Ken S. Butcher

Magnetic Resonance Imaging Criteria for Thrombolysis in Acute Cerebral Infarct

Background and Purpose— Magnetic resonance imaging (MRI) selection of stroke patients eligible for thrombolytic therapy is an emerging application. Although the efficacy of therapy within 3 hours after onset of symptoms with intravenous (IV) tissue plasminogen activator (tPA) has been proven for patients selected with computed tomography (CT), no randomized, double-blinded MRI trial has been published yet. Summary of Review— MRI screening of acute stroke patients before thrombolytic therapy is performed in some cerebrovascular centers. In contrast to the CT trials, MRI pilot studies demonstrate benefit of therapy up to 6 hours after onset of symptoms. This article reviews the literature that has lead to current controlled MRI-based thrombolysis trials. We examined the MRI criteria applied in 5 stroke centers. Along with the personal views of clinicians at these centers, the survey reveals a variety of clinical and MRI technical aspects that must be further investigated: the therapeutic consequence of microbleeds, the use of magnetic resonance angiography, dynamic time windows, and others. Conclusion— MRI is an established application in acute evaluation of stroke patients and may suit as a brain clock, replacing the currently used epidemiological time clock when deciding whether to initiate thrombolytic therapy. MRI criteria for thrombolytic therapy are applied in some cerebrovascular centers, but the results of ongoing clinical trials must be awaited before it is possible to reach consensus.

Perihematomal Edema in Primary Intracerebral Hemorrhage Is Plasma Derived

Background and Purpose— The mechanisms of perihematomal injury in primary intracerebral hemorrhage (ICH) are incompletely understood. An MRI study was designed to elucidate the nature of edema and blood flow changes after ICH. Methods— Perihematomal blood flow and edema were studied prospectively with perfusion-weighted MRI (PWI) and diffusion-weighted MRI in 21 ICH patients. MRI and computed tomography (CT) images were coregistered to ensure perfusion and diffusion changes were outside of the hematoma. Edema volumes were measured on T2-weighted images. Apparent diffusion coefficient (ADC) values of the edematous regions were calculated. Results— Mean patient age was 64.2 years (45 to 89), and median National Institutes of Health stroke scale score was 12 (3 to 24). Median time to MRI was 21 hours (4.5 to 110). Average hematoma volume on CT was 26.1 (4 to 84) mL. PWI demonstrated perihematomal relative mean transit time (rMTT) was significantly correlated with hematoma volume (r =0.60; P =0.004) but not edema volume. Perihematomal oligemia (rMTT >2 s) was present in patients with hematoma volumes of >15 mL (average rMTT 4.6±2.0 s). Perihematomal edema was present in all patients. ADC values within this region (1178±213×10−6 mm2 /s) were increased 29% relative to contralateral homologous regions. Increases in perihematomal ADC predicted edema volume (r =0.54; P =0.012) and this was confirmed with multivariate analysis. Conclusions— Acute perihematomal oligemia occurs in acute ICH but is not associated with MRI markers of ischemia and is unrelated to edema formation. Increased rates of water diffusion in the perihematomal region independently predict edema volume, suggesting the latter is plasma derived.

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.

Perfusion Thresholds in Acute Stroke Thrombolysis

BACKGROUND AND PURPOSEnPerfusion-weighted MRI has been shown to be useful in the early identification of cerebral tissue at risk of infarction during acute ischemia. Identification of threshold perfusion measures that predict infarction may assist in the selection of patients for thrombolysis.nnnMETHODSnMean transit time (MTT), regional cerebral blood flow (rCBF), and regional cerebral blood volume (rCBV) maps were generated in 35 acute stroke patients (17 treated with tissue plasminogen activator and 18 control patients) imaged within 6 hours from symptom onset. Day 90 outcome infarcts (T2-weighted MRI) were superimposed on acute MTT, rCBF, and rCBV maps. Perfusion-weighted MRI measures were then calculated for 2 regions: infarcted and salvaged tissue.nnnRESULTSnMTT was prolonged by 22% in infarcted regions relative to salvaged tissue (P<0.001). rCBF was 10% lower in infarcted tissue than in salvaged regions (P<0.01). rCBV did not differ significantly between infarcted and salvaged regions. When reperfusion occurred, tissue with more severely prolonged MTT was salvaged from infarction relative to patients with persistent hypoperfusion (P<0.05). In contrast, rCBF in salvaged regions did not differ between patients with and without reperfusion. In reperfused patients, an inverse correlation (R=0.93, P<0.001) was found between time of initial MRI scan and MTT delay in salvaged tissue.nnnCONCLUSIONSnBoth increases in MTT and decreases in rCBF predict infarction. Differences in MTT also predict salvage in more severely hypoperfused tissue after reperfusion, suggesting that it is the most clinically useful quantitative perfusion measure. Perfusion thresholds for infarction need to be assessed in the context of symptom duration.

Clinical-Diffusion Mismatch Predicts the Putative Penumbra With High Specificity

Background and Purpose— Perfusion-diffusion (PWI-DWI) mismatch may represent the ischemic penumbra. The complexities associated with perfusion-weighted imaging (PWI) have restricted its use. Mismatch between stroke severity, assessed with the National Institutes of Health Stroke Scale (NIHSS), and the volume of the diffusion-weighted imaging (DWI) lesion (clinical-diffusion mismatch; CDM) has been suggested as a surrogate for PWI-DWI mismatch. We compared CDM with PWI and DWI in acute stroke. Methods— Seventy-nine hemispheric stroke patients were imaged within 24 hours of symptom onset and subacutely (3 to 5 days). CDM was defined as NIHSS ≥8 and DWI ≤25 mL. DWI lesion and PWI (Tmax+4s) volumes were measured by planimetric techniques. Acute PWI-DWI mismatch was examined as a continuous variable (mismatch volume=PWIvol−DWIvol) and a categorical variable (mismatch=PWIvol−DWIvol/DWIvol×100>20%). Early infarct expansion was calculated as DWIsubacute vol/DWIacute vol. Results— In the 54 sub–6-hour patients, CDM detected PWI-DWI mismatch with a specificity of 93% (95% confidence interval [CI], 62% to 99%), a positive predictive value of 95% (95% CI, 77% to 100%), but a sensitivity of only 53% (95% CI, 34% to 68%). Alternate DWI and NIHSS cutpoints did not improve test performance characteristics. In addition, subacute DWI expansion was significantly greater in patients with CDM (P=0.01) compared with those without. Conclusions— CDM (NIH ≥8, DWI ≤25 mL) predicts the presence of PWI-DWI mismatch with high specificity and low sensitivity. CDM also predicts DWI expansion. CDM may be a useful selection tool in acute stroke therapies, including thrombolysis.

Insular Cortical Ischemia Is Independently Associated With Acute Stress Hyperglycemia

Background and Purpose— Acute poststroke hyperglycemia has been associated with larger infarct volumes and a cortical location, regardless of diabetes status. Stress hyperglycemia has been attributed to activation of the hypothalamic-pituitary-adrenal axis but never a specific cortical location. We tested the hypothesis that damage to the insular cortex, a site with autonomic connectivity, results in hyperglycemia reflecting sympathoadrenal dysregulation. Methods— Diffusion-weighted MRI, glycosylated hemoglobin (HbA1c), and blood glucose measurements were obtained in 31 patients within 24 hours of ischemic stroke onset. Acute diffusion-weighted imaging (DWI) lesion volumes were measured, and involvement of the insular cortex was assessed on T2-weighted images. Results— Median admission glucose was significantly higher in patients with insular cortical ischemia (8.6 mmol/L; n=14) compared with those without (6.5 mmol/L; n=17; P =0.006). Multivariate linear regression demonstrated that insular cortical ischemia was a significant independent predictor of glucose level (P =0.001), as was pre-existing diabetes mellitus (P =0.008). After controlling for the effect of insular cortical ischemia, DWI lesion volume was not associated with higher glucose levels (P =0.849). There was no association between HbA1c and glucose level (P =0.737). Conclusions— Despite the small sample size, insular cortical ischemia appeared to be associated with the production of poststroke hyperglycemia. This relationship is independent of pre-existing glycemic status and infarct volume. Neuroendocrine dysregulation after insular ischemia may be 1 aspect of a more generalized acute stress response. Future studies of poststroke hyperglycemia should account for the effect of insular cortical ischemia.

Current intracerebral haemorrhage management

Primary intracerebral haemorrhage (ICH) refers to spontaneous bleeding from intraparenchymal vessels. It accounts for 10-20% of all strokes, with higher incidence rates amongst African and Asian populations. The major risk factors are hypertension and age. In addition to focal neurological findings, patients may present with symptoms of elevated intracranial pressure. The diagnosis of ICH can only be made through neuro-imaging. A CT scan is presently standard, although MRI is increasingly important in the evaluation of acute cerebrovascular disease. A significant proportion of intracerebral haematomas expand in the first hours post-ictus and this is often associated with clinical worsening. There is evidence that the peri-haematomal region is compromised in ICH. This tissue is oedematous, although the precise pathogenesis is controversial. An association between elevated arterial pressure and haematoma expansion has been reported. Although current guidelines recommend conservative management of arterial pressure in ICH, an acute blood pressure lowering trial is overdue. ICH is associated with a high early mortality rate, although a significant number of survivors make a functional recovery. Current medical management is primarily aimed at prevention of complications including pneumonia and peripheral venous thromboembolism. Elevated intracranial pressure may be treated medically or surgically. Although the latter definitively lowers elevated intracranial pressure, the optimal patient selection criteria are not clear. Aggressive treatment of hypertension is essential in the primary and secondary prevention of ICH.

Elevated hematocrit is associated with reduced reperfusion and tissue survival in acute stroke

Background: Elevated hematocrit (Hct) contributes to blood viscosity and has an adverse effect in acute stroke. The authors investigated the influence of Hct on tissue fate using serial MRI in acute stroke patients. Methods: The effects of Hct on reperfusion, penumbral salvage, and infarct expansion in 64 patients presenting within 24 hours of stroke onset were measured. MRI was performed at baseline (<24 hours), days 3 to 5, and 90 days from stroke onset. Results: Median Hct was 42% with a bimodal distribution. There was a strong inverse relationship between Hct and reperfusion (Spearman ρ = −0.74, p < 0.0001). The odds of major reperfusion (>50% resolution of the baseline perfusion-weighted imaging deficit) were significantly lower with increasing Hct (odds ratio [OR] = 0.53; 95% CI = 0.97 to 1.00), independent of age, perfusion, and diffusion lesion volumes and recombinant tissue plasminogen activator (rtPA) administration. There was a trend toward reduced penumbral salvage at days 3 to 5 with increasing Hct (p = 0.06, 95% CI = −4.76 to 0.14). An increasing Hct was a significant predictor of infarct growth (OR = 1.26, 95% CI = 1.00 to 1.59), independent of baseline perfusion and diffusion volumes and glucose. The effect of Hct on reperfusion and infarct expansion was similar irrespective of rtPA administration (p = 0.31) and independent of smoking status. Conclusions: Higher hematocrit (Hct) values have a significant independent association with reduced reperfusion and greater infarct size after ischemic stroke. An elevated Hct may also be a potential physiologic determinant of reduced penumbral salvage.

PWI/DWI Mismatch: Better Definition Required

To the Editor:nnIn their recent study of perfusion-weighted (PWI) and diffusion-weighted (DWI) image analysis, Coutts et al1 have demonstrated the difficulties associated with interpretation of postprocessed perfusion maps. There are, however, more fundamental problems than PWI map interpretation in identifying patients with perfusion-diffusion mismatch. The first is a lack of consensus concerning the definition of mismatch. Although a PWI abnormality that is 20% larger than the volume of the isotropic DWI lesion is often taken to represent significant mismatch, this is somewhat arbitrary.2 Furthermore, it has not been determined which PWI measure best defines the region of abnormal blood flow. Although most imaging groups have accepted that an index from the time domain is the most accurate, there is no agreement as to which is superior, ie, time to peak (TTP), Tmax (deconvolved TTP), or mean transit time (MTT) maps (Figure). In addition, the mathematical techniques used to estimate the true contrast transit times vary between groups. nnnnThe perfusion-weighted image (PWI) is a mean transit time (MTT) map. The hyperintense pixels demonstrate prolongation …

Thrombolysis for concomitant acute stroke and pulmonary embolism.

We report our management of a patient presenting with concomitant cortical stroke and pulmonary embolism. Stroke symptoms and respiratory distress were present for 2 h at the time of initial assessment. The patient was treated with intravenous tissue plasminogen activator (tPA). Intravenous unfractionated heparin was given 24 h after treatment with tPA. The patients neurological and respiratory status both improved following thrombolysis. The treatment options and potential dilemmas are discussed.