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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.

The use of telemedicine has increased significantly during the Corona virus disease 2019 pandemic. This manuscript serves to identify the underlying principles of clinical excellence in telemedicine and to determine whether effective care practices can be generalized as a one-size-fits-all model or must instead be tailored to individual patient populations.A survey assessing care quality and patient satisfaction for patients using telemedicine was created and administered via email to 2 urban cohorts of varying demographics and socioeconomic backgrounds: a population of patients with prior stroke and cerebrovascular disease, and a cohort of patients followed for interstitial lung disease. Results were compared across groups to determine the generalizability of effective practices across populations.Individuals taking part in telemedicine were more likely to be White, more affluent, and woman, regardless of clinical diagnosis compared with a similar cohort of patients seen in-person the year prior. A lower-than-expected number of patients who were Black and of lower socioeconomic status followed up virtually, indicating potential barriers to access. Overall, patients who participated in televisits were satisfied with the experience and felt that the care met their medical needs; however, those who were older were more likely to experience technical difficulties and prefer in-person visits, while those with less education were less likely to feel that their questions were addressed in an understandable way.When thoughtfully designed, telemedicine practices can be an effective model for patient care, though implementation must consider population characteristics including age, education, and socioeconomic status, and strategies such as ease of access versus optimization of communication strategies should be tailored to meet individual patient needs.

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.

Burnout is a syndrome defined by 3 principal components: emotional exhaustion, depersonalization, and diminished feelings of personal accomplishment.1 Burnout negatively affects patient care, affects patient safety, and results in deleterious effects on practitioners.2 A recently published article reports that 73% of neurology residents describe at least one symptom of burnout.3

To investigate patterns of neurologic "awakening" in out-of-hospital cardiac arrest (OHCA) patients using different criteria for prognostication post-arrest.Data was collected on 194 OHCA survivors to hospital admission. Patients were assigned to one of two groups based on whether they received therapeutic hypothermia (TH). Three separate criteria were used to assess neurologic "awakening": motor-GCS=6, total-GCS ≥ 9, and CPC=1 or 2. Demographics, arrest characteristics and intensive care events were compared using unpaired t-test, Chi-square or nonparametric Wilcoxon rank-sum test as appropriate. Primary outcome was the time from arrest to neurologic awakening.Of 194 OHCA survivors, TH was implemented in 94 patients (48%). Compared to conventional care patients, hypothermia treated patients were more likely to be younger (58 vs. 69 years, p0.01),), and have a shockable arrest rhythm (27% vs. 10%, p0.01). Using the three criteria (m-GCS=6, t-GCS ≥ 9CPC=1 or 2), median time to awakening for patients in the hypothermia group versus the conventional therapy group were 6 [4,9] vs. 3 [2,5] days, 3 [3,5] vs. 2 [2,3] days, and 3 [3,6] vs. 2 [2,4] days respectively (all p0.01) and prognostication using these criteria on day 3 yielded discordant results about which patients achieved awakening.Patients undergoing therapeutic hypothermia achieve meaningful neurologic "awakening" beyond 72 h post-arrest. Use of different criteria for the assessment of neurologic "awakening" can yield different prognostication predictions which calls for standardization and validation of a single definition of "awakening" by the resuscitation community.

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.

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 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.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 each0.02), and differences persisted in multivariable regression models.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.

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.

Introduction: Contraindications for intravenous thrombolysis are not infrequent (eg. anticoagulation, recent surgery, unclear last known well). With overwhelming recent evidence supporting the use of endovascular thrombectomy for large-vessel occlusive stroke, we conducted a metaanalysis to compare long-term functional outcome between thrombectomy-alone versus combined IV-tPA and thrombectomy. Hypothesis: Patients with acute ischemic stroke ineligible for IV-tPA treated with thrombectomy-alone have equally favorable long-term functional outcomes to patients treated with combined IV-tPA and thrombectomy Methods: Searched PubMed from 2014-2016 using pre-specified terms for studies that report odds ratio of improvement in mRS score at 90 days comparing thrombectomy vs IV-tPA stratified by whether patients had received IV-tPA. Multivariate adjusted odds ratios were used for the metaanalysis. Pooled odds ratio estimates across trials were synthesized by using a random-effects model based on Mantel-Haenszel methods. The pooled estimates were compared between thrombectomy-alone and combined IV-tPA and thrombectomy. Forest plots constructed. Results: Of the 920 studies, 3 studies reported subgroup analysis with 822 participants, 19.5% (N=160) received thrombectomy-alone, 80.5% (N=662) received combined IV-tPA and thrombectomy. Among patients who received thrombectomy-alone, the pooled odds ratio of good functional outcome at 3 months was 2.48 (1.43-4.30), in the combined IV-tPA and thrombectomy group the pooled odds ratio was 1.85 (1.37-2.49). Conclusions: Endovascular therapy was an effective therapy for patients ineligible for IV-tPA presenting with acute ischemic stroke caused by large vessel occlusive disease. While IV-tPA should not be withheld before thrombectomy in IV-tPA eligible patients, prospective studies are needed to select those who may benefit more from thrombectomy-only treatment.

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.

I thank Dr. Robbins for the comment on our Residency Training article.1 We agree with the concept that patients that appear ungrateful contribute to burn out. It does not serve as a victory, even if great effort and time is put into treating them.

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.

Recombinant tissue plasminogen activator (t-PA) is the only FDA approved therapy for acute ischemic stroke. Cerebral microbleeds (CMBs) or cerebral amyloid angiopathy (CAA) are currently not contraindications, however, data regarding this complex issue are limited. We report 2 cases of fatal intracerebral hemorrhage (sICH) after IV t-PA, each with evidence of CAA. Patients with CAA may have increased risk for IV thrombolysis-associated sICH. We highlight the severe and catastrophic pattern of ICH, which may be a defining characteristic, and discuss the limitations of our current understanding of the risk of thrombolysis-associated ICH in patients with CAA and/or CMBs.

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.