Faculty Bibliography

The novel coronavirus, COVID-19, changed the world within a matter of weeks. The primary action to constrain the spread of the virus is social isolation. Given this public health principle, and the shortage of personal protective equipment during the global pandemic, all health care stakeholders need to reconsider the indications for face-to-face health care encounters in providing patient care. Which encounters are imperative and which ones can be switched to non-face-to-face care? What changes in laws, regulations, payment policies and workflow are needed to enable this transition? (1,2,3).

PURPOSE OF REVIEW/OBJECTIVE:Glioblastoma (GBM) is the most common malignant primary brain tumor, and the available treatment options are limited. This article reviews the recent preclinical and clinical investigations that seek to expand the repertoire of effective medical and radiotherapy options for GBM. RECENT FINDINGS/RESULTS:Recent phase III trials evaluating checkpoint inhibition did not result in significant survival benefit. Select vaccine strategies have yielded promising results in early phase clinical studies and warrant further validation. Various targeted therapies are being explored but have yet to see breakthrough results. In addition, novel radiotherapy approaches are in development to maximize safe dose delivery. A multitude of preclinical and clinical studies in GBM explore promising immunotherapies, targeted agents, and novel radiation modalities. Recent phase III trial failures have once more highlighted the profound tumor heterogeneity and diverse resistance mechanisms of glioblastoma. This calls for the development of biomarker-driven and personalized treatment approaches.

BACKGROUND AND PURPOSE/OBJECTIVE:With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke. However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19. METHODS:We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic. We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls). In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls). RESULTS:<0.001). When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels. When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate. Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls. CONCLUSIONS:We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19. Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased. Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.

The medial temporal lobe (MTL) is traditionally considered to be a system that is specialized for long-term memory. Recent work has challenged this notion by demonstrating that this region can contribute to many domains of cognition beyond long-term memory, including perception and attention. One potential reason why the MTL (and hippocampus specifically) contributes broadly to cognition is that it contains relational representations-representations of multidimensional features of experience and their unique relationship to one another-that are useful in many different cognitive domains. Here, we explore the hypothesis that the hippocampus/MTL plays a critical role in attention and perception via relational representations. We compared human participants with MTL damage to healthy age- and education-matched individuals on attention tasks that varied in relational processing demands. On each trial, participants viewed two images (rooms with paintings). On "similar room" trials, they judged whether the rooms had the same spatial layout from a different perspective. On "similar art" trials, they judged whether the paintings could have been painted by the same artist. On "identical" trials, participants simply had to detect identical paintings or rooms. Patients were significantly and selectively impaired on the similar room task. This work provides further evidence that the hippocampus/MTL plays a ubiquitous role in cognition by virtue of its relational and spatial representations and highlights its important contributions to rapid perceptual processes that benefit from attention.

OBJECTIVE:To investigate the incidence and spectrum of neuroimaging findings and their prognostic role in hospitalized COVID-19 patients in New York City. METHODS:This is a retrospective cohort study of 3218 COVID-19 confirmed patients admitted to a major healthcare system (three hospitals) in New York City between March 1, 2020 and April 13, 2020. Clinical data were extracted from electronic medical records, and particularly data of all neurological symptoms were extracted from the imaging reports. Four neuroradiologists evaluated all neuroimaging studies for acute neuroimaging findings related to COVID-19. RESULTS:14.1% of admitted COVID-19 patients had neuroimaging and this accounted for only 5.5% of the total imaging studies. Acute stroke was the most common finding on neuro-imaging, seen in 92.5% of patients with positive neuro-imaging studies, and present in 1.1% of hospitalized COVID-19 patients. Patients with acute large ischemic and hemorrhagic stroke had much higher mortality risk adjusted for age, BMI and hypertension compared to those COVID-19 patients without neuroimaging. (Odds Ratio 6.02 by LR; Hazard Ratio 2.28 by CRR). CONCLUSIONS:Our study demonstrates acute stroke is the most common neuroimaging finding among hospitalized COVID-19 patients. Detection of an acute stroke is a strong prognostic marker of poor outcome. Our study also highlights the fact there is limited use of neuroimaging in these patients due to multiple logistical constraints.

OBJECTIVE:To update the 2016 American Academy of Neurology (AAN) practice advisory for patients with stroke and patent foramen ovale (PFO). METHODS:The guideline panel followed the AAN 2017 guideline development process to systematically review studies published through December 2017 and formulate recommendations. MAJOR RECOMMENDATIONS/UNASSIGNED:In patients being considered for PFO closure, clinicians should ensure that an appropriately thorough evaluation has been performed to rule out alternative mechanisms of stroke (level B). In patients with a higher risk alternative mechanism of stroke identified, clinicians should not routinely recommend PFO closure (level B). Clinicians should counsel patients that having a PFO is common; that it occurs in about 1 in 4 adults in the general population; that it is difficult to determine with certainty whether their PFO caused their stroke; and that PFO closure probably reduces recurrent stroke risk in select patients (level B). In patients younger than 60 years with a PFO and embolic-appearing infarct and no other mechanism of stroke identified, clinicians may recommend closure following a discussion of potential benefits (absolute recurrent stroke risk reduction of 3.4% at 5 years) and risks (periprocedural complication rate of 3.9% and increased absolute rate of non-periprocedural atrial fibrillation of 0.33% per year) (level C). In patients who opt to receive medical therapy alone without PFO closure, clinicians may recommend an antiplatelet medication such as aspirin or anticoagulation (level C).

INTRODUCTION/BACKGROUND:In addition to neurogenic orthostatic hypotension (nOH), patients with synucleinopathies frequently have hypertension when supine. The long-term consequences of both abnormalities are difficult to disentangle. We aimed to determine if supine hypertension is associated with target organ damage and worse survival in patients with nOH. METHODS:Patients with nOH due to multiple system atrophy (MSA), Parkinson disease (PD), or pure autonomic failure (PAF) were classified into those with or without supine hypertension (systolic BP of at least 140 mmHg or diastolic BP of at least 90 mmHg). Organ damage was assessed by measuring cerebral white matter hyperintensities (WMH), left ventricular hypertrophy (LVH), and renal function. We prospectively followed patients for 30 months (range: 12-66 months) and recorded incident cardiovascular events and all-cause mortality. RESULTS:Fifty-seven patients (35 with probable MSA, 14 with PD and 8 with PAF) completed all evaluations. In addition to nOH (average fall 35 ± 21/17 ± 14 mmHg, systolic/diastolic, mean ± SD), 38 patients (67%) had supine hypertension (systolic BP > 140 mmHg). Compared to those without hypertension, patients with hypertension had higher blood urea nitrogen levels (P = 0.005), lower estimated glomerular filtration rate (P = 0.008), higher prevalence of LVH (P = 0.040), and higher WMH volume (P = 0.019). Longitudinal follow-up of patients for over 2 years (27.1 ± 14.5 months) showed that supine hypertension was independently associated with earlier incidence of cardiovascular events and death (HR = 0.25; P = 0.039). CONCLUSIONS:Supine hypertension in patients with nOH was associated with an increased risk for target organ damage, cardiovascular events, and premature death. Defining management strategies and safe blood pressure ranges in patients with nOH remains an important research question.

Caregivers of individuals with intellectual and developmental disabilities and epilepsy such as Dravet syndrome (DS) must navigate a complex web of state and community services through the transition from child-centered to adult-oriented healthcare. This study examined barriers to successful transition from the caregivers' perspective. Primary caregivers of teenagers or adults with DS who had contemplated or completed transition to adult care were eligible. A three-week, asynchronous, web-based focus group was conducted on Facebook. Data were analyzed in an iterative process based on a Grounded Theory approach. Participants reviewed findings for accuracy. Transition success was defined by how well it ensured adequate care for the child when caregivers became unable to provide it. Existing transition programs were described as "not for our kids." All caregivers reported that transition programs began too late. Challenges to identifying suitable providers were formidable, with 71% of adult patients still being seen by pediatric neurologists. Many adult physicians lacked a general knowledge of DS, yet caregivers perceived that adult physicians were unwilling to listen to caregivers, and few were comfortable accommodating patients with intellectual disabilities and challenging behaviors. Community programs often excluded patients with DS, and rural healthcare disparities created additional barriers. Analysis produced recommendations for improving the transition process including the creation of a certified Transition Navigator position in the clinical setting. The limitations of this focus group analysis include possible selection bias, but our study identified key issues and pathways to improve the transition process for patients with DS and their caregivers.