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Biomedical subjects

Mark W Parsons

Publications and source records attributed to Mark W Parsons.

13 recordsLinked to original sources

CT perfusion source images improve identification of early ischaemic change in hyperacute stroke.

CT perfusion scanning produces dynamic contrast-enhanced brain images, but to generate and interpret the colour maps of cerebral perfusion from these source images requires specialist neuroimaging knowledge. We hypothesized that physicians without such training might still utilise the CT perfusion source images (CTPSI) to diagnose early ischaemic change. Fifteen patients had cerebral non-contrast CT (NCCT) and perfusion CT within 6 hours of hemispheric stroke onset. We tested 15 non-stroke clinicians and radiology trainees, plus three experts, in assessing the presence and extent of early ischaemic change on NCCT versus CTPSI. Day 5-7 CT or MRI was used as the gold standard. Agreement with follow-up imaging was poor for both detection, and extent of early ischaemic change on NCCT (kappa = 0.01-0.11). There was a marked improvement in agreement for both the presence and extent of early ischaemic change on CTPSI (kappa = 0.67-0.83). CTPSI were much more accurate than NCCT in identifying acute ischaemic change. 'Less expert' users accurately identified major early ischaemic change on acute CTPSI. These findings suggest that such physicians might utilise CTPSI to screen potential thrombolysis candidates.

Acute Disease↗

Apparent diffusion coefficient thresholds do not predict the response to acute stroke thrombolysis.

BACKGROUND AND PURPOSE: Apparent diffusion coefficient (ADC) thresholds for tissue infarction have been identified in acute stroke. IV tissue plasminogen activator (tPA) is associated with tissue salvage. We hypothesized that tPA would lower the ADC threshold for infarction. METHODS: ADC and mean transit time (MTT) maps were generated for 26 patients imaged within 6 hours of stroke onset (12 tPA and 14 conservatively managed controls). MTT maps and day-90 T2-weighted images were coregistered to ADC maps. Relative ADC (rADC) values were calculated for initial diffusion-weighted imaging (DWI) lesions, infarct growth regions (final infarct volume-the acute DWI lesion volume), and hypoperfused salvaged regions (HS; MTT map abnormality-the final infarct volume). When relevant, the DWI lesion was subdivided into DWI reversal and DWI infarct regions. RESULTS: Mean DWI lesion rADC was 0.79 in tPA and 0.74 in untreated patients (P=0.097). Mean rADC in HS and infarct growth regions were similar in tPA patients (0.950 and 0.946) and untreated patients (0.957, P=0.76; 0.970, P=0.08, respectively). The rADC in HS tissue was directly correlated with the time to treatment with tPA (r=0.685; P=0.029). DWI reversal was seen in 67% of tPA-treated patients and in 36% of those conservatively managed (Fisher exact test; P=0.238). In the 13 patients with DWI reversal, the mean rADC in these regions (0.81+/-0.07) was significantly higher than in the acute DWI region that infarcted (0.74+/-0.07; P=0.02), although no absolute thresholds could be identified. CONCLUSIONS: The peri-DWI lesion region contains tissue with intermediate ADC values. The fate of this tissue is variable and cannot be predicted based on the ADC alone. DWI expansion occurs in bioenergetically normal tissue, and this is attenuated by tPA in a time-dependent fashion.

Aged↗

Perfusion computed tomography: prediction of final infarct extent and stroke outcome.

The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) has not been previously applied to perfusion CT (CTP). Five raters assigned ASPECTS to baseline noncontrast CT (NCCT), CT angiography source images (CTA-SI), CTP source images (CTP-SI), and CTP maps of cerebral blood volume (CBV), cerebral blood flow (CBF), and mean transit time (MTT) from 37 consecutive patients with less than 6-hour anterior circulation ischemic stroke. Major reperfusion was identified on follow-up imaging. Mean baseline ASPECTS was compared with follow-up imaging ASPECTS. Rates of favorable outcome were compared for dichotomized baseline ASPECTS. In patients with major reperfusion, mean CBV and CTP-SI ASPECTS closely predicted final infarct ASPECTS. In patients without major reperfusion, mean CBF and MTT ASPECTS best predicted final infarct ASPECTS. There were significant increases in rates of favorable outcome for CTP-SI and CBV ASPECTS of greater than 6, versus less than or equal to 6, but not for other baseline CT modalities. ASPECTS applied to CTP is more accurate at identifying the extent of reversible and irreversible ischemia and at predicting final clinical outcome than NCCTor CTA-SI.

Aged↗

The use of PWI and DWI measures in the design of "proof-of-concept" stroke trials.

BACKGROUND AND PURPOSE: The authors used serial magnetic resonance perfusion-weighted imaging (PWI) and diffusion-weighted imaging (DWI) to determine whether major reperfusion and the attenuation of infarct expansion are associated with improved stroke outcome. METHODS: Forty-nine patients were studied with serial magnetic resonance imaging within 6 hours of stroke onset and again at 4 days (subacute studies) and 3 months (outcome studies). Two imaging parameters were examined: infarct expansion between acute and outcome studies and major reperfusion between acute and subacute studies. RESULTS: Patients with major reperfusion (45% of those with acute PWI lesions) were more likely to have little or no disability at outcome (National Institutes of Health Stroke Scale [NIHSS] score < or = 4, P = .0176; Barthel Index [BI] score > or = 90, P = .0547) after adjustment for baseline differences. In contrast, patients with infarct expansion (48%) were more likely to be dead or dependent at outcome (BI < 90, P = .0414; NIHSS score P = .082; modified Rankin Scale score > 2, P < .0001). These measures were used to generate sample size calculations based on hypothetical treatment effects. Therapies postulated to double the proportion of patients with major reperfusion from one third to two thirds would require 41 patients in each group (treated and untreated) to be sufficiently powered to show a difference. Interventions postulated to halve the number of patients with infarct expansion from 50% to 25% would require 66 patients in each group to show a difference. CONCLUSIONS: Infarct expansion and major reperfusion are associated with clinically meaningful changes in stroke outcome. These measures could be used as surrogate markers of outcome in late phase II proof-of-concept stroke studies designed to provide efficacy signals before embarking on large phase III studies with definitive clinical endpoints.

Adult↗

Persistent poststroke hyperglycemia is independently associated with infarct expansion and worse clinical outcome.

BACKGROUND AND PURPOSE: Hyperglycemia at the time of ischemic stroke is associated with increased mortality and morbidity. Animal studies suggest that infarct expansion may be responsible. The influence of persisting hyperglycemia after stroke has not previously been examined. We measured the blood glucose profile after acute ischemic stroke and correlated it with infarct volume changes using T2- and diffusion-weighted MRI. METHODS: We recruited 25 subjects within 24 hours of ischemic stroke symptoms. Continuous glucose monitoring was performed with a glucose monitoring device (CGMS), and 4-hour capillary glucose levels (BGL) were measured for 72 hours after admission. MRI and clinical assessments were performed at acute (median, 15 hours), subacute (median, 5 days), and outcome (median, 85 days) time points. RESULTS: Mean CGMS glucose and mean BGL glucose correlated with infarct volume change between acute and subacute diffusion-weighted MRI (r>or=0.60, P<0.01), acute and outcome MRI (r=0.56, P=0.01), outcome National Institutes of Health Stroke Scale (NIHSS; r>or=0.53, P<0.02), and outcome modified Rankin Scale (mRS; r>or=0.53, P=0.02). Acute and final infarct volume change and outcome NIHSS and mRS were significantly higher in patients with mean CGMS or mean BGL glucose >or=7 mmol/L. Multiple regression analysis indicated that both mean CGMS and BGL glucose levels >or=7 mmol/L were independently associated with increased final infarct volume change. CONCLUSIONS: Persistent hyperglycemia on serial glucose monitoring is an independent determinant of infarct expansion and is associated with worse functional outcome. There is an urgent need to study normalization of blood glucose after stroke.

Acute Disease↗

Acute stroke thrombolysis with intravenous tissue plasminogen activator in an Australian tertiary hospital.

OBJECTIVE: To report initial experience with the use of intravenous tissue plasminogen activator (tPA) to treat acute ischaemic stroke at an Australian tertiary-care hospital. DESIGN: Retrospective audit of computerised hospital stroke database. PARTICIPANTS AND SETTING: All patients with acute ischaemic stroke treated with intravenous tPA between April 1999 and July 2002 at the Royal Melbourne Hospital, VIC. MAIN OUTCOME MEASURES: Times from stroke onset to arrival at the emergency department (ED) and treatment; rates of symptomatic intracerebral haemorrhage (ICH); clinical outcome at three months; and violations of treatment protocol. RESULTS: Of 932 patients admitted with ischaemic stroke, 30 were treated with intravenous tPA. Median time from stroke onset to tPA treatment was 2 h 48 min, and median door-to-needle time was 1 h 49 min. Door-to-needle time improved in the last 12 months of the audit, with four of 15 patients achieving the recommended 60 min. Eleven patients (37%) had excellent clinical outcomes at three-month follow-up (modified Rankin score, 0-1), and 15 (50%) were functionally independent (score, 0-2). Mortality rate was 10%, similar to that of all ischaemic stroke patients during the audit period. Two patients (7%) had symptomatic ICH. Treatment deviated from protocol in seven patients (23%), five of whom received tPA over three hours after stroke onset. CONCLUSION: Rates of favourable outcomes and symptomatic ICH at our hospital were similar to those achieved in international phase III and IV trials in specialised centres.

Aged↗

Diffusion- and perfusion-weighted MRI response to thrombolysis in stroke.

Diffusion- and perfusion-weighted magnetic resonance imaging provides important pathophysiological information in acute brain ischemia. We performed a prospective study in 19 sub-6-hour stroke patients using serial diffusion- and perfusion-weighted imaging before intravenous thrombolysis, with repeat studies, both subacutely and at outcome. For comparison of ischemic lesion evolution and clinical outcome, we used a historical control group of 21 sub-6-hour ischemic stroke patients studied serially with diffusion- and perfusion-weighted imaging. The two groups were well matched for the baseline National Institutes of Health Stroke Scale and magnetic resonance parameters. Perfusion-weighted imaging-diffusion-weighted imaging mismatch was present in 16 of 19 patients treated with tissue plasminogen activator, and 16 of 21 controls. Perfusion-weighted imaging-diffusion-weighted imaging mismatch patients treated with tissue plaminogen activator had higher recanalization rates and enhanced reperfusion at day 3 (81% vs 47% in controls), and a greater proportion of severely hypoperfused acute mismatch tissue not progressing to infarction (82% vs -25% in controls). Despite similar baseline diffusion-weighted imaging lesions, infarct expansion was less in the recombinant tissue plaminogen activator group (14cm(3) vs 56cm(3) in controls). The positive effect of thrombolysis on lesion growth in mismatch patients translated into a greater improvement in baseline to outcome National Institutes of Health Stroke Scale in the group treated with recombinant tissue plaminogen activator, and a significantly larger proportion of patients treated with recombinant tissue plaminogen activator having a clinically meaningful improvement in National Institutes of Health Stroke Scale of > or = 7 points. The natural evolution of acute perfusion-weighted imaging-diffusion-weighted imaging mismatch tissue may be altered by thrombolysis, with improved stroke outcome. This has implications for the use of diffusion- and perfusion-weighted imaging in selecting and monitoring patients for thrombolytic therapy.

Acute Disease↗

Acute hyperglycemia adversely affects stroke outcome: a magnetic resonance imaging and spectroscopy study.

Controversy exists whether acute hyperglycemia is causally associated with worse stroke outcome or simply reflects a more severe stroke. In reversible ischemia models, hyperglycemia is associated with lactic acidosis and conversion of penumbral tissue to infarction. However, the relationship between hyperglycemia, lactic acidosis, and stroke outcome has not been explored in humans. Sixty-three acute stroke patients were prospectively evaluated with serial diffusion-weighted and perfusion-weighted magnetic resonance imaging and acute blood glucose measurements. Patients with hypoperfused at-risk tissue were identified by acute perfusion-diffusion lesion mismatch. As a substudy, acute and subacute magnetic resonance spectroscopy was performed in the 33 most recent patients to assess the relationship between acute blood glucose and lactate production in the ischemic region. In 40 of 63 patients with acute perfusion-diffusion mismatch, acute hyperglycemia was correlated with reduced salvage of mismatch tissue from infarction, greater final infarct size, and worse functional outcome. These correlations were independent of baseline stroke severity, lesion size, and diabetic status. Furthermore, higher acute blood glucose in patients with perfusion-diffusion mismatch was associated with greater acute-subacute lactate production, which, in turn, was independently associated with reduced salvage of mismatch tissue. In contrast, acute blood glucose levels in nonmismatch patients did not independently correlate with outcome measures, nor was there any acute-subacute increase in lactate in this group. Acute hyperglycemia increases brain lactate production and facilitates conversion of hypoperfused at-risk tissue into infarction, which may adversely affect stroke outcome. These findings support the need for randomized controlled trials of aggressive glycemic control in acute stroke.

Acute Disease↗

The influence of diabetes mellitus and hyperglycaemia on stroke incidence and outcome.

Diabetes mellitus is a complex metabolic syndrome with significant effects on the systemic and cerebral vasculature. The incidence and severity of ischaemic stroke are increased by the presence of diabetes, and outcome from stroke is poorer. More than one third of patients admitted with acute stroke are hyperglycaemic at presentation. Reasons for the altered prognosis in diabetes associated stroke are multifactorial. A direct influence of hyperglycaemia at the time of ischaemia is likely to be important. The use of novel methods to delineate stroke topography and pathophysiology such as MR spectroscopy, diffusion and perfusion weighted MRI appear helpful in delineating the effects of hyperglycaemia on stroke pathophysiology. Randomised clinical trials to determine optimal management for patients with hyperglycaemia following stroke are ongoing. Such trials will determine if aggressive control of acute hyperglycaemia following stroke has similar benefits to that observed following acute myocardial infarction. Clinicians responsible for stroke patients should be aware of the importance of adequate glycaemic control in both primary and secondary prevention of stroke.

Diabetes Mellitus↗

Examining the lacunar hypothesis with diffusion and perfusion magnetic resonance imaging.

BACKGROUND: The clinical diagnosis of subcortical cerebral infarction is inaccurate for lesion location and pathogenesis. Clinically suspected small perforating artery occlusions may be embolic infarcts, with important implications for investigation and treatment. New MRI techniques may allow more accurate determination of the stroke mechanism soon after admission. METHODS: In a prospective series of 106 patients evaluated with acute diffusion-weighted MRI (DWI) and perfusion-weighted MRI (PWI) within 24 hours of stroke, we enrolled 19 with a lacunar syndrome. On the basis of the topography, DWI and PWI findings, and outcome T2 MRI, we determined whether the mechanism of infarction was single perforating vessel occlusion or large artery embolism. RESULTS: Thirteen patients had pure motor stroke, 2 had ataxic hemiparesis, and 4 had sensorimotor stroke. Six patients had lacunes on MRI, none with PWI lesions. Four patients had subcortical and distal cortical infarcts on DWI. Nine had solitary restricted striatocapsular infarcts. Seven of these 9 had PWI studies, 5 with PWI lesions. The presence of a PWI lesion reliably differentiated striatocapsular from lacunar infarction for solitary small subcortical infarcts (P=0.03). CONCLUSION: DWI and PWI altered the final diagnosis of infarct pathogenesis from small perforating artery occlusion to large artery embolism in 13 of 19 patients presenting with lacunar syndromes. Lacunes cannot be reliably diagnosed on clinical grounds.

Aged↗