Tracey Baird

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 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.

Improving the Assessment of Outcomes in Stroke Use of a Structured Interview to Assign Grades on the Modified Rankin Scale

Background and Purpose— The modified Rankin Scale is widely used to assess changes in activity and lifestyle after stroke, but it has been criticized for its subjectivity. The purpose of the present study was to compare conventional assessment on the modified Rankin Scale with assessment through a structured interview. Methods— Sixty-three patients with stroke 6 to 24 months previously were interviewed and graded independently on the modified Rankin Scale by 2 observers. These observers then underwent training in use of a structured interview for the scale that covered 5 areas of everyday function. Eight weeks after the first assessment, the same observers reassessed 58 of these patients using the structured interview. Results— Interrater reliability was measured with the &kgr; statistic (weighted with quadratic weights). For the scale applied conventionally, overall agreement between the 2 raters was 57% (&kgr;w=0.78); 1 rater assigned significantly lower grades than the other (P =0.048). On the structured interview, the overall agreement between raters was 78% (&kgr;w=0.93), and there was no overall difference between raters in grades assigned (P =0.17). Rankin grades from the conventional assessment and the structured interview were highly correlated, but there was significantly less disagreement between raters when the structured interview was used (P =0.004). Conclusions— Variability and bias between raters in assigning patients to Rankin grades may be reduced by use of a structured interview. Use of a structured interview for the scale could potentially improve the quality of results from clinical studies in stroke.

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 PURPOSE Perfusion-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. METHODS Mean 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. RESULTS MTT 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. CONCLUSIONS Both 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.

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.

Basilar artery occlusion

Basilar artery occlusion is assumed to carry a grave prognosis, with mortality rates of up to 90%. Diagnosis is often delayed, or even missed, as a result of the variety of clinical presentations seen with this condition. The pathogenesis of occlusion can be secondary to both local atherothrombosis or cardioembolism. The use of noninvasive imaging such as magnetic resonance imaging and computed tomography angiography has improved recognition of clinical syndromes associated with occlusion. Although no randomized studies have been performed, recanalization of the vascular occlusion, particularly with thrombolytic agents, appears to result in improved outcomes in selected patients. However, the optimum timing for therapy is unclear, and reperfusion therapy may need to be combined with definitive vascular treatment of underlying vascular stenosis. Increasing awareness of this condition may reveal the natural history to be more diverse than previously recognized.

Early Recurrent Ischemic Stroke Complicating Intravenous Thrombolysis for Stroke Incidence and Association With Atrial Fibrillation

Background and Purpose— Mechanisms of early neurologic deterioration after treatment with intravenous, recombinant, tissue-type plasminogen activator (IV rt-PA) include symptomatic intracerebral hemorrhage (SICH) and early recurrent ischemic stroke. We observed a number of cases of acute deterioration due to recurrent ischemic events. Methods— We undertook a single-center, retrospective analysis of consecutive acute stroke patients treated with IV rt-PA between January 2006 and December 2008 to define the incidence of early neurologic deterioration (≥4-point drop on the National Institutes of Health Stroke Scale within 72 hours) and its mechanism. Deterioration was attributed to SICH when associated with a PH1 or PH2 hemorrhage on postdeterioration computed tomography scans, to recurrent ischemic stroke when there was clinical and radiologic evidence of a new territorial infarction or new vessel occlusion, and otherwise to evolution of the incident stroke. Results— Of 228 consecutive IV rt-PA-treated patients, 34 (15%) developed early neurologic deterioration, 18 (8%) secondary to incident strokes 10 (4.4%) due to SICH, and 6 (2.6%) due to early recurrent ischemic events, which were significantly associated with atrial fibrillation (present in 5 of 6 patients; 4 paroxysmal, 1 permanent). In 4 patients, sudden clinical deterioration developed during or shortly after IV rt-PA infusion, and in 2, deterioration developed 3 days later. All died 2 days to 2 weeks later. The single case without atrial fibrillation had a recurrent, contralateral, middle cerebral artery stroke during IV rt-PA infusion and multiple high-signal emboli detected by transcranial Doppler. Early recurrent ischemic stroke accounted for 5 of 12 (42%) cases of early neurologic deterioration in patients with atrial fibrillation. Conclusion— In this single-center series, the incidence of early recurrent ischemic stroke after IV rt-PA was 2.6% and was associated with previous atrial fibrillation.

Visual evaluation of perfusion computed tomography in acute stroke accurately estimates infarct volume and tissue viability

Objective: To establish the validity of visual interpretation of immediately processed perfusion computed tomography (CT) maps in acute stroke for prediction of final infarction. Methods: Perfusion CT studies acquired prospectively were reprocessed within six hours of stroke onset using standard CT console software. Four contiguous 5 mm thick images were obtained and maps of time to peak (TTP) and cerebral blood volume (CBV) generated. Volumes of lesions identified only by visual inspection were measured from manually drawn regions of interest. Volumes of tissue with prolonged TTP or reduced CBV were compared with independently calculated volume of infarction on non-contrast CT (NCCT) at 24–48 hours, and with clinical severity using the NIHSS score. Arterial patency at 24–48 h was included in analyses. Results: Studies were analysed from 17 patients 150 minutes (median) after stroke onset. Volume of tissue with prolonged TTP correlated with initial NIHSS (r = 0.62, p = 0.009), and with NCCT final infarct volume when arterial occlusion persisted (r = 0.953, p = 0.012). Volume of tissue with reduced CBV correlated with final infarct volume if recanalisation occurred (r = 0.835, p = 0.001). Recanalisation was associated with lower 24 h NIHSS score (6 (IQR, 5 to 9.5) v 19 (18 to 26), p = 0.027), and in 10 patients given rtPA for MCA M1 occlusion, with lower infarct volume (73 v 431 ml, p = 0.002). Conclusions: Visual evaluation of TTP and CBV maps generated by standard perfusion CT software correlated with 24–48 hour CT infarct volumes. Comparison of TTP and CBV maps yields information on tissue viability. Perfusion CT represents a practical technique to aid acute clinical decision making. Recanalisation was a crucial determinant of clinical and radiological outcome.