The Fornix May Play a Key Role in Korsakoff’s Amnesia Secondary to Subcallosal Artery Infarction

Background: Subcallosal artery infarction injures the fornix and anterior corpus callosum and sometimes causes Korsakoff’s amnesia. We hypothesized that Korsakoff’s amnesia might be caused by fornix dysfunction rather than anterior corpus callosum dysfunction in subcallosal artery infarction. Methods: A systematic review approach was applied to search PubMed and Google Scholar for articles to compare patients who had both bilateral fornix and corpus callosum infarction due to subcallosal artery territory ischemia (vascular event group; V group) with patients who had undergone anterior corpus callosotomy (callosotomy group; C group). Results: The V group comprised 10 patients (mean age, 63 years; median, 69 years; standard deviation (SD), 14.5 years; 5 males, 5 females). The C group comprised 6 patients (mean age, 23.7 years; median, 20 years; SD, 7.3 years; 3 males, 3 females). Six of 10 patients (60%) with subcallosal artery infarction exhibited Korsakoff’s amnesia. One patient showed neither confabulation nor amnesia. Conversely, no amnesia episodes were seen in any patients from the C group (p = 0.034). Conclusion: Fornix injury, rather than anterior corpus callosum injury, might be the major cause of Korsakoff’s amnesia in patients with subcallosal artery infarction.

Statistical reanalysis of vascular event outcomes in primary and secondary vascular prevention trials

Background Vascular prevention trials typically use dichotomous event outcomes although this may be inefficient statistically and gives no indication of event severity. We assessed whether ordinal outcomes would be more efficient and how to best analyse them. Methods Chief investigators of vascular prevention randomised controlled trials that showed evidence of either benefit or harm, or were included in a systematic review that overall showed benefit or harm, shared individual participant data from their trials. Ordered categorical versions of vascular event outcomes (such as stroke and myocardial infarction) were analysed using 15 statistical techniques and their results then ranked, with the result with the smallest p-value given the smallest rank. Friedman and Duncan’s multiple range tests were performed to assess differences between tests by comparing the average ranks for each statistical test. Results Data from 35 trials (254,223 participants) were shared with the collaboration. 13 trials had more than two treatment arms, resulting in 59 comparisons. Analysis approaches (Mann Whitney U, ordinal logistic regression, multiple regression, bootstrapping) that used ordinal outcome data had a smaller average rank and therefore appeared to be more efficient statistically than those that analysed the original binary outcomes. Conclusions Ordinal vascular outcome measures appear to be more efficient statistically than binary outcomes and provide information on the severity of event. We suggest a potential role for using ordinal outcomes in vascular prevention trials.

Immigration Status, Ethnicity, and Long-term Outcomes Following Ischemic Stroke

ObjectiveTo assess the association between immigration status and ethnicity and the outcomes of mortality and vascular event recurrence following ischemic stroke in Ontario, Canada.MethodsWe conducted a retrospective cohort study using linked administrative and clinical registry–based data from 2002 to 2018 and compared hazards of all-cause mortality and vascular event recurrence in immigrants and long-term residents using inverse probability of treatment weighting accounting for age, sex, income, and comorbidities. We stratified analyses by age (≤75 and >75 years) and used interaction terms to evaluate whether the association between immigration status and outcomes varied with age or ethnicity.ResultsWe followed 31,918 adult patients, of whom 2,740 (8.6%) were immigrants, for a median follow-up of 5 years. Immigrants had lower mortality than long-term residents (46.1% vs 64.5%), which was attenuated after adjustment (hazard ratio [HR] 0.94; 95% confidence interval [CI] 0.88–1.00), but persisted in those younger than 75 years (HR 0.82; 0.74–0.91). Compared to their respective ethnic long-term resident counterparts, the adjusted hazard of death was higher in South Asian immigrants, similar in Chinese immigrants, and lower in other immigrants (p value for interaction = 0.003). The adjusted hazard of vascular event recurrence (HR 1.01; 0.92–1.11) was similar in immigrants and long-term residents, and this observation persisted across all age and ethnic groups.ConclusionsLong-term mortality following ischemic stroke is lower in immigrants than in long-term residents, but is similar after adjustment for baseline characteristics, and it is modified by age at the time of stroke and by ethnicity.

Risk factors for symptomatic vascular events in giant cell arteritis: a study of 254 patients with large-vessel imaging at diagnosis

Aims: To identify factors associated with vascular events in patients with giant cell arteritis (GCA). Methods: We performed a retrospective study of GCA patients diagnosed over a 20-year-period, who all underwent vascular imaging evaluation at diagnosis. Symptomatic vascular events were defined as the occurrence of any aortic event (aortic dissection or symptomatic aortic aneurysm), stroke, myocardial infarction, limb or mesenteric ischemia and de novo lower limbs arteritis stage 3 or 4. Patients with symptomatic vascular event (VE+) and without were compared, and risk factors were identified in a multivariable analysis. Results: Thirty-nine (15.4%) of the 254 included patients experienced at least one symptomatic vascular event during follow-up, with a median time of 21.5 months. Arterial hypertension, diabetes, lower limbs arteritis or vascular complication at diagnosis were more frequent in VE+ patients ( p < 0.05), as an abnormal computed tomography (CT)-scan at diagnosis ( p = 0.04), aortitis ( p = 0.01), particularly of the descending thoracic aorta ( p = 0.03) and atheroma ( p = 0.03). Deaths were more frequent in the VE+ group (37.1 versus 10.3%, p = 0.0003). In multivariable analysis, aortic surgery [hazard ratio (HR): 10.46 (1.41–77.80), p = 0.02], stroke [HR: 22.32 (3.69–135.05), p < 0.001], upper limb ischemia [HR: 20.27 (2.05–200.12), p = 0.01], lower limb ischemia [HR: 76.57 (2.89–2027.69), p = 0.009], aortic atheroma [HR: 3.06 (1.06–8.82), p = 0.04] and aortitis of the descending thoracic aorta on CT-scan at diagnosis [HR: 4.64 (1.56–13.75), p = 0.006] were independent predictive factors of a vascular event. Conclusion: In this study on GCA cases with large vessels imaging at diagnosis, aortic surgery, stroke, upper or lower limb ischemia, aortic atheroma and aortitis of the descending thoracic aorta on CT-scan, at GCA diagnosis, were independent predictive factors of a vascular event. Plain language summary Risk factors for symptomatic vascular events in giant cell arteritis This study was performed to identify the risk factors for developing symptomatic vascular event during giant cell arteritis (GCA) because these are poorly known. We performed a retrospective study of GCA patients diagnosed over a 20-year-period, who all underwent vascular imaging evaluation at diagnosis. Patients with symptomatic vascular event (VE+) and without (VE-) were compared, and risk factors were identified in a multivariable analysis. Thirty-nine patients experienced at least one symptomatic vascular event during follow-up, with a median time of 21.5 months. Arterial hypertension, diabetes, lower limbs arteritis or vascular complication at diagnosis were significantly more frequent in VE+ patients, as an abnormal CT-scan at diagnosis, aortitis, particularly of the descending thoracic aorta and atheroma. Deaths were more frequent in the VE+ group. Among 254 GCA patients, 39 experienced at least one vascular event during follow-up. Aortic surgery, stroke, upper and lower limb ischemia were vascular event risk factors. Aortic atheroma and descending thoracic aorta aortitis on CT-scan were vascular event risk factors. This study on GCA cases with large vessels imaging at diagnosis, showed that aortic surgery, stroke, upper or lower limb ischemia, aortic atheroma and aortitis of the descending thoracic aorta on CT-scan, at GCA diagnosis, were independent predictive factors of a vascular event.

Long Term Vascular Outcomes in Patients with Mixed Location Intracerebral Hemorrhage and Microbleeds

ObjectiveTo determine whether mixed location intracerebral hemorrhages/microbleeds (Mixed-ICH) is a risk factor for vascular unfavorable outcome compared to cerebral amyloid angiopathy-related ICH (CAA-ICH) or strictly deep hypertensive intracerebral hemorrhage/microbleeds (HTN-ICH).Methods300 patients with spontaneous ICH were included. Clinical data, neuroimaging markers and follow-up outcomes (recurrent ICH, ischemic stroke and vascular death) were compared between Mixed-ICH (n=148), CAA-ICH (n=32) and HTN-ICH (n=120). The association between follow-up events and neuroimaging markers were explored using multivariable Cox regression models.ResultsPatients with Mixed-ICH are older (65.6±12.1 years vs 58.1±13.3 years, p<0.001) than HTN-ICH, but younger than CAA-ICH (73.3±13.8 years, p=0.001). Compared to CAA-ICH, Mixed-ICH has similar incidence of vascular event (all p>0.05). Compared to HTN-ICH, Mixed-ICH is associated with higher ICH recurrence (hazard ratio [HR]=3.0, 95% confidence interval [CI]: 1.2-7.7), more ischemic stroke (HR=8.2, 95% CI: 1.0-65.8), and vascular composite outcome (HR=3.5, 95% CI: 1.5-8.2) after adjustment for age and sex. In patients with Mixed-ICH, the presence of cortical superficial siderosis (cSS) is associated the development of ICH recurrence (HR=4.8, 95% CI 1.0-23.2), ischemic stroke (HR=8.8, 95% CI: 1.7-45.5), and vascular composite outcome (HR=6.2, 95% CI: 1.9-20.2). The association between cSS and ischemic stroke (p=0.01) or vascular composite outcome (p=0.003) remained significant after further adjustment for other radiological markers.ConclusionsMixed-ICH harbors higher risk of unfavorable vascular outcome than HTN-ICH. Presence of cSS in Mixed-ICH independently predicts vascular event, suggesting the contribution of detrimental effect due to coexisting CAA.

Abstract 17116: Incidence and Costs of Major Atherothrombotic Vascular Events Among Patients With Peripheral Artery Disease After Revascularization

Introduction: Peripheral artery disease (PAD), frequently requiring lower-extremity revascularization (LER), is associated with risk of major atherothrombotic vascular events (acute limb ischemia [ALI], major amputation of vascular etiology, myocardial infarction [MI], ischemic stroke [IS], cardiovascular [CV] death). Understanding the incidence and healthcare costs of such events in PAD patients post-revascularization may be important in translation. Methods: Patients with PAD who underwent LER were identified from Optum Clinformatics Data Mart claims database (Q1 2014 - Q2 2019). The first LER was considered index. Patients were required to be ≥50 years old at index with ≥6 months of prior health plan enrollment. Patients with IS, atrial fibrillation (AF), venous thromboembolism (VTE), intracranial hemorrhage, ESRD, or oral anticoagulant (OAC) use pre-index; or diagnoses of MI 30 days or ALI 14 days pre-index were excluded. Patients were followed until the earliest of 1) end of enrollment/data; 2) diagnosis of AF or VTE; or 3) OAC use. For each major vascular event, the incidence rate was assessed as the number of first events divided by patient-years of observation. Event-related healthcare costs per-patient-year (PPY) were also reported. Results: Of the 38,439 PAD patients meeting the study criteria, 6,675 (17.4%) had a major atherothrombotic vascular event over a median follow-up of 1.0 years (IQR: 0.4-2.1). The composite event incidence rate was 13.81 per 100 patient years [ALI: 5.51; lower-limb amputation: 5.15; MI: 3.19; IS: 2.06; CV-related death: 0.88]. PPY event-related costs ranged from $57,825 for IS to $108,302 for lower-limb amputation (Figure). Conclusions: One in six PAD patients have a major atherothrombotic vascular event within one year post-LER. Costs of these events are high, particularly for limb complications. Therefore, reducing the rate of such events could reduce the overall healthcare costs for this population.

Long-term prognosis after intracerebral haemorrhage

Introduction The aim of this study was to determine the risk of recurrent intracerebral haemorrhage (ICH), ischaemic stroke, all stroke, any vascular event and all-cause mortality in 30-day survivors of ICH, according to age and sex. Patients and methods We linked national hospital discharge, population and cause of death registers to obtain a cohort of Dutch 30-day survivors of ICH from 1998 to 2010. We calculated cumulative incidences of recurrent ICH, ischaemic stroke, all stroke and composite vascular outcome, adjusted for competing risk of death and all-cause mortality. Additionally, we compared survival with the general population. Results We included 19,444 ICH-survivors (52% male; median age 72 years, interquartile range 61–79; 78,654 patient-years of follow-up). First-year cumulative incidence of recurrent ICH ranged from 1.5% (95% confidence interval 0.9–2.3; men 35–54 years) to 2.4% (2.0–2.9; women 75–94 years). Depending on age and sex, 10-year risk of recurrent ICH ranged from 3.7% (2.6–5.1; men 35–54 years) to 8.1% (6.9–9.4; women 55–74 years); ischaemic stroke 2.6% to 7.0%, of all stroke 9.9% to 26.2% and of any vascular event 15.0% to 40.4%. Ten-year mortality ranged from 16.7% (35–54 years) to 90.0% (75–94 years). Relative survival was lower in all age-groups of both sexes, ranging from 0.83 (0.80–0.87) in 35- to 54-year-old men to 0.28 (0.24–0.32) in 75- to 94-year-old women. Discussion ICH-survivors are at high risk of recurrent ICH, of ischaemic stroke and other vascular events, and have a sustained reduced survival rate compared to the general population. Conclusion The high risk of recurrent ICH, other vascular events and prolonged reduced survival-rates warrant clinical trials to determine optimal secondary prevention treatment after ICH.

Myasthenia Gravis Mimicking Acute Cerebrovascular Events

Background and Objective: Myasthenia gravis (MG) is an immune-mediated disorder that can sometimes present acutely with a focal neurological deficit and thus mimic a cerebrovascular event. The objective of this study was to describe the clinical characteristics in a large cohort of patients who were initially misdiagnosed with an acute vascular event and later diagnosed with MG. Methods: This is a retrospective chart review of patients who were initially diagnosed with an acute cerebrovascular event but subsequently found to have MG. The chart review was done for the period from January 2013 to December 2017, and patients with at least one-year follow-up included. Data are reported as means ± SEM, and the results reported using prevalence rates. Results: Twenty-one patients met our inclusion criteria. Among them, 13 (61.9%) were female with a mean age of 56.7 ± 4.07 years. Ten were MGFA class 3a; seven were MGFA class 2b, 3 were MGFA 3b. Eighteen patients were acetylcholine receptor antibody positive; one was MuSK positive, and the rest two seronegative. Slurred speech (8 patients, 38.1%) was the most common symptom that resulted in misdiagnosis, followed by hemibody weakness (7 patients, 33.3%) and dysphagia (3, 14.3%). Smoking (12, 57.1%) and hypertension (11, 52.4%) were common risk factors for cerebrovascular disease. Small vessel disease was suspected the most common etiology (15, 71.4%) of the vascular event. Ten patients had received thrombolytic therapy, and 16 patients were on antiplatelets. 4 patients who presented recurrent symptoms placed on anticoagulants. Conclusion: Acute presentation of bulbar symptoms and hemibody weakness resulted in the misdiagnosis of MG.