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.

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.

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.

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.

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.

Striatal volume loss in HD as measured by MRI and the influence of CAG repeat.

BACKGROUND: Huntington's disease (HD) is an autosomal dominant neurodegenerative disease that results from the expansion of a trinucleotide (CAG) repeat on chromosome 4. Progressive degeneration of the striatum is the pathologic hallmark of the disease. Little is known about the regional selectivity of the neurodegeneration and its relationship to the genetic expansion. METHODS: The authors used high-resolution MRI to determine the relationship between the genetic expansion and the degree of striatal degeneration. Morphometric analyses of the striatum from high-resolution MR images from 27 subjects with HD were compared with those of 24 healthy control subjects. RESULTS AND CONCLUSIONS: Striatal volumes were reduced in subjects with HD as compared with control subjects, in agreement with previously published reports. Left-sided volumes were smaller than right-sided volumes in subjects with HD; in healthy subjects, right-sided volumes were smaller. Finally, volume loss was significantly correlated with CAG repeat number. These results have potential implications for the design and assessment of therapeutic agents in the future.

Ischemic stroke: effects of etiology and patient age on the time course of the core apparent diffusion coefficient.

PURPOSE: To determine whether the evolution of the core apparent diffusion coefficient (ADC) of water in ischemic stroke varies with patient age or infarct etiology. MATERIALS AND METHODS: One hundred forty-seven patients with stroke underwent 236 diffusion-weighted magnetic resonance imaging examinations. Etiologies of lesions were classified according to predefined criteria; in 224 images, the diagnosis of lacune could be firmly established or excluded. ADC was measured in the center of each lesion and in contralateral normal-appearing brain. A model was used to describe the time course of relative ADC (rADC), which is calculated by dividing the lesion ADC by the contralateral ADC, and to test for age- or etiology-related differences in this time course. RESULTS: Transition from decreasing to increasing rADC was estimated at 18.5 hours after stroke onset. In subgroup analysis, transition was earlier in nonlacunes than in lacunes (P =.02). There was a trend toward earlier transition in patients older than the median age of 66.0 years, compared with younger patients (P =.06). Pseudonormalization was estimated at 216 hours. Among nonlacunes, the rate of subsequent rADC increase was more rapid in younger patients than in older patients (P =.001). Within the smaller sample of lacunes, however, no significant age-related difference in this rate was found. CONCLUSION: Differences in ADC depending on the patient's age and infarct etiology suggest differing rates of ADC progression.

Frequency and clinical context of decreased apparent diffusion coefficient reversal in the human brain.

PURPOSE: To determine the probability that regions of decreased apparent diffusion coefficient (ADC) return to normal without persistent symptoms or T2 change and the settings in which these ADC reversals occur. MATERIALS AND METHODS: Three hundred magnetic resonance (MR) imaging studies were selected at random from a database of 7,147 examinations to determine the probability of a pathologically decreased ADC. In cases with decreased ADC, the clinical history was recorded and, if available, follow-up MR imaging findings were evaluated. Five cases of ADC reversal became known during the same period and were evaluated to determine the initial ADC decrease, clinical outcome, and findings at follow-up imaging. RESULTS: Findings in 116 of 300 MR imaging studies revealed regions of decreased ADC. In 49 of 116 studies, follow-up MR imaging examinations were performed at least 4 weeks after the onset of symptoms; ADC did not reverse. Five cases of ADC reversal were identified in the same period, giving an estimated 0.2%-0.4% probability of ADC reversal. Clinical settings were venous sinus thrombosis and seizure (n = 3), hemiplegic migraine (n = 1), and hyperacute arterial infarction (n = 1). Both white matter (n = 3) and gray matter (n = 3) regions were involved. CONCLUSION: Reversal of ADC lesions is rare, occurs in complicated clinical settings, and can involve white or gray matter.

Utility of perfusion-weighted CT imaging in acute middle cerebral artery stroke treated with intra-arterial thrombolysis: prediction of final infarct volume and clinical outcome.

BACKGROUND AND PURPOSE: The goal of this study was to evaluate the utility of perfusion-weighted CT (PWCT) in predicting final infarct volume and clinical outcome in patients with acute middle cerebral artery (MCA) stroke. METHODS: Twenty-two consecutive patients with MCA stem occlusion who underwent intra-arterial thrombolysis within 6 hours of stroke onset had noncontrast CT and CT angiography with whole-brain PWCT imaging before treatment. Infarct volumes were computed from the initial PWCT and follow-up scans; clinical outcome was measured with the modified Rankin scale. RESULTS: Initial PWCT lesion volumes correlated significantly with final infarct volume (P=0.0002) and clinical outcome (P=0.01). For the 10 patients with complete recanalization, the relationship between initial and final lesion volume was especially strong (R(2)=0.94, P<0.0001, slope of regression line=0.92). For those without complete recanalization, there was progression of lesion volume on follow-up imaging (R(2)=0.50, P=0.01, slope of regression line=1.61). All patients with either initial PWCT lesion volumes >100 mL or no recanalization had poor outcomes (Rankin scores, 4 to 6). Mean admission NIH Stroke Scale scores and mean lesion volumes in the poor outcome group were significantly different compared with the good or fair outcome (Rankin scores, 0 to 3) group (21+/-4 versus 17+/-5, P=0.05, and 106+/-79 versus 29+/-37 mL, P=0.01). Patients with initial volumes <100 mL and partial or complete recanalization all had good (Rankin scores, 0 to 2) or fair (Rankin score, 3) outcomes. CONCLUSIONS: Lesion volumes on admission PWCT images approximate final infarct volume for patients with early complete recanalization of MCA stem occlusion. For those without complete recanalization, there is subsequent enlargement of lesion volume on follow-up. Initial PWCT lesion volumes also have predictive value; volumes >100 mL are associated with a poor clinical outcome. In these highly selected patients, initial PWCT lesion volume was a stronger predictor of clinical outcome than was initial NIH Stroke Scale score.

CT angiography in the rapid triage of patients with hyperacute stroke to intraarterial thrombolysis: accuracy in the detection of large vessel thrombus.

PURPOSE: The purpose of this work was to evaluate the accuracy of CT angiography (CTA) for the detection of large vessel intracranial thrombus in clinically suspected hyperacute (<6 h) stroke patients. METHOD: Forty-four consecutive intraarterial thrombolysis candidates underwent noncontrast CT followed immediately by CTA. Axial source and two-dimensional collapsed maximum intensity projection reformatted CTA images were rated for the presence or absence of large vessel occlusion. Five hundred seventy-two circle-of-Willis vessels were reviewed; arteriographic correlation was available for 224 of these. RESULTS: Sensitivity and specificity for the detection of large vessel occlusion were 98.4 and 98.1%; accuracy, calculated using receiver operating characteristic analysis, was 99%. Mean time for acquisition, reconstruction, and analysis of CTA images was approximately 15 min. CONCLUSION: CTA is highly accurate for the detection and exclusion of large vessel intracranial occlusion and may therefore be valuable in the rapid triage of hyperacute stroke patients to intraarterial thrombolytic treatment.

A pilot study of drug-induced hypertension for treatment of acute stroke.

The aim of this pilot study was to determine whether the use of induced hypertension in acute stroke is feasible and associated with neurologic improvement. Phenylephrine was used to raise the systolic blood pressure in patients with acute stroke by 20%, not to exceed 200 mmHG: Of 13 patients treated, 7 improved by 2 points on the NIH Stroke SCALE: No systemic or neurologic complications were seen. The authors conclude that induced hypertension in acute stroke is feasible and likely safe and can improve the neurologic examination in some patients.

Fever in subarachnoid hemorrhage: relationship to vasospasm and outcome.

OBJECTIVE: To investigate the causes of fever in subarachnoid hemorrhage (SAH) and examine its relationship to outcome. BACKGROUND: Fever adversely affects outcome in stroke. Patients with SAH are at risk for cerebral ischemia due to vasospasm (VSP). In these patients, fever may be both caused by, and potentiate, VSP-mediated brain injury. METHODS: The authors prospectively studied patients admitted to a neurologic intensive care unit with nontraumatic SAH, documenting Hunt-Hess grade, Fisher group, Glasgow Coma Score, bacterial culture data, daily transcranial Doppler mean velocities, and maximum daily temperatures. Patients were classified as febrile (temperature above 38.3 degrees C for at least 2 consecutive days) or afebrile (no fever or isolated episodes of temperature above 38.3 degrees C). VSP was verified by either transcranial Doppler or angiographic criteria. Rankin scale scores on discharge were dichotomized into good (0 to 2) or poor (3 to 6) outcomes. RESULTS: Ninety-two consecutive patients were studied. Thirty-eight patients were classified as febrile. No source for infection was found in 10 of 38 (26%) patients. In a multivariate analysis, three variables independently predicted fever occurrence: ventriculostomy (OR, 8.5 [CI, 2.4 to 29.7]), symptomatic VSP (OR, 5.0 [CI, 1.03 to 24.5]), and older age (OR, 1.75 per 10 years [CI, 1.02 to 3.0]). Poor outcome was related to fever (OR, 1.4 per each day febrile [CI, 1.1 to 1.88]), older age (OR, 1.64 per 10 years [CI, 1.04 to 2.58]), and intubation (OR, 21.8 [CI, 5.6 to 84.5]). CONCLUSION: Fever in SAH is associated with vasospasm and poor outcome independently of hemorrhage severity or presence of infection.