Faculty Bibliography

Fluoxetine is a selective serotonin reuptake inhibitor (SSRI) that reduces obsessive-compulsive symptoms. There is limited evidence supporting its efficacy for repetitive behaviors (RRBs) in autistic spectrum disorder (ASD). We conducted a randomized controlled trial (RCT) of fluoxetine in 158 individuals with ASD (5-17 years). Following 14 treatment weeks (mean dose 11.8 mg/day), no significant differences were noted on the Children's Yale-Brown Obsessive Compulsive Scale; the proportion of responders was similar (fluoxetine: 36%; placebo: 41%). There were similar rates of AEs (e.g., insomnia, diarrhea, vomiting); high rates of activation were reported in both groups (fluoxetine: 42%; placebo: 45%). Overly cautious dosing/duration may have prevented attainment of a therapeutic level. Results are consistent with other SSRI RCTs treating RRBs in ASD.Trial Registration: clinicaltrials.gov Identifier: NCT00515320.

Attention is thought to be the gateway between information and learning, yet there is much we do not understand about how students pay attention in the classroom. Leveraging ideas from cognitive neuroscience and psychology, we explore a framework for understanding attention in the classroom, organized along two key dimensions: internal/external attention and on-topic/off-topic attention. This framework helps us to build new theories for why active-learning strategies are effective teaching tools and how synchronized brain activity across students in a classroom may support learning. These ideas suggest new ways of thinking about how attention functions in the classroom and how different approaches to the same active-learning strategy may vary in how effectively they direct students' attention. We hypothesize that some teaching approaches are more effective than others because they leverage natural fluctuations in students' attention. We conclude by discussing implications for teaching and opportunities for future research.

Objective: To study the rate of progression of multiple system atrophy (MSA) and assess for a potential ceiling effect of the Unified Multiple System Atrophy Rating Scale (UMSARS).
Background(s): Disease progression of MSA as measured by UMSARS varied significantly in natural history studies. Reported 1-year UMSARS-1 and UMSARS-2 progression rates ranged from 3.9 to 6.5 and 3.5 to 8.2 respectively. We hypothesize that this variability is due, at least in part, to differences in severity at enrollment and a potential ceiling effect in the scale, so that patients in more advanced stages may appear to worsen less, which would have important implications for clinical trial design.
Method(s): We analyzed the rate of change in the UMSARS in a large international cohort of well-characterized patients with a clinical diagnosis of possible or probable MSA enrolled in the Natural History Study of Synucleinopathies. Annualized progression rates were obtained using 2-year follow-up data.
Result(s): Three hundred and forty nine patients (61.4+/-7.9 years old) with MSA were enrolled. Disease duration was 4.5+/-5.1 years. 143 patients completed 1-year evaluations and 61 completed the 2-year evaluation. The 12-month progression rates were 5.4+/-5.1 for the UMSARS-I, 5.9+/-5.3 for the UMSARS-II, and 11.8+/-9.6 for the total score. The 24-month progression rates were 10.8+/-7.3 for the UMSARS-I, 12.2+/-7.9 for the UMSARSII, and 22.6+/-13.7 for the total score. Annualized progression rates were divided according to their baseline UMSARS-I and UMSARS II. There was a significant (p = 0.0153) inverse relationship between rate of progression and UMSARS-I at baseline. A similar, but not significant trend was observed with UMSARS-II at baseline.
Conclusion(s): The rate of progression as measured by UMSARS is influenced by the baseline disease severity. A possible ceiling effect should be considered when planning enrollment, power calculations, and outcome measures in clinical trials

The correlation of clinical semiology with neuronal firing in human seizures has not been well described. Similarly, the neuronal firing patterns underlying high-frequency oscillations during seizures remain controversial. Using implanted subdural electrodes and a microelectrode array in a patient with focal status epilepticus, in which 40 habitual focal motor seizures and 101 subclinical seizures were captured, the authors analyzed the association of EEG, high-frequency oscillations, and multiunit activity to facial motor semiology. The development of ictal high-frequency oscillations in subdural electrodes overlying face motor cortex was temporally associated with clonic facial movements. In representative seizures selected for multiunit analysis, synchronization of neuronal firing in the adjacent microelectrode array aligned with clinical onset and was greater in clinical seizures compared with subclinical seizures. This report demonstrates the electrophysiologic signatures of focal seizures at the level of neuronal firing, high-frequency oscillations, and EEG as they organize from microscale to macroscale, with clinical correlation.

Recent case-series of small size implied a pathophysiological association between coronavirus disease 2019 (COVID-19) and severe large-vessel acute ischemic stroke. Given that severe strokes are typically associated with poor prognosis and can be very efficiently treated with recanalization techniques, confirmation of this putative association is urgently warranted in a large representative patient cohort to alert stroke clinicians, and inform pre- and in-hospital acute stroke patient pathways. We pooled all consecutive patients hospitalized with laboratory-confirmed COVID-19 and acute ischemic stroke in 28 sites from 16 countries. To assess whether stroke severity and outcomes (assessed at discharge or at the latest assessment for those patients still hospitalized) in patients with acute ischemic stroke are different between patients with COVID-19 and non-COVID-19, we performed 1:1 propensity score matching analyses of our COVID-19 patients with non-COVID-19 patients registered in the Acute Stroke Registry and Analysis of Lausanne Registry between 2003 and 2019. Between January 27, 2020, and May 19, 2020, 174 patients (median age 71.2 years; 37.9% females) with COVID-19 and acute ischemic stroke were hospitalized (median of 12 patients per site). The median National Institutes of Health Stroke Scale was 10 (interquartile range [IQR], 4-18). In the 1:1 matched sample of 336 patients with COVID-19 and non-COVID-19, the median National Institutes of Health Stroke Scale was higher in patients with COVID-19 (10 [IQR, 4-18] versus 6 [IQR, 3-14]), P=0.03; (odds ratio, 1.69 [95% CI, 1.08-2.65] for higher National Institutes of Health Stroke Scale score). There were 48 (27.6%) deaths, of which 22 were attributed to COVID-19 and 26 to stroke. Among 96 survivors with available information about disability status, 49 (51%) had severe disability at discharge. In the propensity score-matched population (n=330), patients with COVID-19 had higher risk for severe disability (median mRS 4 [IQR, 2-6] versus 2 [IQR, 1-4], P<0.001) and death (odds ratio, 4.3 [95% CI, 2.22-8.30]) compared with patients without COVID-19. Our findings suggest that COVID-19 associated ischemic strokes are more severe with worse functional outcome and higher mortality than non-COVID-19 ischemic strokes.

BACKGROUND:Telehealth provides health care to a patient from a provider at a distant location. Prior to the COVID-19 pandemic adoption of telehealth modalities was increasing slowly but steadily. During the public health emergency rapid widespread telehealth implementation has been encouraged to promote patient and provider safety and preserve access to health care. EVIDENCE ACQUISITION/METHODS:Evidence was acquired from English language Internet-searches of medical and business literature and following breaking news on the COVID-19 pandemic and responses from health care stakeholders including policy makers, payers, physicians and health care organizations, and patients. We also had extensive discussions with colleagues who are developing telehealth techniques relevant to neuro-ophthalmology. RESULTS:Regulatory, legal, reimbursement and cultural barriers impeded the widespread adoption of telehealth prior to the COVID-19 pandemic. With the increased use of telehealth in response to the public health emergency, we are rapidly accumulating experience and an evidence base identifying opportunities and challenges related to the widespread adoption of tele-neuro-ophthalmology. One of the major challenges is the current inability to adequately perform funduscopy remotely. CONCLUSIONS:Telehealth is an increasingly recognized means of healthcare delivery. Tele-neuro-ophthalmology adoption is necessary for the sake of our patients, the survival of our subspecialty, and the education of our trainees and students. Telehealth does not supplant but supplements and complements in-person neuro-ophthalmologic care. Innovations in digital optical fundus photography, mobile vision testing applications, artificial intelligence and principles of channel management will facilitate further adoption of tele-neuro-ophthalmology and bring the specialty to the leading edge of healthcare delivery.

BACKGROUND CONTEXT: MBDs are often implicated in or contribute to degenerative disc disease (DDD). Yet, there is limited long-term, postoperative outcome data on the impact of MBDs on 2-year outcomes following 2-3-level lumbar fusion for DDD. PURPOSE: To determine if DDD patients with MBDs have comparable outcomes to those without MBDs following lumbar fusion. STUDY DESIGN/SETTING: Retrospective cohort. PATIENT SAMPLE: New York State Statewide Planning and Research Cooperative System was reviewed from 2009-2013 to identify all patients with DDD who underwent short, lumbar fusion (2-3-levels) with >=2-year follow-up OUTCOME MEASURES: Two-year outcome rates (medical/surgical complications and reoperations).
METHOD(S): The New York State Statewide Planning and Research Cooperative System was reviewed from 2009-2013 to identify all patients with DDD who underwent short, lumbar fusion (2-3 levels) with >=2-year follow-up. Patients with and without MBD (vitamin D deficiency, hyperparathyroidism, osteomalacia, and rickets) were identified. Any patients with osteoporosis or other systemic/endocrine disorders affecting bone quality were excluded. Traumatic, infectious, and neoplastic surgical indications were excluded. Cohorts were compared for demographics and 2-year outcome rates (medical/surgical complications and reoperations). Logistic regression was used to identify covariates associated with medical/surgical complications and revisions.
RESULT(S): A total of 28,959 patients were included (MBD, n=380 (1.33%); no-MBD, n=28,579). MBD pts were older (56.4 vs 53.1 years) and more often female (65.5% vs 49.80%) than no-MBD pts (all p<0.001). MBD pts had longer hospital stays (4.57 days vs 4.11 days, p=0.026), but charges were similar. MBD pts incurred higher rates of wound complications (11.8% vs 6.0%), acute renal failure (11.1% vs 4.7%), pneumonia (9.2% vs 4.4%), and implant related complications (12.1% vs 7.0%); all p<0.001. Rates of pseudarthrosis, PE, pulmonary complications, and UTI were similar between groups. MBDs were associated with developing both medical complications (OR=1.55) and surgical complications (OR=1.79), both p<0.001.
CONCLUSION(S): MBD patients have an increased risk of 2-year postop comps and reoperations following short lumbar fusion for DDD compared to patients without MBD when controlling for demographics and comorbidity profile. These data underscore the importance of preoperative screening and optimization in this patient population. FDA DEVICE/DRUG STATUS: This abstract does not discuss or include any applicable devices or drugs.
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