Non-contrast CT markers of intracerebral hematoma expansion: a reliability study.

OBJECTIVES: We evaluated whether clinicians agree in the detection of non-contrast CT markers of intracerebral hemorrhage (ICH) expansion. METHODS: From our local dataset, we randomly sampled 60 patients diagnosed with spontaneous ICH. Fifteen physicians and trainees (Stroke Neurology, Interventional and Diagnostic Neuroradiology) were trained to identify six density (Barras density, black hole, blend, hypodensity, fluid level, swirl) and three shape (Barras shape, island, satellite) expansion markers, using standardized definitions. Thirteen raters performed a second assessment. Inter- and intra-rater agreement were measured using Gwet's AC1, with a coefficient > 0.60 indicating substantial to almost perfect agreement. RESULTS: Almost perfect inter-rater agreement was observed for the swirl (0.85, 95% CI: 0.78-0.90) and fluid level (0.84, 95% CI: 0.76-0.90) markers, while the hypodensity (0.67, 95% CI: 0.56-0.76) and blend (0.62, 95% CI: 0.51-0.71) markers showed substantial agreement. Inter-rater agreement was otherwise moderate, and comparable between density and shape markers. Inter-rater agreement was lower for the three markers that require the rater to identify one specific axial slice (Barras density, Barras shape, island: 0.46, 95% CI: 0.40-0.52 versus others: 0.60, 95% CI: 0.56-0.63). Inter-observer agreement did not differ when stratified for raters' experience, hematoma location, volume, or anticoagulation status. Intra-rater agreement was substantial to almost perfect for all but the black hole marker. CONCLUSION: In a large sample of raters with different backgrounds and expertise levels, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement. KEY POINTS: • In a sample of 15 raters and 60 patients, only four of nine non-contrast CT markers of ICH expansion showed substantial to almost perfect inter-rater agreement (Gwet's AC1> 0.60). • Intra-rater agreement was substantial to almost perfect for eight of nine hematoma expansion markers. • Only the blend, fluid level, and swirl markers achieved substantial to almost perfect agreement across all three measures of reliability (inter-rater agreement, intra-rater agreement, agreement with the results of a reference reading).

Network meta-analysis can inform the ethical evaluation of trials that randomise away from standard of care: The case of symptomatic carotid stenosis.

OBJECTIVE: Little guidance exists on the conduct of randomised clinical trials (RCT) that seek to randomise patients away from standard of care. We sought to test the technique of network meta-analysis (NMA) to ascertain best available evidence for the purposes of informing the ethical evaluation of RCTs under these circumstances. We used the example of RCTs for patients with symptomatic, moderate to severe carotid stenosis that seek to compare surgical intervention plus medical therapy (standard of care) versus medical therapy (less than standard of care). STUDY DESIGN AND SETTING: Network meta-analysis of RCTs of adults with symptomatic carotid artery stenosis of 50%-99% who were treated with carotid endarterectomy (CEA), carotid artery stenting (CAS), or medical therapy (MT). The primary outcome was any stroke or death until end of follow-up, and secondary outcome was 30-day risk of ipsilateral stroke/death. RESULTS: We analysed eight studies, with 7187 subjects with symptomatic moderate/severe stenosis (50%-99%). CEA was more efficacious than MT (HR = 0.82, 95% credible intervals [95% CrI] = 0.73-0.92) and CAS (HR 0.73, 95% CrI = 0.62-0.85) for the prevention of any stroke/death. At 30 days, the odds of experiencing an ipsilateral stroke/death were significantly lower in the CEA group compared to both MT (OR = 0.58, 95% CrI = 0.47-0.72) and CAS (OR = 0.68, 95% CrI = 0.55-0.83). CONCLUSION: Our results support the feasibility of using NMA to assess best available evidence to inform the ethical evaluation of RCTs seeking to randomise patients away from standard of care. Our results suggest that a strong argument is required to ethically justify the conduct of RCTs that seek to randomise patients away from standard of care in the setting of symptomatic moderate to severe carotid stenosis.

Screening for cognitive impairment in adults with sickle cell disease: A systematic review and meta-analysis.

Neurovascular disease such as symptomatic stroke, silent brain infarcts and vascular cognitive impairment are common complications of sickle cell disease (SCD) that can have devastating consequences on quality of life, employment, and social functioning.  Early recognition of neurovascular disease is a prerequisite for the timely optimization of medical care and to connect patients to adaptive resources. While cognitive impairment has been well described in children, currently available data are limited in adults. As a result, guidance on the optimal cognitive screening strategies in adults is scarce. We conducted a systematic review to identify the different screening tools that have been evaluated in SCD. A meta-analysis was performed to estimate the prevalence of suspected cognitive impairment in this population. In this qualitative synthesis, we present 8 studies that evaluated 6 different screening tools. Patient characteristics that impacted on cognitive screening performance included age, education level, and a prior history of stroke. We report a pooled prevalence of 38% [14-62%] of suspected cognitive impairment. We discuss the relative benefits and limitations of the different screening tools to help clinicians select an adapted approach tailored to their specific patients' needs. Further studies are needed to establish and validate cognitive screening strategies in patients with diverse cultural and educational backgrounds.

Three-month functional outcomes following endovascular thrombectomy during the first wave of the COVID-19 pandemic: a Canadian single-center cohort study.

BACKGROUND: The COVID-19 pandemic has disrupted acute stroke care logistics, including delays in hyperacute management and decreased monitoring following endovascular therapy (EVT). We aimed to assess the impact of the pandemic on 90-day functional outcome among patients treated with EVT. METHODS: This is an observational cohort study including all patients evaluated for an acute stroke between March 30, 2020 and September 30, 2020 (pandemic cohort) and 2019 (reference cohort) in a high-volume Canadian academic stroke center. We collected baseline characteristics, acute reperfusion treatment and management metrics. For EVT-treated patients, we assessed the modified Rankin score (mRS) at 90 days. We evaluated the impact of the pandemic on a 90-day favourable functional status (defined as mRS 0-2) and death using multivariable logistic regressions. RESULTS: Among 383 and 339 patients included in the pandemic and reference cohorts, baseline characteristics were similar. Delays from symptom onset to evaluation and in-house treatment were longer during the early first wave, but returned to reference values in the subsequent months. Among the 127 and 136 EVT-treated patients in each respective cohort, favourable 90-day outcome occurred in 53/99 (53%) vs 52/109 (48%, p=0.40), whereas 22/99 (22%) and 28/109 (26%, p=0.56) patients died. In multivariable regressions, the pandemic period was not associated with 90-day favourable functional status (aOR 1.27, 95% CI 0.60 to 2.56) or death (aOR 0.74, 95% CI 0.33 to 1.63). CONCLUSION: In this single-center cohort study conducted in a Canadian pandemic epicenter, the first 6 months of the COVID-19 pandemic did not impact 90-day functional outcomes or death among EVT-treated patients.

Clinical Utility and Cost of Inpatient Transthoracic Echocardiography Following Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: It is unclear whether it is clinically necessary or cost-effective to routinely obtain a transthoracic echocardiogram (TTE) during inpatient admission for ischemic stroke. METHODS: We assessed consecutive patients presenting with acute ischemic stroke at a comprehensive stroke center from 2015 to 2017 who underwent TTE. We assessed for findings on TTE that would warrant urgent intervention including cardiac thrombus, atrial myxoma, mitral stenosis, valve vegetation, valve dysfunction requiring surgery, and low ejection fraction. Subsequent changes in management included changes in anticoagulation, antibiotics, or valve surgery. We calculated in-hospital resource utilization and associated costs for inpatient TTE using individual direct cost details within a case-costing system. RESULTS: Of 695 patients admitted with acute ischemic stroke, 516 (74%) had a TTE and were included in our analysis. TTE findings were potentially clinically significant in 30 patients (5.8%) and changed management in 17 patients (3.3%). Inpatient admission was prolonged to expedite TTE in 24 patients, while TTE occurred after discharge in 76 patients. After correcting for the cost of TTE, the mean difference in cost to prolong an admission for TTE was $555.52 (USD), or $16 832 per change in management. CONCLUSIONS: Given the low clinical utility of inpatient TTE after acute ischemic stroke and the costs associated with prolonging admission, discharge from hospital should not be delayed solely to obtain TTE.

Identifying sex-specific differences in the carotid revascularisation literature: findings from a scoping review.

OBJECTIVE: No systematic review of the literature has dedicated itself to looking at the management of symptomatic carotid stenosis in female patients. In this scoping review, we aimed to identify all randomised controlled trials (RCTs) that reported sex-specific outcomes for patients who underwent carotid revascularisation, and determine whether sufficient information is reported within these studies to assess short-term and long-term outcomes in female patients. DESIGN, SETTING AND PARTICIPANTS: We systematically searched Medline, Embase, Pubmed and Cochrane libraries for RCTs published between 1991 and 2020 that included female patients and compared either endarterectomy with stenting, or any revascularisation (endarterectomy or stenting) with medical therapy in patients with symptomatic high-grade (>50%) carotid stenosis. RESULTS: From 1537 references examined, 27 eligible studies were identified. Sex-specific outcomes were reported in 13 studies. Baseline patient characteristics of enrolled female patients were reported in 2 of those 13 studies. Common outcomes reported included stroke and death, however, there was significant heterogeneity in the reporting of both periprocedural and long-term outcomes. Sex-specific differences relating to the degree of stenosis and time from index event to treatment are largely limited to studies comparing endarterectomy to medical therapy. Adverse events were not reported by sex. CONCLUSIONS: Only half of the previously published RCTs and systematic reviews report sex-specific outcomes. Detailed analyses on the results of carotid artery intervention for female patients with symptomatic stenosis are limited.

Rationalisations for women-only randomised controlled trials in conditions that affect both sexes: a scoping review protocol.

INTRODUCTION: Women have historically been under-represented in randomised controlled trials (RCTs), including many landmark RCTs that established standards of care. In light of this fact, some modern researchers are calling for replication of earlier landmark trials with women only. This approach is ethically concerning, in that it would require some enrolled women to be deprived of treatments that are currently considered standard of care. OBJECTIVE: In an attempt to better understand the justification of a women-only approach to designing clinical trials, this study looks to systematically categorise the number of women-only RCTs for conditions that affect both men and women and the reasons given within the medical and philosophical literatures to perform them. METHODOLOGY: This scoping review of the literature will search, screen and select articles based on predetermined inclusion/exclusion criteria, after which a grounded theory approach will be used to synthesise the data. It is expected that there will be a variety of reasons given for why a women-only trial may be justified. Electronic databases that will be searched include MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trials Register, Web of Science Proceedings, ClinicalTrials.gov, Philosopher's Index, Phil Papers, JSTOR, Periodicals Archive Online, Project MUSE and the National Reference Centre for Bioethics. SIGNIFICANCE: The scope of this study is to determine published rationales used to justify women-only randomised trials, both in the case of new trials and in the repetition of landmark trials. ETHICS AND DISSEMINATION: Research ethics board approval is not required for this study as there is no participant involvement. Results will be published as a stand-alone manuscript and will inform a larger project related to the ethics of a women-only RCT of carotid intervention for women with symptomatic high-grade carotid stenosis.

Normal Systolic Blood Pressure at Presentation With Acute Ischemic Stroke Predicts Cardioembolic Etiology.

Background Early insight into the possible etiology of ischemic stroke allows for early initiation of mechanism-specific secondary stroke prevention. Initial systolic blood pressure during acute ischemic stroke may relate to stroke etiology. We sought to determine whether normotension at presentation with acute ischemic stroke predicts cardioembolic etiology. Methods and Results All patients presenting with acute ischemic stroke within 12 hours of symptom onset at a comprehensive stroke center from January 2015 to December 2017 were assessed. Normotension was defined as systolic blood pressure ≤130 mm Hg. The primary exposure was blood pressure on arrival at the hospital, and the primary outcome was cardioembolic etiology. Multivariable regression with stepwise selection was used to adjust for relevant covariates. We included 683 patients in our analysis, 303 (44%) of whom were diagnosed with cardioembolic etiology at 6 months. The probability of cardioembolic etiology was inversely associated with systolic blood pressure, and initial systolic blood pressure was significantly associated with cardioembolic etiology (odds ratio: 1.15; 95% CI, 1.05 to 1.26). Normotension was associated with 2.62-fold increased odds of cardioembolic etiology (95% CI, 1.46 to 4.72). Conclusions Normotension at presentation with acute ischemic stroke strongly predicts cardioembolic etiology. These patients may especially benefit from early and prolonged cardiac investigations.

Benefit of carotid revascularisation for women with symptomatic carotid stenosis: protocol for a systematic review.

INTRODUCTION: Carotid intervention in the form of endarterectomy or stenting is the current standard of care for the majority of patients with symptomatic high-grade carotid stenosis. However, some randomised controlled trials (RCT) have demonstrated that women benefited significantly less from intervention than men. It is unclear if this is a true phenomenon or a study sampling artefact, as women were severely under-represented in all RCTs of carotid revascularisation. A systematic review is needed to summarise the existing data and to answer the question of whether a women-only trial for symptomatic patients with ipsilateral carotid stenosis is scientifically necessary and ethically permissible. METHODS AND ANALYSIS: We will systematically search Medline, Embase, PubMed and the Cochrane libraries for all studies with data from RCTs that included women and compared either endarterectomy with stenting or revascularisation (by means of endarterectomy or stenting) with medical therapy in patients with symptomatic carotid stenosis. Search dates will be restricted to 1991-2018. Two reviewers will conduct screening search results, study selection, data extraction and quality assessment. We will include all studies reporting outcomes of interest. Planned subgroup analysis based on revascularisation technique, degree of stenosis and timing of intervention from the index event will be conducted with enough data. ETHICS AND DISSEMINATION: This research is exempt of ethics approval as no primary data will be collected. The results will be published in peer-reviewed journals and disseminated through national and international-level conferences and scientific meetings. The result of this comprehensive review will provide useful information on whether further RCTs are required to study a women-only population with symptomatic carotid disease. PROSPERO REGISTRATION NUMBER: CRD42019134967.

Spastic ataxias.

The presence of spasticity and pyramidal features is a hallmark of some of hereditary ataxias, such as autosomal-recessive spastic ataxia of Charlevoix-Saguenay, other primary spastic ataxias, Friedreich ataxia, or ataxia with isolated vitamin E deficiency. Certain spastic paraplegias, such as spastic paraplegia 7, may present as an ataxic phenotype and often share common pathophysiologic pathways with cerebellar ataxias. Because of the rarity and genetic heterogeneity of these conditions, their molecular diagnosis remains challenging and time consuming. Herein we review the clinical, epidemiologic, and genetic features of the best-defined spastic ataxias with a focus on autosomal-recessive spastic ataxia of Charlevoix-Saguenay, one of the most frequent ataxias worldwide, which presents with a unique early-onset spastic ataxia phenotype. We briefly discuss other genetic and metabolic multisystem disorders where spastic ataxia is a secondary feature. Emphasis is placed on their typical age of onset and key clinical and imaging features that enable discrimination between these complex diseases.