Poststroke acute dysexecutive syndrome, a disorder resulting from minor stroke due to disruption of network dynamics.

Stroke patients with small central nervous system infarcts often demonstrate an acute dysexecutive syndrome characterized by difficulty with attention, concentration, and processing speed, independent of lesion size or location. We use magnetoencephalography (MEG) to show that disruption of network dynamics may be responsible. Nine patients with recent minor strokes and eight age-similar controls underwent cognitive screening using the Montreal cognitive assessment (MoCA) and MEG to evaluate differences in cerebral activation patterns. During MEG, subjects participated in a visual picture-word matching task. Task complexity was increased as testing progressed. Cluster-based permutation tests determined differences in activation patterns within the visual cortex, fusiform gyrus, and lateral temporal lobe. At visit 1, MoCA scores were significantly lower for patients than controls (median [interquartile range] = 26.0 [4] versus 29.5 [3], P = 0.005), and patient reaction times were increased. The amplitude of activation was significantly lower after infarct and demonstrated a pattern of temporal dispersion independent of stroke location. Differences were prominent in the fusiform gyrus and lateral temporal lobe. The pattern suggests that distributed network dysfunction may be responsible. Additionally, controls were able to modulate their cerebral activity based on task difficulty. In contrast, stroke patients exhibited the same low-amplitude response to all stimuli. Group differences remained, to a lesser degree, 6 mo later; while MoCA scores and reaction times improved for patients. This study suggests that function is a globally distributed property beyond area-specific functionality and illustrates the need for longer-term follow-up studies to determine whether abnormal activation patterns ultimately resolve or another mechanism underlies continued recovery.

The Routine Follow-up Head CT: Is it Still a Necessary Step in the Thrombolysis Pathway?

BACKGROUND: The 24-h head computed tomography (CT) scan following intravenous tissue plasminogen activator or mechanical thrombectomy (MT) is currently part of most acute stroke protocols. However, as evidence emerges regarding who is at highest risk for treatment complications, the utility of routine neuroimaging for all patients has become less clear. METHODS: Four hundred seventy-five patients presenting with acute ischemic stroke to Johns Hopkins Bayview Medical Center between 2004 and 2018 and treated with intravenous tissue plasminogen activator and/or MT were evaluated. Neuroimaging performed during the first 48 h of hospitalization was reviewed for edema, hemorrhagic transformation (HT), or other findings altering management. Early imaging (< 24 h), performed for neurologic deterioration, was compared with imaging performed per protocol (24 ± 6 h). Factors predictive of radiographically and clinically significant findings on per-protocol imaging were determined. RESULTS: One hundred fifty-three patients (32%) underwent early imaging. These patients generally had more severe strokes. HT was found in 15% of cases. For the remaining patients (n = 322), imaging at 24 h impacted acute management for only 24 patients: resulting in emergent hemicraniectomy in 1 (0.3%) and leading to additional imaging to monitor asymptomatic HT or edema in 23 (7.1%). Advanced age, higher stroke severity, MT, and atrial fibrillation were associated with significant findings on the 24-h CT scan. Only 2 of the 24 patients had an initial National Institutes of Health Stroke Scale score of < 7. CONCLUSIONS: The 24-h head CT scan does not change management for most patients, particularly those with low National Institutes of Health Stroke Scale scores who do not undergo MT. Consideration should be given to removing routine follow-up imaging from postthrombolysis protocols in favor of an examination-based approach.

Resource Allocation: Stable Patients Remain Stable 12-24 h Post-tPA.

BACKGROUND AND PURPOSE: Stroke patients are currently monitored for neurological deterioration for 24 h following treatment with intravenous tissue plasminogen activator (IV tPA) or mechanical thrombectomy. This requires low nursing ratios and an intensive-care-like setting. As the half-life of IV tPA is short, many patients may not require such prolonged intensive monitoring and could be downgraded much earlier. We evaluate the frequency of neurological deterioration in the 0-12 and 12-24 h post-treatment windows. METHODS: Patients presenting with acute ischemic stroke treated with IV tPA and/or thrombectomy at our institution from 2016-2018 were prospectively followed per protocol for 24 h post-therapy (examinations every 15 min for 2 h, every 30 min for 6 h, and hourly thereafter). Neurological deteriorations were recorded along with interventions and complications. Frequency of deterioration within the 0-12 and 12-24 h post-treatment windows was determined, along with factors associated with decline at each time point. RESULTS: A total of 172 patients were treated (IV:135, IA:65, both:30). Thirty-six (21%) experienced a documented neurologic deterioration [8 due to intracerebral hemorrhage (4.7%)]. Five patients deteriorated in the 12-24 h window; all but one had experienced earlier examination changes. Elevated NIHSS was associated with a higher likelihood of deterioration overall. Early fluctuation was associated with decline after 12 h. CONCLUSIONS: New onset of neurologic deterioration is rare 12-24 h after treatment of acute stroke. Stable patients with low NIHSS scores and no ICU needs may not require intensive monitoring greater than 12 h post-treatment.

Comparison of Traumatic Intracranial Hemorrhage Expansion and Outcomes Among Patients on Direct Oral Anticoagulants Versus Vitamin k Antagonists.

BACKGROUND: With increasing use of direct oral anticoagulants (DOACs) and availability of new reversal agents, the risk of traumatic intracranial hemorrhage (tICH) requires better understanding. We compared hemorrhage expansion rates, mortality, and morbidity following tICH in patients treated with vitamin k antagonists (VKA: warfarin) and DOACs (apixaban, rivaroxaban, dabigatran). METHODS: Retrospective chart review of patients from 2010 to 2017 was performed to identify patients with imaging diagnosis of acute traumatic intraparenchymal, subdural, subarachnoid, and epidural hemorrhage with preadmission use of DOACs or VKAs. We identified 39 patients on DOACs and 97 patients on VKAs. Demographic information, comorbidities, hemorrhage size, and expansion over time, as well as discharge disposition and Glasgow Outcome Scale (GOS) were collected. Primary outcome was development of new or enlargement of tICH within the first 48 h of initial CT imaging. RESULTS: Of 136 patients with mean (SD) age 78.7 (13.2) years, most common tICH subtype was subdural hematoma (N = 102/136; 75%), and most common mechanism was a fall (N = 130/136; 95.6%). Majority of patients in the DOAC group did not receive reversal agents (66.7%). Hemorrhage expansion or new hemorrhage occurred in 11.1% in DOAC group vs. 14.6% in VKA group (p = 0.77) at a median of 8 and 11 h from initial ED admission, respectively (p = 0.82). Patients in the DOAC group compared to VKA group had higher median discharge GOS (4 vs. 3 respectively, p = 0.03), higher percentage of patients with good outcome (GOS 4-5, 66.7% vs. 40.2% respectively, p = 0.005), and higher rate of discharge to home or rehabilitation (p = 0.04). CONCLUSIONS: We report anticoagulation-associated tICH outcomes predominantly due to fall-related subdural hematomas. Patients on DOACs had lower tICH expansion rates although not statistically significantly different from VKA-treated patients. DOAC-treated patients had favorable outcomes versus VKA group following tICH despite low use of reversal strategies. DOAC use may be a safer alternative to VKA in patients at risk of traumatic brain hemorrhage.

Identifying Delirium Early after Stroke: A New Prediction Tool for the Intensive Care Unit.

BACKGROUND: Delirium is common after stroke and associated with poor functional outcomes and mortality. It is unknown whether delirium is a modifiable risk factor, or simply an indicator of prognosis, but in order to intervene successfully, those at greatest risk must be identified early. We created a tool to predict the development of delirium in patients admitted to the intensive care unit for stroke, focusing on factors present on hospital admission. METHODS: Charts of 102 patients admitted to the ICU or IMC after ischemic stroke or intracranial hemorrhage with symptom onset within 72 hours were reviewed. Delirium was identified using the Confusion Assessment Method for the ICU (CAM-ICU). Factors significantly associated with delirium were included in a multivariable logistic regression analysis to create a predictive model. The model was validated in a unique inpatient cohort. RESULTS: In regression analyses, the variables present on admission most strongly associated with the development of delirium after stroke included: age greater than 64 years; intraventricular hemorrhage; intubation; presence of either cognitive dysfunction, aphasia, or neglect; and acute kidney injury. Using these variables in our predictive model, an ROC analysis resulted in an area under the curve of 0.90, and 0.82 in our validation cohort. CONCLUSIONS: Factors available on admission can be used to accurately predict risk of delirium following stroke. Our model can be used to implement more rigorous screening paradigms, allowing for earlier detection and timely treatment. Futures studies will focus on determining if prevention can mitigate the poor outcomes with which delirium is associated.

A Therapeutic International Normalized Ratio Results in Smaller Infarcts and Better Outcomes for Patients with Ischemic Stroke.

BACKGROUND: Prior studies have shown that warfarin is effective for both primary and secondary stroke prevention in individuals with atrial fibrillation. It is also known that those on warfarin with atrial fibrillation often have poorer long-term poststroke outcomes, possibly because cardioembolic strokes tend to be larger and more severe. Less is known regarding the direct effect of the international normalized ratio (INR) value at the time of stroke on severity or long-term functional status. METHODS: We prospectively followed a consecutive series of 112 patients presenting to our institution with acute ischemic stroke between 2013 and 2018 who were on warfarin. Along with INR on admission, data were collected regarding patient demographics, vascular risk factors, stroke characteristics, and functional outcomes. Patients were stratified by INR into "therapeutic" and "subtherapeutic" groups. Stroke severity (NIH Stroke Scale), infarct volume, and outcome (modified Rankin Scale) were assessed on admission, discharge, and follow-up (3 months poststroke). Differences were calculated using Student's t-tests and regression analyses. RESULTS: The average INR on admission was 1.6 for the entire cohort. Seventy six percent were subtherapeutic on admission (INR < 2.0). Therapeutic patients had lower National Institutes of Health Stroke Scale scores on admission (5.9 versus 9.5, P = .033), significantly smaller stroke volumes (19.5 cc versus 49.2 cc, P = .036), and were more likely to show more than 1 digit improvement on follow-up mRS than subtherapeutic patients. CONCLUSIONS: Stroke size and severity is significantly reduced in patients with ischemic strokes who present therapeutic on warfarin. The greater volume of brain saved may ultimately lead to better functional recovery.

Shorter Intensive Care Unit Stays? The Majority of Post-Intravenous tPA (Tissue-Type Plasminogen Activator) Symptomatic Hemorrhages Occur Within 12 Hours of Treatment.

BACKGROUND AND PURPOSE: Symptomatic intracranial hemorrhage (sICH) is a life-threatening complication after treatment with intravenous tPA (tissue-type plasminogen activator) for acute stroke. Currently, patients are monitored for sICH in a neurocritical care unit or intensive care unit-like setting for 24 hours post-treatment-a costly and resource intensive practice. Because the half-life of tPA is much shorter than 24 hours, it is possible that the majority of patients do not require such intensive monitoring. In this study, we evaluate the time period of the highest risk for sICH post-tPA. METHODS: All patients receiving intravenous tPA for acute stroke between 2004 and 2017 at our institution were prospectively followed for sICH for 36 hours after treatment. The mean time from tPA administration to hemorrhage was calculated. Additional data were collected regarding: patient demographics, medical variables, and stroke characteristics. Variables significant in univariate analysis were entered into multivariable logistic regression models to determine factors associated with symptomatic hemorrhage. RESULTS: Three hundred eighty-five patients were administered intravenous tPA. Twenty-one (5.5%) developed sICH. The mean time from administration to hemorrhage was 8.5 hours. Greater than 80% of sICHs occurred before 12 hours post-treatment. The only variable significantly associated with sICH was combination therapy (intravenous tPA and intra-arterial thrombectomy). CONCLUSIONS: sICH associated with the administration of intravenous tPA typically occurs within the first 12 hours of treatment. Longer monitoring in an intensive care unit-like setting may be unnecessary for most individuals.

Cerebral microbleeds shouldn't dictate treatment of acute stroke: a retrospective cohort study evaluating risk of intracerebral hemorrhage.

BACKGROUND: Intravenous tissue plasminogen activator (IV tPA) after acute ischemic stroke carries the risk of symptomatic intracerebral hemorrhage (sICH). Cerebral microbleeds (CMBs) may indicate increased risk of hemorrhage and can be seen on magnetic resonance imaging (MRI). In this study, we examined the association between CMBs and sICH, focusing on the predictive value of their presence, burden, and location. METHODS: Records from all patients presenting to two academic stroke centers with acute ischemic stroke treated with IV tPA over a 5-year period were retrospectively reviewed. Demographic, medical, and imaging variables were evaluated. The presence, number, and location (lobar vs nonlobar) of CMBs were noted on gradient echo MRI sequences obtained during the admission. Univariable and multivariable statistical models were used to determine the relationship between CMBs and hemorrhagic (symptomatic and asymptomatic) transformation. RESULTS: Of 292 patients (mean age 62.8 years (SD 15.3), 49% African-American, 52% women), 21% (n = 62) had at least one CMB, 1% (n = 3) had > 10 CMBs, and 1% (n = 3) were diagnosed with probable cerebral amyloid angiopathy. After treatment, 16% (n = 46) developed hemorrhagic transformation, of which 6 (2%) were sICH. There was no association between CMB presence (p = .135) or location (p = .325) with sICH; however, those with a high CMB burden (> 10 CMB) were more likely to develop sICH (OR 37.8; 95% CI: 2.7-539.3; p = .007). CONCLUSIONS: Our findings support prior findings that a high CMB burden (> 10) in patients with acute stroke treated with IV tPA are associated with a higher risk of sICH. However, the overall rate of sICH in the presence of CMB is very low, indicating that the presence of CMBs by itself should not dictate the decision to treat with thrombolytics.

Collaterals Predict Outcome Regardless of Time Last Known Normal.

BACKGROUND AND PURPOSE: Recent studies suggest that patients with large-vessel ischemic strokes (large-vessel occlusion [LVO]) with favorable imaging may benefit from mechanical thrombolysis even when treated outside the standard 6-hour window. However, many patients in these studies presented with unknown times of onset. We compare outcomes in thrombectomy patients treated at less than versus greater than 6 hours from last known well (LKN), and evaluate whether "unknown time of onset" alters prognosis. METHODS: We retrospectively reviewed patients at 2 comprehensive stroke centers. Student's t and chi-square tests evaluated the association between predetermined clinical and radiographic variables, including unknown time of onset, and outcome (discharge and follow-up National Institutes of Health Stroke Scale score and modified Rankin Scale [mRS] score) for LVOs treated after greater than 6 hours versus 6 hours or less from LKN. Multivariable logistic regression was used to determine the odds of good outcome (mRS score 0-2). RESULTS: A total of 113 patients were treated over 2 years; 31 were treated at greater than 6 hours. Those who were treated at greater than 6 hours and experienced poor outcomes were more likely to have large-artery atherosclerosis (P = .033). There was no difference in outcome for patients outside the window with known (39.1%) versus unknown (60.9%) time of onset. mRS scores at discharge were higher among those outside the window (odds ratio 3.78; 95% confidence interval 1.20-11.89) but not at follow-up. After multivariable regression, favorable collaterals alone were associated with a mRS score of 0-2. CONCLUSIONS: When imaging is favorable, the mRS score at follow-up is comparable regardless of time LKN. Functional outcomes appear to be driven most significantly by the presence of collaterals.

ICAT: a simple score predicting critical care needs after thrombolysis in stroke patients.

BACKGROUND: Patients receiving intravenous thrombolysis (IVT) for acute ischemic stroke are at risk of developing complications, commonly necessitating admission to an intensive care unit (ICU). At present, most IVT is administered in the Emergency Department or in dedicated stroke units, but no evidence-based criteria exist that allow for early identification of patients at increased risk of developing ICU needs. The present study describes a novel prediction score aiming to identify a subpopulation of post-IVT patients at high risk for critical care interventions. METHODS: We retrospectively analyzed data from 301 patients undergoing IVT at our institutions during a 5-year period. Two hundred and ninety patients met inclusion criteria. The sample was randomly divided into a development and a validation cohort. Logistic regression was used to develop a risk score by weighting predictors of critical care needs based on strength of association. RESULTS: Seventy-two patients (24.8%) required critical care interventions. Black race (odds ratio [OR] 3.81, p=0.006), male sex (OR 3.79, p=0.008), systolic blood pressure (SBP; OR 1.45 per 10 mm Hg increase in SBP, p<0.001), and NIH stroke scale (NIHSS; OR 1.09 per 1 point increase in NIHSS, p=0.071) were independent predictors of critical care needs. The optimal model for score development, predicting critical care needs, achieved an AUC of 0.782 in the validation group. The score was named the ICAT (Intensive Care After Thrombolysis) score, assigning the following points: black race (1 point), male sex (1 point), SBP (2 points if 160-200 mm Hg; 4 points if >200 mm Hg), and NIHSS (1 point if 7-12; 2 points if >12). Each 1-point increase in the score was associated with 2.22-fold increased odds for critical care needs (95% CI 1.78-2.76, p<0.001). A score ≥ 2 was associated with over 13 times higher odds of critical care needs compared to a score <2 (OR 13.60, 95% CI 3.23-57.19), predicting critical care with 97.2% sensitivity and 28.0% specificity. CONCLUSION: The ICAT score, combining information about race, sex, SBP, and NIHSS, predicts critical care needs in post-IVT patients and may be helpful when triaging post-IVT patients to the appropriate monitoring environment.

Keep it simple: vascular risk factors and focal exam findings correctly identify posterior circulation ischemia in "dizzy" patients.

BACKGROUND: Dizziness is a common chief complaint of patients presenting to the Emergency Department (ED). Physicians must quickly and accurately identify patients whose etiology is most likely ischemia. Additional tools are available, but often require further training (vestibular testing) or are costly and not always readily available (magnetic resonance imaging (MRI)). This study evaluates the ability of a routine history and simple physical examination to correctly identify dizzy patients with posterior circulation ischemia, and the added utility of CT angiography (CTA). METHODS: We performed a retrospective analysis of all individuals presenting to the ED with a reported chief complaint of dizziness. Neurology was consulted and CTA ordered at the discretion of the ED provider. Demographic, medical, and radiographic variables were evaluated along with final diagnosis. Multivariable logistic regression and ROC analysis were used to determine factors associated with ischemia, the sensitivity of vascular risk factors and focal exam findings in predicting ischemia, and the additional benefit, if any, of CTA. RESULTS: One thousand two-hundred sixteen individuals meeting inclusion criteria presented to the ED over a 2 year period and were included in analysis. One hundred (8.2 %) were diagnosed with posterior circulation ischemia. For the entire cohort, age (OR 1.4 per 10 years, p < 0.0001), systolic blood pressure (OR 1.3 per 10 mmHg, p < 0.0001), and focal exam findings (OR 28.69, p < 0.0001) were most significantly associated with ischemia in multivariable modeling. When age, race, sex, presence of vascular risk factors, and focal neurologic findings were entered into ROC analysis, the AUC for correctly identifying posterior circulation ischemia was 0.90. In the subset of patients who underwent CTA (n = 87), the AUC did not improve (0.78 with and without CTA in ROC analysis, p = 0.52). CONCLUSIONS: A vascular risk assessment and neurological examination are adequate for risk stratification of ischemia in the dizzy patient and should remain the standard evaluation.

Novel score predicting gastrostomy tube placement in intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Dysphagia after intracerebral hemorrhage (ICH) contributes significantly to morbidity, often necessitating placement of a percutaneous endoscopic gastrostomy (PEG) tube. This study describes a novel risk prediction score for PEG placement after ICH. METHODS: We retrospectively analyzed data from 234 patients with ICH presenting during a 4-year period. One hundred eighty-nine patients met inclusion criteria. The sample was randomly divided into a development and a validation cohort. Logistic regression was used to develop a risk score by weighting predictors of PEG placement based on strength of association. RESULTS: Age (odds ratio [OR], 1.64 per 10-year increase in age; 95% confidence interval [CI], 1.02-2.65), black race (OR, 3.26; 95% CI, 0.96-11.05), Glasgow Coma Scale (OR, 0.80; 95% CI, 0.62-1.03), and ICH volume (OR, 1.38 per 10-mL increase in ICH volume) were independent predictors of PEG placement. The final model for score development achieved an area under the curve of 0.7911 (95% CI, 0.6931-0.8892) in the validation group. The score was named the GRAVo score: Glasgow Coma Scale ≤12 (2 points), Race (1 point for black), Age >50 years (2 points), and ICH Volume >30 mL (1 point). A score >4 was associated with ≈12× higher odds of PEG placement when compared with a score ≤4 (OR, 11.81; 95% CI, 5.04-27.66), predicting PEG placement with 46.55% sensitivity and 93.13% specificity. CONCLUSIONS: The GRAVo score, combining information about Glasgow Coma Scale, race, age, and ICH volume, may be a useful predictor of PEG placement in ICH patients.

Infarct volume predicts critical care needs in stroke patients treated with intravenous thrombolysis.

INTRODUCTION: Patients receiving intravenous thrombolysis with recombinant tissue plasminogen activator (IVT) for ischemic stroke are monitored in an intensive care unit (ICU) or a comparable unit capable of ICU interventions due to the high frequency of standardized neurological exams and vital sign checks. The present study evaluates quantitative infarct volume on early post-IVT MRI as a predictor of critical care needs and aims to identify patients who may not require resource intense monitoring. METHODS: We identified 46 patients who underwent MRI within 6 h of IVT. Infarct volume was measured using semiautomated software. Logistic regression and receiver operating characteristics (ROC) analysis were used to determine factors associated with ICU needs. RESULTS: Infarct volume was an independent predictor of ICU need after adjusting for age, sex, race, systolic blood pressure, NIH Stroke Scale (NIHSS), and coronary artery disease (odds ratio 1.031 per cm(3) increase in volume, 95% confidence interval [CI] 1.004-1.058, p = 0.024). The ROC curve with infarct volume alone achieved an area under the curve (AUC) of 0.766 (95% CI 0.605-0.927), while the AUC was 0.906 (95% CI 0.814-0.998) after adjusting for race, systolic blood pressure, and NIHSS. Maximum Youden index calculations identified an optimal infarct volume cut point of 6.8 cm(3) (sensitivity 75.0%, specificity 76.7%). Infarct volume greater than 3 cm(3) predicted need for critical care interventions with 81.3% sensitivity and 66.7% specificity. CONCLUSION: Infarct volume may predict needs for ICU monitoring and interventions in stroke patients treated with IVT.

Predicting symptomatic intracerebral hemorrhage versus lacunar disease in patients with longstanding hypertension.

BACKGROUND AND PURPOSE: Hypertension results in a spectrum of subcortical cerebrovascular disease. It is unclear why some individuals develop ischemia and others develop hemorrhage. Risk factors may differ for each population. We identify factors that predispose an individual to subcortical symptomatic intracerebral hemorrhage (sICH) compared with ischemia. METHODS: Demographic and laboratory data were prospectively collected for hypertensive patients presenting with ischemic stroke or sICH during an 8.5-year period. Neuroimaging was retrospectively reviewed for acute (subcortical lacunes [<2.0 cm] versus subcortical sICH) and chronic (periventricular white matter disease and cerebral microbleeds) findings. We evaluated the impact of age, race, sex, serum creatinine, erythrocyte sedimentation rate, low-density lipoprotein, presence of periventricular white matter disease or cerebral microbleeds, and other factors on the risk of sICH versus acute lacune using multivariate logistic regression. RESULTS: Five hundred seventy-one patients had subcortical pathology. The presence of cerebral microbleeds (adjusted odds ratio [OR], 3.39; confidence interval [CI], 2.09-5.50) was a strong predictor of sICH, whereas severe periventricular white matter disease predicted ischemia (OR, 0.56 risk of sICH; CI, 0.32-0.98). This association was strengthened when the number of microbleeds was evaluated; subjects with >5 microbleeds had an increased risk of sICH (OR, 4.11; CI, 1.96-8.59). It remained significant when individuals with only cortical microbleeds were removed (OR, 1.77, CI, 1.13-2.76). An elevated erythrocyte sedimentation rate (OR, 1.19 per 10 mm/h increase; CI, 1.06-1.34) was significantly associated with sICH, whereas low-density lipoprotein was associated with ischemic infarct (OR, 0.93 risk of sICH per 10 mg/dL increase; CI, 0.86-0.99). CONCLUSIONS: Subclinical pathology is the strongest predictor of the nature of subsequent symptomatic event. Low-density lipoprotein and erythrocyte sedimentation rate may also have a role in risk stratification.

Hyperbolic graph embedding of MEG brain networks to study brain alterations in individuals with subjective cognitive decline.

An expansive area of research focuses on discerning patterns of alterations in functional brain networks from the early stages of Alzheimer's disease, even at the subjective cognitive decline (SCD) stage. Here, we developed a novel hyperbolic MEG brain network embedding framework for transforming high-dimensional complex MEG brain networks into lower-dimensional hyperbolic representations. Using this model, we computed hyperbolic embeddings of the MEG brain networks of two distinct participant groups: individuals with SCD and healthy controls. We demonstrated that these embeddings preserve both local and global geometric information, presenting reduced distortion compared to rival models, even when brain networks are mapped into low-dimensional spaces. In addition, our findings showed that the hyperbolic embeddings encompass unique SCD-related information that improves the discriminatory power above and beyond that of connectivity features alone. Notably, we introduced a unique metric-the radius of the node embeddings-which effectively proxies the hierarchical organization of the brain. Using this metric, we identified subtle hierarchy organizational differences between the two participant groups, suggesting increased hierarchy in the dorsal attention, frontoparietal, and ventral attention subnetworks among the SCD group. Last, we assessed the correlation between these hierarchical variations and cognitive assessment scores, revealing associations with diminished performance across multiple cognitive evaluations in the SCD group. Overall, this study presents the first evaluation of hyperbolic embeddings of MEG brain networks, offering novel insights into brain organization, cognitive decline, and potential diagnostic avenues of Alzheimer's disease.

Follow-up infarct volume on fluid attenuated inversion recovery (FLAIR) imaging in distal medium vessel occlusions: the role of cerebral blood volume index.

BACKGROUND: Distal medium vessel occlusions (DMVOs) contribute substantially to the incidence of acute ischemic strokes (AIS) and pose distinct challenges in clinical management and prognosis. Neuroimaging techniques, such as Fluid Attenuation Inversion Recovery (FLAIR) imaging and cerebral blood volume (CBV) index derived from perfusion imaging, have significantly improved our ability to assess the impact of strokes and predict their outcomes. The primary objective of this study was to investigate relationship between follow-up infarct volume (FIV) as assessed by FLAIR imaging in patients with DMVOs. METHODS: This prospectively collected, retrospective reviewed cohort study included patients from two comprehensive stroke centers within the Johns Hopkins Medical Enterprise, spanning August 2018-October 2022. The cohort consisted of adults with AIS attributable to DMVO. Detailed imaging analyses were conducted, encompassing non-contrast CT, CT angiography (CTA), CT perfusion (CTP), and FLAIR imaging. Univariable and multivariable linear regression models were employed to assess the association between different factors and FIV. RESULTS: The study included 79 patients with DMVO stroke with a median age of 69 years (IQR, 62-77 years), and 57% (n = 45) were female. There was a negative correlation between the CBV index and FIV in a univariable linear regression analysis (Beta = - 16; 95% CI, - 23 to - 8.3; p < 0.001) and a multivariable linear regression model (Beta = - 9.1 per 0.1 change; 95% CI, - 15 to - 2.7; p = 0.006). Diabetes was independently associated with larger FIV (Beta = 46; 95% CI, 16 to 75; p = 0.003). Additionally, a higher baseline ASPECTS was associated with lower FIV (Beta = - 30; 95% CI, - 41 to - 20; p < 0.001). CONCLUSION: Our findings underscore the CBV index as an independent association with FIV in DMVOs, which highlights the critical role of collateral circulation in determining stroke outcomes in this patient population. In addition, our study confirms a negative association of ASPECTS with FLAIR FIV and identifies diabetes as independent factor associated with larger FIV. These insights pave the way for further large-scale, prospective studies to corroborate these findings, thereby refining the strategies for stroke prognostication and management.

Redefining CT perfusion-based ischemic core estimates for the ghost core in early time window stroke.

BACKGROUND AND PURPOSE: In large vessel occlusion (LVO) stroke patients, relative cerebral blood flow (rCBF)<30% volume thresholds are commonly used in treatment decisions. In the early time window, nearly infarcted but salvageable tissue volumes may lead to pretreatment overestimates of infarct volume, and thus potentially exclude patients who may otherwise benefit from intervention. Our multisite analysis aims to explore the strength of relationships between widely used pretreatment CT parameters and clinical outcomes for early window stroke patients. METHODS: Patients from two sites in a prospective registry were analyzed. Patients with LVOs, presenting within 3 hours of last known well, and who were successfully reperfused were included. Primary short-term neurological outcome was percent National Institutes of Health Stroke Scale (NIHSS) change from admission to discharge. Secondary long-term outcome was 90-day modified Rankin score. Spearman's correlations were performed. Significance was attributed to p-value ≤.05. RESULTS: Among 73 patients, median age was 66 (interquartile range 54-76) years. Among all pretreatment imaging parameters, rCBF<30%, rCBF<34%, and rCBF<38% volumes were significantly, inversely correlated with percentage NIHSS change (p<.048). No other parameters significantly correlated with outcomes. CONCLUSIONS: Our multisite analysis shows that favorable short-term neurological recovery was significantly correlated with rCBF volumes in the early time window. However, modest strength of correlations provides supportive evidence that the applicability of general ischemic core estimate thresholds in this subpopulation is limited. Our results support future larger-scale efforts to liberalize or reevaluate current rCBF parameter thresholds guiding treatment decisions for early time window stroke patients.

Prolonged venous transit on perfusion imaging is associated with higher odds of mortality in successfully reperfused patients with large vessel occlusion stroke.

BACKGROUND: Poor venous outflow (VO) profiles are associated with unfavorable outcomes in patients with acute ischemic stroke caused by large vessel occlusion (AIS-LVO), despite achieving successful reperfusion. The objective of this study is to assess the association between mortality and prolonged venous transit (PVT), a novel visual qualitative VO marker on CT perfusion (CTP) time to maximum (Tmax) maps. METHODS: We performed a retrospective analysis of prospectively collected data from consecutive adult patients with AIS-LVO with successful reperfusion (modified Thrombolysis in Cerebral Infarction 2b/2c/3). PVT+ was defined as Tmax ≥10 s timing on CTP Tmax maps in at least one of the following: superior sagittal sinus (proximal venous drainage) and/or torcula (deep venous drainage). PVT- was defined as lacking this in both regions. The primary outcome was mortality at 90 days. In a 1:1 propensity score-matched cohort, regressions were performed to determine the effect of PVT on 90-day mortality. RESULTS: In 127 patients of median (IQR) age 71 (64-81) years, mortality occurred in a significantly greater proportion of PVT+ patients than PVT- patients (32.5% vs 12.6%, P=0.01). This significant difference persisted after matching (P=0.03). PVT+ was associated with a significantly increased likelihood of 90-day mortality (OR 1.22 (95% CI 1.02 to 1.46), P=0.03) in the matched cohort. CONCLUSIONS: PVT+ was significantly associated with 90-day mortality despite successful reperfusion therapy in patients with AIS-LVO. PVT is a simple VO profile marker with potential as an adjunctive metric during acute evaluation of AIS-LVO patients. Future studies will expand our understanding of using PVT in the evaluation of patients with AIS-LVO.

Lower admission stroke severity is associated with good collateral status in distal medium vessel occlusion stroke.

BACKGROUND AND PURPOSE: Distal medium vessel occlusions (DMVOs) are a significant contributor to acute ischemic stroke (AIS), with collateral status (CS) playing a pivotal role in modulating ischemic damage progression. We aimed to explore baseline characteristics associated with CS in AIS-DMVO. METHODS: This retrospective analysis of a prospectively collected database enrolled 130 AIS-DMVO patients from two comprehensive stroke centers. Baseline characteristics, including patient demographics, admission National Institutes of Health Stroke Scale (NIHSS) score, admission Los Angeles Motor Scale (LAMS) score, and co-morbidities, including hypertension, hyperlipidemia, diabetes, coronary artery disease, atrial fibrillation, and history of transient ischemic attack or stroke, were collected. The analysis was dichotomized to good CS, reflected by hypoperfusion index ratio (HIR) <.3, versus poor CS, reflected by HIR ≥.3. RESULTS: Good CS was observed in 34% of the patients. As to the occluded location, 43.8% occurred in proximal M2, 16.9% in mid M2, 35.4% in more distal middle cerebral artery, and 3.8% in distal anterior cerebral artery. In multivariate logistic analysis, a lower NIHSS score and a lower LAMS score were both independently associated with a good CS (odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.82-0.95, p < .001 and OR: 0.77, 95% CI: 0.62-0.96, p = .018, respectively). Patients with poor CS were more likely to manifest as moderate to severe stroke (29.1% vs. 4.5%, p < .001), while patients with good CS had a significantly higher chance of having a minor stroke clinically (40.9% vs. 12.8%, p < .001). CONCLUSIONS: CS remains an important determinant in the severity of AIS-DMVO. Collateral enhancement strategies may be a worthwhile pursuit in AIS-DMVO patients with more severe initial stroke presentation, which can be swiftly identified by the concise LAMS and serves as a proxy for underlying poor CS.