Frailty and outcomes in lacunar stroke.

BACKGROUND: Lacunar strokes (LS) are ischemic strokes of the small perforating arteries of deep gray and white matter of the brain. Frailty has been associated with greater mortality and attenuated response to treatment after stroke. However, the effect of frailty on patients with LS has not been previously described. OBJECTIVE: To analyze the association between frailty and outcomes in LS. METHODS: Patients with LS were selected from the National Inpatient Sample (NIS) 2016-2019 using the International Classification of Disease, 10th edition (ICD-10) diagnosis codes. The 11-point modified frailty scale (mFI-11) was used to group patients into severely frail and non-severely frail cohorts. Demographics, clinical characteristics, and complications were defined. Health care resource utilization (HRU) was evaluated by comparing total hospital charges and length of stay (LOS). Other outcomes studied were discharge disposition and inpatient death. RESULTS: Of 48,980 patients with LS, 10,830 (22.1%) were severely frail. Severely frail patients were more likely to be older, have comorbidities, and pertain to lower socioeconomic status categories. Severely frail patients with LS had worse clinical stroke severity and increased rates of complications such as urinary tract infection (UTI) and pneumonia (PNA). Additionally, severe frailty was associated with unfavorable outcomes and increased HRU. CONCLUSION: Severe frailty in LS patients is associated with higher rates of complications and increased HRU. Risk stratification based on frailty may allow for individualized treatments to help mitigate adverse outcomes in the setting of LS.

Association of Elevated Body Mass Index with Functional Outcome and Mortality following Acute Ischemic Stroke: The Obesity Paradox Revisited.

BACKGROUND: Previous literature has identified a survival advantage in acute ischemic stroke (AIS) patients with elevated body mass indices (BMIs), a phenomenon termed the "obesity paradox." OBJECTIVE: The aim of this study was to evaluate the independent association between obesity and clinical outcomes following AIS. METHODS: Weighted discharge data from the National Inpatient Sample were queried to identify AIS patients from 2015 to 2018. Multivariable logistic regression and Cox proportional hazards modeling were performed to evaluate associations between obesity (BMI ≥ 30) and clinical endpoints following adjustment for acute stroke severity and comorbidity burden. RESULTS: Among 1,687,805 AIS patients, 216,775 (12.8%) were obese. Compared to nonobese individuals, these patients were younger (64 vs. 72 mean years), had lower baseline NIHSS scores (6.9 vs. 7.9 mean score), and a higher comorbidity burden. Multivariable analysis demonstrated independent associations between obesity and lower likelihood of mortality (adjusted odds ratio [aOR] 0.76, 95% confidence interval [CI]: 0.71, 0.82, p < 0.001; hazard ratio 0.84, 95% CI: 0.73, 0.97, p = 0.015), intracranial hemorrhage (aOR 0.87, 95% CI: 0.82, 0.93, p < 0.001), and routine discharge to home (aOR 0.97, 95% CI: 0.95, 0.99; p = 0.015). Mortality rates between obese and nonobese patients were significantly lower across stroke severity thresholds, but this difference was attenuated among high severity (NIHSS > 20) strokes (21.6% vs. 23.2%, p = 0.358). Further stratification of the cohort into BMI categories demonstrated a "U-shaped" association with mortality (underweight aOR 1.58, 95% CI: 1.39, 1.79; p < 0.001, overweight aOR 0.64, 95% CI: 0.42, 0.99; p = 0.046, obese aOR 0.77, 95% CI: 0.71, 0.83; p < 0.001, severely obese aOR 1.18, 95% CI: 0.74, 1.87; p = 0.485). Sub-cohort assessment of thrombectomy-treated patients demonstrated an independent association of obesity (BMI 30-40) with lower mortality (aOR 0.79, 95% CI: 0.65, 0.96; p = 0.015), but not with routine discharge. CONCLUSION: This cross-sectional analysis demonstrates a lower likelihood of discharge to home as well as in-hospital mortality in obese patients following AIS, suggestive of a protective effect of obesity against mortality but not against all poststroke neurological deficits in the short term which would necessitate placement in acute rehabilitation and long-term care facilities.

Transcarotid Access for Mechanical Thrombectomy in Acute Ischemic Stroke: A Meta-Analysis and Systematic Review.

OBJECTIVES: Despite the success of mechanical thrombectomy in large vessel acute ischemic stroke, recanalization may fail due to difficult anatomic access or peripheral arterial occlusive disease. In these cases, transcarotid access may be used as an alternative, but it has not gained prominence due to safety concerns. Our objective was to assess the efficacy and safety of transcarotid access for mechanical thrombectomy. MATERIALS AND METHODS: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used to perform a systematic review with articles published from 2010 to 2020 summarizing pre-intervention characteristics, techniques utilized, and outcomes of patients undergoing mechanical thrombectomy via trans-carotid puncture. We performed a meta-analysis of clinical outcomes, reperfusion times and overall complications rates of trans-carotid approach. RESULTS: Six studies describing 80 total attempts at carotid access, 72 of which were successful (90% success rate), were included. Direct carotid puncture was most often used as a rescue technique (87% of patients) secondary to failed femoral access. Successful recanalization was achieved in 76% of patients. 90 day modified Rankin Scale ≤ 2 was achieved in 28% of patients. Carotid puncture-reperfusion time was 32 min (CI = 24-40, p < 0.001). Cervical complications occurred at a rate of 26.5% (95% CI = 17%-38%). Only 1.3% (1/80 patients) had a fatal outcome and 96% of complications required no intervention. CONCLUSIONS: Our results on the safety and efficacy of transcarotid access suggests that this approach is a viable alternative to failed thrombectomy when transfemoral or trans-radial access may be impractical.

Endovascular Thrombectomy for Treatment of Acute Ischemic Stroke During Pregnancy and the Early Postpartum Period.

BACKGROUND AND PURPOSE: Acute ischemic stroke (AIS) is a rare occurrence during pregnancy and the postpartum period. Existing literature evaluating endovascular mechanical thrombectomy (MT) for this patient population is limited. METHODS: The National Inpatient Sample was queried from 2012 to 2018 to identify and characterize pregnant and postpartum patients (up to 6 weeks following childbirth) with AIS treated with MT. Complications and outcomes were compared with nonpregnant female patients treated with MT and to other pregnant and postpartum patients managed medically. Complex samples regression models and propensity score matching were implemented to assess adjusted associations and to address confounding by indication, respectively. RESULTS: Among 4590 pregnant and postpartum patients with AIS, 180 (3.9%) were treated with MT, and rates of utilization increased following the MT clinical trial era (2015-2018; 1.9% versus 5.3%, P=0.011). Compared with nonpregnant patients with AIS treated with MT, they experienced lower rates of intracranial hemorrhage (11% versus 24%, P=0.069) and poor functional outcome (50% versus 72%, P=0.003) at discharge. Pregnant/postpartum status was independently associated with a lower likelihood of development of intracranial hemorrhage (adjusted odds ratio, 0.26 [95% CI, 0.09-0.70]; P=0.008) following multivariable analysis adjusting for age, illness severity, and stroke severity. Following propensity score matching, pregnant and postpartum patients treated with MT and those medically managed differed in frequency of venous thromboembolism (17% versus 0%, P=0.001) and complications related to pregnancy (44% versus 64%, P=0.034), but not in functional outcome at discharge or hospital length of stay. Pregnant and postpartum women treated with MT did not experience mortality or miscarriage during hospitalization. CONCLUSIONS: This large-scale analysis utilizing national claims data suggests that MT is a safe and efficacious therapy for AIS during pregnancy and the postpartum period. In the absence of prospective clinical trials, population-based cross-sectional analyses such as the present study provide valuable clinical insight.

Index Admission Characteristics and All-Cause Readmissions Analysis in Younger and Older Adults with Intracerebral Hemorrhage.

INTRODUCTION: Intracerebral hemorrhage (ICH) comprises 15-20% of all strokes with debilitating consequences. Data regarding characteristics and outcomes of primary ICH in the young are lacking, given its rarity, making comparisons between younger and older cohorts difficult to perform. Nationally representative administrative databases enable analysis of such rare events. OBJECTIVE: To determine the baseline characteristics, all-cause readmission rates, and reasons for primary ICH in younger and older adults using a nationally representative database. METHODS: A retrospective cohort analysis was performed using the Nationwide Readmissions Database 2013. Validated ICD-9-CM codes identified index ICH admissions, comorbidities, demographics, behavioral risk factors, procedures, and Elixhauser and Charlson Comorbidity indices. We compared "younger" (age ≤ 45 years) and "older" (age > 45) index ICH admissions by weighted 30-day all-cause readmission rates, primary diagnosis code for 30-day readmissions, most common comorbidities during the index hospitalization, and Kaplan-Meier cumulative risk of readmission up to 1 year. RESULTS: Older admissions had higher comorbidity scores and mortality, but both groups had similar total comorbidities. Younger admissions exhibited longer length of stay with more procedures performed. Vascular anomalies (aneurysm 7.2 vs. 4.6% and arteriovenous malformation 5.9 vs. 0.8%) and behavioral risk factors (smoking 26.5 vs. 23.0%, alcohol abuse 6.7 vs. 4.6%, and substance use 13.5 vs. 2.9%) were more prevalent in younger admissions, while older patients had more cardiovascular comorbidities. All-cause 30-day readmission rates (13.1 vs. 13.0%) and 1-year cumulative risk of readmission (log-rank p value 0.7209) were similar. Readmissions in the younger cohort were primarily for neurological conditions, and those in the older cohort were for systemic conditions. CONCLUSIONS: Adults <45 years with ICH had similar total comorbidities as older adults but more procedures, longer hospital stay, and more behavioral risk factors. Readmission rates were similar though reasons differed; younger patients were more for neurological reasons than for other systemic causes.

Significant Mortality Associated With COVID-19 and Comorbid Cerebrovascular Disease: A Quantitative Systematic Review.

We report the first quantitative systematic review of cerebrovascular disease in coronavirus disease 2019 (COVID-19) to provide occurrence rates and associated mortality. Through a comprehensive search of PubMed we identified 8 cohort studies, 5 case series, and 2 case reports of acute cerebrovascular disease in patients with confirmed COVID-19 diagnosis. Our first meta-analysis utilizing the identified publications focused on comorbid cerebrovascular disease in recovered and deceased patients with COVID-19. We performed 3 additional meta-analyses of proportions to produce point estimates of the mortality and incidence of acute cerebrovascular disease in COVID-19 patients. Patient's with COVID-19 who died were 12.6 times more likely to have a history of cerebrovascular disease. We estimated an occurrence rate of 2.6% (95% confidence interval, 1.2-5.4%) for acute cerebrovascular disease among consecutively admitted patients with COVID-19. While for those with severe COVID-19' we estimated an occurrence rate of 6.5% (95% confidence interval, 4.4-9.6%). Our analysis estimated a rate of 35.5% for in-hospital mortality among COVID-19 patients with concomitant acute cerebrovascular disease. This was consistent with a mortality rate of 34.0% which we obtained through an individual patient analysis of 47 patients derived from all available case reports and case series. COVID-19 patients with either acute or chronic cerebrovascular disease have a high mortality rate with higher occurrence of cerebrovascular disease in patients with severe COVID-19.

Safety and efficacy of a novel robotic transcranial doppler system in subarachnoid hemorrhage.

Delayed cerebral ischemia (DCI) secondary to vasospasm is a determinate of outcomes following non-traumatic subarachnoid hemorrhage (SAH). SAH patients are monitored using transcranial doppler (TCD) to measure cerebral blood flow velocities (CBFv). However, the accuracy and precision of manually acquired TCD can be operator dependent. The NovaGuide robotic TCD system attempts to standardize acquisition. This investigation evaluated the safety and efficacy of the NovaGuide system in SAH patients in a Neuro ICU. We retrospectively identified 48 NovaGuide scans conducted on SAH patients. Mean and maximum middle cerebral artery (MCA) CBFv were obtained from the NovaGuide and the level of agreement between CBFv and computed tomography angiography (CTA) for vasospasm was determined. Safety of NovaGuide acquisition of CBFv was evaluated based on number of complications with central venous lines (CVL) and external ventricular drains (EVD). There was significant agreement between the NovaGuide and CTA (Cohen's Kappa = 0.74) when maximum MCA CBFv ≥ 120 cm/s was the threshold for vasospasm. 27/48 scans were carried out with CVLs and EVDs present without negative outcomes. The lack of adverse events associated with EVDs/CVLs and the strong congruence between maximal MCA CBFv and CTA illustrates the diagnostic utility of the NovaGuide.

Bihemispheric ischemic strokes in patients with COVID-19.

BACKGROUND: There is emerging evidence that COVID-19 can trigger thrombosis because of a hypercoagulable state, including large-vessel occlusion ischemic strokes. Bihemispheric ischemic stroke is uncommon and is thought to indicate an embolic source. Here, we examine the findings and outcomes of patients with bihemispheric stroke in the setting of COVID-19. METHODS: We performed a retrospective cohort study at a quaternary academic medical center between March 1, 2020, and April 30, 2020. We identified all patients with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection who presented with simultaneous bihemispheric ischemic strokes. RESULTS: Of 637 COVID-19 admissions during the 2-month period, 13 had a diagnosis of acute ischemic stroke, including 5 who developed bihemispheric cerebral infarction. Three of those 5 (60%) were female, median age was 54 (range 41-67), and all five were being managed for severe COVID-19-related pneumonia complicated by acute kidney injury and liver failure before the diagnosis of cerebral infarction was established. Five presented with elevated ferritin, lactate dehydrogenase, and interleukin-6 (IL-6) levels, and four had lymphopenia and elevated D-dimer levels. All patients underwent neuroimaging with computed tomography for persistent depressed mentation, with or without a focal neurologic deficit, demonstrating multifocal ischemic strokes with bihemispheric involvement. Outcome was poor in all patients: two were discharged to a rehabilitation facility with moderate-to-severe disability and three (60%) patients died. CONCLUSIONS: Stroke is implicated in SARS-CoV-2 infection. Although causality cannot be established, we present the imaging and clinical findings of patients with COVID-19 and simultaneous bihemispheric ischemic strokes. Multifocal ischemic strokes with bihemispheric involvement should be considered in COVID-19 patients with severe infection and poor neurologic status and may be associated with poor outcomes.

Endovascular thrombectomy with and without preceding intravenous thrombolysis for treatment of large vessel anterior circulation stroke: A cross-sectional analysis of 50,000 patients.

INTRODUCTION: The safety and efficacy of intravenous thrombolysis (IVT) before endovascular thrombectomy (EVT) for large vessel occlusion stroke remains a highly contested and unanswered clinical question. We aim to characterize the clinical profile, complications, and discharge disposition of EVT patients treated with and without preceding IVT using a large, nationally-representative sample. METHODS: The National Inpatient Sample was queried from 2015 to 2018 to identify adult patients with anterior circulation stroke treated with EVT with and without preceding IVT. Multivariable logistic regression analysis and propensity-score matching were employed to assess adjusted associations with clinical endpoints and to address confounding by indication for IVT, respectively. RESULTS: Among 48,525 patients identified, 40.7% (n = 19,735) received IVT prior to EVT. On unadjusted analysis, patients treated with IVT bridging therapy experienced higher rates of intracranial hemorrhage (26% vs. 24%, p = 0.003) and routine discharge to home with or without services (33% vs. 27%, p < 0.001), a lower frequency of thromboembolic complications (3% vs. 5%, p < 0.001), and lower rates of extended hospital stays (eLOS) (20% vs. 24%, p < 0.001). Multivariable logistic regression analysis adjusting for demographic and baseline clinical characteristics demonstrated independent associations of IVT bridging therapy with intracranial hemorrhage (aOR 1.28, 95% CI 1.15, 1.43; p < 0.001), thromboembolic complications (aOR 0.66, 95% CI 0.53, 0.83; p < 0.001), routine discharge (aOR 1.27, 95% CI 1.15, 1.40; p < 0.001), and eLOS (aOR 0.76, 95% CI 0.68, 0.85; p < 0.001). Sensitivity testing confirmed these findings. CONCLUSION: Preceding IVT was associated with favorable functional outcomes following endovascular therapy. Prospective randomized clinical trials are warranted for further evaluation.

Assessment of the Patient With Intracerebral Hemorrhage: A Review of the Literature.

Spontaneous nontraumatic intracerebral hemorrhage is associated with high morbidity and mortality. Given the risk of rapid neurological deterioration, early identification with rapid neuroimaging is vital. Predictors of outcome, such as spot sign and intracerebral hemorrhage score, can help guide management goals. Management should be aimed at prevention of hematoma expansion, treatment of increased intracranial pressure, and prevention of secondary brain injury and medical complications.

Time to Wake-Up: Extending the Window for Management of Unknown-Onset Strokes.

The term "Wake-Up Stroke" is applied to a patient who displays no symptoms before sleep, but wakes with neurologic deficits suggestive of stroke. The current guidelines for acute ischemic stroke limit intravenous tissue plasminogen activator use to stroke patients in whom symptom onset or last known well is less than 4.5 hours. Approximately one-third of acute ischemic stroke patients present with unknown time of symptom onset and are often not eligible for intravenous reperfusion therapy in clinical practice. This review provides an overview of several earlier trials that used advanced neuroimaging to determine eligibility for reperfusion therapy in patients with unknown stroke onset. The reassuring results of these earlier trials that led to recent thrombolysis trials specifically targeted at "wake-up stroke" patients are discussed in this review. Ongoing studies aim to expand our knowledge regarding the safety and efficacy of thrombolysis in these patients.

Management of Small Unruptured Intracranial Aneurysms: To Treat or Not to Treat?

Unruptured intracranial aneurysms measuring <7 mm in diameter have become increasingly prevalent due to advances in diagnostic imaging. The most feared complication is aneurysm rupture leading to a subarachnoid hemorrhage. Based on the current literature, the 3 main treatments for an unruptured intracranial aneurysm are conservative management with follow-up imaging, endovascular coiling, or surgical clipping. However, there remains no consensus on the best treatment approach. The natural history of the aneurysm and risk factors for aneurysm rupture must be considered to individualize treatment. Models including population, hypertension, age, size of aneurysm, earlier subarachnoid hemorrhage from a prior aneurysm, site of aneurysm score, Unruptured Intracranial Aneurysm Treatment Score, and advanced neuroimaging can assist physicians in assessing the risk of aneurysm rupture. Macrophages and other inflammatory modulators have been elucidated as playing a role in intracranial aneurysm progression and eventual rupture. Further studies need to be conducted to explore the effects of therapeutic drugs targeting inflammatory modulators.