Although pregnancy-associated stroke is uncommon, the risk of stroke is greatly increased above the low baseline rate in young patients during late pregnancy and, even more so, during the puerperium. Stroke is a major contributor to the serious morbidity and mortality of pregnancy. The physiological hormonally mediated changes in circulation, vascular tissue structure, and coagulability, and the pathological state of pre-eclampsia-eclampsia contribute to this increased risk of stroke. Pregnancy-associated strokes are roughly evenly divided among hemorrhagic strokes, mainly from rupture of aneurysms and arteriovenous malformations (AVMs); ischemic strokes, mainly from late pregnancy and postpartum cerebral venous thrombosis; and strokes associated with pre-eclampsia-eclampsia, with a contribution from cardioembolism, especially in populations at risk from a high rate of underlying rheumatic valvular heart disease. Awareness of the types of stroke to expect during pregnancy will facilitate early diagnosis. This article discusses the pathogenesis of pregnancy-associated stroke, its epidemiology, and some diagnostic and therapeutic issues unique to pregnancy.

HomeStrokeVol. 52, No. 9Treat or Retreat: Reasons for Deferral of Endovascular Therapy for Large Vessel Occlusion Stroke Free AccessEditorialPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessEditorialPDF/EPUBTreat or Retreat: Reasons for Deferral of Endovascular Therapy for Large Vessel Occlusion Stroke Erica Camargo, MD, MMSc, PhD Ashutosh P. JadhavMD, PhD Erica CamargoErica Camargo Correspondence to: Erica Camargo, MD, MMSc, PhD, Stroke Service, Massachusetts General Hospital, Harvard Medical School, 175 Cambridge St, Suite 340, Boston, MA 02114. Email E-mail Address: [email protected] https://orcid.org/0000-0002-3722-6463 Stroke Service, Massachusetts General Hospital; and Harvard Medical School, Boston, MA (E.C.). and Ashutosh P. JadhavAshutosh P. Jadhav Department of Neurosurgery, Barrow Neurological Institute, Phoenix, AZ (A.P.J.). Originally published22 Jul 2021https://doi.org/10.1161/STROKEAHA.121.034361Stroke. 2021;52:2754–2756This article is a commentary on the followingReasons for Not Performing Mechanical Thrombectomy: A Population-Based Study of Stroke CodesSee related article, p 2746Endovascular therapy (EVT) has revolutionized the care of patients with acute ischemic stroke (AIS) and is now recognized as one of the most effective interventions to improve clinical outcomes, with a number needed to treat as low as 2 to 3.1–5 Despite its benefits, EVT has been mainly applied to baseline functionally independent patients with severe clinical symptoms in the setting of a proximal large vessel occlusion of the anterior circulation with small core volume. Furthermore, access to EVT-capable centers may be limited. Hence, the percentage of patients that currently receive EVT for AIS has been reported as low as 1.9% to 20.6% in industrialized nations.6,7In this issue of Stroke, Guisado-Alonso et al8 address an important question: are there opportunities to increase the number of patients eligible for EVT? The authors analyzed data from a large, well-established prospective stroke code registry (Codi Ictus Catalunya, Stroke Code Catalonia) in Catalonia, Spain. They analyzed variables that were associated with deferral of EVT for AIS, and the proportion of patients that could potentially receive EVT if barriers were excluded. In Codi Ictus Catalunya, Stroke Code Catalonia, a code stroke was activated for patients with a positive Face, Arms, Speech, Time screen, baseline functional independence (modified Rankin Scale score [mRS]<3) and who were within 8 hours of suspected symptoms onset. Criteria for EVT were more restrictive and included: mRS score of ≤1, Alberta Stroke Program Early CT Score ≤6, National Institutes of Health Stroke Scale score (NIHSS) ≥6, and initiation of EVT within 8 hours of symptoms onset. As expected, patients that did not only receive EVT had milder strokes but also had less improvement in NIHSS when compared with the EVT group. Absence of large vessel occlusion (LVO, in 42%) was the most common reason for deferral of EVT. However, for the 667 patients who had an LVO, EVT was deferred in 10.5% of cases because of an unfavorable neuroimaging profile; in 8.1% due to age, mRS or medical comorbidities indicating a likely poor functional outcome; in 7.2% because the thrombus was deemed inaccessible; and in 7% because deficits were considered too mild. Half of the occlusions deemed inaccessible were of the middle cerebral artery (MCA) M2 segment. This study was performed in the first half of 2018, during which time the DAWN (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention With Trevo) and DEFUSE-3 (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke) trials were published.9,10 Hence, the therapeutic time window was expanded to the extended time window in Codi Ictus Catalunya, Stroke Code Catalonia to conform to stroke guidelines. Due to this, only 0.7% of patients with LVO were denied EVT based on a therapeutic time window of >8 hours. The authors concluded that if the above potentially modifiable reasons for not performing EVT were excluded, the eligibility of EVT for all ischemic stroke code patients in Codi Ictus Catalunya, Stroke Code Catalonia could increase from 18.4% to 43.1%.The potentially modifiable reasons for not performing EVT are much debated in the literature. A radiological profile is deemed unfavorable for EVT when there is a large baseline infarct (core >70 cm3 or Alberta Stroke Program Early CT Score <6) and absence of salvageable penumbra. Patients with such radiological profiles have largely been excluded from major clinical trials, although this landscape is evolving. Data from the HERMES (Highly Effective Reperfusion evaluated in Multiple Endovascular Stroke) collaboration suggest that patients that have low Alberta Stroke Program Early CT Score (2–5) or large core receiving EVT experience reduced mortality and improved 90-day mRS when compared with patients receiving medical management, without an increased risk of symptomatic intracranial hemorrhage.11,12 A meta-analysis of studies involving EVT in 1196 patients with Alberta Stroke Program Early CT Score <5 showed no difference in the rates of mortality between EVT and medical management, but a significant benefit in 90-day mRS for the EVT group.13 There are multiple ongoing studies of EVT for patients with large cores.Older patients and those with poor functional baseline are often deprived of thrombectomy for AIS. However, in most of the landmark EVT trials, all adult patients were eligible for study inclusion. In these trials, older patients achieved similar benefits from EVT as compared to younger patients.1–5 This was confirmed by the HERMES collaboration, which showed that the benefit of EVT was highest in the subgroup of patients ≥80 years of age.11 Similarly, a recent study comparing EVT outcomes in nonagenarians to adults ≤69 years old showed similar rates of favorable disposition and of in-hospital deaths between the 2 groups.14 Patients with baseline disability are also often excluded from clinical trials of EVT and in clinical practice. A recent study challenged this construct, suggesting that patients with premorbid disability (mRS score 2–4) undergoing EVT achieve benefit in terms of accumulated disability.15Multiple studies have addressed the risks and benefit of EVT for medium vessel occlusions. A retrospective study of 522 patients with ischemic stroke due to M2 occlusions demonstrated safety of EVT. Furthermore, EVT led to a significantly higher likelihood of favorable outcome at 90 days when compared with best medical management.16 However, randomized clinical trial data are lacking. In an analysis of the HERMES collaboration data, AIS patients with MCA-M2 occlusions receiving EVT had favorable clinical outcomes at 90 days when compared with controls, especially for those with proximal M2 occlusions and with dominant M2 segment occlusions.17 Additional studies have shown that EVT of MCA-M2 occlusions is feasible and that recanalization rates and outcomes are similar to, or even more favorable than, EVT of MCA-M1 occlusions.18–20 However, it should be noted that results may be confounded by the fact that patients with MCA-M2 occlusions are more likely to have lower baseline NIHSS scores and may receive intravenous thrombolytic therapy more frequently.20 Very distal thrombectomy (MCA-M3) and thrombectomy of the anterior cerebral and posterior cerebral arteries has been successfully performed.21Many studies of EVT for AIS have excluded patients with NIHSS score <6. However, a substantial proportion of patients with low NIHSS that receive the best medical care experience poor long-term outcomes.22 Furthermore, the disability experienced varies according to the type of deficit incurred. The question as to which patients with low NIHSS might benefit from EVT remains unresolved. In the Safe Implementation of Thrombolysis International Stroke Thrombolysis Register, ≈25% of patients with NIHSS score 0–5 had an LVO. Early neurological deterioration occurred in 9% of patients with LVO as opposed to 3.1% of patients without LVO. This was most significant for patients with internal carotid artery terminus or MCA-M1 occlusions.23 Many studies comparing EVT to best medical management for patients with AIS and low NIHSS have been performed. Unfortunately, there is wide heterogeneity in the design of these studies, and they have yielded conflicting results. This too is a topic of ongoing investigation in clinical trials.24In the current study, eligibility for enrollment was weighted toward anterior circulation strokes, patients with high NIHSS scores and with good functional baseline. Thus, future studies should address these specific gaps. Furthermore, while the projected percentage of increased access to EVT is promising, this must be considered in the context of a study undertaken in a well-developed stroke network with advanced emergency medical services integration, and experienced stroke neurologists and interventionalists. Therefore, the generalizability of this study may be limited. Although these thought-provoking findings are exploratory, this data is relevant in informing future clinical trials and will hopefully further propel interest in expanding the role and availability of EVT in AIS care. While treatment expansion will likely increase the number needed to treat of EVT from 2 to 3 to a higher number, studies like this one indicate that current strategies are potentially leading to under-treatment, particularly as the number needed to treat for other conditions such as percutaneous coronary intervention for myocardial infarction are in the range of 29 to 45.25DisclosuresNone.FootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Disclosures, see page 2755.Correspondence to: Erica Camargo, MD, MMSc, PhD, Stroke Service, Massachusetts General Hospital, Harvard Medical School, 175 Cambridge St, Suite 340, Boston, MA 02114. Email [email protected]orgReferences1. Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, et al.; MR CLEAN Investigators. 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Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke.N Engl J Med. 2015; 372:2285–2295. doi: 10.1056/NEJMoa1415061CrossrefMedlineGoogle Scholar5. Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Román L, Serena J, Abilleira S, Ribó M, et al.; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke.N Engl J Med. 2015; 372:2296–2306. doi: 10.1056/NEJMoa1503780CrossrefMedlineGoogle Scholar6. Aguiar de Sousa D, von Martial R, Abilleira S, Gattringer T, Kobayashi A, Gallofre M, Fazekas F, Szikora I, Feigin V, Caso V, et al.. Access to and delivery of acute ischaemic stroke treatments: a survey of National Scientific Societies and Stroke Experts in 44 European Countries.Eur Stroke J. 2019; 4:13–28.Google Scholar7. Bosson N, Gausche-Hill M, Saver JL, Sanossian N, Tadeo R, Clare C, Perez L, Williams M, Rasnake S, Nguyen PL; Los Angeles County Stroke Data Collaborative. Increased access to and use of endovascular therapy following implementation of a 2-tiered regional stroke system.Stroke. 2020; 51:908–913. doi: 10.1161/STROKEAHA.119.027756LinkGoogle Scholar8. Guisado-Alonso D, Martínez-Domeño A, Prats-Sánchez L, Delgado-Mederos R, Camps-Renom P, Abilleira S, Pérez de la Ossa N, Ramos-Pachon A, Cardona P, Rodriguez-Campello A, et al.. Reasons for not performing mechanical thrombectomy: a population-based study of stroke codes.Stroke. 2021; 52:2746–2753. doi: 10.1161/STROKEAHA.120.032648LinkGoogle Scholar9. Nogueira RG, Jadhav AP, Haussen DC, Bonafe A, Budzik RF, Bhuva P, Yavagal DR, Ribo M, Cognard C, Hanel RA, et al.; DAWN Trial Investigators. Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct.N Engl J Med. 2018; 378:11–21. doi: 10.1056/NEJMoa1706442CrossrefMedlineGoogle Scholar10. Albers GW, Marks MP, Kemp S, Christensen S, Tsai JP, Ortega-Gutierrez S, McTaggart RA, Torbey MT, Kim-Tenser M, Leslie-Mazwi T, et al.; DEFUSE 3 Investigators. Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging.N Engl J Med. 2018; 378:708–718. doi: 10.1056/NEJMoa1713973CrossrefMedlineGoogle Scholar11. Goyal M, Menon BK, van Zwam WH, Dippel DW, Mitchell PJ, Demchuk AM, Dávalos A, Majoie CB, van der Lugt A, de Miquel MA, et al.; HERMES Collaborators. Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials.Lancet. 2016; 387:1723–1731. doi: 10.1016/S0140-6736(16)00163-XCrossrefMedlineGoogle Scholar12. Campbell BCV, Majoie CBLM, Albers GW, Menon BK, Yassi N, Sharma G, van Zwam WH, van Oostenbrugge RJ, Demchuk AM, Guillemin F, et al.; HERMES Collaborators. Penumbral imaging and functional outcome in patients with anterior circulation ischaemic stroke treated with endovascular thrombectomy versus medical therapy: a meta-analysis of individual patient-level data.Lancet Neurol. 2019; 18:46–55. doi: 10.1016/S1474-4422(18)30314-4CrossrefMedlineGoogle Scholar13. Diestro JDB, Dmytriw AA, Broocks G, Chen K, Hirsch JA, Kemmling A, Phan K, Bharatha A. Endovascular thrombectomy for low ASPECTS large vessel occlusion ischemic stroke: a systematic review and meta-analysis.Can J Neurol Sci. 2020; 47:612–619. doi: 10.1017/cjn.2020.71Google Scholar14. Agarwal S, Huang J, Scher E, Farkas J, Arcot K, Gordon D, Turkel-Parrella D, Tiwari A, Liff J, Yaghi S, et al.. Mechanical thrombectomy in nonagenarians: a propensity score matched analysis.J Stroke Cerebrovasc Dis. 2020; 29:104870. doi: 10.1016/j.jstrokecerebrovasdis.2020.104870Google Scholar15. Regenhardt RW, Young MJ, Etherton MR, Das AS, Stapleton CJ, Patel AB, Lev MH, Hirsch JA, Rost NS, Leslie-Mazwi TM. Toward a more inclusive paradigm: Thrombectomy for stroke patients with pre-existing disabilities [published online October 30, 2020].J Neurointerv Surg. doi: 10.1136/neurintsurg-2020-016783Google Scholar16. Sarraj A, Sangha N, Hussain MS, Wisco D, Vora N, Elijovich L, Goyal N, Abraham M, Mittal M, Feng L, et al.. Endovascular therapy for acute ischemic stroke with occlusion of the middle cerebral artery M2 segment.JAMA Neurol. 2016; 73:1291–1296. doi: 10.1001/jamaneurol.2016.2773CrossrefMedlineGoogle Scholar17. Menon BK, Hill MD, Davalos A, Roos YBWEM, Campbell BCV, Dippel DWJ, Guillemin F, Saver JL, van der Lugt A, Demchuk AM, et al.. Efficacy of endovascular thrombectomy in patients with M2 segment middle cerebral artery occlusions: meta-analysis of data from the HERMES Collaboration.J Neurointerv Surg. 2019; 11:1065–1069. doi: 10.1136/neurintsurg-2018-014678CrossrefMedlineGoogle Scholar18. Baharvahdat H, Ooi YC, Khatibi K, Ponce Mejia LL, Kaneko N, Nour M, Szeder V, Jahan R, Tateshima S, Vinuela F, et al.. Increased rate of successful first passage recanalization during mechanical thrombectomy for M2 occlusion.World Neurosurg. 2020; 139:e792–e799. doi: 10.1016/j.wneu.2020.04.159Google Scholar19. de Havenon A, Narata AP, Amelot A, Saver JL, Bozorgchami H, Mattle HP, Ribo M, Andersson T, Zaidat OO; ARISE II Investigators. Benefit of endovascular thrombectomy for m2 middle cerebral artery occlusion in the ARISE II study [published online November 20, 2020].J Neurointerv Surg. doi: 10.1136/neurintsurg-2020-016427Google Scholar20. Alexander C, Caras A, Miller WK, Tahir R, Mansour TR, Medhkour A, Marin H. M2 segment thrombectomy is not associated with increased complication risk compared to M1 segment: a meta-analysis of recent literature.J Stroke Cerebrovasc Dis. 2020; 29:105018. doi: 10.1016/j.jstrokecerebrovasdis.2020.105018Google Scholar21. Grossberg JA, Rebello LC, Haussen DC, Bouslama M, Bowen M, Barreira CM, Belagaje SR, Frankel MR, Nogueira RG. Beyond large vessel occlusion strokes: distal occlusion thrombectomy.Stroke. 2018; 49:1662–1668. doi: 10.1161/STROKEAHA.118.020567LinkGoogle Scholar22. Romano JG, Smith EE, Liang L, Gardener H, Camp S, Shuey L, Cook A, Campo-Bustillo I, Khatri P, Bhatt DL, et al.. Outcomes in mild acute ischemic stroke treated with intravenous thrombolysis: a retrospective analysis of the Get With the Guidelines-Stroke registry.JAMA Neurol. 2015; 72:423–431. doi: 10.1001/jamaneurol.2014.4354CrossrefMedlineGoogle Scholar23. Mazya MV, Cooray C, Lees KR, Toni D, Ford GA, Bar M, Frol S, Moreira T, Sekaran L, Švigelj V, et al.. Minor stroke due to large artery occlusion. When is intravenous thrombolysis not enough? Results from the SITS International Stroke Thrombolysis Register.Eur Stroke J. 2018; 3:29–38. doi: 10.1177/2396987317746003Google Scholar24. McCarthy DJ, Tonetti DA, Stone J, Starke RM, Narayanan S, Lang MJ, Jadhav AP, Gross BA. More expansive horizons: a review of endovascular therapy for patients with low NIHSS scores.J Neurointerv Surg. 2021; 13:146–151. doi: 10.1136/neurintsurg-2020-016583Google Scholar25. Huynh T, Perron S, O'Loughlin J, Joseph L, Labrecque M, Tu JV, Théroux P. Comparison of primary percutaneous coronary intervention and fibrinolytic therapy in ST-segment-elevation myocardial infarction: Bayesian hierarchical meta-analyses of randomized controlled trials and observational studies.Circulation. 2009; 119:3101–3109. doi: 10.1161/CIRCULATIONAHA.108.793745LinkGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsRelated articlesReasons for Not Performing Mechanical Thrombectomy: A Population-Based Study of Stroke CodesDaniel Guisado-Alonso, et al. Stroke. 2021;52:2746-2753 September 2021Vol 52, Issue 9Article InformationMetrics Download: 1,054 © 2021 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.121.034361PMID: 34289709 Originally publishedJuly 22, 2021 Keywordsmiddle cerebral arteryEditorialsNational Institutes of Healthischemic strokethrombectomyneuroimagingPDF download SubjectsCerebrovascular ProceduresAngiographyRevascularizationTreatmentIschemic Stroke

Pregnancy and the puerperium confer an increased risk for ischemic as well as hemorrhagic stroke, with incidence rates being 3-fold higher as compared with nonpregnant women. A meta-analysis of the epidemiologic characteristics and risk factors for stroke in pregnancy found that the mean age ranged from 22 to 33 years, and the crude incidence rate was 30 in 100,000 (95% confidence interval [CI], 18.8?49.4 in 100,000), which was nearly 3 times that of nonpregnant women of childbearing age suffering a stroke.1 The rate of ischemic and hemorrhagic stroke was 12.2 in 100,000 pregnancies, whereas for cerebral venous sinus thrombosis (CVST) the rate

Background. Although recent evidence has shown a new role of fluoxetine in motor rehabilitation, results are mixed. We conducted a randomized clinical trial to evaluate whether combining repetitive transcranial magnetic stimulation (rTMS) with fluoxetine increases upper limb motor function in stroke. Methods. Twenty-seven hemiparetic patients within 2 years of ischemic stroke were randomized into 3 groups: Combined (active rTMS + fluoxetine), Fluoxetine (sham rTMS + fluoxetine), or Placebo (sham rTMS + placebo fluoxetine). Participants received 18 sessions of 1-Hz rTMS in the unaffected primary motor cortex and 90 days of fluoxetine (20 mg/d). Motor function was assessed using Jebsen-Taylor Hand Function (JTHF) and Fugl-Meyer Assessment (FMA) scales. Corticospinal excitability was assessed with TMS. Results. After adjusting for time since stroke, there was significantly greater improvement in JTHF in the combined rTMS + fluoxetine group (mean improvement: -214.33 seconds) than in the placebo (-177.98 seconds, P = 0.005) and fluoxetine (-50.16 seconds, P < 0.001) groups. The fluoxetine group had less improvement than placebo on both scales (respectively, JTHF: -50.16 vs -117.98 seconds, P = 0.038; and FMA: 6.72 vs 15.55 points, P = 0.039), suggesting that fluoxetine possibly had detrimental effects. The unaffected hemisphere showed decreased intracortical inhibition in the combined and fluoxetine groups, and increased intracortical facilitation in the fluoxetine group. This facilitation was negatively correlated with motor function improvement (FMA, r2 = -0.398, P = 0.0395). Conclusion. Combined fluoxetine and rTMS treatment leads to better motor function in stroke than fluoxetine alone and placebo. Moreover, fluoxetine leads to smaller improvements than placebo, and fluoxetine's effects on intracortical facilitation suggest a potential diffuse mechanism that may hinder beneficial plasticity on motor recovery.

Pregnancy confers a substantially increased risk of stroke in women. The period of highest risk of stroke is the peripartum/postpartum phase, coinciding with the highest risk for hypertensive disorders of pregnancy and peak gestational hypercoagulability. Hemorrhagic stroke is the most common type of obstetric stroke. Hypertensive disorders of pregnancy are important contributors to obstetric stroke and predispose women to premature cardiovascular disease. The rate of stroke associated with hypertensive disorders of pregnancy has increased in the United States. Other conditions associated with obstetric stroke include posterior reversible encephalopathy, reversible cerebral vasoconstriction syndrome, and cerebral venous sinus thrombosis.

Ischemic stroke describes a condition in which inadequate blood flow leads to lack of oxygenation to the brain tissue and ensuing neuronal death. There are multiple causes of ischemic stroke, each of which may indicate different antithrombotic management strategies. The goal of this review is to provide information about antithrombotic therapies for secondary stroke prevention based on etiology of stroke.

Pregnancy places women at a higher risk for hemorrhagic and ischemic strokes. This review discusses the pathophysiological mechanisms underlying this increased risk, management considerations for pregnant patients, and ways to decrease the risk of stroke in this patient population. Rates of ischemic and hemorrhagic pregnancy-associated stroke have increased over the past 20 years, particularly events associated with hypertensive disorders of pregnancy. There is a growing body of evidence supporting the use of acute reperfusion therapies in ischemic pregnancy-associated stroke including tissue plasminogen activator (tPA) and endovascular thrombectomy. While the unique physiology of pregnancy places women at a higher risk of stroke, acute ischemic stroke management in pregnant patients should closely mirror the management of non-pregnant patients. Secondary stroke prevention agents should be selected with consideration of the pregnancy.

Selective serotonin reuptake inhibitors (SSRIs) are currently widely used in the field of the neuromodulation not only because of their anti-depressive effects but also due to their ability to promote plasticity and enhance motor recovery in patients with stroke. Recent studies showed that fluoxetine promotes motor recovery after stroke through its effects on the serotonergic system enhancing motor outputs and facilitating long term potentiation, key factors in motor neural plasticity. However, little is known in regards of the exact mechanisms underlying these effects and several aspects of it remain poorly understood. In this manuscript, we discuss evidence supporting the hypothesis that SSRIs, and in particular fluoxetine, modulate inhibitory pathways, and that this modulation enhances reorganization and reestablishment of excitatory-inhibitory control; these effects play a key role in learning induced plasticity in neural circuits involved in the promotion of motor recovery after stroke. This discussion aims to provide important insights and rationale for the development of novel strategies for stroke motor rehabilitation.

In this article, the authors review stroke preventive strategies in a diverse group of conditions, namely the nonatherosclerotic cerebral arteriopathies, migraine-associated or migraine-induced stroke, and cerebral venous sinus thrombosis. Although these conditions are less common causes of stroke in the aggregate, they are frequent causes of stroke in teenagers and young adults. Aside from posing unique diagnostic challenges, their management is limited by the absence of randomized clinical trials or high-level evidence that is specific to these conditions. Therapeutic decision-making is largely based on expert opinion, clinical experience, and retrospective studies; it is often empiric. It remains uncertain whether otherwise routine secondary stroke preventive strategies, such as long-term antiplatelet treatment, lipid-lowering medications, and antihypertensive agents, are applicable to patients with stroke from a cerebral arteriopathy or migraine-associated stroke.

Intracranial atherosclerotic stenosis (ICAS) is responsible for ≈8% of ischemic strokes and 34% of dementia diagnoses in the United States Despite targeted reduction of LDL-cholesterol using statins, treatment of hypertension, and use of antiplatelet agents, the risk of recurrent ischemic stroke is ≈14% over 1 year for patients with severe ICAS. Intracranial atherosclerosis may also be a major contributor to variations in stroke incidence and mortality and to disparities in stroke burden among minority populations in the United States Among patients with brain ischemic events, Asians and blacks had disproportionately more intracranial atherosclerosis than Whites. ICAS is also thought to be associated with cognitive deficits of varying severity, including impaired executive function, slowing of activity and thinking, and even anterograde amnesia. Despite its clinical importance, there is minimal data, especially in the United States, about the prevalence of ICAS. Estimates of the prevalence of ICAS are based either on autopsy series or on the detection of arterial calcification, magnetic resonance angiography (MRA) of selected Background and Purpose—Intracranial atherosclerotic stenosis (ICAS) is a common cause of stroke, but little is known about its epidemiology. We studied the prevalence of ICAS and its association with vascular risk factors using highresolution magnetic resonance angiography in a US cardiovascular cohort. Methods—The Atherosclerosis Risk in Communities (ARIC) study recruited participants from 4 US communities from 1987 to 1989. Using stratified sampling, we selected 1980 participants from visit 5 (2011–2013) for high-resolution 3T-magnetic resonance angiography. All images were analyzed in a centralized laboratory, and ICAS was graded as: no stenosis, <50% stenosis, 50% to 69% stenosis, 70% to 99% stenosis, and complete occlusion. We calculated per-vessel and per-person prevalence of ICAS (weighted for n=6538 visit 5 participants) and also estimated the US prevalence. We used multivariable logistic regression to identify variables independently associated with ICAS. Results—Subjects who had an adequate magnetic resonance angiography (n=1765) were aged 67 to 90 years, 41% were men, 70% were white, and 29% were black. ICAS was prevalent in 31% of participants and 9% had ICAS ≥50%. Estimated US prevalence of ICAS ≥50% for 65 to 90 years old was 8% for whites and 12% for blacks. Older age, black race, higher systolic blood pressure, and higher low-density lipoprotein cholesterol levels were associated with increased odds of ICAS, whereas higher levels of high-density lipoprotein cholesterol and use of cholesterol-lowering medications were associated with decreased odds of ICAS. Body mass index and smoking were not associated with ICAS. Conclusions—The prevalence of ICAS in older adults is high, and it could be a target for primary prevention of stroke and dementia in this population. (Stroke. 2016;47:1187-1193. DOI: 10.1161/STROKEAHA.115.011292.)

In this chapter we review the optimal imaging modalities for subacute and chronic stroke. We discuss the utility of computed tomography (CT) and multimodal CT imaging. Further, we analyze the importance of specific magnetic resonance imaging sequences, such as diffusion-weighted imaging for acute ischemic stroke, T2/fluid-attenuated inversion recovery for subacute and chronic stroke, and susceptibility imaging for detection of intracranial hemorrhages. Different ischemic stroke mechanisms are reviewed, and how these imaging modalities may aid in the determination of such. Further, we analyze how topographic patterns in ischemic stroke may provide important clues to the diagnosis, in addition to the temporal evolution of the stroke. Lastly, specific cerebrovascular occlusive diseases are reviewed, with emphasis on the optimal imaging modalities and their findings in each condition.

Background and Purpose— Patients with large vessel occlusion strokes (LVOS) may be better served by direct transfer to endovascular capable centers avoiding hazardous delays between primary and comprehensive stroke centers. However, accurate stroke field triage remains challenging. We aimed to develop a simple field scale to identify LVOS. Methods— The Field Assessment Stroke Triage for Emergency Destination (FAST-ED) scale was based on items of the National Institutes of Health Stroke Scale (NIHSS) with higher predictive value for LVOS and tested in the Screening Technology and Outcomes Project in Stroke (STOPStroke) cohort, in which patients underwent computed tomographic angiography within the first 24 hours of stroke onset. LVOS were defined by total occlusions involving the intracranial internal carotid artery, middle cerebral artery-M1, middle cerebral artery-2, or basilar arteries. Patients with partial, bihemispheric, and anterior+posterior circulation occlusions were excluded. Receiver operating characteristic curve, sensitivity, specificity, positive predictive value, and negative predictive value of FAST-ED were compared with the NIHSS, Rapid Arterial Occlusion Evaluation (RACE) scale, and Cincinnati Prehospital Stroke Severity (CPSS) scale. Results— LVO was detected in 240 of the 727 qualifying patients (33%). FAST-ED had comparable accuracy to predict LVO to the NIHSS and higher accuracy than RACE and CPSS (area under the receiver operating characteristic curve: FAST-ED=0.81 as reference; NIHSS=0.80, P =0.28; RACE=0.77, P =0.02; and CPSS=0.75, P =0.002). A FAST-ED ≥4 had sensitivity of 0.60, specificity of 0.89, positive predictive value of 0.72, and negative predictive value of 0.82 versus RACE ≥5 of 0.55, 0.87, 0.68, and 0.79, and CPSS ≥2 of 0.56, 0.85, 0.65, and 0.78, respectively. Conclusions— FAST-ED is a simple scale that if successfully validated in the field, it may be used by medical emergency professionals to identify LVOS in the prehospital setting enabling rapid triage of patients.

IMPORTANCE Limited data exist regarding the natural history of proximal intracranial arterial occlusions. OBJECTIVE To investigate the outcomes of patients who had an acute ischemic stroke attributed to an anterior circulation proximal intracranial arterial occlusion. DESIGN, SETTING, AND PARTICIPANTS A prospective cohort study at 2 university-based hospitals from 2003 to 2005 in which nonenhanced computed tomography scans and computed tomography angiograms were obtained at admission of all adult patients suspected of having an ischemic stroke in the first 24 hours of symptom onset. EXPOSURE Anterior circulation proximal intracranial arterial occlusion. MAIN OUTCOMES AND MEASURES Frequency of good outcome (defined as a modified Rankin Scale score of ≤ 2) and mortality at 6 months. RESULTS A total of 126 patients with a unilateral complete occlusion of the intracranial internal carotid artery (ICA; 26 patients: median National Institutes of Health Stroke Scale [NIHSS] score, 11 [interquartile range, 5-17]), of the M1 segment of the middle cerebral artery (MCA; 52 patients: median NIHSS score, 13 [interquartile range, 6-16]), or of the M2 segment of the MCA (48 patients: median NIHSS score, 7 [interquartile range, 4-15]) were included. Of these 3 groups of patients, 10 (38.5%), 20 (38.5%), and 26 (54.2%) with ICA, MCA-M1, and MCA-M2 occlusions, respectively, achieved a modified Rankin Scale score of 2 or less, and 6 (23.1%), 12 (23.1%), and 10 (20.8%) were dead at 6 months. Worse outcomes were seen in patients with a baseline NIHSS score of 10 or higher, with a modified Rankin Scale score of 2 or less achieved in only 7.1% (1 of 14), 23.5% (8 of 34), and 22.7% (5 of 22) of patients and mortality rates of 35.7% (5 of 14), 32.4% (11 of 34), and 40.9% (9 of 22) among patients with ICA, MCA-M1, and MCA-M2 occlusions, respectively. Age (odds ratio, 0.94 [95% CI, 0.91-0.98]), NIHSS score (odds ratio, 0.73 [95% CI, 0.64-0.83]), and strength of leptomeningeal collaterals (odds ratio, 2.37 [95% CI, 1.08-5.20]) were independently associated with outcome, whereas the level of proximal intracranial arterial occlusion (ICA vs MCA-M1 vs MCA-M2) was not. CONCLUSIONS AND RELEVANCE The natural history of proximal intracranial arterial occlusion is variable, with poor outcomes overall. Stroke severity and collateral flow appear to be more important than the level of proximal intracranial arterial occlusion in determining outcomes. Our results provide useful data for proper patient selection and sample size calculations in the design of new clinical trials aimed at recanalization therapies.

Background: The role of neuroimaging in assessing prognosis in comatose cardiac survivors appears promising, but little is known regarding the import of particular spatial patterns. We report a specific spatial imaging abnormality on magnetic resonance imaging (MRI) that portends a poor prognosis: bilateral hippocampal hyperintensities on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences. Methods: Eighty sequential comatose cardiac arrest patients underwent MRI scans. Qualitative and quantitative regional analyses were performed. Patients were categorized as HIPPO+ (n = 18) or HIPPO- (n = 62) based on whether they had bilateral hippocampal hyperintensities. Poor outcome was defined by a modified Rankin Scale (mRS) score >= 4 at 6 months. Results: Patients with bilateral hippocampal abnormalities had a higher frequency of poor outcome (P = .032). HIPPO+ patients suffered more severe cerebral injury, with lower whole brain apparent diffusion coefficient values (P = .043) and a greater number of affected regions on DWI (P = .001) and FLAIR (P = .001) than HIPPO- patients. The hippocampal approach was 100% specific for a poor prognosis; only 1 patient survived and remained in a vegetative state. Conclusions: Bilateral hippocampal hyperintensities on MRI may be a specific imaging finding that is indicative of poor prognosis in patients who suffer global hypoxic-ischemic injury. More research on the prognostic significance of this and similar neuroimaging patterns is indicated.

Background and Purpose— To determine the effect of intravenous tissue plasminogen activator (IV-tPA) on outcomes in patients with severe major anterior circulation ischemic stroke. Methods— Prospectively, 649 patients with acute stroke had admission National Institutes of Health stroke scale (NIHSS) scores, noncontrast computed tomography (CT), CT angiography (CTA), and 6-month outcome assessed using modified Rankin scale. IV-tPA treatment decisions were made before CTA, at the time of noncontrast CT scanning, as per routine clinical protocol. Severe symptoms were defined as NIHSS>10. Poor outcome was defined as modified Rankin scale >2. Major occlusions were identified on CTA. Univariate and multivariate stepwise-forward logistic regression analyses of the full cohort were performed. Results— Of 649 patients, 188 (29%) patients presented with NIHSS>10, and 64 out of 188 (34%) patients received IV-tPA. Admission NIHSS, large artery occlusion, and IV-tPA all independently predicted good outcomes; however, a significant interaction existed between IV-tPA and occlusion ( P <0.001). Of the patients who presented with NIHSS>10 with anterior circulation occlusion, twice the percentage had good outcomes if they received IV-tPA (17 out of 49 patients, 35%) than if they did not (13 out of 77 patients, 17%; P =0.031). The number needed to treat was 7 (95% confidence interval, 3–60). Conclusions— IV-tPA treatment resulted in significantly better outcomes in patients with severely symptomatic stroke with major anterior circulation occlusions. The 35% good outcome rate was similar to rates found in endovascular therapy trials. Vascular imaging may help in patient selection and stratification for trials of IV-thrombolytic and endovascular therapies.

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/BASIS− (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/BASIS−; 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.

In clinical practice, magnetic resonance imaging (MRI) is commonly used to assess the severity of a cardiac arrest patient’s cerebral injury, utilizing treating neurologists’ imaging interpretation. We sought to determine whether clinical interpretation of diffusion-weighted imaging (DWI) helps to determine poor outcome in comatose cardiac arrest patients.

Objective: We explored the association of two simple office based tests, walking speed (WS) and hand grip strength (HGS), with the risks of incident dementia and stroke/TIA, and with brain MRI and cognition. Background Frailty and lower physical performance are frequent findings in persons with a wide range of subclinical and clinical brain injuries, and have been associated with an increased risk of dementia in the elderly. However, their predictive value in a middle-aged community sample is uncertain. Design/Methods: Stroke- and dementia-free Framingham Offspring (n=2,410; mean age 62, 54% female) had WS, HGS, brain MRI and cognitive function assessed between 1999 and 2005. We related age-standardized HGS and WS to baseline volumetric brain MRI and age- and education-standardized cognitive function using multivariable logistic regression, and to incident stroke and dementia on follow-up using Cox models. All analyses were adjusted for age, sex and vascular risk factors. Results: Over a follow-up period of up to 11years 34 persons developed incident dementia (28 AD) and 79 incident stroke/TIA. Slower WS was associated with a higher risk of dementia (HR=1.50[95%CI 1.07-2.11]/SDU,p=0.020) as well as with lower total cerebral brain volume[TCBV] (β=-0.17±0.06,p=0.007) and poorer performance on tests of memory (visual reproduction[VR],β=-0.06±0.02,p=0.009; paired associate learning[PAS],β=-0.07±0.02,p= Conclusions: In a middle-aged community sample, WS and HGS were associated, respectively, with the risks of incident dementia and of stroke/TIA and with markers of subclinical brain injury. Thus WS and HGS might serve as clinical markers of the need for a more detailed assessment of brain function. Supported by: The dedication of the Framingham Heart Study participants, the National Heart, Lung and Blood Institute9s Framingham Heart Study (Contract No. N01-HC-25195) and by grants from the National Institute of Neurological Disorders and Stroke (NS17950) and the National Institute on Aging (AG08122, AG16495, AG033193, AG031287, P30AG013846). Disclosure: Dr. Camargo has nothing to disclose. Dr. Beiser has nothing to disclose. Dr. Tan has nothing to disclose. Dr. Au has nothing to disclose. Dr. DeCarli has received personal compensation for activities wtih Merck Pharmaceutical, Avanir, Bayer Pharmaceuticals, and Pfizer as a consultant.Dr. DeCarli has received personal compensation in an editorial capacity for Alzheimer9s Disease and Associated Disorders.Dr. DeCarli has received research support from Merck. Dr. Pikula has nothing to disclose. Dr. Kelly-Hayes has nothing to disclose. Dr. Kase has nothing to disclose. Dr. Wolf has nothing to disclose. Dr. Seshadri has nothing to disclose.