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Comparison of serum neurodegenerative biomarkers among hospitalized COVID-19 patients versus non-COVID subjects with normal cognition, mild cognitive impairment, or Alzheimer's dementia

Frontera, Jennifer A; Boutajangout, Allal; Masurkar, Arjun V; Betensky, Rebecca A; Ge, Yulin; Vedvyas, Alok; Debure, Ludovic; Moreira, Andre; Lewis, Ariane; Huang, Joshua; Thawani, Sujata; Balcer, Laura; Galetta, Steven; Wisniewski, Thomas
INTRODUCTION/BACKGROUND:Neurological complications among hospitalized COVID-19 patients may be associated with elevated neurodegenerative biomarkers. METHODS:Among hospitalized COVID-19 patients without a history of dementia (N = 251), we compared serum total tau (t-tau), phosphorylated tau-181 (p-tau181), glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCHL1), and amyloid beta (Aβ40,42) between patients with or without encephalopathy, in-hospital death versus survival, and discharge home versus other dispositions. COVID-19 patient biomarker levels were also compared to non-COVID cognitively normal, mild cognitive impairment (MCI), and Alzheimer's disease (AD) dementia controls (N = 161). RESULTS:Admission t-tau, p-tau181, GFAP, and NfL were significantly elevated in patients with encephalopathy and in those who died in-hospital, while t-tau, GFAP, and NfL were significantly lower in those discharged home. These markers correlated with severity of COVID illness. NfL, GFAP, and UCHL1 were higher in COVID patients than in non-COVID controls with MCI or AD. DISCUSSION/CONCLUSIONS:Neurodegenerative biomarkers were elevated to levels observed in AD dementia and associated with encephalopathy and worse outcomes among hospitalized COVID-19 patients.
PMID: 35023610
ISSN: 1552-5279
CID: 5116752

Editors' Note: Fish Intake and MRI Burden of Cerebrovascular Disease in Older Adults

Lewis, Ariane; Galetta, Steven
PMID: 35437268
ISSN: 1526-632x
CID: 5192422

Training in Neurology: Objective Structured Clinical Examination Case to Teach and Model Feedback Skills in Neurology Residency

LaRocque, Joshua J; Grossman, Scott; Kurzweil, Arielle M; Lewis, Ariane; Zabar, Sondra; Balcer, Laura; Galetta, Steven L; Zhang, Cen
We describe an educational intervention for neurology residents aimed at developing feedback skills. An objective structured clinical examination case was designed to simulate the provision of feedback to a medical student. After the simulated case session, residents received structured, individualized feedback on their performance and then participated in a group discussion about feedback methods. Survey data were collected from the standardized medical student regarding residents' performance and from residents for assessments of their performance and of the OSCE case. This manuscript aims to describe this educational intervention and to demonstrate the feasibility of this approach for feedback skills development.
PMID: 35169006
ISSN: 1526-632x
CID: 5163442

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; Hinson, H E; Olm-Shipman, Casey M; Da Silva, Ivan; Cervantes-Arslanian, Anna M; Carlson, Andrew P; Sivakumar, Sanjeev; Shah, Vishank A; Bonomo, Jordan B; Hatton, Kevin W; Kapinos, Gregory; Hughes, Christopher G; Rodríguez-Vega, Gloria M; Mainali, Shraddha; Chang, Cherylee W J; Dissin, Jonathan; Wang, Jing; Mailloux, Patrick T; Dhar, Rajat; Naik, Bhiken I; Sarwal, Aarti; Muehlschlegel, Susanne; Nobleza, Christa O'Hana S; Shapshak, Angela Hays; Wyler, David A; Latorre, Julius Gene S; Varelas, Panayiotis N; Ansari, Safdar A; Krishnamoorthy, Vijay; Rao, Shyam S; Ivan Da Silva, Demetrios J Kutsogiannis; Akbari, Yama; Rosenblatt, Kathryn; Roberts, Debra E; Kim, Jennifer A; Batra, Ayush; Srinivasan, Vasisht; Williamson, Craig A; Cai, Xuemei; George, Pravin; Pizzi, Michael A; Luk, K H Kevin; Berger, Karen; Babi, Marc-Alain; Hirsch, Karen G; Lay, Cappi C; Fontaine, Gabriel V; Lewis, Ariane; Lamer-Rosen, Amanda B; Kalanuria, Atul; Khawaja, Ayaz M; Rabinstein, Alejandro A; Andrews, Charles M; Badjatia, Neeraj; McDonagh, David L; Rajajee, Venkatakrishna; Dombrowski, Keith E; Daniels, Justin D; O'Phelan, Kristine H; Birrer, Kara L; Davis, Nicole C; Marino, Kaylee K; Li, Fanny; Sharma, Archit; Tesoro, Eljim P; Sadan, Ofer; Mehta, Yatin B; Boone, Myles Dustin; Barthol, Colleen; López Delgado, Hubiel J; Maricela, García Arellano; Mijangos-Mendez, Julio C; Lopez-Pulgarin, Jose A; Terrett, Luke A; Rigamonti, Andrea; Couillard, Philippe; Chassé, Michaël; Al-Jehani, Hosam M; Cunto, Eleonora R; Villalobos, Luis M; Rocchetti, Nicolás S; Aparicio, Gabriela; Domeniconi, Gustavo G; Gemelli, Nicolas A; Badano, Mariana F; Costilla, Cesar M; Caporal, Paula; Camerlingo, Sebastián; Balasini, Carina; López, Rossana G; Mario, Mauri; Ilutovich, Santiago A; Torresan, Gabriela V; Mazzola, Ana M; Daniela, E; Olmos, K; Maldonado, Roberto Mérida; La Fuente Zerain, Gustavo; Paiva, Wellingson Silva; Falcão, Antônio Eiras; Rojas, Salomón; Franco, Gilberto Paulo Pereira; Azevedo, Renata A; Kurtz, Pedro; Balbo, Flor G; Carreno, Jose N; Rubiano, Andres M; Ciro, Juan Diego; Zulma Urbina, C; Pinto, Diego Barahona; Gómez, Pedro César Gutiérrez; Castillo, L; Ranero, Jorge Luis; Apodaca, Julio C; Gómez Arriola, Natalia E; Reátegui, Rocío Nájar; Chumbe, Maria M; Rodriguez Tucto, Xandra Yanina; Davila Flores, Rafael E; Mora, Jacobo E; Al-Suwaidan, Faisal Abdulrahman; Abulhasan, Yasser B; Belay, Hanna Demissie; Kebede, Dawit K; Ewunetu, Mulugeta Biyadgie; Molla, Sisay; Tulu, Fitsum Alemu; Gebremariam, Senay A; Tibar, Houyam; Yimer, Fasika Tesfaneh; Farombi, Temitope Hannah; Xavier, Nshimiyimana Francios; Osman, Jama; Padayachy, Llewellyn C; Vander Laenen, Margot J; Breitenfeld, Tomislav; Takala, Riikka; Lasocki, Sigismond; Czorlich, Patrick; Poli, Sven; Neumann, Bernhard; Lochner, Piergiorgio; Menon, Sanjay; Wartenberg, Katja E; Wolf, Stefan; Etminan, Nima; Konczalla, Juergen; Schubert, Gerrit A; Wittstock, Matthias; Bösel, Julian; Robba, Chiara; De Cassai, Alessandro; Alampi, Daniela; Zugni, Nicola; Fuselli, Ennio; Bilotta, Federico; Stival, Eleonora; Castioni, Carlo Alberto; Tringali, Eleonora; Gelormini, Domenico; Dias, Celeste; Badenes, Rafael; Ramos-Gómez, Luis A; Llompart-Pou, Juan A; Tena, Susana Altaba; Merlani, Paolo; van den Bergh, Walter M; Hoedemaekers, Cornelia W; Abdo, Wilson F; van der Jagt, Mathieu; Gorbachov, Sergii; Dinsmore, J E; Reddy, Ugan; Tattum, L; Aneman, Anders; Rhodes, Jonathan K J; Sopheak, Pak; Jian, Song; Chan, Matthew Tv; Nagayama, Masao; Suzuki, Hidenori; Luthra, Ankur; Zirpe, Kapil G; Pratheema, R; Sethuraman, Manikandan; Tripathy, Swagata; Mahajan, Charu; Deb, Kallol; Gupta, Devendra; Gupta, Nidhi; Kapoor, Indu; Tandon, Monica S; Singhal, Vasudha; Parakh, Anil; Moningi, Srilata; Garg, Mudit; Sandhu, Kavita; Ali, Zulfiqar; Sharma, Vivek Bharti; Kumar, Subodh; Kumar, Prashant; Aggarwal, Deepesh G; Shukla, Urvi B; Dixit, Subhal; Nafissi, Shahriar; Mokhtari, Majid; Shrestha, Gentle S; Puvanendiran, Shanmugam; Sakchinabut, Sarunkorn; Kaewwinud, Jeerawat; Thirapattaraphan, Porntip; Petsakul, Suttasinee; Nuchpramool, Pruchwilai; Nitikaroon, Phongsak; Thaksin, Niyutta; Vongsfak, Jirapong; Sarapuddin, Gemmalynn B; Van Bui, Tuan; Seppelt, Oceania Ian M; Bhonagiri, Deepak; Winearls, James R; Flower, Oliver J; Westerlund, Torgeir A; Van Oosterwyck, Wout
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: 5326642

The Uniform Determination of Death Act is Being Revised

Lewis, Ariane
The Uniform Determination of Death Act (UDDA), the recommended legal statute for determination of death in the United States, was initially formulated in 1981. Forty years later, because of the concerns of experts in medicine, law, ethics, and philosophy, the Uniform Law Commission (ULC) created a drafting committee to update the UDDA. The drafting committee, which has until 2023 to propose revisions to the ULC Executive Committee, will need to determine how to address the following key questions about the UDDA: (1) Should the term "irreversible" be replaced by the term "permanent"? (2) Is absence of hypothalamic-pituitary-axis-induced antidiuretic hormone secretion included in "all functions of the entire brain," and if so, how can we reconcile the fact that this is not tested in the medical standards for determination of death by neurologic criteria published by the American Academy of Neurology and the Society of Critical Care Medicine, American Academy of Pediatrics, and Child Neurology Society? (3) What are the accepted medical standards for determination of death? (4) Is consent needed to determine death? and (5) How should objections to the use of neurologic criteria to declare death be handled? Once the ULC finalizes revisions to the UDDA, individual states will have the opportunity to decide whether to adopt the revisions in whole or in part. Hopefully, the revised UDDA will provide clarity and consistency about the legal distinction between life and death for physicians, lawyers, and the public at large. The events that led to the formation of the drafting committee and the potential consequences of revising the UDDA are discussed herein.
PMID: 35102538
ISSN: 1556-0961
CID: 5153472

Early Neurorehabilitation and Recovery from Disorders of Consciousness After Severe COVID-19

Gurin, Lindsey; Evangelist, Megan; Laverty, Patricia; Hanley, Kaitlin; Corcoran, John; Herbsman, Jodi; Im, Brian; Frontera, Jennifer; Flanagan, Steven; Galetta, Steven; Lewis, Ariane
BACKGROUND:Early neurorehabilitation improves outcomes in patients with disorders of consciousness (DoC) after brain injury, but its applicability in COVID-19 is unknown. We describe our experience implementing an early neurorehabilitation protocol for patients with COVID-19-associated DoC in the intensive care unit (ICU) and evaluate factors associated with recovery. METHODS:During the initial COVID-19 surge in New York City between March 10 and May 20, 2020, faced with a disproportionately high number of ICU patients with prolonged unresponsiveness, we developed and implemented an early neurorehabilitation protocol, applying standard practices from brain injury rehabilitation care to the ICU setting. Twenty-one patients with delayed recovery of consciousness after severe COVID-19 participated in a pilot early neurorehabilitation program that included serial Coma Recovery Scale-Revised (CRS-R) assessments, multimodal treatment, and access to clinicians specializing in brain injury medicine. We retrospectively compared clinical features of patients who did and did not recover to the minimally conscious state (MCS) or better, defined as a CRS-R total score (TS) ≥ 8, before discharge. We additionally examined factors associated with best CRS-R TS, last CRS-R TS, hospital length of stay, and time on mechanical ventilation. RESULTS:Patients underwent CRS-R assessments a median of six (interquartile range [IQR] 3-10) times before discharge, beginning a median of 48 days (IQR 40-55) from admission. Twelve (57%) patients recovered to MCS after a median of 8 days (IQR 2-14) off continuous sedation; they had lower body mass index (p = 0.009), lower peak serum C-reactive protein levels (p = 0.023), higher minimum arterial partial pressure of oxygen (p = 0.028), and earlier fentanyl discontinuation (p = 0.018). CRS-R scores fluctuated over time, and the best CRS-R TS was significantly higher than the last CRS-R TS (median 8 [IQR 5-23] vs. 5 [IQR 3-18], p = 0.002). Earlier fentanyl (p = 0.001) and neuromuscular blockade (p = 0.015) discontinuation correlated with a higher last CRS-R TS. CONCLUSIONS:More than half of our cohort of patients with prolonged unresponsiveness following severe COVID-19 recovered to MCS or better before hospital discharge, achieving a clinical benchmark known to have relatively favorable long-term prognostic implications in DoC of other etiologies. Hypoxia, systemic inflammation, sedation, and neuromuscular blockade may impact diagnostic assessment and prognosis, and fluctuations in level of consciousness make serial assessments essential. Early neurorehabilitation of these patients in the ICU can be accomplished but is associated with unique challenges. Further research should evaluate factors associated with longer-term neurologic recovery and benefits of early rehabilitation in patients with severe COVID-19.
PMCID:8491764
PMID: 34611810
ISSN: 1556-0961
CID: 5067712

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

Revise the UDDA to Align the Law with Practice through Neuro-Respiratory Criteria

Omelianchuk, Adam; Bernat, James; Caplan, Art; Greer, David; Lazaridis, Christos; Lewis, Ariane; Pope, Thaddeus; Ross, Lainie Friedman; Magnus, David
Although the Uniform Determination of Death Act (UDDA) has served as a model statute for 40 years, there is a growing recognition that the law must be updated. One issue being considered by the Uniform Law Commission's Drafting Committee to revise the UDDA is whether the text "all functions of the entire brain, including the brainstem" should be changed. Some argue that the absence of diabetes insipidus indicates that some brain functioning continues in many individuals who otherwise meet the "accepted medical standards" like the American Academy of Neurology's. The concern is that the legal criteria and the medical standards used to determine death by neurological criteria are not aligned. We argue for the revision of the UDDA to more accurately specify legal criteria which align with the medical standards: brain injury leading to permanent loss of a) the capacity for consciousness, b) the ability to breathe spontaneously, and c) brainstem reflexes. We term these criteria "neuro-respiratory criteria" and show that they are well-supported in the literature for physiological and social reasons justifying their use in the law.
PMID: 35078943
ISSN: 1526-632x
CID: 5154492

Strengths and Weaknesses of the Research Enterprise During the Pandemic

Lewis, Ariane
PMID: 35500235
ISSN: 1536-5166
CID: 5215942

A thematic analysis of a survey of hospital chaplains on death by neurologic criteria

Kitamura, Elizabeth; Lewis, Ariane
INTRODUCTION/UNASSIGNED:Little is known about chaplains' views on brain death/death by neurologic criteria (BD/DNC). Thematic analysis of comments made by hospital chaplains about BD/DNC can illuminate their perspectives on working with patients, families, and interdisciplinary teams during assessment for BD/DNC. MATERIALS AND METHODS/UNASSIGNED:In an electronic survey distributed to members of five chaplaincy organizations between February and July 2019, we elicited free-text comments about BD/DNC. We performed a thematic analysis of the comments. RESULTS/UNASSIGNED:Four themes were present: (1) definition of life and death, (2) respect with a subtheme of physician obligation, (3) collaboration with a subtheme of communication, and (4) education with a subtheme of scepticism. CONCLUSIONS/UNASSIGNED:Hospital chaplains are essential members of the interdisciplinary team involved in BD/DNC evaluation. They aim to ensure the interaction between families and the interdisciplinary team at the boundary of life and death and the intersection between religion and medicine is respectful, collaborative, and educational.
PMID: 35189776
ISSN: 1528-6916
CID: 5172032