Dynamically Normalized Pupillometry for Detecting Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage.

OBJECTIVES: Delayed cerebral ischemia (DCI) is a major driver of morbidity after aneurysmal subarachnoid hemorrhage (aSAH). Quantitative pupillometry has been shown to be of prognostic value after acute neurological injury. However, the evidence for the use of pupillometric features for the detection of DCI has been conflicting. The aim of this study was to investigate the prognostic value of frequent pupillometric monitoring for DCI detection. DESIGN: Observational cohort study from a prospective aSAH registry. SETTING: Tertiary referral center. PATIENTS: Adult patients with confirmed aSAH admitted to the ICU between March 2019 and December 2023. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One hundred fourteen patients were included, of which 31 (27.2%) suffered from DCI. All patients underwent frequent pupillometry (every 3 hr). We determined the absolute value of the neurological pupil index (NPi) and constriction velocity (CV), and their value normalized to the maximal recorded value between the admission and the pupillometry measure to account for personalized baselines. The association between pupillometry values and the occurrence of DCI within 6-24 hours was investigated. Normalized CV had the best discriminative performance to identify DCI within 8 hours, with an area under the receiver operating characteristic curve of 0.82 (95% CI, 0.69-0.91). NPi, as well as non-normalized metrics, were not significantly associated with DCI. CONCLUSIONS: Normalized CV has a clinically and statistically significant association with the occurrence of DCI after aSAH. Frequent quantitative pupillometry could improve the multimodal monitoring of patients after aSAH with the goal of improving the identification of patients likely to benefit from therapeutic interventions.

Sex differences in functional outcomes of intravenous thrombolysis among patients with lacunar stroke.

Background: This study aimed to assess if there are sex differences in the functional outcome of intravenous thrombolysis (IVT) among patients with lacunar stroke (LS). Methods: Consecutive patients admitted from 1 January 2014 to 31 January 2020 to hospitals participating in the Swiss Stroke Registry presenting with LS and treated with IVT were included. The study population was then divided into two groups based on patient sex, and a multivariable ordinal logistic regression analysis was performed to uncover sex differences in the modified Rankin Scale (mRS) score at 90 days after stroke. Results: A total of 413 patients with LS were treated with IVT: 177 (42.9%) women and 236 (57.1%) men. Women were older than men (median age 74 years, 25th-75th percentiles 67-84 years versus 70 years, 25th-75th percentiles 60-80 years, value of p 0.001) and, after adjustment for meaningful variables, showed more frequently increased odds of a higher mRS score at 90 days after stroke (adjusted odds ratio 1.49, 95% confidence interval 1.01-2.19, value of p 0.044). Conclusion: This study showed that female sex increased the odds of a worse functional response to IVT in patients with LS. Future studies should further elucidate the mechanisms underlying such sex differences.

Intracerebral haemorrhage in patients taking different types of oral anticoagulants: a pooled individual patient data analysis from two national stroke registries.

BACKGROUND: We investigated outcomes in patients with intracerebral haemorrhage (ICH) according to prior anticoagulation treatment with Vitamin K antagonists (VKAs), direct oral anticoagulants (DOACs) or no anticoagulation. METHODS: This is an individual patient data study combining two prospective national stroke registries from Switzerland and Norway (2013-2019). We included all consecutive patients with ICH from both registries. The main outcomes were favourable functional outcome (modified Rankin Scale 0-2) and mortality at 3 months. RESULTS: Among 11 349 patients with ICH (mean age 73.6 years; 47.6% women), 1491 (13.1%) were taking VKAs and 1205 (10.6%) DOACs (95.2% factor Xa inhibitors). The median percentage of patients on prior anticoagulation was 23.7 (IQR 22.6-25.1) with VKAs decreasing (from 18.3% to 7.6%) and DOACs increasing (from 3.0% to 18.0%) over time. Prior VKA therapy (n=209 (22.3%); adjusted ORs (aOR), 0.64; 95% CI, 0.49 to 0.84) and prior DOAC therapy (n=184 (25.7%); aOR, 0.64; 95% CI, 0.47 to 0.87) were independently associated with lower odds of favourable outcome compared with patients without anticoagulation (n=2037 (38.8%)). Prior VKA therapy (n=720 (49.4%); aOR, 1.71; 95% CI, 1.41 to 2.08) and prior DOAC therapy (n=460 (39.7%); aOR, 1.28; 95% CI, 1.02 to 1.60) were independently associated with higher odds of mortality compared with patients without anticoagulation (n=2512 (30.2%)). CONCLUSIONS: The spectrum of anticoagulation-associated ICH changed over time. Compared with patients without prior anticoagulation, prior VKA treatment and prior DOAC treatment were independently associated with lower odds of favourable outcome and higher odds of mortality at 3 months. Specific reversal agents unavailable during the study period might improve outcomes of DOAC-associated ICH in the future.

CADMUS: A Novel MRI-Based Classification of Spontaneous Intracerebral Hemorrhage Associated With Cerebral Small Vessel Disease

BACKGROUND AND OBJECTIVES: Cerebral small vessel disease (SVD) is the major cause of intracerebral hemorrhage (ICH). There is no comprehensive, easily applicable classification of ICH subtypes according to the presumed underlying SVD using MRI. We developed an MRI-based classification for SVD-related ICH. METHODS: We performed a retrospective study in the prospectively collected Swiss Stroke Registry (SSR, 2013-2019) and the Stroke InvestiGation in North And central London (SIGNAL) cohort. Patients with nontraumatic, SVD-related ICH and available MRI within 3 months were classified as Cerebral Amyloid angiopathy (CAA), Deep perforator arteriopathy (DPA), Mixed CAA-DPA, or Undetermined SVD using hemorrhagic and nonhemorrhagic MRI markers (CADMUS classification). The primary outcome was inter-rater reliability using Gwet's AC1. Secondary outcomes were recurrent ICH/ischemic stroke at 3 months according to the CADMUS phenotype. We performed Firth penalized logistic regressions and competing risk analyses. RESULTS: The SSR cohort included 1,180 patients (median age [interquartile range] 73 [62-80] years, baseline NIH Stroke Scale 6 [2-12], 45.6% lobar hematoma, systolic blood pressure on admission 166 [145-185] mm Hg). The CADMUS phenotypes were as follows: mixed CAA-DPA (n = 751 patients, 63.6%), undetermined SVD (n = 203, 17.2%), CAA (n = 154, 13.1%), and DPA (n = 72, 6.3%), with a similar distribution in the SIGNAL cohort (n = 313). Inter-rater reliability was good (Gwet's AC1 for SSR/SIGNAL 0.69/0.74). During follow-up, 56 patients had 57 events (28 ICH, 29 ischemic strokes). Three-month event rates were comparable between the CADMUS phenotypes. DISCUSSION: CADMUS, a novel MRI-based classification for SVD-associated ICH, is feasible and reproducible and may improve the classification of ICH subtypes in clinical practice and research.

Effectiveness of the preventive administration of vasoactive amines in counterbalancing significant patient blood pressure drops following nimodipine administration during mechanical thrombectomy procedures.

BACKGROUND: Focal vasospasm (FV) of the occluded vessel can occur during the endovascular treatment of acute ischemic stroke (AIS). Nimodipine is commonly used to treat vasospasm and can play a role in distinguishing it from artery narrowing due to iatrogenic dissection or residual clot. However, nimodipine administration can result in arterial hypotension and subsequent enlargement of the ischemic core. OBJECTIVE: To assess the efficacy of preventive and continuous vasoactive amine infusion to counterbalance nimodipine-induced hypotension. METHODS: We reviewed data from a prospective registry of patients treated for AIS between January 2019 and January 2022 who were administered nimodipine. All patients were equipped with an arterial cannula for invasive blood pressure measurement and given vasoactive amines preemptively before general anesthesia and throughout the procedure. Data obtained from invasive monitoring of mean arterial blood pressure (MABP) in a time-lapse of 25 min before and after nimodipine administration were analyzed. RESULTS: MABP significantly decreased after nimodipine administration but remained within the recommended range (81.79 ± 0.49 mmHg). Nimodipine was effective in reducing FV caused by stent retriever passage in 76.3% of cases. Furthermore, it proved valuable in diagnosing iatrogenic dissection (9.2%), residual clot (10.5%), or intracranial stenosis (4%). CONCLUSIONS: Infusion of vasoactive amines effectively counteracted the intraarterial nimodipine effect, thus avoiding frank arterial hypotension during endovascular treatment. Nimodipine has been useful in differentiating the diagnosis of FV resulting from mechanical thrombectomy and other potential causes, such as iatrogenic dissection or residual clot.