Stroke Prevention in Symptomatic Large Artery Intracranial Atherosclerosis Practice Advisory: Report of the AAN Guideline Subcommittee.

BACKGROUND AND OBJECTIVES: To review treatments for reducing the risk of recurrent stroke or death in patients with symptomatic intracranial atherosclerotic arterial stenosis (sICAS). METHODS: The development of this practice advisory followed the process outlined in the American Academy of Neurology Clinical Practice Guideline Process Manual, 2011 Edition, as amended. The systematic review included studies through November 2020. Recommendations were based on evidence, related evidence, principles of care, and inferences. MAJOR RECOMMENDATIONS: Clinicians should recommend aspirin 325 mg/d for long-term prevention of stroke and death and should recommend adding clopidogrel 75 mg/d to aspirin for up to 90 days to further reduce stroke risk in patients with severe (70%-99%) sICAS who have low risk of hemorrhagic transformation. Clinicians should recommend high-intensity statin therapy to achieve a goal low-density lipoprotein cholesterol level <70 mg/dL, a long-term blood pressure target of <140/90 mm Hg, at least moderate physical activity, and treatment of other modifiable vascular risk factors for patients with sICAS. Clinicians should not recommend percutaneous transluminal angioplasty and stenting for stroke prevention in patients with moderate (50%-69%) sICAS or as the initial treatment for stroke prevention in patients with severe sICAS. Clinicians should not routinely recommend angioplasty alone or indirect bypass for stroke prevention in patients with sICAS outside clinical trials. Clinicians should not recommend direct bypass for stroke prevention in patients with sICAS. Clinicians should counsel patients about the risks of percutaneous transluminal angioplasty and stenting and alternative treatments if one of these procedures is being contemplated.

Lipid Levels and Short-Term Risk of Recurrent Brain Infarcts in Symptomatic Intracranial Stenosis.

OBJECTIVES: Hyperlipidemia is a strong risk factor for intracranial atherosclerotic disease (ICAD) and clinical stroke recurrence. We explored the effect of serum lipid levels on subclinical infarct recurrence in the Mechanisms of earlY Recurrence in Intracranial Atherosclerotic Disease (MYRIAD) study. MATERIALS AND METHODS: We included enrolled MYRIAD patients with lipid measurements and brain MRI at baseline and brain MRI at 6-8 weeks. Infarct recurrence was defined as new infarcts in the territory of the symptomatic artery on brain MRI at 6-8 weeks compared to baseline brain MRI. We assessed the association between baseline total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels and recurrent infarct at 6-8 weeks using multivariable logistic regression. RESULTS: Among 74 patients (mean age 64.2±12.9 years, 59.5% were white, 60.8% men), 20 (27.0%) had new or recurrent infarcts. Mean HDL-C (37.2 vs. 43.9 mg/dL, P=0.037) was lower and TG (113.5 vs. 91.3 mg/dL, P=0.008) was higher while TC (199.8 vs. 174.3 mg/dL, P=0.061) and LDL-C (124.3 vs. 101.2 mg/dL, P=0.053) were nominally higher among those with recurrent infarcts than those without. LDL-C (adj. OR 1.022, 95% CI 1.004-1.040, P=0.015) and TG (adj. OR 1.009, 95% CI 1.001-1.016, P=0.021) were predictors of recurrent infarct at 6-8 weeks adjusting for other clinical and imaging factors. CONCLUSIONS: Baseline cholesterol markers can predict early infarct recurrence in patients with symptomatic ICAD. More intensive and rapid lipid lowering drugs may be required to reduce risk of early recurrence.

Predictors of Early Infarct Recurrence in Patients With Symptomatic Intracranial Atherosclerotic Disease.

BACKGROUND AND PURPOSE: While prior studies identified risk factors for recurrent stroke in patients with symptomatic intracranial atherosclerotic disease, few have assessed risk factors for early infarct recurrence. METHODS: We performed a post hoc analysis of the MYRIAD study (Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease) of intracranial atherosclerotic disease patients with recent (<21 days) stroke/transient ischemic attack, 50% to 99% stenosis and who underwent 6- to 8-week magnetic resonance imaging (MRI) per protocol. Infarct recurrence was defined as new infarcts in the territory of the symptomatic artery on brain MRI at 6 to 8 weeks compared to index brain MRI. Qualifying events and clinical and imaging outcomes were centrally ascertained by 2 independent reviewers. We assessed the association between baseline clinical and imaging variables and recurrent infarct in bivariate models and multivariable logistic regression to identify independent predictors of infarct recurrence. RESULTS: Of 105 enrolled patients in MYRIAD, 89 (84.8%) were included in this analysis (mean age, 64±12 years, 54 [60.7%] were male, and 53 [59.6%] were White). The median time from qualifying event to MRI was 51+16 days, on which 22 (24.7%) patients had new or recurrent infarcts. Younger age (57.7 versus 66.0 years; P<0.01), diabetes (32.6% versus 14.6%, P=0.05), index stroke (31.3% versus 4.6%, P=0.01), anterior circulation location of stenosis (29.7% versus 12.0%, P=0.08), number of diffusion-weighted imaging lesions (>1: 40.0%, 1: 26.9% versus 0: 4.4%, P<0.01), and borderzone infarct pattern (63.6% versus 25.0%, P=0.01) on baseline MRI were associated with new or recurrent infarcts. Age (adjusted odds ratio, 0.93 [95% CI, 0.89-0.98], P<0.01) and number of diffusion-weighted imaging lesions (adjusted odds ratio, 3.24 [95% CI, 1.36-7.71], P<0.01) were independently associated with recurrent infarct adjusting for hypertension, diabetes, and stenosis location (anterior versus posterior circulation). CONCLUSIONS: An index multi-infarct pattern is associated with early recurrent infarcts, a finding that might be explained by plaque instability and artery-to-artery embolism. Further investigation of plaque vulnerability in intracranial atherosclerotic disease is needed. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02121028.

Imaging Patterns of Recurrent Infarction in the Mechanisms of Early Recurrence in Intracranial Atherosclerotic Disease (MyRIAD) Study.

Introduction: While much is known about recurrent clinical events in patients with intracranial atherosclerotic disease (ICAD), there is limited data on characteristics of recurrent infarcts. Methods: The NIH-funded MyRIAD prospective, observational study was designed to identify mechanisms of ischemia and predictors of recurrence in ICAD. Recurrent infarction was assessed on MRI at 6-8 weeks. We reviewed the DWI/ADC and FLAIR sequences in patients with recurrent stroke and characterized the number of infarcts, infarct location, size, and patterns based on whether they were borderzone (BZ), perforator (SC/P), cortical or territorial (C/T), and mixed. Temporal characteristics were delineated by ADC/FLAIR correlation. Results: Of the 89 patients with 6-8 weeks MRI, 22 (24.7%) had recurrent infarcts in the territory of the symptomatic artery. Recurrent infarcts were evident on DWI in 63.6% and single infarcts in 54.5%. The median recurrent infarct volume was 2.0 cm3 compared to median index infarct volumes of 2.5 cm3. A mixed infarct pattern was most common (40.9%), followed by borderzone (22.7%), cortical or territorial (27.3%), while only 9.1% were in a perforator artery distribution. Amongst those with a mixed pattern, 8/9 had a borderzone distribution infarct as part of their mixed infarct pattern. Conclusion: These findings provide novel data on the characteristics of early recurrent infarcts in patients with symptomatic ICAD.

Magnesium, hemostasis, and outcomes in patients with intracerebral hemorrhage.

OBJECTIVE: We tested the hypothesis that admission serum magnesium levels are associated with hematoma volume, hematoma growth, and functional outcomes in patients with intracerebral hemorrhage (ICH). METHODS: Patients presenting with spontaneous ICH were enrolled in an observational cohort study that prospectively collected demographic, clinical, laboratory, radiographic, and outcome data. We performed univariate and adjusted multivariate analyses to assess for associations between serum magnesium levels and initial hematoma volume, final hematoma volume, and in-hospital hematoma growth as radiographic measures of hemostasis, and functional outcome measured by the modified Rankin Scale (mRS) at 3 months. RESULTS: We included 290 patients for analysis. Admission serum magnesium was 2.0 ± 0.3 mg/dL. Lower admission magnesium levels were associated with larger initial hematoma volumes on univariate (p = 0.02), parsimoniously adjusted (p = 0.002), and fully adjusted models (p = 0.006), as well as greater hematoma growth (p = 0.004, p = 0.005, and p = 0.008, respectively) and larger final hematoma volumes (p = 0.02, p = 0.001, and p = 0.002, respectively). Lower admission magnesium level was associated with worse functional outcomes at 3 months (i.e., higher mRS; odds ratio 0.14, 95% confidence interval 0.03-0.64, p = 0.011) after adjustment for age, admission Glasgow Coma Scale score, initial hematoma volume, time from symptom onset to initial CT, and hematoma growth, with evidence that the effect of magnesium is mediated through hematoma growth. CONCLUSIONS: These data support the hypothesis that magnesium exerts a clinically meaningful influence on hemostasis in patients with ICH.

Challenges in the Medical Management of Symptomatic Intracranial Stenosis in an Urban Setting.

BACKGROUND AND PURPOSE: Since the SAMMPRIS trial (Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis), aggressive medical management (AMM), which includes dual antiplatelet therapy (DAPT) and high-dose statin (HDS) therapy, is recommended for patients with symptomatic intracranial atherosclerotic disease. However, limited data on the real-world application of this regimen exist. We hypothesized that recurrent stroke risk among patients treated with AMM is similar to the medical arm of the SAMMPRIS cohort. METHODS: Using a prospective registry, we identified all patients admitted between August 2012 and March 2015 with (1) confirmed ischemic stroke or transient ischemic attack; (2) independently adjudicated symptomatic intracranial atherosclerotic disease; and (3) follow-up at 30 days. We analyzed 30-day risk of recurrent ischemic stroke stratified by treatment: (1) AMM: DAPT plus HDS therapy, (2) HDS alone, and (3) DAPT alone. We also assessed 30-day risk among patients who met prespecified SAMMPRIS eligibility criteria. RESULTS: Among 99 patients who met study criteria (51.5% male, 54.5% black, mean age 68.2±11.2 years), 49 (48.5%) patients were treated with AMM, 69 (69.7%) with DAPT, and 73 (73.7%) with HDS therapy. At 30 days, 20 (20.2%) patients had recurrent strokes in the territory of stenosis. Compared with the risk in the medical arm of SAMMPRIS (4.4%), the 30-day risk of recurrent stroke was 20.4% in AMM patients, 21.5% in HDS patients, 22.4% in DAPT patients, and 23.2% in SAMMPRIS-eligible patients (all P<0.001). CONCLUSIONS: Recurrent stroke risk within 30 days in patients with symptomatic intracranial atherosclerotic disease was higher than that observed in the medical arm of SAMMPRIS even in the subgroup receiving AMM. Replication of the SAMMPRIS findings requires further prospective study.

Refining Prognosis for Intracerebral Hemorrhage by Early Reassessment.

BACKGROUND: Prognostic assessments, which are crucial for decision-making in critical illnesses, have shown unsatisfactory reliability. We compared the accuracy of a widely used prognostic score against a model derived from clinical data obtained 5 days after admission for patients with intracerebral hemorrhage (ICH), a condition for which prognostication has proven notoriously challenging and prone to bias. METHODS: Patients enrolled in a prospective observational cohort study of spontaneous ICH underwent hourly Glasgow Coma Scale (GCS) assessment. Outcome was measured at 3 months using the modified Rankin Scale (mRS). We analyzed the change in correlation between GCS and 3-month mRS scores from admission through day 5, and compared the performance of a parsimonious set of day 5 clinical variables against the ICH score. RESULTS: Data was collected on 254 subjects. The ICH score and day 5 GCS score were both correlated with 3-month mRS score (p < 0.001), but the correlation was stronger with day 5 GCS score (p < 0.05 by Fisher z-transformation). Premorbid mRS score, intraventricular hemorrhage and day 5 GCS score were independent predictors of outcome (all p < 0.05 in ordinal regression model). While ICH score correctly classified good (mRS 0-3) vs. poor (mRS 4-6) outcome in 73% of cases, the day 5 model correctly classified 83% of cases. CONCLUSIONS: A simple reassessment after 5 days of care significantly improves the accuracy of prognosticating outcome in patients with ICH. These data confirm the feasibility and potential utility of early reassessments in refining prognosis for patients who survive early stabilization of a severe neurologic injury.

Quality of life in patients with TIA and minor ischemic stroke.

OBJECTIVE: We investigated health-related quality of life (HRQOL) in patients with TIA and minor ischemic stroke (MIS) using Neuro-QOL, a validated, patient-reported outcome measurement system. METHODS: Consecutive patients with TIA or MIS who had (1) modified Rankin Scale (mRS) score of 0 or 1 at baseline, (2) initial NIH Stroke Scale score of ≤5, (3) no acute reperfusion treatment, and (4) 3-month follow-up, were recruited. Recurrent stroke, disability by mRS and Barthel Index, and Neuro-QOL scores in 5 prespecified domains were prospectively recorded. We assessed the proportion of patients with impaired HRQOL, defined as T scores more than 0.5 SD worse than the general population average, and identified predictors of impaired HRQOL using logistic regression. RESULTS: Among 332 patients who met study criteria (mean age 65.7 years, 52.4% male), 47 (14.2%) had recurrent stroke within 90 days and 41 (12.3%) were disabled (mRS >1 or Barthel Index <95) at 3 months. Any HRQOL impairment was noted in 119 patients (35.8%). In multivariate analysis, age (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.04), initial NIH Stroke Scale score (adjusted OR 1.39, 95% CI 1.17-1.64), recurrent stroke (adjusted OR 2.10, 95% CI 1.06-4.13), and proxy reporting (adjusted OR 3.94, 95% CI 1.54-10.10) were independent predictors of impaired HRQOL at 3 months. CONCLUSIONS: Impairment in HRQOL is common at 3 months after MIS and TIA. Predictors of impaired HRQOL include age, index stroke severity, and recurrent stroke. Future studies should include HRQOL measures in outcome assessment, as these may be more sensitive to mild deficits than traditional disability scales.