Audit of CT reporting standards in cases of intracerebral haemorrhage at a comprehensive stroke centre in Australia.

INTRODUCTION: Multiple CT-derived biomarkers that are predictive of intracerebral haemorrhage (ICH) growth and outcome have been described in the literature, but the extent to which these appear in imaging reports of ICH is unknown. The aim of this retrospective process audit was to determine which of the known predictors of ICH outcome was recorded in reports of the disease, with a view to providing reporting recommendations, as appropriate. METHOD: We examined the initial CT report of patients diagnosed with ICH presenting to a metropolitan comprehensive stroke centre and meeting inclusion criteria during the audit period between 1 March 2013 and 28 February 2014. Each report was assessed for the inclusion of the following ICH characteristics: the number of measurement dimensions; volume; location; hydrocephalus; shape; density; 'CTA spot sign' (where CTA was performed). RESULTS: A total of 100 patients met audit inclusion criteria. At least one ICH dimension was recorded in 90% of reports; however, 39% did not include the measurements in three dimensions and volume was reported in just 6%. No ICH dimension was recorded in 10% of reports. With the exception of density and shape, reporting of other CT features exceeded 95%. Where CTA was performed (58%), 14 (24%) of 58 reported the 'CTA spot sign' status. CONCLUSION: In this audit, volume was the most under-reported of the established ICH characteristics predictive of ICH outcome. Readily calculated from multiplanar reformats using the ABC/2 technique, the routine reporting of ICH volume is recommended. More reporting attention to ICH density heterogeneity and shape irregularity is encouraged, given their emerging importance. Where acute CTA is performed, the presence of any dynamic haemorrhage (CTA spot sign) should be reported.

Magnetic resonance imaging in adults with epilepsy: a pictorial essay.

This pictorial essay highlights the role of the radiologist as a member of the adult epilepsy multidisciplinary team, and gives an overview of MRI-evident epileptogenic lesions.

Failure of collateral blood flow is associated with infarct growth in ischemic stroke.

Changes in collateral blood flow, which sustains brain viability distal to arterial occlusion, may impact infarct evolution but have not previously been demonstrated in humans. We correlated leptomeningeal collateral flow, assessed using novel perfusion magnetic resonance imaging (MRI) processing at baseline and 3 to 5 days, with simultaneous assessment of perfusion parameters. Perfusion raw data were averaged across three consecutive slices to increase leptomeningeal collateral vessel continuity after subtraction of baseline signal analogous to digital subtraction angiography. Changes in collateral quality, Tmax hypoperfusion severity, and infarct growth were assessed between baseline and days 3 to 5 perfusion-diffusion MRI. Acute MRI was analysed for 88 patients imaged 3 to 6 hours after ischemic stroke onset. Better collateral flow at baseline was associated with larger perfusion-diffusion mismatch (Spearman's Rho 0.51, P<0.001) and smaller baseline diffusion lesion volume (Rho -0.70, P<0.001). In 30 patients without reperfusion at day 3 to 5, deterioration in collateral quality between baseline and subacute imaging was strongly associated with absolute (P=0.02) and relative (P<0.001) infarct growth. The deterioration in collateral grade correlated with increased mean Tmax hypoperfusion severity (Rho -0.68, P<0.001). Deterioration in Tmax hypoperfusion severity was also significantly associated with absolute (P=0.003) and relative (P=0.002) infarct growth. Collateral flow is dynamic and failure is associated with infarct growth.

EPITHET: Positive Result After Reanalysis Using Baseline Diffusion-Weighted Imaging/Perfusion-Weighted Imaging Co-Registration.

BACKGROUND AND PURPOSE: the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET) was a prospective, randomized, double-blinded, placebo-controlled, phase II trial of alteplase between 3 and 6 hours after stroke onset. The primary outcome of infarct growth attenuation on MRI with alteplase in mismatch patients was negative when mismatch volumes were assessed volumetrically, without coregistration, which underestimates mismatch volumes. We hypothesized that assessing the extent of mismatch by coregistration of perfusion and diffusion MRI maps may more accurately allow the effects of alteplase vs placebo to be evaluated. METHODS: patients were classified as having mismatch if perfusion-weighted imaging divided by coregistered diffusion-weighted imaging volume ratio was >1.2 and total coregistered mismatch volume was ≥ 10 mL. The primary outcome was a comparison of infarct growth in alteplase vs placebo patients with coregistered mismatch. RESULTS: of 99 patients with baseline diffusion-weighted imaging and perfusion-weighted imaging, coregistration of both images was possible in 95 patients. Coregistered mismatch was present in 93% (88/95) compared to 85% (81/95) with standard volumetric mismatch. In the coregistered mismatch patients, of whom 45 received alteplase and 43 received placebo, the primary outcome measure of geometric mean infarct growth was significantly attenuated by a ratio of 0.58 with alteplase compared to placebo (1.02 vs 1.77; 95% CI, 0.33-0.99; P=0.0459). CONCLUSIONS: when using coregistration techniques to determine the presence of mismatch at study entry, alteplase significantly attenuated infarct growth. This highlights the necessity for a randomized, placebo-controlled, phase III clinical trial of alteplase using penumbral selection beyond 3 hours.

MR imaging characteristics of protoplasmic astrocytomas.

INTRODUCTION: Protoplasmic astrocytomas are a poorly recognized and uncommon subtype of astrocytoma. While usually categorized with other low-grade gliomas, there is literature to suggest that protoplasmic astrocytomas have differences in biology compared to other gliomas in this group. This paper presents the MR imaging characteristics of a series of eight protoplasmic astrocytomas. METHODS: We retrospectively reviewed MR images and histopathology of eight consecutive cases of histologically proven protoplasmic astrocytomas. RESULTS: Patients ranged from 17 to 51 years of age with a 5:3 male to female ratio. The tumors were located in the frontal or temporal lobes and tended to be large, well defined, and had a very high signal on T2 (close to cerebrospinal fluid). Generally, a large proportion of the tumor showed substantial signal suppression on T2 fluid-attenuated inversion recovery (FLAIR). Six of the eight lesions also demonstrated a partial or complete rim of reduced apparent diffusion coefficient (ADC) around the T2 FLAIR suppressing portion. CONCLUSIONS: The possibility that a primary cerebral neoplasm represents a protoplasmic astrocytoma should be considered in a patient with a large frontal or temporal tumor that has a very high signal on T2 with a large proportion of the tumor showing substantial T2 FLAIR suppression. A further clue is a partial or complete rim of reduced ADC.

Brain imaging in transient ischemic attack--redefining TIA.

Transient ischemic attack (TIA) has recently been redefined to incorporate the latest clinical and neuroimaging information that has shed new light on TIA pathophysiology. Patients suffering from TIA are at a substantial risk of subsequent stroke, but quantifying this risk is difficult as TIA patients are a heterogeneous population and there are multiple TIA mimics. Clinical scores for prediction of stroke risk are principally based on patient history and potentially understate actual risk. Magnetic resonance imaging (MRI), in particular diffusion-weighted imaging (DWI) performed in the first days following TIA, reveals relevant focal ischemic abnormalities in 21-68% of patients. These lesions predict stroke recurrence, functional dependence and subsequent vascular events. Adding imaging information to clinical scores improves prediction of stroke risk following TIA. Alongside clinical judgement, use of MRI has the potential to change the management of TIA patients and is the imaging modality of choice for this condition.

Postthrombolysis blood pressure elevation is associated with hemorrhagic transformation.

BACKGROUND AND PURPOSE: Reliable predictors of hemorrhagic transformation (HT) after stroke thrombolysis have not been identified. We analyzed hemorrhage in a randomized trial of tissue plasminogen activator (t-PA) vs placebo in ischemic stroke patients. We hypothesized that acute diffusion-weighted imaging (DWI) lesion volumes would be larger and blood pressures would be higher in patients with HT. METHODS: HT was assessed 2 to 5 days after treatment in 97 patients. Hemorrhage was assessed by using susceptibility-weighted imaging sequences and was classified as petechial hemorrhagic infarction (HI) or parenchymal hematoma (PH). RESULTS: PH was more frequent in t-PA- (11/49) than in placebo- (4/48) treated patients (P=0.049). Patients with PH had larger DWI lesion volumes (63.1+/-56.1 mL) than did those without HT (27.6+/-39.0 mL, P=0.033). There were no differences in baseline systolic blood pressure (SBP) between patients with and without hemorrhage. Weighted average SBP 24 hours after treatment was higher in patients with PH (159.4+/-18.8 mL, P<0.011) relative to those without HT (143.1+/-20.0 mL). Multinomial logistic regression indicated that PH was predicted by DWI lesion volume (odds ratio=1.16 per 10 mL; 95% CI, 1.03 to 1.30), atrial fibrillation (odds ratio=9.33; 95% CI, 2.30 to 37.94), and 24-hour weighted average SBP (odds ratio=1.59 per 10 mm Hg; 95% CI, 1.14 to 2.23). CONCLUSIONS: Pretreatment DWI lesion volume and postthrombolysis BP are both predictive of HT. Consideration should be given to excluding patients with very large baseline DWI volumes from t-PA therapy and to more stringent BP control after stroke thrombolysis.

Density and shape as CT predictors of intracerebral hemorrhage growth.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) growth predicts mortality and functional outcome. We hypothesized that irregular hematoma shape and density heterogeneity, reflecting active, multifocal bleeding or a variable bleeding time course, would predict ICH growth. METHODS: Three raters examined baseline sub-3-hour CT brain scans of 90 patients in the placebo arm of a Phase IIb trial of recombinant activated Factor VII in ICH. Each rater, blinded to growth data, independently applied novel 5-point categorical scales of density and shape to randomly presented baseline CT images of ICH. Density and shape were defined as either homogeneous/regular (Category 1 to 2) or heterogeneous/irregular (Category 3 to 5). Within- and between-rater reliability was determined for these scales. Growth was assessed as a continuous variable and using 3 binary definitions: (1) any ICH growth; (2) >or=33% or >or=12.5 mL ICH growth; and (3) radial growth >1 mm between baseline and 24-hour CT scan. Patients were divided into tertiles of baseline ICH volume: "small" (0 to 10 mL), "medium" (10 to 25 mL), and "large" (25 to 106 mL). RESULTS: Inter- and intrarater agreements for the novel scales exceeded 85% (+/-1 category). Median growth was significantly higher in the large-volume group compared with the small group (P<0.001) and in heterogeneous compared with homogeneous ICH (P=0.008). Median growth trended higher in irregular ICHs compared with regular ICHs (P=0.084). Small ICHs were more regularly shaped (43%) than medium (17%) and large (3%) ICHs (P<0.001). Small ICHs were more homogeneous (73%) compared with medium (37%) and large (17%) ICHs (P<0.001). Adjusting for baseline ICH volume and time to scan, density heterogeneity, but not shape irregularity, independently predicted ICH growth (P=0.046) on a continuous growth scale. CONCLUSIONS: Large ICHs were significantly more irregular in shape, heterogeneous in density, and had greater growth. Density heterogeneity independently predicted ICH growth using some definitions.

Radiologically atypical congenital posterior fossa dermoid cyst presenting late in life.

We report the case of a 74-year-old woman who presented with deterioration in gait, short-term memory loss and urinary incontinence. She had a past history of excision of a cervical dermal sinus tract at the age of 5 years. CT scan in 2004 revealed ventriculomegaly and an extremely hypodense ovoid structure lying in the midline low posterior fossa with calcification anteriorly. On MRI, the lesion was hypointense on T1-eighted and hyperintense on T2-weighted images, with incomplete suppression on fluid-attenuated inversion-recovery images and marked restriction on diffusion weighted images. Cerebrospinal fluid isotope study revealed non-communicating hydrocephalus. Posterior fossa crainectomy and removal of the lesion was undertaken. Pathological study revealed a dermoid cyst. Post-operatively, her hydrocephalus persisted and a ventriculo-atrial shunt was inserted with excellent functional recovery.

Effects of alteplase beyond 3 h after stroke in the Echoplanar Imaging Thrombolytic Evaluation Trial (EPITHET): a placebo-controlled randomised trial.

BACKGROUND: Whether intravenous tissue plasminogen activator (alteplase) is effective beyond 3 h after onset of acute ischaemic stroke is unclear. We aimed to test whether alteplase given 3-6 h after stroke onset promotes reperfusion and attenuates infarct growth in patients who have a mismatch in perfusion-weighted MRI (PWI) and diffusion-weighted MRI (DWI). METHODS: We prospectively and randomly assigned 101 patients to receive alteplase or placebo 3-6 h after onset of ischaemic stroke. PWI and DWI were done before and 3-5 days after therapy, with T2-weighted MRI at around day 90. The primary endpoint was infarct growth between baseline DWI and the day 90 T2 lesion in mismatch patients. Major secondary endpoints were reperfusion, good neurological outcome, and good functional outcome. Patients, caregivers, and investigators were unaware of treatment allocations. Primary analysis was per protocol. This study is registered with ClinicalTrials.gov, number NCT00238537. FINDINGS: We randomly assigned 52 patients to alteplase and 49 patients to placebo. Mean age was 71.6 years, and median score on the National Institutes of Health stroke scale was 13. 85 of 99 (86%) patients had mismatch of PWI and DWI. The geometric mean infarct growth (exponential of the mean log of relative growth) was 1.24 with alteplase and 1.78 with placebo (ratio 0.69, 95% CI 0.38-1.28; Student's t test p=0.239); the median relative infarct growth was 1.18 with alteplase and 1.79 with placebo (ratio 0.66, 0.36-0.92; Wilcoxon's test p=0.054). Reperfusion was more common with alteplase than with placebo and was associated with less infarct growth (p=0.001), better neurological outcome (p<0.0001), and better functional outcome (p=0.010) than was no reperfusion. INTERPRETATION: Alteplase was non-significantly associated with lower infarct growth and significantly associated with increased reperfusion in patients who had mismatch. Because reperfusion was associated with improved clinical outcomes, phase III trials beyond 3 h after treatment are warranted.

Rapid assessment of perfusion-diffusion mismatch.

BACKGROUND AND PURPOSE: For MR perfusion-diffusion (PWI-DWI) mismatch to become routine in thrombolysis patient selection, rapid and reliable assessment tools are required. We examined interrater variability in PWI/DWI volume measurements and developed a rapid assessment tool based on the Alberta Stroke Program Early CT Scores (ASPECTS) system. METHODS: DWI and PWI were performed in 35 patients with stroke <6 hours after symptom onset. DWI lesion and PWI (time to peak) volumes were measured with planimetric techniques by 4 raters and the 95% limits of agreement calculated. ASPECT scores were assessed separately by 4 investigators (2 experienced and 2 inexperienced) for DWI (MR DWI scores) and PWI (MR time to peak scores). MR mismatch scores were calculated as MR DWI-MR time to peak scores. RESULTS: Interobserver variability was much greater for PWI (95% limit of agreement=+/-72.3 mL) than for DWI (95% limit of agreement=+/-12.6 mL). A semiautomated PWI volume (time to peak+2 s) was therefore used to calculate mismatch volume. MR mismatch scores >or=2 predicted 20% PWI-DWI mismatch by volume with mean 78% sensitivity (range, 72% to 84%) and 88% specificity (range, 83% to 90%). There was excellent agreement on mismatch classification using MR mismatch scores between experienced raters (weighted kappa scores of 0.94) with agreement in 34 of 35 cases. Agreement was less consistent between inexperienced raters (weighted kappa=0.49, 28 of 35 cases). CONCLUSIONS: Variability in planimetric mismatch measurements arises primarily from differences in PWI volume assessment. High specificity and interrater reliability may make MR mismatch scores an ideal rapid screening tool for potential thrombolysis patients.

Differential prognosis of isolated cortical swelling and hypoattenuation on CT in acute stroke.

BACKGROUND AND PURPOSE: The Alberta Stroke Program Early CT Score (ASPECTS) is a validated method of assessing parenchymal ischemic changes, including focal swelling and hypoattenuation. The hypothesis that these signs result from different pathophysiological processes was tested by comparing CT with diffusion and perfusion- weighted MRI. METHODS: MRI and CT were performed, within 2 hours of each other, in 30 ischemic stroke patients <17 hours after symptom onset. Relative apparent diffusion coefficient, relative cerebral blood flow, and relative cerebral blood volume were calculated for individual cortical ASPECTS regions. Regional infarction was assessed on days 3 to 5. RESULTS: Isolated focal swelling was seen in 25 ASPECTS cortical regions from 6 patients. Cortical hypoattenuation was observed in 25 regions from 11 patients. Median relative apparent diffusion coefficient was significantly lower in hypoattenuated regions (0.84; interquartile range, 0.66 to 0.91) relative to those with focal swelling (0.97; interquartile range, 0.91 to 1.01; P<0.001). Median relative cerebral blood flow in focal swelling regions (81.0%; interquartile range, 70.4 to 93.0) was similar to that of tissue that appeared normal on CT (71.8%; interquartile range, 47.1 to 94.5). In hypoattenuated regions, relative cerebral blood flow was significantly decreased (37.0%; interquartile range, 25.6 to 70.2; P=0.002). Median relative cerebral blood volume was increased (121.1%; interquartile range, 112.0 to 130.3) in focal swelling regions, relative to normal-appearing tissue (94.7%; interquartile range, 62.0 to 114.6; P<0.001), but decreased in hypoattenuated regions (58.9%; interquartile range, 47.5 to 92.7; P=0.012). Infarction occurred in all hypoattenuated regions, but only in 32% of those with focal swelling. CONCLUSIONS: Elevated relative cerebral blood volume and normal relative apparent diffusion coefficient in ASPECTS regions with focal swelling on CT is consistent with penumbral tissue. Isolated focal swelling is not always associated with infarction. These results support removal of focal swelling from the ASPECTS system.

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.

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 > or =8 and DWI < or =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 x 100>20%). Early infarct expansion was calculated as DWI(subacute vol/DWI(acute 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 > or =8, DWI < or =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.

Acute complications of dopamine agonist treatment for macroprolactinoma - how uncommon?

Dopamine agonists are first line treatment for prolactinomas. This treatment can cause serious complications in patients with invasive macroprolactinomas. This study reviewed 195 patients attending the endocrine clinic and/or undergoing surgery for pituitary tumours at The Royal Melbourne Hospital in a seven-year period (1996-2002). Thirty three patients had macroprolactinoma (diameter >10 mm). Eleven of them were treated with dopamine agonist prior to surgery and four developed severe complications. This study suggests that the severe complications of dopamine agonist therapy may be higher than previously reported. All patients should be educated about these complications and their early recognition.

Transverse sinus septum: a new aetiology of idiopathic intracranial hypertension?

A venographic cryptic stenosis at the junction of middle and lateral third of the transverse sinus has been observed in patients suffering from idiopathic intracranial hypertension. After reviewing the anatomical and embryological literature of the transverse sinus, 20 transverse sinuses were explored (in a pilot study of 10 human cadavers) in order to determine the anatomical basis of this stenosis. The presence of septa of varying sizes was observed. We conclude that the presence of a large septum is one of the causes of venographic cryptic stenosis observed in these patients and might be one of the aetiological factors involved in idiopathic intracranial hypertension.

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+/-213x10(-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.

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.

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.

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.