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Background: Patients with high-grade symptomatic intracranial stenosis (≥70%) have an increased risk of recurrent stroke despite medical treatment with antiplatelet or anticoagulant therapy. Intracranial stenting has been proposed as a viable treatment option for this high-risk patient population; however, evaluation of this therapy in randomized multicenter trials is needed. In this article, we present the design and methods of the Vitesse Intracranial Stent Study for Ischemic Therapy (VISSIT) trial for symptomatic intracranial stenosis. Methods: The VISSIT trial is a randomized control study designed to evaluate the safety, probable benefit, and effectiveness of the PHAROS Vitesse neurovascular balloon-expandable stent system plus medical therapy versus medical therapy alone in patients with cerebral or retinal ischemia due to neurovascular stenosis (≥70%) for preventing the primary composite end point: stroke in the same territory (distal to the target lesion) as the presenting event within 12 months of randomization or hard transient ischemic attack in the same territory (distal to the target lesion) as the presenting event from day 2 through month 12 postrandomization. Results: Enrollment began in February 2009 and was halted in January 2012 with 112 subjects enrolled into the study. Clinical follow-up will continue for the planned period of 12 months postrandomization. Conclusions: The VISSIT trial may provide valuable insight into the use of balloon-expandable intracranial stent as a treatment option for high-risk patients. Lessons learned from this trial may better guide future clinical trial design on best patient selection, stenting techniques, and periprocedural management. [Copyright &y& Elsevier]

Background: To date, no ischemic stroke outcome prediction scores have been validated for use in the setting of both endovascular and non-endovascular stroke treatments. The Totaled Health Risks in Vascular Events (THRIVE) score has been previously validated in patients undergoing endovascular stroke treatment, and we hypothesized that it would perform similarly well in patients receiving intravenous tissue plasminogen activator (tPA) or no acute therapy. Methods: We compared the performance of the THRIVE score between patients in the National Institutes of Neurological Disorders and Stroke (NINDS) tPA trial and patients in the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trials of endovascular stroke treatment. The predictive performance of the THRIVE score was compared using receiver operator characteristic (ROC) curve analysis. In the NINDS cohort, separate analyses were also performed for patients receiving tPA versus those receiving placebo. Results: ROC curve analysis revealed a good prediction of outcomes across the range of THRIVE scores in both the NINDS and MERCI datasets. As we have previously found in the MERCI datasets, the THRIVE score, which encompasses the National Institutes of Health Stroke Scale (NIHSS) score, age, and chronic disease burden, was a better predictor of outcomes than NIHSS and age alone in the NINDS trial dataset. THRIVE score and tPA administration both strongly predicted outcome, but these effects were statistically independent. Conclusions: The THRIVE score provides accurate prediction of long-term neurologic outcomes in patients with acute ischemic stroke regardless of treatment modality. Both the THRIVE score and tPA administration predict outcome, but the THRIVE score does not influence the impact of tPA on outcome, and tPA administration does not influence the impact of THRIVE score on outcome. [Copyright &y& Elsevier]

Background: There are limited data on the safety of periprocedural heparin in acute ischemic stroke endovascular therapy. Methods: A post hoc analysis was performed on patients enrolled in the Multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI) trial to compare baseline characteristics and clinical outcomes between patients who received periprocedural heparin (HEP+) with patients who did not receive periprocedural heparin (HEP−). Data on periprocedural heparin use or nonuse was collected on patients enrolled between February 1, 2006 and July 31, 2006. Results: Of 51 patients included in the analysis cohort, 24 (47%) received periprocedural heparin with a median dose of 3000 U. Baseline and procedural characteristics were similar between the 2 groups, although HEP+ patients were more likely to have vertebral or basilar occlusion than HEP− patients (16.7% v 0%; P = .04). There was no significant difference in rates of hemorrhage, procedural complications, or 90-day mortality between the 2 groups. In multivariable analysis, a 90-day good outcome (modified Rankin scale score of 0-2) was associated with age (odds ratio [OR] 0.92; 95% confidence interval [CI] 0.86-0.98; P = .0104), final revascularization success (OR 6.86; 95% CI 1.39-33.81; P = .0179), and periprocedural heparin use (OR 5.89; 95% CI 1.34-25.92; P = .0189). Conclusions: In this small subgroup of the Multi MERCI trial, periprocedural heparin use in acute ischemic stroke endovascular therapy was not associated with increased rates of intracerebral hemorrhage or 90-day mortality. The improved 90-day good outcome among patients undergoing mechanical thrombectomy combined with periprocedural heparin warrants further study in a larger cohort. [Copyright &y& Elsevier]

Airway management is central to the resuscitation of the neurologically ill. These patients often have evolving processes that threaten the airway and adequate ventilation. Therefore, airway, ventilation, and sedation were chosen as an Emergency Neurological Life Support (ENLS) protocol. Reviewed topics include airway management; the decision to intubate; when and how to intubate with attention to cardiovascular status; mechanical ventilation settings; and the use of sedation, including how to select sedative agents based on the patient's neurological status. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a subset of stroke resulting from bleeding within the brain parenchyma of the brain. It is potentially lethal, and survival depends on ensuring an adequate airway, reversal of coagulopathy, and proper diagnosis. ICH was chosen as an emergency neurological life support (ENLS) protocol because intervention within the first critical hour may improve outcome, and it is helpful to have a protocol to drive care quickly and efficiently. [ABSTRACT FROM AUTHOR]

Bacterial meningitis and viral encephalitis, particularly herpes simplex encephalitis (HSE), are severe neurological infections that, if not treated promptly and effectively, lead to poor neurological outcome or death. Because treatment is more effective if given early, the topic of meningitis and encephalitis was chosen as an Emergency Neurological Life Support protocol. This protocol provides a practical approach to recognition of and urgent treatment for bacterial meningitis and HSE, including imaging and spinal fluid analysis, and discusses the choice of empirical treatments until the cause of infection is determined. Though uncommon in its full form, the typical clinical triad of headache, fever, and neck stiffness should alert the clinical practitioner to the syndromes. Early attention to the airway and maintaining normotension is crucial in treatment of these patients, as is rapid treatment with anti-infectives and, in some cases, corticosteroids. [ABSTRACT FROM AUTHOR]

Acute non-traumatic weakness may be life-threatening if it involves respiratory muscles or is associated with dysautonomia. Most patients presenting with an acute muscle weakness have a worsening neurologic disorder that requires a rapid, systematic approach, and detailed neurologic localization of the findings. In many patients, urgent laboratory tests are needed and may involve neuroimaging. Because acute weakness is a common presenting sign of neurological emergencies, it was chosen as an Emergency Neurological Life Support protocol. An inclusive list of causes of acute weakness is explored, both by presenting complaint and anatomical location, with an outline of the key features of the history, examination, investigations, and treatment for each diagnosis. [ABSTRACT FROM AUTHOR]

Patients with prolonged or rapidly recurring convulsions lasting more than 5 min are in status epilepticus (SE) and require immediate resuscitation. Although there are relatively few randomized clinical trials, available evidence and experience suggest that early and aggressive treatment of SE improves patient outcomes, for which reason it was chosen as an Emergency Neurologic Life Support protocol. The current approach to the emergency treatment of SE emphasizes rapid initiation of adequate doses of first line therapy, as well as accelerated second line anticonvulsant drugs and induced coma when these fail, coupled with admission to a unit capable of neurologic critical care and electroencephalography monitoring. This protocol not only will focus on the initial treatment of SE but also review subsequent steps in the protocol once the patient is hospitalized. [ABSTRACT FROM AUTHOR]

Acute spinal cord compression (SCC) is the most serious of the diseases of the cord and should be accorded special attention in neurocritical care. Patients with SCC have a combination of motor and sensory dysfunction that has a distribution referable to one, or a few contiguous, spinal levels. Bowel and bladder dysfunction and neck or back pain are usually part of the clinical presentation but are not uniformly present. Because interventions are time-sensitive, the recognition and treatment of SCC was chosen as an ENLS protocol. [ABSTRACT FROM AUTHOR]

Acute ischemic stroke is a neurological emergency that can be treated with time-sensitive interventions, including intravenous thrombolysis and endovascular approaches. Extensive study has demonstrated that rapid assessment and treatment are essential to improving neurological outcome. For this reason, acute ischemic stroke was chosen as an Emergency Neurological Life Support protocol. The protocol focuses on the first hour following the onset of neurological deficit. [ABSTRACT FROM AUTHOR]

Subarachnoid hemorrhage (SAH) is a neurological emergency because it may lead to sudden neurological decline and death and, depending on the cause, has treatment options that can return a patient to normal. Because there are interventions that can be life-saving in the first hour of onset, SAH was chosen as an Emergency Neurological Life Support protocol. [ABSTRACT FROM AUTHOR]

Coma is an acute failure of neuronal systems governing arousal and awareness and represents a neurological emergency. When encountering a comatose patient, the clinician must have an organized approach to detect easily remedial causes, prevent ongoing neurologic injury, and determine a hierarchy of diagnostic tests, treatments, and neuromonitoring. Coma was chosen as an Emergency Neurological Life Support (ENLS) protocol because timely medical and surgical interventions can be life-saving, and the initial work-up of such patients is critical to establishing a correct diagnosis. [ABSTRACT FROM AUTHOR]

Cardiac arrest is the most common cause of death in North America. Neurocritical care interventions, including therapeutic hypothermia (TH), have significantly improved neurological outcomes in patients successfully resuscitated from cardiac arrest. Therefore, resuscitation following cardiac arrest was chosen as an Emergency Neurological Life Support protocol. Patients remaining comatose following resuscitation from cardiac arrest and who are not bleeding are potential candidates for TH. This protocol will review induction, maintenance, and re-warming phases of TH, along with management of TH side effects. Aggressive shivering suppression is necessary with this treatment to ensure the maintenance of a target temperature. Ancillary testing, including electrocardiography, computed tomography imaging of the brain, continuous electroencephalography, monitoring, and correction of electrolyte, blood gas, and hematocrit changes are also necessary to optimize outcomes. [ABSTRACT FROM AUTHOR]

Background: Aphasia is a disabling chronic stroke symptom, but the prognosis for patients presenting with aphasia in the hyperacute window has not been well characterized. The purpose of this study is to assess the prognosis for recovery of language function in subjects presenting with aphasia caused by ischemic stroke within 12 hours of symptom onset. Methods: Subjects presenting with aphasia were identified from a prospective cohort study of 669 subjects presenting emergently with acute stroke. Subjects were characterized by demographics, serial clinical examinations, unenhanced computed tomography, and computed tomographic angiography. Aphasia severity was assessed by National Institutes of Health Stroke Scale (NIHSS) examinations performed at baseline, discharge, and 6 months. Demographic, clinical, and imaging factors were assessed for prognostic impact. Results: Aphasia was present in 30% of subjects (n = 204). Of the 166 aphasic patients alive at discharge (median 5 days), aphasia improved in 57% and resolved in 38%. In the 102 aphasic subjects evaluated at 6 months, aphasia improved in 86% and completely resolved in 74% of subjects. Among aphasic subjects with “mild” stroke (initial NIHSS <5), aphasia resolved in 90% of subjects by 6 months. Factors significantly associated with better outcome included clinically and radiographically smaller strokes and lower prestroke disability. Conclusions: The prognosis for full recovery of aphasia present in the hyperacute window is good. Radiographic and clinical markers indicating lesser extent of ischemia correlated to greater recovery. Given the excellent prognosis for language recovery in mild stroke, the net benefit of thrombolysis in such cases is uncertain. [ABSTRACT FROM AUTHOR]

Purpose: To improve ischemic stroke outcome prediction using imaging information from a prospective cohort who received admission CT angiography (CTA). Methods: In a prospectively designed study, 649 stroke patients diagnosed with acute ischemic stroke had admission NIH stroke scale scores, noncontrast CT (NCCT), CTA, and 6-month outcome assessed using the modified Rankin scale (mRS) scores. Poor outcome was defined as mRS>2. Strokes were classified as ''major'' by the (1) Alberta Stroke Program Early CT Score (ASPECTS+) if NCCT ASPECTS was≤7; (2) Boston Acute Stroke Imaging Scale (BASIS+) if they were ASPECTS+ or CTA showed occlusion of the distal internal carotid, proximal middle cerebral, or basilar arteries; and (3) NIHSS for scores>10. Results: Of 649 patients, 253 (39.0%) had poor outcomes. NIHSS, BASIS, and age, but not ASPECTS, were independent predictors of outcome. BASIS and NIHSS had similar sensitivities, both superior to ASPECTS (p<0.0001). Combining NIHSS with BASIS was highly predictive: 77.6% (114/147) classified as NIHSS>10/BASIS+ had poor outcomes, versus 21.5% (77/358) with NIHSS≤10/BASIS2 (p<0.0001), regardless of treatment. The odds ratios for poor outcome is 12.6 (95% CI: 7.9 to 20.0) in patients who are NIHSS>10/BASIS+ compared to patients who are NIHSS#10/BASIS2; the odds ratio is 5.4 (95% CI: 3.5 to 8.5) when compared to patients who are only NIHSS.10 or BASIS+. Conclusions: BASIS and NIHSS are independent outcome predictors. Their combination is stronger than either instrument alone in predicting outcomes. The findings suggest that CTA is a significant clinical tool in routine acute stroke assessment. [ABSTRACT FROM AUTHOR]

Introduction: Despite extensive inpatient workup including telemetry monitoring, a significant proportion of stroke is classified as cryptogenic at hospital discharge. It is possible that a significant proportion of cryptogenic stroke is a result of intermittent atrial fibrillation (AF). Thirty-day cardiac event monitors (30-DEM) may increase the rate of AF detection compared with standard investigations that include a combination of electrocardiography, cardiac telemetry, and short-term Holter monitoring. Methods: Charts were reviewed of patients who were admitted to a university stroke center or who were evaluated in the outpatient clinic during a 9-month period to determine whether the cause of stroke was cryptogenic. As a matter of protocol, such patients typically underwent 30-DEM and the results of such monitoring were documented along with the duration of inpatient cardiac monitoring if relevant. Results: In all, 218 patients with a diagnosis of ischemic stroke or transient ischemic attack were identified. Of the strokes, 36 (16.5%) were classified as cryptogenic. Twenty patients with cryptogenic stroke or transient ischemic attack were evaluated with 30-DEM. Four (20%) were found to have AF, and all 4 patients were treated with warfarin. Conclusion: The 30-DEM changed the medical treatment of 20% of patients with otherwise cryptogenic stroke because of the detection of intermittent AF despite no detection of AF on electrocardiography and inpatient telemetry monitoring in the majority of patients. Further prospective studies of extended cardiac event monitors in the setting of cryptogenic stroke are warranted. [Copyright &y& Elsevier]

Introduction: Intraarterial thrombolysis and mechanical embolectomy have been studied for endovascular treatment of stroke. The MERCI and Multi MERCI trials of mechanical embolectomy with or without adjuvant intraarterial thrombolysis demonstrated effective recanalization, but with a higher mortality compared with control patients in the PROACT II trial of intraarterial thrombolysis. Differences in trial design may account for this mortality difference.Methods: We identified patients in the MERCI and Multi MERCI trials who would have been eligible for PROACT II. Rates of good outcome (mRS < or =2) and mortality at 90 days were compared, adjusting for differences in baseline NIHSS score and age.Results: Sixty-eight patients enrolled in MERCI and 81 enrolled in Multi MERCI were eligible for PROACT II. In both unadjusted and adjusted analyses, PROACT II-eligible embolectomy patients showed a trend toward better clinical outcomes compared to the PROACT II control arm (adjusted, MERCI 35.4% [p = ns], Multi MERCI 42.8% [p = 0.048], PROACT II control, 25.4%). In both unadjusted and adjusted analyses, mortality rates did not significantly differ between embolectomy patients and PROACT II control patients (adjusted analysis, MERCI 29.1%, Multi MERCI 18.0%, PROACT II control, 27.1%). Compared with the PROACT II treatment group, embolectomy groups showed similar rates of good outcome and mortality.Conclusions: Differences in mortality and proportion of good outcome between the MERCI/Multi MERCI trials and the PROACT II trial are explained by differences in study design and baseline characteristics of patients. Mechanical embolectomy and IA thrombolysis may each be reasonable strategies for acute stroke; a randomized trial is necessary to confirm these results. [ABSTRACT FROM AUTHOR]

The purpose of this study was to compare the results of perfusion computed tomography (PCT) with those of 15O2/H2 15O positron emission tomography (PET) in a subset of Carotid Occlusion Surgery Study (COSS) patients. Six patients enrolled in the COSS underwent a standard-of-care PCT in addition to the 15O2/H2 15O PET study used for selection for extracranial–intracranial bypass surgery. PCT and PET studies were coregistered and then processed separately by different radiologists. Relative measurement of cerebral blood flow (CBF) and oxygen extraction fraction (OEF) were calculated from PET. PCT datasets were processed using different arterial input functions (AIF). Relative PCT and PET CBF values from matching regions of interest were compared using linear regression model to determine the most appropriate arterial input function for PCT. Also, PCT measurements using the most accurate AIF were evaluated for linear regression with respect to relative PET OEF values. The most accurate PCT relative CBF maps with respect to the gold standard PET CBF were obtained when CBF values for each arterial territory are calculated using a dedicated AIF for each territory ( R 2 = 0.796, p < 0.001). PCT mean transit time (MTT) is the parameter that showed the best correlation with the count-based PET OEF ratios ( R 2 = 0.590, p < 0.001). PCT relative CBF compares favorably to PET relative CBF in patients with chronic carotid occlusion when processed using a dedicated AIF for each territory. The PCT MTT parameter correlated best with PET relative OEF. [ABSTRACT FROM AUTHOR]

Postictal (“Todd’s”) paralysis, or “epileptic hemiplegia,” is a well-known complication of focal or generalized epileptic seizures. However, it is unclear whether the pathophysiology of Todd’s paralysis is related to alterations in cerebral perfusion. We report CT perfusion findings in a patient presenting with postictal aphasia and right hemiparesis. A 62-year-old woman with a history of alcohol abuse, closed head injury and posttraumatic epilepsy, presented with acute onset aphasia and right hemiparesis. A non-contrast head CT scan demonstrated no acute hemorrhage. Left hemispheric ischemia was suspected, and the patient was considered for acute thrombolytic therapy. MRI revealed a subtle increase in signal intensity involving the left medial temporal, hippocampal and parahippocampal regions on both T2-weighted FLAIR and diffusion-weighted sequences. CT angiography and CT perfusion study were performed. The CT perfusion study and CT angiography demonstrated a dramatic reduction in cerebral blood flow and blood volume involving the entire left hemisphere, but with relative symmetry of mean transit time, ruling out a large vessel occlusion. Clinical resolution of the aphasia and hemiparesis occurred within a few hours, and correlated with normalization of perfusion to the left hemisphere (detected by MR perfusion). This unique case is the first in which clinical evidence of Todd’s paralysis has been correlated with reversible postictal hemispheric changes on CT and MR perfusion studies. This is important because CT perfusion study is being used more and more in the diagnosis of acute stroke, and one needs to be careful to not misinterpret the data. [ABSTRACT FROM AUTHOR]

Background and Purpose: Whether cardiac dysfunction contributes to morbidity and mortality after subarachnoid hemorrhage (SAH) remains controversial. The objective of this study was to test the hypothesis that cardiovascular abnormalities are independently related to in-patient mortality after SAH.Methods: This was a prospective cohort study of patients with aneurysmal SAH. Heart rate and blood pressure were measured, a blood sample was obtained, and echocardiography was performed on three study days, starting as soon after admission as possible. The cardiovascular predictor variables were heart rate, systolic blood pressure (SBP), cardiac troponin I (cTi) level, B-type natriuretic peptide (BNP) level, and left ventricular ejection fraction. The primary outcome measure was in-patient mortality. The association between each predictor variable and mortality was quantified by multivariate logistic regression, including relevant covariates and reporting odds ratios (OR) and 95% confidence intervals (CI).Results: The study included 300 patients. An initial BNP level greater than 600 pg/mL was markedly associated with death (OR 37.7, p < 0.001). On the third study day (9.1 +/- 4.1 days after SAH symptom onset), a cTi level greater than 0.3 mg/L (OR 7.6, p = 0.002), a heart rate of 100 bpm or greater (OR 4.9, p = 0.009), and a SBP less than 130 mmHg (OR 6.7, p = 0.007) were significantly associated with death.Conclusions: Cardiovascular abnormalities are independent predictors of in-patient mortality after SAH. Though these effects may be explained by a reduction in cerebral perfusion pressure or other mechanisms, further research is required to determine whether or not they are causal in nature. [ABSTRACT FROM AUTHOR]

Introduction: Cardiac abnormalities that have been reported after subarachnoid hemorrhage (SAH) include the release of cardiac biomarkers, electrocardiographic changes, and left ventricular (LV) systolic dysfunction. The mechanisms of cardiac dysfunction after SAH remain controversial. The aim of this study was to determine the prevalence of LV regional wall motion abnormalities (RWMA) after SAH and to quantify the independent effects of specific demographic and clinical variables in predicting the development of RWMA.Methods: Three hundred patients hospitalized with SAH were prospectively studied with serial echocardiography. The primary outcome measure was the presence of RWMA. The predictor variables included the admission Hunt & Hess grade, age, gender, cardiac risk factors, aneurysm location, plasma catecholamine levels, cardiac troponin I (cTi) level, heart rate (HR), blood pressure, and phenylephrine dose. Univariate and multivariate logistic regression was performed with adjustment for serial measurements, reporting odds ratios (OR) and 95% confidence intervals (CI).Results: In this study, 817 echocardiograms were analysed. RWMA were detected in 18% of those studied. The prevalence of RWMA in patients with Hunt & Hess grades 3 - 5 was 35%. Among patients with a peak cTi level greater than 1.0 m g/L, 65% had RWMA. Multivariate analysis demonstrated that high Hunt & Hess grade (OR 4.22 for grade 3 - 5 versus grade 1 - 2, p = 0.046), a cTi level greater than 1.0 microg/L (OR 10.47, p = 0.001), a history of prior cocaine or amphetamine use (OR 5.50, p = 0.037), and higher HR (OR 1.34 per 10 bpm increase, p = 0.024) were predictive of RWMA.Conclusions: RWMA were frequent after SAH. High-grade SAH, an elevation in cTi levels, a history of prior stimulant drug use, and tachycardia are independent predictors of RWMA. [ABSTRACT FROM AUTHOR]

Objective: We aimed to assess the impact of time to endovascular thrombectomy (EVT) on clinical outcomes in the DAWN trial, while also exploring the potential effect modification of mode of stroke onset on this relationship. Methods: The association between every 1‐h treatment delay with 90‐day functional independence (modified Rankin Scale [mRS] score 0–2), symptomatic intracranial hemorrhage, and 90‐day mortality was explored in the overall population and in three modes of onset subgroups (wake‐up vs. witnessed vs. unwitnessed). Results: Out of the 205 patients, 98 (47.8%) and 107 (52.2%) presented in the 6 to 12 hours and 12 to 24 hours time window, respectively. Considering all three modes of onset together, there was no statistically significant association between time last seen well to randomization with either functional independence or mortality at 90 days in either the endovascular thrombectomy (mRS 0–2 1‐hour delay OR 1.07; 95% CI 0.93–1.24; mRS 6 OR 0.84; 95% CI 0.65–1.03) or medical management (mRS 0–2 1‐hour delay OR 0.98; 95% CI 0.80–1.14; mRS 6 1‐hour delay OR 0.94; 95% CI 0.79–1.09) groups. Moreover, there was no significant interaction between treatment effect and time (p = 0.439 and p = 0.421 for mRS 0–2 and 6, respectively). However, within the thrombectomy group, the models that tested the association between time last seen well to successful reperfusion (modified Treatment in Cerebral Infarction ≥2b) and 90‐day functional independence showed a significant interaction with mode of presentation (p = 0.013). This appeared to be driven by a nominally positive slope for both witnessed and unwitnessed strokes versus a significantly (p = 0.018) negative slope in wake‐up patients. There was no association between treatment times and symptomatic intracranial hemorrhage. Interpretation: Mode of onset modifies the effect of time to reperfusion on thrombectomy outcomes, and should be considered when exploring different treatment paradigms in the extended window. ANN NEUROL 2024;96:356–364 [ABSTRACT FROM AUTHOR]