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In the United States, acute low back pain, with or without radiculopathy, is the leading cause of years lived with disability and the third ranking cause of disability-adjusted life-years. Uncomplicated acute low back pain and/or radiculopathy is a benign, self-limited condition that does not warrant any imaging studies. Imaging is considered in those patients who have had up to 6 weeks of medical management and physical therapy that resulted in little or no improvement in their back pain. It is also considered for those patients presenting with red flags, raising suspicion for a serious underlying condition, such as cauda equina syndrome, malignancy, fracture, or infection. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Cerebrovascular disease is a broad topic. This document focuses on the imaging recommendations for the varied clinical scenarios involving intracranial aneurysms, vascular malformations, and vasculitis, which all carry high risk of morbidity and mortality. Additional imaging recommendations regarding complications of these conditions, including subarachnoid hemorrhage and vasospasm, are also covered. While each variant presentation has unique imaging recommendations, the major focus of this document is neurovascular imaging techniques. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Syncope and presyncope lead to well over one million emergency room visits in the United States each year. Elucidating the cause of syncope or presyncope, which are grouped together given similar etiologies and outcomes, can be exceedingly difficult given the diverse etiologies. This becomes more challenging as some causes, such as vasovagal syncope, are relatively innocuous while others, such as cardiac-related syncope, carry a significant increased risk of death. While the mainstay of syncope and presyncope assessment is a detailed history and physical examination, imaging can play a role in certain situations. In patients where a cardiovascular etiology is suspected based on the appropriate history, physical examination, and ECG findings, resting transthoracic echocardiography is usually considered appropriate for the initial imaging. While no imaging studies are considered usually appropriate when there is a low probability of cardiac or neurologic pathology, chest radiography may be appropriate in certain clinical situations. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Key Clinical Points Acute Ischemic Stroke Treatment for patients with acute ischemic stroke is guided by the time from the onset of stroke, the severity of neurologic deficit, and findings on neuro...

Movement disorders and neurodegenerative diseases are a variety of conditions that involve progressive neuronal degeneration, injury, or death. Establishing the correct diagnosis of a movement disorder or neurodegenerative process can be difficult due to the variable features of these conditions, unusual clinical presentations, and overlapping symptoms and characteristics. MRI has an important role in the initial assessment of these patients, although a combination of imaging and laboratory and genetic tests is often needed for complete evaluation and management. This document summarizes the imaging appropriateness data for rapidly progressive dementia, chorea, Parkinsonian syndromes, suspected neurodegeneration with brain iron accumulation, and suspected motor neuron disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Degenerative disease of the central nervous system is a growing public health concern. The primary role of neuroimaging in the workup of patients with probable or possible Alzheimer disease has typically been to exclude other significant intracranial abnormalities. In general, the imaging findings in structural studies, such as MRI, are nonspecific and have limited potential in differentiating different types of dementia. Advanced imaging methods are not routinely used in community or general practices for the diagnosis or differentiation of forms of dementia. Nonetheless, in patients who have been evaluated by a dementia expert, FDG-PET helps to distinguish Alzheimer disease from frontotemporal dementia. In patients with suspected dementia with Lewy bodies, functional imaging of the dopamine transporter (ioflupane) using SPECT may be helpful. In patients with suspected normal-pressure hydrocephalus, DTPA cisternography and HMPAO SPECT/CT brain may provide assessment. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Ataxia can result from an abnormality in the cerebellum, spinal cord, peripheral nerves, and/or vestibular system. Pathology involving the brain, such as infarct or hydrocephalus, can also present with ataxia as part of the symptom constitution, or result in symptoms that mimic ataxia. Clinical evaluation by history and careful neurological examination is important to help with lesion localization, and helps determine where imaging should be focused. In the setting of trauma with the area of suspicion in the brain, a head CT without intravenous contrast is the preferred initial imaging choice. If vascular injury is suspected, CTA of the neck can be helpful. When the area of suspicion is in the spine, CT or MRI of the spine can be considered to assess for bony or soft-tissue injury, respectively. In the setting of ataxia unrelated to recent trauma, MRI is the preferred imaging modality, tailored to assess the brain or spine depending on the area of suspected pathology. The use of intravenous contrast is generally helpful. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Neuroendocrine dysfunction includes suspected hyper- and hypofunction of the pituitary gland. Causative lesions may include primary masses of the pituitary such as pituitary microadenomas and macroadenomas, as well as extrinsic masses, typically centered in the suprasellar cistern. Clinical syndromes related to hormonal dysfunction can be caused by excessive hormonal secretion or by inhibited secretion due to mass effect upon elements of the hypothalamic-pituitary axis. Additionally, complications such as hemorrhage may be seen in the setting of an underlying mass and can result in hormonal dysfunction. MRI with high-resolution protocols is the best first-line test to evaluate the sella turcica and parasellar region. CT provides complementary information regarding bony anatomy, and may be appropriate as a first-line test in certain instances, but it provides less detail and lesion characterization when compared to MRI. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Patients with acute ischemic stroke often undergo magnetic resonance imaging (MRI) in addition to computed tomography (CT), but its association with clinical outcomes is uncertain.To assess whether clinical outcomes of patients with acute ischemic stroke with initial CT alone were noninferior to those with additional MRI.A retrospective observational propensity score-matched cohort study of clinical outcomes at discharge and 1 year for patients hospitalized with acute ischemic stroke was conducted at an academic medical center between January 2015 and December 2017. Data collection from an electronic medical record system performed from May 2020 through January 2022 was not completely blinded. Noninferiority margins were based on the designs of previous randomized clinical trials of ischemic stroke treatments. Statistical analysis was performed in January 2022. Participants were adults hospitalized with acute ischemic stroke with admission diagnosis based on CT. Exclusion criteria were primarily missing data. From 508 eligible patients, all 123 cases with additional MRI were propensity-score matched to 123 controls without.MRI after initial diagnosis.Death or dependence at hospital discharge (modified Rankin Scale score of 3-6) and stroke or death occurring in survivors within 1 year after discharge.Among 246 participants, the median age was 68 years (IQR, 58-78.8 years) and 131 (53.0%) were men. Death or dependence at discharge occurred more often in patients with additional MRI (59 of 123 [48.0%]) than in those with CT alone (52 of 123 [42.3%]; absolute difference, 5.7%; 95% CI, -6.7% to 18.1%), meeting the -7.50% criterion for noninferiority. Stroke or death within 1 year after discharge determined for 225 of 235 (96%) survivors occurred more often in patients with additional MRI (22 of 113 [19.5%]) than in those with CT alone (14 of 112 [12.5%]; relative risk, 1.14; 95% CI, 0.86-1.50), meeting the 0.725 relative risk criterion for noninferiority.This propensity score-matched cohort study of patients hospitalized with acute ischemic stroke found that a diagnostic imaging strategy of initial CT alone was noninferior to initial CT plus additional MRI with regard to clinical outcomes at discharge and at 1 year. Further research is needed to determine which patients hospitalized with acute ischemic stroke benefit from MRI.

Echocardiography employs ultrasound to evaluate cardiac function, structure and pathology. The clinical value in secondary ischemic stroke prevention depends on identification of associated conditions for which a change in treatment from antiplatelet agents and risk factor intervention leads to improved outcomes. Such therapeutically relevant findings include primarily intracardiac thrombus, valvular heart disease and, in highly selected patients, patent foramen ovale (PFO). Echocardiography in unselected patients with ischemic stroke has a very low yield of therapeutically relevant findings and is not cost-effective. With the exception of PFO, findings on echocardiography that are therapeutically relevant for secondary stroke prevention are almost always associated with history, signs or symptoms of cardiac or systemic disease. Choice of specific echocardiographic modalities should be based on the specific pathology or pathologies that are under consideration for the individual clinical situation. Transthoracic echocardiography (TTE) with agitated saline has comparable accuracy to transesophageal echocardiography (TEE) for PFO detection. For other therapeutically relevant pathologies, with the possible exception of left ventricular thrombus (LVT), TEE is more sensitive than TTE. Professional societies recommend TTE as the initial test but these recommendations do not take cost into account. In contrast, cost-effectiveness studies have determined that the most sensitive echocardiographic modality should be selected as the initial and only test.

Introduction: Human immunodeficiency virus (HIV)-infected individuals are at high risk for ischemic stroke. We measured cerebral blood flow (CBF), oxygen extraction fraction (OEF), and autoregulation in HIV infected subjects and controls. Methods: In treatment-naive HIV infected subjects and age-, gender-, and race-matched controls, OEF was measured by using MRI T2*-weighted echo-planar imaging sequences and CBF was measured by MRI pulsed arterial spin labeling (PASL) approach. Static cerebral autoregulation was determined by measuring changes in CBF and OEF, in response to ≈10% reductions in MAP induced by using IV Nicardipine infusion. All images were acquired using a Siemens 3T MR scanner (Treo, Siemens Medical Systems Inc). Cerebral autoregulation was measured globally and regionally in gray matter (GM), white matter (WM) and subcortical GM. Autoregulatory Index (AI) was computed using the equation AI = %CBF change/% MAP change supplemented by CBF associated OEF changes. Nominal p-values are uncorrected for multiple comparisons. Results: Forty-one treatment naive HIV-infected subjects and 47 age-, gender-, race-matched controls participated. HIV-infected subjects had higher CBF in cortical GM compared to the controls (76.8± 12 mL/100 g/min versus 71.6 ± 11 mL/100 g/min; p= 0.04), but not in white matter (30.9± 8 mL/100 g/min versus 30.0 ± 8 mL/100 g/min; p = 0.60) or subcortical GM (62.8± 13 mL/100 g/min versus 61.3 ± 13 mL/100 g/min; p = 0.57). Whole brain (WB), GM, WM, and subcortical GM, OEF were similar between the groups (p > .05). The median AI were similar between cases and controls in WB (0.40 vs 0.18, p=0.86), GM (0.10 vs. 0.16, p=0.87), WM (0.80 vs. 0.87, p=0.31), and subcortical GM (1.65 vs. 1.77, p=0.26). A 12-month follow-up (N=30) in HIV-subjects on antiretroviral therapy did not produce a significant change in CBF or OEF in the WB, GM, WM, or subcortical GM (Paired sample t test p>0.05). Similarly, no changes were noted on the AI (Wilcoxon Match Rank test p>0.05). Conclusions: AI was similar between HIV cases and control and remained so after 12-months of antiretroviral therapy. We found no evidence of a defect in autoregulation to explain the high-risk of ischemic stroke documented in other studies.

Visual loss can be the result of an abnormality anywhere along the visual pathway including the globe, optic nerve, optic chiasm, optic tract, thalamus, optic radiations or primary visual cortex. Appropriate imaging analysis of visual loss is facilitated by a compartmental approach that establishes a differential diagnosis on the basis of suspected lesion location and specific clinical features. CT and MRI are the primary imaging modalities used to evaluate patients with visual loss and are often complementary in evaluating these patients. One modality may be preferred over the other depending on the specific clinical scenario. Depending on the pattern of visual loss and differential diagnosis, imaging coverage may require targeted evaluation of the orbits and/or assessment of the brain. Contrast is preferred when masses and inflammatory processes are differential considerations. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Background and Purpose— The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations in a single document for clinicians caring for adult patients with acute arterial ischemic stroke. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 Acute Ischemic Stroke (AIS) Guidelines and are an update of the 2018 AIS Guidelines. Methods— Members of the writing group were appointed by the American Heart Association (AHA) Stroke Council’s Scientific Statements Oversight Committee, representing various areas of medical expertise. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. An update of the 2013 AIS Guidelines was originally published in January 2018. This guideline was approved by the AHA Science Advisory and Coordinating Committee and the AHA Executive Committee. In April 2018, a revision to these guidelines, deleting some recommendations, was published online by the AHA. The writing group was asked review the original document and revise if appropriate. In June 2018, the writing group submitted a document with minor changes and with inclusion of important newly published randomized controlled trials with >100 participants and clinical outcomes at least 90 days after AIS. The document was sent to 14 peer reviewers. The writing group evaluated the peer reviewers’ comments and revised when appropriate. The current final document was approved by all members of the writing group except when relationships with industry precluded members from voting and by the governing bodies of the AHA. These guidelines use the American College of Cardiology/AHA 2015 Class of Recommendations and Level of Evidence and the new AHA guidelines format. Results— These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings. Conclusions— These guidelines provide general recommendations based on the currently available evidence to guide clinicians caring for adult patients with acute arterial ischemic stroke. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.

BACKGROUND: There are limited data on outcomes of extracranial-intracranial (EC-IC) bypass in patients with recurrent hemispheric syndromes due to atherosclerotic internal carotid artery occlusion (AICAO). OBJECTIVE: To compare clinical outcomes and efficacy of EC-IC bypass surgery in patients with and without recurrent hemispheric syndromes associated with AICAO in the Carotid Occlusion Surgery Study (COSS). METHODS: In patients enrolled in the COSS trial, we compared baseline characteristics and clinical outcomes for participants with (rHEMI+) and without recurrent hemispheric ischemia (rHEMI−) prior to randomization into surgical vs medical groups. The primary outcome was all stroke and death from randomization through 30 d and ipsilateral ischemic stroke within 2 yr. RESULTS: Of 195 randomized participants, 100 were rHEMI+ (50 in each group). Baseline characteristics between rHEMI+ and rHEMI− participants were similar except rHEMI+ were more likely to have had previous stroke prior to randomization (61% vs 20%, P

Headache is one of the most common human afflictions. In most cases, headaches are benign and idiopathic, and resolve spontaneously or with minor therapeutic measures. Imaging is not required for many types of headaches. However, patients presenting with headaches in the setting of "red flags" such as head trauma, cancer, immunocompromised state, pregnancy, patients 50 years or older, related to activity or position, or with a corresponding neurological deficit, may benefit from CT, MRI, or noninvasive vascular imaging to identify a treatable cause. This publication addresses the initial imaging strategies for headaches associated with the following features: severe and sudden onset, optic disc edema, "red flags," migraine or tension-type, trigeminal autonomic origin, and chronic headaches with and without new or progressive features. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Ataxia can result from an abnormality in the cerebellum, spinal cord, peripheral nerves, and/or vestibular system. Pathology involving the brain, such as infarct or hydrocephalus, can also present with ataxia as part of the symptom constitution, or result in symptoms that mimic ataxia. Clinical evaluation by history and careful neurological examination is important to help with lesion localization, and helps determine where imaging should be focused. In the setting of trauma with the area of suspicion in the brain, a head CT without intravenous contrast is the preferred initial imaging choice. If vascular injury is suspected, CTA of the neck can be helpful. When the area of suspicion is in the spine, CT or MRI of the spine can be considered to assess for bony or soft-tissue injury, respectively. In the setting of ataxia unrelated to recent trauma, MRI is the preferred imaging modality, tailored to assess the brain or spine depending on the area of suspected pathology. The use of intravenous contrast is generally helpful. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Background and Purpose— We aimed to examine perfusion changes between 3 and 6 and 6 and 24 hours after stroke onset and their impact on tissue outcome. Methods— Acute ischemic stroke patients underwent perfusion magnetic resonance imaging at 3, 6, and 24 hours after stroke onset and follow-up fluid-attenuated inversion recovery at 1 month to assess tissue fate. Mean transit time prolongation maps (MTTp=MTT–[median MTT of contralateral hemisphere]) were obtained at 3 (MTTp 3 h ), 6 (MTTp 6 h ), and 24 hours (MTTp 24 h ). Perfusion changes between 3 and 6 hours (ΔMTTp 3_6 ) and 6 and 24 hours (ΔMTTp 6_24 ) were calculated. A 2-step analysis was performed to evaluate the impact of ΔMTTp 3_6 and ΔMTTp 6_24 on tissue fate. First, a voxel-based multivariable logistic regression was performed for each individual patient with MTTp 3 h , ΔMTTp 3_6 , and ΔMTT 6_24 as independent variables and tissue fate as outcome. Second, Wilcoxon signed-rank tests on logistic regression coefficients were performed across patients to evaluate whether ΔMTTp 3_6 and ΔMTT 6_24 had significant impact on tissue fate for varying severities of baseline perfusion. Results— Perfusion change was common during both time periods: 85% and 81% of patients had perfusion improvement during 3- to 6- and 6- and 24-hour time intervals, respectively. ΔMTT 3_6 significantly influenced 1-month infarct probability across a wide range of baseline perfusion (MTTp 0–15 s). ΔMTT 6_24 also impacted 1-month infarct probability, but its influence was restricted to tissue with milder baseline ischemia (MTTp 0–10 s). Conclusions— Brain tissue with mild to moderate ischemia can be salvaged by reperfusion even after 6 hours. Such tissue could be targeted for intervention beyond current treatment windows.

Objective To determine the diagnostic value of acute infarcts in multiple cerebral circulations (AIMCC) on MRI diffusion-weighted imaging (DWI) for cardioembolism (CE) stroke subtype in adult patients hospitalized with acute ischemic stroke, we conducted a systematic literature review and meta-analysis. Methods MEDLINE was searched via PubMed for articles reporting patients hospitalized with acute ischemic stroke with MRI DWI categorized as AIMCC vs other and use of Trial of Org 10172 in Acute Stroke Treatment (TOAST) Criteria for cardioembolism subtype. Measures of diagnostic accuracy were calculated from the retrieved studies. Results Seven eligible articles comprised 5813 patients. Bivariate random effects models estimated sensitivity 0.19 (95% CI, 0.13 to 0.27), specificity 0.89 (0.86 to 0.91), positive predictive value 0.37 (0.30 to 0.45), negative predictive value 0.76 (0.7 to 0.82), positive likelihood ratio 1.70 (1.13 to 2.57) and negative likelihood ratio 0.91 (0.83 to 1). Interpretation The pattern of AIMCC on DWI is of limited diagnostic value. It is not sufficiently accurate to exclude cardiac pathology by a negative test nor does a positive test indicate a major increase in the probability of identifying a potential cardioembolic source.

The purpose of these guidelines is to provide an up-to-date comprehensive set of recommendations for clinicians caring for adult patients with acute arterial ischemic stroke in a single document. The intended audiences are prehospital care providers, physicians, allied health professionals, and hospital administrators. These guidelines supersede the 2013 guidelines and subsequent updates.Members of the writing group were appointed by the American Heart Association Stroke Council's Scientific Statements Oversight Committee, representing various areas of medical expertise. Strict adherence to the American Heart Association conflict of interest policy was maintained. Members were not allowed to participate in discussions or to vote on topics relevant to their relations with industry. The members of the writing group unanimously approved all recommendations except when relations with industry precluded members voting. Prerelease review of the draft guideline was performed by 4 expert peer reviewers and by the members of the Stroke Council's Scientific Statements Oversight Committee and Stroke Council Leadership Committee. These guidelines use the American College of Cardiology/American Heart Association 2015 Class of Recommendations and Levels of Evidence and the new American Heart Association guidelines format.These guidelines detail prehospital care, urgent and emergency evaluation and treatment with intravenous and intra-arterial therapies, and in-hospital management, including secondary prevention measures that are appropriately instituted within the first 2 weeks. The guidelines support the overarching concept of stroke systems of care in both the prehospital and hospital settings.These guidelines are based on the best evidence currently available. In many instances, however, only limited data exist demonstrating the urgent need for continued research on treatment of acute ischemic stroke.

Background: Reliable methods used to measure cerebral hemodynamics, metabolism and autoregulation are time-consuming and invasive. Objectives: We sought to measure cerebral blood flow (CBF), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ), in the whole brain, gray and white matter and detect physiological changes in humans under normal and ≈10% reductions in mean arterial pressure (MAP). Methods: CBF was measured using pseudo continuous arterial spin labeling (pCASL). OEF was measured using a MRI asymmetric spin echo-planar imaging (EPI). The arterial content of oxygen (CaO 2 ) was computed. CMRO 2 was calculated using the equation CMRO 2 =CaO 2 xCBFxOEF. Cerebral autoregulation was determined by measuring changes in CBF, OEF and CMRO 2 in response to ≈10% reductions in MAP in stroke-free controls induced by IV Nicardipine infusion. Autoregulation was measured in the whole brain, gray matter and white matter. Autoregulatory Index (AI) was computed using the equation AI = %CBF change/% MAP change supplemented by CBF associated OEF changes. Results: A total of 30 subjects were consented (Mean age 31, 93% male, 40% white, 43% black and 17% others). At baseline, CBF was measured in the whole brain (52.5±9.5 ml/100g/min), gray matter (72.0±13.0 ml/100g/min) and white matter (30.2±8.4 ml/100g/min). OEF was measured in the whole brain (0.32±0.02), gray matter (0.33±0.02) and white matter (0.30±0.01). CMRO 2 was measured in the whole brain (3.2±0.8 ml/100g/min), gray matter (4.6±1.1 ml/100g/min) and white matter (1.8±0.5 ml/100g/min). A target of 10% MAP lowering was successfully achieved in 18 subjects, resulting in a change of mean CBF in the whole brain (52 vs. 50, p=0.1), gray matter (72 vs. 69, p=0.2) and white matter (30 vs. 28, p=0.08). This translated to a AI of 0.3 ± 0.9 in the whole brain, 0.2±1.0 in the gray matter and 0.5±1.7 in the white matter. These CBF changes corroborated with no significant changes in OEF and CMRO 2 . Conclusions: MR measurement of CBF, OEF and CMRO 2 , in the whole brain, gray and white matter was comparable to measures obtained by invasive methods. Differences in these measures, as well as AI in the gray and white matter, may help understand cerebrovascular diseases that affect white matter such as lacunar strokes.

Background: There are limited data on the baseline characteristics and clinical outcomes of patients who have recurrent hemispheric syndromes in the territory of symptomatic atherosclerotic internal carotid artery occlusion (AICAO). Methods: Baseline characteristics and clinical outcomes were compared between patients with (rHEM+) and without (rHEM-) recurrent ipsilateral hemispheric syndromes at the time of randomization into the Carotid Occlusion Surgery Study (COSS) based on local investigator clinical impression. Results: Of 195 participants who were randomized, 100 (51%) were rHEM+ (50 in each study arm) and 95 were rHEM-(48 nonsurgical, 47 surgical). Baseline characteristics between rHEM+ and rHEM- participants were similar except that rHEM+ participants were more likely to have had a previous stroke prior to entry event (59% vs 22%, p < 0.001) and to have had TIA vs stroke as the entry event (61% vs 20%, p 0.10). For the nonsurgical participants, there was no statistically significant difference in the primary endpoint for those rHEM+ vs rHEM- (26.3% vs 18.9%, p=.410) Conclusion: Patients with recurrent hemispheric stroke syndromes enrolled in the COSS trial were more likely to have had previous stroke and to have TIAs as the entry event to randomization. Given the lack of surgical treatment benefit seen in these patients, early aggressive risk factor measures should be prioritized to reduce recurrent strokes, including blood pressure control which was associated with a 70% reduction in stroke in the nonsurgical group in COSS ( Neurology 2014; 82:1027-1032).

Background and purpose: The study aimed to assess the efficiency (percent treated) of existing in-hospital stroke alert activation criteria and to improve these criteria. Methods: 209 patient records from in-hospital stroke alerts at an academic medical center between January 2015 and December 2016 were reviewed retrospectively. Patients were sorted into five categories by final diagnosis: cerebral ischemia, cerebral hemorrhage, seizure, delirium or toxic/metabolic encephalopathy, and other. Acute treatment result of any in-hospital stroke was recorded. The study team determined adherence to the institution’s existing in-hospital stroke alert activation criteria. To improve efficiency a new set of in-hospital stroke alert activation criteria called “S3TOP for Stroke” was then developed. The checklist for “S3TOP for Stroke” guides hospital staff to assess the following items: symptoms, sedation, sugar, time, oxygenation and pulse. The checklist was then retrospectively applied to the 209 records. Results: Of 209 patients who received in-hospital stroke alerts according to existing activation criteria: 192 (91.9%) met existing criteria, and 14 (6.7%) received acute stroke treatment. Applying the “S3TOP for Stroke” checklist to the study group excluded 56 of these and included all 14 (14/153 =9.2%) who received acute stroke treatment. Conclusions: This study found good adherence with poor efficiency for existing institutional stroke alert activation criteria. Retrospectively, the “S3TOP for Stroke” checklist improved efficiency. Prospective testing of this algorithm is underway.

Introduction and Hypothesis: Approximately a third of stroke/TIA events occur in patients taking daily Aspirin. We studied the comparative effectiveness of FDA approved antiplatelet agents (Aspirin, Clopidogrel, and Aspirin-dipyridamole or ASA+DP) in prevention of recurrent vascular events in stroke/TIA patients on Aspirin. Methods: Consecutive patients identified as having stroke or TIA were screened and enrolled into this prospective longitudinal registry. Patients on dual antiplatelet therapy or oral anticoagulants were excluded. Patient’s etiological stroke subtype, medication history, medication compliance and Aspirin Platelet Function Test were assessed at baseline. Changes in antiplatelet regimen including Aspirin dose, Clopidogrel, ASA+DP, changes in statin therapy were recorded. Follow up 6 and 12 month phone visits were conducted to assess primary outcomes (stroke/TIA, MI, death), adjudicated by chart review. Results: A total of 183 subjects (mean age 68+12, 58% males, 50% white, 44% African-American) were enrolled over a 24 month period on Aspirin. Majority (63%) had ischemic stroke (NIHSS: 0-21) and remaining (37%) had TIA (ABCD 2 : 2-7). Ischemic strokes were attributed to penetrating artery disease (41%), large artery atherosclerosis (35%), other/undetermined (18%), and cardiogenic (6%). After 12-months, 4.9% of participants on Clopidogrel, 15.1% of participants on aspirin and 35.3% of participants on ASA+DP had a primary outcome (p=0.006), depicted in the Kaplan-Meier curve. Changes in Aspirin dose from 81mg to 325mg or statin therapy regimen did not appear to impact primary outcome. Conclusions: This study shows a significant difference in secondary vascular event within 12 months of stroke/TIA on Aspirin, with effectiveness recorded in the order: Clopidogrel>Aspirin>ASA+DP. A larger randomized pragmatic trial may help ascertain this finding and clarify if specific subtype benefit from specific antiplatelet agent. Figure

Goal: Significant proportions of stroke/transient ischemic attack events occur in patients taking daily aspirin. We studied the comparative effectiveness of Food and Drug Administration approved antiplatelet agents (aspirin, clopidogrel, and aspirin-dipyridamole combination) in prevention of recurrent vascular events in stroke/transient ischemic attack patients on aspirin.Materials and Methods: Consecutive patients having stroke or transient ischemic attack were screened and enrolled into this registry. Patients on long-term dual antiplatelet therapy or oral anticoagulants were excluded. Patient’s etiological stroke subtype, medication history, medication compliance, and Aspirin Platelet Function Test were assessed at baseline. Changes in antiplatelet regimen and statin therapy were also recorded. Follow up 6 and 12-month phone visits were conducted to assess primary outcomes of major adverse cardiovascular events that included a composite of death, myocardial infarction and stroke or transient ischemic attack.Result: One-hundred-eighty subjects (mean age ± SD= 68 ± 12 years, 59% male, 51% white, 49% African-American) were enrolled over 24-months. Majority (64%) had ischemic stroke (NIHSS: 0-21) and remaining (36%) had transient ischemic attack (ABCD2: 2-7). Within 12-months of the index cerebrovascular event, 3 (5.9%) participants on clopidogrel, 21 (18.8%) participants on aspirin and 7 (41.2%) participants on aspirin-dipyridamole combination had a composite vascular event (Log rank p=0.0011).Conclusion: This study shows a significant difference in major adverse cardiovascular event within 12 months of stroke/ transient ischemic attack on Aspirin, with effectiveness recorded in the order: clopidogrel>aspirin> aspirin-dipyridamole combination. A larger randomized pragmatic trial may help ascertain this finding and clarify if specific stroke subtypes benefit from specific antiplatelet agents.

We evaluated safety and feasibility of high-pressure transvenous limb perfusion in an upper extremity of adult patients with muscular dystrophy, after completing a similar study in a lower extremity. A dose escalation study of single-limb perfusion with 0.9% saline was carried out in nine adults with muscular dystrophies under intravenous analgesia. Our study demonstrates that it is feasible and definitely safe to perform high-pressure transvenous perfusion with 0.9% saline up to 35% of limb volume in the upper extremities of young adults with muscular dystrophy. Perfusion at 40% limb volume is associated with short-lived physiological changes in peripheral nerves without clinical correlates in one subject. This study provides the basis for a phase 1/2 clinical trial using pressurized transvenous delivery into upper limbs of nonambulatory patients with Duchenne muscular dystrophy. Furthermore, our results are applicable to other conditions such as limb girdle muscular dystrophy as a method for delivering regional macromolecular therapeutics in high dose to skeletal muscles of the upper extremity.

Primary angiitis of the central nervous system (PACNS) is a vasculitis of small arteries and veins of unknown cause restricted to the central nervous system (CNS), and controversy and disagreement exist over the means to establish the diagnosis. Cerebral arteriography, cerebrospinal fluid examination, and MRI singly or in combination do not have sufficiently demonstrated positive predictive value to establish the diagnosis. An alternative diagnosis is established at biopsy in 35% of cases. Histologic confirmation is required for the diagnosis of PACNS. Patients without histologic confirmation should not be included in case reports, case series, or reviews.

We report two patients with midbrain infarction with pupil-sparing third nerve palsies and hemiataxia: one with contralateral ataxia (Claude's syndrome) and one with ipsilateral ataxia (which we refer to as reverse Claude's syndrome). We highlight the importance of a thorough neurologic evaluation with partial oculomotor palsies and describe, to our knowledge, the fourth account in the literature of a pupil-sparing third nerve palsy with ipsilateral cerebellar ataxia.

Gaining insights into brain oxygen metabolism has been one of the key areas of research in neurosciences. Extensive efforts have been devoted to developing approaches capable of providing measures of brain oxygen metabolism not only under normal physiological conditions but, more importantly, in various pathophysiological conditions such as cerebral ischemia. In particular, quantitative measures of cerebral metabolic rate of oxygen using positron emission tomography (PET) have been shown to be capable of discerning brain tissue viability during ischemic insults. However, the complex logistics associated with oxygen-15 PET have substantially hampered its wide clinical applicability. In contrast, magnetic resonance imaging (MRI)-based approaches have provided quantitative measures of cerebral oxygen metabolism similar to that obtained using PET. Given the wide availability, MRI-based approaches may have broader clinical impacts, particularly in cerebral ischemia, when time is a critical factor in deciding treatment selection. In this article, we review the pathophysiological basis of altered cerebral hemodynamics and oxygen metabolism in cerebral ischemia, how quantitative measures of cerebral metabolism were obtained using the Kety–Schmidt approach, the physical concepts of non-invasive oxygen metabolism imaging approaches, and, finally, clinical applications of the discussed imaging approaches.

Hypoglycemia is the most common complication of diabetes, causing morbidity and death. Recurrent hypoglycemia alters the cascade of physiological and behavioral responses that maintain euglycemia. The extent to which these responses are normally triggered by decreased whole-brain cerebral glucose metabolism (CMRglc) has not been resolved by previous studies. We measured plasma counterregulatory hormonal responses and whole-brain CMRglc (along with blood-to-brain glucose transport rates and brain glucose concentrations) with 1-[11C]-d-glucose positron emission tomography during hyperinsulinemic glucose clamps at nominal plasma glucose concentrations of 90, 75, 60, and 45 mg/dL (5.0, 4.2, 3.3, and 2.5 mmol/L) in 18 healthy young adults. Clear evidence of hypoglycemic physiological counterregulation was first demonstrated between 75 mg/dL (4.2 mmol/L) and 60 mg/dL (3.3 mmol/L) with increases in both plasma epinephrine (P = 0.01) and glucagon (P = 0.01). In contrast, there was no statistically significant change in CMRglc (P = 1.0) between 75 mg/dL (4.2 mmol/L) and 60 mg/dL (3.3 mmol/L), whereas CMRglc significantly decreased (P = 0.02) between 60 mg/dL (3.3 mmol/L) and 45 mg/dL (2.5 mmol/L). Therefore, the increased epinephrine and glucagon secretion with declining plasma glucose concentrations is not in response to a decrease in whole-brain CMRglc.

While several MRI parameters are used to assess tissue perfusion during hyperacute stroke, it is unclear which is optimal for measuring clinically relevant reperfusion. We directly compared mean transit time (MTT) prolongation (MTTp), time-to-peak (TTP), and time-to-maximum (Tmax) to determine which best predicted neurological improvement and tissue salvage following early reperfusion. Acute ischemic stroke patients underwent three MRIs:4.5 h (tp1), at 6 h (tp2), and at 1 month after onset. Perfusion deficits at tp1 and tp2 were defined by MTTp, TTP, or Tmax beyond four commonly used thresholds. Percent reperfusion (%Reperf) was calculated for each parameter and threshold. Regression analysis was used to fit %Reperf for each parameter and threshold as a predictor of neurological improvement [defined as admission National Institutes of Health Stroke Scale (NIHSS)-1 month NIHSS (∆NIHSS)] after adjusting for baseline clinical variables. Volume of reperfusion, for each parameter and threshold, was correlated with tissue salvage, defined as tp1 perfusion deficit volume-final infarct volume. Fifty patients were scanned at 2.7 and 6.2 h after stroke onset. %Reperf predicted ∆NIHSS for all MTTp thresholds, for Tmax6 s and8 s, but for no TTP thresholds. Tissue salvage significantly correlated with reperfusion for all MTTp thresholds and with Tmax6 s, while there was no correlation with any TTP threshold. Among all parameters, reperfusion defined by MTTp was most strongly associated with ∆NIHSS (MTTp3 s, P = 0.0002) and tissue salvage (MTTp3 s and 4 s, P 0.0001). MTT-defined reperfusion was the best predictor of neurological improvement and tissue salvage in hyperacute ischemic stroke.

Object The Carotid Occlusion Surgery Study (COSS) was a large, prospective clinical trial that examined whether superficial temporal artery–middle cerebral artery (STA-MCA) bypass, in addition to best medical therapy, reduced the risk of ipsilateral ischemic stroke in patients with carotid artery occlusion and hemodynamic cerebral ischemia. Despite improved cerebral hemodynamics and excellent bypass graft patency rates, COSS failed to show a benefit for the surgical group with respect to ipsilateral stroke recurrence at 2 years after treatment. This was due to a lower than expected rate of recurrent ipsilateral stroke in the medically treated group and a high rate of perioperative ipsilateral strokes in the surgical group. Critics of the trial have cited surgeon inexperience and technical difficulties related to the performance of the bypass graft as a leading cause of failure of the trial. Methods The authors retrospectively identified all patients from the COSS with an ipsilateral, perioperative (< 30 days) ischemic stroke after STA-MCA cortical branch anastomosis. Study records, operative notes, stroke adjudication forms, and imaging studies were reviewed. Ischemic strokes were characterized as bypass graft related or non–bypass graft related based on clinical and radiographic findings. Results Fourteen of 93 surgically treated patients experienced an ipsilateral, perioperative ischemic stroke. Postoperatively, the mean oxygen extraction fraction (OEF) ratio between the symptomatic and asymptomatic cerebral hemisphere significantly improved in these patients (1.30 ± 0.18 preoperative vs 1.12 ± 0.11 postoperative; p = 0.02), but did not normalize. In this cohort, total MCA occlusion time during the anastomosis (54.3 ± 23.5 minutes) was no different from the MCA occlusion time in those surgical patients who did not have a perioperative stroke (45.4 ± 24.2 minutes, p = 0.2). Bypass graft patency rates in patients with a perioperative stroke were 92% at 30 days (11 of 12 patients with patency data) and 83% at last follow-up visit (10 of 12 patients with patency data). These patency rates were not significantly different from those achieved at 30 days (100%; 76 of 76 patients with patency data; p = 0.14) and at last follow-up (99%; 71 of 72 patients with patency data; p = 0.052) in patients without a perioperative stroke. Eighty-six percent (12 of 14 patients) of strokes were likely attributable to factors unrelated to the STA-MCA anastomosis. Only 21% of strokes (3 of 14 patients) were in the territory of the recipient vessel and likely related to technical performance of the anastomosis itself. One patient was thought to have dual stroke mechanisms. Conclusions Only a small minority of ipsilateral, perioperative ischemic strokes in the COSS could be attributed to technical problems of the bypass anastomosis. The majority of ischemic strokes could not be ascribed to this cause and were most likely due to patient hemodynamic fragility and the inability of patients to tolerate surgery.

Object The Carotid Occlusion Surgery Study (COSS) was conducted to determine if superficial temporal artery–middle cerebral artery (STA-MCA) bypass, when added to the best medical therapy, would reduce subsequent ipsilateral stroke in patients with complete internal carotid artery (ICA) occlusion and an elevated oxygen extraction fraction (OEF) in the cerebral hemisphere distal to the occlusion. A recent publication documented the methodology of the COSS in detail and briefly outlined the major findings of the trial. The surgical results of the COSS are described in detail in this report. Methods The COSS was a prospective, parallel-group, 1:1 randomized, open-label, blinded-adjudication treatment trial. Participants, who had angiographically demonstrated complete occlusion of the ICA causing either a transient ischemic attack or ischemic stroke within 120 days and hemodynamic cerebral ischemia indicated by an increased OEF measured by PET, were randomized to either surgical or medical treatment. One hundred ninety-five patients were randomized: 97 to the surgical group and 98 to the medical group. The surgical patients underwent an STA-MCA cortical branch anastomosis. Results In the intention-to-treat analysis, the 2-year rates for the primary end point were 21% for the surgical group and 22.7% for the medical group (p = 0.78, log-rank test). Fourteen (15%) of the 93 patients who had undergone an arterial bypass had a primary end point ipsilateral hemispheric stroke in the 30-day postoperative period, 12 within 2 days after surgery. The STA-MCA arterial bypass patency rate was 98% at the 30-day postoperative visit and 96% at the last follow-up examination. The STA-MCA arterial bypass markedly improved, although it did not normalize, the level of elevated OEF in the symptomatic cerebral hemisphere. Five surgically treated and 1 nonsurgically treated patients in the surgical group had a primary end point ipsilateral hemispheric stroke after the 30-day postoperative period. No baseline characteristics or intraoperative variables revealed those who would experience a procedure-related stroke. Conclusions Despite excellent bypass graft patency and improved cerebral hemodynamics, STA-MCA anastomosis did not provide an overall benefit regarding ipsilateral 2-year stroke recurrence, mainly because of a much better than expected stroke recurrence rate (22.7%) in the medical group, but also because of a significant postoperative stroke rate (15%). Clinical trial registration no.: NCT00029146.

Statins may promote vasodilation following subarachnoid hemorrhage (SAH) and improve the response to blood pressure elevation. We sought to determine whether simvastatin increases cerebral blood flow (CBF) and alters the response to induced hypertension after SAH. Statin-naive patients admitted

Although the long-term treatment of hypertension is effective for secondary stroke prevention, the optimal management of blood pressure in the setting of acute ischemic stroke has been controversial. This chapter discusses the available evidence and current guidelines supporting the management of blood pressure in the setting of acute ischemic stroke. For patients that are candidates for thrombolysis, reduction and maintenance of the BP within the current guidelines is indicated as it likely reduces the risk of hemorrhagic complications. For all other patients, there is no clear benefit and potentially harm for acute blood pressure reduction.