Faculty Bibliography

BACKGROUND AND PURPOSE/OBJECTIVE:With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke. However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19. METHODS:We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic. We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls). In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls). RESULTS:<0.001). When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels. When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate. Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls. CONCLUSIONS:We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19. Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased. Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.

OBJECTIVE:To update the 2016 American Academy of Neurology (AAN) practice advisory for patients with stroke and patent foramen ovale (PFO). METHODS:The guideline panel followed the AAN 2017 guideline development process to systematically review studies published through December 2017 and formulate recommendations. MAJOR RECOMMENDATIONS/UNASSIGNED:In patients being considered for PFO closure, clinicians should ensure that an appropriately thorough evaluation has been performed to rule out alternative mechanisms of stroke (level B). In patients with a higher risk alternative mechanism of stroke identified, clinicians should not routinely recommend PFO closure (level B). Clinicians should counsel patients that having a PFO is common; that it occurs in about 1 in 4 adults in the general population; that it is difficult to determine with certainty whether their PFO caused their stroke; and that PFO closure probably reduces recurrent stroke risk in select patients (level B). In patients younger than 60 years with a PFO and embolic-appearing infarct and no other mechanism of stroke identified, clinicians may recommend closure following a discussion of potential benefits (absolute recurrent stroke risk reduction of 3.4% at 5 years) and risks (periprocedural complication rate of 3.9% and increased absolute rate of non-periprocedural atrial fibrillation of 0.33% per year) (level C). In patients who opt to receive medical therapy alone without PFO closure, clinicians may recommend an antiplatelet medication such as aspirin or anticoagulation (level C).

BACKGROUND:Little data exists on outcomes of mechanical thrombectomy (MT) in nonagenarians. We aimed to compare the procedural and discharge outcomes of MT for acute ischemic stroke (AIS) in nonagenarians versus younger patients. METHODS:Procedural outcomes and discharge disposition were compared in propensity score-matched groups of nonagenarians versus patients aged≤69 with AIS who underwent MT. Patients aged 70-89 were excluded in order to compare nonagenarians to a younger cohort that most closely approximates the age of patients in the seminal MT trials. Good discharge disposition was defined as a discharge to home or acute rehabilitation. RESULTS:Of 3010 AIS patients, 46/297(16%) nonagenarians underwent MT compared to 159/1337(12%) aged≤69 (P = 0.091). Of 78 propensity score-matched patients (N = 39 ≥90, N = 39 ≤69), the median admission NIHSS was 22 versus 20, median ASPECTS was 9 versus 9, pre-stroke mRS<4 was 82% versus 87%, 18% versus 8% received IV tPA, and mTICI≥2b was 90% versus 90%, respectively (all P>0.05). Revascularization time (569 versus 372 min), door to groin puncture time (82 versus 71 min) and groin puncture to revascularization times (39 versus 24 min) were similar in between nonagenarians and ≤69, respectively (both P>0.05). Symptomatic ICH (2.6% versus 10.3%; p = 0.165) and in-hospital death rates (10% vs 26%; p = 0.077) trended lower among nonagenarians versus aged≤69. Good discharge disposition occurred in 44% of nonagenarians versus 51% aged≤69 years (p = 0.496). CONCLUSIONS:In propensity score analysis, 90% of nonagenarians achieved successful recanalization and almost half (44%) were discharged to home/acute rehabilitation, which was similar to a younger (aged≤69 years) cohort.

BACKGROUND AND PURPOSE/OBJECTIVE:Understanding factors associated with ischemic stroke despite therapeutic anticoagulation is an important goal to improve stroke prevention strategies in patients with atrial fibrillation (AF). We aim to determine factors associated with therapeutic or supratherapeutic anticoagulation status at the time of ischemic stroke in patients with AF. METHODS:The Initiation of Anticoagulation after Cardioembolic stroke (IAC) study is a multicenter study pooling data from stroke registries of eight comprehensive stroke centers across the United States. Consecutive patients hospitalized with acute ischemic stroke in the setting of AF were included in the IAC cohort. For this study, we only included patients who reported taking warfarin at the time of the ischemic stroke. Patients not on anticoagulation and patients who reported use of a direct oral anticoagulant were excluded. Analyses were stratified based on therapeutic (INR ≥2) versus subtherapeutic (INR <2) anticoagulation status. We used binary logistic regression models to determine factors independently associated with anticoagulation status after adjustment for pertinent confounders. In particular, we sought to determine whether atherosclerosis with 50% or more luminal narrowing in an artery supplying the infarct (a marker for a competing atherosclerotic mechanism) and small stroke size (≤ 10 mL; implying a competing small vessel disease mechanism) related to anticoagulant status. RESULTS:Of the 2084 patients enrolled in the IAC study, 382 patients met the inclusion criteria. The mean age was 77.4 ± 10.9 years and 52.4% (200/382) were women. A total of 222 (58.1%) subjects presented with subtherapeutic INR. In adjusted models, small stroke size (OR 1.74 95% CI 1.10-2.76, p = 0.019) and atherosclerosis with 50% or more narrowing in an artery supplying the infarct (OR 1.96 95% CI 1.06-3.63, p = 0.031) were independently associated with INR ≥2 at the time of their index stroke. CONCLUSION/CONCLUSIONS:Small stroke size (≤ 10 ml) and ipsilateral atherosclerosis with 50% or more narrowing may indicate a competing stroke mechanism. There may be important opportunities to improve stroke prevention strategies for patients with AF by targeting additional ischemic stroke mechanisms to improve patient outcomes.

BACKGROUND AND PURPOSE/OBJECTIVE:Acute rehabilitation is known to enhance stroke recovery. However, poststroke lethargy and fatigue can hinder participation in rehabilitation therapies. We hypothesized that in patients with moderate to severe stroke complicated by poststroke fatigue and lethargy early stimulant therapy with modafinil increases favorable discharge disposition defined as transfer to acute inpatient rehabilitation or home. METHODS:We retrospectively reviewed a cohort of patients with acute stroke admitted to the stroke service over a 3-year period. All patients 18 years or older with confirmed ischemic or hemorrhagic stroke, an NIHSS greater than or equal to 5 and documentation of fatigue/lethargy in clinical documentation were included. We compared patients that were treated with modafinil 50-200 mg to those managed with standard care. The primary outcome measure was discharge disposition. Secondary outcome was 90 day modified Rankin score (mRS). Statistical significance was determined using chi-square test for association and logistic regression models. Logistic regression models were derived in 2 ways with both raw data and an adjusted model that accounted for age, sex, and NIHSS score to account for the lack of randomization. RESULTS:This study included 199 stroke patients (145 ischemic, 54 hemorrhagic). Seventy-two (36.2%) were treated with modafinil and 129 (64.8%) were discharged to acute inpatient rehabilitation, while none were recommended for discharge home. Median NIHSS for modafinil patients was 13.5 versus 11 for standard care patients (P = .059). In adjusted models, modafinil was associated with higher odds of favorable discharge disposition (OR 2.00, 95% CI 1.01-3.95). Favorable outcome at 90 days defined as mRS less than or equal to 2 occurred more frequently with modafinil (5.6% versus 3.3%) but this did not achieve statistical significance (P > .1). These results occurred despite the modafinil group requiring longer ICU stays and having more in-hospital complications such as infections and need for percutaneous gastrostomy tubes. The benefit of modafinil was seen across all subgroups except those with severe stroke (NIHSS ≥ 15). There were no significant adverse events associated with modafinil administration. CONCLUSIONS:Modafinil use in acute in-hospital stroke patients with moderate stroke complicated by lethargy and fatigue was associated with improved discharge disposition. Randomized controlled trials are needed to further study the safety, efficacy, and long-term effects of modafinil in this patient population.

Background and Purpose- The first of the 2 NINDS (National Institute of Neurological Disorders and Stroke) Study trials did not show a significant increase in early neurological improvement, defined as National Institutes of Health Stroke Scale (NIHSS) improvement by ≥4, with alteplase treatment. We hypothesized that early neurological improvement defined as a percentage change in NIHSS (percent change NIHSS) at 24 hours is superior to other definitions in predicting 3-month functional outcomes and using this definition there would be treatment benefit of alteplase over placebo at 24 hours. Methods- We analyzed the NINDS rt-PA Stroke Study (Parts 1 and 2) trial data. Percent change NIHSS was defined as ([admission NIHSS score-24-hour NIHSS score]×100/admission NIHSS score] and delta NIHSS as (admission NIHSS score-24-hour NIHSS score). We compared early neurological improvement using these definitions between alteplase versus placebo patients. We also used receiver operating characteristic curve to determine the predictive association of early neurological improvement with excellent 3-month functional outcomes (Barthel Index score of 95-100 and modified Rankin Scale score of 0-1), good 3-month functional outcome (modified Rankin Scale score of 0-2), and 3-month infarct volume. Results- There was a significantly greater improvement in the 24-hour median percent change NIHSS among patients treated with alteplase compared with the placebo group (28% versus 15%; P=0.045) but not median delta NIHSS (3 versus 2; P=0.471). Receiver operating characteristic curve comparison showed that percent change NIHSS (ROC_percent) was better than delta NIHSS (ROC_delta) and admission NIHSS (ROC_admission) with regards to excellent 3-month Barthel Index (ROC_percent, 0.83; ROC_delta, 0.76; ROC_admission, 0.75), excellent 3-month modified Rankin Scale (ROC_percent, 0.83; ROC_delta, 0.74; ROC_admission, 0.78), and good 3-month modified Rankin Scale (ROC_percent, 0.83; ROC_delta, 0.76; ROC_admission, 0.78). Conclusions- In the NINDS rt-PA trial, alteplase was associated with a significant percent change improvement in NIHSS at 24 hours. Percent change in NIHSS may be a better surrogate marker of thrombolytic activity and 3-month outcomes.

INTRODUCTION/BACKGROUND:The glial-lymphatic pathway is a fluid-clearance pathway consisting of a para-arterial route for the flow of cerebrospinal fluid along perivascular spaces and subsequently toward the brain interstitium. In this case series we aim to investigate an empirical demonstration of glymphatic clearance of extravasated iodine following perforation incurred during endovascular therapy on serial CT. METHODS AND RESULTS/RESULTS:Six consecutive cases of endovascular perforation during thrombectomy performed between 2005 and 2018 were retrospectively collected by searching our internal database of total 446 thrombectomies. Two cases were excluded because care was withdrawn shortly following the procedure and no follow-up imaging was available. One case was excluded because a ventricular drain was placed. Three cases were hence included in this analysis. All three cases demonstrated progressive absorption of contrast by the brain parenchyma with eventual contrast disappearance. CONCLUSION/CONCLUSIONS:We described a likely in vivo CT correlate of the glymphatic system in a cohort of patients who sustained intraprocedural extravasation during thrombectomy for acute ischemic stroke.