Research priorities in neurocritical care.

This summary of the last session of the First Neurocritical Care Research Conference reviews the discussions about research priorities in neurocritical care. The first presentation reviewed current projects funded by the National Institute of Neurological Disorders and Stroke at the National Institutes of Health and potential models to follow including an independent Neurocritical Care Network or the creation of such a network with the goal of collaborating with already existing ones. Experienced neurointensivists then presented their views on the most common and important research questions that need to be answered and investigated in the field. Finally, utility of clinical registries was discussed emphasizing their importance as hypothesis generators. During the group discussion, interests in comparative effectiveness research, the use of physiological endpoints from monitoring and alternate trial design were expressed.

Functional contrast-enhanced CT for evaluation of acute ischemic stroke does not increase the risk of contrast-induced nephropathy.

BACKGROUND AND PURPOSE: Concerns have recently grown regarding the safety of iodinated contrast agents used for CTA and CTP imaging. We tested whether the incidence of AN, defined by a >or=25% increase in the post-contrast scan creatinine level, was higher among patients with ischemic stroke who underwent a functional contrast-enhanced CT protocol compared with those who had no iodinated contrast administration. MATERIALS AND METHODS: The contrast-exposed group consisted of 575 patients with acute ischemic stroke who underwent CTA (n = 313), CTA/CTP (n = 224), or CTA/CTP followed by conventional angiography (n = 38) within 24 hours of stroke onset and were consecutively enrolled in a prospective cohort study. The nonexposed group consisted of 343 patients with ischemic stroke, consecutively admitted to the same institution, who did not receive iodinated contrast material. Patients were stratified by baseline eGFR. In the primary analysis, the Fisher exact test was used to compare the incidence of AN between the contrast-exposed and the nonexposed patients at 24, 48, and 72 hours and on a cumulative basis. A secondary analysis compared the incidence of AN in patients who underwent conventional angiography following CTA/CTP versus patients who underwent CTA/CTP only. RESULTS: The incidence of AN was 5% in the exposed and 10% in the nonexposed group (P = .003). Patients who underwent conventional angiography after contrast CT were at no greater risk of AN than patients who underwent CTA/CTP alone (26 patients, 5%; and 2 patients, 5%, respectively; P = .7). CONCLUSIONS: Administration of a contrast-enhanced CT protocol involving CTA/CTP and conventional angiography in selected patients does not appear to increase the incidence of CIN.

A score to predict early risk of recurrence after ischemic stroke.

BACKGROUND: There is currently no instrument to stratify patients presenting with ischemic stroke according to early risk of recurrent stroke. We sought to develop a comprehensive prognostic score to predict 90-day risk of recurrent stroke. METHODS: We analyzed data on 1,458 consecutive ischemic stroke patients using a Cox regression model with time to recurrent stroke as the response and clinical and imaging features typically available to physician at admission as covariates. The 90-day risk of recurrent stroke was calculated by summing up the number of independent predictors weighted by their corresponding beta-coefficients. The resultant score was called recurrence risk estimator at 90 days or RRE-90 score (available at: http://www.nmr.mgh.harvard.edu/RRE-90/). RESULTS: Sixty recurrent strokes (54 had baseline imaging) occurred during the follow-up period. The risk adjusted for time to follow-up was 6.0%. Predictors of recurrence included admission etiologic stroke subtype, prior history of TIA/stroke, and topography, age, and distribution of brain infarcts. The RRE-90 score demonstrated adequate calibration and good discrimination (area under the ROC curve [AUC] = 0.70-0.80), which was maintained when applied to a separate cohort of 433 patients (AUC = 0.70-0.76). The model's performance was also maintained for predicting early (14-day) risk of recurrence (AUC = 0.80). CONCLUSIONS: The RRE-90 is a Web-based, easy-to-use prognostic score that integrates clinical and imaging information available in the acute setting to quantify early risk of recurrent stroke. The RRE-90 demonstrates good predictive performance, suggesting that, if validated externally, it has promise for use in creating individualized patient management algorithms and improving clinical practice in acute stroke care.

Severity of leukoaraiosis correlates with clinical outcome after ischemic stroke.

BACKGROUND: Leukoaraiosis (LA) is closely associated with aging, a major determinant of clinical outcome after ischemic stroke. In this study we sought to identify whether LA, independent of advancing age, affects outcome after acute ischemic stroke. METHODS: LA volume was quantified in 240 patients with ischemic stroke and MRI within 24 hours of symptom onset. We explored the relationship between LA volume at admission and clinical outcome at 6 months, as assessed by the modified Rankin Scale (mRS). An ordinal logistic regression model was developed to analyze the independent effect of LA volume on clinical outcome. RESULTS: Bivariate analyses showed a significant correlation between LA volume and mRS at 6 months (r = 0.19, p = 0.003). Mean mRS was 1.7 +/- 1.8 among those in the lowest (< or =1.2 mL) and 2.5 +/- 1.9 in the highest (>9.9 mL) quartiles of LA volume (p = 0.01). The unfavorable prognostic effect of LA volume on clinical outcome was retained in the multivariable model (p = 0.002), which included age, gender, stroke risk factors (hypertension, diabetes mellitus, atrial fibrillation), previous history of brain infarction, admission plasma glucose level, admission NIH Stroke Scale score, IV rtPA treatment, and acute infarct volume on MRI as covariates. CONCLUSIONS: The volume of leukoaraiosis is a predictor of clinical outcome after ischemic stroke and this relationship persists after adjustment for important prognostic factors including age, initial stroke severity, and infarct volume.

Perfusion CT Imaging Follows Clinical Severity in Left Hemispheric Strokes.

OBJECTIVE: The purpose of this study was to assess how imaging findings on admission perfusion CT (PCT) and follow-up noncontrast CT (NCT), and their changes over time, correlate with clinical scores of stroke severity measured on admission, at discharge and at 6-month follow-up. METHODS: Fifty-two patients with suspected hemispheric acute ischemic stroke underwent a PCT within the first 24 h of symptom onset and a follow-up NCT of the brain between 24 h and 3 months after the initial stroke CT study. NIH Stroke Scale (NIHSS) scores were recorded for each patient at admission, discharge and 6 months; modified Rankin scores were determined at discharge and 6 months. Baseline PCT and follow-up NCT were analyzed quantitatively (volume of ischemic/infarcted tissue) and semiquantitatively (anatomical grading score derived from the Alberta Stroke Program Early CT Score). The correlation between imaging volumes/scores and clinical scores was assessed. Analysis was performed for all patients considered together and separately for those with right and left hemispheric strokes. RESULTS: Significant correlations were found between clinical scores and both quantitative and semiquantitative imaging. The volume of the acute PCT mean transit time lesion showed best correlation with admission NIHSS scores (R2 = 0.61, p < 0.001). This association was significantly better for left hemispheric strokes (R(2) = 0.80, p < 0.001) than for right hemispheric strokes (R2 = 0.39, p = 0.131). Correlation between imaging and NIHSS scores was better than correlation between imaging and modified Rankin scores (p = 0.047). The correlation with discharge clinical scores was better than that with 6-month clinical scores (p = 0.012). CONCLUSIONS: Baseline PCT and follow-up NCT volumes predict stroke severity at baseline, discharge and, to a lesser extent, 6 months. The correlation is stronger for left-sided infarctions. This finding supports the use of PCT as a surrogate stroke outcome measure.

Sex as a predictor of outcomes in patients treated with thrombolysis for acute stroke.

OBJECTIVE: To determine the association between sex and functional outcomes after thrombolytic treatment for acute ischemic stroke in the context of a clinical trial. METHODS: We analyzed predictors of outcome among patients treated with recombinant tissue plasminogen activator (rtPA) in the Glycine Antagonist in Neuroprotection for Patients with Acute Stroke Americas trial, a multicenter, randomized, double-blind, placebo-controlled study of a putative neuroprotectant. RESULTS: Among 1,367 trial patients, 333 (24%) were treated with rtPA within 3 hours. The proportion of patients achieving good functional outcomes at 3 months differed by sex (47.5% of men vs 30.3% of women had Barthel Index [BI] > or = 95; 32.2% of men vs 23.4% of women had modified Rankin Score [mRS] < or = 1). NIH Stroke Score was similar by sex. Men were more likely to have good functional outcomes after adjusting for relevant covariates: for BI > or = 95, adjusted odds ratio (OR) 3.28 (1.74 to 6.17); for mRS < or = 1, adjusted OR 2.12 (1.11 to 4.03). Survival was worse among men: adjusted OR 0.45 (0.20 to 1.01). Other predictors of functional outcomes included age, stroke side, severity, complications, and infections. CONCLUSIONS: Among tissue plasminogen activator-treated patients in this clinical trial population, men were approximately three times as likely to have good functional outcomes, despite elevated mortality. Thrombolysis for stroke may not reverse the tendency for women to have worse functional outcomes after stroke.

Association between tPA therapy and raised early matrix metalloproteinase-9 in acute stroke.

BACKGROUND: Matrix metalloproteinase-9 (MMP9) is expressed in acute ischemic stroke and up-regulated by tissue plasminogen activator (tPA) in animal models. The authors investigated plasma MMP9 and its endogenous inhibitor, tissue inhibitor of metalloproteinase (TIMP1), in tPA-treated and -untreated stroke patients. METHODS: Nonstroke control subjects and consecutive ischemic stroke patients presenting within 8 hours of onset were enrolled. Blood was sampled within 8 hours and at 24 hours, 2 to 5 days and 4 to 6 weeks. MMP9 and TIMP1 were analyzed by ELISA and gel zymography. RESULTS: Fifty-two cases (26 tPA treated, 26 tPA untreated) and 27 nonstroke control subjects were enrolled. Hyperacute MMP9 was elevated in tPA-treated vs tPA-untreated patients (medians 43 vs 28 ng/mL; p = 0.01). tPA therapy independently predicted hyperacute MMP9 after adjustment for stroke severity, volume, and hemorrhagic transformation (p = 0.01). There was a trend toward lower hyperacute TIMP1 levels in tPA-treated vs tPA-untreated patients (p = 0.06). Hyperacute MMP9 was correlated to poor 3-month modified Rankin Scale outcome (r = 0.58, p = 0.0005). CONCLUSION: Tissue plasminogen activator independently predicted plasma matrix metalloproteinase-9 (MMP9) in the first 8 hours after human ischemic stroke. As MMP9 may be an important mediator of hemorrhagic transformation, alternative thrombolytic agents or therapeutic MMP9 inhibition may increase the safety profile of acute stroke thrombolysis.

Neuroanatomic correlates of stroke-related myocardial injury.

BACKGROUND: Myocardial injury can occur after ischemic stroke in the absence of primary cardiac causes. The neuroanatomic basis of stroke-related myocardial injury is not well understood. OBJECTIVE: To identify regions of brain infarction associated with myocardial injury using a method free of the bias of an a priori hypothesis as to any specific location. METHODS: Of 738 consecutive patients with acute ischemic stroke, the authors identified 50 patients in whom serum cardiac troponin T (cTnT) elevation occurred in the absence of any apparent cause within 3 days of symptom onset. Fifty randomly selected, age- and sex-matched patients with ischemic stroke without cTnT elevation served as controls. Diffusion-weighted images with outlines of infarction were co-registered to a template, averaged, and then subtracted to find voxels that differed between the two groups. Voxel-wise p values were determined using a nonparametric permutation test to identify specific regions of infarction that were associated with cTnT elevation. RESULTS: The study groups were well balanced with respect to stroke risk factors, history of coronary artery disease, infarction volume, and frequency of right and left middle cerebral artery territory involvement. Brain regions that were a priori associated with cTnT elevation included the right posterior, superior, and medial insula and the right inferior parietal lobule. Among patients with right middle cerebral artery infarction, the insular cluster was involved in 88% of patients with and 33% without cTnT elevation (odds ratio: 15.00; 95% CI: 2.65 to 84.79). CONCLUSIONS: Infarctions in specific brain regions including the right insula are associated with elevated serum cardiac troponin T level indicative of myocardial injury.

First-pass quantitative CT perfusion identifies thresholds for salvageable penumbra in acute stroke patients treated with intra-arterial therapy.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether, in acute stroke patients treated with intra-arterial (IA) recanalization therapy, CT perfusion (CTP) can distinguish ischemic brain tissue destined to infarct from that which will survive. METHODS: Dynamic CTP was obtained in 14 patients within 8 hours of stroke onset, before IA therapy. Initial quantitative cerebral blood volume (CBV) and flow (CBF) values were visually segmented and normalized in the "infarct core" (region 1: reduced CBV and CBF, infarction on follow-up), "penumbra that infarcts" (region 2: normal CBV, reduced CBF, infarction on follow-up), and "penumbra that recovers" (region 3: normal CBV, reduced CBF, normal on follow-up). Normalization was accomplished by dividing the ischemic region of interest value by that of a corresponding, contralateral, uninvolved region, which resulted in CBV and CBF "ratios." Separate CBV and CBF values were obtained in gray matter (GM) and white matter (WM). RESULTS: Mean CBF ratios for regions 1, 2, and 3 were 0.19 +/- 0.06, 0.34 +/- 0.06, and 0.46 +/- 0.09, respectively (all P < .001). Mean CBV ratios for regions 1, 2, and 3 were similarly distinct (all P < .05). Absolute CBV and CBF values for regions 2 and 3 were not significantly different. All regions with CBF ratio <0.32, CBV ratio <0.68, CBF <12.7 mL/100 g/min, or CBV <2.2 mL/100 g infarcted. No region with CBF ratio >0.44 infarcted. GM versus WM CBF and CBV values were significantly different for region 2 compared with region 3 (P < .05). CONCLUSIONS: In acute stroke patients, quantitative CTP can distinguish ischemic tissue likely to infarct from that likely to survive.

SSRI and statin use increases the risk for vasospasm after subarachnoid hemorrhage.

BACKGROUND: Use of medications with vasoconstrictive or vasodilatory effects can potentially affect the risk for vasospasm after aneurysmal subarachnoid hemorrhage (SAH). METHODS: Using International Classification of Diseases-9 diagnostic codes followed by medical record review, the authors identified 514 patients with SAH admitted between 1995 and 2003 who were evaluated for vasospasm between days 4 and 14. The authors determined risks for vasospasm, symptomatic vasospasm, and poor clinical outcomes in patients with documented pre-hemorrhagic use of calcium channel blockers, beta-receptor blockers, ACE inhibitors, aspirin, selective serotonin reuptake inhibitors (SSRIs), non-SSRI vasoactive antidepressants, or statins. RESULTS: Vasospasm developed in 62%, and symptomatic vasospasm in 29% of the cohort. On univariate analysis, the risk for all vasospasm tended to increase in patients taking SSRIs (p = 0.09) and statins (p = 0.05); SSRI use increased the risk for symptomatic vasospasm (p = 0.028). The Cochran-Armitage trend test showed that the proportion of patients taking SSRIs and statins increased significantly across three worsening categories (none, asymptomatic, symptomatic) of vasospasm. Logistic regression analysis showed that SSRI use tended to predict all vasospasm (O.R. 2.01 [0.91 to 4.45]), and predicted symptomatic vasospasm (O.R. 1.42 [1.06 to 4.33]). Statin exposure increased the risk for vasospasm (O.R. 2.75 [1.16 to 6.50]), perhaps from abrupt statin withdrawal (O.R. 2.54 [0.78 to 8.28]). Age < 50 years, Hunt-Hess grade 4 or 5, and Fisher Group 3 independently predicted all vasospasm, symptomatic vasospasm, poor discharge clinical status, and death. CONCLUSION: Selective serotonin reuptake inhibitor and statin users have a higher risk for subarachnoid hemorrhage-related vasospasm. Whether the underlying disease indication, direct actions, or rebound effects from abrupt drug withdrawal account for the associated risk warrants further investigation.

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.

Cooling for Acute Ischemic Brain Damage (COOL AID): a feasibility trial of endovascular cooling.

OBJECTIVE: To report results of a randomized pilot clinical feasibility trial of endovascular cooling in patients with ischemic stroke. METHODS: Forty patients with ischemic stroke presenting within 12 hours of symptom onset were enrolled in the study. An endovascular cooling device was inserted into the inferior vena cava of those randomized to hypothermia. A core body temperature of 33 degrees C was targeted for 24 hours. All patients underwent clinical assessment and MRI initially, at days 3 to 5 and days 30 to 37. RESULTS: Eighteen patients were randomized to hypothermia and 22 to receive standard medical management. Thirteen patients reached target temperature in a mean of 77 +/- 44 minutes. Most tolerated hypothermia well. Clinical outcomes were similar in both groups. Mean diffusion-weighted imaging (DWI) lesion growth in the hypothermia group (n = 12) was 90.0 +/- 83.5% compared with 108.4 +/- 142.4% in the control group (n = 11) (NS). Mean DWI lesion growth in patients who cooled well (n = 8) was 72.9 +/- 95.2% (NS). CONCLUSIONS: Induced moderate hypothermia is feasible using an endovascular cooling device in most patients with acute ischemic stroke. Further studies are needed to determine if hypothermia improves outcome.

Establishment of primary stroke centers: a survey of physician attitudes and hospital resources.

OBJECTIVES: To survey US physicians involved in acute stroke care to determine the proportion of hospitals that currently meet the recommended Brain Attack Coalition (BAC) criteria for Primary Stroke Centers (PSC) and obtain opinions regarding the value of stroke centers. METHODS: A survey regarding the BAC guidelines for the establishment of stroke centers was mailed to 3,245 US neurologists, neurosurgeons, and emergency physicians. RESULTS: A total of 1,032 responses were received. Seventy-nine percent (range by specialty 58 to 98%) of respondents believed there was a need for stroke centers. If formal stroke center designation were established, 81% (range 72 to 90%) would like their hospital to become a PSC. Although 77% of respondents believed that their hospital currently met recommended criteria for a PSC, only 7% actually meet all recommended elements. However, 44% of hospitals already provide most acute stroke services. The BAC criteria most frequently lacking were continuing medical education for professional stroke center staff, stroke training for emergency department staff, formal establishment of a stroke unit, and designation of a stroke center director. CONCLUSIONS: The majority of emergency medicine and neuroscience physician respondents involved in acute stroke care support the designation of primary stroke centers. Although respondents globally overestimated the extent to which their facilities currently meet BAC recommended criteria for PSC, detailed responses suggested that over 40% of hospitals possess substantial existing acute stroke care resources and are poised to function as PSC with modest additional administrative and financial commitment.

Evidence for more widespread cerebral pathology in early HD: an MRI-based morphometric analysis.

BACKGROUND: Most clinical symptoms of Huntington disease (HD) have been attributed to striatal degeneration, but extrastriatal degeneration may play an important role in the clinical symptoms because postmortem studies demonstrate that almost all brain structures atrophy. OBJECTIVE: To fully characterize the morphometric changes that occur in vivo in HD. METHODS: High-resolution 1.5 mm T1-weighted coronal scans were acquired from 18 individuals in early to mid-stages of HD and 18 healthy age-matched controls. Cortical and subcortical gray and white matter were segmented using a semiautomated intensity contour-mapping algorithm. General linear models for correlated data of the volumes of brain regions were used to compare groups, controlling for age, education, handedness, sex, and total brain volumes. RESULTS: Subjects with HD had significant volume reductions in almost all brain structures, including total cerebrum, total white matter, cerebral cortex, caudate, putamen, globus pallidus, amygdala, hippocampus, brainstem, and cerebellum. CONCLUSIONS: Widespread degeneration occurs in early to mid-stages of HD, may explain some of the clinical heterogeneity, and may impact future clinical trials.

Cerebral vasoconstriction and stroke after use of serotonergic drugs.

Serotonin (5-hydroxytryptamine) is a potent vasoconstrictor amine. The authors report three patients who developed thunderclap headache, reversible cerebral arterial vasoconstriction, and ischemic strokes (i.e., the Call-Fleming syndrome). The only cause for vasoconstriction was recent exposure to serotonergic drugs in all patients, and to pseudoephedrine in one patient. These cases, and the literature, suggest that the use of serotonin-enhancing drugs can precipitate a cerebrovascular syndrome due to reversible, multifocal arterial narrowing.

Small aneurysms as a cause of thromboembolic stroke.

OBJECTIVE AND IMPORTANCE: A small percentage of patients with intracranial aneurysms present with embolic stroke distal to the site of the aneurysm. Thromboembolism typically occurs in large or giant aneurysms where reduction of flow within the aneurysm is thought to increase the possibility of clot formation. Only a few examples are available in the literature of patients with smaller aneurysms who develop embolic infarction distal to the lesion. We have experience with two such patients with an apparent common pathophysiology. CLINICAL PRESENTATION: Patient 1 with a distal left middle cerebral artery infarct was found to have an 18 mm carotid artery bifurcation aneurysm (patient age 49 years). Patient 2 had a 7 mm right middle cerebral artery aneurysm with a small distal embolus (patient age 65 years). At surgery both patients were found to have atherosclerotic disease involving the aneurysm base and parent vessel. In each instance, the aneurysm was opened during temporary vessel occlusion and microendarterectomy was performed. Occlusion of one of the major arterial branches exiting the aneurysm was also present with anterior cerebral artery occlusion in the case of ICA bifurcation lesion and MCA branch occlusion in the case of the MCA aneurysm. Both patients made a good recovery following surgery. CONCLUSION: In small aneurysms with atherosclerotic disease distal thromboembolism may occur. Surgical treatment with microendarterectomy is appropriate to prevent further emboli and potential for subarachnoid hemorrhage. (Fig. 5, Ref. 16.)

Potential influence of acute CT on inpatient costs in patients with ischemic stroke.

RATIONALE AND OBJECTIVES: Patients presenting with ischemic brain symptoms have widely variable outcomes dependent to some degree on the pathologic basis of their stroke syndrome. The purpose of this study was to determine the cost implications of the emergency use of a computed tomographic (CT) protocol comprising unenhanced CT, head and neck CT angiography, and whole-brain CT perfusion. MATERIALS AND METHODS: By using a retrospective patient database from a tertiary care facility and publicly available cost data, the authors derived the potential savings from the use of CT angiography. CT perfusion, or both at hospital arrival by means of a cost model. The cost of the CT angiography-CT perfusion protocol was determined from Medicare reimbursement rates and compared with that of traditional imaging protocols. Cost savings were estimated as a decrease in the length of stay for most stroke patients, whereas the most benign (lacunar) strokes were assumed to be managed in a non-acute setting. Misdiagnosis cost (erroneously not admitting a patient with nonlacunar stroke) was calculated as the cost of a severe complication. Sensitivity testing included varying the percentage of misdiagnosed patients and admitting patients with lacunar stroke. RESULTS: The nationwide net savings that would result from the adoption of the CT angiography-CT perfusion protocol are in the $1.2 billion range (-$154 million to $2.1 billion) when patients with lacunar strokes are treated nonacutely and $1.8 billion when those patients are admitted for acute care. CONCLUSION: The results demonstrate the potential effect of implementing a CT angiography-CT perfusion protocol. In particular, prompt CT angiography-CT perfusion imaging could have an effect on the cost of acute care in the treatment of stroke.

Diagnostic value of apparent diffusion coefficient hyperintensity in selected patients with acute neurologic deficits.

BACKGROUND AND PURPOSE: A pattern of decreased intensity on apparent diffusion coefficient (ADC) maps is useful in the early detection of ischemic brain injury. Less information exists with regard to patients with acute neurologic deficits in whom there is abnormal conventional magnetic resonance imaging (MRI) and increased ADC intensity. METHODS: The authors identified 13 patients with acute neurologic deficits who underwent diffusion MRI and had calculated ADC maps demonstrating hyper-intensity in regions characterized by computed tomography hypodensity and MRI T2 hyperintensity. The initial and follow-up imaging characteristics and clinical syndromes were recorded. RESULTS: Clinical syndromes included hypertensive encephalopathy, posterior leukoencephalopathy, hyperperfusion following carotid endarterectomy, venous sinus thrombosis, HIV encephalopathy, and brain tumor. Diffusion-weighted imaging (DWI) was hyperintense in 3 of 13 patients, isointense in 4 of 13 patients, heterogeneous in 3 of 13 patients, and hypointense in 3 of 13 patients. The ADC values in these regions were significantly higher than those in control regions (P < .0001). At early follow-up, MRI abnormalities resolved completely in 3 of 13 patients and partially in 9 of 13 patients. MRI abnormalities were unchanged in 1 patient. CONCLUSIONS: In the evaluation of patients with acute neurologic deficits, ADC hyperintensity may identify a subset of patients with vasogenic edema of nonischemic etiology. Frequently, these conditions are potentially reversible if appropriately managed. DWI and conventional images alone are not sufficient to identify these neurologic conditions.