W J McKay

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

Background and Purpose We used 99mTc-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 developed at least partial reperfusion (streptokinase, 65%; control, 52%) on the second study but not significantly so (P=.43). Similarly, the proportion of each hypoperfused region that reperfused (P=.74) and the reduction in the size of the perfusion defect (P =.06) were higher in the streptokinase group but did not reach statistical significance. When all patients were considered, those who did not reperfuse had higher mortality rates (P=.008), less neurological improvement (P=.016), and more functional disability (P < .001) than patients who had reperfusion or normal perfusion initially. Conclusions These findings suggest that at least some reperfusion during the first 48 hours of ischemic stroke is a common natural occurrence and is of prognostic significance. The observed trend toward better reperfusion indexes among patients treated with streptokinase is encouraging, but larger controlled trials are required to answer this definitively.

No evidence of hypoxic tissue on 18F-fluoromisonidazole PET after intracerebral hemorrhage

Article abstract We studied six patients after intracerebral hemorrhage (ICH) and eight controls using positron emission tomography (PET) with to determine whether a zone of tissue hypoxia, possibly representing “penumbral” tissue, exists surrounding an intracerebral hemorrhage. None of the stroke patients, studied 24 to 43 hours after symptom onset, nor any of the controls exhibited areas of tissue hypoxia on 18F-fluoromisonidazole PET images. These findings may have implications for the treatment of intracerebral hemorrhage with neuroprotective strategies.

Changes in cerebral tissue perfusion during the first 48 hours of ischaemic stroke: relation to clinical outcome.

BACKGROUND--One major therapeutic strategy to minimise the extent of infarction after ischaemic stroke is to improve early reperfusion using thrombolytic agents. However, reperfusion may be hazardous and the period during which reperfusion may have a beneficial effect on tissue and clinical outcome is not known. METHODS--Fifty three patients were studied with serial cerebral perfusion (99mTcHMPAO SPECT) during the first 48 hours of ischaemic stroke to determine if changes in tissue perfusion during this time were prognostically significant. Single and multiple linear regression non-parametric analyses were used to include other factors during the same period which may influence outcome. RESULTS--In univariate analysis age, neurological score at admission, SPECT perfusion defect size in the first 24 hours, and percentage change in cerebral tissue perfusion at 24-48 hours (all P < 0.01) correlated significantly with the Barthel score at three months. In multiple linear regression analysis only age (P < 0.01) and percentage change in cerebral tissue perfusion at 24-48 hours (P < 0.01) provided independent prognostic information at three months. CONCLUSIONS--Changes in cerebral tissue perfusion during the first 48 hours of ischaemic stroke are significant outcome predictors and therapeutic effort aimed at increasing perfusion during this period seem to be justified.

Sensitivity and Specificity of 99mTc-HMPAO SPECT Cerebral Perfusion Measurements During the First 48 Hours for the Localization of Cerebral Infarction

BACKGROUND AND PURPOSE There is no routinely used method for imaging the location of the extent and severity of cerebral tissue perfusion changes during the first hours of ischemic stroke, the period during which therapeutic intervention is most likely to be successful. Cerebral perfusion measurements with single-photon emission CT (SPECT) may potentially provide this information rapidly and noninvasively. In this study, the sensitivity and specificity of 99mTc-hexamethylpropyleneamine oxime (HMPAO) SPECT cerebral perfusion measurements during the first 48 hours of cerebral ischemia for the localization of cerebral infarction were determined. METHODS One hundred and four patients with acute ischemic stroke underwent 99mTc-HMPAO SPECT and CT scanning during the first 48 hours. In each patient, the location of the SPECT perfusion abnormality was compared with the location of infarction on a second brain CT acquired at a mean of 8 days after stroke. RESULTS During the first 48 hours of ischemic stroke, the sensitivity of 99mTc-HMPAO SPECT in locating the site of infarction was 79% (110/139), and the specificity was 95% (362/381). SPECT was more sensitive in the localization of the vascular territory of cortical infarction (sensitivity, 93%) than pure subcortical infarcts (sensitivity, 47%). During the first 48 hours, SPECT was significantly more sensitive than brain CT (sensitivity of brain CT during the first 48 hours, 35%; P < .001, Mann-Whitney U test). CONCLUSIONS HMPAO SPECT measurement provides a widely available and practical technique of locating cerebral ischemia acutely and demonstrates high sensitivity and specificity within the first 48 hours for the localization of the vascular territory of cerebral infarction. It is most sensitive for cortical ischemia but is limited by its resolution in the subcortex, particularly of white matter perfusion changes.

Early reperfusion in the 'spectacular shrinking deficit' demonstrated by single-photon emission computed tomography.

The “spectacular shrinking deficit” (SSD) refers to a syndrome of profound hemispheric ischemia that resolves rapidly over hours to days, leaving patients with minimal residual neurologic deficits. The SSD is postulated to result from rapid embolic lysis, fragmentation, and migration along the internal carotid/middle cerebral artery axis, leading to restored tissue perfusion before irreversible tissue damage has occurred. We performed serial single-photon emission computed tomographic (SPECT) cerebral perfusion measurements during the first 48 hours in 36 patients admitted with major hemispheric ischemia, to compare the cerebral perfusion changes between patients who developed SSD (n = 5) and those who did not (n = 31). The two groups were similar for severity of neurologic deficit, time of SPECT study, and size of perfusion defect on the SPECT images. Patients with SSD were younger (p = 0.02, Mann-Whitney U), demonstrated significantly greater tissue reperfusion during the first 48 hours (p < 0.011, and had smaller infarcts on CT (p = 0.02). This syndrome provides an opportunity to understand the mechanism by which early reperfusion may result in early tissue salvage and clinical recovery.

Asymmetries of cerebral perfusion in a stroke-age population

Cerebral perfusion measurements with(99m)Tc-hexamethylpropyleneamine oxime single photon emission computed tomography (HMPAO SPECT) are potentially clinically useful in the investigation of patients with acute ischaemic stroke. The normal side-to-side asymmetry on(99m)Tc-HMPAO SPECT images may be greater in the stroke-age population than in younger age groups. To assess the extent of variation we studied 66 volunteers with(99m)Tc-HMPAO SPECT who were closely age matched to a stroke population and who had normal CT and extracranial and intracranial vascular ultrasonography. By measuring the side-to-side ratios in 19 regions of interest, the normal side-to-side perfusion asymmetry was determined and, as a secondary aim, variations in regional asymmetry were correlated with age. After repeated measurement analysis of variance (ANOVA), the normal range of side-to-side ratios in this population was 1.003+/-0.145 (mean+/-1.96 SD, ANOVA). The two regions with the greatest side-to-side asymmetry values were (1) the superior lateral temporal cortex (higher on the right relative to the left) and (2) the superior parietal cortex (higher on the left relative to the right). The orbitofrontal and posterior temporal cortices demonstrated significantly increased bidirectional variation with age (P< 0.05). In a stroke-age population hemispheric perfusion is relatively symmetrical and a side-to-side variation of greater than +/-14.5% may be defined as pathological. This value is higher than that reported in younger volunteers suggesting that there is a mild increase in the side-to-side perfusion asymmetry with age. Increased variation in the orbitofrontal and posterior temporal cortices occurs with age and should be borne in mind when interpreting HMPAO SPECT studies. Copyright 1999 Harcourt Publishers Ltd.

Use of [18F]-fluorodeoxyglucose positron emission tomography in monitoring response of recurrent neurotropic desmoplastic melanoma to radiotherapy

A 35-year-old man originally sought treatment in 1985 for an ulcerating lesion on the lower lip. When the lesion was resected, histology showed an amelanotic neurotropic variant of desmoplastic melanoma invading deep into the muscle of the lip around small nerves and blood vessels; staining was positive for S-100 protein. Repeat excisions were performed twice during the next 2 months, before histologically complete removal was attained.

HMPAO SPECT Measures Reperfusion After Thrombolytic Therapy in Acute Stroke

The introduction of thrombolytic therapy is potentially a major advance in the management of patients with acute stroke. Important applications of Single Photon Emission Computed Tomography (SPECT) may be the early identification of the site (and possibly severity) of cerebral ischemia, and the measurement of reperfusion after thrombolytic therapy. We are using hexamethyl-propyleneamine oxime (HMPAO) SPECT to measure cerebral perfusion before and after streptokinase administration in patients entered into the Australian Streptokinase (ASK [1]) Trial. We are aiming to measure the degree of cerebral reperfusion within the first 48 h of ischemic stroke, and to correlate this with thrombolytic administration and functional outcome.

Reperfusion in Patients with the “Spectacular Shrinking Deficit” Demonstrated by 99mTc-hexamethylpropyleneamine Oxime Single Photon Emission Computed Tomography

The “spectacular shrinking deficit” (SSD) [1–4] refers to a syndrome of profound hemispheric ischemia that resolves rapidly over hours to days leaving patients with minimal residual neurological deficits. It is postulated that the SSD results from rapid clot lysis, fragmentation, and migration along the internal carotid-middle cerebral arterial axis, with tissue perfusion being restored before irreversible damage has occurred. Clot migration has been demonstrated angiographically in this syndrome [4]; however, the tissue perfusion changes have not previously been described.