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Stroke is one of the most common acute neurological disorders and a leading cause of disability worldwide. Evidence-based treatments over the last two decades have driven a revolution in the clinical management and design of stroke services. We need a highly skilled, multidisciplinary workforce that includes neurologists as core members to deliver modern stroke care. In the UK, the dedicated subspecialty training programme for stroke medicine has recently been integrated into the neurology curriculum. All neurologists will be trained to contribute to each aspect of the stroke care pathway. We discuss how training in stroke medicine is evolving for neurologists and the opportunities and challenges around practising stroke medicine in the UK and beyond., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. No commercial re-use. See rights and permissions. Published by BMJ Group.)

A female patient in her 70s presented with mild slurred speech. Clinical assessment revealed only minor dysarthria. A stroke protocol CT study was performed comprising a non-contrast CT head, CT angiogram (CTA) and CT perfusion (CTP) imaging. Despite a normal non-contrast CT head, CTP imaging demonstrated a large left anterior circulation territory abnormality compatible with core infarct. The CTA displayed absent left middle cerebral artery opacification and an abnormal pattern of thalamic and posterior fossa structure enhancement. Following a neuroradiology review, it was identified that the contrast bolus had been administered into the right brachial artery causing direct arterial opacification of the right vertebral/carotid arteries and their distal branches. No contrast was present in the left carotids or distal left intracranial anterior circulation giving the false impression of a large vessel occlusion. The patient was subsequently discharged without receiving inappropriate reperfusion therapy. This case highlights the role of technical factors influencing CT interpretation, particularly when performed by artificial intelligence/automated analysis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Osteopathia striata with cranial sclerosis (OSCS) is a rare X-linked dominant sclerosing osteodysplasia, due to AMER1 pathogenic variants. Characteristic features include craniofacial sclerosis and long-bone metaphyseal striations. Moyamoya disease (a type of progressive cerebral vasculopathy) and other types of cerebral vascular disease are not currently clearly associated with OSCS (except for two separate case reports), and can often first present with stroke. Through informal networks with UK-based bone experts and the UK skeletal dysplasia group, three cases from the UK and Ireland were identified. Medical literature was also reviewed to identify the known cases of OSCS with the described complications. We report four females, in whom OSCS and cerebral vasculopathy co-exist, with varying clinical outcomes. There appears to be an emerging association between OSCS and cerebral vasculopathy, which pre-disposes patients to stroke. Given this, screening OSCS patients for cerebral vasculopathy may be of value, especially pre-surgery. Further research regarding optimal screening and management is needed. The mechanism of cerebral vasculopathy and its progression remain unclear., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chronic kidney disease (CKD) and atrial fibrillation (AF) are increasing in prevalence globally and share common risk factors.Our aim was to characterise real-world evidence on direct oral anticoagulant (DOAC) prescribing for people with AF and CKD, in terms of adherence, persistence and renal dose titration., Methods: PubMed, EMBASE and CINAHL were searched from inception to June 2022. Our search terms included a combination of Medical Subject Headings (MeSH) terms and keywords including 'atrial fibrillation', 'chronic kidney disease', 'adherence', 'persistence', 'direct oral anticoagulants' and 'dosing'. Data extraction and quality assessment were undertaken by two reviewers independently. Meta-analyses for pooled estimates were performed using DerSimonian and Laird random-effects models. Age, sex, diabetes, hypertension and heart failure were chosen as variables of interest., Results: From 19 studies, a total of 252 117 patients were included with CKD and AF. Meta-analysis was only possible in seven studies with 128 406 patients, five on DOAC dose titration and two on adherence. There were insufficient studies on persistence. Our meta-analysis of dosing showed that 68% of patients with CKD and AF had correct dosing. There was no evidence to show any association between correct DOAC dosing and variables of interest. Overall, 67% of patients were DOAC adherent., Conclusion: Adherence and correct dosing of DOACs were suboptimal compared with other medications in the pooled studies with respect to CKD and AF. Thus, further research is required as the lack of generalisation of findings is a rate-limiting factor for improved DOAC management in AF and CKD., Prospero Registration Number: CRD;42022344491., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Spontaneous spinal cord infarction is significantly less common than cerebrovascular disease. Because of the tight anatomical distribution of pathways in the cord, small spinal cord infarcts usually give more obvious symptoms and signs than similar lesions in the brain. Large epidemiological stroke studies have generally not included spinal cord stroke and so the incidence of vascular syndromes in the spinal cord is unknown. Management and prevention strategies for spontaneous spinal cord infarcts stem from small case series and case reports. Patient outcomes from spinal cord infarction are better with prompt recognition, timely management and prevention of associated medical complications arising from paraplegia, tetraplegia, neurogenic bladder and bowel dysfunction. The process of rehabilitation following spinal cord infarction is an evolving area., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aim: Whether cerebral microbleeds cause cognitive impairment remains uncertain. We analyzed whether cerebral microbleeds are associated with cognitive dysfunction in patients with symptomatic cerebral small vessel disease, and whether this association is independent of other neuroimaging markers of cerebral small vessel disease., Methods: We analyzed consecutive patients with MRI-confirmed lacunar stroke included in DNA-Lacunar-2 multicenter study. Cerebral microbleeds were graded using the Brain Observer Microbleed Rating Scale (BOMBS). Neuropsychological assessment was performed using the Brief Memory and Executive Test (BMET). We analyzed the association between cerebral microbleeds, BMET, and the following subdomains: executive function/processing speed and orientation/memory. We also searched for an independent association between cerebral microbleeds and vascular cognitive impairment, defined as BMET ≤ 13., Results: Out of 688 included patients, cerebral microbleeds were detected in 192 (27.9%). After adjusting for white matter hyperintensities severity, lacune count, and other confounders, both the presence and the number of cerebral microbleeds were significantly associated with impaired cognitive performance [β = -13.0; 95% CI = (-25.3, -0.6) and β = -13.1; 95% CI = (-19.8, -6.4), respectively]. On analysis of specific cognitive domains, associations were present for executive function/processing speed [β = -5.8; 95% CI = (-9.3, -2.2) and β = -4.3; 95% CI = (-6.2, -2.4), respectively] but not for orientation/memory [β = -0.4; 95% CI = (-4.0, 3.2) and β = -2.1; 95% CI = (-4.0, 0.1), respectively]. We also found an independent association between the presence and the number of cerebral microbleeds and vascular cognitive impairment [adjusted OR = 1.48; 95% CI = (1.01, 2.18) and OR = 1.43; 95% CI = (1.15, 1.79), respectively]., Conclusion: In a large cohort of symptomatic cerebral small vessel disease patients, after controlling for other neuroimaging markers of cerebral small vessel disease severity, cerebral microbleeds were associated with cognitive dysfunction. Executive function and processing speed were predominantly impaired. This might suggest a causal role of cerebral microbleeds in determining vascular cognitive impairment.

Aims: To explore younger adults' experiences of stroke rehabilitation to inform practice, education and future health policy., Design: Qualitative analysis of digital and other media sources on public platforms., Methods: Between March and June 2020, the experiences of younger adult stroke survivors aged 18 to 45 at the time of the stroke were collected. Data were gathered from publicly available sources, including social media, and from English-speaking users. In total, 117 accounts from 103 participants were identified from films, autobiographical books, blogs, websites, videos, Twitter and Instagram. Data analysis followed narrative and multimodal analysis with a focus on rehabilitation needs., Results: Younger adult stroke survivors make sense of their experience by reflecting on how stroke has impacted their lives. Accounts reflected an emotional journey between the past self, the present self and evolving self, as well as associated challenges such as the impact on relationships and careers. The majority of accounts presented transitions as problematic, including the receipt of the initial diagnosis, or sometimes misdiagnosis, to returning home and achieving long-term rehabilitation goals. Specialist stroke nurses were considered essential in the rehabilitation process., Conclusion: A complex process of recovery follows stroke for younger adult stroke populations. Challenges to the rehabilitation process need to be better understood and the role of nursing highlighted in future service provision. A series of age-related challenges were highlighted that require attention to improve the care and support offered., Impact: This article informs clinicians, educators, and policymakers of the age-related needs of young adult stroke survivors. Focusing on the individual and the development of age-appropriate person-centred stroke care is important. The study highlights the role of stroke nursing and challenges the current policy focus on older stroke populations as well as arguing for greater awareness of age-appropriate stroke rehabilitation in younger adults following stroke., (© 2021 John Wiley & Sons Ltd.)

Strokectomy means surgical excision of infarcted brain tissue post-stroke with preservation of skull integrity, distinguishing it from decompressive hemicraniectomy. Both can mitigate malignant middle cerebral artery (MCA) syndrome but evidence regarding strokectomy is sparse. Here, we report our data and meta-analysis of strokectomy compared to hemicraniectomy for malignant MCA infarction. All malignant MCA stroke cases requiring surgical intervention in a large tertiary centre (January 2012-December 2017, N = 24) were analysed for craniotomy diameter, complications, length of follow-up and outcome measured using the modified Rankin score (mRS). Good outcome was defined as mRS 0-3 at 12 months. In a meta-analysis, outcome from strokectomy (pooled from our cohort and published strokectomy studies) was compared with hemicraniectomy (our cohort pooled with published DECIMAL, DESTINY and HAMLET clinical trial data). In our series (N = 24, 12/12 F/M; mean age: 45.83 ± 8.91, range 29-63 years), 4 patients underwent strokectomy (SC) and 20 hemicraniectomy (HC). Among SC patients, craniotomy diameter was smaller, relative to HC patients (86 ± 13.10 mm, 120 ± 4.10 mm, respectively; p = 0.003), complications were less common (25%, 55%) and poor outcomes were less common (25%, 70%). In the pooled data (N = 41 SC, 71 HC), strokectomy tended towards good outcome more than hemicraniectomy (OR 2.2, 95% CI 0.99-4.7; p = 0.051). In conclusion, strokectomy may be non-inferior, lower risk and cost saving relative to hemicraniectomy sufficiently to be worthy of further investigation and maybe a randomised trial., (© 2020. The Author(s).)

Stroke is the UK's leading cause of disability. Stroke rehabilitation can maximise recovery and improve quality of life. This article discusses some post-stroke impairments, including hemiplegia, dysphagia, communication impairments and neglect, and how rehabilitation can address these. Developing techniques of adaptation or compensation is vital, since the extent of stroke recovery is dependent on successful neuroplasticity, with healthy neurons adapting to compensate for damaged ones.

Elucidating the causes of stroke is key to developing effective preventive strategies. The Mendelian randomization approach leverages genetic variants related to an exposure of interest to investigate the effects of varying that exposure on disease risk. The random allocation of genetic variants at conception reduces confounding from environmental factors and thus strengthens causal inference, analogous to treatment allocation in a randomized controlled trial. With the recent explosion in the availability of human genetic data, Mendelian randomization has proven a valuable tool for studying risk factors for stroke. In this review, we provide an overview of recent developments in the application of Mendelian randomization to unravel the pathophysiology of stroke subtypes and identify therapeutic targets for clinical translation. The approach has offered novel insight into the differential effects of risk factors and antihypertensive, lipid-lowering, and anticoagulant drug classes on risk of stroke subtypes. Analyses have further facilitated the prioritization of novel drug targets, such as for inflammatory pathways underlying large artery atherosclerotic stroke and for the coagulation cascade that contributes to cardioembolic stroke. With continued methodological advances coupled with the rapidly increasing availability of genetic data related to a broad range of stroke phenotypes, the potential for Mendelian randomization in this context is expanding exponentially.

Background and Purpose: Metabolic traits affect ischemic stroke (IS) risk, but the degree to which this varies across different ethnic ancestries is not known. Our aim was to apply Mendelian randomization to investigate the causal effects of type 2 diabetes (T2D) liability and lipid traits on IS risk in African ancestry individuals, and to compare them to estimates obtained in European ancestry individuals., Methods: For African ancestry individuals, genetic proxies for T2D liability and circulating lipids were obtained from a meta-analysis of the African Partnership for Chronic Disease Research study, the UK Biobank, and the Million Veteran Program (total N=77 061). Genetic association estimates for IS risk were obtained from the Consortium of Minority Population Genome-Wide Association Studies of Stroke (3734 cases and 18 317 controls). For European ancestry individuals, genetic proxies for the same metabolic traits were obtained from Million Veteran Program (lipids N=297 626, T2D N=148 726 cases, and 965 732 controls), and genetic association estimates for IS risk were obtained from the MEGASTROKE study (34 217 cases and 406 111 controls). Random-effects inverse-variance weighted Mendelian randomization was used as the main method, complemented with sensitivity analyses more robust to pleiotropy., Results: Higher genetically proxied T2D liability, LDL-C (low-density lipoprotein cholesterol), total cholesterol and lower genetically proxied HDL-C (high-density lipoprotein cholesterol) were associated with increased risk of IS in African ancestry individuals (odds ratio per doubling the odds of T2D liability [95% CI], 1.09 [1.07-1.11]; per standard-deviation increase in LDL-C, 1.12 [1.04-1.21]; total cholesterol: 1.23 [1.06-1.43]; HDL-C, 0.93 [0.89-0.99]). There was no evidence for differences in these estimates when performing analyses in European ancestry individuals., Conclusions: Our analyses support a causal effect of T2D liability and lipid traits on IS risk in African ancestry individuals, with Mendelian randomization estimates similar to those obtained in European ancestry individuals.

Aims: Heart failure (HF) and atrial fibrillation (AF) may coexist and influence each other. However, characteristics, anticoagulant treatment, and outcomes of contemporary AF patients with concurrent HF are ill-defined. This study analyses characteristics, treatment, and 2 year outcomes in newly diagnosed Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) patients with vs. without HF., Methods and Results: GARFIELD-AF is the world's largest observational AF patient study. At enrolment, 11 758 of 52 072 patients (22.6%) had HF; 76.3% were New York Heart Association class II-III. Patients with HF had comparable demographics, blood pressure, and heart rate but more likely had permanent (15.6% vs. 11.9%) or persistent AF (18.9% vs. 13.8%), acute coronary syndromes (16.7% vs. 8.9%), vascular disease (40.8% vs. 20.2%), and moderate-to-severe chronic kidney disease (14.6% vs. 9.0%) than those without. Anticoagulant prescription was similar between the two groups. At 2 year follow-up, patients with HF showed a greater risk of all-cause mortality [hazard ratio (HR), 2.06; 95% confidence interval (CI), 1.91-2.21; P < 0.0001], cardiovascular mortality (HR, 2.91; 95% CI, 2.58-3.29; P < 0.0001), acute coronary syndromes (HR, 1.25; 95% CI, 1.02-1.52; P = 0.03), and stroke/systemic embolism (HR, 1.24; 95% CI, 1.07-1.43; P = 0.0044). Major bleeding rate was comparable (adjusted HR, 1.00; 95% CI, 0.84-1.18; P = 0.968). Among patients without HF at baseline, incidence of new HF was low [0.69 (95% CI, 0.63-0.75) per 100 person-years], whereas propensity to develop worsening HF was higher in those with HF [1.62 (95% CI, 1.45-1.80) per 100 person-years]., Conclusions: Patients with AF and HF have a high risk of all-cause and cardiovascular mortality and stroke/systemic embolism and may develop worsening HF., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objectives: We sought to identify baseline demographics and procedural factors that might independently predict in-hospital stroke following transcatheter aortic valve implantation (TAVI)., Background: Stroke is a recognized, albeit infrequent, complication of TAVI. Established predictors of procedure-related in-hospital stroke; however, remain poorly defined., Methods: We conducted an observational cohort analysis of the multicenter UK TAVI registry. The primary outcome measure was the incidence of in-hospital stroke., Results: A total of 8,652 TAVI procedures were performed from 2007 to 2015. There were 205 in-hospital strokes reported by participating centers equivalent to an overall stroke incidence of 2.4%. Univariate analysis showed that the implantation of balloon-expandable valves caused significantly fewer strokes (balloon-expandable 96/4,613 [2.08%] vs. self-expandable 95/3,272 [2.90%]; p = .020). After multivariable analysis, prior cerebrovascular disease (CVD) (odds ratio [OR] 1.51, 95% confidence interval [CI 1.05-2.17]; p = .03), advanced age at time of operation (OR 1.02 [0.10-1.04]; p = .05), bailout coronary stenting (OR 5.94 [2.03-17.39]; p = .008), and earlier year of procedure (OR 0.93 [0.87-1.00]; p = .04) were associated with an increased in-hospital stroke risk. There was a reduced stroke risk in those who had prior cardiac surgery (OR 0.62 [0.41-0.93]; p = .01) and a first-generation balloon-expandable valve implanted (OR 0.72 [0.53-0.97]; p = .03). In-hospital stroke significantly increased 30-day (OR 5.22 [3.49-7.81]; p < .001) and 1-year mortality (OR 3.21 [2.15-4.78]; p < .001)., Conclusions: In-hospital stroke after TAVI is associated with substantially increased early and late mortality. Factors independently associated with in-hospital stroke were previous CVD, advanced age, no prior cardiac surgery, and deployment of a predominantly first-generation self-expandable transcatheter heart valve., (© 2020 Wiley Periodicals LLC.)

A 53 year old female with a background of hypertension, hypothyroidism and Raynaud's was admitted with an acute ischaemic stroke and referred to the renal team after a routine urine dip revealed microscopic haematuria and nephrotic-range proteinuria. Blood tests revealed renal impairment, a monoclonal IgM kappa paraprotein, low complement C4 concentration and a positive rheumatoid factor. Active cryoglobulinaemia was suspected and testing demonstrated type II cryoglobulins secondary to the monoclonal IgM kappa paraprotein. Bone marrow biopsy was normal. Renal biopsy revealed cryoglobulinaemia associated membranoproliferative glomerulonephritis. Treatment with steroids and rituximab improved renal function and proteinuria. This case fits within the evolving spectrum of disorders now termed Monoclonal Gammopathy of Renal Significance and highlights the value of biopsying and treating these patients early.

Objectives: To assess the prevalence of high on-clopidogrel platelet reactivity (HCPR) in patients with ischaemic stroke or transient ischaemic attack (IS/TIA), their outcome and genetic basis of on-treatment response variability in IS/TIA patients., Methods: We conducted a comprehensive search of PubMed and EMBASE from their inceptions to March 9, 2019. Studies that reported absolute numbers/percentages of HCRP at any time point after IS/TIA onset evaluated with any type of platelet function tests, clinical outcomes and genotyping data were included., Results: Among 21 studies of 4312 IS/TIA patients treated with clopidogrel, the pooled prevalence of HCPR was 28% (95%CI: 24-32%; high heterogeneity: I 2  = 88.2%, p < 0.001). Heterogeneity degree diminished across groups defined by the HCPR testing method. Clopidogrel non-responder IS/TIA patients had poorer outcome compared to responders (RR = 2.09, 95%CI: 1.61-2.70; p = 0.036; low heterogeneity across studies: I 2  = 27.4%, p = 0.210). IS/TIA carriers of CYP2C19*2 or CYP2C19*3 loss of function alleles had a higher risk of HCPR compared to wild type (RR = 1.69, 95%CI: 1.47-1.95; p < 0.001; I 2  = 0.01%, p = 0.475)., Conclusions: This systematic review shows a high prevalence of clopidogrel resistance in IS/TIA and poor outcome in these patients. CYP2C19 polymorphisms may potentially influence clopidogrel resistance., Competing Interests: Declaration of Competing Interest None., (Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to identify very early incidence of hemiplegic shoulder pain within 72hours (HSP), how clinical assessment was related to pain at 8-10 week follow-up and explore current standard therapy/management., Design: Observational, prospective., Setting: Teaching hospital hyper-acute and follow-up stroke services., Participants: 121 consecutive patients with confirmed cerebral infarct/haemorrhage recruited within 72hours of stroke onset., Interventions: N/A., Main Outcome Measures: Subjective report of pain severity and aggravating factors: using numerical rating scales and pain questionnaire (ShoulderQ), shoulder abductor and flexor muscle strength (Oxford MRC Scale), Neer's Test of sub-acromial pain, shoulder subluxation and soft tissue shoulder palpation., Results: At initial assessment (<72hours), 35% (42/121) reported HSP. At follow-up (8-10 weeks), 44% (53/121) had pain: pain persisted in 32 of the original 42, resolved in 10 and had developed since initial assessment in 21. Pain at follow-up was associated with a statistically significant higher frequency of severe shoulder muscle weakness (MRC grade ≤2) and gleno-humeral subluxation at initial assessment. Soft tissue palpation and Neer's Test detected pain but did not predict development of HSP. 50/121 patients had 140 therapy interventions, particularly targeted to those with a higher HSP risk., Conclusion: This study reports HSP at an earlier time point after stroke than previous publications. Patients with severe arm weakness and/or shoulder subluxation within 72hours are at significantly higher risk of HSP at 8-10 weeks. These data highlight the high incidence of HSP, the non-standardized therapy approach, and can inform sample size calculations for future intervention studies., Clinical Trial Registration: NCT02574000 (clinicaltrials.gov)., (Copyright © 2019 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.)

Purpose: There is a paucity of research into self-management strategies employed by stroke survivors outside of formal rehabilitation. This study aimed to explore stroke survivors' experiences of, and strategies for self-managing their severely impaired upper limb. Materials and methods: English-speaking stroke survivors whose upper limb had been non-functional at 3 months post-stroke took part in interviews ( n  = 16), a focus group ( n  = 6) and a survey ( n  = 20). Quantitative data were analysed descriptively. Qualitative data were analysed through thematic framework analysis using NVivo © software. Results: Participants' median (range) age group was 50-59 years (30-39, 70+). Median (range) time post-stroke was 39 months (4 months, 46 years). The overarching theme across the data was "choosing and expanding." Participants enacted professionally driven management strategies for their affected arm, and then chose to continue with what worked for them. Strategies were expanded through self-discovery and interaction with peers. There were sadness and frustration at the loss of arm function, but also satisfaction and self-confidence when progress was being made. Participants described an attitude of not giving up and remaining hopeful. Conclusions: These findings extend our understanding about how individuals manage their severely impaired upper limb and can be used to inform a novel stroke self-management intervention.Implications for rehabilitationStroke survivors' experiences of managing the severely affected upper limb may inform rehabilitation practice to foster self-management.Rehabilitation professionals may actively support stroke survivors in choosing from, and expanding on professionals' advice and guidance.Maintaining a positive and hopeful outlook is important to many stroke survivors. Professionals should be mindful of the potential impact of their interactions and negative predictions.Stroke survivors' experiences of managing the severely affected upper limb may inform the development of a novel tailored self-management intervention.

Background and Aim: Neutrophil-lymphocyte ratio (NLR) and lymphocyte-monocyte ratio (LMR) are associated with clinical outcomes in malignancy, cardiovascular disease and stroke. Here we investigate their association with outcome after acute ischaemic stroke treated by mechanical thrombectomy (MT)., Methods: Patients were selected using audit data for MT for acute anterior circulation ischaemic stroke at a UK centre from May 2016-July 2017. Clinical and laboratory data including neutrophil, lymphocyte and monocyte count tested before and 24 h after MT were collected. Poor functional outcome was defined as modified Rankin Scale (mRS) of 3-6 at 3 months. Multivariable logistic regression analyses were performed to explore the relationship of NLR and LMR with functional outcome., Results: One hundred twenty-one patients (mean age 66.4 ± 16.7, 52% female) were included. Higher NLR (adjusted OR 0.022, 95% CI, 0.009-0.34, p = 0.001) and lower LMR (adjusted OR - 0.093, 95% CI (- 0.175)-(- 0.012), p = 0.025) at 24-h post-MT were significantly associated with poorer functional outcome when controlling for age, baseline NIHSS score, infarct size, presence of good collateral supply, recanalisation and symptomatic intracranial haemorrhage on multivariate logistic regression. Admission NLR or LMR were not significant predictors of mRS at 3 months. The optimal cut-off values of NLR and LMR at 24-h post-MT that best discriminated poor outcome were 5.5 (80% sensitivity and 60% specificity) and 2.0 (80% sensitivity and 50% specificity), respectively on receiver operating characteristic curve analysis., Conclusion: NLR and LMR tested at 24 h after ictus or intervention may predict 3-month functional outcome.

Background: Atrial fibrillation (AF) is the most common clinical arrhythmia and one of the major causes of stroke, heart failure, sudden death, and cardiovascular morbidity. Despite substantial advances in (interventional) rhythm control treatment during the last decade, anticoagulation for stroke prevention remains a major component of AF treatment., Hypothesis: There are important sex-specific differences in AF-related stroke, resulting from sex-specific mechanisms and therapeutic differences., Methods: This review summarizes available data on sex differences in risk assessment and prevention of stroke and highlights current knowledge gaps in AF-related stroke mechanisms, prevention and management that warrant further research., Results: Increased thrombotic risk in women is multifactorial, involving hormonal changes after menopause, structural, endocrine and lifestyle/social factors and their interactions. It is clear from randomized studies that women benefit from anticoagulant treatment and that their bleeding risk is similar to men. Women should therefore receive equivalent treatment to men, based on the validated criteria for anticoagulation therapy. However, women are not represented equally in the large randomized studies and sex-related information in many fields is lacking., Conclusions: Female sex is an established risk factor for stroke in AF patients. The evidence for sex-specific differences in stroke risk assessment and stroke prevention is accumulating. However, the underlying biological mechanisms remain incompletely understood and further studies are required in order to decrease AF-related morbidity and mortality., (© 2019 The Authors. Clinical Cardiology published by Wiley Periodicals, Inc.)

Background: Protein convertase subtilisin-kexin type 9 (PCSK9) inhibitors effectively clear low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). We evaluated stroke admissions potentially eligible for more intensive cholesterol treatment., Methods: Retrospective analysis of consecutive admissions to a hyperacute stroke unit over 5 months in 2017. Records were individually searched. Data were collected on diagnosis, risk factors, and stroke work-up. European Society of Cardiology and European Atherosclerosis Society guidelines for the management of dyslipidaemias were used for screening patients eligible for PCSK9 inhibitors., Results: Of 650 patient admissions: 351 (54%) had acute ischemic stroke or transient ischemic attack (TIA), 80 (12%) hemorrhage, and 219 (34%) mimic syndromes. Patients with hemorrhage (n = 80), mimic syndromes (n = 219), and absent LDL-C, or non-HDL-C testing (n = 27) were subsequently excluded. 324 patients with acute ischemic stroke and TIA were further screened for PCSK9-inhibitor treatment eligibility. Forty-one (13%) patients with LDL-C greater than or equal to 1.8mmol/L (≥70 mg/dL) on maximal tolerated statin dose and with concomitant "very high vascular risk" were identified. "Very high vascular risk" was defined as a documented history of cardiovascular disease and/or peripheral arterial disease. Of 41 patients eligible for PCSK9 inhibitors, median age was 82 years (range 53-96); median vascular risk factors were 2 (range 1-5); 7 (17%) had TIA; 13 (31%) had history of preceding cerebrovascular events, 13 (31%) diabetes mellitus, 17 (42%) cardioembolic events, 9 (22%) lacunar syndrome, 11 (22%) symptomatic internal carotid artery stenosis (n = 9 were >70%), and 4 (10%) undetermined aetiology. Eighty-three percent patients eligible for PCSK9 inhibitors also had non-HDL-C values greater than or equal to 2.6 mmol/L., Conclusions: Up to 13% of unselected acute ischemic stroke or TIA patients admitted to a hyper-acute stroke unit were potentially suitable for more intensive cholesterol treatment. Our data may act as a useful guide for sample size selection in future stroke trials testing PCSK9 inhibitors., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Background: Treatment with anticoagulants, including direct oral anticoagulants (DOACs), should be considered for patients diagnosed with atrial fibrillation (AF) deemed at risk of ischaemic stroke. There are limited real world data related to the characteristics of patients with non-valvular AF who were not taking anticoagulants at the time of first ischaemic stroke and their subsequent DOAC treatment for the secondary prevention of stroke. Furthermore, little is known about patient adherence and experiences of DOAC treatment, especially for patients with non-valvular AF receiving DOAC therapy for the secondary prevention of stroke., Methods: This is a UK mixed methodology, non-interventional study, involving retrospective and prospective medical record reviews and a prospective patient survey, in progress in six UK National Health Service secondary/tertiary care centres. The study comprises two groups of patients. Group 1 will include 300 eligible consenting patients with a first ischaemic stroke associated with non-valvular AF untreated with anticoagulants in the 12 months prior to stroke. Group 2 will include a subgroup of 150 patients from Group 1 initiated on one of the DOACs targeting activated Factor X (n = 50 on apixaban, n = 50 on edoxaban and n = 50 on rivaroxaban). The primary endpoint of the study is the CHA 2 DS 2 -VASc Risk Score prior to initiation of anticoagulation for patients included in Group 1. Secondary endpoints to be evaluated in Group 1 include patient demographics, clinical characteristics, relevant medical history, anticoagulant therapy initiated for secondary prevention of stroke, and relevant concomitant medication. Secondary endpoints to be evaluated in Group 2 include the time between stroke and DOAC initiation; prescribing of DOACs, other anticoagulants and concomitant medication; clinical assessments and hospital resource use; patient reported outcome measures, including the Morisky Medication Adherence Scale questionnaire and the Treatment Satisfaction Questionnaire for Medication., Discussion: This mixed methodology study will provide new real world insights into the characteristics and management pathways and patient-reported experiences of this important group of patients. It is anticipated that the results of this study will provide the medical community and patients with important information to inform clinical decision-making and help facilitate meaningful improvements in the care of patients with non-valvular AF.

Background and Purpose- Carotid endarterectomy (CEA) reduces the risk of stroke in recently symptomatic patients and less so in asymptomatic patients. Recent evidence suggests that the number of CEAs may be declining. The aim of this study was to investigate annual patterns of CEA in asymptomatic and symptomatic patients in England from 2011 to 2017. Methods- Data from the National Vascular Registry were used to describe (1) the number of CEA procedures in England and its 9 geographic regions from 2011 to 2017, (2) the characteristics of patients undergoing CEA, and (3) whether rates of CEA correlated with the number of vascular arterial units within each region. Annual stroke incidence for each region was derived from official population figures and the number of index stroke admissions per year. Results- The overall number of CEAs performed in England fell from 4992 in 2011 to 3482 in 2017, a 30% decline. Among symptomatic patients, there was a 25% decline, the number of CEAs falling from 4270 to 3217. In asymptomatic patients, there were 722 CEAs performed in 2011 and 265 in 2017, a 63% decline. CEAs per 100 000 adults within all regions declined over time but the size of change varied across the regions (range, 1.7-5.5 per 100 000). The regional numbers of CEAs per year were associated with changes in the regional stroke incidence, the proportion of CEAs performed in asymptomatic patients, and the number of hospitals performing CEA. Conclusions- This population-based study revealed a 63% decline in CEAs among asymptomatic patients between 2011 and 2017, possibly because of changing attitudes in the role of CEA. Reasons for the 25% decline in CEAs among symptomatic patients are unclear as UK guidelines on CEA have not changed for these patients. Whether the proportion of symptomatic patients with 50% to 99% ipsilateral stenosis has changed requires investigation.

Current national guidelines advocate intravenous thrombolysis to treat patients with acute ischaemic stroke presenting within 4.5 hours from symptom onset, and thrombectomy for patients with anterior circulation ischaemic stroke from large vessel occlusion presenting within 6 hours from onset. However, a substantial group of patients presents with acute ischaemic stroke beyond these time windows or has an unknown time of onset. Recent studies are set to revolutionise treatment for these patients. Using MRI diffusion/FLAIR (fluid-attenuated inversion recovery) mismatch, it is possible to identify patients within 4.5 hours from onset and safely deliver thrombolysis. Using CT perfusion imaging, it is possible to identify subjects with a middle cerebral artery syndrome who have an extensive area of ischaemic brain but as yet have only a small area of infarction who may benefit from urgent thrombectomy in up to 24 hours. Here, we highlight the recent advances in late window stroke treatment and their potential contribution to clinical practice., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Adults presenting to stroke services are frequently faced with the challenge of adjusting to a different life following a stroke. Difficulties often include cognitive impairments, such as memory deficits, attention and language difficulties, and mood disturbances such as anxiety and depression. It has been highlighted that psychological care for this group is just as important as physical rehabilitation. Psychological expertise may therefore be required for the multitude of problems that occur after a stroke. UK National guidelines recommend routine assessment and management of mood and cognition after stroke. The aim of this study was to evaluate a new stroke clinical neuropsychology service developed by the Department of Neuropsychology and Clinical Health Psychology, in order to meet the needs of stroke survivors and their families referred into a large acute hospital. This involved using a different skill mix of staff across one post delivering a service in an acute inpatient stroke unit. This model was evaluated and results revealed that the model delivered increased patient access to neuropsychological support, an expansion in provision of clinical work, along with positive multidisciplinary team feedback. This finding is key as where resources are limited, clinical services may benefit from adopting a 'skill mix' model to meet the varying needs of their patients in a timely manner. This model serves to raise the value of psychology to medical services., Competing Interests: Competing interests: None declared.

Background: CT perfusion (CTP) and diffusion or perfusion MRI might assist patient selection for endovascular thrombectomy. We aimed to establish whether imaging assessments of irreversibly injured ischaemic core and potentially salvageable penumbra volumes were associated with functional outcome and whether they interacted with the treatment effect of endovascular thrombectomy on functional outcome., Methods: In this systematic review and meta-analysis, the HERMES collaboration pooled patient-level data from all randomised controlled trials that compared endovascular thrombectomy (predominantly using stent retrievers) with standard medical therapy in patients with anterior circulation ischaemic stroke, published in PubMed from Jan 1, 2010, to May 31, 2017. The primary endpoint was functional outcome, assessed by the modified Rankin Scale (mRS) at 90 days after stroke. Ischaemic core was estimated, before treatment with either endovascular thrombectomy or standard medical therapy, by CTP as relative cerebral blood flow less than 30% of normal brain blood flow or by MRI as an apparent diffusion coefficient less than 620 μm 2 /s. Critically hypoperfused tissue was estimated as the volume of tissue with a CTP time to maximum longer than 6 s. Mismatch volume (ie, the estimated penumbral volume) was calculated as critically hypoperfused tissue volume minus ischaemic core volume. The association of ischaemic core and penumbral volumes with 90-day mRS score was analysed with multivariable logistic regression (functional independence, defined as mRS score 0-2) and ordinal logistic regression (functional improvement by at least one mRS category) in all patients and in a subset of those with more than 50% endovascular reperfusion, adjusted for baseline prognostic variables. The meta-analysis was prospectively designed by the HERMES executive committee, but not registered., Findings: We identified seven studies with 1764 patients, all of which were included in the meta-analysis. CTP was available and assessable for 591 (34%) patients and diffusion MRI for 309 (18%) patients. Functional independence was worse in patients who had CTP versus those who had diffusion MRI, after adjustment for ischaemic core volume (odds ratio [OR] 0·47 [95% CI 0·30-0·72], p=0·0007), so the imaging modalities were not pooled. Increasing ischaemic core volume was associated with reduced likelihood of functional independence (CTP OR 0·77 [0·69-0·86] per 10 mL, p interaction =0·29; diffusion MRI OR 0·87 [0·81-0·94] per 10 mL, p interaction =0·94). Mismatch volume, examined only in the CTP group because of the small numbers of patients who had perfusion MRI, was not associated with either functional independence or functional improvement. In patients with CTP with more than 50% endovascular reperfusion (n=186), age, ischaemic core volume, and imaging-to-reperfusion time were independently associated with functional improvement. Risk of bias between studies was generally low., Interpretation: Estimated ischaemic core volume was independently associated with functional independence and functional improvement but did not modify the treatment benefit of endovascular thrombectomy over standard medical therapy for improved functional outcome. Combining ischaemic core volume with age and expected imaging-to-reperfusion time will improve assessment of prognosis and might inform endovascular thrombectomy treatment decisions., Funding: Medtronic., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background and Purpose- Intrathecal baclofen (ITB) is an effective treatment for managing patients with severe poststroke spasticity, who can experience continued pain and decline in their quality of life (QoL). SISTERS (Spasticity In Stroke-Randomized Study) was a randomized, controlled, open-label, multicenter, phase 4 study to evaluate ITB therapy versus conventional medical management (CMM) with oral antispastic medications for treatment of poststroke spasticity. Methods- Poststroke patients with spasticity in ≥2 extremities and an Ashworth Scale score of ≥3 in ≥2 affected lower extremity muscle groups were randomized (1:1) to ITB (N=31) or CMM (N=29). Both treatment arms received physiotherapy throughout. The primary outcome was the change in average Ashworth Scale score in the lower extremities of the affected side from baseline to month 6. Here, we report results for secondary outcomes: pain via the Numeric Pain Rating Scale, health-related QoL by the EuroQol-5 dimensional 3 level utility score and health status visual analog scale score, stroke-specific QoL, and patient satisfaction. Analyses were performed on an intention-to-treat basis. Results- We observed significant treatment effects in favor of ITB over CMM for changes from baseline to month 6 in Numeric Pain Rating Scale scores for actual pain (ITB versus CMM: mean, -1.17 [SD, 3.17] versus 0.00 [3.29]; median, -1.00 versus 0.00; P=0.0380) and least pain (mean, -1.61 [2.29] versus 0.24 [3.07]; median, -1.00 versus 0.00; P=0.0136), and EuroQol-5 dimensional 3 level utility scores (mean, +0.09 [0.26] versus +0.01 [0.16]; median, +0.07 versus 0.00; P=0.0197). Between-group differences were not statistically significant for EuroQol-5 dimensional 3 level visual analog scale, stroke-specific QoL summary, or Numeric Pain Rating Scale worst pain scores, although ITB patients showed greater numeric improvements from baseline during follow-up. More ITB patients than CMM patients (73% versus 48%) were satisfied with the spasticity reduction at month 6. Conclusions- These data support that ITB therapy is associated with improvements in pain and QoL in poststroke patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT01032239.

Objective: To consider the potential of self-help relaxation training to treat depression after stroke., Design: Randomized controlled trial with cross-over at three months., Setting: Community., Participants: In total, 21 people with stroke, aged 49-82 years., Intervention: Autogenic relaxation CD., Main Measure: Hospital Anxiety and Depression Scale-Depression (HADS-D) subscale., Results: No difference in depression change scores was identified between the treatment and control groups; however, on two follow-ups, significant positive differences relative to screening were found for the treatment group (at 2 months Z = -2.55, P = .011 and 12 months Z = -2.44, P = .015). A partial η 2  = .07 was identified., Conclusion: Self-help relaxation holds promise as a self-help treatment for depression after stroke. Findings from this trial, considered with others of relaxation for depression, suggest that a study including a total of 80 participants would likely be sufficient to establish efficacy of the treatment, relative to controls, in those with stroke.

Background: Intrathecal baclofen (ITB) is a treatment option for patients with severe poststroke spasticity (PSS) who have not reached their therapy goal with other interventions., Methods: 'Spasticity In Stroke-Randomised Study' (SISTERS) was a randomised, controlled, open-label, multicentre phase IV study to evaluate the efficacy and safety of ITB therapy versus conventional medical management (CMM) with oral antispastic medications for treatment of PSS. Patients with chronic stroke with spasticity in ≥2 extremities and an Ashworth Scale (AS) score ≥3 in at least two affected muscle groups in the lower extremities (LE) were randomised (1:1) to ITB or CMM. Both treatment arms received physiotherapy throughout. The primary outcome was the change in the average AS score in the LE of the affected body side from baseline to month 6. Analyses were performed for all patients as randomised (primary analysis) and all randomised patients as treated (safety analysis)., Results: Of 60 patients randomised to ITB (n=31) or CMM (n=29), 48 patients (24 per arm) completed the study. The primary analysis showed a significant effect of ITB therapy over CMM (mean AS score reduction, -0.99 (ITB) vs -0.43 (CMM); Hodges-Lehmann estimate, -0.667(95.1%CI -1.0000 to -0.1667); P=0.0140). More patients reported adverse events while receiving ITB (24/25 patients, 96%; 149 events) compared with CMM (22/35, 63%; 77 events), although events were generally consistent with the known safety profile of ITB therapy., Conclusions: These data support the use of ITB therapy as an alternative to CMM for treatment of generalised PSS in adults., Trial Registration Number: NCT01032239; Results., Competing Interests: Competing interests: MC, MZ and LS report personal fees from Medtronic during the conduct of the study. GF reports grants from Allergan, Ipsen, Merz and Mallinckrodt during the conduct of the study. JW reports personal fees from Medtronic during the conduct of the study, and personal fees from Allergan, Merz, Ipsen, and Medtronic outside the submitted work. AA, NB, AC and ML are all employees of Medtronic and report personal fees from Medtronic during the conduct of the study. All other authors declare no competing interests., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Diffusion-weighted imaging (DWI) has transformed the radiological assessment of a variety of cerebral pathologies, in particular acute stroke. In neuroimaging studies, DWI can also be used to evaluate pathology outside the brain parenchyma, although it is sometimes underutilized for this purpose. In this pictorial review, the principles of DWI are outlined, and 13 cases of abnormal diffusion outside the brain parenchyma are illustrated in order to show DWI as a useful sequence for the evaluation of the following recommended review areas: the dural venous sinuses, internal carotid arteries, meninges, ventricles, cavernous sinus and orbits, skull base and lymph nodes.

Objectives: To determine whether shoulder orthoses prevent or reduce gleno-humeral subluxation and hemiplegic shoulder pain., Data Sources: OVID SP, MEDLINE, AMED, CINAHL, PEDro and the Cochrane Central Register of Controlled Trials., Review Methods: We included: randomised or quasi-randomised controlled trials, controlled before and after studies and observational studies. Two reviewers independently screened, critically appraised papers using the PEDro tool, and extracted data. A descriptive synthesis was performed as there were insufficient data for meta-analysis., Results: Eight studies were included, totalling 186 participants: One randomised controlled trial with 41 participants, one quasi-randomised with 14 participants, one before and after controlled study with 40 participants and five observational studies with 91 participants met the inclusion criteria. Findings suggest that applying an orthosis to an already subluxed shoulder immediately reduced vertical subluxation on X-ray but improvements were not maintained when orthosis was removed. Orthoses with both proximal and distal attachments improved shoulder pain in the majority of stroke patients when worn for four weeks (starting several days or weeks post-stroke). There was no increase in adverse effects of contracture, spasticity or hand oedema when compared to no orthosis. Orthoses were generally well-tolerated and most patients rated the orthosis as comfortable to wear., Conclusion: Observational studies suggest that orthoses reduce vertical subluxation whilst in-situ. Available evidence from heterogeneous studies after stroke suggests that orthoses may reduce pain and are well-tolerated with prolonged use. No studies have tested whether subluxation and pain can be prevented by immediate post-stroke application of orthoses.

Background: There is no robust evidence that screening patients with acute stroke for dysphagia reduces the risk of stroke-associated pneumonia (SAP), or of how quickly it should be done after admission. We aimed to identify if delays in bedside dysphagia screening and comprehensive dysphagia assessments by a speech and language therapist (SALT) were associated with patients' risk of SAP., Methods: Nationwide, registry-based, prospective cohort study of patients admitted with acute stroke in England and Wales. Multilevel multivariable logistic regression models were fitted, adjusting for patient variables and stroke severity. The exposures were time from (1) admission to bedside dysphagia screen, and (2) admission to comprehensive dysphagia assessment., Results: Of 63 650 patients admitted with acute stroke, 55 838 (88%) had a dysphagia screen, and 24 542 (39%) a comprehensive dysphagia assessment. Patients with the longest delays in dysphagia screening (4th quartile adjusted OR 1.14, 1.03 to 1.24) and SALT dysphagia assessment (4th quartile adjusted OR 2.01, 1.76 to 2.30) had a higher risk of SAP. The risk of SAP increased in a dose-response manner with delays in SALT dysphagia assessment, with an absolute increase of pneumonia incidence of 1% per day of delay., Conclusions: Delays in screening for and assessing dysphagia after stroke, are associated with higher risk of SAP. Since SAP is one of the main causes of mortality after acute stroke, early dysphagia assessment may contribute to preventing deaths from acute stroke and could be implemented even in settings without access to high-technology specialist stroke care., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Systemic thrombolysis with rt-PA is contraindicated in patients with acute ischemic stroke anticoagulated with dabigatran. This expert opinion provides guidance on the use of the specific reversal agent idarucizumab followed by rt-PA and/or thrombectomy in patients with ischemic stroke pre-treated with dabigatran. The use of idarucizumab followed by rt-PA is covered by the label of both drugs.

Stroke services have been centralised in several countries in recent years. Diagnosing acute stroke is challenging and a high proportion of patients admitted to stroke units are diagnosed as a non-stroke condition (stroke mimics). This study aims to describe the stroke mimic patient group, including their impact on stroke services. We analysed routine clinical data from 2,305 consecutive admissions to a stroke unit at St George's Hospital, London. Mimic groupings were derived from 335 individual codes into 17 groupings. From 2,305 admissions, 555 stroke mimic diagnoses were identified (24.2%) and 72% of stroke mimics had at least one stroke risk factor. Common mimic diagnoses were headache, seizure and syncope. Medically unexplained symptoms and decompensation of underlying conditions were also common. Median length of stay was 1 day; a diagnosis of dementia (p=0.028) or needing MRI (p=0.006) was associated with a longer stay. Despite emergency department assessment by specialist clinicians and computed tomography brain, one in four suspected stroke patients admitted to hospital had a non-stroke diagnosis. Stroke mimics represent a heterogeneous patient group with significant impacts on stroke services. Co-location of stroke and acute neurology services may offer advantages where service reorganisation is being considered., (© Royal College of Physicians 2016. All rights reserved.)

Background: Prognosis after intracerebral hemorrhage (ICH) is poor and care-limiting decisions may worsen outcomes., Aims: To determine whether in current UK stroke practice, key acute care decisions are associated with stroke subtype (ICH/ischemic) and whether these decisions are independently associated with survival., Methods: We extracted data describing all stroke patients included in a UK quality register between 1 April 2013 and 31 March 2014. Key care decisions in our analyses were transfer to higher level care on admission and palliation in the first 72 h. We used multivariable regression models to test for associations between stroke subtype (ICH/ischemic), key care decisions, and survival., Results: A total of 65,818 patients were included in the final analysis. After ICH (n = 7020/65,818, 10.7%), 10.5% were palliated on the day of admission and 19.3% by 72 h (vs. 0.7% and 3.3% for ischemic stroke). Although a greater proportion were admitted directly to higher level care after ICH (3.7% vs. 1.5% for ischemic stroke), ICH was not independently associated with the decision to admit to higher level care (adjusted odds ratio (OR): 1.12, 95% confidence interval (95%CI): 0.95-1.31, p = 0.183). However, ICH was strongly associated with the decision to commence palliative care on the day of admission (OR: 7.27, 95%CI: 6.31-8.37, p < 0.001). Palliative care was independently associated with risk of death by 30 days regardless of stroke subtype., Conclusions: When compared to ischemic stroke, patients with ICH are much more likely to commence palliative care during the first 72 h of their care, independent of level of consciousness, age, and premorbid health., (© 2016 World Stroke Organization.)