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Social Determinants of Health Attenuate the Relationship Between Race and Ethnicity and White Matter Hyperintensity Severity but not Microbleed Presence in Patients with Intracerebral Hemorrhage

Bauman, Kristie M; Yaghi, Shadi; Lewis, Ariane; Agarwal, Shashank; Changa, Abhinav; Dogra, Siddhant; Litao, Miguel; Sanger, Matthew; Lord, Aaron; Ishida, Koto; Zhang, Cen; Czeisler, Barry; Torres, Jose; Dehkharghani, Seena; Frontera, Jennifer A; Melmed, Kara R
BACKGROUND:The association between race and ethnicity and microvascular disease in patients with intracerebral hemorrhage (ICH) is unclear. We hypothesized that social determinants of health (SDOHs) mediate the relationship between race and ethnicity and severity of white matter hyperintensities (WMHs) and microbleeds in patients with ICH. METHODS:We performed a retrospective observational cohort study of patients with ICH at two tertiary care hospitals between 2013 and 2020 who underwent magnetic resonance imaging of the brain. Magnetic resonance imaging scans were evaluated for the presence of microbleeds and WMH severity (defined by the Fazekas scale; moderate to severe WMH defined as Fazekas scores 3-6). We assessed for associations between sex, race and ethnicity, employment status, median household income, education level, insurance status, and imaging biomarkers of microvascular disease. A mediation analysis was used to investigate the influence of SDOHs on the associations between race and imaging features. We assessed the relationship of all variables with discharge outcomes. RESULTS:We identified 233 patients (mean age 62 [SD 16]; 48% female) with ICH. Of these, 19% were Black non-Hispanic, 32% had a high school education or less, 21% required an interpreter, 11% were unemployed, and 6% were uninsured. Moderate to severe WMH, identified in 114 (50%) patients, was associated with age, Black non-Hispanic race and ethnicity, highest level of education, insurance status, and history of hypertension, hyperlipidemia, or diabetes (p < 0.05). In the mediation analysis, the proportion of the association between Black non-Hispanic race and ethnicity and the Fazekas score that was mediated by highest level of education was 65%. Microbleeds, present in 130 (57%) patients, was associated with age, highest level of education, and history of diabetes or hypertension (p < 0.05). Age, highest level of education, insurance status, and employment status were associated with discharge modified Rankin Scale scores of 3-6, but race and ethnicity was not. CONCLUSIONS:The association between Black non-Hispanic race and ethnicity and moderate to severe WMH lost significance after we adjusted for highest level of education, suggesting that SDOHs may mediate the association between race and ethnicity and microvascular disease.
PMID: 34918215
ISSN: 1556-0961
CID: 5084672

Perceptions Regarding the SARS-CoV-2 Pandemic's Impact on Neurocritical Care Delivery: Results From a Global Survey

Lele, Abhijit V; Wahlster, Sarah; Alunpipachathai, Bhunyawee; Awraris Gebrewold, Meron; Chou, Sherry H-Y; Crabtree, Gretchen; English, Shane; Der-Nigoghossian, Caroline; Gagnon, David J; Kim-Tenser, May; Karanjia, Navaz; Kirkman, Matthew A; Lamperti, Massimo; Livesay, Sarah L; Mejia-Mantilla, Jorge; Melmed, Kara; Prabhakar, Hemanshu; Tumino, Leandro; Venkatasubba Rao, Chethan P; Udy, Andrew A; Videtta, Walter; Moheet, Asma M
BACKGROUND:The SARS-CoV-2 (COVID-19) pandemic has impacted many facets of critical care delivery. METHODS:An electronic survey was distributed to explore the pandemic's perceived impact on neurocritical care delivery between June 2020 and March 2021. Variables were stratified by World Bank country income level, presence of a dedicated neurocritical care unit (NCCU) and experiencing a COVID-19 patient surge. RESULTS:Respondents from 253 hospitals (78.3% response rate) from 47 countries (45.5% low/middle income countries; 54.5% with a dedicated NCCU; 78.6% experienced a first surge) participated in the study. Independent of country income level, NCCU and surge status, participants reported reductions in NCCU admissions (67%), critical care drug shortages (69%), reduction in ancillary services (43%) and routine diagnostic testing (61%), and temporary cancellation of didactic teaching (44%) and clinical/basic science research (70%). Respondents from low/middle income countries were more likely to report lack of surge preparedness (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.8-5.8) and struggling to return to prepandemic standards of care (OR, 12.2; 95% CI, 4.4-34) compared with respondents from high-income countries. Respondents experiencing a surge were more likely to report conversion of NCCUs and general-mixed intensive care units (ICUs) to a COVID-ICU (OR 3.7; 95% CI, 1.9-7.3), conversion of non-ICU beds to ICU\ beds (OR, 3.4; 95% CI, 1.8-6.5), and deviations in critical care and pharmaceutical practices (OR, 4.2; 95% CI 2.1-8.2). Respondents from hospitals with a dedicated NCCU were less likely to report conversion to a COVID-ICU (OR, 0.5; 95% CI, 0.3-0.9) or conversion of non-ICU to ICU beds (OR, 0.5; 95% CI, 0.3-0.9). CONCLUSION/CONCLUSIONS:This study reports the perceived impact of the COVID-19 pandemic on global neurocritical care delivery, and highlights shortcomings of health care infrastructures and the importance of pandemic preparedness.
PMID: 34882104
ISSN: 1537-1921
CID: 5110392

Tachycardia is associated with mortality and functional outcome after thrombectomy for acute ischemic stroke

Krieger, Penina; Zhao, Amanda; Croll, Leah; Irvine, Hannah; Torres, Jose; Melmed, Kara R; Lord, Aaron; Ishida, Koto; Frontera, Jennifer; Lewis, Ariane
BACKGROUND:The relationship between cardiac function and mortality after thrombectomy for acute ischemic stroke is not well elucidated. METHODS:We analyzed the relationship between cardiac function and mortality prior to discharge in a cohort of patients who underwent thrombectomy for acute ischemic stroke at two large medical centers in New York City between December 2018 and November 2020. All analyses were performed using Welch's two sample t-test and logistic regression accounting for age, initial NIHSS and post-procedure ASPECTS score, where OR is for each unit increase in the respective variables. RESULTS:Of 248 patients, 41 (16.5%) died prior to discharge. Mortality was significantly associated with higher initial heart rate (HR; 89 ± 19 bpm vs 80 ± 18 bpm, p = 0.004) and higher maximum HR over entire admission (137 ± 26 bpm vs 114 ± 25 bpm, p < 0.001). Mortality was also associated with presence of NSTEMI/STEMI (63% vs 29%, p < 0.001). When age, initial NIHSS score, and post-procedure ASPECTS score were included in multivariate analysis, there was still a significant relationship between mortality and initial HR (OR 1.03, 95% CI 1.01- 1.05, p = 0.02), highest HR over the entire admission (OR 1.03, 95% CI 1.02-1.05, p < 0.001), and presence of NSTEMI/STEMI (OR 3.76, 95% CI 1.66-8.87, p = 0.002). CONCLUSIONS:Tachycardia is associated with mortality in patients who undergo thrombectomy. Further investigation is needed to determine whether this risk is modifiable.
PMID: 35367848
ISSN: 1532-8511
CID: 5192412

Trajectories of Neurologic Recovery 12 Months After Hospitalization for COVID-19: A Prospective Longitudinal Study

Frontera, Jennifer A; Yang, Dixon; Medicherla, Chaitanya; Baskharoun, Samuel; Bauman, Kristie; Bell, Lena; Bhagat, Dhristie; Bondi, Steven; Chervinsky, Alexander; Dygert, Levi; Fuchs, Benjamin; Gratch, Daniel; Hasanaj, Lisena; Horng, Jennifer; Huang, Joshua; Jauregui, Ruben; Ji, Yuan; Kahn, D Ethan; Koch, Ethan; Lin, Jessica; Liu, Susan; Olivera, Anlys; Rosenthal, Jonathan; Snyder, Thomas; Stainman, Rebecca; Talmasov, Daniel; Thomas, Betsy; Valdes, Eduard; Zhou, Ting; Zhu, Yingrong; Lewis, Ariane; Lord, Aaron S; Melmed, Kara; Meropol, Sharon B; Thawani, Sujata; Troxel, Andrea B; Yaghi, Shadi; Balcer, Laura J; Wisniewski, Thomas; Galetta, Steven
BACKGROUND/OBJECTIVES/OBJECTIVE:Little is known about trajectories of recovery 12-months after hospitalization for severe COVID. METHODS:We conducted a prospective, longitudinal cohort study of patients with and without neurological complications during index hospitalization for COVID-19 from March 10, 2020-May 20, 2020. Phone follow-up batteries were performed at 6- and 12-months post-COVID symptom onset. The primary 12-month outcome was the modified Rankin Scale (mRS) comparing patients with or without neurological complications using multivariable ordinal analysis. Secondary outcomes included: activities of daily living (Barthel Index), telephone Montreal Cognitive Assessment (t-MoCA) and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. Changes in outcome scores from 6 to 12-months were compared using non-parametric paired-samples sign test. RESULTS:Twelve-month follow-up was completed in N=242 patients (median age 65, 64% male, 34% intubated during hospitalization) and N=174 completed both 6- and 12-month follow-up. At 12-months 197/227 (87%) had ≥1 abnormal metric: mRS>0 (75%), Barthel<100 (64%), t-MoCA≤18 (50%), high anxiety (7%), depression (4%), fatigue (9%) and poor sleep (10%). 12-month mRS scores did not differ significantly among those with (N=113) or without (N=129) neurological complications during hospitalization after adjusting for age, sex, race, pre-COVID mRS and intubation status (adjusted OR 1.4, 95% CI0.8-2.5), though those with neurological complications had higher fatigue scores (T-score 47 vs 44, P=0.037). Significant improvements in outcome trajectories from 6- to 12-months were observed in t-MoCA scores (56% improved, median difference 1 point, P=0.002), and Neuro-QoL anxiety scores (45% improved, P=0.003). Non-significant improvements occurred in fatigue, sleep and depression scores in 48%, 48% and 38% of patients, respectively. Barthel and mRS scores remained unchanged between 6 and 12-months in >50% of patients. DISCUSSION/CONCLUSIONS:At 12-months post-hospitalization for severe COVID, 87% of patients had ongoing abnormalities in functional, cognitive or Neuro-QoL metrics and abnormal cognition persisted in 50% of patients without a prior history of dementia/cognitive abnormality. Only fatigue severity differed significantly between patients with or without neurological complications during index hospitalization. However, significant improvements in cognitive (t-MoCA) and anxiety (Neuro-QoL) scores occurred in 56% and 45% of patients, respectively, between 6- to 12-months. These results may not be generalizable to those with mild/moderate COVID.
PMID: 35314503
ISSN: 1526-632x
CID: 5192402

Stroke epidemiology and outcomes in the modern era of left ventricular assist devices

Ibeh, Chinwe; Melmed, Kara R; Yuzefpolskaya, Melana; Colombo, Paolo C; Willey, Joshua Z
The care for the patients with end-stage heart failure has been revolutionized by the introduction of durable left ventricular assist devices, providing a substantial improvement in patient survival and quality of life and an alternative to heart transplantation. The newest devices have lower instances of mechanical dysfunction and associated pump thrombosis. Despite these improvements in complications, the use of continuous flow assist devices is still associated with high rates of thrombotic and hemorrhagic complications, most notably stroke in approximately 10% of continuous flow assist devices patients per year. With the newest HeartMate 3 devices, there have been lower observed rates of stroke, which has in part been achieved by both improvements in pump technology and knowledge of the risk factors for stroke and neurological complications. The therapeutic options available to clinicians to reduce the risk of stroke, including management of hypertension and antithrombotics, will be reviewed in this manuscript.
PMID: 35034222
ISSN: 1573-7322
CID: 5131262

Toxic Metabolic Encephalopathy in Hospitalized Patients with COVID-19

Frontera, Jennifer A; Melmed, Kara; Fang, Taolin; Granger, Andre; Lin, Jessica; Yaghi, Shadi; Zhou, Ting; Lewis, Ariane; Kurz, Sebastian; Kahn, D Ethan; de Havenon, Adam; Huang, Joshua; Czeisler, Barry M; Lord, Aaron; Meropol, Sharon B; Troxel, Andrea B; Wisniewski, Thomas; Balcer, Laura; Galetta, Steven
BACKGROUND:Toxic metabolic encephalopathy (TME) has been reported in 7-31% of hospitalized patients with coronavirus disease 2019 (COVID-19); however, some reports include sedation-related delirium and few data exist on the etiology of TME. We aimed to identify the prevalence, etiologies, and mortality rates associated with TME in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients. METHODS:We conducted a retrospective, multicenter, observational cohort study among patients with reverse transcriptase-polymerase chain reaction-confirmed SARS-CoV-2 infection hospitalized at four New York City hospitals in the same health network between March 1, 2020, and May 20, 2020. TME was diagnosed in patients with altered mental status off sedation or after an adequate sedation washout. Patients with structural brain disease, seizures, or primary neurological diagnoses were excluded. The coprimary outcomes were the prevalence of TME stratified by etiology and in-hospital mortality (excluding comfort care only patients) assessed by using a multivariable time-dependent Cox proportional hazards models with adjustment for age, race, sex, intubation, intensive care unit requirement, Sequential Organ Failure Assessment scores, hospital location, and date of admission. RESULTS:Among 4491 patients with COVID-19, 559 (12%) were diagnosed with TME, of whom 435 of 559 (78%) developed encephalopathy immediately prior to hospital admission. The most common etiologies were septic encephalopathy (n = 247 of 559 [62%]), hypoxic-ischemic encephalopathy (HIE) (n = 331 of 559 [59%]), and uremia (n = 156 of 559 [28%]). Multiple etiologies were present in 435 (78%) patients. Compared with those without TME (n = 3932), patients with TME were older (76 vs. 62 years), had dementia (27% vs. 3%) or psychiatric history (20% vs. 10%), were more often intubated (37% vs. 20%), had a longer hospital length of stay (7.9 vs. 6.0 days), and were less often discharged home (25% vs. 66% [all P < 0.001]). Excluding comfort care patients (n = 267 of 4491 [6%]) and after adjustment for confounders, TME remained associated with increased risk of in-hospital death (n = 128 of 425 [30%] patients with TME died, compared with n = 600 of 3799 [16%] patients without TME; adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.02-1.52, P = 0.031), and TME due to hypoxemia conferred the highest risk (n = 97 of 233 [42%] patients with HIE died, compared with n = 631 of 3991 [16%] patients without HIE; aHR 1.56, 95% CI 1.21-2.00, P = 0.001). CONCLUSIONS:TME occurred in one in eight hospitalized patients with COVID-19, was typically multifactorial, and was most often due to hypoxemia, sepsis, and uremia. After we adjustment for confounding factors, TME was associated with a 24% increased risk of in-hospital mortality.
PMID: 33725290
ISSN: 1556-0961
CID: 4817682

Increase in Ventricle Size and the Evolution of White Matter Changes on Serial Imaging in Critically Ill Patients with COVID-19

Agarwal, Shashank; Melmed, Kara; Dogra, Siddhant; Jain, Rajan; Conway, Jenna; Galetta, Steven; Lewis, Ariane
BACKGROUND:Evolution of brain magnetic resonance imaging (MRI) findings in critically ill patients with coronavirus disease 2019 (COVID-19) is unknown. METHODS:We retrospectively reviewed 4530 critically ill patients with COVID-19 admitted to three tertiary care hospitals in New York City from March 1 to June 30, 2020 to identify patients who had more than one brain MRI. We reviewed the initial and final MRI for each patient to (1) measure the percent change in the bicaudate index and third ventricular diameter and (2) evaluate changes in the presence and severity of white matter changes. RESULTS:Twenty-one patients had two MRIs separated by a median of 22 [Interquartile range (IQR) 14-30] days. Ventricle size increased for 15 patients (71%) between scans [median bicaudate index 0.16 (IQR 0.126-0.181) initially and 0.167 (IQR 0.138-0.203) on final imaging (p < 0.001); median third ventricular diameter 6.9 mm (IQR 5.4-10.3) initially and 7.2 mm (IQR 6.4-10.8) on final imaging (p < 0.001)]. Every patient had white matter changes on the initial and final MRI; between images, they worsened for seven patients (33%) and improved for three (14%). CONCLUSIONS:On serial imaging of critically ill patients with COVID-19, ventricle size frequently increased over several weeks. White matter changes were often unchanged, but in some cases they worsened or improved, demonstrating there is likely a spectrum of pathophysiological processes responsible for these changes.
PMID: 33674942
ISSN: 1556-0961
CID: 4823352

COVID-19 associated brain/spinal cord lesions and leptomeningeal enhancement: A meta-analysis of the relationship to CSF SARS-CoV-2

Lewis, Ariane; Jain, Rajan; Frontera, Jennifer; Placantonakis, Dimitris G; Galetta, Steven; Balcer, Laura; Melmed, Kara R
BACKGROUND AND PURPOSE/OBJECTIVE:We reviewed the literature to evaluate cerebrospinal fluid (CSF) results from patients with coronavirus disease 2019 (COVID-19) who had neurological symptoms and had an MRI that showed (1) central nervous system (CNS) hyperintense lesions not attributed to ischemia and/or (2) leptomeningeal enhancement. We sought to determine if these findings were associated with a positive CSF severe acute respiratory syndrome associated coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR). METHODS:We performed a systematic review of Medline and Embase from December 1, 2019 to November 18, 2020. CSF results were evaluated based on the presence/absence of (1) ≥ 1 CNS hyperintense lesion and (2) leptomeningeal enhancement. RESULTS:In 117 publications, we identified 193 patients with COVID-19 who had an MRI of the CNS and CSF testing. There were 125 (65%) patients with CNS hyperintense lesions. Patients with CNS hyperintense lesions were significantly more likely to have a positive CSF SARS-CoV-2 PCR (10% [9/87] vs. 0% [0/43], p = 0.029). Of 75 patients who had a contrast MRI, there were 20 (27%) patients who had leptomeningeal enhancement. Patients with leptomeningeal enhancement were significantly more likely to have a positive CSF SARS-CoV-2 PCR (25% [4/16] vs. 5% [2/42], p = 0.024). CONCLUSION/CONCLUSIONS:The presence of CNS hyperintense lesions or leptomeningeal enhancement on neuroimaging from patients with COVID-19 is associated with increased likelihood of a positive CSF SARS-CoV-2 PCR. However, a positive CSF SARS-CoV-2 PCR is uncommon in patients with these neuroimaging findings, suggesting they are often related to other etiologies, such as inflammation, hypoxia, or ischemia.
PMID: 34105198
ISSN: 1552-6569
CID: 4900822

Cerebrospinal fluid from COVID-19 patients with olfactory/gustatory dysfunction: A review

Lewis, Ariane; Frontera, Jennifer; Placantonakis, Dimitris G; Galetta, Steven; Balcer, Laura; Melmed, Kara R
OBJECTIVE:We reviewed the literature on cerebrospinal fluid (CSF) testing in patients with altered olfactory/gustatory function due to COVID-19 for evidence of viral neuroinvasion. METHODS:We performed a systematic review of Medline and Embase to identify publications that described at least one patient with COVID-19 who had altered olfactory/gustatory function and had CSF testing performed. The search ranged from December 1, 2019 to November 18, 2020. RESULTS:We identified 51 publications that described 70 patients who met inclusion criteria. Of 51 patients who had CSF SARS-CoV-2 PCR testing, 3 (6%) patients had positive results and 1 (2%) patient had indeterminate results. Cycle threshold (Ct; the number of amplification cycles required for the target gene to exceed the threshold, which is inversely related to viral load) was not provided for the patients with a positive PCR. The patient with indeterminate results had a Ct of 37 initially, then no evidence of SARS-CoV-2 RNA on repeat testing. Of 6 patients who had CSF SARS-CoV-2 antibody testing, 3 (50%) were positive. Testing to distinguish intrathecal antibody synthesis from transudation of antibodies to the CSF via breakdown of the blood-brain barrier was performed in 1/3 (33%) patients; this demonstrated antibody transmission to the CSF via transudation. CONCLUSION/CONCLUSIONS:Detection of SARS-CoV-2 in CSF via PCR or evaluation for intrathecal antibody synthesis appears to be rare in patients with altered olfactory/gustatory function. While pathology studies are needed, our review suggests it is unlikely that these symptoms are related to viral neuroinvasion.
PMID: 34146842
ISSN: 1872-6968
CID: 4936832

Anticoagulation use and Hemorrhagic Stroke in SARS-CoV-2 Patients Treated at a New York Healthcare System

Kvernland, Alexandra; Kumar, Arooshi; Yaghi, Shadi; Raz, Eytan; Frontera, Jennifer; Lewis, Ariane; Czeisler, Barry; Kahn, D Ethan; Zhou, Ting; Ishida, Koto; Torres, Jose; Riina, Howard A; Shapiro, Maksim; Nossek, Erez; Nelson, Peter K; Tanweer, Omar; Gordon, David; Jain, Rajan; Dehkharghani, Seena; Henninger, Nils; de Havenon, Adam; Grory, Brian Mac; Lord, Aaron; Melmed, Kara
BACKGROUND AND PURPOSE/OBJECTIVE:While the thrombotic complications of COVID-19 have been well described, there are limited data on clinically significant bleeding complications including hemorrhagic stroke. The clinical characteristics, underlying stroke mechanism, and outcomes in this particular subset of patients are especially salient as therapeutic anticoagulation becomes increasingly common in the treatment and prevention of thrombotic complications of COVID-19. METHODS:We conducted a retrospective cohort study of patients with hemorrhagic stroke (both non-traumatic intracerebral hemorrhage and spontaneous non-aneurysmal subarachnoid hemorrhage) who were hospitalized between March 1, 2020, and May 15, 2020, within a major healthcare system in New York, during the coronavirus pandemic. Patients with hemorrhagic stroke on admission and who developed hemorrhage during hospitalization were both included. We compared the clinical characteristics of patients with hemorrhagic stroke and COVID-19 to those without COVID-19 admitted to our hospital system between March 1, 2020, and May 15, 2020 (contemporary controls), and March 1, 2019, and May 15, 2019 (historical controls). Demographic variables and clinical characteristics between the individual groups were compared using Fischer's exact test for categorical variables and nonparametric test for continuous variables. We adjusted for multiple comparisons using the Bonferroni method. RESULTS:During the study period in 2020, out of 4071 patients who were hospitalized with COVID-19, we identified 19 (0.5%) with hemorrhagic stroke. Of all COVID-19 with hemorrhagic stroke, only three had isolated non-aneurysmal SAH with no associated intraparenchymal hemorrhage. Among hemorrhagic stroke in patients with COVID-19, coagulopathy was the most common etiology (73.7%); empiric anticoagulation was started in 89.5% of these patients versus 4.2% in contemporary controls (p ≤ .001) and 10.0% in historical controls (p ≤ .001). Compared to contemporary and historical controls, patients with COVID-19 had higher initial NIHSS scores, INR, PTT, and fibrinogen levels. Patients with COVID-19 also had higher rates of in-hospital mortality (84.6% vs. 4.6%, p ≤ 0.001). Sensitivity analyses excluding patients with strictly subarachnoid hemorrhage yielded similar results. CONCLUSION/CONCLUSIONS:We observed an overall low rate of imaging-confirmed hemorrhagic stroke among patients hospitalized with COVID-19. Most hemorrhages in patients with COVID-19 infection occurred in the setting of therapeutic anticoagulation and were associated with increased mortality. Further studies are needed to evaluate the safety and efficacy of therapeutic anticoagulation in patients with COVID-19.
PMID: 32839867
ISSN: 1556-0961
CID: 4574182