Julio A. Chalela

Magnetic resonance imaging and computed tomography in emergency assessment of patients with suspected acute stroke: a prospective comparison

BACKGROUND Although the use of magnetic resonance imaging (MRI) for the diagnosis of acute stroke is increasing, this method has not proved more effective than computed tomography (CT) in the emergency setting. We aimed to prospectively compare CT and MRI for emergency diagnosis of acute stroke. METHODS We did a single-centre, prospective, blind comparison of non-contrast CT and MRI (with diffusion-weighted and susceptibility weighted images) in a consecutive series of patients referred for emergency assessment of suspected acute stroke. Scans were independently interpreted by four experts, who were unaware of clinical information, MRI-CT pairings, and follow-up imaging. RESULTS 356 patients, 217 of whom had a final clinical diagnosis of acute stroke, were assessed. MRI detected acute stroke (ischaemic or haemorrhagic), acute ischaemic stroke, and chronic haemorrhage more frequently than did CT (p<0.0001, for all comparisons). MRI was similar to CT for the detection of acute intracranial haemorrhage. MRI detected acute ischaemic stroke in 164 of 356 patients (46%; 95% CI 41-51%), compared with CT in 35 of 356 patients (10%; 7-14%). In the subset of patients scanned within 3 h of symptom onset, MRI detected acute ischaemic stroke in 41 of 90 patients (46%; 35-56%); CT in 6 of 90 (7%; 3-14%). Relative to the final clinical diagnosis, MRI had a sensitivity of 83% (181 of 217; 78-88%) and CT of 26% (56 of 217; 20-32%) for the diagnosis of any acute stroke. INTERPRETATION MRI is better than CT for detection of acute ischaemia, and can detect acute and chronic haemorrhage; therefore it should be the preferred test for accurate diagnosis of patients with suspected acute stroke. Because our patient sample encompassed the range of disease that is likely to be encountered in emergency cases of suspected stroke, our results are directly applicable to clinical practice.

Comparison of MRI and CT for Detection of Acute Intracerebral Hemorrhage

CONTEXT Noncontrast computed tomography (CT) is the standard brain imaging study for the initial evaluation of patients with acute stroke symptoms. Multimodal magnetic resonance imaging (MRI) has been proposed as an alternative to CT in the emergency stroke setting. However, the accuracy of MRI relative to CT for the detection of hyperacute intracerebral hemorrhage has not been demonstrated. OBJECTIVE To compare the accuracy of MRI and CT for detection of acute intracerebral hemorrhage in patients presenting with acute focal stroke symptoms. DESIGN, SETTING, AND PATIENTS A prospective, multicenter study was performed at 2 stroke centers (UCLA Medical Center and Suburban Hospital, Bethesda, Md), between October 2000 and February 2003. Patients presenting with focal stroke symptoms within 6 hours of onset underwent brain MRI followed by noncontrast CT. MAIN OUTCOME MEASURES Acute intracerebral hemorrhage and any intracerebral hemorrhage diagnosed on gradient recalled echo (GRE) MRI and CT scans by a consensus of 4 blinded readers. RESULTS The study was stopped early, after 200 patients were enrolled, when it became apparent at the time of an unplanned interim analysis that MRI was detecting cases of hemorrhagic transformation not detected by CT. For the diagnosis of any hemorrhage, MRI was positive in 71 patients with CT positive in 29 (P<.001). For the diagnosis of acute hemorrhage, MRI and CT were equivalent (96% concordance). Acute hemorrhage was diagnosed in 25 patients on both MRI and CT. In 4 other patients, acute hemorrhage was present on MRI but not on the corresponding CT--each of these 4 cases was interpreted as hemorrhagic transformation of an ischemic infarct. In 3 patients, regions interpreted as acute hemorrhage on CT were interpreted as chronic hemorrhage on MRI. In 1 patient, subarachnoid hemorrhage was diagnosed on CT but not on MRI. In 49 patients, chronic hemorrhage, most often microbleeds, was visualized on MRI but not on CT. CONCLUSION MRI may be as accurate as CT for the detection of acute hemorrhage in patients presenting with acute focal stroke symptoms and is more accurate than CT for the detection of chronic intracerebral hemorrhage.

Magnetic resonance perfusion imaging in acute ischemic stroke using continuous arterial spin labeling.

BACKGROUND AND PURPOSE Continuous arterial spin-labeled perfusion MRI (CASL-PI) uses electromagnetically labeled arterial blood water as a diffusible tracer to noninvasively measure cerebral blood flow (CBF). We hypothesized that CASL-PI could detect perfusion deficits and perfusion/diffusion mismatches and predict outcome in acute ischemic stroke. METHODS We studied 15 patients with acute ischemic stroke within 24 hours of symptom onset. With the use of a 6-minute imaging protocol, CASL-PI was measured at 1.5 T in 8-mm contiguous supratentorial slices with a 3.75-mm in-plane resolution. Diffusion-weighted images were also obtained. Visual inspection for perfusion deficits, perfusion/diffusion mismatches, and effects of delayed arterial transit was performed. CBF in predetermined vascular territories was quantified by transformation into Talairach space. Regional CBF values were correlated with National Institutes of Health Stroke Scale (NIHSS) score on admission and Rankin Scale (RS) score at 30 days. RESULTS Interpretable CASL-PI images were obtained in all patients. Perfusion deficits were consistent with symptoms and/or diffusion-weighted imaging abnormalities. Eleven patients had hypoperfusion, 3 had normal perfusion, and 1 had relative hyperperfusion. Perfusion/diffusion mismatches were present in 8 patients. Delayed arterial transit effect was present in 7 patients; serial imaging in 2 of them showed that the delayed arterial transit area did not succumb to infarction. CBF in the affected hemisphere correlated with NIHSS and RS scores (P=0.037 and P=0.003, Spearman rank correlation). The interhemispheric percent difference in middle cerebral artery CBF correlated with NIHSS and RS scores (P=0.007 and P=0.0002, respectively). CONCLUSIONS CASL-PI provides rapid noninvasive multislice imaging in acute ischemic stroke. It depicts perfusion deficits and perfusion/diffusion mismatches and quantifies regional CBF. CASL-PI CBF asymmetries correlate with severity and outcome. Delayed arterial transit effects may indicate collateral flow.

Early blood–brain barrier disruption in human focal brain ischemia

Loss of integrity of the blood–brain barrier (BBB) resulting from ischemia/reperfusion is believed to be a precursor to hemorrhagic transformation (HT) and poor outcome. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in human focal brain ischemia and tested for associations with reperfusion, HT, and poor outcome (modified Rankin score >2). BBB disruption was found in 47 of 144 (33%) patients, having a median time from stroke onset to observation of 10.1 hours. Reperfusion was found to be the most powerful independent predictor of early BBB disruption (p = 0.018; odds ratio, 4.09; 95% confidence interval, 1.28–13.1). HT was observed in 22 patients; 16 (72.7%) of those also had early BBB disruption (p < 0.001; odds ratio, 8.11; 95% confidence interval, 2.85–23.1). In addition to baseline severity (National Institutes of Health Stroke Scale score >6), early BBB disruption was found to be an independent predictor of HT. Because the timing of the disruption was early enough to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by this imaging biomarker may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome. Ann Neurol 2004

Reliability and Validity of Estimating the NIH Stroke Scale Score from Medical Records

BACKGROUND AND PURPOSE The aim of our study was to determine whether the National Institutes of Health Stroke Scale (NIHSS) can be estimated retrospectively from medical records. The NIHSS is a quantitative measure of stroke-related neurological deficit with established reliability and validity for use in prospective clinical research. Recently, retrospective observational studies have estimated NIHSS scores from medical records for quantitative outcome analysis. The reliability and validity of estimation based on chart review has not been determined. METHODS Thirty-nine patients were selected because their NIHSS scores were formally measured at admission and discharge. Handwritten notes from medical records were abstracted and NIHSS scores were estimated by 6 raters who were blinded to the actual scores. Estimated scores were compared among raters and with the actual measured scores. RESULTS Interrater reliability was excellent, with an intraclass correlation coefficient of 0.82. Scores were well calibrated among the 6 raters. Estimated NIHSS scores closely approximated the actual scores, with a probability of 0.86 of correctly ranking a set of patients according to 5-point interval categories (as determined by the area under the receiver-operator characteristic curve). Patients with excellent outcomes (NIHSS score of </=5) could be identified with sensitivity of 0.72 and specificity of 0.89. There were no significant differences between these parameters at admission and discharge. CONCLUSIONS For the purposes of retrospective studies of acute stroke outcome, the NIHSS can be abstracted from medical records with a high degree of reliability and validity.

Acetaminophen for altering body temperature in acute stroke: a randomized clinical trial.

Background and Purpose— Mild alterations in temperature have prominent effects on ischemic cell injury and stroke outcome. Elevated core body temperature (CBT), even if mild, may exacerbate neuronal injury and worsen outcome, whereas hypothermia is potentially neuroprotective. The antipyretic effects of acetaminophen were hypothesized to reduce CBT. Methods— This was a randomized, controlled clinical trial at 2 university hospitals. Patients were included if they had stroke within 24 hours of onset of symptoms, National Institutes of Health Stroke Scale (NIHSS) score ≥5, initial CBT <38.5°C, and white blood cell count <12 600 cells/mm3; they were excluded if they had signs of infection, severe medical illness, or contraindication to acetaminophen. CBT was measured every 30 minutes. Patients were randomized to receive acetaminophen 650 mg or placebo every 4 hours for 24 hours. The primary outcome measure was mean CBT during the 24-hour study period; the secondary outcome measure was the change in NIHSS. Results— Thirty-nine patients were randomized. Baseline CBT was the same: 36.96°C for acetaminophen versus 36.95°C for placebo (P =0.96). During the study period, CBT tended to be lower in the acetaminophen group (37.13°C versus 37.35°C), a difference of 0.22°C (95% CI, −0.08°C to 0.51°C;P =0.14). Patients given acetaminophen tended to be more often hypothermic <36.5°C (OR, 3.4; 95% CI, 0.83 to 14.2;P =0.09) and less often hyperthermic >37.5°C (OR, 0.52; 95% CI, 0.19 to 1.44;P =0.22). The change in NIHSS scores from baseline to 48 hours did not differ between the groups (P =0.93). Conclusions— Early administration of acetaminophen (3900 mg/d) to afebrile patients with acute stroke may result in a small reduction in CBT. Acetaminophen may also modestly promote hypothermia <36.5°C or prevent hyperthermia >37.5°C. These effects are unlikely to have robust clinical impact, and alternative or additional methods are needed to achieve effective thermoregulation in stroke patients.

Early magnetic resonance imaging findings in patients receiving tissue plasminogen activator predict outcome: Insights into the pathophysiology of acute stroke in the thrombolysis era†

We measured ischemic brain changes with diffusion and perfusion MRI in 42 ischemic stroke patients before and 2 hours (range approximately 1.5 to 4.5 hours) after standard intravenous tissue plasminogen activator (tPA) therapy. The median time from stroke onset to tPA was 131 minutes. Clinical and MRI variables (change in perfusion and/or diffusion weighted lesion volume) were compared between those with excellent outcome defined as 3‐month modified Rankin score (mRS) of 0 to 1 and those with incomplete recovery (mRS >1). In multivariate logististic regression analysis, the most powerful independent predictor for excellent outcome was improved brain perfusion: hypoperfusion volume on mean transit time (MTT) map decrease >30% from baseline to 2‐hour post tPA scan (p=0.009; odds ratio [95% confidence interval], 20.7 [2.1‐203.9]). Except for age < 70 years, no other baseline clinical or imaging variable was an independent predictor of outcome. We propose MTT lesion volume decrease more than 30% 2 hours after tPA as an early marker of long‐term clinical benefit of thrombolytic therapy.

MRI identification of early white matter injury in anoxic–ischemic encephalopathy

Background: Anoxic–ischemic encephalopathy (AIE) affects the gray matter more than the white matter. Recent animal experiments suggest that the white matter is more sensitive to ischemia than previously thought. The authors describe the MRI findings in seven patients with AIE who demonstrate early preferential involvement of the white matter. Materials and methods: A retrospective case series study was performed, including seven patients with AIE who underwent MRI of the brain within 7 days of insult. Demographic information, type of insult, clinical examination findings, EEG findings, and clinical outcome were obtained. MRI studies were reviewed with specific attention to the cortex, deep gray matter, and the white matter structures. Mean apparent diffusion coefficient (ADC) was calculated in regions of interest placed in the cerebellar hemispheres, putamen, thalamus, splenium of corpus callosum, centrum semiovale, and medial frontal cortex. Results: The causes of AIE were cardiac arrhythmias in two patients, myocardial infarction in one, drug overdose in two, carbon monoxide poisoning in one, and respiratory failure and sepsis in one. The median time to MRI was 2.5 days. Symmetric areas of restricted diffusion were found in the periventricular white matter tracts (7/7 patients), the corpus callosum (6/7 patients), internal capsule (5/7 patients), and the subcortical association fibers (3/7 patients). ADC maps confirmed the restricted diffusion. Gray matter involvement was seen in three patients, and was more prominent on conventional imaging sequences compared with diffusion-weighted imaging. A subtle decrease in mean ADC was seen in cortex. Conclusions: Prominent, symmetric restricted diffusion can occur early after AIE in white matter, whereas gray matter involvement may be less prominent. Further studies involving a larger sample and serial imaging are required to confirm these preliminary findings.

Impact of Establishing a Primary Stroke Center at a Community Hospital on the Use of Thrombolytic Therapy: The NINDS Suburban Hospital Stroke Center Experience

Background and Purpose— To increase the proportion of ischemic stroke patients treated with thrombolytic therapy, the establishment of primary stroke centers in community hospitals has been advocated. We evaluated the use of thrombolytic therapy before and after institution of a primary stroke center in a community hospital. Methods— The availability of an on-call stroke emergency response team was the only significant additional resource required for this hospital. All eligible patients were treated with intravenous tissue plasminogen activator (tPA). The number of patients with cerebrovascular disease, number and proportion of patients treated with tPA, times to treatment, and patient outcomes were recorded during the first 2 years of the stroke center. Results— During the 12 months before institution of the stroke center, 3 ischemic stroke patients (1.5%) were treated with tPA. During the 2-year period of around-the-clock coverage, 44 of 420 ischemic stroke patients (10.5%) were treated with intravenous tPA, a significant increase in tPA use (P <0.0001). Conclusions— Establishment of a primary stroke center at a community hospital resulted in a substantial increase in the proportion of patients receiving thrombolytic therapy for ischemic stroke. If this experience is generalized, the beneficial impact of primary stroke centers on stroke outcomes and costs to the healthcare system may be substantial.

Early ischemic lesion recurrence within a week after acute ischemic stroke

Previous observations suggested that multiple ischemic lesions on diffusion‐weighted imaging (DWI) are common in acute stroke patients. We hypothesized that a source of these multiple lesions was the recurrence of ischemic lesions within a week after a clinically symptomatic stroke. We analyzed 99 acute ischemic stroke patients scanned within 6 hours of onset and at subsequent times within the first week. Ischemic lesion recurrence was defined as any new lesion separate from the index lesion. Recurrent lesions occurring outside initial perfusion deficit were termed ‘distant lesion recurrence’. We estimated the hazard ratio (HR) of recurrence associated with clinical and imaging characteristics using log‐rank test. Any lesion recurrence was found in 34%, with distant lesion recurrence in 15%, while clinical recurrence was evident in 2%. Initial multiple DWI lesions were associated with any lesion recurrence (HR, 2.83; 95% confidence interval [CI], 1.65–10.29; p = 0.002) and with distant lesion recurrence (HR, 5.99; 95% CI, 4.05–64.07; p < 0.0001). Large‐artery atherosclerosis was the most frequent stroke subtype associated with any lesion recurrence (p = 0.026). These results may indicate a prolonged state of increased ischemic risk over the first week and suggest DWI as a possible surrogate measure for recurrent stroke. Ann Neurol 2003