Faculty Bibliography

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.

We reviewed the literature on cerebrospinal fluid (CSF) studies in patients who had a seizure in the setting of COVID-19 infection to evaluate for evidence of viral neuroinvasion. We performed a systematic review of Medline and Embase to identify publications that reported one or more patients with COVID-19 who had a seizure and had CSF testing preformed. The search ranged from December 1st 2019 to November 18th 2020. We identified 56 publications which described 69 unique patients who met our inclusion criteria. Of the 54 patients whose past medical history was provided, 2 (4%) had epilepsy and 1 (2%) had a prior seizure in the setting of hyperglycemia, but the remaining 51 (94%) had no history of seizures. Seizure was the initial symptom of COVID-19 for 15 (22%) patients. There were 26 (40%) patients who developed status epilepticus. SARS-CoV-2 PCR testing was performed in the CSF for 45 patients; 6 (13%) had a positive CSF SARS-CoV-2 PCR, only 1 (17%) of whom had status epilepticus. The cycle thresholds were not reported. Evaluation for CSF SARS-CoV-2 antibodies (directly or indirectly, via testing for CSF oligoclonal bands or immunoglobulins) was performed in 26 patients, only 2 (8%) of whom had evidence of intrathecal antibody synthesis. Of the 11 patients who had CSF autoimmune antibody panels tested, 1 had NMDA antibodies and 1 had Caspr-2 antibodies. Detection of SARS-CoV-2 in the CSF of patients with seizures who have COVID-19 is uncommon. Our review suggests that seizures in this patient population are not likely due to direct viral invasion of the brain.

When making decisions about goals-of-care for a patient who lacks decision-making capacity, surrogates sometimes have internal disagreements, particularly if there are complicated family dynamics. Here, I describe the evolution of end-of-life discussions for a patient who had a catastrophic stroke amongst a family who had preexisting discord.

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.

OBJECTIVES/OBJECTIVE:Systemic inflammatory response syndrome (SIRS) and hematoma expansion are independently associated with worse outcomes after intracerebral hemorrhage (ICH), but the relationship between SIRS and hematoma expansion remains unclear. MATERIALS AND METHODS/METHODS:We performed a retrospective review of patients admitted to our hospital from 2013 to 2020 with primary spontaneous ICH with at least two head CTs within the first 24 hours. The relationship between SIRS and hematoma expansion, defined as ≥6 mL or ≥33% growth between the first and second scan, was assessed using univariable and multivariable regression analysis. We assessed the relationship of hematoma expansion and SIRS on discharge mRS using mediation analysis. RESULTS:Of 149 patients with ICH, 83 (56%; mean age 67±16; 41% female) met inclusion criteria. Of those, 44 (53%) had SIRS. Admission systolic blood pressure (SBP), temperature, antiplatelet use, platelet count, initial hematoma volume and rates of infection did not differ between groups (all p>0.05). Hematoma expansion occurred in 15/83 (18%) patients, 12 (80%) of whom also had SIRS. SIRS was significantly associated with hematoma expansion (OR 4.5, 95% CI 1.16 - 17.39, p= 0.02) on univariable analysis. The association remained statistically significant after adjusting for admission SBP and initial hematoma volume (OR 5.72, 95% CI 1.40 - 23.41, p= 0.02). There was a significant indirect effect of SIRS on discharge mRS through hematoma expansion. A significantly greater percentage of patients with SIRS had mRS 4-6 at discharge (59 vs 33%, p=0.02). CONCLUSION/CONCLUSIONS:SIRS is associated with hematoma expansion of ICH within the first 24 hours, and hematoma expansion mediates the effect of SIRS on poor outcome.

BACKGROUND:Assessing the impact of coronavirus disease 2019 (COVID-19) on intensive care unit (ICU) providers' perceptions of resource availability and evaluating the factors associated with emotional distress/burnout can inform interventions to promote provider well-being. METHODS:Between 23 April and 7 May 2020, we electronically administered a survey to physicians, nurses, respiratory therapists (RTs), and advanced practice providers (APPs) caring for COVID-19 patients in the United States. We conducted a multivariate regression to assess associations between concerns, a reported lack of resources, and 3 outcomes: a primary outcome of emotional distress/burnout and 2 secondary outcomes of (1) fear that the hospital is unable to keep providers safe; and (2) concern about transmitting COVID-19 to their families/communities. RESULTS:We included 1651 respondents from all 50 states: 47% were nurses, 25% physicians, 17% RTs, and 11% APPs. Shortages of intensivists and ICU nurses were reported by 12% and 28% of providers, respectively. The largest supply restrictions reported were for powered air purifying respirators (56% reporting restricted availability). Provider concerns included worries about transmitting COVID-19 to their families/communities (66%), emotional distress/burnout (58%), and insufficient personal protective equipment (PPE; 40%). After adjustment, emotional distress/burnout was significantly associated with insufficient PPE access (adjusted relative risk [aRR], 1.43; 95% confidence interval [CI], 1.32-1.55), stigma from community (aRR, 1.32; 95% CI, 1.24-1.41), and poor communication with supervisors (aRR, 1.13; 95% CI, 1.06-1.21). Insufficient PPE access was the strongest predictor of feeling that the hospital is unable to keep providers safe and worries about transmitting infection to their families/communities. CONCLUSIONS:Addressing insufficient PPE access, poor communication from supervisors, and community stigma may improve provider mental well-being during the COVID-19 pandemic.

BACKGROUND/UNASSIGNED:There are multiple factors that may cause end-of-life conflict in the critical care setting. These include severe illness, family distress, lack of awareness about a patient's wishes, prognostic uncertainty, and the participation of multiple providers in goals-of-care discussions. METHODS/UNASSIGNED:Case report and discussion of the associated ethical issues. RESULTS/UNASSIGNED:We present a case of a patient with a pontine stroke, in which the family struggled with decision-making about goals-of-care, leading to fluctuation in code status from Full Code to Do Not Resuscitate-Comfort Care, then back to Full Code, and finally to Do Not Resuscitate-Do Not Intubate. We discuss factors that contributed to this situation and methods to avoid conflict. Additionally, we review the effects of discord at the end-of-life on patients, families, and the healthcare team. CONCLUSION/UNASSIGNED:It is imperative that healthcare teams proactively collaborate with families to minimize end-of-life conflict by emphasizing decision-making that prioritizes the best interest and autonomy of the patient.

BACKGROUND:Little is known regarding long-term outcomes of patients hospitalized with COVID-19. METHODS:We conducted a prospective study of 6-month outcomes of hospitalized COVID-19 patients. Patients with new neurological complications during hospitalization who survived were propensity score-matched to COVID-19 survivors without neurological complications hospitalized during the same period. The primary 6-month outcome was multivariable ordinal analysis of the modified Rankin Scale(mRS) comparing patients with or without neurological complications. Secondary outcomes included: activities of daily living (ADLs;Barthel Index), telephone Montreal Cognitive Assessment and Neuro-QoL batteries for anxiety, depression, fatigue and sleep. RESULTS:Of 606 COVID-19 patients with neurological complications, 395 survived hospitalization and were matched to 395 controls; N = 196 neurological patients and N = 186 controls completed follow-up. Overall, 346/382 (91%) patients had at least one abnormal outcome: 56% had limited ADLs, 50% impaired cognition, 47% could not return to work and 62% scored worse than average on ≥1 Neuro-QoL scale (worse anxiety 46%, sleep 38%, fatigue 36%, and depression 25%). In multivariable analysis, patients with neurological complications had worse 6-month mRS (median 4 vs. 3 among controls, adjusted OR 1.98, 95%CI 1.23-3.48, P = 0.02), worse ADLs (aOR 0.38, 95%CI 0.29-0.74, P = 0.01) and were less likely to return to work than controls (41% versus 64%, P = 0.04). Cognitive and Neuro-QOL metrics were similar between groups. CONCLUSIONS:Abnormalities in functional outcomes, ADLs, anxiety, depression and sleep occurred in over 90% of patients 6-months after hospitalization for COVID-19. In multivariable analysis, patients with neurological complications during index hospitalization had significantly worse 6-month functional outcomes than those without.