

Reperfusion after thrombolytic therapy in ischemic stroke measured by single-photon emission computed tomography.

Baird

Donnan

Austin

et al. 1994

“…Although the number of patients included in this study is very small, the data are consistent with clinical response observed in our patients and with other studies of cerebral perfusion and thrombolysis in the literature. [3][4][5] One implication of our study is that clinical criteria alone without confirmatory measurement of cerebral perfusion is sufficient to establish that most patients who qualify for rtPA therapy on clinical grounds also have a significant cerebral ischemic lesion. The patient population in this SPECT study did not include those with brain stem infarcts but did include patients suspected of having either cortical or lacunar hemispheric strokes.…”

Section: Discussionmentioning

confidence: 99%

tPA-Associated Reperfusion After Acute Stroke Demonstrated by SPECT

Grotta

Alexandrov

1998

Purpose-The aim of our study was twofold: to determine the frequency and magnitude of perfusion defect in stroke patients who qualify for rtPA therapy within 3 hours of stroke onset and to determine the ability of rtPA to improve perfusion by 24 hours. Subjects and Methods-Patients with suspected hemispheric stroke who fulfilled entry criteria into the National Institute of Neurological Disorders and Stroke (NINDS) rt-PA Stroke Study and also had pretreatment injection of 99m Tc-HMPAO, with single-photon emission computed tomography (SPECT) performed using a triple-head camera at baseline and 24 hours, were included. Results-All 12 patients who qualified for rtPA therapy had perfusion defects on baseline SPECT (SPECT graded scale [SGS] score range, 16 to 79). MeanϮSD perfusion defect was comparable in rtPA (nϭ4)versus placebo (nϭ5) A lthough rtPA therapy within the first 3 hours after the onset of acute stroke symptoms results in improved outcome, the urgency of this therapy precludes extensive diagnostic studies before treatment. Therefore, in the NINDS study that demonstrated the efficacy of rtPA, there was no requirement to demonstrate a perfusion defect prior to treatment. Furthermore, while it is assumed that the effectiveness of rtPA was due to its ability to improve reperfusion during the immediate poststroke period, this was not documented by comparing baseline with 24-hour studies of cerebral blood flow in the rtPA versus placebo groups. At our center, which was one of the participants in the NINDS rt-PA Stroke Study, we tried to obtain SPECT cerebral perfusion studies at baseline and after 24 hours in as many patients as possible during the study. We report the baseline results in all 12 patients who had SPECT scans carried out within 3 hours of symptom onset and the baseline compared with 24-hour SPECT studies in all 5 placebo-treated and 4 rtPA-treated patients. Subjects and Methods Selection of PatientsAll patients admitted to Hermann Hospital (Houston, Tex), where we carried out the NINDS rtPA study, were considered for inclusion.The inclusion and exclusion criteria for the NINDS study have been published 1 and for the most part were the inclusion and exclusion criteria for the present SPECT analysis, because all patients studied with SPECT were being considered simultaneously for inclusion into the NINDS rtPA trial. In addition, to be included in this SPECT substudy, all patients had to receive the injection of isotope ( 99m Tc-HMPAO) for SPECT within 3 hours of symptom onset but before rtPA administration, all had to have technically adequate SPECT scans carried out at baseline and again after 24 hours, and all had to have suspected hemispheric infarcts. Of the 12 patients meeting these criteria and included in this analysis, 8 were randomized into the NINDS rtPA versus placebo study and one was treated with openlabel rtPA soon after the study was completed. Three were not treated with thrombolytics. Some of these patients were included in a previous publication 2 that validated our SPECT meth...

“…These tissue compartments were indicated in some of our patients by those ROIs within infarcted tissue clustering at normal FMZ values (Fig 5). For the decision on the potential of therapeutic strategies-reperfusion, neuroprotection, or rehabilitationthe study of the intactness of GABAergic receptors by BZR ligands might yield useful information in addition to the detection of the impairment in blood supply by SPECT or PET, [44][45][46][47][48] which was shown to be reversed by intravenous recombinant tissue plasminogen activator followed by clinical improvement. 49 However, as indicated by the high correlation between FMZ distribution within the first 2 minutes after injection and rCBF measured by H 2 15 O, regional perfusion can also be assessed semiquantitatively by FMZ.…”

Section: Discussionmentioning

confidence: 99%

Permanent Cortical Damage Detected by Flumazenil Positron Emission Tomography in Acute Stroke

Heiss¹,

Grond²,

Thiel³

et al. 1998

103

Background and Purpose-Therapy of acute ischemic stroke can only be effective as long as neurons are viable and tissue is not infarcted. Since ␥-aminobutyric acid receptors are abundant in the cortex and sensitive to ischemic damage, specific radioligands to their subunits, the central benzodiazepine receptors (BZR), may be useful as indicators of neuronal integrity and as markers of irreversible damage. To test this hypothesis we studied the binding of the BZR ligand [ 11 C]flumazenil (FMZ) early after ischemic stroke in comparison to the extent of final infarcts and hypometabolic cortical areas. Methods-In 10 patients cerebral blood flow, cerebral metabolic rate for oxygen (CMRO 2 ), oxygen extraction fraction (OEF), and FMZ binding were studied by positron emission tomography 3.5 to 16 hours after onset of their first hemispheric stroke. Early changes in flow, oxygen metabolism, and FMZ binding were compared with permanent disturbances in glucose metabolism, and the size of the final infarcts was determined on MRI or CT 12 to 22 days after the stroke. Results-In all patients except one cerebral blood flow was disturbed, with marked decreases in eight and a hyperperfusion in one patient corresponding to the location of neurological deficits. In these areas CMRO 2 was also reduced but to a variable degree, inducing highly variable OEF. Areas with markedly decreased CMRO 2 (Ͻ60 mol/100 g per minute) corresponded to regions with decreased FMZ binding (Ͻ4.0 times the mean value in the white matter). In all patients the final cortical infarcts were visible on the early FMZ images. Infarcts could be discriminated from noninfarcted cortex by decreased FMZ binding despite a wide range of OEF. In finally hypometabolic cortex FMZ binding was initially decreased or normal, with OEF covering a wide range; this suggested neuronal loss and/or deactivation as the cause of metabolic disturbance. Additionally, a highly significant correlation was found between FMZ distribution within the first 2 minutes after injection and regional cerebral blood flow. Conclusions-These results demonstrate that permanently and irreversibly damaged cortex can be detected by reduced FMZ binding early after stroke. Since FMZ distribution additionally images regional cerebral perfusion, BZR radioligands have a potential as clinically useful tracers in patients with acute ischemic stroke. The evidence of tissue damage furnished by these tracers might be of relevance for the selection of individual therapeutic strategies. (Stroke. 1998;29:454-461.)