Faculty Bibliography

COVID-19 is a highly infectious viral disease caused by the novel coronavirus SARS-CoV-2. While it was initially regarded as a strictly respiratory illness, the impact of COVID-19 on multiple organs is increasingly recognized. The brain is among the targets of COVID-19, and it can be impacted in multiple ways, both directly and indirectly. Direct brain infection by SARS-CoV-2 may occur via axonal transport via the olfactory nerve, eventually infecting the olfactory cortex and other structures in the temporal lobe, and potentially the brain stem. A hematogenous route, which involves viral crossing of blood-brain barrier, is also possible. Secondary mechanisms involve hypoxia due to respiratory failure, as well as aberrant immune response leading to various forms of encephalopathy, white matter damage, and abnormal blood clotting resulting in stroke. Multiple neurological symptoms of COVID-19 have been described. These involve anosmia/ageusia, headaches, seizures, mental confusion and delirium, and coma. There is a growing concern that in a number of patients, long-term or perhaps even permanent cognitive impairment will persist well after the recovery from acute illness. Furthermore, COVID-19 survivors may be at increased risk for developing neurodegenerative diseases years or decades later. Since COVID-19 is a new disease, it will take months or even years to characterize the exact nature, scope, and temporal extent of its long-term neurocognitive sequelae. To that end, rigorous and systematic longitudinal follow-up will be required. For this effort to succeed, appropriate protocols and patient registries should be developed and put in place without delay now.

BACKGROUND:The coronavirus disease 2019 (COVID-19) pandemic has severely affected ICUs and critical care health-care providers (HCPs) worldwide. RESEARCH QUESTION:How do regional differences and perceived lack of ICU resources affect critical care resource use and the well-being of HCPs? STUDY DESIGN AND METHODS:Between April 23 and May 7, 2020, we electronically administered a 41-question survey to interdisciplinary HCPs caring for patients critically ill with COVID-19. The survey was distributed via critical care societies, research networks, personal contacts, and social media portals. Responses were tabulated according to World Bank region. We performed multivariate log-binomial regression to assess factors associated with three main outcomes: limiting mechanical ventilation (MV), changes in CPR practices, and emotional distress and burnout. RESULTS:We included 2,700 respondents from 77 countries, including physicians (41%), nurses (40%), respiratory therapists (11%), and advanced practice providers (8%). The reported lack of ICU nurses was higher than that of intensivists (32% vs 15%). Limiting MV for patients with COVID-19 was reported by 16% of respondents, was lowest in North America (10%), and was associated with reduced ventilator availability (absolute risk reduction [ARR], 2.10; 95% CI, 1.61-2.74). Overall, 66% of respondents reported changes in CPR practices. Emotional distress or burnout was high across regions (52%, highest in North America) and associated with being female (mechanical ventilation, 1.16; 95% CI, 1.01-1.33), being a nurse (ARR, 1.31; 95% CI, 1.13-1.53), reporting a shortage of ICU nurses (ARR, 1.18; 95% CI, 1.05-1.33), reporting a shortage of powered air-purifying respirators (ARR, 1.30; 95% CI, 1.09-1.55), and experiencing poor communication from supervisors (ARR, 1.30; 95% CI, 1.16-1.46). INTERPRETATION:Our findings demonstrate variability in ICU resource availability and use worldwide. The high prevalence of provider burnout and its association with reported insufficient resources and poor communication from supervisors suggest a need for targeted interventions to support HCPs on the front lines.

Objective/UNASSIGNED:-related neurodevelopmental disorder in 33 individuals. Methods/UNASSIGNED:using American College of Medical Genetics and Genomics/Association of Molecular Pathology criteria, largely identified via clinical exome sequencing. Genetic reports were reviewed. Clinical data were collected by retrospective chart review and caregiver report including standardized parent report measures. Results/UNASSIGNED:-related disorders to include 33 individuals, aged 2-38 years, both females and males, with 11 different de novo missense variants, most within the nuclear localization signal. The major features of the phenotype include developmental delay/intellectual disability, severe language impairment, motor problems, growth, and musculoskeletal disturbances. Minor features include dysmorphic features, epilepsy, neuropsychiatric diagnoses such as autism spectrum disorder, and cortical visual impairment. Although rare, we report early stroke and premature death with this condition. Conclusions/UNASSIGNED:-related disorders continues to expand as the allelic spectrum and identification of affected males increases.

OBJECTIVE:To correlate intraoperative changes of the laryngeal adductor reflex (LAR), alone or in combination with corticobulbar motor evoked potential of vocal muscles (vocal-CoMEPs), with postoperative laryngeal function after posterior fossa and brainstem surgery. METHODS:We monitored 53 patients during cerebellar-pontine angle and brainstem surgeries. Vocal-CoMEPs and LAR were recorded from an endotracheal tube with imbedded electrodes or hook-wires electrodes. A LAR significant change (LAR-SC) defined as ≥ 50% amplitude decrement or loss, was classified as either transient or permanent injury to the vagus or medullary pathways by the end of the surgery. RESULTS:All patients with permanent LAR loss (n = 5) or LAR-SC (n = 3), developed postoperative laryngeal dysfunction such as aspiration/pneumonia and permanent swallowing deficits (5.6%). Vocal-CoMEP findings refined postoperative vocal motor dysfunction. All seven patients with transient LAR-SC or loss, reverted by changing the surgical approach, did not present permanent deficits. CONCLUSIONS:Permanent LAR-SCs or loss correlated with postoperative laryngeal dysfunction and predicted motor and sensory dysfunction of the vagus nerve and reflexive medullary pathways. In contrast, a LAR-SC or loss, averted by a timely surgical adjustment, prevented irreversible damage. SIGNIFICANCE/CONCLUSIONS:Monitoring of the LAR, with vocal-CoMEPs, may enhance safety to resect complex posterior fossa and brainstem lesions.

During the height of the pandemic in NYC (March-June 2020), the NYU Langone Health Lysosomal Storage Disorders (LSD) Program reached out to 183 patients to provide information on how to mitigate exposure to COVID19 and to ascertain who had been exposed and/or infected. 139 patients were successfully contacted. Recommendations on how to safely continue enzyme replacement therapy (ERT) or substrate reduction therapy (SRT) were provided. 135 of the 139 respondents during March 2020-June 2020 had Gaucher disease (GD). Twenty-six patients with GD endorsed 2 or more symptoms consistent with COVID19 infection and/or were confirmed to have COVID19 either through RT-PCR test for SARS-CoV-2 RNA or through antibodies to the virus. The remaining 4 who had suspected or confirmed COVID19 infection were patients with Fabry (2), Pompe (1), and Mucopolysaccharidosis Type IIIA (1). This case series describes the impact of COVID19 on 30 patients with LSDs with details of symptomatology, duration of illness, and treatment. Baseline demographics were collected including age, sex, genotype, current disease burden, LSD treatment history, biomarkers and co-morbidities. At time of infection, 21 patients were on ERT (20 GD, 1 PD), 3 on SRT for GD, and 6 were naive to therapy. There was only 1 hospitalization of a 55 year old woman with GD on ERT that resulted in ARDS who subsequently died due to SARS-CoV-2. Her co-morbidities included morbid obesity, COPD, hypertension and diabetes. Her GD burden was minimal. The rest of the affected patients had a mild to moderate COVID19 course. In conclusion, patients with LSDs experienced varied symptomatology and severity from COVID19 infection, ranging from asymptomatic to critically ill. Risk factors included baseline health status regardless of specific LSD, age, and associated co-morbidities. The sample is too small to make conclusions on specific impact of treatment status on COVID19 severity.-.
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BACKGROUND:Assays that specifically measure α-synuclein seeding activity in biological fluids could revolutionize the diagnosis of Parkinson's disease. Recent improvements in α-synuclein real-time quaking-induced conversion assays of cerebrospinal fluid have dramatically reduced reaction times from 5-13 days down to 1-2 days. OBJECTIVE:To test our improved assay against a panel of cerebrospinal fluid specimens from patients with Parkinson's disease and healthy controls from the MJ Fox Foundation/NINDS BioFIND collection. METHODS:Specimens collected from healthy controls and patients with clinically typical moderate-to-advanced Parkinson's disease were tested without prior knowledge of disease status. Correlative analyses between assay parameters and clinical measures were performed by an independent investigator. RESULTS:BioFIND samples gave positive signals in 105/108 (97%) Parkinson's disease cases versus 11/85 (13%) healthy controls. Receiver operating characteristic analyses of diagnosis of cases versus healthy controls gave areas under the curve of 95%. Beyond binary positive/negative determinations, only weak correlations were observed between various assay response parameters and Parkinson's disease clinical measures or other cerebrospinal fluid analytes. Of note, REM sleep behavioral disorder questionnaire scores correlated with the reaction times needed to reach 50% maximum fluorescence. Maximum fluorescence was inversely correlated with Unified Parkinson's Disease Rating Scale motor scores, which was driven by the patients without REM sleep behavioral disorder. CONCLUSIONS:Our improved α-synuclein seed amplification assay dramatically reduces the time needed to diagnose Parkinson's disease while maintaining the high-performance standards associated with previous α-synuclein seed assays, supporting the clinical utility of this assay for Parkinson's disease diagnosis.