Faculty Bibliography

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.

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.

The COVID-19 pandemic dramatically affected the operations of New York City hospitals during March and April of 2020. This article describes the transformation of a neurology division at a 450-bed tertiary care hospital in a multi-ethnic community in Brooklyn during this initial wave of COVID-19. In lieu of a mass redeployment of staff to internal medicine teams, we report a novel method for a neurology division to participate in a hospital's expansion of care for patients with COVID-19 while maintaining existing team structures and their inherent supervisory and interpersonal support mechanisms.

OBJECTIVE: To determine the impact of therapeutic infusion of IV immunoglobulin (IVIg) on John Cunningham virus antibody (JCV Ab) serostatus and level in serum. METHODS: We carried out a retrospective analysis of serum levels of JCV Ab among STRATIFY-2 trial enrollees from 2 multiple sclerosis centers who were exposed to IVIg during the trial. For the subset of eligible patients, we estimated mean linear trends while on IVIg and after stopping IVIg with a linear mixed-effects model. RESULTS: The JCV Ab seropositivity rate in the group of patients that was recently exposed to IVIg was 100%, which is significantly higher than in the IVIg-naive population (58%, p < 0.001). The seropositivity rate in the patient group with remote IVIg exposure was similar to that in the IVIg-naive population (67%, p = 0.68, Fisher exact test). The slope of the linear trend line after stopping IVIg decreased significantly by -0.310 units per 100 days (95% confidence interval, -0.611 to -0.008; p = 0.04). CONCLUSIONS: Recent IVIg exposure is invariably associated with JCV Ab seropositivity. After stopping IVIg, JCV Ab levels tend to decrease with time, and seroreversion to innately Ab-negative status can occur.

Objective. To compare periventricular lesions in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOsd). Materials and Methods. Sagittal and axial fluid attenuated inversion recovery (FLAIR) sequences of 20 NMOsd and 40 group frequency-matched MS patients were evaluated by two neuroradiologists. On axial FLAIR, periventricular area was characterized as free of lesions/smooth-bordered ("type A") or jagged-bordered ("type B") pattern. On sagittal FLAIR, the images were evaluated for presence of "Dawson's fingers." Results. Type A pattern was observed in 80% of NMOsd patients by Reader 1 and 85% by Reader 2 but only in 5% MS patients by either Reader. Type B was seen in 15% NMOsd patients by Reader 1 and 20% by Reader 2 and in 95% MS patients by either Reader. Dawson's fingers were observed in no NMOsd patients by Reader 1 and 5% by Reader 2. In MS, Dawson's fingers were seen in 92.5% patients by Reader 1 and 77.5% by Reader 2. The differences in periventricular patterns and Dawson's finger detection between NMOsd and MS were highly significant (P < 0.001). Conclusions. Dawson's fingers and "jagged-bordered" periventricular hyperintensities are typical of MS and almost never seen in NMOsd, which suggests a practical method for differentiating the two diseases.

Background: Sound lateralization is dependent upon precise timing of neuronal discharges in the auditory brainstem. Slowed processing speed in auditory brainstem pathways interferes with MS patients' ability to lateralize sound. A test of sound lateralization may be useful for detecting subtle brainstem deficits even among minimally impaired MS subjects. Objective: To determine whether a test of sound lateralization may be more sensitive to differences between controls and minimally impaired MS subjects than standard cognitive tasks. Design/Methods: 16 healthy controls and 45 MS subjects were recruited. Patients were divided into three disability strata: No Disability (Expanded Disability Status Scale (EDSS) =0; N=15), Mild Disability (EDSS=1 to 3.5; N=17), and Moderate Disability (EDSS=4 to 6.5; N=13). Using an interleaved staircase method, the interaural time difference (ITD) to a dichotically presented 910 Hz tone burst was varied to determine ITD thresholds for the tone localized just to the right or just to the left of center. Two standard tests used to assess processing speed, the Paced Auditory Serial Addition Test (PASAT3 and PASAT2) and the Symbol Digit Modalities Test (SDMT), were also administered. Results: Right and left threshold ITDs were averaged to provide a deviation score for each subject. The mean threshold ITD score was lowest for controls (M=196.9 mus, SD=76.4), increased for the No and Mild Disability groups (M=280.7 mus, SD=77.5 and M=268.8 mus, SD=105.3, respectively), and was greatest for the Moderate Disability group ( M=342.3 mus, SD=62.2). A MANOVA showed highly significant effects for IDT (p<.001, eta2=.28) and for the three other dependent variables (PASAT3, p<0.02; eta2=.23; PASAT2, p<.01, eta2=.18; SDMT, p<.001, eta2=.30). However, post hoc analysis showed that only the IDT test was sensitive to differences between controls and each MS group including, most importantly, the No Disability group(p<0.02). Conclusions: In our study, sound localization was the only te!

Objective: To test the utility of a backward masking task for assessing speed of processing in Multiple Sclerosis (MS) on a millisecond scale. Background: Slowed speed of processing is a central component of cognitive impairment in patients with MS. Standard methods of assessing speed of processing, such as the Processing Speed Index, Symbol Digit Modalities Test, or the Paced Auditory Serial Addition Test provide a global measure of processing speed, but do not capture more subtle changes that might occur in the millisecond range. In the present study, we used a backward masking paradigm, in which the stimulus to be reported is followed by a masking pattern. A longer interstimulus interval (ISI) needed to correctly identify the primary stimulus is indicative of slower processing speed and the ISIs producing backward masking would be expected to occur in the range of less than 100 milliseconds. Method/Design: 11 healthy controls and 42 MS patients with scores on the Expanded Disability Status Scale (EDSS) ranging from 0 to 6.5 were recruited for the study. Stimuli consisted of 4 to 6 lower-case- letter words presented on a computer screen. The stimulus word was followed by a mask of upper-case letters forming a nonsense word. The letters of the mask overlay the stimulus word. The ISI between the stimulus word and mask was increased in increments of 5 milliseconds (msec) until the subject was unable to report the word correctly. At that point, 5 iterations of the staircase method were presented to zero in on the threshold ISI. Results: A regression analysis with EDSS as the independent variable and Backward Masking ISI threshold as the dependent measure showed that EDSS was a significant predictor of ISI threshold (unstandardized coefficient B=7.51, t(51)=4.58, p<.001). EDSS also accounted for a significant amount of the variance in ISI scores (R2=.28, F(1,51)=20.96, p<.001). ISI thresholds ranged from an average of 45 msec for controls to an average of 115 msec for EDSS of 6.5. The slope (B) in!