Faculty Bibliography

Despite the severity of coronavirus disease 2019 (COVID-19) being more frequently related to acute respiratory distress syndrome and acute cardiac and renal injuries, thromboembolic events have been increasingly reported. We report a unique series of young patients with COVID-19 presenting with cerebral venous system thrombosis. Three patients younger than 41 years of age with confirmed Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) infection had neurologic findings related to cerebral venous thrombosis. They were admitted during the short period of 10 days between March and April 2020 and were managed in an academic institution in a large city. One patient had thrombosis in both the superficial and deep systems; another had involvement of the straight sinus, vein of Galen, and internal cerebral veins; and a third patient had thrombosis of the deep medullary veins. Two patients presented with hemorrhagic venous infarcts. The median time from COVID-19 symptoms to a thrombotic event was 7 days (range, 2-7 days). One patient was diagnosed with new-onset diabetic ketoacidosis, and another one used oral contraceptive pills. Two patients were managed with both hydroxychloroquine and azithromycin; one was treated with lopinavir-ritonavir. All patients had a fatal outcome. Severe and potentially fatal deep cerebral thrombosis may complicate the initial clinical presentation of COVID-19. We urge awareness of this atypical manifestation.

Background/UNASSIGNED:We explored factors associated with admission and discharge code status after nontraumatic intracranial hemorrhage. Methods/UNASSIGNED:We extracted data from patients admitted to our institution between January 1, 2013, and March 1, 2016 with nontraumatic intracerebral hemorrhage or subarachnoid hemorrhage who had a discharge modified Rankin Scale (mRS) of 4 to 6. We reviewed data based on admission and discharge code status. Results/UNASSIGNED:.06). There was no significant difference between discharge code status and sex, age, marital status, premorbid mRS, discharge GCS, or bleed severity. Conclusions/UNASSIGNED:Limitation of code status after nontraumatic intracranial hemorrhage appears to be associated with older age, white race, worse APACHE II score, and active cancer. The role of palliative care after intracranial hemorrhage and the racial disparity in limitation and de-escalation of treatment deserves further exploration.

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.

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.

BACKGROUND AND PURPOSE/OBJECTIVE:Early neurologic improvement (ENI) in patients treated with alteplase has been shown to correlate with functional outcome. However, the definition of ENI remains controversial and has varied across studies. We hypothesized that ENI defined as a percentage change in the National Institute of Health Stroke Scale (NIHSS) score (percent change NIHSS score) at 24-hours would better correlate with favorable outcomes at 3 months than ENI defined as the change in NIHSS score (delta NIHSS score) at 24 hours. METHODS:Retrospective analysis of prospectively collected single-center quality improvement data was performed of all acute ischemic stroke (AIS) patients treated with alteplase. We examined delta NIHSS score and percent change NIHSS score in unadjusted and adjusted logistic regression models as predictors of a favorable outcome at 3 months (defined as mRS 0-1). RESULTS:Among 586 patients who met the inclusion criteria, 194 (33.1%) had a favorable outcome at 3 months. In fully adjusted models, both delta NIHSS score (OR per point decrease 1.27; 95% confidence interval [CI] 1.19-1.36) and percent change NIHSS score (OR per 10 percent decrease 1.17; 95% CI 1.12-1.22) were associated with favorable functional outcome at 3 months. Receiver operating characteristic (ROC) curve comparison showed that the area under the ROC curve for percent change NIHSS score (.755) was greater than delta NIHSS score (.613) or admission NIHSS (.694). CONCLUSIONS:Percentage change in NIHSS score may be a better surrogate marker of ENI and functional outcome in AIS patients after receiving acute thrombolytic therapy. More studies are needed to confirm our findings.

Spontaneous cervical artery dissection (sCAD) is a major cause of stroke in young adults. Multiple sCAD is a rarer, more poorly understood presentation of sCAD that has been increasingly attributed to cervical trauma such as spinal manipulation or genetic polymorphisms in extracellular matrix components. The authors present the case of a 49-year-old, otherwise healthy woman, who over the course of 2 weeks developed progressive, hemodynamically significant, bilateral internal carotid artery and vertebral artery dissections. Collateral response involved extensive external carotid artery-internal carotid artery anastomoses via the ophthalmic artery, which were instrumental in maintaining perfusion because circle of Willis and leptomeningeal anastomotic responses were hampered by the dissection burden in the corresponding collateral vessels. Endovascular intervention by placement of Pipeline embolization devices and Atlas stents in bilateral internal carotid arteries was successfully performed. No syndromic or systemic etiology was discovered during a thorough workup.

BACKGROUND AND PURPOSE/OBJECTIVE:Patients with intracerebral hemorrhage (ICH) frequently present with hypertension, but it is unclear if this is due to pre-existing hypertension (prHTN) or to the bleed itself or associated pain. We sought to assess the relationship between prHTN and admission systolic blood pressure (aBP) and bleed severity. METHODS:We retrospectively assessed the relationship between prHTN and aBP and NIHSS in patients with ICH at 3 institutions. RESULTS:Of 251 patients, 170 (68%) had prHTN based on history of hypertension/antihypertensive use. Median aBP was significantly higher in those with prHTN (155 mm Hg (IQR 135-181) versus 139 mm Hg (IQR 124-158), P < .001). Patients with left ventricular hypertrophy (LVH) on electrocardiogram (ECG) or transthoracic echocardiogram (TTE) had significantly higher aBP than those without LVH (median aBP 195 mm Hg (IQR 155-216) for patients with LVH on ECG versus 147 mm Hg (IQR 129-163) for patients with no LVH on ECG, P < .001; median aBP 181 mm Hg (IQR 153-214) for patients with LVH on TTE versus 152 mm Hg (IQR 137-169) for patients with no LVH on TTE, P = .01). prHTN was associated with a higher median NIHSS (11 (IQR 3-20) for patients with history of hypertension/antihypertensive use versus 6 (IQR 1-14) for patients without this history (P = .02); 9 (IQR 3-19) versus 5 (IQR 2-13) for patients with/without LVH on ECG (P = .085); and 10 (IQR 5-18) versus 5 (IQR 1-13) for patients with/without LVH on TTE (P = .046). CONCLUSIONS:Patients with ICH who have prHTN have higher aBP and NIHSS, suggesting that prHTN may worsen reactive hypertension in the setting of ICH.