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Significance Patients with small infarcts often demonstrate a poststroke acute dysexecutive syndrome resulting in failure to successfully re-integrate into society. The mechanism is poorly understood given that lesions are small and do not typically involve areas classically associated with cognitive decline. This knowledge gap makes designing treatment strategies difficult. We used MEG to evaluate changes in cerebral processing in individuals with small strokes. MEG showed a decrease in the amplitude of activation and temporal dispersion of activation peaks in areas responsible for visual word processing, along with an inability to modulate activity in response to task difficulty. These changes suggest disruption of network dynamics resulting in inefficient processing. Functional connectivity studies to isolate affected networks are the critical next step., Stroke patients with small central nervous system infarcts often demonstrate an acute dysexecutive syndrome characterized by difficulty with attention, concentration, and processing speed, independent of lesion size or location. We use magnetoencephalography (MEG) to show that disruption of network dynamics may be responsible. Nine patients with recent minor strokes and eight age-similar controls underwent cognitive screening using the Montreal cognitive assessment (MoCA) and MEG to evaluate differences in cerebral activation patterns. During MEG, subjects participated in a visual picture–word matching task. Task complexity was increased as testing progressed. Cluster-based permutation tests determined differences in activation patterns within the visual cortex, fusiform gyrus, and lateral temporal lobe. At visit 1, MoCA scores were significantly lower for patients than controls (median [interquartile range] = 26.0 [4] versus 29.5 [3], P = 0.005), and patient reaction times were increased. The amplitude of activation was significantly lower after infarct and demonstrated a pattern of temporal dispersion independent of stroke location. Differences were prominent in the fusiform gyrus and lateral temporal lobe. The pattern suggests that distributed network dysfunction may be responsible. Additionally, controls were able to modulate their cerebral activity based on task difficulty. In contrast, stroke patients exhibited the same low-amplitude response to all stimuli. Group differences remained, to a lesser degree, 6 mo later; while MoCA scores and reaction times improved for patients. This study suggests that function is a globally distributed property beyond area-specific functionality and illustrates the need for longer-term follow-up studies to determine whether abnormal activation patterns ultimately resolve or another mechanism underlies continued recovery.

Purpose: To characterize and predict early post-stroke cognitive impairment by describing cognitive changes in stroke patients 4–8 weeks post-infarct, determining the relationship between cognitive ability and functional status at this early time point, and identifying the in-hospital risk factors associated with early dysfunction.Materials and Methods: Data were collected for 214 patients with ischemic stroke and 39 non-stroke controls. Montreal Cognitive Assessment (MoCA) exams were administered at post-hospitalization clinic visits approximately 4–8 weeks after infarct. MoCA scores were compared for patients with: no stroke, minor stroke [NIH Stroke Scale (NIHSS) < 5], and major stroke. Ordinal logistic regression was performed to assess the relationship between MoCA score and functional status [modified Rankin Scale score (mRS)] at follow-up. Predictors of MoCA < 26 and < 19 (cutoffs for mild and severe cognitive impairment, respectively) at follow-up were identified by multivariable logistic regression using variables available during hospitalization.Results: Post stroke cognitive impairment was common, with 66.8% of patients scoring < 26 on the MoCA and 22.9% < 19. The average total MoCA score at follow-up was 18.7 (SD 7.0) among major strokes, 23.6 (SD 4.8) among minor strokes, and 27.2 (SD 13.0) among non-strokes (p = N = 201), a lack of pre-stroke employment, admission NIHSS > 6, and left-sided infarct predicted a follow-up MoCA < 26 (c-statistic 0.75); while admission NIHSS > 6 and infarct volume > 17 cc predicted a MoCA < 19 (c-statistic 0.75) at follow-up.Conclusion: Many patients experience early post-stroke cognitive dysfunction that significantly impacts function during a critical time period for decision-making regarding return to work and future independence. Dysfunction measured at 4–8 weeks can be predicted during the inpatient hospitalization. These high-risk individuals should be identified for targeted rehabilitation and counseling to improve longer-term post-stroke outcomes.

The role of interventional neuroradiology has expanded in the past decades as the safety of cerebral angiogram has improved. Not only is the use of diagnostic angiography increasing, the role of intervention in neurologic injury has increased dramatically as well. Angiography is not solely a means of diagnosis; an increasing number of interventions are now being used to treat injuries such as acute stroke, intracranial stenosis, cerebral aneurysms, and cerebral vasospasm through a variety of modalities including intraarterial medications, stents, and embolizations. Even though the safety of cerebral angiography and neurointerventional procedures has improved, the most common neurologic complication remains stroke. This chapter is designed to serve as a primer in clinical neurologic examination.

Background and Purpose— Symptomatic intracranial hemorrhage (sICH) is a life-threatening complication after treatment with intravenous tPA (tissue-type plasminogen activator) for acute stroke. Currently, patients are monitored for sICH in a neurocritical care unit or intensive care unit-like setting for 24 hours post-treatment—a costly and resource intensive practice. Because the half-life of tPA is much shorter than 24 hours, it is possible that the majority of patients do not require such intensive monitoring. In this study, we evaluate the time period of the highest risk for sICH post-tPA. Methods— All patients receiving intravenous tPA for acute stroke between 2004 and 2017 at our institution were prospectively followed for sICH for 36 hours after treatment. The mean time from tPA administration to hemorrhage was calculated. Additional data were collected regarding: patient demographics, medical variables, and stroke characteristics. Variables significant in univariate analysis were entered into multivariable logistic regression models to determine factors associated with symptomatic hemorrhage. Results— Three hundred eighty-five patients were administered intravenous tPA. Twenty-one (5.5%) developed sICH. The mean time from administration to hemorrhage was 8.5 hours. Greater than 80% of sICHs occurred before 12 hours post-treatment. The only variable significantly associated with sICH was combination therapy (intravenous tPA and intra-arterial thrombectomy). Conclusions— sICH associated with the administration of intravenous tPA typically occurs within the first 12 hours of treatment. Longer monitoring in an intensive care unit-like setting may be unnecessary for most individuals.

Background and Purpose Recent studies suggest that patients with large-vessel ischemic strokes (large-vessel occlusion [LVO]) with favorable imaging may benefit from mechanical thrombolysis even when treated outside the standard 6-hour window. However, many patients in these studies presented with unknown times of onset. We compare outcomes in thrombectomy patients treated at less than versus greater than 6 hours from last known well (LKN), and evaluate whether “unknown time of onset“ alters prognosis. Methods We retrospectively reviewed patients at 2 comprehensive stroke centers. Student's t and chi-square tests evaluated the association between predetermined clinical and radiographic variables, including unknown time of onset, and outcome (discharge and follow-up National Institutes of Health Stroke Scale score and modified Rankin Scale [mRS] score) for LVOs treated after greater than 6 hours versus 6 hours or less from LKN. Multivariable logistic regression was used to determine the odds of good outcome (mRS score 0-2). Results A total of 113 patients were treated over 2 years; 31 were treated at greater than 6 hours. Those who were treated at greater than 6 hours and experienced poor outcomes were more likely to have large-artery atherosclerosis (P = .033). There was no difference in outcome for patients outside the window with known (39.1%) versus unknown (60.9%) time of onset. mRS scores at discharge were higher among those outside the window (odds ratio 3.78; 95% confidence interval 1.20-11.89) but not at follow-up. After multivariable regression, favorable collaterals alone were associated with a mRS score of 0-2. Conclusions When imaging is favorable, the mRS score at follow-up is comparable regardless of time LKN. Functional outcomes appear to be driven most significantly by the presence of collaterals.

Objective Individuals with “minor stroke” lack a dense hemiparesis or aphasia; however, commonly endorse persistent cognitive and motor problems despite low NIHSS scores. They also report problems with mood, energy, and the ability to think clearly that are less well characterized. Socioeconomic factors and stroke severity can influence patient-reported outcomes. In this study we explore patient-reported outcomes and the influence of these factors after minor stroke. Patients and Methods Patients returning to clinic post-stroke with an NIHSS of ≤ 4 were administered a scale to quantify problems with daily activities and resulting functional burden, along with measures of fatigue and depression. T-tests, chi square analysis, and linear regression were used to compare functional outcomes of patients to controls (TIA or stroke mimic (n = 40)), and evaluate the association between patient-reported outcomes, stroke characteristics, and socioeconomic factors. Results 151 stroke patients were seen a mean 83.6 days post-infarct. Patients reported more problems (11.7 versus 6.9, p = 0.02), resulting in higher functional burden (26.5 versus 12.3, p = 0.01), increased depression (p = 0.07), and greater fatigue (p = 0.02) compared to controls. There was no relationship between stroke characteristics (other than NIHSS), baseline education, income, marital status, or living situation and perception of recovery; however, those actively working prior to their stroke reported better outcomes across all categories (p for each Conclusion Prior occupational status may represent an important prognostic indicator for patients with minor stroke. Individuals working at the time of their infarct report better functional outcomes irrespective of age or stroke severity.

As early as the 18th century, Morgagni recognized intracerebral hemorrhage (ICH)1; however, ICH diagnostics advanced markedly after noninvasive brain imaging with CT and MRI became available. Although the literature has a plethora of reported risk factors and causes, our knowledge of a cause(s) for an individual ICH remains limited. The paucity of effective treatment options for ICH reflects our lack of understanding and classification of ICH subtypes, their natural history, and the long-term prognosis. Several causative classifications for ischemic strokes (i.e., TOAST [Trial of Org 10172 in Acute Stroke Treatment], Causative Classification of Stroke, and ASCO [atherosclerosis, small vessel disease, cardiac source, other cause]) exist (with consequential tailored treatment strategies), but no such widely used classification existed for ICH until recently. Classification of ICHs usually followed anatomical location, providing only limited information on actual bleeding sources.2 Furthermore, the use of terms such as primary, secondary, or spontaneous ICH often seems arbitrary. Recently, 2 novel, mechanistic ICH classifications were introduced: namely, the SMASH-U and the H-ATOMIC.3,4 Both etiologic classifications have good interrater agreement.3,4 SMASH-U classification is easy and quick to execute, and is predictive of outcome.3 In H-ATOMIC classification, the etiology is scored with 3 degrees of certainty for each category: possible, probable, and definite equaling to 3, 2, and 1 point(s), respectively.4 SMASH-U may be better suited to clinical, and H-ATOMIC to scientific, purposes.

Introduction: Reversible cerebral vasoconstriction syndrome (RCVS) typically affects young patients and left untreated can result in hemorrhage or ischemic stroke. Though the disorder has been well characterized in the literature, the most appropriate way to diagnose, treat, and evaluate therapeutic response remains unclear. In previous studies, transcranial Doppler ultrasound (TCD) has shown elevated velocities indicative of vasospasm. This imaging modality is noninvasive and inexpensive; an attractive option for diagnosis and therapeutic monitoring if it is sensitive enough to detect changes in the acute setting given that RCVS often affects the distal vessels early in the course of disease. There is also limited data that calcium channel blockade may be effective in treating vasospasm secondary to RCVS, though the agent of choice, formulation, and dose are unclear. Methods: We report a small cohort of seven patients presenting with thunderclap headache whose vascular imaging was consistent with RCVS. All were treated with calcium channel blockade and monitored with TCD performed every 1–2 days. Results: On presentation, TCD correlated with standard neuroimaging findings of vasospasm (on MR, CT, and conventional angiography). TCD was also able to detect improvement in velocities in the acute setting that correlated well with initiation of calcium channel blockade. Long-acting verapamil appeared to have the greatest effect on velocities compared to nimodipine and shorter-acting calcium channel blockers. Conclusion: Though small, our cohort demonstrates potential utility of TCD to monitor RCVS, and relative superiority of extended-release verapamil over other calcium channel blockers, illustrating the need for larger randomized trials.

Background and Purpose: The National Institute of Health Stroke Scale (NIHSS) is rapid and reproducible, a seemingly attractive metric for the documentation of clinical progress in patients presenting with ischemic stroke. Many institutions have adopted it into daily clinical practice. Unfortunately, the scale may not adequately capture all forms of functional change. We evaluate its utility as a measure of recovery in patients treated with intravenous tissue plasminogen activator (IV tPA) for ischemic stroke. Methods: We prospectively evaluated the difference in the rate of improvement based on NIHSS (a ≥4 point change based on previous trials) versus physician-documented subjective and objective measures in 41 patients’ status post IV tPA treatment. The NIHSS 24 hours posttreatment, on discharge, and at follow-up were compared to NIHSS on admission using tests of proportions and McNemar tests of paired data. Secondary analyses were performed defining significant improvement as NIHSS changes of 1 to 3 points. Results: The mean NIHSS improved from 9 to 6, 24 hours post-tPA. Of the 41 patients, 29 improved by physician documentation, although only 11 of the 29 met the NIHSS criteria ( P < .001; McNemar P < .001). On discharge, 20 of the 41 patients met the NIHSS criteria; however, the proportion “better” by physician documentation (71%) remained significantly higher ( P = .04; McNemar P = .004). The mean postdischarge follow-up NIHSS was 2. Twenty of the 21 patients improved by documentation versus 16 of the 21 by NIHSS ( P = .08, McNemar P = .125). Using NIHSS changes of 1 to 3 increased sensitivity for detecting improvement but remained lower than physician documentation. Conclusion: The NIHSS has many advantages; however, it may miss functional changes when used in place of a comprehensive neurological examination to measure improvement poststroke.

Rapid identification of stroke mimics, such as seizures, is a critical part of the evaluation of patients presenting with acute focal neurological deficits. The primary role of CT perfusion is in identification of patients with acute ischemic stroke who may be candidates for reperfusion therapy, but also holds promise as a modality for identifying a seizure etiology. We review the literature on this topic and attempt to define characteristic CT perfusion findings at various points along the ictal-interictal (epileptic) continuum. We suggest an approach for using CT perfusion to differentiate stroke from seizure in patients with acute onset focal neurological deficits.

A 60-year-old woman with no known medical history presented with acute-onset altered mental status and aphasia. She was in her usual state of health until the time of presentation. She was found to have left middle and posterior cerebral artery (MCA and PCA) acute ischemic strokes and subsequently developed refractory status epilepticus. CT angiography showed moderate stenosis of the proximal left internal carotid artery (ICA), occlusion of the right ICA at its origin, and near-complete occlusion of the left vertebral artery (figure). Strokes were attributed to large-vessel atherosclerotic disease in the setting of multiple vascular risk factors including diabetes (A1c 13.5%), hypertension, and hyperlipidemia (low-density lipoprotein 244 mg/dL).

Background Up to 25% of acute stroke patients first note symptoms upon awakening. We hypothesized that patients awaking with stroke symptoms may be safely treated with intravenous alteplase (IV tPA) using non-contrast head CT (NCHCT), if they meet all other standard criteria. Methods The SAfety of Intravenous thromboLytics in stroke ON awakening (SAIL ON) was a prospective, open-label, single treatment arm, pilot safety trial of standard dose IV tPA in patients who presented with stroke symptoms within 0–4.5 hours of awakening. From January 30, 2013, to September 1, 2015, twenty consecutive wakeup stroke patients selected by NCHCT were enrolled. The primary outcome was symptomatic intracerebral hemorrhage (sICH) in the first 36 hours. Secondary outcomes included NIH stroke scale (NIHSS) at 24 hours; and modified Rankin Score (mRS), NIHSS, and Barthel index at 90 days. Results The average age was 65 years (range 47–83); 40% were women; 50% were African American. The average NIHSS was 6 (range 4–11). The average time from wake-up to IV tPA was 205 minutes (range 114–270). The average time from last known well to IV tPA was 580 minutes (range 353–876). The median mRS at 90 days was 1 (range 0–5). No patients had sICH; two of 20 (10%) had asymptomatic ICH on routine post IV tPA brain imaging. Conclusions Administration of IV tPA was feasible and may be safe in wakeup stroke patients presenting within 4.5 hours from awakening, screened with NCHCT. An adequately powered randomized clinical trial is needed. Clinical trial registration ClinicalTrials.gov NCT01643902.

Background Intravenous tissue plasminogen activator (IV tPA) after acute ischemic stroke carries the risk of symptomatic intracerebral hemorrhage (sICH). Cerebral microbleeds (CMBs) may indicate increased risk of hemorrhage and can be seen on magnetic resonance imaging (MRI). In this study, we examined the association between CMBs and sICH, focusing on the predictive value of their presence, burden, and location. Methods Records from all patients presenting to two academic stroke centers with acute ischemic stroke treated with IV tPA over a 5-year period were retrospectively reviewed. Demographic, medical, and imaging variables were evaluated. The presence, number, and location (lobar vs nonlobar) of CMBs were noted on gradient echo MRI sequences obtained during the admission. Univariable and multivariable statistical models were used to determine the relationship between CMBs and hemorrhagic (symptomatic and asymptomatic) transformation. Results Of 292 patients (mean age 62.8 years (SD 15.3), 49% African-American, 52% women), 21% (n = 62) had at least one CMB, 1% (n = 3) had > 10 CMBs, and 1% (n = 3) were diagnosed with probable cerebral amyloid angiopathy. After treatment, 16% (n = 46) developed hemorrhagic transformation, of which 6 (2%) were sICH. There was no association between CMB presence (p = .135) or location (p = .325) with sICH; however, those with a high CMB burden (> 10 CMB) were more likely to develop sICH (OR 37.8; 95% CI: 2.7–539.3; p = .007). Conclusions Our findings support prior findings that a high CMB burden (> 10) in patients with acute stroke treated with IV tPA are associated with a higher risk of sICH. However, the overall rate of sICH in the presence of CMB is very low, indicating that the presence of CMBs by itself should not dictate the decision to treat with thrombolytics.

Introduction: Meta-analysis of 13 studies suggested that combined mechanical thrombectomy (MT) with intravenous thrombolysis (IV-tPA) is more effective than MT alone. Limited economic analyses have explored this topic. We aimed to determine the cost-effectiveness of combined vs MT alone therapy in patients with large-vessel occlusive stroke. Hypothesis: Combined MT with IV-tPA is more cost-effective than MT alone. Methods: Markov model was constructed to simulate health outcomes and costs of two therapies (combined MT with IV-tPA, MT alone) over a 20 years lifetime horizon. The model incorporated an acute phase (0-90 days) and a rest of life phase (>90 days) with modified Rankin categories at 90days as the primary health states. Probabilities, utilities, and cost data were obtained from published sources. Incremental costs, quality-adjusted life-year (QALY), net monetary benefits, incremental cost-effectiveness ratio (ICER) were derived from the models. The willingness-to-pay was set to ICER $50,000/QALY. Results: Table 1 summarizes the base-case values and cost-effectiveness outcomes. Combined MT and IV-tPA led to improved quality-of-life and increased life expectancy; however, it was at slightly higher costs compared to MT alone. Combined MT with IV-tPA yielded 13.5 QALYs and accrued $220,227 in lifetime costs, whereas MT alone yielded 12.5 QALYs and accrued $185,714 in lifetime costs. Combined MT with IV-tPA costs $1,468 per QALY higher than MT alone group. The higher costs in combined therapy were driven by the costs of long-term care in stroke survivors with severe disability. Net monetary benefit was higher in the combined therapy by 14,988 points suggesting that combined MT with IV-tPA was more cost-effective than MT alone. Conclusions: Combined MT with IV-tPA is more cost effective than MT alone in patients with large vessel occlusive stroke. Randomized clinical trials to directly compare between combined MT with IVT vs MT alone seem warranted.

Background For ischemic stroke, the chance of improved recovery is directly impacted by length of time from symptom onset to administration of intravenous tissue plasminogen activator (IV tPA). Despite the importance of rapid treatment, stroke centers struggle with achieving consistent door-to-needle times of less than 60 minutes. Methods We implemented a change in our response to the acute stroke patient by adding a dedicated stroke nurse and a nursing flow sheet focused on critical benchmarks before treatment. We collected data on patients treated with IV tPA preintervention and postintervention to determine whether our process increased the number of patients receiving tPA in less than 60 minutes. One hundred thirty-eight patients (n = 78 pre and 60 post) treated between 2009 and 2013 were included. Student t tests and χ tests were used to compare door-to-needle times preintervention and postintervention. Results By implementing this new approach, the mean time to treatment decreased from 82 to 78 minutes (P = .583). The percentage of patients successfully treated within 60 minutes of arrival improved from 28% to 52% (P = .005). Stroke severity and need for additional imaging were associated with increased time to treatment. Conclusion The use of a stroke nurse and a nursing flow sheet as part of the acute stroke assessment significantly increases the proportion of patients treated with IV tPA within 60 minutes from hospital arrival.

Introduction. Using electroencephalography (EEG) and histology in patients with diffuse encephalopathy, Gloor et al reported that paroxysmal synchronous discharges (PSDs) on EEG required combined cortical gray (CG) and “subcortical” gray (SCG) matter pathology, while polymorphic delta activity (PDA) occurred in patients with white matter pathology. In patients with encephalopathy, we compared EEG findings and magnetic resonance imaging (MRI) to determine if MRI reflected similar pathological EEG correlations. Methods. Retrospective case control study of 52 cases with EEG evidence of encephalopathy and 50 controls without evidence of encephalopathy. Review of clinical, EEG and MRI data acquired within 4 days of each other. Results. The most common EEG finding in encephalopathy was background slowing, in 96.1%. We found PSDs in 0% of cases with the combination of CG and SCG abnormalities. Although 13.5% (n = 7) had PSDs on EEG; 3 of these had CG and 4 had SCG abnormalities. A total of 73.1% (38/52) had white matter abnormalities—of these 28.9% (11/38) had PDA. Conclusion. PSDs were found with either CG or “SCG” MRI abnormalities and did not require a combination of the two. In agreement with Gloor et al, PDA occurred with white matter MRI abnormalities in the absence of gray matter abnormalities.

Background and Purpose— The purpose is to determine whether patching during carotid endarterectomy (CEA) affects the perioperative and long-term risks of restenosis, stroke, death, and myocardial infarction as compared with primary closure. Methods— We identified all patients who were randomized and underwent CEA in Carotid Revascularization Endarterectomy versus Stenting Trial. CEA patients who received a patch were compared with patients who underwent CEA with primary closure without a patch. We compared periprocedural and 4-year event rates, 2-year restenosis rates, and rates of reoperation between the 2 groups. We further analyzed results by surgeon specialty. Results— There were 1151 patients who underwent CEA (753 [65%] with patch and 329 [29%] with primary closure). We excluded 44 patients who underwent eversion CEA and 25 patients missing CEA data (5%). Patch use differed by surgeon specialty: 89% of vascular surgeons, 6% of neurosurgeons, and 76% of thoracic surgeons patched. Comparing patients who received a patch versus those who did not, there was a significant reduction in the 2-year risk of restenosis, and this persisted after adjustment by surgeon specialty (hazard ratio, 0.35; 95% confidence interval, 0.16–0.74; P =0.006). There were no significant differences in the rates of periprocedural stroke and death (hazard ratio, 1.58; 95% confidence interval, 0.33–7.58; P =0.57), in immediate reoperation (hazard ratio, 0.6; 95% confidence interval, 0.16–2.27; P =0.45), or in the 4-year risk of ipsilateral stroke (hazard ratio, 1.23; 95% confidence interval, 0.42–3.63; P =0.71). Conclusions— Patch closure in CEA is associated with reduction in restenosis although it is not associated with improved clinical outcomes. Thus, more widespread use of patching should be considered to improve long-term durability. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00004732.

Objective Aphasia is a common presentation of ischemic stroke, often diagnosed in the acute setting using tools such as the NIH Stroke Scale (NIHSS). Due to the vascular distribution of the middle cerebral artery, it is often accompanied by other symptoms such as weakness, sensory loss, or visual changes. Isolated aphasia due to ischemia is possible, but language problems mimicking aphasia syndromes can also be seen with other diagnoses such as metabolic abnormalities or dementia. In this study, we determine the incidence of aphasia-only strokes using the NIHSS, and factors associated with a higher likelihood of ischemia. Patients and methods Over a 2 year period, 788 patients presented to our Emergency Department with symptoms of acute stroke. Data were collected regarding patient demographics, medical history, presenting symptoms (based on NIHSS), work-up results, and final diagnosis. The incidence of aphasia-only stroke was calculated. Student’s t-tests and chi square analysis were used to determine factors associated with ischemia. Results Of 788 patients, 21 (3%) presented with isolated “aphasia”. None of the 21 had infarcts on neuroimaging. Three (14%) were diagnosed with possible transient ischemic attacks and the rest with stroke mimics. Toxic/metabolic disturbances were the most common mimics (39%). Prior history of stroke or transient ischemic attack was associated with ischemia over mimic (p = 0.023). Conclusions Strokes affecting language without motor or sensory deficits are uncommon. In the acute setting, isolated “aphasia” is most often due to a stroke mimic; however can occur rarely, particularly in those with prior history of ischemia.

Patients receiving intravenous thrombolysis with recombinant tissue plasminogen activator (IVT) for ischemic stroke are monitored in an intensive care unit (ICU) or a comparable unit capable of ICU interventions due to the high frequency of standardized neurological exams and vital sign checks. The present study evaluates quantitative infarct volume on early post-IVT MRI as a predictor of critical care needs and aims to identify patients who may not require resource intense monitoring.We identified 46 patients who underwent MRI within 6 h of IVT. Infarct volume was measured using semiautomated software. Logistic regression and receiver operating characteristics (ROC) analysis were used to determine factors associated with ICU needs.Infarct volume was an independent predictor of ICU need after adjusting for age, sex, race, systolic blood pressure, NIH Stroke Scale (NIHSS), and coronary artery disease (odds ratio 1.031 per cm(3) increase in volume, 95% confidence interval [CI] 1.004-1.058, p = 0.024). The ROC curve with infarct volume alone achieved an area under the curve (AUC) of 0.766 (95% CI 0.605-0.927), while the AUC was 0.906 (95% CI 0.814-0.998) after adjusting for race, systolic blood pressure, and NIHSS. Maximum Youden index calculations identified an optimal infarct volume cut point of 6.8 cm(3) (sensitivity 75.0%, specificity 76.7%). Infarct volume greater than 3 cm(3) predicted need for critical care interventions with 81.3% sensitivity and 66.7% specificity.Infarct volume may predict needs for ICU monitoring and interventions in stroke patients treated with IVT.

Stroke is common and disabling. The extensive literature on motor recovery after ischemic stroke and substantial advances to improve function1 capture only part of the story. The clinical and research communities increasingly recognize the importance of poststroke cognitive decline and patient-reported metrics, including mood, fatigue, and quality of life, in satisfaction with recovery.2,3 We lack evidence on how to best improve these symptoms after ischemic stroke, and even less data exist on recovery after other types of cerebrovascular events such as intracranial hemorrhage and TIA. A better understanding of recovery of function across cerebrovascular disease subtypes would inform discussions with patients and families and could help identify appropriate effective interventions to improve poststroke morbidity and quality of life.

Background Intracerebral hemorrhage ( ICH ) carries high risk for short‐term mortality. We sought to identify race‐specific predictors of mortality in ICH patients. Methods and Results We used 2 databases, the Johns Hopkins clinical stroke database and the Nationwide Inpatient Sample ( NIS ). We included 226 patients with the primary diagnosis of spontaneous ICH from our stroke database between 2010 and 2013; in the NIS , 42 077 patients met inclusion criteria. Logistic regression was used to assess differences in predictors of mortality in blacks compared to whites. In our clinical stroke database, Glasgow Coma Scale ( GCS ; P =0.016), ICH volume ( P =0.013), intraventricular haemorrhage ( IVH ; P =0.023), and diabetes mellitus ( P =0.037) were predictors of mortality in blacks, whereas GCS ( P =0.007), ICH volume ( P =0.005), age ( P =0.002), chronic kidney disease ( P =0.003), and smoking ( P =0.010) predicted mortality in whites. Among patients with IVH , blacks had over 7 times higher odds of mortality compared to whites (odds ratio [ OR ], 7.27; P value for interaction, 0.017) and were more likely to present with hydrocephalus ( OR , 2.76; P =0.026). In the NIS , black ICH patients had higher rates of external ventricular drain ( EVD ) placement compared to whites (9.7% vs 5.0%; P OR , 1.32; 95% CI , 1.20–1.46). Comparison of a race‐specific ICH score to the original ICH score showed that the various ICH score components have differential relevance for ICH score performance by race. Conclusions IVH and age differentially predict mortality among blacks and whites. Blacks have higher rates of obstructive hydrocephalus and more frequently require EVD placement compared to their white counterparts.

Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort. A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis. Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P

INTRODUCTION: Primary central nervous system vasculitis (PCNSV) is a rare inflammatory arteriopathy confined to the brain, spinal cord, and leptomeninges. Because of its nonspecific presentation and difficulties in making a positive diagnosis, empiric treatment is often instituted. CASE SERIES: We report a case series of 5 patients who were admitted or transferred to the Johns Hopkins Hospital with a clinical history and magnetic resonance imaging findings suggestive of PCNSV. Four patients had received at least 1 course of immunosuppression with high-dose intravenous (IV) corticosteroids and/or a corticosteroid-sparing agent. Each underwent an extensive workup including 4-vessel cerebral angiography and, in the majority of cases, brain biopsy to evaluate for mimics of PCNSV. In each of the 5 cases, an alternative diagnosis was found. CONCLUSIONS: We propose a cautious, multistep approach to the diagnosis of PCNSV, which takes into account more common diagnoses and avoids the pitfalls of empiric treatment.

Background and Purpose— Superficial siderosis is a neurodegenerative disease caused by toxic accumulation of hemosiderin on the surface of the brain and spinal cord for which there is no known effective treatment. Methods— Oral deferiprone, a lipid-soluble iron chelator with ability to cross the blood–brain barrier, at a dose of 30 mg/kg per day was tested for safety in an open pilot study in 10 subjects with superficial siderosis. Results— Over a 90-day period, deferiprone had no significant adverse effects on hematologic, liver, or neurological function. Ad hoc MRI assessments of the brain indicated a reduction in hemosiderin deposition in some subjects. Conclusions— Deferiprone proved safe in this small population of superficial siderosis subjects. There was MRI evidence of reduced hemosiderin deposition with deferiprone. Prospectively designed efficacy studies are necessary to determine the clinical efficacy of deferiprone in superficial siderosis.

Background Patients receiving intravenous thrombolysis (IVT) for acute ischemic stroke are at risk of developing complications, commonly necessitating admission to an intensive care unit (ICU). At present, most IVT is administered in the Emergency Department or in dedicated stroke units, but no evidence-based criteria exist that allow for early identification of patients at increased risk of developing ICU needs. The present study describes a novel prediction score aiming to identify a subpopulation of post-IVT patients at high risk for critical care interventions. Methods We retrospectively analyzed data from 301 patients undergoing IVT at our institutions during a 5-year period. Two hundred and ninety patients met inclusion criteria. The sample was randomly divided into a development and a validation cohort. Logistic regression was used to develop a risk score by weighting predictors of critical care needs based on strength of association. Results Seventy-two patients (24.8 %) required critical care interventions. Black race (odds ratio [OR] 3.81, p =0.006), male sex (OR 3.79, p =0.008), systolic blood pressure (SBP; OR 1.45 per 10 mm Hg increase in SBP, p 200 mm Hg), and NIHSS (1 point if 7–12; 2 points if >12). Each 1-point increase in the score was associated with 2.22-fold increased odds for critical care needs (95 % CI 1.78–2.76, p

Background and Purpose— Intravenous alteplase (rtPA) remains the only approved treatment for acute ischemic stroke, but its use remains limited. In a previous pilot dose-escalation study, intravenous tenecteplase showed promise as a potentially safer alternative. Therefore, a Phase IIB clinical trial was begun to (1) choose a best dose of tenecteplase to carry forward; and (2) to provide evidence for either promise or futility of further testing of tenecteplase versus rtPA. If promise was established, then the trial would continue as a Phase III efficacy trial comparing the selected tenecteplase dose to standard rtPA. Methods— The trial began as a small, multicenter, randomized, double-blind, controlled clinical trial comparing 0.1, 0.25, and 0.4 mg/kg tenecteplase with standard 0.9 mg/kg rtPA in patients with acute stroke within 3 hours of onset. An adaptive sequential design used an early (24-hour) assessment of major neurological improvement balanced against occurrence of symptomatic intracranial hemorrhage to choose a “best” dose of tenecteplase to carry forward. Once a “best” dose was established, the trial was to continue until at least 100 pairs of the selected tenecteplase dose versus standard rtPA could be compared by 3-month outcome using the modified Rankin Scale in an interim analysis. Decision rules were devised to yield a clear recommendation to either stop for futility or to continue into Phase III. Results— The trial was prematurely terminated for slow enrollment after only 112 patients had been randomized at 8 clinical centers between 2006 and 2008. The 0.4-mg/kg dose was discarded as inferior after only 73 patients were randomized, but the selection procedure was still unable to distinguish between 0.1 mg/kg and 0.25 mg/kg as a propitious dose at the time the trial was stopped. There were no statistically persuasive differences in 3-month outcomes between the remaining tenecteplase groups and rtPA. Symptomatic intracranial hemorrhage rates were highest in the discarded 0.4-mg/kg tenecteplase group and lowest (0 of 31) in the 0.1-mg/kg tenecteplase group. Neither promise nor futility could be established. Conclusion— This prematurely terminated trial has demonstrated the potential efficiency of a novel design in selecting a propitious dose for future study of a new thrombolytic agent for acute stroke. Given the truncation of the trial, no convincing conclusions can be made about the promise of future study of tenecteplase in acute stroke.

Chik et al. describe the case of a woman who developed a severe 'thunderclap' headache, followed by generalized tonic–clonic seizures, shortly after giving birth. A head CT scan revealed a subarachnoid hemorrhage, and an angiogram showed areas of vasoconstriction in the cerebral arteries that were consistent with a diagnosis of postpartum cerebral angiopathy. Background. A 33-year-old woman experienced a thunderclap headache immediately postpartum. The headache recurred over the next 10 days, and the patient also developed generalized tonic–clonic seizures. A subarachnoid hemorrhage was demonstrated on a head CT scan. Investigations. Physical examination, laboratory tests, brain CT scan, brain MRI scan, brain magnetic resonance angiogram, brain magnetic resonance venogram, cerebral angiography, transcranial Doppler ultrasound, EEG. Diagnosis. Postpartum cerebral angiopathy. Management. NSAIds and opioid analgesics administered on postpartum day 3 provided partial headache relief. The next day, a blood patch was performed and intravenous caffeine, fluid and opioid analgesia were given to treat a suspected dural puncture headache. Following diagnosis of postpartum cerebral angiopathy on postpartum day 10, nimodipine was initiated to treat the vasospasm, and the headache was treated with opioid analgesics and toradol, followed by naproxen. The patient also received a 3-day course of intravenous magnesium sulfate.

Background: The patterns on diffusion-weighted (DWI) MRI may be predictive of stroke etiology. In this retrospective study, we assessed whether DWI bright lesions termed ‘pearls’ predicted the presence of large-vessel arterial stenosis as the etiology of stroke. Methods: All stroke and transient ischemic attack admissions to an academic hospital over a 2-year period were reviewed. Patients without DWI, with hemorrhagic strokes or with nonvascular disease were excluded. Two vascular neurologists reviewed medical records and classified the probable stroke etiology by modified TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. Another investigator, blinded to the clinical diagnoses, reviewed MRI images only. A ‘pearl’ was defined as a DWI bright lesion 20 mm or less in diameter. A ’string of pearls’ was defined as 3 or more pearls in a line found unilaterally in the anterior circulation. ‘Scattered pearls’ were classified as 3 or more pearls distributed such that no single line could connect them, also found unilaterally in the anterior circulation. Results: Fifty-six percent of the patients with either ‘pearls’ sign were classified as TOAST 1 or 2, with this classification only found in 33% of the patients with other DWI patterns (p = 0.0009). If either ‘pearl’ sign was seen on MRI, a patient was 2.65 times (95% CI = 1.32–5.32) more likely to have either extracranial or intracranial large-vessel stenosis. Conclusions: The presence of either ‘string of pearls’ or ‘scattered pearls’ on MRI was associated with an independently determined mechanism of intracranial or extracranial arterial stenosis. In patients with acute stroke distributions consistent with either of these patterns, additional vascular imaging should be considered.

For acute stroke patients who arrive at the hospital within 3 h of symptom onset, the focus of care involves screening for eligibility to receive intravenous tissue plasminogen activator. The publication of the National Institute of Neurological Disorders and Stroke recombinant tissue-type plasminogen activator (tPA, or alteplase) study in 1995 (Marler, J.R. 1995, New England Journal of Medicine333: 1581-1587) spurred protocol changes, which continue to evolve, throughout the health care system in an effort to streamline the patient through the Emergency Medical System. The need to expedite patient evaluation involving emergency department, laboratory, radiology, and clinical neurology testing is clear and has been a focus of many stroke centers. For some patients, intravenous thrombolysis within 3 h has a dramatic effect on outcome. However, that is not the only course of action for acute stroke patients. This article will review some of the effective treatments for stroke patients beyond the first 3 h of their care.

Background and Purpose: Diffusion–perfusion mismatch has been used to estimate salvageable tissue and predict potential for recovery in acute stroke. Location of the salvageable tissue may be as important as volume or percentage in predicting potential for recovery of specific functions. Impaired naming, a common and disabling deficit after left hemisphere stroke, is often associated with tissue dysfunction of left Brodmann area (BA) 37, posterior inferior temporal cortex. We tested the hypothesis that the presence of diffusion–perfusion mismatch within left BA 37 predicts probability and extent of short-term improvement of naming. Methods: One hundred five patients with acute left hemisphere ischemic stroke had diffusion-weighted imaging, perfusion-weighted imaging, a test of picture naming, and other language tests at admission and 2 to 4 days later. Linear regression was used to determine whether diffusion–perfusion mismatch in any BA in language cortex, total volume of mismatch, or diffusion or perfusion abnormality predicted degree of improvement in naming by days 3 to 5. Results: The presence of >20% diffusion–perfusion mismatch in left BA 37 and total volumes of diffusion and perfusion abnormality at day 1 each independently predicted degree of improvement in naming. Mismatch in this area did not predict the degree of improvement in other language tests or the NIH Stroke Scale in this study. Conclusions/Relevance: Diffusion–perfusion mismatch in left Brodmann area 37 was strongly associated with acute improvement in naming, independently of volume or percentage of total mismatch or diffusion or perfusion abnormality. These data indicate that mismatch in a particular area is a marker of salvageable tissue and an important predictor of potential for recovery of functions that depend on that area. Location of mismatch before treatment may help to predict potential benefits of reperfusion. GLOSSARY: ADC = apparent diffusion coefficient; BA = Brodmann area; DWI = diffusion-weighted imaging; NIHSS = NIH Stroke Scale; PWI = perfusion-weighted imaging; TE = echo time; TR = repetition time; TTP = time to peak.

Stroke patients undergoing intravenous thrombolysis (IVT) are at increased risk for critical care interventions and mortality. Cardiac troponin elevation is common in stroke patients; however, its prognostic significance is unclear. The present study evaluates troponin elevation as a predictor of critical care needs and mortality in post-IVT patients and describes racial differences in its predictive accuracy.Logistic regression and receiver operating characteristics (ROC) analysis were used to determine racial differences in the predictive accuracy of troponin elevation for critical care needs and mortality in post-IVT patients.Troponin elevation predicted critical care needs in white (odds ratio [OR] 29.40, 95% confidence interval [CI] 4.86-177.81) but not black patients (OR 0.50, 95% CI 0.14-1.78; P value for interaction.001). Adding troponin elevation to a prediction model for critical care needs in whites improved the area under the curve from 0.670 to 0.844 (P = .006); however, addition of troponin elevation did not improve the model in blacks (area under the curve 0.843 vs 0.851, P = .54). Troponin elevation was associated with in-hospital mortality in whites (OR 21.94, 95% CI 3.51-137.11) but not blacks (OR 1.10, 95% CI 0.19-6.32, P value for interaction .022).Troponin is a useful predictor of poor outcome in white but not black post-IVT stroke patients.

Background and Objective: The National Institute of Health Stroke Scale (NIHSS) is the most commonly used metric to evaluate stroke severity and improvement following intervention. Despite its advantages as a rapid, reproducible screening tool, it may be too insensitive to adequately capture functional improvement following treatment. We evaluated the difference in rate of improvement by previously accepted criteria (change of ≥4 NIHSS points) versus physician documentation in patients receiving IV tissue plasminogen activator (tPA) for acute ischemic stroke. Methods: Prospectively collected data on all patients receiving IV tPA over a 15 month period were retrospectively reviewed. NIHSS 24 hours post-treatment and on discharge were extrapolated based on examination and compared to NIHSS on presentation. NIHSS scores at post-discharge follow-up were also recorded. Two reviewers evaluated the medical record and determined improvement based on physician documentation. Using tests of proportion, ‘significant improvement’ by NIHSS was compared to physician documentation at each time point. Results: Forty-one patients were treated with IV tPA. The mean admission NIHSS was 8.6 and improved to 6.4 24 hours post-tPA. Twenty-nine of 41 patients (79%) were “better” by documentation; however only 11/41 (27%) met NIHSS criteria for improvement (p compared to documentation Conclusion: The NIHSS may inadequately capture functional improvement post-treatment, especially in the days immediately following intervention.

Background: Acute ischemic stroke accounts for nearly 800,000 inpatient hospitalizations annually in the United States. Post-discharge disposition varies greatly among stroke survivors. The transition to home or nursing facilities post-hospitalization provides an opportunity to improve quality of life; but also increases the potential for miscommunication between patients, care givers, and health care providers. This may result in the need for hospital readmission, which further complicates patient care. A timely post-discharge neurology clinic visit would be the ideal forum to address miscommunication and reduce readmission. Without dedicated infrastructure, it is difficult to see patients quickly, resulting in a poor follow-up rate. Our Stroke Center sought to improve transitions for stroke survivors with the addition of a neurology nurse case manager, creation of a targeted post-discharge plan, and implementation of the Bayview Stroke Intervention Clinic (BaSIC). Methods: Beginning in September 2013, all patients admitted with acute ischemic stroke were assessed by our case manager prior to discharge and a specific post-discharge plan was developed including a plan for follow-up within 4-6 weeks. This was achieved with the implementation of a weekly neurology clinic dedicated to post-stroke care, staffed by two cerebrovascular neurologists. To gauge the effectiveness of our intervention to improve follow-up rates and decrease hospital readmissions, we retrospectively compared stroke patients discharged in fiscal year 2013 (prior to implementation) to those discharged in 2014. Annual readmission rates as well as follow-up rates in neurology clinic at 30, 60 and 90 day post-discharge intervals were assessed. Results: With implementation of targeted post-discharge planning and BaSIC clinic, the 30 day follow-up rate (2.6% pre versus 8.4% post; p=0.01), 60 day follow-up rate (8.3% pre versus 16% post; p=0.01), and 90 day follow-up rate (14.4% pre versus 20.6% post; p=0.10) all improved. Hospital readmissions fell from 10.5% to 8.7% (p=0.63). Conclusion: Implementation of a targeted post-discharge plan and specialized stroke follow-up clinic decreases readmissions and increases follow-up visits with neurology.

We identified areas of the brain that are critical for naming pictures of objects, using a new methodology for testing which components of a network of brain regions are essential for that task. We identified areas of hypoperfusion and structural damage with magnetic resonance perfusion- and diffusion-weighted imaging immediately after stroke in 87 individuals with impaired picture naming. These individuals were reimaged after 3–5 d, after a subset of patients underwent intervention to restore normal blood flow, to determine areas of the brain that had reperfused. We identified brain regions in which reperfusion was associated with improvement in picture naming. Restored blood flow to left posterior middle temporal/fusiform gyrus, Broca's area, and/or Wernicke's area accounted for most acute improvement after stroke. Results show that identifying areas of reperfusion that are associated with acute improvement of a function can reveal the brain regions essential for that function.

Background and Purpose— Dysphagia after intracerebral hemorrhage (ICH) contributes significantly to morbidity, often necessitating placement of a percutaneous endoscopic gastrostomy (PEG) tube. This study describes a novel risk prediction score for PEG placement after ICH. Methods— We retrospectively analyzed data from 234 patients with ICH presenting during a 4-year period. One hundred eighty-nine patients met inclusion criteria. The sample was randomly divided into a development and a validation cohort. Logistic regression was used to develop a risk score by weighting predictors of PEG placement based on strength of association. Results— Age (odds ratio [OR], 1.64 per 10-year increase in age; 95% confidence interval [CI], 1.02–2.65), black race (OR, 3.26; 95% CI, 0.96–11.05), Glasgow Coma Scale (OR, 0.80; 95% CI, 0.62–1.03), and ICH volume (OR, 1.38 per 10-mL increase in ICH volume) were independent predictors of PEG placement. The final model for score development achieved an area under the curve of 0.7911 (95% CI, 0.6931–0.8892) in the validation group. The score was named the GRAVo score: Glasgow Coma Scale ≤12 (2 points), Race (1 point for black), Age >50 years (2 points), and ICH Volume >30 mL (1 point). A score >4 was associated with ≈12× higher odds of PEG placement when compared with a score ≤4 (OR, 11.81; 95% CI, 5.04–27.66), predicting PEG placement with 46.55% sensitivity and 93.13% specificity. Conclusions— The GRAVo score, combining information about Glasgow Coma Scale, race, age, and ICH volume, may be a useful predictor of PEG placement in ICH patients.

Background and Purpose — Early reperfusion is a predictor of good outcome in acute ischemic stroke. We investigated whether middle cerebral artery (MCA) occlusions have a better clinical outcome and proportion of recanalization compared with internal carotid artery (ICA) occlusion after standard treatment with intravenous (IV) tissue plasminogen activator (tPA). Patients — In a retrospective analysis of our prospective stroke database between January 7, 1998, and January 30, 2002, we identified 36 consecutive patients who were treated with IV tPA within 3 hours after symptom onset of a stroke in the distribution of a documented ICA or MCA occlusion. The National Institutes of Health Stroke Scale (NIHSS) score was recorded before tPA, at 24 hours, 3 days, and 3 months after stroke. Three-month outcome was recorded by modified Rankin scale. Magnetic resonance angiography or computed tomographic angiography was obtained before tPA. The presence of recanalization was assessed by transcranial Doppler and/or magnetic resonance angiography within 3 days after stroke onset. Results — Nineteen patients had MCA occlusion, and 17 had ICA-plus-MCA occlusion before tPA. Although there was no difference in age and NIHSS at day 0 between the 2 groups, the MCA group had a lower day 3 NIHSS score compared with the ICA group ( P =0.006) in an ANCOVA. In addition, patients who had a MCA occlusion had lower day 1 and 3 NIHSS scores compared with the ICA group ( P =0.04 and P =0.03, respectively; Wilcoxon rank sum). Similarly, NIHSS was significantly lower in patients who recanalized on days 1 and 3 ( P =0.004 and P =0.003 respectively, Wilcoxon rank sum). When we adjusted for NIHSS score at day 0 in an ANCOVA, the adjusted mean was lower in the group that recanalized compared with the group that did not recanalize ( P P =0.001, Fisher exact test). The 3-month modified Rankin scale was not different between the 2 groups. Conclusions — Despite comparable age and NIHSS scores before IV tPA, MCA occlusions have lower day 1 and 3 NIHSS scores and higher proportion of recanalization compared with ICA occlusions. A combined IV/intra-arterial or mechanical thrombolysis may be needed to achieve early recanalization in ICA occlusions.

Intravenous tissue plasminogen activator is the mainstay for the treatment of acute ischemic stroke in patients presenting within 4.5 hours of symptom onset. Studies have demonstrated that treating patients early leads to improved long term outcomes. MR imaging currently allows quantification of the ischemic penumbra in order to better identify individuals most likely to benefit from intervention, irrespective of “time last seen normal.” Its increasing use in clinical practice has demonstrated individual differences in rate of infarction. One explanation for this variability is a difference in collateral blood flow. We report two cases that highlight the individual variability of infarction rate, and discuss potential underlying mechanisms that may influence treatment decisions and outcomes.

Background: Hypertension damages small vessels, resulting in both lacunar infarction and subcortical intracerebral hemorrhage (ICH). Substance abuse has also been linked to small vessel pathology. This study explores whether the use of specific substances (e.g., cocaine, tobacco) is associated with subcortical ICH over ischemia in hypertensive individuals. Methods: Patients with hypertension, admitted with lacunar infarcts (measuring 1 drink per day (women), >2 drinks per day (men). Logistic regression was performed with ICH as the dependent variable comparing those presenting with ICH to those presenting with ischemia. Results: Of the 580 patients included in analysis, 217 (37%) presented with ICH. The average age was similar between the two groups (64.7 versus 66.3 years). Illicit/controlled drug use was associated with a significantly increased risk of ICH over stroke in unadjusted models (25 versus 15%, p = 0.02), with the largest effect seen in users ≥65 years old (not statistically significant). Smoking was associated with ischemia over ICH in a dose-dependent manner: any history of smoking OR 1.84, CI 1.19–2.84; current use OR 2.23, CI 1.37–3.62; heavy use OR 2.48, CI 1.50–4.13. Alcohol use was not preferentially associated with either outcome (p = 0.29). Conclusion: In hypertensive patients, tobacco use is associated with an increased risk of subcortical ischemia compared to ICH, while use of illicit/controlled substances appears to be predictive of hemorrhage.

Objective: To compare how at-risk tissue and core infarction were defined in two major trials that tested the use of MRI in selecting acute stroke patients for endovascular recanalization therapy. Methods: MRIs from 12 patients evaluated for possible endovascular therapy were processed using the methods published from two major trials, MR RESCUE and DEFUSE 2. Specifically, volumes of at-risk tissue and core infarction were generated from each patient’s MRI. MRIs were then classified as whether or not they met criteria for salvageable tissue: “penumbral pattern” for MR RESCUE and/or “target profile” for DEFUSE 2 as defined by each trial. Results: Volumes of at-risk tissue measured by the two definitions were correlated (p = 0.017) while the volumes of core infarct were not (p = 0.059). The volume of at-risk tissue was consistently larger when defined by the penumbral pattern than the target profile while the volume of core infarct was consistently larger when defined by the target profile than the penumbral pattern. When these volumes were used to classify the MRI scans, 9 out of 12 patients (75%) were classified as having a penumbral pattern, while only 4 out of 12 patients (33%) were classified as having a target profile. Of the 9 patients classified as penumbral pattern, 5 (55%) were classified differently by the target profile. Interpretation: Our analysis found that the MR RESCUE trial defined salvageable tissue in a way that made it more likely for patients be labeled as favorable for treatment. For the cohort of patients examined in this study, had they been enrolled in both trials, most of the patients identified as having salvageable tissue by the MR RESCUE trial would not have been considered to have salvageable tissue in the DEFUSE 2 trial. Caution should be taken in concluding that MRI selection for endovascular therapy is not effective as imaging selection criteria were substantially different between the two trials.

The results of trials that study patients with defined lesions (atrial fibrillation without valvular heart disease, various severities of carotid artery stenosis in the neck, intracranial artery stenosis) are very helpful for clinicians caring for patients with those conditions. On the other hand, trials that group all patients with brain ischemia together are not very helpful. Modern technology now makes it possible to define quickly and safely: (1) the location, nature, and severity of causative cerebrovascular, cardiac, and aortic lesions; (2) blood constituents and coagulability; and, (3) the presence, location, and severity of ischemic brain damage. As in all medicine, treatment should be aimed at the cause of disease, not the time course and severity of present damage. Clearly, more trials are needed in patients who have been studied thoroughly using modern technology. Until then, clinicians must understand the context of the trial data to determine if the results are applicable to Mr. or Ms. Jones, and the patients sitting before them in the office or in the hospital bed.

The average age of patients undergoing cardiac surgery and the number of comorbidities they possess will continue to increase as surgical technology advances. Toxic/metabolic encephalopathy, hemispheric strokes, hypoxic injury, and peripheral nerve lesions all can occur as a result of cardiac surgery. Therefore, an understanding of the neurologic risk, recognizable syndromes, and preventative measures will continue to be important. Careful preoperative assessment, operative risk factor reduction, and careful postoperative assessments and management may reduce the neurologic risk for cardiac surgery.

Symptomatic intracranial hemorrhage (sICH) is a known complication following administration of intravenous tissue plasminogen activator (IV tPA) for acute ischemic stroke. sICH results in high rates of death or long-term disability. Our ability to predict its occurrence is important in clinical decision making and when counseling families. The initial National Institute of Neurological Disorders and Stroke (NINDS) investigators developed a list of relative contraindications to IV tPA meant to decrease the risk of subsequent sICH. To date, the impact of renal impairment has not been well studied. In the current study we evaluate the potential association between renal impairment and post-tPA intracranial hemorrhage (ICH). Admission serum creatinine and estimated glomerular filtration rate (eGFR) were recorded in 224 patients presenting within 4.5 hours from symptom onset and treated with IV tPA based on NINDS criteria. Neuroimaging was obtained 1 day post-tPA and for any change in neurologic status to evaluate for ICH. Images were retrospectively evaluated for hemorrhage by a board-certified neuroradiologist and 2 reviewers blinded to the patient’s neurologic status. Medical records were reviewed retrospectively for evidence of neurologic decline indicating a “symptomatic” hemorrhage. sICH was defined as subjective clinical deterioration (documented by the primary neurology team) and hemorrhage on neuroimaging that was felt to be the most likely cause. Renal impairment was evaluated using both serum creatinine and eGFR in a number of ways: 1) continuous creatinine; 2) any renal impairment by creatinine (serum creatinine >1.0 mg/dL); 3) continuous eGFR; and 4) any renal impairment by eGFR (eGFR 1.0 mg/dL) was not associated with combined symptomatic and asymptomatic intracranial bleeding (p = 0.359); however, there was an adjusted 5.5-fold increased odds of sICH when creatinine was >1.0 mg/dL (95% confidence interval, 1.08–28.39), and the frequency of sICH for patients with elevated serum creatinine was 10.6% (12/113), versus 1.8% (2/111) in those with normal renal function (p = 0.010). Our study suggests that renal impairment is associated with higher risk of sICH after administration of IV tPA. As IV tPA is an important and effective treatment for acute ischemic stroke, a multicenter study is needed to determine whether the observation that renal dysfunction is associated with sICH from this retrospective study holds true in a larger prospective trial.

BACKGROUND AND PURPOSE: Intravenous (IV) tissue plasminogen activator (tPA) is the only Food and Drug Administration (FDA)-approved treatment for acute ischemic stroke. Post tPA patients are typically monitored in an intensive care unit (ICU) for at least 24 hours. However, rigorous evidence to support this practice is lacking. This study evaluates factors that predict ICU needs after IV thrombolysis. METHODS: A retrospective chart review was performed for 153 patients who received intravenous tPA for acute ischemic stroke. Data on stroke risk factors, physiologic parameters on presentation, and stroke severity were collected. The timing and nature of an intensive care intervention, if needed, was recorded. Using multivariable logistic regression, we determined factors associated with requiring ICU care. RESULTS: African American race (Odds Ratio [OR] 8.05, 95% Confidence Interval [CI] 2.65-24.48), systolic blood pressure, and National Institutes of Health Stroke Scale (NIHSS) (OR 1.20 per point increase, 95% CI 1.09-1.31) were predictors of utilization of ICU resources. Patients with an NIHSS≥10 had a 7.7 times higher risk of requiring ICU resources compared to patients who presented with an NIHSS

In this issue of Neurology ®, a report from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study1 indicates that albuminuria, but not estimated glomerular filtration rate (eGFR), independently predicted stroke events, particularly in black participants. Black participants who had a stroke were 5 times more likely …

Introduction: Many patients with acute ischemic stroke also have an indication for anticoagulation. A major concern in these patients is whether they are at increased risk for intracranial bleeding, and if so, what factors further increase their risk. We evaluated stroke patients with an indication for anticoagulation to determine what factors are associated with increased risk of intracranial bleeding. Methods: Patients presenting with acute ischemic stroke and an indication for anticoagulation were included in analysis. Data were collected in the following categories: demographics (age, race, gender), medical profile (blood pressure, glycemic control, statin use/LDL, renal function [divided into GFR categories- 0: GFR ≥60, 1: GFR 30-59, or 2: GFR Results: 143 patients (mean age 63.5 years) met criteria and were included in analysis. 117 were placed on anticoagulation. The most common indications for anticoagulation were atrial fibrillation (35.6%), deep vein thrombosis (27.3%), presence of a hypercoagulable state (18.2%), and pulmonary embolism (17.5%). The difference in bleeding rates between those placed on anticoagulation and those treated with an antiplatelet agent was not statistically significant (25.6% versus 23.1%, χ2=0.785), but all of the intracranial hemorrhages (n=8) and symptomatic bleeds (n=9) occurred in the anticoagulated group. Age (OR= 1.31 per 10 year increment, 95% CI 0.98-1.74), volume (OR= 1.13 per 10 cc’s, 95% CI 1.05-1.21), and worsening GFR category (OR= 1.81, 95% CI 1.01-3.26) were predictors of intracranial bleeding. Odds of hemorrhage was predicted by exponentiating the equation: -3.823563 + (0.0120706)*(Volume) + (0.5939482)*(GFR Category) + (0.0266442)*(Age). Probability of hemorrhage can then be calculated. Conclusions: Probability of intracranial bleeding in patients with acute ischemic stroke and an indication for anticoagulation can be calculated based on an individual’s age, stroke volume, and GFR. This score can be used to assist with prognosis and clinical management. While anticoagulation does not appear to increase risk of bleeding, it does tend to result in larger, more symptomatic bleeds.

Objective To evaluate whether EEG performed within 30min of referral by an ED physician helps establish diagnosis and/or changes management and in which clinical setting. Methods Single-center prospective cohort intervention study 1day/week, of sequentially referred adult patients with clinical seizures or altered mental status (AMS). Standard EEGs were performed by an EEG technician using a commercially available cap, interpreted by an epileptologist, immediately reported to the ED physician and a utility survey completed. Quality and interpretation of 20min EEGs was compared to pre-specified 5min segments of each EEG using the kappa coefficient. Results Over 1year, 82 patients underwent ED EEG. Tonic clonic seizure activity had occurred in 33%. Mean time for EEG setup was 13.1±6.2min. EEG assisted the diagnosis in 51%, changed ED management in 4% and would be ordered again if EEG was available in 46%. Positive utility of EEG was significantly associated with toxicologic, psychiatric and endocrine/metabolic causes of AMS vs. other causes ( p p =0.007). Independent predictors of whether ED EEG would be ordered if available were witnessed seizures ( p =0.01), no prior head trauma ( p =0.001) and survey respondent being a physician assistant (vs. MD) ( p =0.02). The 5 (vs. 20) min EEG presented good agreement on waveform shape/amplitude (kappa=0.78), artifact (kappa=0.75) and interpretation categories (all kappa levels ⩾0.70). Conclusions Rapid availability of standard full-montage EEG in the ED is feasible and helps establish a diagnosis in about half of AMS patients, but rarely changes management. An abbreviated 5min full-montage EEG presents adequate reliability which may improve use in the ED. Significance Specific presentations of AMS offer the best diagnostic benefit for EEG in the ED.

Acute ischemic stroke is a common disorder with a significant impact on morbidity and mortality in the United States. The number of interventions for acute stroke patients has increased over the past 15 years and patients increasingly require intensive care. There are several issues that are specific to ischemic stroke patients in intensive care unit (ICU) settings, including the care of the postthrombolytic stroke patient, respiratory issues in stroke care, evaluation of worsening or change in neurological status, and attention to factors that affect the ischemic penumbra. The management of the stroke patient in the critical care setting is discussed in this article.

The treatment of acute stroke changed dramatically since the publication of the NINDS trail for IV rt-PA for acute stroke. While this was not the first trial, it was the first positive trial. Subsequently there has been an explosion in acute treatment modalities since the NINDS trial showed that acute stroke treatment is feasible. The following chapter reviews the thrombolysis trials, the inclusion and exclusion criteria of intravenous and intra-arterial use of pharmacologic and mechanical thrombolysis in acute ischemic stroke. Also discussed are the new pharmacotherapies and mechanical devices that will hopefully expand the treatment window and make thrombolysis safer and more effective.

Background and Purpose Patients who receive intravenous (IV) tissue plasminogen activator (tPA) for ischemic stroke are currently monitored in an intensive care unit (ICU) or a comparable stroke unit for at least 24 hours due to the high frequency of neurological exams and vital sign checks. The present study evaluates ICU needs in patients with diffusion-weighted imaging (DWI) negative MRI after IV tPA. Methods A retrospective chart review was performed for 209 patients who received IV tPA for acute stroke. Data on stroke risk factors, physiologic parameters, stroke severity, MRI characteristics, and final diagnosis were collected. The timing and nature of ICU interventions, if needed, was recorded. Multivariable logistic regression was used to determine factors associated with subsequent ICU needs. Results Patients with cerebral infarct on MRI after tPA had over 9 times higher odds of requiring ICU care compared to patients with DWI negative MRI (OR 9.2, 95% CI 2.49–34.15). All DWI negative patients requiring ICU care did so by the end of tPA infusion (p = 0.006). Among patients with DWI negative MRI, need for ICU interventions was associated with higher NIH Stroke Scale (NIHSS) scores (p