Faculty Bibliography

BACKGROUND AND PURPOSE/OBJECTIVE:Hypertension is a known risk factor for intracerebral hemorrhage (ICH), but it is unclear whether blood pressure (BP) at hospital arrival can be used to distinguish hypertensive ICH from non-hypertensive etiologies. PATIENTS AND METHODS/METHODS:We performed a single-center cohort study using data from consecutive ICH patients over 12 months. ICH characteristics including etiology were prospectively adjudicated by two attending neurologists. Using adjusted linear regression models, we compared first recorded systolic BPs (SBP) and mean arterial pressures (MAP) in patients with hypertensive vs. other ICH etiologies. We then used area under the ROC curve (AUC) analysis to determine the accuracy of admission BP in differentiating between hypertensive and non-hypertensive ICH. RESULTS:Of 311 patients in our cohort (mean age 70.6 ± 15.6, 50% male, 83% white), the most frequent ICH etiologies were hypertension (50%) and cerebral amyloid angiopathy (CAA; 22%). Mean SBP and MAP for patients with hypertensive ICH was 175.1 ± 32.9 mmHg and 120.4 ± 22.9 mmHg, respectively, compared to 156.4 ± 28.0 mmHg and 109.6 ± 20.3 mmHg in non-hypertensive ICH (p < .001). Adjusted models showed that hypertensive ICH patients had higher BPs than those with CAA (mean SBP difference 10.7 mmHg [95% CI 0.8-20.5]; mean MAP difference 8.1 mmHg [1.1-15.0]) and especially patients with other non-CAA causes (mean SBP difference 23.9 mmHg [15.3-32.4]; mean MAP difference 14.5 mmHg [8.5-20.6]). However, on a patient-level, arrival BP did not reliably discriminate between hypertensive and non-hypertensive etiologies (AUC 0.660 [0.599-0.720]). CONCLUSIONS:Arrival BP differs between hypertensive and non-hypertensive ICH but should not be used as a primary determinant of etiology, as hypertension may be implicated in various subtypes of ICH.

On May 22-24, 2019, the 15th Antiepileptic Drug and Device (AEDD) Trials Conference was held, which focused on current issues related to AEDD development from preclinical models to clinical prognostication. The conference featured regulatory agencies, academic laboratories, and healthcare companies involved in emerging epilepsy therapies and research. The program included discussions around funding and support for investigations in epilepsy and neurologic research, clinical trial design and integrated outcome measures for people with epilepsy, and drug development and upcoming disease-modifying therapies. Finally, the conference included updates from the preclinical, clinical, and device pipeline. Summaries of the talks are provided in this paper, with the various pipeline therapeutics in the listed tables to be outlined in a subsequent publication.

OBJECTIVE:To outline changes made to a neurology residency program in response to coronavirus disease 2019 (COVID-19). METHODS:In early March 2020, the first cases of COVID-19 were announced in the United States. New York City quickly became the epicenter of a global pandemic, and our training program needed to rapidly adapt to the increasing number of inpatient cases while being mindful of protecting providers and continuing education. Many of these changes unfolded over days, including removing residents from outpatient services, minimizing the number of residents on inpatient services, deploying residents to medicine services and medical intensive care units, converting continuity clinic patient visits to virtual options, transforming didactics to online platforms only, and maintaining connectedness in an era of social distancing. We have been able to accomplish this through daily virtual meetings among leadership, faculty, and residents. RESULTS:Over time, our program has successfully rolled out initiatives to service the growing number of COVID-related inpatients while maintaining neurologic care for those in need and continuing our neurologic education curriculum. CONCLUSION/CONCLUSIONS:It has been necessary and feasible for our residency training program to undergo rapid structural changes to adapt to a medical crisis. The key ingredients in doing this successfully have been flexibility and teamwork. We suspect that many of the implemented changes will persist long after the COVID-19 crisis has passed and will change the approach to neurologic and medical training.

OBJECTIVE:To determine the impact of socioeconomic status (SES) on sudden unexpected death in epilepsy (SUDEP) rates. METHODS:We queried all decedents presented for medico-legal investigation at 3 medical examiner (ME) offices across the country (New York City, Maryland, San Diego County) in 2009 to 2010 and 2014 to 2015. We identified all decedents for whom epilepsy/seizure was listed as cause/contributor to death or comorbid condition on the death certificate. We then reviewed all available reports. Decedents determined to have SUDEP were included for analysis. We used median income in the ZIP code of residence as a surrogate for SES. For each region, zip code regions were ranked by median household income and divided into quartiles based on total population for 2 time periods. Region-, age-, and income-adjusted epilepsy prevalence was estimated in each zip code. SUDEP rates in the highest and lowest SES quartiles were evaluated to determine disparity. Examined SUDEP rates in 2 time periods were also compared. RESULTS:< 0.0001). CONCLUSION/CONCLUSIONS:ME-investigated SUDEP incidence was significantly higher in people with the lowest SES compared to the highest SES. The difference persisted over a 5-year period despite decreased overall SUDEP rates.

Background/UNASSIGNED:Delayed parkinsonism and dystonia are recognized phenomena in osmotic demyelinating syndrome (ODS). Dopamine receptor agonists and levodopa have been reported to benefit select patients. Case report/UNASSIGNED:We report a patient with ODS with severe pseudobulbar deficits, parkinsonism and dystonia, poorly responsive to levodopa, who experienced a remarkable improvement with pramipexole. Discussion/UNASSIGNED:A marked response to pramipexole with lack of response to levodopa suggests a pre-synaptic source for his deficits coupled with injuries to non-nigral compensatory structures. Highlights/UNASSIGNED:This case highlights a dramatic response of osmotic demyelination-induced parkinsonism/dystonia to pramipexole. A lack of response to levodopa suggests deficits in the pre-synaptic nigral as well as non-nigral compensatory structures.

The COVID-19 pandemic is causing world-wide social dislocation, operational and economic dysfunction, and high rates of morbidity and mortality. Medical practices are responding by developing, disseminating and implementing unprecedented changes in health care delivery. Telemedicine has rapidly moved to the frontline of clinical practice due to the need for prevention and mitigation strategies; these have been encouraged, facilitated, and enabled by changes in government rules and regulations and payer-driven reimbursement policies.We describe our neurology department's situational transformation from in-person outpatient visits to a largely virtual neurology practice in response to the COVID-19 pandemic. Two key factors enabled our rapid deployment of virtual encounters in neurology and its subspecialties. The first was a well-established robust information technology infrastructure supporting virtual urgent care services at our institution; this connected physicians directly to patients using both the physician's and the patient's own mobile devices. The second is the concept of one patient, one chart, facilitated by a suite of interconnected electronic medical record (EMR) applications on several different device types.We present our experience with conducting general teleneurology encounters using secure synchronous audio and video connections integrated with an EMR. This report also details how we perform virtual neurological examinations that are clinically meaningful, and how we document, code and bill for these virtual services. Many of these processes can be used by other neurology providers, regardless of their specific practice model. We then discuss potential roles for teleneurology after the COVID-19 global pandemic has been contained.

Introduction: Advances in the understanding of the mechanisms that lead to Lewy body pathology in Parkinson disease (PD) have yielded rationales for tackling neurodegeneration associated with α-Synuclein (α-Syn) misfolding, aggregation and/or its related spreading. Immunization therapies targeting distinct α-Syn epitopes (conformational and linear) that aim to limit extracellular spread in the brain, are now in development. Completed and ongoing studies have enrolled early PD patients without considering individual clinical differences and assume a common pathogenetic mechanism of the disease. Such approaches have led to disappointing results; this is most likely attributed to trial methodology and inadequate patient selection rather than underlying target biology.Areas covered - This review presents the status of immunotherapies that target α-Syn epitopes in PD. Mechanisms associated with neurodegeneration are examined along with the limitations of current antibody research strategies and ongoing clinical trials. Patient stratification based on disease progression is discussed and the article culminates with author suggestions on how to progress future clinical trials.Expert opinion - The efficacy of passive and active immunotherapies is inadequately evaluated in ongoing clinical trials where participating patients have various progression rates, genetic backgrounds and clinical phenotypes. Future disease-modifying studies can overcome these limitations by enrolling patients based on progression pathways and genotypic contribution to disease manifestations.

Due to severe motor impairments and the lack of expressive language abilities seen in most patients with Rett Syndrome (RTT), it has proven extremely difficult to obtain accurate measures of auditory processing capabilities in this population. Here, we examined early auditory cortical processing of pure tones and more complex phonemes in females with Rett Syndrome (RTT), by recording high-density auditory evoked potentials (AEP), which allow for objective evaluation of the timing and severity of processing deficits along the auditory processing hierarchy. We compared AEPs of 12 females with RTT to those of 21 typically developing (TD) peers aged 4-21 years, interrogating the first four major components of the AEP (P1: 60-90 ms; N1: 100-130 ms; P2: 135-165 ms; and N2: 245-275 ms). Atypicalities were evident in RTT at the initial stage of processing. Whereas the P1 showed increased amplitude to phonemic inputs relative to tones in TD participants, this modulation by stimulus complexity was absent in RTT. Interestingly, the subsequent N1 did not differ between groups, whereas the following P2 was hugely diminished in RTT, regardless of stimulus complexity. The N2 was similarly smaller in RTT and did not differ as a function of stimulus type. The P2 effect was remarkably robust in differentiating between groups with near perfect separation between the two groups despite the wide age range of our samples. Given this robustness, along with the observation that P2 amplitude was significantly associated with RTT symptom severity, the P2 has the potential to serve as a monitoring, treatment response, or even surrogate endpoint biomarker. Compellingly, the reduction of P2 in patients with RTT mimics findings in animal models of RTT, providing a translational bridge between pre-clinical and human research.

Systemic and structural barriers limit dental health for individuals with special healthcare needs (SHCN), who have poorer dental hygiene, higher rates of dental disorders, and less access to oral care. We aimed to understand these barriers directly from the patient and caregiver population as well as review the literature on oral health of individuals with SHCN. We reviewed the literature on individuals and caregivers of those with SHCN to identify barriers to dental healthcare faced by these individuals. We focused on clinical and educational interventions to support clinicians treating this population. For the literature review, PubMed, Google, and Google Scholar were searched. We also relied upon the knowledge gained during the course of routine clinical care and patient advocacy activities. Published manuscripts were searched for the following Medical Subject Heading (MeSH) term: "Dental Care for Disabled" and the following subheading: pharmacology, adverse effects, ethics, methods, standards, and therapy. Relatively few dentists have formal training on caring for those with SHCN. Barriers faced by these individuals include accessibility, comorbidities, communication challenges, and barriers to home oral hygiene. Strong care coordination and communication between dentists, caregivers, and other providers is essential for positive outcomes. Our current dental healthcare system has failed to meet the needs of those with SHCN. The comfort and dignity of the patient are of paramount importance.