Epileptic Seizure Induced by Head-Up Tilt: A Case Series Study.

PURPOSE: Epilepsy and syncope can be difficult to distinguish, with misdiagnosis resulting in unnecessary or incorrect treatment and disability. Combined tilt-table and video EEG (vEEG) testing (tilt-vEEG) is infrequently used to parse these entities even at large centers. Because of the discovery of a rare case of epileptic seizure induced by head-up tilt (HUT) (no prior cases have been published), the authors sought to verify the rarity of this phenomenon. METHODS: An observational, retrospective case series study of all combined tilt-vEEG studies performed at Stanford Health Care over a 2-year period was performed. Studies were grouped into categories: (1) abnormal tilt and normal vEEG; (2) abnormal vEEG and normal tilt; (3) abnormal vEEG and abnormal tilt; (4) normal tilt and normal vEEG, with neurologic symptoms; and (5) normal tilt and normal vEEG without neurologic symptoms. RESULTS: Sixty-eight percent of patients had an abnormal study (categories A-C), with only 3% having both an abnormal tilt and an abnormal EEG (category C). Of these, one patient had a focal epileptic seizure induced by HUT. With HUT positioning, the patient stopped answering questions and vEEG showed a left temporal seizure; systolic blood pressure abruptly dropped to 89 mm Hg (64 mm Hg below baseline); heart rate did not change, but pacemaker showed increased firing (threshold: <60 bpm). CONCLUSIONS: Combined tilt-table and vEEG evaluation was able to identify a previously unreported scenario-head-up tilt provocation of an epileptic seizure-and improve treatment. Combined tilt and vEEG testing should be considered for episodes that persist despite treatment to confirm proper diagnosis.

Impact of high-density EEG in presurgical evaluation for refractory epilepsy patients.

OBJECTIVE: Electrical source localization (ESI) can help to identify the seizure onset zone or propagation zone, but it is unclear how dipole localization techniques influence surgical planning. METHODS: Patients who received a high density (HD)-EEG from 7/2014-7/2019 at Stanford were included if they met the following inclusion criteria: (1) adequate epileptiform discharges were recorded for source localization analysis, (2) underwent surgical treatment, which was at least 6 months before the survey. Interictal ESI was performed with the LORETA method on age matched MRIs. Six neurophysiologists from the Stanford Epilepsy Program independently reviewed each case through an HIPPA-protected online survey. The same cases were presented again with additional data from the HD-EEG study. Ratings of how much the HD-EEG findings added value and in what way were recorded. RESULTS: Fifty out of 202 patients met the inclusion criteria, providing a total of 276 h of HDEEG recordings. All patients had video EEG recordings and at least one brain MRI, 88 % had neuropsychological testing, 78 % had either a PET or SPECT scan. Additional HD-EEG information was rated as helpful in 83.8 %, not useful in 14.4 % and misleading in 1.8 % of cases. In 20.4 % of cases the HD-EEG information altered decision-making in a major way, such as choosing a different surgical procedure, avoidance of invasive recording or suggesting placement of invasive electrodes in a lobe not previously planned. In 21.5 % of cases, HD-EEG changed the plan in a minor way, e.g., extra invasive electrodes near the previously planned sites in the same sub-lobar region. In 42.3 % cases, HD-EEG did not change their plan but provided confirmation. In cases with normal MRI, additional HD-EEG information was more likely to change physicians' decision making during presurgical process when compared to the cases with MRI-visible lesions (53.3 % vs. 34.3 %, p = 0.002). Among patients achieving Engel class I/II outcome, the concordance rate of HD-EEG and resection zone was 64.7 % versus 35.3 % with class III/IV (p = 0.028). CONCLUSION: HD-EEG assists presurgical planning for refractory epilepsy patients, with a higher yield in patients with non-lesional MRIs. Concordance of HD-EEG dipole analysis localization and resection site is a favorable outcome indicator.

Complex negative emotions induced by electrical stimulation of the human hypothalamus.

BACKGROUND: Stimulation of the ventromedial hypothalamic region in animals has been reported to cause attack behavior labeled as sham-rage without offering information about the internal affective state of the animal being stimulated. OBJECTIVE: To examine the causal effect of electrical stimulation near the ventromedial region of the human hypothalamus on the human subjective experience and map the electrophysiological connectivity of the hypothalamus with other brain regions. METHODS: We examined a patient (Subject S20_150) with intracranial electrodes implanted across 170 brain regions, including the hypothalamus. We combined direct electrical stimulation with tractography, cortico-cortical evoked potentials (CCEP), and functional connectivity using resting state intracranial electroencephalography (EEG). RESULTS: Recordings in the hypothalamus did not reveal any epileptic abnormalities. Electrical stimulations near the ventromedial hypothalamus induced profound shame, sadness, and fear but not rage or anger. When repeated single-pulse stimulations were delivered to the hypothalamus, significant responses were evoked in the amygdala, hippocampus, ventromedial-prefrontal and orbitofrontal cortices, anterior cingulate, as well as ventral-anterior and dorsal-posterior insula. The time to first peak of these evoked responses varied and earliest propagations correlated best with the measures of resting-state EEG connectivity and structural connectivity. CONCLUSION: This patient's case offers details about the affective state induced by the stimulation of the human hypothalamus and provides causal evidence relevant to current theories of emotion. The complexity of affective state induced by the stimulation of the hypothalamus and the profile of hypothalamic electrophysiological connectivity suggest that the hypothalamus and its connected structures ought to be seen as causally important for human affective experience.

Patient and Clinician Perspectives of New and Return Ambulatory Teleneurology Visits.

BACKGROUND AND OBJECTIVES: To evaluate the adoption and perceived utility of video visits for new and return patient encounters in ambulatory neurology subspecialties. METHODS: Video visits were launched in an academic, multi-subspecialty, ambulatory neurology clinic in March 2020. Adoption of video visits for new and return patient visits was assessed using clinician-level scheduling data from March 22 to May 16, 2020. Perceived utility of video visits was explored via a clinician survey and semistructured interviews with clinicians and patients/caregivers. Findings were compared across 5 subspecialties and 2 visit types (new vs return). RESULTS: Video visits were adopted rapidly; all clinicians (n = 65) integrated video visits into their workflow within the first 6 weeks, and 92% of visits were conducted via video, although this varied by subspecialty. Utility of video visits was higher for return than new patient visits, as indicated by surveyed (n = 48) and interviewed clinicians (n = 30), aligning with adoption patterns. Compared with in-person visits, clinicians believed that it was easier to achieve a similar physical examination, patient-clinician rapport, and perceived quality of care over video for return rather than new patient visits. Of the 25 patients/caregivers interviewed, most were satisfied with the care provided via video, regardless of visit type, with the main limitation being the physical examination. DISCUSSION: Teleneurology was robustly adopted for both new and return ambulatory neurology patients during the COVID-19 pandemic. Return patient visits were preferred over new patient visits, but both were feasible. These results provide a foundation for developing targeted guidelines for sustaining teleneurology in ambulatory care.

Rapid Implementation of Video Visits in Neurology During COVID-19: Mixed Methods Evaluation.

BACKGROUND: Telemedicine has been used for decades. Despite its many advantages, its uptake and rigorous evaluation of feasibility across neurology's ambulatory subspecialties has been sparse. However, the COVID-19 pandemic prompted health care systems worldwide to reconsider traditional health care delivery. To safeguard health care workers and patients, many health care systems quickly transitioned to telemedicine, including across neurology subspecialties, providing a new opportunity to evaluate this modality of care. OBJECTIVE: To evaluate the accelerated implementation of video visits in ambulatory neurology during the COVID-19 pandemic, we used mixed methods to assess adoption, acceptability, appropriateness, and perceptions of potential sustainability. METHODS: Video visits were launched rapidly in ambulatory neurology clinics of a large academic medical center. To assess adoption, we analyzed clinician-level scheduling data collected between March 22 and May 16, 2020. We assessed acceptability, appropriateness, and sustainability via a clinician survey (n=48) and semistructured interviews with providers (n=30) completed between March and May 2020. RESULTS: Video visits were adopted rapidly; overall, 65 (98%) clinicians integrated video visits into their workflow within the first 6 implementation weeks and 92% of all visits were conducted via video. Video visits were largely considered acceptable by clinicians, although various technological issues impacted their satisfaction. Video visits were reported to be more convenient for patients, families, and caregivers than in-person visits; however, access to technology, the patient's technological capacity, and language difficulties were considered barriers. Many clinicians expressed optimism about future utilization of video visits in neurology. They believed that video visits promote continuity of care and can be incorporated into their practice long-term, although several insisted that they can never replace the in-person examination. CONCLUSIONS: Video visits are an important addition to clinical care in ambulatory neurology and are anticipated to remain a permanent supplement to in-person visits, promoting patient care continuity, and flexibility for patients and clinicians alike.

Epilepsy-Definition, Classification, Pathophysiology, and Epidemiology.

Seizures affect the lives of 10% of the global population and result in epilepsy in 1 to 2% of people around the world. Current knowledge about etiology, diagnosis, and treatments for epilepsy is constantly evolving. As more is learned, appropriate and updated definitions and classification systems for seizures and epilepsy are of the utmost importance. Without proper definitions and classification, many individuals will be improperly diagnosed and incorrectly treated. It is also essential for research purposes to have proper definitions, so that appropriate populations can be identified and studied. Imprecise definitions, failure to use accepted terminology, or inappropriate use of terminology hamper our ability to study and advance the field of epilepsy. This article begins by discussing the pathophysiology and epidemiology of epilepsy, and then covers the accepted contemporary definitions and classifications of seizures and epilepsies.

Status epilepticus and other EEG findings in patients with COVID-19: A case series.

PURPOSE: Neurological manifestations of COVID-19 infection include impaired consciousness, strokes, and seizures. Limited reports describing EEG abnormalities in patients with COVID-19 have been published. These articles reported nonspecific encephalopathic patterns, epileptiform discharges, and rarely seizures. Our primary aim was to assess EEG abnormalities in patients with COVID-19 and evaluate for epileptiform activity or seizures. METHODS: We identified five critically ill adult patients with COVID-19 who underwent EEG monitoring. All patients had Ceribell™ rapid response EEG initially and two continued with conventional long-term video EEG. RESULTS: All 5 patients had encephalopathy and 3 also had seizure-like movements, thus prompting EEG monitoring. EEGs all showed nonspecific markers of encephalopathy including diffuse slowing and generalized rhythmic delta activity. Two also had epileptiform discharges reaching 2-3 Hz at times, with one patient in nonconvulsive status epilepticus and the other developing clinical status epilepticus with myoclonic movements. EEG and clinical symptoms improved with anti-seizure medications. CONCLUSION: Status epilepticus was present in 2 out of our cohort of 5 critically ill patients who underwent EEG monitoring. These findings highlight the importance of EEG monitoring in high-risk patients with COVID-19 and encephalopathy. EEG recordings in such patients can identify pathological patterns that will benefit from treatment with anti-seizure medications.

Selective Participation of Single Cortical Neurons in Neuronal Avalanches.

Neuronal avalanches are scale-invariant neuronal population activity patterns in the cortex that emerge in vivo in the awake state and in vitro during balanced excitation and inhibition. Theory and experiments suggest that avalanches indicate a state of cortex that improves numerous aspects of information processing by allowing for the transient and selective formation of local as well as system-wide spanning neuronal groups. If avalanches are indeed involved with information processing, one might expect that single neurons would participate in avalanche patterns selectively. Alternatively, all neurons could participate proportionally to their own activity in each avalanche as would be expected for a population rate code. Distinguishing these hypotheses, however, has been difficult as robust avalanche analysis requires technically challenging measures of their intricate organization in space and time at the population level, while also recording sub- or suprathreshold activity from individual neurons with high temporal resolution. Here, we identify repeated avalanches in the ongoing local field potential (LFP) measured with high-density microelectrode arrays in the cortex of awake nonhuman primates and in acute cortex slices from young and adult rats. We studied extracellular unit firing in vivo and intracellular responses of pyramidal neurons in vitro. We found that single neurons participate selectively in specific LFP-based avalanche patterns. Furthermore, we show in vitro that manipulating the balance of excitation and inhibition abolishes this selectivity. Our results support the view that avalanches represent the selective, scale-invariant formation of neuronal groups in line with the idea of Hebbian cell assemblies underlying cortical information processing.

Comparative neuropsychological effects of carbamazepine and eslicarbazepine acetate.

People with epilepsy are at increased risk for neuropsychological dysfunction due to multiple factors, of which the most amendable are antiseizure medications (ASMs). Antiseizure medication effectiveness is frequently determined by tolerability. In this study, we compared the neuropsychological effects of eslicarbazepine acetate (ESL) and carbamazepine immediate-release (CBZ) using a randomized, double-blind, crossover design in healthy volunteers with a 2-week titration and 4-week maintenance phase in each treatment arm (CBZ = 400 mg BID and ESL = 800 mg qAM). Neuropsychological testing was performed at the initial visit, repeated at 1st baseline nondrug condition, end treatment #1, 2nd nondrug condition one month after treatment #1, end treatment #2, and 3rd nondrug condition one month after treatment #2. Neuropsychological testing was conducted 2 h after morning dose and included computer (i.e., dual task test, selective attention test, symbol digit, verbal memory, visuospatial memory, and 1- & 2-back continuous performance) and noncomputer tasks (i.e., Medical College of Georgia (MCG) paragraph memory, Stroop, Symbol Digit Modalities Test, Profile of Mood States). z-Scores calculated from nondrug conditions were used to compare ESL and CBZ for the 23 completers. Follow-up analyses included individual test scores and distribution of individual raw means. Mean blood levels on test day were CBZ = 8.9 µg/ml and ESL = 15.3 µg/ml. Omnibus z-score was significantly better for ESL (p = .0001). For individual measures, executive function and selective attention tests were statistically significantly better for ESL. Individual test raw means favored ESL over CBZ on 22 of 30 measures (p = .016, 2-tailed sign test). Eslicarbazepine acetate demonstrated less adverse neuropsychological effects than CBZ.

Modified ketogenic diets in adults with refractory epilepsy: Efficacious improvements in seizure frequency, seizure severity, and quality of life.

OBJECTIVE: This study evaluates the efficacy of a modified ketogenic diet (MKD) on seizure frequency, severity, and quality of life (QOL), as well as potential complications of MKD therapy among adults with drug-resistant epilepsy (DRE). METHODS: Changes in seizure frequency, severity, QOL, and side effects were retrospectively examined among adults, ≥17 years of age, with DRE (≥2 antiepileptic drugs [AEDs]), after 3 months of MKD therapy. Attention was paid to medication or vagus nerve stimulator (VNS) changes as well to evaluate potential confounders. RESULTS: A total of 60% (n = 33) of the 55 individuals reported ≥50% seizure frequency improvement, 42 (76%) reported improvement in seizure severity, and 48 (87%) reported improvement in QOL. More patients following a modified ketogenic diet - 15 g net carbohydrate daily (MKD-15) (95%) compared with a MKD-50 (69%) reported improvement in QOL (p = 0.02). Weight among the entire sample declined from 77.5 (20) kg to 73.9 (19.0) kg (p < 0.0001), and total cholesterol (TC), low density lipoprotein (LDL), and total cholesterol:high density lipoprotein (TC:HDL) increased significantly (p = 0.03, p = 0.04, and p = 0.02, respectively). Free carnitine values were available for a select number of patients, 26 (47%) at baseline, and 7 (13%) at follow-up, of which 8 (31%) at baseline, and 2 (29%) at follow-up had carnitine deficiency (<25 nmol/mL). Constipation was noted in 5 patients (9%), and no kidney stones were reported during the study period. There were no statistical differences in number or dose changes for AED or VNS during the study period. SIGNIFICANCE: Modified ketogenic diet therapies reduce seizure frequency and severity and improve QOL among adults with DRE with few side effects outside of weight loss, a desired outcome among many adults with DRE. More restrictive MKDs may offer improved seizure severity and QOL. Modified ketogenic diet therapy increases LDL cholesterol, which may be cardioprotective if related to an increase in LDL particle size with high saturated fat intake; however, more research is needed examining LDL particle size changes among those receiving MKD therapy.

Do certain subpopulations of adults with drug-resistant epilepsy respond better to modified ketogenic diet treatments? Evaluation based on prior resective surgery, type of epilepsy, imaging abnormalities, and vagal nerve stimulation.

OBJECTIVE: Adults with drug-resistant epilepsy (DRE) are among the most challenging to treat. This study assessed whether specific subpopulations of adult patients with refractory epilepsy responded differently to modified ketogenic diet (MKD) therapy. METHODS: Changes in seizure frequency, severity, and quality of life (QOL) were retrospectively analyzed based on pre-MKD surgical history, type of epilepsy, imaging findings, and vagal nerve stimulation (VNS) history among adults, ≥17 years of age, with DRE, receiving MKD therapy for three months. Additionally, particular attention was made to medication and VNS adjustments. RESULTS: Responder rates in seizure frequency, severity, and QOL reported among those with prior surgery were 56%, 75%, and 94%, respectively. Among those with focal epilepsy: 57%, 76%, and 76% had improvements in seizure frequency, seizure severity, and QOL, respectively whereas 83% improvement was seen for all three measures in those with generalized epilepsy. Among those with abnormal imaging: just over 50% reported improvements on all measures. For those with VNS, 53%, 63%, and 95% had improvements in seizure frequency, seizure severity, and QOL, respectively. No statistical differences in seizure frequency, severity, or QOL were noted between groups based on prediet surgical history, seizure type, imaging abnormalities, or VNS history. Compared with expected improvement from medication adjustment alone, significant improvement was seen for all groups; notably, the Z-test for proportions for the surgery group, when compared with placebo responder rates at 20%, was 3.6, p < 0.001. CONCLUSIONS: Modified ketogenic diet therapies are effective in improving seizure frequency, severity, and QOL and may offer the best chance for improvement among those whose seizures have persisted despite surgical intervention and VNS therapy. All types of epilepsy respond to MKDs, and possibly those with generalized epilepsy may respond better.

The new definition and classification of seizures and epilepsy.

This review discusses the updated classifications of seizures and the epilepsies, which were recently published by the International League Against Epilepsy (ILAE). While it is always a challenge to learn a new classification system, particularly one that has remained essentially unchanged for over three decades, these new classifications allow for the inclusion of some previously unclassifiable seizure types and utilize more intuitive terminology. In this review, we specifically discuss the use of these new classifications for patients, clinicians, and researchers.

Magnetoencephalography and New Imaging Modalities in Epilepsy.

The success of epilepsy surgery is highly dependent on correctly identifying the entire epileptogenic region. Current state-of-the-art for localizing the extent of surgically amenable areas involves combining high resolution three-dimensional magnetic resonance imaging (MRI) with electroencephalography (EEG) and magnetoencephalography (MEG) source modeling of interictal epileptiform activity. Coupling these techniques with newer quantitative structural MRI techniques, such as cortical thickness measurements, however, may improve the extent to which the abnormal epileptogenic region can be visualized. In this review we assess the utility of EEG, MEG and quantitative structural MRI methods for the evaluation of patients with epilepsy and introduce a novel method for the co-localization of a structural MRI measurement to MEG and EEG source modeling. When combined, these techniques may better identify the extent of abnormal structural and functional areas in patients with medically intractable epilepsy.

'Tickling' seizures originating in the left frontoparietal region.

We report a 10-year-old boy with mild developmental delay and epilepsy with new events of right back tickling and emotional upset. These initially appeared behavioral, causing postulation of habit behaviors or psychogenic nonepileptic seizures. Several ictal and interictal EEGs were unrevealing. Continuous EEG revealed only poorly localized frontal ictal activity. Given that his clinical symptoms suggested a parietal localization, double-density EEG electrodes were placed to better localize the epileptogenic and symptomatogenic zones. These revealed evolution of left greater than right frontoparietal discharges consistent with seizures at the time of the attacks. Medical management has significantly reduced the patient's seizures.

Treatment of Established Status Epilepticus.

Status epilepticus is the most severe form of epilepsy, with a high mortality rate and high health care costs. Status epilepticus is divided into four stages: early, established, refractory, and super-refractory. While initial treatment with benzodiazepines has become standard of care for early status epilepticus, treatment after benzodiazepine failure (established status epilepticus (ESE)) is incompletely studied. Effective treatment of ESE is critical as morbidity and mortality increases dramatically the longer convulsive status epilepticus persists. Phenytoin/fosphenytoin, valproic acid, levetiracetam, phenobarbital, and lacosamide are the most frequently prescribed antiseizure medications for treatment of ESE. To date there are no class 1 data to support pharmacologic recommendations of one agent over another. We review each of these medications, their pharmacology, the scientific evidence in support and against each in the available literature, adverse effects and safety profiles, dosing recommendations, and limitations of the available evidence. We also discuss future directions including the established status epilepticus treatment trial (ESETT). Substantial further research is urgently needed to identify these patients (particularly those with non-convulsive status epilepticus), elucidate the most efficacious antiseizure treatment with head-to-head randomized prospective trials, and determine whether this differs for convulsive vs. non-convulsive ESE.