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.

Guidelines for the Early Management of Patients With Acute Ischemic Stroke: 2019 Update to the 2018 Guidelines for the Early Management of Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association.

Despite the global impact and advances in understanding the pathophysiology of cerebrovascular diseases, the term "stroke" is not consistently defined in clinical practice, in clinical research, or in assessments of the public health. The classic definition is mainly clinical and does not account for advances in science and technology. The Stroke Council of the American Heart Association/American Stroke Association convened a writing group to develop an expert consensus document for an updated definition of stroke for the 21st century. Central nervous system infarction is defined as brain, spinal cord, or retinal cell death attributable to ischemia, based on neuropathological, neuroimaging, and/or clinical evidence of permanent injury. Central nervous system infarction occurs over a clinical spectrum: Ischemic stroke specifically refers to central nervous system infarction accompanied by overt symptoms, while silent infarction by definition causes no known symptoms. Stroke also broadly includes intracerebral hemorrhage and subarachnoid hemorrhage. The updated definition of stroke incorporates clinical and tissue criteria and can be incorporated into practice, research, and assessments of the public health.

An Updated Definition of Stroke for the 21st Century A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association

As the availability and quality of imaging techniques improve, doctors are identifying more patients with no history of transient ischaemic attack or stroke in whom imaging shows brain infarcts. Until recently, little was known about the relevance of these lesions. In this systematic review, we give an overview of the frequency, causes, and consequences of MRI-defined silent brain infarcts, which are detected in 20% of healthy elderly people and up to 50% of patients in selected series. Most infarcts are lacunes, of which hypertensive small-vessel disease is thought to be the main cause. Although silent infarcts, by definition, lack clinically overt stroke-like symptoms, they are associated with subtle deficits in physical and cognitive function that commonly go unnoticed. Moreover, the presence of silent infarcts more than doubles the risk of subsequent stroke and dementia. Future studies will have to show whether screening and treating high-risk patients can effectively reduce the risk of further infarcts, stroke, and dementia.

https://www.thelancet.com/pdfs/journals/laneur/PIIS1474-4422(07)70170-9.pdf

Silent brain infarcts: a systematic review

The blood–brain barrier (BBB) is formed by brain endothelial cells lining the cerebral microvasculature, and is an important mechanism for protecting the brain from fluctuations in plasma composition, and from circulating agents such as neurotransmitters and xenobiotics capable of disturbing neural function. The barrier also plays an important role in the homeostatic regulation of the brain microenvironment necessary for the stable and co-ordinated activity of neurones. The BBB phenotype develops under the influence of associated brain cells, especially astrocytic glia, and consists of more complex tight junctions than in other capillary endothelia, and a number of specific transport and enzyme systems which regulate molecular traffic across the endothelial cells. Transporters characteristic of the BBB phenotype include both uptake mechanisms (e.g. GLUT-1 glucose carrier, L1 amino acid transporter) and efflux transporters (e.g. P-glycoprotein). In addition to a role in long-term barrier induction and maintenance, astrocytes and other cells can release chemical factors that modulate endothelial permeability over a time-scale of seconds to minutes. Cell culture models, both primary and cell lines, have been used to investigate aspects of barrier induction and modulation. Conditioned medium taken from growing glial cells can reproduce some of the inductive effects, evidence for involvement of diffusible factors. However, for some features of endothelial differentiation and induction, the extracellular matrix plays an important role. Several candidate molecules have been identified, capable of mimicking aspects of glial-mediated barrier induction of brain endothelium; these include TGFβ, GDNF, bFGF, IL-6 and steroids. In addition, factors secreted by brain endothelial cells including leukaemia inhibitory factor (LIF) have been shown to induce astrocytic differentiation. Thus endothelium and astrocytes are involved in two-way induction. Short-term modulation of brain endothelial permeability has been shown for a number of small chemical mediators produced by astrocytes and other nearby cell types. It is clear that endothelial cells are involved in both long- and short-term chemical communication with neighbouring cells, with the perivascular end feet of astrocytes being of particular importance. The role of barrier induction and modulation in normal physiology and in pathology is discussed.

/pdf/astrocyte-endothelial-interactions-and-blood-brain-barrier-3eip6zehhy.pdf

Astrocyte–endothelial interactions and blood–brain barrier permeability*

Editor's Choice - Management of Atherosclerotic Carotid and Vertebral Artery Disease: 2017 Clinical Practice Guidelines of the European Society for Vascular Surgery (ESVS).

Objective: To assess the relationship between asymptomatic carotid stenosis, neuropsychological test performance, and silent MRI lesions. Methods: Performance on several neuropsychological tests was compared in 189 subjects with ultrasound-assessed carotid stenosis and 201 control subjects without carotid stenosis, recruited from a population health study. Subjects with a previous history of stroke were excluded. The test battery included tests of attention, psychomotor speed, memory, language, speed of information processing, motor functioning, intelligence, and depression. Sagittal T1-weighted and axial and coronal T2-weighted spin echo MRI was performed, and presence of MRI lesions (white matter hyperintensities, lacunar and cortical infarcts) was recorded. Results: Subjects with carotid stenosis had significantly lower levels of performance in tests of attention, psychomotor speed, memory, and motor functioning, independent of MRI lesions. There were no significant differences in tests of speed of information processing, word association, or depression. Cortical infarcts and white matter hyperintensities were equally distributed among persons with and without carotid stenosis. Lacunar infarcts were more frequent in the stenosis group ( p = 0.03). Conclusions: Carotid stenosis was associated with poorer neuropsychological performance. This could not be explained by a higher proportion of silent MRI lesions in persons with asymptomatic carotid stenosis, making it less likely that the cognitive impairment was caused by silent emboli.

Reduced neuropsychological test performance in asymptomatic carotid stenosis: The Tromsø Study.

Objective The present study was conducted to validate S-100 protein as a marker of brain damage after minor head injury. Methods We studied 50 patients with minor head injuries and Glasgow Coma Scale scores of 13 to 15 in whom computed tomographic scans of the brain revealed no abnormalities. Serum levels of S-100 protein were measured at admittance and hourly thereafter until 12 hours after injury. Magnetic resonance imaging and baseline neuropsychological examinations were performed within 48 hours, and neuropsychological follow-up was conducted at 3 months postinjury. Results Fourteen patients (28%) had detectable serum levels of S-100 protein (mean peak value, 0.4 microg/L [standard deviation, +/- 0.3]). The S-100 protein levels were highest immediately after the trauma, and they declined each hour thereafter. At 6 hours postinjury, the serum level was below the detection limit (0.2 microg/L) in five (36%) of the patients with initially detectable levels. Magnetic resonance imaging revealed brain contusions in five patients, four of whom demonstrated detectable levels of S-100 protein in serum. The proportion of patients with detectable serum levels was significantly higher when magnetic resonance imaging revealed a brain contusion. In patients with detectable serum levels, we observed a trend toward impaired neuropsychological functioning on measures of attention, memory, and information processing speed. Conclusion Determination of S-100 protein levels in serum provides a valid measure of the presence and severity of traumatic brain damage if performed within the first hours after minor head injury.

Traumatic brain damage in minor head injury: relation of serum S-100 protein measurements to magnetic resonance imaging and neurobehavioral outcome.

OBJECTIVE: To determine if fatigue in patients with systemic lupus erythematosus (SLE) is associated with levels of serum cytokines, antiphospholipid antibodies (aPL), or other disease features. METHODS: In a cross sectional study 57 Caucasian patients with SLE were subjected to clinical neurological examination and cerebral magnetic resonance imaging (MRI). Fatigue was evaluated by Fatigue Severity Scale (FSS) and disease activity by SLE Disease Activity Index (SLEDAI). Serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin 2 (IL-2), IL-6, IL-10, transforming growth factor-beta (TGF-beta), interferon-alpha (IFN-alpha), anticardiolipin antibody (aCL) IgG and IgM, as well as anti-beta2-glycoprotein I antibody (anti-beta2-GPI) IgG and IgM were analyzed by ELISA. RESULTS: Four of 5 patients with SLE had fatigue (FSS score > or = 3). There were no associations between fatigue and any sociodemographic variables, medication for SLE, disease activity, cerebral infarcts, serum cytokines, aCL or beta2-GPI antibodies, or any routine hematological, biochemical, or immunological tests. CONCLUSION: Fatigue is a common phenomenon in patients with SLE. There is no association to disease activity or other markers of disease or inflammation. Fatigue is a complex phenomenon, and cytokine involvement in brain tissue not reflected by cytokine serum concentrations in this study cannot be excluded. Alternatively, psychosocial factors may well be the dominant predictor of fatigue in patients with SLE.

https://www.jrheum.org/content/jrheum/29/3/482.full.pdf

Fatigue in patients with systemic lupus erythematosus: lack of associations to serum cytokines, antiphospholipid antibodies, or other disease characteristics.

Cognitive dysfunction is found in a considerable proportion of patients with systemic lupus erythematosus (SLE). SPECT provides an estimate of regional cerebral blood flow (rCBF) which has been claimed to be sensitive to detect brain involvement in SLE. It is, however, uncertain if these perfusion defects are related to cognitive dysfunction. In the present study we investigated whether cerebral dysfunction assessed by neuropsychological measures was associated with changes in rCBE Fifty-two SLE patients were examined with a battery of neuropsychological tests and MRI of the brain. For each patient 99mTC-HMPAO-SPECT was performed with the visual cortex as reference, and a reduction in rCBF of > 15% was considered abnormal. Regional CBF was performed with an automated computer program quantitatively estimating blood perfusion in 16 symmetrical sectors of the brain. Several sectors of the brain showed varying areas of reduced rCBF with the temporal lobes most frequently involved. There were generally no associations between cognitive level of functioning and reduced rCBF. MRI demonstrated cerebral infarcts in 9 (17%) patients. In general rCBF was reduced in all sectors of the brain in patients with infarcts, although statistical significant difference in rCBF between patients with and without infarcts was only seen in the parietal lobe. Several neuropsychological functions were influenced by the presence of cerebral infarcts. There was no significant association between immunological measures and SPECT findings or neuropsychological measures. Neuropsychological dysfunction in SLE was associated with the presence of cerebral infarcts detected by MRI, but not by changes in rCBF. SPECT seems to add little if any information to that obtained by clinical examination, neuropsychological testing, and MRI. Since anticoagulation may prevent cerebral infarcts, such prophylactic intervention may be of importance in preventing cognitive deterioration.

Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow.

An autostereoscopic display with image quality comparable to ordinary 2D displays has recently been developed. The purpose of our study was to evaluate whether the visualization of static 3D models from intracranial time-of-flight (TOF) MR angiography (MRA) was improved by this display. Maximum Intensity Projection (MIP) and Volume Rendering (VR) 3D models of intracranial arteries were created from ten TOF MRA datasets. Thirty-one clinically relevant intracranial arterial segments were marked in the TOF source images. A total of 217 markings were used. The markings were displayed in the 3D models as overlying red dots. Three neuroradiologists viewed the static 3D models on the autostereoscopic display, with the display operating either in autostereoscopic mode or in 2D mode. The task of the neuroradiologists was to correctly identify the marked artery. A paired comparison was made between arterial identification in autostereoscopic and 2D display mode. In 314 MIP 3D models, 233 arterial markings (74%) were correctly identified with the display operating in autostereoscopic mode versus 179 (57%) in 2D mode. Odds ratio for correct identification with autostereoscopic mode versus 2D mode was 2.17 (95% confidence interval 1.55–3.04, P < 0.001). In 337 VR 3D models, 256 markings (76%) were correctly identified using autostereoscopic mode and 229 (68%) using 2D mode (odds ratio 1.49, 95% confidence interval 1.06–2.09, P = 0.021). The visualization of intracranial arteries in static 3D models from TOF MRA can be improved by the use of an autostereoscopic display.

Eva A. Jacobsen

Papers

Reduced neuropsychological test performance in asymptomatic carotid stenosis: The Tromsø Study.

Traumatic brain damage in minor head injury: relation of serum S-100 protein measurements to magnetic resonance imaging and neurobehavioral outcome.

Fatigue in patients with systemic lupus erythematosus: lack of associations to serum cytokines, antiphospholipid antibodies, or other disease characteristics.

Neuropsychological dysfunction in systemic lupus erythematosus is not associated with changes in cerebral blood flow.

An autostereoscopic 3D display can improve visualization of 3D models from intracranial MR angiography.