Patterns of antiseizure medication utilization in the Human Epilepsy Project.

OBJECTIVE: This study was undertaken to ascertain the natural history and patterns of antiseizure medication (ASM) use in newly diagnosed focal epilepsy patients who were initially started on monotherapy. METHODS: The data were derived from the Human Epilepsy Project. Differences between the durations of the most commonly first prescribed ASM monotherapies were assessed using a Cox proportional hazards model. Subjects were classified into three groups: monotherapy, sequential monotherapy, and polytherapy. RESULTS: A total of 443 patients were included in the analysis, with a median age of 32 years (interquartile range [IQR] = 20-44) and median follow-up time of 3.2 years (IQR = 2.4-4.2); 161 (36.3%) patients remained on monotherapy with their initially prescribed ASM at the time of their last follow-up. The mean (SEM) and median (IQR) duration that patients stayed on monotherapy with their initial ASM was 2.1 (2.0-2.2) and 1.9 (.3-3.5) years, respectively. The most commonly prescribed initial ASM was levetiracetam (254, 57.3%), followed by lamotrigine (77, 17.4%), oxcarbazepine (38, 8.6%), and carbamazepine (24, 5.4%). Among those who did not remain on the initial monotherapy, 167 (59.2%) transitioned to another ASM as monotherapy (sequential monotherapy) and 115 (40.8%) ended up on polytherapy. Patients remained significantly longer on lamotrigine (mean = 2.8 years, median = 3.1 years) compared to levetiracetam (mean = 2.0 years, median = 1.5 years) as a first prescribed medication (hazard ratio = 1.5, 95% confidence interval = 1.0-2.2). As the study progressed, the proportion of patients on lamotrigine, carbamazepine, and oxcarbazepine as well as other sodium channel agents increased from a little more than one third (154, 34.8%) of patients to more than two thirds (303, 68.4%) of patients. SIGNIFICANCE: Slightly more than one third of focal epilepsy patients remain on monotherapy with their first prescribed ASM. Approximately three in five patients transition to monotherapy with another ASM, whereas approximately two in five end up on polytherapy. Patients remain on lamotrigine for a longer duration compared to levetiracetam when it is prescribed as the initial monotherapy.

Drug-resistant epilepsy: Definition, pathophysiology, and management.

There are currently >51 million people with epilepsy (PWE) in the world and every year >4.9 million people develop new-onset epilepsy. The cornerstone of treatment in PWE is drug therapy with antiseizure medications (ASMs). However, about one-third of PWE do not achieve seizure control and do not respond well to drug therapy despite the use of appropriate ASMs [drug-resistant epilepsy (DRE)]. The aims of the current narrative review are to discuss the definition of DRE, explain the biological underpinnings and clinical biomarkers of this condition, and finally to suggest practical management strategies to tackle this issue appropriately, in a concise manner.

The cenobamate-clobazam interaction- evidence of synergy in addition to pharmacokinetic interaction.

OBJECTIVES: Report insights into the pharmacokinetic and pharmacodynamic interaction between cenobamate (CNB) and clobazam (CLB), derived from data in patients enrolled at our center in a global multicenter open-label safety study of CNB. MATERIALS & METHODS: Patients in this study either took CLB at baseline (n = 6) or had CLB added after CNB titration to maximal dose (n = 5) in addition to other antiseizure medications. Clobazam was always administered as a single bedtime dose. Random serum concentrations of CLB and N-desmethylclobazam (N-CLB) were obtained. RESULTS: Baseline daily CLB doses were 20-50 mg. Sedation began in the six baseline CLB patients at CNB doses of 25-100 mg. The N-CLB/ CLB ratio increased proportionally to the CNB dose. CLB was stopped in all six patients, five of whom were ≥50% responders. Seizure control deteriorated after stopping CLB, with only one remaining responder. Clobazam was restarted at 5 mg/d in five of the six patients. At the last follow-up, four of these patients were continuing CLB; two were seizure-free and 2 were ≥50% responders. Among the five patients that added 5 mg/d CLB de novo, three were responders. All patients were still on CNB at the end of the study. DISCUSSION: Data suggest starting CLB dose reduction at CNB doses of 25-100 mg/d. Due to possible synergy, the addition of low-dose CLB could be considered in patients with incomplete response to CNB.

Epilepsy with anterior temporal encephaloceles: Baseline characteristics, post-surgical outcomes, and comparison to mesial temporal sclerosis.

OBJECTIVE: To review clinical and neuropsychological characteristics and natural history of a series of patients with temporal lobe epilepsy (TLE) and anterior temporal encephaloceles (ATE) and compare them to a similar series of TLE patients with mesial temporal sclerosis (MTS) to identify characteristics suggestive of ATE-related epilepsy. METHODS: Patients with epilepsy and ATE were identified via clinic encounters and consensus epilepsy surgery conference at a Level 4 epilepsy center. The drug-resistant subset of these patients who underwent epilepsy surgery (twenty-two of thirty-five) were compared to age- and laterality-matched patients with MTS. Clinical, neuropsychological, electrophysiologic, and surgical data were abstracted through chart review. RESULTS: In comparison with MTS, ATE patients were more often female, had significantly later onset of epilepsy, and did not have prior febrile seizures. In addition, ATE patients were more likely to have chronic headaches and other historical features consistent with idiopathic intracranial hypertension (IIH). Failure to identify ATE on initial imaging was common. Most patients had limited temporal cortical resections sparing mesial structures. Of the twenty ATE patients who had a long-term postsurgical follow-up, seventeen (85%) had International League Against Epilepsy (ILAE) Class 1 or 2 outcomes. SIGNIFICANCE: A shorter duration of epilepsy, female gender, and lack of history of febrile seizures may suggest ATE as an etiology of refractory TLE in adults. Targeted encephalocele resections can result in seizure freedom, underscoring the importance of encephalocele identification.

Retrospective analysis of nurse-administered fall assessment scales in the Epilepsy Monitoring Unit.

INTRODUCTION: Inpatient falls within the Epilepsy Monitoring Unit (EMU) are a common, and potentially preventable adverse event contributing to morbidity for patients living with epilepsy. Accurate fall risk screening is important to identify and efficiently allocate proper safety measures to high-risk patients, especially in EMUs with limited resources. We sought to compare existing screening tools for the ability to predict falls in the EMU. METHODS: This is a retrospective, single-center, case-controlled, comparative analysis of 7 nurse-administered fall risk assessment tools (NAFRAT) of patients admitted to the Vanderbilt University Medical Center (VUMC) EMU. Analysis of categorical data was compared using chi-square analysis while quantitative distributions were compared using student's t-test. RESULTS: A total of 56 patient records (28 falls and 28 controls) were included in the analysis. Epilepsy Monitoring Unit falls were most common within the first 3 days of admission (p = .0094). Pre-admission documentation of falls was a strong predictor of falls within the EMU (p < .0001). Epilepsy Monitoring Unit falls were associated with documented falls after EMU discharge (p = .011). The John Hopkins fall risk assessment tool (JHFRAT) accurately stratified fall risk in the fall group compared to the control (p = .008), however, none of the 7 NAFRATs demonstrated significant categorical differences among the epilepsy subgroups. There was a significant difference in the distribution of quantitative scores, higher in the fall group according to the Morse Fall Scale (MFS) (p = 0.012), JHFRAT (p = 0.003), Schmid Fall Risk Assessment Scale (p = 0.029) and Hester-Davis Scale (p = 0.049). The modified Conley (p = 0.03) and Morse scale (p = 0.025) demonstrated differences in the distribution of quantitative scores in the epilepsy subgroups. CONCLUSION: The findings of this study demonstrate variable accuracy of NAFRATs in assessing fall risk among patients admitted to the EMU, particularly among patients with epilepsy. The findings underscore the need for a validated, EMU-specific, fall assessment tool that accurately stratifies fall risk and inform efficient use of patient-specific fall prevention resources and protocols.

Mood and Anxiety Disorders and Suicidality in Patients With Newly Diagnosed Focal Epilepsy: An Analysis of a Complex Comorbidity.

BACKGROUND AND OBJECTIVES: Mood, anxiety disorders, and suicidality are more frequent in people with epilepsy than in the general population. Yet, their prevalence and the types of mood and anxiety disorders associated with suicidality at the time of the epilepsy diagnosis are not established. We sought to answer these questions in patients with newly diagnosed focal epilepsy and to assess their association with suicidal ideation and attempts. METHODS: The data were derived from the Human Epilepsy Project study. A total of 347 consecutive adults aged 18-60 years with newly diagnosed focal epilepsy were enrolled within 4 months of starting treatment. The types of mood and anxiety disorders were identified with the Mini International Neuropsychiatric Interview, whereas suicidal ideation (lifetime, current, active, and passive) and suicidal attempts (lifetime and current) were established with the Columbia Suicidality Severity Rating Scale (CSSRS). Statistical analyses included the t test, χ2 statistics, and logistic regression analyses. RESULTS: A total of 151 (43.5%) patients had a psychiatric diagnosis; 134 (38.6%) met the criteria for a mood and/or anxiety disorder, and 75 (21.6%) reported suicidal ideation with or without attempts. Mood (23.6%) and anxiety (27.4%) disorders had comparable prevalence rates, whereas both disorders occurred together in 43 patients (12.4%). Major depressive disorders (MDDs) had a slightly higher prevalence than bipolar disorders (BPDs) (9.5% vs 6.9%, respectively). Explanatory variables of suicidality included MDD, BPD, panic disorders, and agoraphobia, with BPD and panic disorders being the strongest variables, particularly for active suicidal ideation and suicidal attempts. DISCUSSION: In patients with newly diagnosed focal epilepsy, the prevalence of mood, anxiety disorders, and suicidality is higher than in the general population and comparable to those of patients with established epilepsy. Their recognition at the time of the initial epilepsy evaluation is of the essence.

Temporal intermittent rhythmic theta activity (TIRTA): A marker of epileptogenicity?

Objective: To describe a novel EEG rhythm, temporal intermittent rhythmic theta activity (TIRTA), and its potential association with epilepsy. Methods: We report TIRTA on scalp EEG in a series of 12 patients, all of whom were found to have epilepsy. The clinical and electroencephalographic characteristics of each patient were reviewed. In addition, features that may distinguish TIRTA from benign EEG patterns, including rhythmic temporal theta bursts of drowsiness (RTTBD), were identified. Results: TIRTA was unilateral in all cases. For all patients, TIRTA was seen in the awake and drowsy states. Eight patients also had TIRTA observed during N2 sleep. The average frequency of TIRTA was 5.5 Hz and the average duration of a train of TIRTA was 5.25 s. In seven cases the morphology was notched in appearance. Temporal intermittent rhythmic delta activity (TIRDA) was seen in seven patients on the same side as TIRTA. Eleven patients also had ipsilateral temporal sharp waves. Abnormal MRI (6/12) and or PET (5/5) findings were ipsilateral to TIRTA. Conclusions: In this preliminary report we suggest that TIRTA may be a novel marker of potential epileptogenicity, possibly representing a higher frequency variant of TIRDA.

Efficacy of cenobamate for uncontrolled focal seizures in patients with previous epilepsy-related surgery: Post hoc analysis of a phase 3, multicenter, open-label study.

OBJECTIVE: This post hoc analysis of 10 US study sites from a long-term open-label phase 3 study of adjunctive cenobamate evaluated the efficacy of cenobamate in patients with prior epilepsy-related surgery. METHODS: Patients with uncontrolled focal seizures despite taking stable doses of 1-3 concomitant antiseizure medications (ASMs) received increasing doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) at 2-week intervals over 12 weeks (target dose, 200 mg/day). Further increases up to 400 mg/day using biweekly 50-mg/day increments were allowed during the maintenance phase. Dose adjustments of cenobamate and concomitant ASMs were allowed. Data were assessed until the last clinic visit on or after September 1, 2019. RESULTS: Of the 240 eligible patients, 85 had prior epilepsy-related surgery and 155 were nonsurgical patients. Baseline focal seizure frequency per 28 days was numerically higher among prior surgery (mean=25.9/median=4.1/range=0.3-562.3) versus nonsurgical (mean=13.8/median=2.4/range=0.2-534.2) patients. Among all patients, 100 % seizure reduction ≥ 12 months at any consecutive month interval occurred in 30.6 % (26/85) prior surgery and 39.4 % (61/155; p > 0.05) nonsurgical patients (cenobamate treatment median duration=32.9 months). Among the 177 patients still receiving cenobamate at the data cutoff, 29.2 % (19/65) of prior surgery and 36.6 % (41/112; p > 0.05) of nonsurgical patients had 100 % seizure reduction ≥ 12 months at the data cutoff. Cenobamate was well tolerated. CONCLUSIONS: This post hoc analysis supports the efficacy of cenobamate in patients with refractory focal seizures despite prior surgery. These findings suggest cenobamate may be considered early in the treatment regimen, including, in some patients, before surgery is considered.

Network connectivity in primary generalized tonic-clonic seizures.

OBJECTIVE: To determine EEG spatiospectral activation and connectivity in the generalized tonic-clonic seizure (GTCS) semiological subtypes. METHODS: 39 patients with genetic generalized epilepsy (GGE) who had GTCS (n = 58) during video-EEG monitoring were identified in the Vanderbilt Epilepsy database. GTCSs were classified as absence tonic-clonic, myoclonic tonic-clonic, or tonic-clonic. Patient characteristics and semiological features were compared. Spectral power and node degree, a network measure of connectivity, were calculated at two seizure epochs, electrographic and tonic-start. RESULTS: Different GTCS subtypes occurred within individual patients. At electrographic-onset, all subtypes activated midline frontal cortex at delta/theta and beta frequencies but differed in network connectivity. In all subtypes, GTCS evolution from electrographic to tonic-start associated with preserved beta frequency spectral power, but reduced connectivity and delta/theta power. CONCLUSIONS: Our findings suggest that at GTCS onset, the subtypes activate similar cortical regions and their different initial semiologies relate to their distinct onset long-range connectivity. Upon transition to the tonic-start epoch, the ictal activity is predominantly conveyed by ß frequency activity and connectivity. SIGNIFICANCE: Future neurostimulation therapies for medically intractable GTCSs may target the same brain regions for all GTCS subtypes and may be most effective prior to the tonic-start epoch.

Update on Antiseizure Medications 2022.

EDITORS NOTE: The article "Update on Antiseizure Medications 2022" by Dr Abou-Khalil was first published in the February 2016 Epilepsy issue of Continuum: Lifelong Learning in Neurology as "Antiepileptic Drugs," and at the request of the Editor-in-Chief was updated by Dr Abou-Khalil for the 2019 issue and again for this issue.

This article is an update from the article on antiepileptic drug therapy (now referred to as antiseizure medication therapy ) published in the two previous Continuum issues on epilepsy and is intended to cover the vast majority of agents currently available to the neurologist in the management of patients with epilepsy. Treatment of epilepsy starts with antiseizure medication monotherapy. Knowledge of the spectrum of efficacy, clinical pharmacology, and modes of use for individual antiseizure medications is essential for optimal treatment for epilepsy. This article addresses antiseizure medications individually, focusing on key pharmacokinetic characteristics, indications, and modes of use. Since the most recent version of this article was published, two new antiseizure medications, cenobamate and fenfluramine, have been approved by the US Food and Drug Administration (FDA), and the indications of some approved medications have been expanded. Older antiseizure medications are effective but have tolerability and pharmacokinetic disadvantages. Several newer antiseizure medications have undergone comparative trials demonstrating efficacy equal to and tolerability at least equal to or better than older antiseizure medications as first-line therapy for focal epilepsy. The list includes lamotrigine, oxcarbazepine, levetiracetam, topiramate, zonisamide, and lacosamide. Pregabalin was found to be less effective than lamotrigine. Lacosamide, pregabalin, and eslicarbazepine have undergone successful trials of conversion to monotherapy for focal epilepsy. Other newer antiseizure medications with a variety of mechanisms of action are suitable for adjunctive therapy. Antiseizure medications marketed since 2016 have benefited from the FDA policy allowing a drug's efficacy as adjunctive therapy in adults to be extrapolated to efficacy in monotherapy. In addition, efficacy in adults can be extrapolated for efficacy in children 4 years of age and older. Both extrapolations require data demonstrating that an antiseizure medication has equivalent pharmacokinetics between its original approved use and its extrapolated use. Rational antiseizure medication combinations should avoid antiseizure medications with unfavorable pharmacokinetic interactions or pharmacodynamic interactions related to mechanism of action. Knowledge of antiseizure medication pharmacokinetics, efficacy, and tolerability profiles facilitates the choice of appropriate antiseizure medication therapy for patients with epilepsy.

Determinants of postictal agitation and recovery after tonic-clonic seizures in generalized and focal epilepsy.

OBJECTIVE: The postictal state after bilateral tonic-clonic seizures is often prolonged and can have significant impact on a patient's quality of life. Considerable variability exists in the magnitude of postictal agitation and in the speed of recovery, the determinants of which are not well understood. We studied postictal behavior after tonic-clonic seizures in various epilepsy localizations, focusing on postictal agitation and time to responsiveness. METHODS: We retrospectively identified 15 adult patients each with idiopathic generalized, left temporal lobe, right temporal lobe and frontal lobe epilepsy. Localization in focal epilepsy was validated by good outcome after resective surgery at one-year of follow-up. The first tonic-clonic seizure with reliable video and EEG for each patient was analyzed by two reviewers, one of whom was blinded to clinical data. Clinical, ictal and postictal variables were collected for each patient and analyzed. Postictal agitation was classified as mild and marked. RESULTS: We reviewed 60 tonic-clonic seizures, 15 in each of four patient groups. Postictal agitation was observed in 14 patients (23.3%; marked in one and mild in 13). Postictal agitation was most common in patients with left temporal (seven patients) and least common in idiopathic generalized epilepsy (one patient) groups (p=0.035). Based on subgroup analysis (n=28), time to responsiveness was 6.6 minutes for frontal, 7.2 minutes for generalized, 10 minutes for right temporal and 15.7 minutes for the left temporal groups (p<0.05 for frontal vs. left temporal, generalized vs. left temporal). Time to responsiveness was longer in patients with agitation than without (13.9 minutes vs. 7.7 minutes; p=0.048). Patient ictal and postictal characteristics demonstrated no relationship to agitation or latency to postictal recovery. SIGNIFICANCE: To mitigate harm, patients must be monitored carefully after tonic-clonic seizures, especially patients with left temporal lobe epilepsy. Studies evaluating medical and behavioral interventions to promote postictal recovery are needed.

Post hoc analysis of a phase 3, multicenter, open-label study of cenobamate for treatment of uncontrolled focal seizures: Effects of dose adjustments of concomitant antiseizure medications.

OBJECTIVE: To report post hoc results on how adjustments to baseline antiseizure medications (ASMs) in a subset of study sites (10 US sites) from a long-term, open-label phase 3 study of adjunctive cenobamate affected tolerability, efficacy, and retention. METHODS: Patients with uncontrolled focal seizures taking stable doses of one to three ASMs were administered increasing doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) over 12 weeks at 2-week intervals (target dose = 200 mg/day). Further increases to 400 mg/day by 50 mg/day biweekly increments were allowed during maintenance phase. Dose adjustments of cenobamate and concomitant ASMs were allowed. Data were assessed until last visit, at data cut-off, on or after September 1, 2019. RESULTS: A total of 240 patients meeting eligibility criteria were assessed (median [max] exposure 30.2 [43.0] months), with 177 patients continuing cenobamate at data cut-off. Most common baseline concomitant ASMs were lacosamide, levetiracetam, lamotrigine, zonisamide, and clobazam. For most baseline concomitant ASMs, ~70% of patients taking that ASM were continuing cenobamate at data cut-off. Patients continuing cenobamate had greater mean ASM dose reductions and percent dose changes from baseline vs those who discontinued. Of patients continuing cenobamate, 24.6% discontinued one or more concomitant ASMs completely. Dose decreases for all concomitant ASMs generally occurred during titration or early maintenance phases and were mostly due to central nervous system (CNS)-related adverse events such as somnolence, dizziness, unsteady gait, and fatigue. Responder rates from ≥50% through 100% for patients continuing cenobamate were generally similar regardless of concomitant ASMs (of those most commonly taken), with ~81% being ≥50% responders and ~12% achieving 100% seizure reduction in the maintenance phase, which lasted up to 40.2 (median = 29.5) months. SIGNIFICANCE: Concomitant ASM dose reductions were associated with more patients remaining on cenobamate. This is likely due to efficacy and improved tolerability, with overall reduced concomitant drug burden in patients with uncontrolled seizures despite taking one to three baseline concomitant ASMs.

Efficacy of cenobamate for uncontrolled focal seizures: Post hoc analysis of a Phase 3, multicenter, open-label study.

OBJECTIVE: To report long-term post hoc efficacy and safety data from 10 US study sites from an open-label Phase 3 study of adjunctive cenobamate (NCT02535091). METHODS: Patients with uncontrolled focal seizures taking stable doses of 1-3 antiseizure medications (ASMs) were administered increasing daily doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) over 12 weeks at 2-week intervals (target dose = 200 mg/day). Further increases to 400 mg/day by 50-mg/day increments biweekly were allowed during the maintenance phase. Dose adjustments of cenobamate and concomitant ASMs were allowed. Data were assessed until the last clinic visit on or after September 1, 2019. RESULTS: Of 255 patients, 240 with focal aware motor, focal impaired awareness, or focal to bilateral tonic-clonic seizure data while on treatment were evaluated (median [maximum] exposure = 30.2 [43.0] months across the entire study). Median baseline seizure frequency/28 days was 2.8 (mean = 18.1). Of the 240 patients, 177 (73.8%) were continuing cenobamate treatment at data cutoff. The ≥50% responder rate for the total treatment duration was 71.7% (172/240). During titration, the ≥50% responder rates were 48.1% during Weeks 1-4 (12.5-25 mg/day cenobamate) and 61.7% during Weeks 5-8 (50-100 mg/day cenobamate). Among all patients who received a dose of cenobamate in the maintenance phase (n = 214), 13.1% (28/214) and 40.2% (86/214) achieved 100% and ≥90% seizure reduction during their entire maintenance treatment duration (median = 29.5 months). Among all patients, 87 (36.3%) had any consecutive ≥12-month duration of 100% seizure reduction. Common treatment-emergent adverse events among all 240 patients included fatigue (34.6%), dizziness (32.1%), and somnolence (29.6%). SIGNIFICANCE: This post hoc analysis of a subset of patients from the long-term open-label study showed high rates of sustained 100% and ≥90% seizure reduction, with many achieving response early during titration. These findings suggest durable seizure frequency reduction with cenobamate in adults with uncontrolled focal seizures.

Seizure clusters.

Acute repetitive seizures, also called seizure clusters, are common phenomena in patients with epilepsy. They are a burden on patients and their caregivers and may be very disruptive to the patients' lives. They may progress to prolonged seizures or status epilepticus if they are not aborted as soon as possible. However, their definition, recognition, and classification still suffer from a lack of consensus among healthcare professionals in the field. This review aims to shed light on various aspects of seizure clusters with particular attention to their treatments.

Enhanced rates of detection and treatment of depression and anxiety disorders among adult patients with epilepsy using automated EMR-based screening.

OBJECTIVE: Depression and anxiety disorders are common among patients with epilepsy (PWE). These comorbidities have been shown to influence prognosis and may have a greater impact on quality of life than seizure control. Despite guideline recommendations and expert consensus to regularly screen for and treat both conditions, there is evidence that they are underdiagnosed and undertreated. Our goal was to test a novel screening method to determine if it would increase the rate of detecting and treating depression and anxiety disorders among PWE. METHOD: The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and the Brief Epilepsy Anxiety Survey Instrument (brEASI) were selected as validated screening instruments for depression and anxiety disorders, respectively. They were sent via an electronic medical record-linked patient portal to all patients of four epileptologists 48 h prior to their clinic appointment. We evaluated whether this increased the rate of detecting and treating depression and anxiety disorders relative to a historical control group. RESULTS: A total of 563 patients were included of whom 351 were sent the screening instruments. 62.7% of patients completed the screening instruments of whom 47.7% screened positive for either depression only (16.4%), anxiety disorders only (5.5%) or both (25.9%); a statistically significant increase relative to the control group. There was also a significantly increased proportion of patients for whom treatment was initiated for depression (p < 0.01), anxiety disorders (p < 0.01), or both (p < 0.01). CONCLUSIONS: We identified an easily applicable and efficient means of enhancing detection and treatment rates for depression and anxiety disorders among PWE in a busy clinic setting.

Near SUDEP during bilateral stereo-EEG monitoring characterized by diffuse postictal EEG suppression.

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in patients with refractory epilepsy. The pathophysiology of SUDEP is unknown. Postictal phenomena such as postconvulsive immobility (PI), postictal generalized electroencephalography (EEG) suppression (PGES), arousal deficits, cardiac arrhythmias, central apneas, and obstructive apneas due to laryngospasms have been suggested to contribute to SUDEP. We present, to our knowledge, the first case of a near-SUDEP event in a patient undergoing intracranial, stereotactic EEG (sEEG) monitoring. This case spotlights potential mediators of SUDEP, most notably the striking PGES and postictal apnea. The nature of the sEEG investigation illustrates the extent of cortical and subcortical postictal EEG suppression and showcases a transient return of cerebral activity likely to be missed on scalp-EEG recording. Critically, this case emphasizes the importance of continuous cardiorespiratory monitoring and underscores the importance of postictal arousal as a pathophysiological mechanism in SUDEP.

Baseline neuropsychological characteristics in patients with epilepsy with left temporal lobe encephaloceles compared with left mesial temporal sclerosis.

BACKGROUND: Temporal lobe encephaloceles (TE) are increasingly recognized as a cause of drug-resistant temporal lobe epilepsy. Improved recognition of these lesions offers an opportunity to treat them with a limited resection sparing the hippocampus. However, as they can be difficult to identify on imaging, additional clues pointing to the diagnosis can be helpful. We sought to understand the baseline cognitive/neuropsychological profile in patients with left temporal lobe epilepsy caused by encephaloceles compared with that caused by mesial temporal sclerosis (MTS), a common entity in the differential diagnosis. METHODS: Neuropsychological testing, including language (semantic and phonemic fluency and naming), verbal memory, intelligence quotient (IQ), and executive function measures were compared across two groups (five patients with left TE and five age- and gender-matched patients with left MTS). Other clinical variables related to cognition, including patient age, electroencephalographic characteristics, epilepsy duration, and factors related to antiseizure medication dosing, were also compared between groups. RESULTS: More patients with left MTS had atypical language lateralization (3/5 with right-sided language in the group with MTS compared with 0/5 in the group with TE). Patients with MTS had significantly worse scores on the Verbal Comprehension Index (VCI) subscore of the Wechsler Adult Intelligence Scale (WAIS; p = 0.026). General IQ was also worse in patients with MTS (p = 0.028). There was a trend towards worse executive function in patients with MTS as measured on Trails B (p = 0.096). Other measures related to language and verbal memory did not differ significantly between the groups nor did other relevant clinical variables, except epilepsy duration, which was significantly longer in patients with MTS (p = 0.0001). CONCLUSIONS: This pilot study demonstrates few significant differences between the groups with left MTS and TE surveyed. A higher rate of atypical language lateralization was noted in patients with left MTS. The higher baseline global IQ and VCI scores in patients with left TE compared with patients with MTS may be attributable to longer duration of epilepsy in patients with left MTS. Future work with a larger sample size will focus on establishing a unique neuropsychological profile related to epilepsy due to TE.

Misdiagnosis of lamotrigine toxicity as posterior circulation transient ischemic attack or stroke.

PURPOSE: Lamotrigine (LTG) is one of the most used antiseizure medications (ASMs). Titration is indicated for incomplete seizure control, but toxicity with vertigo, ataxia, and diplopia may ensue. Lamotrigine concentration would be the optimal diagnostic test. However, patients often receive a stroke evaluation when presenting to the emergency department (ED), leading to unnecessary cost and delayed management. We investigated the frequency of stroke evaluation for symptoms associated with LTG toxicity and attempted to identify factors leading to this expensive evaluation. METHODS: We identified adult patients treated with LTG who presented to an emergency room with dizziness, ataxia, or diplopia and received a negative stroke evaluation, between 2003 and 2018. They were among 972 patients treated with LTG for epilepsy. We collected age at time of occurrence, symptoms presented, imaging studies performed, LTG dose and serum concentration, and the time the result was available. As a denominator, we also identified patients who developed clinical LTG toxicity during the same time period. RESULTS: Thirteen patients with LTG toxicity had 16 negative stroke evaluations in the emergency room. Their mean age was 62 years (range: 43-79) as compared with 47 years for all patients treated with LTG (p < 0.0005). The mean daily LTG dose was 621 mg (range: 300-900 mg). A LTG serum concentration was requested on the day of evaluation in 7 instances, though the result was never available until at least the next day. In 4 instances, the LTG level was drawn 1-3 days after presentation. Five of the patients in this group were among 71 patients with clinical LTG toxicity and LTG concentration >20. CONCLUSION: Emergency departments will frequently call a stroke alert for patients taking LTG and presenting with symptoms consistent with LTG toxicity, particularly in seniors at greater risk of stroke. This adds not only expense but also radiation and contrast exposure from computed tomography (CT) studies. We recommend that a rapid LTG assay be made available and always ordered in patients receiving LTG, avoiding the considerable expense of an unnecessary stroke evaluation.

Development of a System for Postmarketing Population Pharmacokinetic and Pharmacodynamic Studies Using Real-World Data From Electronic Health Records.

Postmarketing population pharmacokinetic (PK) and pharmacodynamic (PD) studies can be useful to capture patient characteristics affecting PK or PD in real-world settings. These studies require longitudinally measured dose, outcomes, and covariates in large numbers of patients; however, prospective data collection is cost-prohibitive. Electronic health records (EHRs) can be an excellent source for such data, but there are challenges, including accurate ascertainment of drug dose. We developed a standardized system to prepare datasets from EHRs for population PK/PD studies. Our system handles a variety of tasks involving data extraction from clinical text using a natural language processing algorithm, data processing, and data building. Applying this system, we performed a fentanyl population PK analysis, resulting in comparable parameter estimates to a prior study. This new system makes the EHR data extraction and preparation process more efficient and accurate and provides a powerful tool to facilitate postmarketing population PK/PD studies using information available in EHRs.