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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

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

A prospective study of long-term outcomes among hospitalized COVID-19 patients with and without neurological complications

Frontera, Jennifer A; Yang, Dixon; Lewis, Ariane; Patel, Palak; Medicherla, Chaitanya; Arena, Vito; Fang, Taolin; Andino, Andres; Snyder, Thomas; Madhavan, Maya; Gratch, Daniel; Fuchs, Benjamin; Dessy, Alexa; Canizares, Melanie; Jauregui, Ruben; Thomas, Betsy; Bauman, Kristie; Olivera, Anlys; Bhagat, Dhristie; Sonson, Michael; Park, George; Stainman, Rebecca; Sunwoo, Brian; Talmasov, Daniel; Tamimi, Michael; Zhu, Yingrong; Rosenthal, Jonathan; Dygert, Levi; Ristic, Milan; Ishii, Haruki; Valdes, Eduard; Omari, Mirza; Gurin, Lindsey; Huang, Joshua; Czeisler, Barry M; Kahn, D Ethan; Zhou, Ting; Lin, Jessica; Lord, Aaron S; Melmed, Kara; Meropol, Sharon; Troxel, Andrea B; Petkova, Eva; Wisniewski, Thomas; Balcer, Laura; Morrison, Chris; Yaghi, Shadi; Galetta, Steven
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.
PMID: 34000678
ISSN: 1878-5883
CID: 4876752

Decompressive Hemicraniectomy for Large Hemispheric Strokes

Lin, Jessica; Frontera, Jennifer A
Large hemispheric infarcts occur in up to 10% of all ischemic strokes and can cause devastating disability. Significant research and clinical efforts have been made in hopes of mitigating the morbidity and mortality of this disease. Areas of interest include identifying predictors of malignant edema, optimizing medical and surgical techniques, selecting the patient population that would benefit most from decompressive hemicraniectomy, and studying the impact on quality of life of those who survive. Decompressive surgery can be a life-saving measure, and here we discuss the most up-to-date literature and provide a review on the surgical management of large hemispheric ischemic strokes.
PMID: 33719518
ISSN: 1524-4628
CID: 4850982

Prevalence and Predictors of Prolonged Cognitive and Psychological Symptoms Following COVID-19 in the United States

Frontera, Jennifer A; Lewis, Ariane; Melmed, Kara; Lin, Jessica; Kondziella, Daniel; Helbok, Raimund; Yaghi, Shadi; Meropol, Sharon; Wisniewski, Thomas; Balcer, Laura; Galetta, Steven L
Background/Objectives/UNASSIGNED:Little is known regarding the prevalence and predictors of prolonged cognitive and psychological symptoms of COVID-19 among community-dwellers. We aimed to quantitatively measure self-reported metrics of fatigue, cognitive dysfunction, anxiety, depression, and sleep and identify factors associated with these metrics among United States residents with or without COVID-19. Methods/UNASSIGNED:We solicited 1000 adult United States residents for an online survey conducted February 3-5, 2021 utilizing a commercial crowdsourcing community research platform. The platform curates eligible participants to approximate United States demographics by age, sex, and race proportions. COVID-19 was diagnosed by laboratory testing and/or by exposure to a known positive contact with subsequent typical symptoms. Prolonged COVID-19 was self-reported and coded for those with symptoms ≥ 1 month following initial diagnosis. The primary outcomes were NIH PROMIS/Neuro-QoL short-form T-scores for fatigue, cognitive dysfunction, anxiety, depression, and sleep compared among those with prolonged COVID-19 symptoms, COVID-19 without prolonged symptoms and COVID-19 negative subjects. Multivariable backwards step-wise logistic regression models were constructed to predict abnormal Neuro-QoL metrics. Results/UNASSIGNED:= 0.047), but there were no significant differences in quantitative measures of anxiety, depression, fatigue, or sleep. Conclusion/UNASSIGNED:Prolonged symptoms occurred in 25% of COVID-19 positive participants, and NeuroQoL cognitive dysfunction scores were significantly worse among COVID-19 positive subjects, even after accounting for demographic and stressor covariates. Fatigue, anxiety, depression, and sleep scores did not differ between COVID-19 positive and negative respondents.
PMID: 34349633
ISSN: 1663-4365
CID: 5005972

Corticoreticulospinal tract neurophysiology in healthy and chronic stroke subjects [Meeting Abstract]

Taga, M; Charalambous, C C; Raju, S; Lin, J; Stern, E; Schambra, H M
Background: The corticoreticulospinal tract (CReST) is a major descending motor pathway in humans, but little is known about its relative innervation of proximal versus distal upper extremity (UE) muscles. In addition, CReST is believed to reorganize after corticospinal injury, but changes in its projections to different paretic muscles remain unknown. Here, we used transcranial magnetic stimulation (TMS) to probe the functional connectivity of the contralesional CReST to an arm muscle (biceps (BIC)) and an intrinsic hand muscle (first dorsal interosseous (FDI)) in healthy and stroke subjects.
Method(s): In this cross-sectional observational study, we examined 15 healthy (F: 7; mean age: 54 (44-81) years; mean UE Fugl-Meyer Assessment (FMA) score: 65 (63-66)) and 16 chronic stroke subjects (F: 10; mean age 62 (44-85) years; mean UE FMA score: 49 (23-64); mean time since stroke: 5 (0.5-14.4) years). We applied TMS to the contralesional hemisphere (assigned in healthy subjects) to elicit ipsilateral motor evoked potentials (iMEPs). We measured contralesional CReST functional connectivity (iMEP presence/absence) and projection strength (iMEP size; mV*ms) to the paretic BIC and FDI. We also measured paretic muscle maximum voluntary contraction and segmental FMA subscores. We examined differences in CReST projections between muscles and subject groups using Fisher's exact tests and general linear mixed models, and examined neurophysiologicalbehavioral relationships with Pearson's and Spearman's correlations.
Result(s): The contralesional CReST made functional connections to both muscles of most subjects (iMEP presence/absence: healthy BIC 14/1, healthy FDI 15/0; stroke BIC 11/5, stroke FDI 15/1). CReST functional connectivity did not differ between muscles in either healthy or stroke subjects (all p>0.172), and did not differ between subject groups for either muscle (all p=1.0). However, CReST projection strength for the muscles diverged between subject groups, manifesting as larger iMEPs in FDIs than BICs in healthy subjects (1.9 mV*ms, p=0.042) and larger iMEPs in BICs than FDIs in stroke subjects (1.0 mV*ms, p=0.042). Muscle iMEP sizes did not significantly differ between healthy and stroke subjects. Muscle strength related to iMEP size in only the paretic BIC of stroke subjects (r(6)=0.853, p=0.007). There was no relationship between FMA subscores and iMEP size for either muscle in either subject group.
Conclusion(s): Our findings indicate that the contralesional CReST has readily identifiable connections to the paretic BIC and FDI. In healthy subjects, the identification of a stronger CReST projection strength to the FDI challenges the notion of a proximal innervation bias by the reticulospinal tract. The shift in projection strength to the BIC after stroke reinforces the concept that the CReST reorganizes after CST injury, with circumscribed behavioral relevance. To confirm a recovery role of the CReST, a longitudinal observation of recovering behavior relating to changing CReST neurophysiology is required.
ISSN: 1552-6844
CID: 5082532

Examining the relationship between motor control and abnormal synergies during arm and index finger movement in chronic stroke patients [Meeting Abstract]

Taga, M; Hong, Y N G; Charalambous, C C; Raju, S; Lin, J; Stern, E; Mazzoni, P; Roh, J; Schambra, H M
Introduction: With the corticospinal tract (CST), the corticoreticulospinal tract (CReST) is a major descending motor pathway with widespread bilateral innervation. In animals, CST damage causes a loss of motor control and prompts reorganization in the CReST, possibly with stronger connectivity to arm flexors (e.g. biceps (BIC)) than finger abductors (e.g. first dorsal interosseous (FDI)). CReST reorganization may also contribute to widespread muscle co-activations (i.e. abnormal synergy expression) in the paretic upper extremity (UE). Here, we posited that CReST reorganization after stroke targets the BIC more than the FDI in humans. We predicted that CReST activity, manifesting as abnormal synergy expression, would be more strongly evoked by skilled arm flexion than finger abduction in stroke patients.
Method(s): We studied the paretic UE of 14 chronic stroke patients (F: 8; mean age: 64 (44-85) years; mean post-stroke time: 5 (0.5-14.4) years) and the matched UE of 14 healthy controls (F: 6; mean age: 55 (36-81) years). Subjects used their arm or index finger to move an onscreen cursor through an arc-shaped channel while the remainder of the UE was restrained.We recorded effector kinematics with an infrared camera and electromyographic (EMG) signals from triceps (TRI), deltoid (DLT), BIC, extensor digitorum, flexor carpi radialis (FCR), flexor digitorum superficialis (FDS), and FDI. To quantify movement error, we calculated the average radial distance between the cursor path and the outer channel edge. To quantify abnormal muscle synergies, we applied a non-negative matrix factorization algorithm to the EMG data to identify muscle synergies and calculated the similarity of the synergy vectors between patients and controls; higher similarity scores indicate more normal synergy patterns. We calculated muscle co-activations using correlations between EMG signals of each muscle-pair. We examined group differences with independent t-tests and control-synergy relationships with correlations.
Result(s): Movement errors were higher in patients than controls for the arm (p<0.01) and trended higher for the finger (p=0.074). In the arm, movement errors were inversely related to synergy similarity scores (p<0.01). Higher errors also related to greater FDI-FCR, BIC-TRI, BIC-DLT, and TRI-DLT coactivation (all p<0.05). In the finger, movement errors were unrelated to synergy similarity scores. Lower movement errors related to greater FDSTRI co-activation (p<0.05).
Discussion(s): In the arm, we found that as motor control worsened, the expression of abnormal synergies increased, indicating that CReST activation may increase with loss of CST function. Muscle co-activation was widespread in the UE, in keeping with CReST's multilevel spinal branching. We did not find a relationship between motor control and synergy expression with finger movement, although the long-range co-contraction between the FDS and TRI may speak to a CST-driven stabilizing strategy. Our findings strengthen the notion that CReST reorganization after stroke may preferentially target the arm flexor and its synergies.
ISSN: 1552-6844
CID: 5082542

Differences in Admission Blood Pressure Among Causes of Intracerebral Hemorrhage

Lin, Jessica; Piran, Pirouz; Lerario, Mackenzie P; Ong, Hanley; Gupta, Ajay; Murthy, Santosh B; Díaz, Iván; Stieg, Philip E; Knopman, Jared; Falcone, Guido J; Sheth, Kevin N; Fink, Matthew E; Merkler, Alexander E; Kamel, Hooman
Background and Purpose- It is unknown whether admission systolic blood pressure (SBP) differs among causes of intracerebral hemorrhage (ICH). We sought to elucidate an association between admission BP and ICH cause. Methods- We compared admission SBP across ICH causes among patients in the Cornell Acute Stroke Academic Registry, which includes all adults with ICH at our center from 2011 through 2017. Trained analysts prospectively collected demographics, comorbidities, and admission SBP, defined as the first recorded value in the emergency department or on transfer from another hospital. ICH cause was adjudicated by a panel of neurologists using the SMASH-U criteria. We used ANOVA to compare mean admission SBP among ICH causes. We used multiple linear regression to adjust for age, sex, race, Glasgow Coma Scale score, and hematoma size. In secondary analyses, we compared hourly SBP measurements during the first 72 hours after admission, using mixed-effects linear models adjusted for the covariates above plus antihypertensive agents. Results- Among 484 patients with ICH, admission SBP varied significantly across ICH causes, ranging from 138 (±24) mm Hg in those with structural vascular lesions to 167 (±35) mm Hg in those with hypertensive ICH (P<0.001). The mean admission SBP in hypertensive ICH was 17 (95% CI, 11-24) mm Hg higher than in ICH of all other causes combined. These differences remained significant after adjustment for age, sex, race, Glasgow Coma Scale score, and hematoma size (P<0.001), and this persisted throughout the first 72 hours of hospitalization (P<0.001). Conclusions- In a single-center ICH registry, SBP varied significantly among ICH causes, both on admission and during hospitalization. Our results suggest that BP in the acute post-ICH setting is at least partly associated with ICH cause rather than simply representing a physiological reaction to the ICH itself.
PMID: 31818231
ISSN: 1524-4628
CID: 4889742

Subacute Progressive Ptosis, Ophthalmoplegia, Gait Instability, and Cognitive Changes

Lin, Jessica; Pellinen, Jacob C; Galetta, Steven L
PMID: 29946691
ISSN: 2168-6157
CID: 3162872

Discontinuation of Postoperative Prophylactic Antibiotics After Noninstrumented Spinal Surgery: Results of a Quality Improvement Project

Lewis, Ariane; Lin, Jessica; James, Herbert; Hill, Travis C; Sen, Rajeev; Pacione, Donato
Background/UNASSIGNED:Numerous medical society guidelines recommend discontinuation of antibiotics at a maximum of 24 hours after noninstrumented spinal surgery, even when a drain is left in place. As a result of these recommendations, our institution's Neurosurgery Quality Improvement Committee decided to stop administering prolonged prophylactic systemic antibiotics (PPSAs) to patients with drains after noninstrumented spinal surgery. Methods/UNASSIGNED:We retrospectively reviewed data for patients who had noninstrumented spinal surgery performed by a neurosurgeon at our institution between December 2012 and July 2014 (PPSA period) and December 2014 and July 2016 (non-PPSA period) and had a drain left in place postoperatively. In the PPSA period, patients received antibiotics until drain removal. In the non-PPSA period, patients received antibiotics for a maximum of 24 hours. Results/UNASSIGNED:= .24). Conclusion/UNASSIGNED:After discontinuing PPSAs for patients with noninstrumented spinal procedures, as is recommended for quality improvement, we saw a nonsignificant increase in our rate of SSIs. Further monitoring of this population is warranted.
PMID: 29977443
ISSN: 1941-8744
CID: 3185882