Faculty Bibliography

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.

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.

BACKGROUND:Persistent cognitive symptoms have been reported following COVID-19 hospitalization. We investigated the relationship between demographics, social determinants of health (SDOH) and cognitive outcomes 6-months after hospitalization for COVID-19. METHODS:We analyzed 6-month follow-up data collected from a multi-center, prospective study of hospitalized COVID-19 patients. Demographic and SDOH variables (age, race/ethnicity, education, employment, health insurance status, median income, primary language, living arrangements, and pre-COVID disability) were compared between patients with normal versus abnormal telephone Montreal Cognitive Assessments (t-MOCA; scores<18/22). Multivariable logistic regression models were constructed to evaluate predictors of t-MoCA. RESULTS:Of 382 patients available for 6-month follow-up, 215 (56%) completed the t-MoCA (n = 109/215 [51%] had normal and n = 106/215 [49%] abnormal results). 14/215 (7%) patients had a prior history of dementia/cognitive impairment. Significant univariate predictors of abnormal t-MoCA included older age, ≤12 years of education, unemployment pre-COVID, Black race, and a pre-COVID history of cognitive impairment (all p < 0.05). In multivariable analyses, education ≤12 years (adjusted OR 5.21, 95%CI 2.25-12.09), Black race (aOR 5.54, 95%CI 2.25-13.66), and the interaction of baseline functional status and unemployment prior to hospitalization (aOR 3.98, 95%CI 1.23-12.92) were significantly associated with abnormal t-MoCA scores after adjusting for age, history of dementia, language, neurological complications, income and discharge disposition. CONCLUSIONS:Fewer years of education, Black race and unemployment with baseline disability were associated with abnormal t-MoCA scores 6-months post-hospitalization for COVID-19. These associations may be due to undiagnosed baseline cognitive dysfunction, implicit biases of the t-MoCA, other unmeasured SDOH or biological effects of SARS-CoV-2.

Background/UNASSIGNED:Prior to the COVID-19 pandemic, about half of patients from populations that sought care in neurology tried complementary and integrative therapies (CITs). With the increased utilization of telehealth services, we sought to determine whether patients also increased their use of virtual CITs. Methods/UNASSIGNED:We examined datasets from two separate cross-sectional surveys that included cohorts of patients with neurological disorders. One was a dataset from a study that examined patient and provider experiences with teleneurology visits; the other was a study that assessed patients with a history of COVID-19 infection who presented for neurologic evaluation. We assessed and reported the use of virtual (and non-virtual) CITs using descriptive statistics, and determined whether there were clinical characteristics that predicted the use of CITs using logistic regression analyses. Findings/UNASSIGNED:Patients who postponed medical treatment for non-COVID-19-related problems during the pandemic were more likely to seek CITs. Virtual exercise, virtual psychotherapy, and relaxation/meditation smartphone applications were the most frequent types of virtual CITs chosen by patients. In both studies, age was a key demographic factor associated with mobile/virtual CIT usage. Interpretations/UNASSIGNED:Our investigation demonstrates that virtual CIT-related technologies were utilized in the treatment of neurologic conditions during the pandemic, particularly by those patients who deferred non-COVID-related care.

One sentence summary: The purpose of this investigation was to expand the evidence base on CITs delivered by telehealth by evaluating CIT use in patients who presented to a large urban tertiary care neurology practice and to examine predictors of CIT use during the pandemic.
Background(s): Patients with neurological disorders may seek treatment options in addition to those recommended by their providers. Prior to the COVID-19 pandemic, about half of patients from populations that sought care in neurology tried complementary and integrative therapies (CITs). Given the reductions in in-person visits and the increases in teleneurology visits, we sought to determine whether patients increased their use of virtual complementary and integrative therapies.
Method(s): By examining two separate datasets that included cohorts of patients with neurological disorders, we assessed patients' use of virtual (and non-virtual) CITs and determined whether there were clinical characteristics that predicted their use. The two studies that comprised this report included one that examined patient and provider experiences with teleneurology visits, and another that assessed patients with a history of COVID-19 infection who presented for neurologic evaluation.
Result(s): Patients who postponed medical treatment for non-COVID- 19- related problems during the pandemic were more likely to seek CITs. Virtual exercise, virtual psychotherapy and relaxation/meditation smartphone applications were the most frequent types of virtual CITs chosen by patients. In both studies, age was a key demographic factor associated with mobile/ virtual CIT usage.
Conclusion(s): Data from our investigations demonstrated that, in addition to its other roles in teleneurology, CIT-related technologies might be utilized in the treatment of neurologic conditions

OBJECTIVE:To determine the prevalence and associated mortality of well-defined neurologic diagnoses among COVID-19 patients, we prospectively followed hospitalized SARS-Cov-2 positive patients and recorded new neurologic disorders and hospital outcomes. METHODS:We conducted a prospective, multi-center, observational study of consecutive hospitalized adults in the NYC metropolitan area with laboratory-confirmed SARS-CoV-2 infection. The prevalence of new neurologic disorders (as diagnosed by a neurologist) was recorded and in-hospital mortality and discharge disposition were compared between COVID-19 patients with and without neurologic disorders. RESULTS:Of 4,491 COVID-19 patients hospitalized during the study timeframe, 606 (13.5%) developed a new neurologic disorder in a median of 2 days from COVID-19 symptom onset. The most common diagnoses were: toxic/metabolic encephalopathy (6.8%), seizure (1.6%), stroke (1.9%), and hypoxic/ischemic injury (1.4%). No patient had meningitis/encephalitis, or myelopathy/myelitis referable to SARS-CoV-2 infection and 18/18 CSF specimens were RT-PCR negative for SARS-CoV-2. Patients with neurologic disorders were more often older, male, white, hypertensive, diabetic, intubated, and had higher sequential organ failure assessment (SOFA) scores (all P<0.05). After adjusting for age, sex, SOFA-scores, intubation, past history, medical complications, medications and comfort-care-status, COVID-19 patients with neurologic disorders had increased risk of in-hospital mortality (Hazard Ratio[HR] 1.38, 95% CI 1.17-1.62, P<0.001) and decreased likelihood of discharge home (HR 0.72, 95% CI 0.63-0.85, P<0.001). CONCLUSIONS:Neurologic disorders were detected in 13.5% of COVID-19 patients and were associated with increased risk of in-hospital mortality and decreased likelihood of discharge home. Many observed neurologic disorders may be sequelae of severe systemic illness.

Objective/UNASSIGNED:The study objective was to examine predictors of sleep disturbance and strain among caregivers of persons living with dementia (PLWD). Methods/UNASSIGNED:This cross-sectional study utilized a sample of community-dwelling older adults and their family caregivers drawn from the 2017 National Health and Aging Trends Study and National Study of Caregiving. Multivariable logistic regression was used to assess the association between caregiver and PLWD characteristics and a composite measure of caregiving strain. High caregiving strain was defined as a total score of ≥ 5 on the 6 caregiving strain items (e.g., emotional difficulty, no time for self). We used multivariable proportional odds models to examine predictors of caregiver sleep-related outcomes (trouble falling back to sleep and interrupted sleep), after adjusting for other caregiver and PLWD factors. Results/UNASSIGNED:Of the 1,142 family caregivers, 65.2% were female, 15% were Black, and 14% were Hispanic. Average age was 60 years old. Female caregivers were more likely to report high level of strain compared to male caregivers (OR: 2.61, 95% CI = 1.56, 4.39). Compared to non-Hispanic Whites, non-Hispanic Black and Hispanic caregivers had reduced odds of reporting greater trouble falling back asleep [OR = 0.55, CI (0.36, 0.82) and OR = 0.56, CI (0.34, 0.91), respectively]. The odds of reporting greater trouble falling back asleep was significantly greater among caregivers with high blood pressure vs. caregivers without high blood pressure [OR = 1.62, CI (1.12, 2.33)]. Conclusion/UNASSIGNED:In this cross-sectional study, caregivers with greater sleep difficulty (trouble falling back asleep) were more likely to report having high blood pressure. We found no racial/ethnic differences in interrupted sleep among caregivers to PLWD. These results suggest that interventions to improve sleep among caregivers to PLWD may decrease poor cardiovascular outcomes in this group.

OBJECTIVE:To investigate whether paresthesia of the lower extremities following exposure to the World Trade Center (WTC) disaster was associated with signs of neuropathy, metabolic abnormalities, or neurotoxin exposures. METHODS:Case-control study comparing WTC-exposed paresthesia cases with "clinic controls" (WTC-exposed subjects without paresthesias), and "community controls" (WTC-unexposed persons). RESULTS:Neurological histories and examination findings were significantly worse in cases than controls. Intraepidermal nerve fiber densities were below normal in 47% of cases and sural to radial sensory nerve amplitude ratios were less than 0.4 in 29.4%. Neurologic abnormalities were uncommon among WTC-unexposed community controls. Metabolic conditions and neurotoxin exposures did not differ among groups. CONCLUSIONS:Paresthesias among WTC-exposed individuals were associated with signs of neuropathy, small and large fiber disease. The data support WTC-related exposures as risk factors for neuropathy, and do not support non-WTC etiologies.

We examined whether time to onset of paresthesia was associated with indicators of severity of World Trade Center (WTC) exposure. We analyzed data from 3411 patients from the Bellevue Hospital-WTC Environmental Health Center. Paresthesia was defined as present if the symptom occurred in the lower extremities with frequency "often" or "almost continuous." We plotted hazard functions and used the log-rank test to compare time to onset of paresthesia between different exposure groups. We also used Cox regression analysis to examine risk factors for time-to-paresthesia after 9/11/2001 and calculate hazard ratios adjusted for potential confounders. We found significantly elevated hazard ratios for paresthesia for (a) working in a job that required cleaning of WTC dust in the workplace; and (b) being heavily exposed to WTC dust on September 11, 2001, after adjusting for age, race/ethnicity, depression, anxiety, post-traumatic stress disorder, and body mass index. These observational data are consistent with the hypothesis that exposure to WTC dust or some other aspect of cleaning WTC dust in the workplace, is associated with neuropathy and paresthesia. Further neurological evaluations of this and other WTC-exposed populations is warranted.

BACKGROUND:Case reports suggest there may be an association between celiac disease (CD) and myasthenia gravis (MG). METHODS:We identified 29,086 individuals with CD in Sweden from 1969 to 2008. We compared these individuals with 144,480 matched controls. Hazard ratios (HRs) for future MG (identified through ICD codes) were estimated using Cox regression. RESULTS:During 326,376 person-years of follow-up in CD patients, there were 7 MG cases (21/million person-years) compared to 22 MG cases in controls during 1,642,273 years of follow-up (14/million person-years) corresponding to a HR of 1.48 (95% CI = 0.64-3.41). HRs did not differ when stratifying for age, sex or calendar period. HRs were highest in the first year after follow-up, though insignificant. Individuals with CD were at no increased risk of MG more than 5 years after CD diagnosis (HR = 0.70; 95% CI = 0.16-3.09). CONCLUSION/CONCLUSIONS:This study found no increased risk of MG in patients with CD.