Faculty Bibliography

OBJECTIVES/OBJECTIVE:African American (AA) children affected by autism spectrum disorder (ASD) experience delays in diagnosis and obstacles to service access, as well as a disproportionate burden of intellectual disability (ID) as documented in surveillance data recently published by the US Centers for Disease Control and Prevention. Our objective in this study was to analyze data from the largest-available repository of diagnostic and phenotypic information on AA children with ASD, and to explore the wide variation in outcome within the cohort as a function of sociodemographic risk and specific obstacles to service access for the purpose of informing a national approach to resolution of these disparities. METHODS:Parents of 584 AA children with autism consecutively enrolled in the Autism Genetic Resource Exchange across 4 US data collection sites completed event history calendar interviews of the diagnostic odysseys for their children with ASD. These data were examined in relation to developmental outcomes of the children with autism and their unaffected siblings. RESULTS:The average age of ASD diagnosis was 64.9 months (±49.6), on average 42.3 months (±45.1) after parents' first concerns about their children's development. The relationship between timing of diagnosis and ASD severity was complex, and ID comorbidity was not predicted in a straightforward manner by familial factors associated with cognitive variation in the general population. CONCLUSIONS:These findings document significant opportunity to expedite diagnosis, the need to further understand causes of ID comorbidity, and the necessity to identify effective approaches to the resolution of disparities in severity-of-outcome for AA children with autism.

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.

Objective: To confirm: 1) clinical efficacy and safety of once-daily oral ampreloxetine in a 4-week double-blind (

Objective: To develop a clinical score to distinguish between the parkinsonian variant of multiple system atrophy (MSA-P) and Parkinson's disease (PD).
Background(s): The differential diagnosis between MSA-P and PD is often difficult, particularly early in the disease course.
Method(s): We compared patients with probable MSA-P and with PD with a disease duration of <3 years, selected from those who were enrolled in the Natural History Study of the Synucleinopathies, an international prospective observational study. Detailed clinical neurological, and autonomic parameters were assessed at enrollment using UMSARS part I, II and IV; Schrag quality of life (QoL) scale; burden of autonomic dysfunction by COMPASS-31 scale; smell function using the UPSIT; cardiovascular autonomic function using heart rate variability during deep-breathing, analysis of the Valsalva maneuver, orthostatic stress test, plasma catecholamine levels during supine rest and after head-up tilt; and cognitive evaluation using MoCA. Positive and negative likelihood ratios (LR) were obtained for each variable assessed. Multiple iterations of a composite score based on sequential addition of variables with the highest diagnostic accuracy were created by multiplying each variable's LR and applying a logarithmic function.
Result(s): Fifty-eight MSA-P and 53 PD patients had a disease duration of less than 3 years. The vast majority of patients had been diagnosed within the last 12 months (81% MSA-P and 66% PD patients). MSA-P patients were more frequently female (53% vs. 30% p<0.05) and younger at diagnosis (63+/-8 years vs. 71+/-8 years, p<0.001). A 7-item score comprising the bladder weighted subscore of the COMPASS-31, UMSARS's part 1, UPSIT, hyperreflexia, the motor subscore of Schrag's MSA quality of life scale, falls within 3 years of diagnosis, and new or increased snoring resulted in a ROC curve AUC of 0.983, with excellent 93% sensitivity and 98% specificity to distinguish early MSA-P from PD.
Conclusion(s): We propose a scale of 7 clinical items to distinguish early stage MSA-P from PD. It considers urinary function, olfactory function, corticospinal signs, performance of activities of daily living, motor symptoms burden on quality of life, frequent early falls and sleep disordered breathing. We are now prospectively validating the scale to determine its predictive value in our prodromal cohort. (Figure Presented)

Inaccurate subjective seizure counting poses treatment and diagnostic challenges and thus suboptimal quality in epilepsy management. The limitations of existing hospital- and home-based monitoring solutions are motivating the development of minimally invasive, subscalp, implantable electroencephalography (EEG) systems with accompanying cloud-based software. This new generation of ultra-long-term brain monitoring systems is setting expectations for a sea change in the field of clinical epilepsy. From definitive diagnoses and reliable seizure logs to treatment optimization and presurgical seizure foci localization, the clinical need for continuous monitoring of brain electrophysiological activity in epilepsy patients is evident. This paper presents the converging solutions developed independently by researchers and organizations working at the forefront of next generation EEG monitoring. The immediate value of these devices is discussed as well as the potential drivers and hurdles to adoption. Additionally, this paper discusses what the expected value of ultra-long-term EEG data might be in the future with respect to alarms for especially focal seizures, seizure forecasting, and treatment personalization.

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.