Faculty Bibliography

The epilepsies are commonly accompanied by widespread abnormalities in cerebral white matter. ENIGMA-Epilepsy is a large quantitative brain imaging consortium, aggregating data to investigate patterns of neuroimaging abnormalities in common epilepsy syndromes, including temporal lobe epilepsy, extratemporal epilepsy, and genetic generalized epilepsy. Our goal was to rank the most robust white matter microstructural differences across and within syndromes in a multicentre sample of adult epilepsy patients. Diffusion-weighted MRI data were analysed from 1069 healthy controls and 1249 patients: temporal lobe epilepsy with hippocampal sclerosis (n = 599), temporal lobe epilepsy with normal MRI (n = 275), genetic generalized epilepsy (n = 182) and non-lesional extratemporal epilepsy (n = 193). A harmonized protocol using tract-based spatial statistics was used to derive skeletonized maps of fractional anisotropy and mean diffusivity for each participant, and fibre tracts were segmented using a diffusion MRI atlas. Data were harmonized to correct for scanner-specific variations in diffusion measures using a batch-effect correction tool (ComBat). Analyses of covariance, adjusting for age and sex, examined differences between each epilepsy syndrome and controls for each white matter tract (Bonferroni corrected at P < 0.001). Across 'all epilepsies' lower fractional anisotropy was observed in most fibre tracts with small to medium effect sizes, especially in the corpus callosum, cingulum and external capsule. There were also less robust increases in mean diffusivity. Syndrome-specific fractional anisotropy and mean diffusivity differences were most pronounced in patients with hippocampal sclerosis in the ipsilateral parahippocampal cingulum and external capsule, with smaller effects across most other tracts. Individuals with temporal lobe epilepsy and normal MRI showed a similar pattern of greater ipsilateral than contralateral abnormalities, but less marked than those in patients with hippocampal sclerosis. Patients with generalized and extratemporal epilepsies had pronounced reductions in fractional anisotropy in the corpus callosum, corona radiata and external capsule, and increased mean diffusivity of the anterior corona radiata. Earlier age of seizure onset and longer disease duration were associated with a greater extent of diffusion abnormalities in patients with hippocampal sclerosis. We demonstrate microstructural abnormalities across major association, commissural, and projection fibres in a large multicentre study of epilepsy. Overall, patients with epilepsy showed white matter abnormalities in the corpus callosum, cingulum and external capsule, with differing severity across epilepsy syndromes. These data further define the spectrum of white matter abnormalities in common epilepsy syndromes, yielding more detailed insights into pathological substrates that may explain cognitive and psychiatric co-morbidities and be used to guide biomarker studies of treatment outcomes and/or genetic research.

Physician-patient collaboration was recognized as a critical core of participatory medicine more than a century ago. However, the subsequent focus on scientific research to enable cures and increased dominance of physicians in health care subordinated patients to a passive role. This paternalistic model weakened in the past 50 years-as women, minorities, and the disabled achieved greater rights, and as incurable chronic diseases and unrelieved pain disorders became more prevalent-promoting a more equitable role for physicians and patients. By 2000, a shared decision-making model became the pinnacle for clinical decisions, despite a dearth of data on health outcomes, or the model's reliance on single patient or solo practitioner studies, or evidence that no single model could fit all clinical situations. We report about a young woman with intractable epilepsy due to a congenital brain malformation whose family and medical specialists used a collaborative decision-making approach. This model positioned the health professionals as supporters of the proactive family, and enabled them all to explore and co-create knowledge beyond the clinical realm. Together, they involved other members of the community in the decisions, while harnessing diverse relationships to allow all family members to achieve positive levels of health, despite the resistance of the seizures to medical treatment and the incurable nature of the underlying disease.

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/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.

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.

OBJECTIVE:To assess relative rates and clinical features of patients with genetic generalized epilepsy (GGE), focal epilepsy (FE), and developmental encephalopathic epilepsy (DEE) in the North American SUDEP Registry (NASR). METHODS:We identified all adjudicated definite, definite plus, and probable sudden unexpected death in epilepsy (SUDEP) cases (n = 262) and determined epilepsy type (GGE, FE, or DEE) from medical record review including history, imaging and EEG results, genetics, and next-of-kin interviews. RESULTS:Of the 262 SUDEP cases, 41 occurred in GGE, 95 in FE, 24 in DEE, and 102 were unclassifiable. GGE cases comprised 26% of NASR cases with an epilepsy syndrome diagnosis. The relative frequency of FE:GGE was slightly lower (2.3:1) than in population cohorts (2.1-6:1). Compared to patients with FE, patients with GGE had similar (1) ages at death and epilepsy onset and rates of (2) terminal and historical antiseizure medication adherence; (3) abnormal cardiac pathology; (4) illicit drug/alcohol use histories; and (5) sleep state when SUDEP occurred. CONCLUSIONS:GGE cases were relatively overrepresented in NASR. Because GGEs are less often treatment-resistant than FE or DEE, seizure type rather than frequency may be critical. Many people with GGE predominantly have generalized tonic-clonic seizures (GTCS) when they have uncontrolled or breakthrough seizures, whereas patients with FE more commonly experience milder seizures. Future mechanistic SUDEP studies should assess primary and focal-to-bilateral GTCS to identify potential differences in postictal autonomic and arousal disorders and to determine the differential role that lifestyle factors have on breakthrough seizures and seizure types in GGE vs FE to effectively target SUDEP mechanisms and prevention.

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.

OBJECTIVE:Survivors of prolonged (> 2 weeks) post-cardiac arrest (CA) coma are expected to remain permanently disabled. We aimed to investigate three outlier patients who ultimately achieved independent functional outcomes after prolonged post-CA coma to identify electroencephalographic (EEG) markers of their recovery potential. For validation purposes, we also aimed to evaluate these markers in an independent cohort of post-CA patients. METHODS:We identified three patients with late recovery from coma (17-37 days) following CA who recovered to functionally independent behavioral levels. We performed spectral power analyses of available EEGs during prominent burst suppression patterns (BSP) present in all three patients. Using identical methods, we also assessed the relationship of intra-burst spectral power and outcomes in a prospectively enrolled cohort of post-CA patients. We performed chart reviews of common clinical, imaging, EEG prognostic variables and clinical outcomes for all patients. RESULTS:All three patients with late recovery from coma lacked evidence of overwhelming cortical injury but demonstrated prominent BSP on EEG. Spectral analyses revealed a prominent theta (~4-7Hz) feature dominating the bursts during BSP in these patients. In the prospective cohort, similar intra-burst theta spectral features were evident in patients with favorable outcomes; patients with BSP and unfavorable outcomes showed either no features, transient burst features or decreasing intra-burst frequencies with time. INTERPRETATION/CONCLUSIONS:BSP with theta (~4-7Hz) peak intra-burst spectral power after CA may index a recovery potential. We discuss our results in the context of optimizing metabolic substrate availability and stimulating the cortico-thalamic system during recovery from prolonged post-CA coma. This article is protected by copyright. All rights reserved.