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Life stressors significantly impact long-term outcomes and post-acute symptoms 12-months after COVID-19 hospitalization

Frontera, Jennifer A; Sabadia, Sakinah; Yang, Dixon; de Havenon, Adam; Yaghi, Shadi; Lewis, Ariane; Lord, Aaron S; Melmed, Kara; Thawani, Sujata; Balcer, Laura J; Wisniewski, Thomas; Galetta, Steven L
BACKGROUND:Limited data exists evaluating predictors of long-term outcomes after hospitalization for COVID-19. METHODS:We conducted a prospective, longitudinal cohort study of patients hospitalized for COVID-19. The following outcomes were collected at 6 and 12-months post-diagnosis: disability using the modified Rankin Scale (mRS), activities of daily living assessed with the Barthel Index, cognition assessed with the telephone Montreal Cognitive Assessment (t-MoCA), Neuro-QoL batteries for anxiety, depression, fatigue and sleep, and post-acute symptoms of COVID-19. Predictors of these outcomes, including demographics, pre-COVID-19 comorbidities, index COVID-19 hospitalization metrics, and life stressors, were evaluated using multivariable logistic regression. RESULTS:Of 790 COVID-19 patients who survived hospitalization, 451(57%) completed 6-month (N = 383) and/or 12-month (N = 242) follow-up, and 77/451 (17%) died between discharge and 12-month follow-up. Significant life stressors were reported in 121/239 (51%) at 12-months. In multivariable analyses, life stressors including financial insecurity, food insecurity, death of a close contact and new disability were the strongest independent predictors of worse mRS, Barthel Index, depression, fatigue, and sleep scores, and prolonged symptoms, with adjusted odds ratios ranging from 2.5 to 20.8. Other predictors of poor outcome included older age (associated with worse mRS, Barthel, t-MoCA, depression scores), baseline disability (associated with worse mRS, fatigue, Barthel scores), female sex (associated with worse Barthel, anxiety scores) and index COVID-19 severity (associated with worse Barthel index, prolonged symptoms). CONCLUSIONS:Life stressors contribute substantially to worse functional, cognitive and neuropsychiatric outcomes 12-months after COVID-19 hospitalization. Other predictors of poor outcome include older age, female sex, baseline disability and severity of index COVID-19.
PMID: 36379135
ISSN: 1878-5883
CID: 5383312

Aggregation-Seeding Forms of α-Synuclein Are Not Detected in Acute Coronavirus Disease 2019 Cerebrospinal Fluid [Letter]

Russo, Marco J; MacLeod, Karen; Lamoureux, Jennifer; Lebovitz, Russ; Pleshkevich, Maria; Steriade, Claude; Wisniewski, Thomas; Frontera, Jennifer A; Kang, Un Jung
PMID: 36208476
ISSN: 1531-8257
CID: 5351812

Markers of infection and inflammation are associated with post-thrombectomy mortality in acute stroke

Irvine, Hannah; Krieger, Penina; Melmed, Kara R; Torres, Jose; Croll, Leah; Zhao, Amanda; Lord, Aaron; Ishida, Koto; Frontera, Jennifer; Lewis, Ariane
OBJECTIVE:We explored the relationship between markers of infection and inflammation and mortality in patients with acute ischemic stroke who underwent thrombectomy. METHODS:We performed retrospective chart review of stroke patients who underwent thrombectomy at two tertiary academic centers between December 2018 and November 2020. Associations between discharge mortality, WBC count, neutrophil percentage, fever, culture data, and antibiotic treatment were analyzed using the Wilcoxon rank sum test, Student's t-test, and Fisher's exact test. Independent predictors of mortality were identified with multivariable analysis. Analyses were repeated excluding COVID-positive patients. RESULTS:Of 248 patients who underwent thrombectomy, 41 (17 %) died prior to discharge. Mortality was associated with admission WBC count (11 [8-14] vs. 9 [7-12], p = 0.0093), admission neutrophil percentage (78 % ± 11 vs. 71 % ± 14, p = 0.0003), peak WBC count (17 [13-22] vs. 12 [9-15], p < 0.0001), fever (71 % vs. 27 %, p < 0.0001), positive culture (44 % vs. 15 %, p < 0.0001), and days treated with antibiotics (3 [1-7] vs. 1 [0-4], p < 0.0001). After controlling for age, admission NIHSS and post-thrombectomy ASPECTS score, mortality was associated with admission WBC count (OR 13, CI 1.32-142, p = 0.027), neutrophil percentage (OR 1.03, CI 1.0-1.07, p = 0.045), peak WBC count (OR 301, CI 24-5008, p < 0.0001), fever (OR 24.2, CI 1.77-332, p < 0.0001), and positive cultures (OR 4.24, CI 1.87-9.62, p = 0.0006). After excluding COVID-positive patients (n = 14), peak WBC count, fever and positive culture remained independent predictors of mortality. CONCLUSION/CONCLUSIONS:Markers of infection and inflammation are associated with discharge mortality after thrombectomy. Further study is warranted to investigate the causal relationship of these markers with clinical outcome.
PMID: 36272394
ISSN: 1872-6968
CID: 5359072

Correction to: Proceedings of the Second Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness

Mainali, Shraddha; Aiyagari, Venkatesh; Alexander, Sheila; Bodien, Yelena; Boerwinkle, Varina; Boly, Melanie; Brown, Emery; Brown, Jeremy; Claassen, Jan; Edlow, Brian L; Fink, Ericka L; Fins, Joseph J; Foreman, Brandon; Frontera, Jennifer; Geocadin, Romergryko G; Giacino, Joseph; Gilmore, Emily J; Gosseries, Olivia; Hammond, Flora; Helbok, Raimund; Claude Hemphill, J; Hirsch, Karen; Kim, Keri; Laureys, Steven; Lewis, Ariane; Ling, Geoffrey; Livesay, Sarah L; McCredie, Victoria; McNett, Molly; Menon, David; Molteni, Erika; Olson, DaiWai; O'Phelan, Kristine; Park, Soojin; Polizzotto, Len; Javier Provencio, Jose; Puybasset, Louis; Venkatasubba Rao, Chethan P; Robertson, Courtney; Rohaut, Benjamin; Rubin, Michael; Sharshar, Tarek; Shutter, Lori; Sampaio Silva, Gisele; Smith, Wade; Stevens, Robert D; Thibaut, Aurore; Vespa, Paul; Wagner, Amy K; Ziai, Wendy C; Zink, Elizabeth; Suarez, Jose I
PMID: 35715614
ISSN: 1556-0961
CID: 5249932

Bridging Knowledge Gaps in the Diagnosis and Management of Neuropsychiatric Sequelae of COVID-19

Frontera, Jennifer A; Simon, Naomi M
Importance/UNASSIGNED:Neuropsychiatric symptoms have been reported as a prominent feature of postacute sequelae of COVID-19 (PASC), with common symptoms that include cognitive impairment, sleep difficulties, depression, posttraumatic stress, and substance use disorders. A primary challenge of parsing PASC epidemiology and pathophysiology is the lack of a standard definition of the syndrome, and little is known regarding mechanisms of neuropsychiatric PASC. Observations/UNASSIGNED:Rates of symptom prevalence vary, but at least 1 PASC neuropsychiatric symptom has been reported in as many as 90% of patients 6 months after COVID-19 hospitalization and in approximately 25% of nonhospitalized adults with COVID-19. Mechanisms of neuropsychiatric sequelae of COVID-19 are still being elucidated. They may include static brain injury accrued during acute COVID-19, neurodegeneration triggered by secondary effects of acute COVID-19, autoimmune mechanisms with chronic inflammation, viral persistence in tissue reservoirs, or reactivation of other latent viruses. Despite rapidly emerging data, many gaps in knowledge persist related to the variable definitions of PASC, lack of standardized phenotyping or biomarkers, variability in virus genotypes, ascertainment biases, and limited accounting for social determinants of health and pandemic-related stressors. Conclusions and Relevance/UNASSIGNED:Growing data support a high prevalence of PASC neuropsychiatric symptoms, but the current literature is heterogeneous with variable assessments of critical epidemiological factors. By enrolling large patient samples and conducting state-of-the-art assessments, the Researching COVID to Enhance Recovery (RECOVER), a multicenter research initiative funded by the National Institutes of Health, will help clarify PASC epidemiology, pathophysiology, and mechanisms of injury, as well as identify targets for therapeutic intervention.
PMID: 35767287
ISSN: 2168-6238
CID: 5281182

The Curing Coma Campaign International Survey on Coma Epidemiology, Evaluation, and Therapy (COME TOGETHER)

Helbok, Raimund; Rass, Verena; Beghi, Ettore; Bodien, Yelena G; Citerio, Giuseppe; Giacino, Joseph T; Kondziella, Daniel; Mayer, Stephan A; Menon, David; Sharshar, Tarek; Stevens, Robert D; Ulmer, Hanno; Venkatasubba Rao, Chethan P; Vespa, Paul; McNett, Molly; Frontera, Jennifer
BACKGROUND:Although coma is commonly encountered in critical care, worldwide variability exists in diagnosis and management practices. We aimed to assess variability in coma definitions, etiologies, treatment strategies, and attitudes toward prognosis. METHODS:As part of the Neurocritical Care Society Curing Coma Campaign, between September 2020 and January 2021, we conducted an anonymous, international, cross-sectional global survey of health care professionals caring for patients with coma and disorders of consciousness in the acute, subacute, or chronic setting. Survey responses were solicited by sequential emails distributed by international neuroscience societies and social media. Fleiss κ values were calculated to assess agreement among respondents. RESULTS:The survey was completed by 258 health care professionals from 41 countries. Respondents predominantly were physicians (n = 213, 83%), were from the United States (n = 141, 55%), and represented academic centers (n = 231, 90%). Among eight predefined items, respondents identified the following cardinal features, in various combinations, that must be present to define coma: absence of wakefulness (81%, κ = 0.764); Glasgow Coma Score (GCS) ≤ 8 (64%, κ = 0.588); failure to respond purposefully to visual, verbal, or tactile stimuli (60%, κ = 0.552); and inability to follow commands (58%, κ = 0.529). Reported etiologies of coma encountered included medically induced coma (24%), traumatic brain injury (24%), intracerebral hemorrhage (21%), and cardiac arrest/hypoxic-ischemic encephalopathy (11%). The most common clinical assessment tools used for coma included the GCS (94%) and neurological examination (78%). Sixty-six percent of respondents routinely performed sedation interruption, in the absence of contraindications, for clinical coma assessments in the intensive care unit. Advanced neurological assessment techniques in comatose patients included quantitative electroencephalography (EEG)/connectivity analysis (16%), functional magnetic resonance imaging (7%), single-photon emission computerized tomography (6%), positron emission tomography (4%), invasive EEG (4%), and cerebral microdialysis (4%). The most commonly used neurostimulants included amantadine (51%), modafinil (37%), and methylphenidate (28%). The leading determinants for prognostication included etiology of coma, neurological examination findings, and neuroimaging. Fewer than 20% of respondents reported routine follow-up of coma survivors after hospital discharge; however, 86% indicated interest in future research initiatives that include postdischarge outcomes at six (85%) and 12 months (65%). CONCLUSIONS:There is wide heterogeneity among health care professionals regarding the clinical definition of coma and limited routine use of advanced coma assessment techniques in acute care settings. Coma management practices vary across sites, and mechanisms for coordinated and sustained follow-up after acute treatment are inconsistent. There is an urgent need for the development of evidence-based guidelines and a collaborative, coordinated approach to advance both the science and the practice of coma management globally.
PMID: 35141860
ISSN: 1556-0961
CID: 5156252

Proceedings of the Second Curing Coma Campaign NIH Symposium: Challenging the Future of Research for Coma and Disorders of Consciousness

Mainali, Shraddha; Aiyagari, Venkatesh; Alexander, Sheila; Bodien, Yelena; Boerwinkle, Varina; Boly, Melanie; Brown, Emery; Brown, Jeremy; Claassen, Jan; Edlow, Brian L; Fink, Erika L; Fins, Joseph J; Foreman, Brandon; Frontera, Jennifer; Geocadin, Romergryko G; Giacino, Joseph; Gilmore, Emily J; Gosseries, Olivia; Hammond, Flora; Helbok, Raimund; Claude Hemphill, J; Hirsch, Karen; Kim, Keri; Laureys, Steven; Lewis, Ariane; Ling, Geoffrey; Livesay, Sarah L; McCredie, Victoria; McNett, Molly; Menon, David; Molteni, Erika; Olson, DaiWai; O'Phelan, Kristine; Park, Soojin; Polizzotto, Len; Javier Provencio, Jose; Puybasset, Louis; Venkatasubba Rao, Chethan P; Robertson, Courtney; Rohaut, Benjamin; Rubin, Michael; Sharshar, Tarek; Shutter, Lori; Sampaio Silva, Gisele; Smith, Wade; Stevens, Robert D; Thibaut, Aurore; Vespa, Paul; Wagner, Amy K; Ziai, Wendy C; Zink, Elizabeth; I Suarez, Jose
This proceedings article presents actionable research targets on the basis of the presentations and discussions at the 2nd Curing Coma National Institutes of Health (NIH) symposium held from May 3 to May 5, 2021. Here, we summarize the background, research priorities, panel discussions, and deliverables discussed during the symposium across six major domains related to disorders of consciousness. The six domains include (1) Biology of Coma, (2) Coma Database, (3) Neuroprognostication, (4) Care of Comatose Patients, (5) Early Clinical Trials, and (6) Long-term Recovery. Following the 1st Curing Coma NIH virtual symposium held on September 9 to September 10, 2020, six workgroups, each consisting of field experts in respective domains, were formed and tasked with identifying gaps and developing key priorities and deliverables to advance the mission of the Curing Coma Campaign. The highly interactive and inspiring presentations and panel discussions during the 3-day virtual NIH symposium identified several action items for the Curing Coma Campaign mission, which we summarize in this article.
PMID: 35534661
ISSN: 1556-0961
CID: 5214202

Endovascular Revascularization of Multi Segment Chronically Occluded ICA [Case Report]

Mulchan, Nicholas; Yeun, Phillip; Frontera, Jennifer; Farkas, Jeffrey; Berekashvili, Ketevan; Sanger, Matthew; Torres, Jose; Tiwari, Ambooj
This case report describes a novel endovascular method for treating chronically occluded internal carotid artery (COICA). The patient is a 55-year-old male with vascular risk factors who presented to an outside institution with right-sided weakness and dysarthria, was diagnosed as having a stroke, and discharged with medical management. The patient's symptoms failed to improve throughout the week prompting him to visit another outside institution, where computed tomography (CT) angiography showed bilateral occlusion of the ICAs at their origins extending intracranially. The patient was then transferred to our hospital, where head CT revealed bilateral acute infarcts predominantly in the left centrum ovale/corona radiata and left temporoparietal region. CT perfusion showed a large area of hypoperfusion in the entire left hemisphere as well as part of the right hemisphere (mismatch volume of 438-526 mL). The patient had significant neurological deficits despite sustained high perfusion pressure, so the following morning, the patient was taken for angiography showing complete occlusion of the left ICA with support mostly from the left external carotid artery (ECA)/ophthalmic collateralization. The microcatheter was able to be advanced to the level of the ophthalmic segment of the left ICA, so the decision was made to proceed with stenting from the left ophthalmic ICA to the cervical ICA. Seven consecutive coronary-carotid stents were placed to essentially reconstruct the left ICA. Post-stenting, the patient was treated with an Integrilin drip and transitioned to Aspirin and Brilinta the following morning. The patient's symptoms markedly improved after the procedure. CT perfusion, as well as diffusion magnetic resonance imaging (MRI), revealed recovery of the patient's penumbra and stability of the existing infarcts despite the delayed nature of revascularization respectively. This is a rarely reported study in literature describing the successful deployment of multiple stents in recreating the ICA from its extracranial to intracranial portion.
PMID: 35576859
ISSN: 1532-8511
CID: 5275882

Pre-admission antithrombotic use is associated with 3-month mRS score after thrombectomy for acute ischemic stroke

Krieger, Penina; Melmed, Kara R; Torres, Jose; Zhao, Amanda; Croll, Leah; Irvine, Hannah; Lord, Aaron; Ishida, Koto; Frontera, Jennifer; Lewis, Ariane
In patients who undergo thrombectomy for acute ischemic stroke, the relationship between pre-admission antithrombotic (anticoagulation or antiplatelet) use and both radiographic and functional outcome is not well understood. We sought to explore the relationship between pre-admission antithrombotic use in patients who underwent thrombectomy for acute ischemic stroke at two medical centers in New York City between December 2018 and November 2020. Analyses were performed using analysis of variance and Pearson's chi-squared tests. Of 234 patients in the analysis cohort, 65 (28%) were on anticoagulation, 64 (27%) were on antiplatelet, and 105 (45%) with no antithrombotic use pre-admission. 3-month Modified Rankin Scale (mRS) score of 3-6 was associated with pre-admission antithrombotic use (71% anticoagulation vs. 77% antiplatelet vs. 56% no antithrombotic, p = 0.04). There was no relationship between pre-admission antithrombotic use and Thrombolysis in Cerebral Iinfarction (TICI) score, post-procedure Alberta Stroke Program Early CT Score (ASPECTS) score, rate of hemorrhagic conversion, length of hospital admission, discharge NIH Stroke Scale (NIHSS), discharge mRS score, or mortality. When initial NIHSS score, post-procedure ASPECTS score, and age at admission were included in multivariate analysis, pre-admission antithrombotic use was still significantly associated with a 3-month mRS score of 3-6 (OR 2.36, 95% CI 1.03-5.54, p = 0.04). In this cohort of patients with acute ischemic stroke who underwent thrombectomy, pre-admission antithrombotic use was associated with 3-month mRS score, but no other measures of radiographic or functional outcome. Further research is needed on the relationship between use of specific anticoagulation or antiplatelet agents and outcome after acute ischemic stroke, but moreover, improve stroke prevention.
PMID: 35864280
ISSN: 1573-742x
CID: 5279342

Consensus Clinical Guidance for Diagnosis and Management of Adult COVID-19 Encephalopathy Patients

Michael, Benedict D; Walton, Dean; Westenberg, Erica; García-Azorín, David; Singh, Bhagteshwar; Tamborska, Arina A; Netravathi, M; Chomba, Mashina; Wood, Greta K; Easton, Ava; Siddiqi, Omar K; Jackson, Thomas A; Pollak, Thomas A; Nicholson, Timothy R; Nair, Shalini; Breen, Gerome; Prasad, Kameshwar; Thakur, Kiran T; Chou, Sherry H-Y; Schmutzhard, Erich; Frontera, Jennifer A; Helbok, Raimund; Padovani, Alessandro; Menon, David K; Solomon, Tom; Winkler, Andrea S
Encephalopathy, a common condition among patients hospitalized with COVID-19, can be a challenge to manage and negatively affect prognosis. While encephalopathy may present clinically as delirium, subsyndromal delirium, or coma and may be a result of systemic causes such as hypoxia, COVID-19 has also been associated with more prolonged encephalopathy due to less common but nevertheless severe complications, such as inflammation of the brain parenchyma (with or without cerebrovascular involvement), demyelination, or seizures, which may be disproportionate to COVID-19 severity and require specific management. Given the large number of patients hospitalized with severe acute respiratory syndrome coronavirus-2 infection, even these relatively unlikely complications are increasingly recognized and are particularly important because they require specific management. Therefore, the aim of this review is to provide pragmatic guidance on the management of COVID-19 encephalopathy through consensus agreement of the Global COVID-19 Neuro Research Coalition. A systematic literature search of MEDLINE, medRxiv, and bioRxiv was conducted between January 1, 2020, and June 21, 2021, with additional review of references cited within the identified bibliographies. A modified Delphi approach was then undertaken to develop recommendations, along with a parallel approach to score the strength of both the recommendations and the supporting evidence. This review presents analysis of contemporaneous evidence for the definition, epidemiology, and pathophysiology of COVID-19 encephalopathy and practical guidance for clinical assessment, investigation, and both acute and long-term management.
PMID: 35872617
ISSN: 1545-7222
CID: 5276142