Faculty Bibliography

OBJECTIVE:The combined spatiotemporal dynamics underlying sign language production remains largely unknown. To investigate these dynamics as compared to speech production we utilized intracranial electrocorticography during a battery of language tasks. METHODS:We report a unique case of direct cortical surface recordings obtained from a neurosurgical patient with intact hearing and bilingual in English and American Sign Language. We designed a battery of cognitive tasks to capture multiple modalities of language processing and production. RESULTS:We identified two spatially distinct cortical networks: ventral for speech and dorsal for sign production. Sign production recruited peri-rolandic, parietal and posterior temporal regions, while speech production recruited frontal, peri-sylvian and peri-rolandic regions. Electrical cortical stimulation confirmed this spatial segregation, identifying mouth areas for speech production and limb areas for sign production. The temporal dynamics revealed superior parietal cortex activity immediately before sign production, suggesting its role in planning and producing sign language. CONCLUSIONS:Our findings reveal a distinct network for sign language and detail the temporal propagation supporting sign production.

OBJECTIVE:To determine time trends and distinguishing autopsy findings of sudden unexpected death in epilepsy (SUDEP) in the U.S. METHODS:We identified the decedents where epilepsy/seizure was listed as cause/contributor to death, or comorbid condition on death certificate among all decedents who underwent medico-legal investigation at three medical examiner (ME) offices across the country: New York City (2009-2016), San Diego County (2008-2016), and Maryland (2000-2016). After reviewing all available reports, deaths classified as definite/probable/near SUDEP or SUDEP plus were included for analysis. Mann-Kendall trend test was used to analyze temporal trends in SUDEP rate for 2009-2016. Definite SUDEPs were compared to sex- and age ± 2 years-matched non-SUDEP deaths with a history of epilepsy regarding autopsy findings, circumstances, and comorbidities. RESULTS:1086 SUDEP cases were identified. There was a decreasing trend in ME-investigated SUDEP incidence between 2009-2016 (z= -2.2 S= -42 p= 0.028) among three regions. There was a 28% reduction in ME-investigated SUDEP incidence from 2009-2012 to 2013-2016 (CI: 17%-38%, p<0.0001). We found no correlation between SUDEP rates and the month of year or day of week. There was no difference between SUDEP and non-SUDEP deaths regarding neurodevelopmental abnormalities, pulmonary congestion/edema, and myocardial fibrosis. CONCLUSIONS:There was a decreasing monotonic trend in ME-investigated SUDEP incidence over eight years, with a 28% reduction in incidence from 2009-2012 to 2013-2016. Unlike SIDS and sudden cardiac death, we found no correlation between SUDEP and the season of year or day of week. No autopsy findings distinguished SUDEP from non-SUDEP deaths.

OBJECTIVE:The efficacy of cannabidiol (CBD) with and without concomitant clobazam (CLB) was evaluated in stratified analyses of four large randomized controlled trials, two in Lennox-Gastaut syndrome and two in Dravet syndrome. METHODS:Each trial of CBD (Epidiolex® in the US; Epidyolex® in the EU; 10 and 20 mg/kg/day) was evaluated by CLB use. The treatment ratio was analyzed using negative binomial regression for changes in seizure frequency and logistic regression for the 50% responder rate, where the principle analysis combined both indications and CBD doses in a stratified meta-analysis. Pharmacokinetic data were examined for an exposure/response relationship based on CLB presence/absence. Safety data were analyzed using descriptive statistics. RESULTS:The meta-analysis favored CBD vs. placebo regardless of CLB use. The treatment ratio (95% CI) of CBD over placebo for the average reduction in seizure frequency was 0.59 (0.52, 0.68; p<0.0001) with CLB and 0.85 (0.73, 0.98; p=0.0226) without CLB, and the 50% responder rate odds ratio (95% CI) was 2.51 (1.69, 3.71; p<0.0001) with CLB and 2.40 (1.38, 4.16; p=0.0020) without CLB. Adverse events (AEs) related to somnolence, rash, pneumonia, or aggression were more common in patients with concomitant CLB. There was a significant exposure/response relationship for CBD and its active metabolite. CONCLUSIONS:These results indicate CBD is efficacious with and without CLB, but do not exclude the possibility of a synergistic effect associated with the combination of agents. The safety and tolerability profile of CBD without CLB shows a lower rate of certain AEs than with CLB.

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.

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.

OBJECTIVES/OBJECTIVE:To provide information on the impact of the COVID-19 pandemic on people with epilepsy and provide consensus recommendations on how to provide the best possible care for people with epilepsy while avoiding visits to urgent care facilities and hospitalizations during the Novel Coronavirus pandemic. METHODS:Authors individually scored statements on a scale of -10 (strongly disagree) to +10 (strongly agree). 5/11 recommendations for physicians and 3/5 recommendations for individuals/families were rated by all authors as 7 or above (strongly agree) on the first round of rating. Subsequently, a tele-conference was held where statements for which there was a lack of strong consensus were revised. RESULTS:After revision, all consensus recommendations received a score of 7 or above. The recommendations focus on administration of as much care as possible at home to keep people with epilepsy out of health care facilities, where they are likely to encounter COVID-19 (including strategies for rescue therapy), as well as minimization of risk of seizure exacerbation through adherence, and through ensuring a regular supply of medication. We also provide helpful links to additional helpful information for people with epilepsy and health providers. CONCLUSION/CONCLUSIONS:These recommendation may help healthcare professionals provide optimal care to people with epilepsy during the coronavirus pandemic.

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.

Objectives/UNASSIGNED:Clinically relevant neuroanatomy is challenging to teach, learn and remember since many functionally important structures are visualized best using histology stains from serial 2D planar sections of the brain. In clinical patients, the locations of specific structures then must be inferred from spatial position and surface anatomy. A 3D MRI dataset of neuroanatomy has several advantages including simultaneous multi-planar visualization in the same brain, direct end-user manipulation of the data and image contrast identical to clinical MRI. We created 3D MRI datasets of the postmortem brain with high spatial and contrast resolution for simultaneous multi-planar visualization of complex neuroanatomy. Materials and Methods/UNASSIGNED:; time = 7 h). Besides resolution, this sequence has multiple adjustments to improve contrast compared to a clinical protocol, including 93% reduced turbo factor and 77% reduced effective echo time. Results/UNASSIGNED:This MRI microscopy protocol provided excellent contrast resolution of small nuclei and internal myelinated pathways within the basal ganglia, thalamus, brainstem, and cerebellum. Contrast was sufficient to visualize the presence and variation of horizontal layers in the cerebral cortex. 3D isotropic resolution datasets facilitated simultaneous multi-planar visualization and efficient production of specific tailored oblique image orientations to improve understanding of complex neuroanatomy. Conclusion/UNASSIGNED:structure visualization.

OBJECTIVE:R) in surgical tissue from patients with temporal lobe epilepsy and hippocampal sclerosis (TLE/HS) with SUDEP risk factors. METHODS:R in seven regions of interest: temporal cortex, temporal lobe white matter, CA1, CA4, dentate gyrus, subiculum, and amygdala and relative to glial and neuronal densities with glial fibrillary acidic protein (GFAP) and neuronal nuclear antigen (NeuN). RESULTS:R was present in the amygdala in high-risk than in low-risk cases. There was no significant difference in neuronal loss or gliosis between the risk groups or differences for ADK labeling. SIGNIFICANCE/CONCLUSIONS:R in the high-risk group could contribute to periictal amygdala dysfunction in SUDEP.