Faculty Bibliography

OBJECTIVES/OBJECTIVE:We report a case of immune myopathy with perimysial pathology associated with anti-glycyl-transfer RNA synthetase (anti-EJ) antibody and an excellent treatment response. METHODS:Chart review. RESULTS:A 36-year-old woman presented with 3 months of fatigue, weight loss, progressive weakness in a scapuloperoneal distribution, and dysphagia. Nerve conduction studies, electromyography, and ultrasound suggested an irritable myopathy. She had marked elevations of creatine kinase and positive anti-glycyl-transfer RNA synthetase (anti-EJ) antibodies. A left biceps muscle biopsy revealed inflammation of the perimysium and surrounding perimysial blood vessels with focal fragmentation of the perimysium. Further evaluation revealed interstitial lung disease. Treatment with prednisone and mycophenolate mofetil led to marked clinical improvement of her symptoms. CONCLUSIONS:Our case adds to the growing spectrum of inflammatory myopathies and highlights the importance of performing a comprehensive, multisystem workup.

The autonomic nervous system (ANS) plays a complex role in the regulation of the immune system, with generally inhibitory effects via activation of β-adrenergic receptors on immune cells. We hypothesized that HIV-associated autonomic neuropathy (HIV-AN) would result in immune hyperresponsiveness which could be depicted using network analyses. Forty-two adults with well-controlled HIV underwent autonomic testing to yield the Composite Autonomic Severity Score (CASS). The observed range of CASS was 2-5, consistent with normal to moderate HIV-AN. To construct the networks, participants were divided into 4 groups based on the CASS (i.e., 2, 3, 4 or 5). Forty-four blood-based immune markers were included as nodes in all networks and the connections (i.e., edges) between pairs of nodes were determined by their bivariate Spearman's Rank Correlation Coefficient. Four centrality measures (strength, closeness, betweenness and expected influence) were calculated for each node in each network. The median value of each centrality measure across all nodes in each network was calculated as a quantitative representation of network complexity. Graphical representation of the four networks revealed greater complexity with increasing HIV-AN severity. This was confirmed by significant differences in the median value of all four centrality measures across the networks (p ≤ 0.025 for each). Among people with HIV, HIV-AN is associated with stronger and more numerous positive correlations between blood-based immune markers. Findings from this secondary analysis can be used to generate hypotheses for future studies investigating HIV-AN as a mechanism contributing to the chronic immune activation observed in HIV.

BACKGROUND AND OBJECTIVES/UNASSIGNED:HIV-associated autonomic neuropathy (HIV-AN) is common; however, its clinical effect is unclear. Previously, it was shown that the composite autonomic severity score is associated with markers of morbidity such as the Veterans Affair Cohort Study index. In addition, it is known that cardiovascular autonomic neuropathy due to diabetes is associated with poor cardiovascular outcomes. This study aimed to evaluate whether HIV-AN is predictive of important adverse clinical outcomes. METHOD/UNASSIGNED:The electronic medical records of HIV-infected participants who underwent autonomic function tests at the Mount Sinai Hospital between April 2011 and August 2012 were reviewed. The cohort was stratified into those who had no or mild autonomic neuropathy (HIV-AN [-], CASS ≤3) and those with moderate or severe autonomic neuropathy (HIV-AN [+], CASS >3). The primary outcome was a composite of the incidence of death from any cause, new major cardiovascular or cerebrovascular event, or development of severe renal or hepatic disease. Time-to-event analysis was performed using Kaplan-Meier analysis and multivariate Cox proportional hazards regression models. RESULTS/UNASSIGNED:One hundred eleven of 114 participants had follow-up data (median follow-up for HIV-AN (-) was 94.00 months, and HIV-AN (+) was 81.29 months) and were included in the analysis. Participants were followed until March 1, 2020. The HIV-AN (+) group (N = 42) was significantly associated with the presence of hypertension, higher HIV-1 viral load, and more abnormal liver function. Seventeen (40.48%) events occurred in the HIV-AN (+) group, and 11 (15.94%) occurred in the HIV-AN (-) group. Six (14.29%) cardiac events occurred in the HIV-AN (+) group, whereas 1 (1.45%) occurred in the HIV-AN (-) group. The other subgroups of the composite outcome had a similar trend. The adjusted Cox proportional hazards model showed that the presence of HIV-AN predicted our composite outcome (HR 3.85, CI 1.61-9.20). DISCUSSION/UNASSIGNED:These findings suggest that HIV-AN is associated with the development of severe morbidity and mortality in people living with HIV. People living with HIV with autonomic neuropathy may benefit from closer cardiac, renal, and hepatic surveillance.

To identify autonomic neuropathy (AN) phenotypes, we used principal component analysis on data from participants (N = 209) who underwent standardized autonomic testing including quantitative sudomotor axon reflex testing, and heart rate and blood pressure at rest and during tilt, Valsalva, and standardized deep breathing. The analysis identified seven clusters: 1) normal, 2) hyperadrenergic features without AN, 3) mild AN with hyperadrenergic features, 4) moderate AN, 5) mild AN with hypoadrenergic features, 6) borderline AN with hypoadrenergic features, 7) mild balanced deficits across parasympathetic, sympathetic and sudomotor domains. These findings demonstrate a complex relationship between adrenergic and other aspects of autonomic function.

PURPOSE/OBJECTIVE:Resting heart rate variability (HRV) is an important biomarker linking mental health to cardiovascular outcomes. However, resting HRV is also impaired in autonomic neuropathy, a common and underdiagnosed complication of common medical conditions which is detected by testing autonomic reflexes. We sought to describe the relationship between autonomic reflex abnormalities and resting HRV, taking into consideration medical comorbidities and demographic variables. METHODS:Participants (n = 209) underwent a standardized autonomic reflex screen which was summarized as the Composite Autonomic Severity Score (CASS) and included measures of reflexive HRV, e.g., heart rate with deep breathing (HRDB). Resting HRV measures were: pNN50 (percentage of NN intervals that differ by > 50 ms) and cvRMSSD (adjusted root mean square of successive differences). RESULTS:In univariate analyses, lower resting HRV was associated with: older age, higher CASS, neuropathy on examination, hypertension, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, and psychiatric disease. Adaptive regression spline analysis revealed that HRDB explained 27% of the variability in resting HRV for participants with values of HRDB in the normal range. Outside this range, there was no linear relationship because: (1) when HRDB was low (indicating autonomic neuropathy), resting HRV was also low with low variance; and (2) when HRDB was high, the variance in resting HRV was high. In multivariate models, only HRDB was significantly independently associated with cvRMSSD and pNN50. CONCLUSION/CONCLUSIONS:Subclinical autonomic neuropathy, as evidenced by low HRDB and other autonomic reflexes, should be considered as a potential confounder of resting HRV in research involving medically and demographically diverse populations.

A 38-year-old male presented with a three-week history of bilateral lower extremity choreiform movements. History included sleep abnormalities, rushed and unintelligible speech, with delusions two to six months prior to presentation. He also developed mild dysphagia, staring spells, and anterograde amnesia. On examination, he had pressured speech, asynchronous cycling movements of the bilateral lower extremities persisting during sleep, occasional ballistic movements of the upper extremities, and ataxia. Magnetic resonance imaging (MRI) of the brain showed high cortical signal change in bilateral parieto-occipital cortices with evidence of medullary olive hypertrophy bilaterally. Electroencephalography showed generalized slowing without periodic spikes. Cerebrospinal fluid was positive for protein 14-3-3 and real-time quaking-induced conversion. Genetic testing was positive for autosomal dominant prion protein gene (PRNP) genetic mutation. The patient passed away three months after discharge. This case provides previously undescribed imaging and movement abnormalities in a patient with familial Creutzfeldt-Jakob disease (CJD), and suggests that CJD should not be removed from the differential in patients with these atypical findings.

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.

INTRODUCTION/BACKGROUND:The coronavirus disease 2019 (Covid-19) pandemic has led to challenges in provision of care, clinical assessment and communication with families. The unique considerations associated with evaluation of catastrophic brain injury and death by neurologic criteria in patients with Covid-19 infection have not been examined. METHODS:We describe the evaluation of six patients hospitalized at a health network in New York City in April 2020 who had Covid-19, were comatose and had absent brainstem reflexes. RESULTS:Four males and two females with a median age of 58.5 (IQR 47-68) were evaluated for catastrophic brain injury due to stroke and/or global anoxic injury at a median of 14 days (IQR 13-18) after admission for acute respiratory failure due to Covid-19. All patients had hypotension requiring vasopressors and had been treated with sedative/narcotic drips for ventilator dyssynchrony. Among these patients, 5 had received paralytics. Apnea testing was performed for 1 patient due to the decision to withdraw treatment (n = 2), concern for inability to tolerate testing (n = 2) and observation of spontaneous respirations (n = 1). The apnea test was aborted due to hypoxia and hypotension. After ancillary testing, death was declared in three patients based on neurologic criteria and in three patients based on cardiopulmonary criteria (after withdrawal of support (n = 2) or cardiopulmonary arrest (n = 1)). A family member was able to visit 5/6 patients prior to cardiopulmonary arrest/discontinuation of organ support. CONCLUSION/CONCLUSIONS:It is feasible to evaluate patients with catastrophic brain injury and declare brain death despite the Covid-19 pandemic, but this requires unique considerations.