Faculty Bibliography

PURPOSE/OBJECTIVE:Corona virus disease 2019 (COVID-19) refers to coronavirus disease secondary to SARS-CoV2 infection mainly affecting the human respiratory system. The SARS-CoV2 has been reported to have neurotropic and neuroinvasive features and neurological sequalae with wide range of reported neurological manifestations, including cerebrovascular disease, skeletal muscle injury, meningitis, encephalitis, and demyelination, as well as seizures and focal status epilepticus. In this case series, we analyzed the continuous video-EEGs of patients with COVID-19 infection to determine the presence of specific EEG features or epileptogenicity. METHODS:All continuous video-EEG tracings done on SARS-CoV2-positive patients during a 2-week period from April 5, 2020, to April 19, 2020, were reviewed. The demographics, clinical characteristics, imaging, and EEG features were analyzed and presented. RESULTS:Of 23 patients undergoing continuous video-EEG, 16 were COVID positive and were included. Continuous video-EEG monitoring was ordered for "altered mental status" in 11 of 16 patients and for "clinical seizure" in 5 of 16 patients. None of the patients had seizures or status epilepticus as a presenting symptom of COVID-19 infection. Instead, witnessed clinical seizures developed as results of COVID-19-related medical illness(es): anoxic brain injury, stroke/hemorrhage, lithium (Li) toxicity (because of kidney failure), hypertension, and renal disease. Three patients required therapeutic burst suppression because of focal nonconvulsive status epilepticus, status epilepticus/myoclonus secondary to anoxic injury from cardiac arrest, and one for sedation (and with concomitant EEG abnormalities secondary to Li toxicity). CONCLUSIONS:In this observational case series of 16 patients with COVID-19 who were monitored with continuous video-EEG, most patients experienced a nonspecific encephalopathy. Clinical seizures and electrographic status epilepticus were the second most commonly observed neurological problem.

Patients often recognize unmet needs that can improve patient-provider experiences in disease treatment management. These needs are rarely captured and may be hard to quantify in difficult-to-treat disease states such as drug-resistant epilepsy (DRE). To further understand challenges living with and managing DRE, a team of medical anthropologists conducted ethnographic field assessments with patients to qualitatively understand their experience with DRE across the United States. In addition, healthcare provider assessments were conducted in community clinics and Comprehensive Epilepsy Centers to further uncover patient-provider treatment gaps. We identified four distinct stages of the treatment and management journey defined by patients' perceived control over their epilepsy: Gripped in the Panic Zone, Diligently Tracking to Plan, Riding a Rollercoaster in the Dark, and Reframing Priorities to Redefine Treatment Success. We found that patients sought resources to streamline communication with their care team, enhanced education on treatment options beyond medications, and long-term resources to protect against a decline in control over managing their epilepsy once drug-resistant. Likewise, treatment management optimization strategies are provided to improve current DRE standard of care with respect to identified patient-provider gaps. These include the use of digital disease management tools, standardizing neuropsychiatrists into patients' initial care team, and introducing surgical and non-pharmacological treatment options upon epilepsy and DRE diagnoses, respectively. This ethnographic study uncovers numerous patient-provider gaps, thereby presenting a conceptual framework to advance DRE treatment. Further Incentivization from professional societies and healthcare systems to support standardization of the treatment optimization strategies provided herein into clinical practice is needed.

OBJECTIVE:In countries where health coverage is not universal, there is ample evidence of disparities in healthcare, often associated with insurance. People with seizures, similar to those living with any complicated chronic medical comorbidity, need further health-related attention to improve their quality-of-life outcomes. METHODS:We conducted a retrospective cohort study of the National Inpatient Sample (NIS) component of the Healthcare Cost and Utilization Project (HCUP) national database between 1997-2014. The analysis focused on the mortality rate, and patients with a principal admission diagnosis of seizure at the time of discharge were identified. Primary Payer Status (PPS) included Medicare, Medicaid, private, and uninsured. Multivariate linear regression modeling was conducted to examine the contribution of the predictive variables to in-hospital mortality. RESULTS:Between 1997-2014, 4,594,213 seizure-related discharges was recorded. The overall mean patient age was 41.69 ± 0.98 years, and 58.1 % were female. The average age during this period decreased significantly in Medicare, increased substantially in uninsured, without significant change in Medicaid and private. Patients in Medicare had the highest length of stay (LOS) (4.49 ± 0.29 days), and uninsured (2.79 ± 0.15) had the least. Over time, there was a significant increase in the number of seizure discharges in Medicare, Medicaid, and private insurance. However, there was a significant decrease in in-hospital mortality in Medicare, Medicaid, and private, with the most prominent decline in Medicare. Risk-adjusted for age, gender, LOS, illness severity, and time, regression results showed Medicare has a significantly higher association with less in-hospital mortality compared with other insurances. CONCLUSIONS:Our study showed a significant increase in the number of seizure diagnoses at discharge in Medicare, Medicaid, and private in the United States between 1997-2014; however, there was a decrease in the in-hospital mortality rate across all insurance payers. Uninsured patients had the highest mortality rate after Medicare without risk justification. Risk-stratified models confirmed Medicare was significantly associated with a less in-hospital mortality rate.

The vagus nerve stimulation (VNS) Therapy® System is the first FDA-approved medical device therapy for the treatment of drug-resistant epilepsy. Over the past two decades, the technology has evolved through multiple iterations resulting in software-related updates and implantable lead and generator hardware improvements. Healthcare providers today commonly encounter a range of single- and dual-pin generators (models 100, 101, 102, 102R, 103, 104, 105, 106, 1000) and related programming systems (models 250, 3000), all of which have their own subtle, but practical differences. It can therefore be a daunting task to go through the manuals of these implant models for comparison, some of which are not readily available. In this review, we highlight the technological evolution of the VNS Therapy System with respect to device approval milestones and provide a comparison of conventional open-loop vs. the latest closed-loop generator models. Battery longevity projections and an in-depth examination of stimulation mode interactions are also presented to further differentiate amongst generator models.

"Burst-suppression" pattern consists of complete attenuation of background between bursts of mixed frequencies, variable morphology and waveforms. It is a subgroup of periodic patterns seen in severe cerebral damage, anesthesia or prematurity. Here, we present a 46-year-old woman with post-anoxic encephalopathy on cooling protocol with two electrographically similar patterns of burst-suppression (one with a clinical ictal correlate of isolated eye movements), as well as three electroclinical seizures. The literature on rare clinical phenomenon of isolated eye movements associated with burst-suppression is reviewed, with the conclusion that the presented case suggests an ictal origin.

Digital health technologies for people with epilepsy (PWE) include internet-based resources and mobile apps for seizure management. Since non-pharmacological interventions, such as listening to specific Mozart's compositions, cognitive therapy, psychosocial and educational interventions were shown to reduce epileptic seizures, these modalities can be integrated into mobile software and delivered by mobile medical apps as digital therapeutics. Herein, we describe: (1) a survey study among PWE about preferences to use mobile software for seizure control, (2) a rationale for developing digital therapies for epilepsy, (3) creation of proof-of-concept mobile software intended for use as an adjunct digital therapeutic to reduce seizures, and (4) broader applications of digital therapeutics for the treatment of epilepsy and other chronic disorders. A questionnaire was used to survey PWE with respect to preferred features in a mobile app for seizure control. Results from the survey suggested that over 90% of responders would be interested in using a mobile app to manage their seizures, while 75% were interested in listening to specific music that can reduce seizures. To define digital therapeutic for the treatment of epilepsy, we designed and created a proof-of-concept mobile software providing digital content intended to reduce seizures. The rationale for all components of such digital therapeutic is described. The resulting web-based app delivered a combination of epilepsy self-care, behavioral interventions, medication reminders and the antiseizure music, such as the Mozart's sonata K.448. To improve long-term patient engagement, integration of mobile medical app with music and multimedia streaming via smartphones, tablets and computers is also discussed. This work aims toward development and regulatory clearance of software as medical device (SaMD) for seizure control, yielding the adjunct digital therapeutic for epilepsy, and subsequently a drug-device combination product together with specific antiseizure medications. Mobile medical apps, music, therapeutic video games and their combinations with prescription medications present new opportunities to integrate pharmacological and non-pharmacological interventions for PWE, as well as those living with other chronic disorders, including depression and pain.

The focal and network concepts of epilepsy present different aspects of electroclinical phenomenon of seizures. Here, we present a 23-year-old man undergoing surgical evaluation with left fronto-temporal electrocorticography (ECoG) and microelectrode-array (MEA) in the middle temporal gyrus (MTG). We compare action-potential (AP) and local field potentials (LFP) recorded from MEA with ECoG. Seizure onset in the mesial-temporal lobe was characterized by changes in the pattern of AP-firing without clear changes in LFP or ECoG in MTG. This suggests simultaneous analysis of neuronal activity in differing spatial scales and frequency ranges provide complementary insights into how focal and network neurophysiological activity contribute to ictal activity.

OBJECTIVES/OBJECTIVE:The Automatic Stimulation Mode (AutoStim) feature of the Model 106 Vagus Nerve Stimulation (VNS) Therapy System stimulates the left vagus nerve on detecting tachycardia. This study evaluates performance, safety of the AutoStim feature during a 3-5-day Epilepsy Monitoring Unit (EMU) stay and long- term clinical outcomes of the device stimulating in all modes. MATERIALS AND METHODS/METHODS:The E-37 protocol (NCT01846741) was a prospective, unblinded, U.S. multisite study of the AspireSR(®) in subjects with drug-resistant partial onset seizures and history of ictal tachycardia. VNS Normal and Magnet Modes stimulation were present at all times except during the EMU stay. Outpatient visits at 3, 6, and 12 months tracked seizure frequency, severity, quality of life, and adverse events. RESULTS:Twenty implanted subjects (ages 21-69) experienced 89 seizures in the EMU. 28/38 (73.7%) of complex partial and secondarily generalized seizures exhibited ≥20% increase in heart rate change. 31/89 (34.8%) of seizures were treated by Automatic Stimulation on detection; 19/31 (61.3%) seizures ended during the stimulation with a median time from stimulation onset to seizure end of 35 sec. Mean duty cycle at six-months increased from 11% to 16%. At 12 months, quality of life and seizure severity scores improved, and responder rate was 50%. Common adverse events were dysphonia (n = 7), convulsion (n = 6), and oropharyngeal pain (n = 3). CONCLUSIONS:The Model 106 performed as intended in the study population, was well tolerated and associated with clinical improvement from baseline. The study design did not allow determination of which factors were responsible for improvements.