Faculty Bibliography

BACKGROUND:Asymmetric hemispheric loss of dopaminergic neurons is one of the characteristic features of Parkinson's disease (PD). However, it is still debated if right or left asymmetry differently affects cognitive and motor progression. OBJECTIVES/OBJECTIVE:The objective of this study was to investigate, for the first time, the relevance of dopamine transporter (DAT) asymmetry on cognitive and motor manifestations at onset and at 4-year progression in drug-naïve PD. METHODS:From the Parkinson's Progression Markers Initiative multicenter cohort, we identified 249 right-handed patients with PD with baseline asymmetry greater than 20% in putamen DAT binding at single-photon emission computed tomography. A predominant putamen asymmetry was found on the left in 143 patients (PD-left), and on the right side in 106 patients (PD-right); we compared them with 196 healthy controls. Patients were followed longitudinally (2-year and 4-year visits), examining their clinical, cognitive, and imaging data. RESULTS:At baseline, the PD-left group showed worse performance on the Symbol Digit Modality Test, an attention and processing-speed test, and lower cerebrospinal fluid β-amyloid levels than the PD-right group. These differences were maintained at follow-up, declining over time in both groups. By contrast, the PD-right group showed greater motor impairment at baseline, which increased over 4 years. Striatal DAT binding decreased over time in both groups, but the PD-right group showed a steeper decline, particularly during the first 2-year follow-up. Putaminal asymmetry assessed at baseline was maintained over time. CONCLUSIONS:These findings suggest that hemispheric asymmetric dopaminergic denervation influences PD cognitive and motor performance as well as progression. Predominant right hemisphere nigrostriatal dopaminergic loss is associated with greater motor severity, whereas more pronounced left hemisphere denervation affects cognitive manifestations at onset and their progression. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Traumatic brain injury (TBI) is one of the main causes of death worldwide. It is a complex injury that influences cellular physiology, causes neuronal cell death, and affects molecular pathways in the brain. This in turn can result in sensory, motor, and behavioral alterations that deeply impact the quality of life. Repetitive mild TBI can progress into chronic traumatic encephalopathy (CTE), a neurodegenerative condition linked to severe behavioral changes. While current animal models of TBI and CTE such as rodents, are useful to explore affected pathways, clinical findings therein have rarely translated into clinical applications, possibly because of the many morphofunctional differences between the model animals and humans. It is therefore important to complement these studies with alternative animal models that may better replicate the individuality of human TBI. Comparative studies in animals with naturally evolved brain protection such as bighorn sheep, woodpeckers, and whales, may provide preventive applications in humans. The advantages of an in-depth study of these unconventional animals are threefold. First, to increase knowledge of the often-understudied species in question; second, to improve common animal models based on the study of their extreme counterparts; and finally, to tap into a source of biological inspiration for comparative studies and translational applications in humans.

The COVID-19 pandemic has had an unprecedented impact on people and healthcare services. The disruption to chronic illnesses, such as epilepsy, may relate to several factors ranging from direct infection to secondary effects from healthcare reorganization and social distancing measures.

Background and aims: Routine examinations for patients with stroke include clinical assessment using the National Institute of Health Stroke Scale (NIHSS). Although this score accurately predicts the outcome of stroke, the NIHSS is weighted for anterior circulation. No reliable clinical assessment tool has been established for predicting the functional outcome of posterior circulation ischemic stroke. We aimed to develop a stroke scale based on clinical assessment that can increase the yield of detection of posterior circulation ischemic strokes in acute settings, the Langone Augmented Posterior-fossa Stroke Scale (LAPSS).
Method(s): A retrospective, dual campus, single center record review of patients that have been diagnosed with posterior fossa circulation strokes between 12/2018-11 /2019 will be conducted. We will catalog the presenting symptoms, calculate their prevalence, and use this information to adjust the current proposed LAPSS. The validity of the LAPSS will then be tested by retrospectively applying it to all patients that presented with symptoms of posterior fossa ischemic strokes.
Result(s): We project 120 patients will fit the inclusion criteria. The sensitivity, specificity, positive predictive value, and negative predictive value of LAPSS will be calculated. Inter-rater reliability will be assessed using ANOVA to define an intraclass correlation coefficient. Primary clinical outcome in patients with suspected posterior fossa stroke will be independent functional outcome (mRS 2).
Conclusion(s): The NIHSS has been shown to detect <60% of posterior circulation strokes in previous studies. We anticipate that the LAPSS will increase the sensitivity of the NIHSS to increase the overall yield of detection of posterior circulation strokes.
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Background: Although a more aggressive disease course has been reported in African-American (AA) patients with multiple sclerosis (MS) in comparison with Caucasian (CA) patients, differences in disability outcomes might be partly related to socioeconomic factors limiting access to cure or influencing lifestyle choices.
Aim(s): To assess the impact of demographics, socioeconomic status and comorbidities on disability differences between AA and CA MS patients.
Method(s): As part of an ongoing longitudinal study, 120 MS patients (60 AA, 60 CA) and 82 HC (43 AA, 39 CA) were prospectively enrolled. All subjects included in the study self-identified as AA or CA. Data on demographic, socioeconomic and clinical status of all subjects were collected. Differences in disability scales between AA and CA MS patients were assessed via ordinal logistic or multivariable linear regression, as appropriate, entering in the final model demographic features (age, gender), indirect indicators of socioeconomic status (educational level, body mass index) and comorbidities.
Result(s): No difference in disease management (diagnostic delay, number of therapeutic switches, treatment with first or second line disease modifying therapies) was present between the two groups. No differences in strength, sensitivity, balance and verbal fluency were detected between AA and CA MS patients. Differences in Expanded Disability Status Scale, walking endurance and verbal memory disappeared in the models including socioeconomic status and comorbidities. On the contrary, even in complex models accounting for confounders, AA showed higher Multiple Sclerosis Severity Score (3.17 vs 1.96, p=0.017), worse manual dexterity (9-hole peg test 25.34 vs 22.44, p=0.005; grooved pegboard test 12.65 vs 15.02, p=0.001; finger tapping test non dominant hand 48.53 vs 52.94, p=0.009), and worse cognitive performance in the attentional, visuospatial and executive domains (symbol digit modality test 50.82 vs 56.78, p=0.014; multitasking test 3.93 vs 5.13, p=0.002; brief visuospatial memory test 16.43 vs 20.90, p<0.001; Stroop test 37.76 vs 44.29, p=0.020).
Conclusion(s): AA patients with MS present a more severe disability status than CA patients. Observed differences are only partly accounted for by sociodemographic factors

BACKGROUND:To enhance knowledge about religious objections to brain death/death by neurologic criteria (BD/DNC), we surveyed hospital chaplains about their experience with and beliefs about BD/DNC. METHODS:We distributed an online survey to five chaplaincy organizations between February and July 2019. RESULTS:There were 512 respondents from all regions of the USA; they were predominantly Christian (450 of 497; 91%), board certified (413 of 490; 84%), and employed by community hospitals (309 of 511; 61%). Half (274 of 508; 56%) of the respondents had been involved in a case in which a family objected to BD/DNC on the basis of their religious beliefs. In 20% of cases involving a religious objection, the patient was Buddhist, Hindu, Jewish, or Muslim. Most respondents believed that a person who is declared brain dead in accordance with the American Academy of Neurology standard is dead (427 of 510; 84%). A minority of respondents believed that a family should be able to choose whether an assessment for determination of BD/DNC is performed (81 of 512; 16%) or whether organ support is discontinued after BD/DNC (154 of 510; 30%). These beliefs were all significantly related to lack of awareness that BD/DNC is the medical and legal equivalent of cardiopulmonary death throughout the USA and that organ support is routinely discontinued after BD/DNC, outside of organ donation. CONCLUSIONS:Hospital chaplains, who work at the intersection between religion and medicine, commonly encounter religious objections to BD/DNC. To prepare them for these situations, they should receive additional education about BD/DNC and management of religious objections to BD/DNC.

BACKGROUND:Infusion therapy refers to the intravenous administration of medicines and fluids for the treatment of status migrainosus, severe persistent headaches, or chronic headache. Headache practices and centers offer this treatment for patients as an alternative to the emergency department (ED) setting. However, little information is available in the literature on understanding the operations of an infusion center. OBJECTIVE:We sought to survey the Inpatient Headache & Emergency Medicine specialty section and the Academic Program Directors listserv of the American Headache Society (AHS) to better understand current practices. METHODS:A survey was advertised and distributed to the listservs of both the Inpatient Headache & Emergency Medicine specialty section and the Academic Program Directors, which combined included both academic and private practices. In addition, the survey was available on laptops at related events at an annual AHS meeting in Scottsdale. RESULTS:Of the 127 members of the combined group of both listservs, 50 responded with an overall survey response rate of 39%. Ten out of fifty were from programs with more than one responder completing the survey, leaving 40 unique headache programs. Academic programs made up the majority of programs (85%, 34/40). The total of 40 participating programs is comparable with the 47 academic headache programs listed on the American Migraine Foundation website at the time of the survey. Of the academic programs surveyed, most were hospital based (n = 23) compared with a satellite location (n = 11). Of all programs surveyed, 68% (27/40) offered infusion therapy. Of those that did not have an infusion practice (n = 13), the most common reason cited was insufficient staffing (n = 8). Key highlights of the survey included the following: The majority of programs offering infusions obtain prior authorization before scheduling (70%, 19/27) and offer patient availability 5 days/week (78%, 21/27) typically only during business hours (81%, 22/27). Programs reported that they typically give three to four medications during each infusion session (72%, 18/25). Treatment paradigms varied between programs. Programs surveyed were concentrated in the Northeast and Midwest regions of the United States. CONCLUSION/CONCLUSIONS:The limited number of headache infusion centers overall may contribute to the limited ability of headache infusion centers to prevent ED migraine visits. Headache patients can have unpredictable headache onset, and most of the infusion practices surveyed appeared to adapt to this by offering infusions most days during a work week. However, this need for multiple days per week may also explain the most common reason for not having an infusion practice, which is insufficient staffing. Various treatment paradigms are implemented by different practitioners, and future studies will have to focus on investigation of best practice.

PURPOSE:This study characterizes the association of risk factors including race, ethnicity, and insurance status with presenting visual acuity (VA) and diabetic retinopathy (DR) severity in patients initiating treatment with anti-vascular endothelial growth factor (VEGF) therapy for diabetic macular edema (DME). DESIGN:Retrospective, cross-sectional study. PARTICIPANTS:The Academy Intelligent Research in Sight (IRIS) Registry database was queried for patients who initiated anti-VEGF injection treatment for DME between 2012 and 2020 (n = 203 707). METHODS:Multivariate regression analyses were conducted to understand how race, ethnicity, insurance status, and geographic location were associated with baseline features. MAIN OUTCOME MEASURES:Visual acuity and DR severity. RESULTS:Patients on Medicare and private insurance presented with higher baseline VA compared with patients on Medicaid (median of 2.31 and 4.17 greater Early Treatment Diabetic Retinopathy Scale [ETDRS] letters, respectively P < 0.01). White and non-Hispanic patients presented with better VA compared with their counterparts (median of 0.68 and 2.53 greater ETDRS letters, respectively; P < 0.01). Black and Hispanic patients presented with a worse baseline DR severity compared with White and non-Hispanic patients (odds ratio, 1.23 and 1.71, respectively; P < 0.01). CONCLUSIONS:There are ethnic and insurance-based disparities in VA and disease severity upon initiation of anti-VEGF therapy for DME treatment. Public health initiatives could improve timely initiation of treatment.

Background: Ocrelizumab (OCR), a humanized, anti-CD20 antibody therapy for multiple sclerosis (MS), is given at 6-month intervals. Some patients on OCR report worsening of MS-related symptoms in the weeks leading up to their infusion ('wearing-off' phenomena), but there are no published reports quantifying symptom variation in relation to the timing of OCR infusions.
Objective(s): We will measure symptom burden using SymptoMScreen, NeuroQol and WPAI:MS at 3 points in each infusion cycle over 2 infusion cycles and also obtain Ocrelizumab concentration (PK), neurofilament light chain (NfL), B-cell subsets, and routine clinical labs prior to each infusion.
Aim(s): To quantitate change in symptom burden throughout the infusion cycle in OCR-treated MS patients and to determine which clinical and paraclinical variables correlate with symptom worsening.
Method(s): Prospective, observational, two-center study enrolled patients with relapsing and progressive forms of MS that are initiating OCR or who have been on OCR for >= 1 year (ClinicalTrials. gov Identifier: NCT04855617). All patients receive MS care at NYU MS Care Center (NYU) in New York, NY, or the Elliot Lewis MS Center for MS (ELC) in Wellesley, MA. Patients aged 18-80 and with EDSS scores between 0-7 are eligible for enrollment.
Result(s): 110 participants were enrolled and are actively followed in the study (55 from NYU/55 from ELC). At baseline visit, the mean age was 46.0+/-12.7 years; 64.6% were female; 31.8% were non-White; 20.0% were Hispanic/ Latino; disease duration was 12.6+/-9.6 years; OCR treatment duration was 2.8+/-1.0 years; mean EDSS was 3.3+/-2.1 (EDSS<4, n=69 (62.7%), EDSS>=4, n=41 (37.3%)). Breakdown by disease subtypes was: relapsing-remitting, n=68 (61.8%), secondary progressive, n=24 (21.8%), primary progressive, n=18 (16.4%). Among 58 patients who completed at least 2 questionnaires to date, the symptom burden, as assessed with the SymptoMScreen, was unchanged from week 4 post-infusion to week 12 post-infusion (p-values ranged from 0.2-0.9 for each of the 11 individual domains by Wilcoxon nonparametric test).
Conclusion(s): SymBOLS, designed to assess for the wearing-off effect in OCR-treated patients, has successfully enrolled 110 patients across two US sites. Preliminary data suggest there are no changes to symptom burden during the first half of the infusion cycle. Additional data regarding changes during the second half of the cycle as well as NeuroQoL and work productivity (WPAI) data will be presented

OBJECTIVE:Pituitary carcinoma is a rare tumor, defined as a tumor of adenohypophyseal cells with systemic or craniospinal metastasis. We present a case of a growth hormone (GH)-secreting pituitary carcinoma with a review of literature to better characterize this disease. DESIGN:Case report and literature review of 25 cases of GH-secreting pituitary carcinomas RESULTS: The age of diagnosis of GH-secreting carcinomas ranged 24-69 years old with a mean age of 44.4 with 52% of cases present in females. Mean latency period between diagnosis of acromegaly and transition to pituitary carcinoma was 11.4 years with mean survival being 3.4 years. CONCLUSION:Growth hormone (GH)-secreting pituitary carcinomas are rare and hard to distinguish from aggressive pituitary adenomas. From review of literature, treatment options include debulking surgery, radiotherapy, or chemotherapy with dismal outcomes. There are no diagnostic markers or features which can predict metastatic progression of these tumors. Future studies with genomic landscapes and relevant tumor markers are needed to identify pituitary tumors most likely to metastasize.