Overview of acute seizure management in US nursing homes.

INTRODUCTION: Residents in NH are more likely to be diagnosed with epilepsy or seizures, which are associated with higher mortality and complicate care. This setting provides unique challenges in the treatment of seizures however, little is known about current management practices in NH. Most studies in the literature concentrate on the use of antiseizure medications (ASMs) but little is known about the management of the acute seizure and clinical guidance is needed to ensure the safety of this vulnerable population. The objective of this study was to survey current practices, identifying knowledge deficits and inform future educational endeavors, including acute seizure action plans (ASAPs). METHODS: A survey was developed pertaining to a broad spectrum of clinical aspects in the management of acute seizures in NH, distinguishing first time seizures from those in the setting of a known seizure disorder. It was sent to NH medical directors throughout the US and data was gathered from those who had at least one new case of new onset/epilepsy in the last 3 years. RESULTS: Ninety-one NH directors responded with 52 % having a seizure protocol. Nurses are responsible in the majority of cases for protocol activation. Regardless of the patient's seizure history, rescue medications are given in the majority of cases, oral benzodiazepines, followed by intravenous and then rectal benzodiazepines. Newer intranasal and intramuscular formulations of benzodiazepines were less frequently prescribed. The most commonly prescribed ASM is levetiracetam, followed by lamotrigine, valproic acid and phenytoin. Staff training and in-service education occur infrequently. Respondents thought no-cost seizure education would be highly beneficial. CONCLUSIONS AND IMPLICATIONS: Only approximately half of NH have protocols for the acute management of seizures. Rescue medications are given regardless of seizure history and often older ASMs are used for long-term management. Our study highlights areas of knowledge deficits and treatment areas for improvement, identifying the need and potential for ASAPs in NHs.

Safety and Efficacy of Cenobamate for the Treatment of Focal Seizures in Older Patients: Post Hoc Analysis of a Phase III, Multicenter, Open-Label Study.

BACKGROUND: Cenobamate is an antiseizure medication (ASM) approved in the US and Europe for the treatment of uncontrolled focal seizures. OBJECTIVE: This post hoc analysis of a phase III, open-label safety study assessed the safety and efficacy of adjunctive cenobamate in older adults versus the overall study population. METHODS: Adults aged 18-70 years with uncontrolled focal seizures taking stable doses of one to three ASMs were enrolled in the phase III, open-label safety study; adults aged 65-70 years from that study were included in our safety analysis. Discontinuations due to adverse events and treatment-emergent adverse events (TEAEs) were assessed throughout the study in all patients who received one or more doses of cenobamate (safety study population). Efficacy was assessed post hoc in patients who had adequate seizure data available (post hoc efficacy population); we assessed patients aged 65-70 years from that population. Overall, 100% responder rates were assessed in the post hoc efficacy maintenance-phase population in 3-month intervals. Concomitant ASM drug load changes were also measured. For each ASM, drug load was defined as the ratio of actual drug dose/day to the World Health Organization defined daily dose (DDD). RESULTS: Of 1340 patients (mean age 39.7 years) in the safety study population, 42 were ≥ 65 years of age (mean age 67.0 years, 52.4% female). Median duration of exposure was 36.1 and 36.9 months for overall patients and older patients, respectively, and mean epilepsy duration was 22.9 and 38.5 years, respectively. At 1, 2, and 3 years, 80%, 72%, and 68% of patients overall, and 76%, 71%, and 69% of older patients, respectively, remained on cenobamate. Common TEAEs (≥ 20%) were somnolence and dizziness in overall patients, and somnolence, dizziness, fall, fatigue, balance disorder, and upper respiratory tract infection in older patients. Falls in older patients occurred after a mean 452.1 days of adjunctive cenobamate treatment (mean dose 262.5 mg/day; mean concomitant ASM drug load 2.46). Of 240 patients in the post hoc efficacy population, 18 were ≥ 65 years of age. Mean seizure frequency at baseline was 18.1 seizures/28 days for the efficacy population and 3.1 seizures/28 days for older patients. Rates of 100% seizure reduction within 3-month intervals during the maintenance phase increased over time for the overall population (n = 214) and older adults (n = 15), reaching 51.9% and 78.6%, respectively, by 24 months. Mean percentage change in concomitant ASM drug load, not including cenobamate, was reduced in the overall efficacy population (31.8%) and older patients (36.3%) after 24 months of treatment. CONCLUSIONS: Results from this post hoc analysis showed notable rates of efficacy in older patients taking adjunctive cenobamate. Rates of several individual TEAEs occurred more frequently in older patients. Further reductions in concomitant ASMs may be needed in older patients when starting cenobamate to avoid adverse effects such as somnolence, dizziness, and falls. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov NCT02535091.

Pharmacological treatment for older adults with epilepsy and comorbid neurodegenerative disorders.

PURPOSE OF REVIEW: An increased interest in epilepsy in older adults has emerged as the global population ages. The purpose of this article is to review the literature regarding the pharmacological treatment of epilepsy in older adults, highlighting issues specifically pertinent to those living with comorbid neurodegenerative disorders. RECENT FINDINGS: Although new original research remains sparse, in the last 5 years, there has been a growing number of studies addressing the relationship between epilepsy and neurodegenerative disorders. Accurate diagnosis is incredibly challenging with electroencephalogram findings often requiring circumspect interpretation. Older individuals are often excluded from or under-represented in clinical trials, and there are sparse guidelines offered on the management of these patients, with even less available in reference to those with neurodegenerative comorbidities. SUMMARY: We propose that seizures occurring earlier in the neurodegenerative process should be treated aggressively, with the goal to inhibit neuro-excitotoxicity and the associated neuronal loss. By strategically choosing newer antiseizure medications with less adverse effects and a holistic approach to treatment, a patient's time living independently can be conserved. In addition, we advocate for original, multinational collaborative research efforts.

The epidemiology of epilepsy in older adults: A narrative review by the ILAE Task Force on Epilepsy in the Elderly.

In an aging world, it is important to know the burden of epilepsy affecting populations of older persons. We performed a selective review of epidemiological studies that we considered to be most informative, trying to include data from all parts of the world. We emphasized primary reports rather than review articles. We reviewed studies reporting the incidence and prevalence of epilepsy that focused on an older population as well as studies that included a wider age range if older persons were tabulated as a subgroup. There is strong evidence that persons older than approximately 60 years incur an increasing risk of both acute symptomatic seizures and epilepsy. In wealthier countries, the incidence of epilepsy increases sharply after age 60 or 65 years. This phenomenon was not always observed among reports from populations with lower socioeconomic status. This discrepancy may reflect differences in etiologies, methods of ascertainment, or distribution of ages; this is an area for more research. We identified other areas for which there are inadequate data. Incidence data are scarcer than prevalence data and are missing for large areas of the world. Prevalence is lower than would be expected from cumulative incidence, possibly because of remissions, excess mortality, or misdiagnosis of acute symptomatic seizures as epilepsy. Segmentation by age, frailty, and comorbidities is desirable, because "epilepsy in the elderly" is otherwise too broad a concept. Data are needed on rates of status epilepticus and drug-resistant epilepsy using the newer definitions. Many more data are needed from low-income populations and from developing countries. Greater awareness of the high rates of seizures among older adults should lead to more focused diagnostic efforts for individuals. Accurate data on epilepsy among older adults should drive proper allocation of treatments for individuals and resources for societies.

Clinical Reasoning: A 47-Year-Old Man With an Upper Respiratory Infection, Acute Confusion, Dysarthria, and Ataxia.

A patient presenting with acute confusion, dysarthria, and appendicular ataxia with gait instability warrants a broad differential including emergent consideration of acute ischemic or hemorrhagic stroke. Moreover, in acute to subacute presentations, a wide array of etiologies including infectious causes, toxins, or autoimmune conditions may be considered. This article features a 47-year-old man who presented acutely with confusion, severe dysarthria, left upper extremity dysmetria, and unsteady gait. In this case, these neurologic signs were preceded by symptoms of an upper respiratory infection. In addition, MRI brain without contrast demonstrated a small focus of hyperintensity on diffusion-weighted imaging in the splenium of the corpus callosum with apparent diffusion coefficient match. The article illustrates a diagnostic approach in evaluating a patient with this constellation of clinical and radiologic findings, as well as pertinent management considerations. A comprehensive overview of other potential causative factors of the imaging findings is described to augment the reader's differential diagnosis. Finally, a literature review pertaining to the revealed diagnosis highlights the epidemiologic relevance and important clinical pearls.

Management of epilepsy in older adults: A critical review by the ILAE Task Force on Epilepsy in the elderly.

Older adults represent a highly heterogeneous population, with multiple diverse subgroups. Therefore, an individualized approach to treatment is essential to meet the needs of each unique subgroup. Most comparative studies focusing on treatment of epilepsy in older adults have found that levetiracetam has the best chance of long-term seizure freedom. However, there is a lack of studies investigating other newer generation antiseizure medications (ASMs). Although a number of randomized clinical trials have been performed on older adults with epilepsy, the number of participants studied was generally small, and they only investigated short-term efficacy and tolerability. Quality of life as an outcome is often missing but is necessary to understand the effectiveness and possible side effects of treatment. Prognosis needs to move beyond the focus on seizure control to long-term patient-centered outcomes. Dosing studies with newer generation ASMs are needed to understand which treatments are the best in the older adults with different comorbidities. In particular, more high-level evidence is required for older adults with Alzheimer's disease with epilepsy and status epilepticus. Future treatment studies should use greater homogeneity in the inclusion criteria to allow for clearer findings that can be comparable with other studies to build the existing treatment evidence base.

Epilepsy: Workup and Management in Adults.

When managing epilepsy, there is a temptation to focus care with respect to the last and the next seizure. However, epilepsy is a multifaceted chronic condition and should be treated as such. Epilepsy comes with many physical risks, psychological effects, and socioeconomic ramifications, demanding a long-term commitment from the treating physician. Patients with epilepsy, compared to other chronically ill patient populations, have a worse quality of life, family function, and less social support. The majority of patients are well controlled on antiseizure drugs. However, approximately one-third will continue to have seizures despite optimized medical management. The primary aim of this article is to explore the long-term management of chronic epilepsy, and to address some of the particular needs of patients with chronic epilepsy.

Could the 2017 ILAE and the four-dimensional epilepsy classifications be merged to a new "Integrated Epilepsy Classification"?

Over the last few decades the ILAE classifications for seizures and epilepsies (ILAE-EC) have been updated repeatedly to reflect the substantial progress that has been made in diagnosis and understanding of the etiology of epilepsies and seizures and to correct some of the shortcomings of the terminology used by the original taxonomy from the 1980s. However, these proposals have not been universally accepted or used in routine clinical practice. During the same period, a separate classification known as the "Four-dimensional epilepsy classification" (4D-EC) was developed which includes a seizure classification based exclusively on ictal symptomatology, which has been tested and adapted over the years. The extensive arguments for and against these two classification systems made in the past have mainly focused on the shortcomings of each system, presuming that they are incompatible. As a further more detailed discussion of the differences seemed relatively unproductive, we here review and assess the concordance between these two approaches that has evolved over time, to consider whether a classification incorporating the best aspects of the two approaches is feasible. To facilitate further discussion in this direction we outline a concrete proposal showing how such a compromise could be accomplished, the "Integrated Epilepsy Classification". This consists of five categories derived to different degrees from both of the classification systems: 1) a "Headline" summarizing localization and etiology for the less specialized users, 2) "Seizure type(s)", 3) "Epilepsy type" (focal, generalized or unknown allowing to add the epilepsy syndrome if available), 4) "Etiology", and 5) "Comorbidities & patient preferences".

Age is but a number when considering epilepsy surgery in older adults.

BACKGROUND: A quarter of patients with newly diagnosed epilepsy are older, yet they are less likely to be offered resective surgery potentially because of clinical bias that they incur increased surgical risks. There are few peer-reviewed case series that address this cohort and their outcomes. OBJECTIVE: In the context of current literature, the objective of this study was to report on all epilepsy surgeries in patients aged 50 years or older from a tertiary care center over 15 years with an average follow-up period of 6 years. METHODS: Patients with epilepsy who underwent surgery between 2001 and 2016 were reviewed retrospectively. Inclusion criteria were age > 50 at surgery, availability of presurgical evaluation data, and minimum one year of follow-up data. We identified 34 patients. Seizure outcome was evaluated using the Engel classification system. RESULTS: Thirty-four patients aged 50 years and older out of 276 underwent epilepsy surgery. Average age at time of surgery was 55 years, and average duration of epilepsy was 30 years. Average length of follow-up was 6 years (1-15 years). Twenty-two out of 34 patients (64%) were seizure-free (Engel class I) at their last follow-up visit. Patients with lesional pathology on neuroimaging were more likely to achieve seizure freedom (p < 0.02). Parameters associated with poorer outcome included extratemporal epileptogenic focus (p = 0.07) and bitemporal interictal epileptiform activity (p = 0.003). CONCLUSION: Our study cohort is one of the largest and most representative outcome studies of this age group, following the cohort for 6 years. Our findings demonstrated that when considering epilepsy surgery in an older adult, their age should not play a determining role in the decision-a finding that is more common in modern literature.

Treatment with lacosamide impedes generalized seizures in a rodent model of cortical dysplasia.

OBJECTIVE: Epilepsy is a common neurologic disorder resulting in spontaneous, recurrent seizures. About 30-40% of patients are not responsive to pharmacologic therapies. This may be due to the differences between individual patients such as etiology, underlying pathophysiology, and seizure focus, and it highlights the importance of new drug discovery and testing in this field. Our goal was to determine the efficacy of lacosamide (LCM), a drug approved for the treatment of focal seizures, in a model of generalized epilepsy with cortical dysplasia (CD). We sought to compare LCM to levetiracetam (LEV), a drug that is currently used for the treatment of both partial and generalized epilepsy and to test its proficiency. METHODS: Pregnant rats were irradiated to produce pups with malformed cortices in a model of CD, which will be referred to as the "first hit." Adult animals, developed normally (NL) and irradiated (XRT), were surgically implanted with electroencephalography (EEG) electrodes. Baseline EEG was recorded on all rats prior to pretreatments with either LCM, LEV, or placebo (PBO). After 30 min, all rats were injected with a subconvulsive dose of pentylenetetrazole (PTZ), a γ-aminobutyric acid receptor A (GABAA ) antagonist used to provoke generalized seizures as a "second hit." RESULTS: LCM and LEV were both effective against seizures induced by PTZ. XRT rats had a higher seizure incidence with longer and more severe seizures than NL rats. Seizure duration was decreased with both LCM and LEV in all animals. In XRT rats, there was a significant reduction in acute seizure incidence and severity with both LCM and LEV after PTZ injection. SIGNIFICANCE: Our results suggest that LCM could be used as a potential treatment option for generalized epilepsy with CD as the underlying pathology.

Predicting seizure freedom after two or more chronic invasive evaluations in patients with intractable epilepsy.

OBJECTIVE: In patients with intractable epilepsy, failure to localize and/or resect the epileptic focus after invasive monitoring is multifactorial. Rarely do these patients return for a second invasive evaluation, and their outcome is not clearly characterized. This study aims to determine the seizure outcome after a second invasive electroencephalographic (EEG) evaluation, and its possible predictors. METHODS: We retrospectively reviewed 30 patients who underwent two or more invasive evaluations at Cleveland Clinic between 1980 and 2007. Clinical, surgical, imaging, and pathology information was analyzed using a multivariate regression model. A favorable outcome was defined as complete seizure freedom, allowing for auras and seizures restricted to the first postoperative week. RESULTS: Ten patients (33%) became seizure free after the second operation (mean follow-up duration 3.13 years [range 6 months-17 years]). Seizure freedom was more likely in patients reporting fewer seizures per month preoperatively (mean 19 seizures/mo), and in those with a predominantly regional/lateralized scalp EEG ictal pattern (32% seizure free), as opposed to those with higher seizure frequency (mean 70 seizures/month; P = 0.02) or diffuse ictal EEGs (0% seizure free; P = 0.04). There was a significant association between acute postoperative seizures and failure of repeat surgery (P = 0.0083). In 17 of 30 patients, at least one complication was reported (57%) after the second invasive evaluation compared with a complication rate of 23% after the first invasive evaluation. CONCLUSIONS: A second invasive evaluation may lead to seizure freedom in one-third of patients. However, this must be weighed against the increased complication rate with reoperation.

Ictal head turning in frontal and temporal lobe epilepsy.

PURPOSE: To quantitatively evaluate the difference of ictal head turning movements between patients with temporal lobe epilepsy (TLE) and frontal lobe epilepsy (FLE). METHODS: We investigated 38 seizures of 31 patients with unilateral TLE and 22 seizures of 14 patients with unilateral FLE where head turning occurred in the seizure evolution. The head movements were defined as ipsilateral or contralateral in reference to the lateralization of the patient's focal epilepsy syndrome. Head movements were quantified by either referencing the head position with manually placed markers or by automatic detection of infrared marked reference points. The time of onset, duration, and angular speed of the head movements were computed, and interindividual and intraindividual analyses were performed. KEY FINDINGS: All of the TLE seizures had both contralateral and ipsilateral head turning, whereas all FLE had contralateral head turning; only 6 of 22 seizures were associated with ipsilateral head turning. Ipsilateral head turning always preceded contralateral head turning in both TLE and FLE. The head turning occurred significantly sooner after clinical seizure onset in FLE than in TLE patients (ipsilateral 0.5 vs. 16.0 s, contralateral: 4.5 vs. 21.3 s; p < 0.001). Furthermore, the duration of head turning was shorter in FLE for contralateral head turning (4.1 s) than in TLE (contralateral 6.0 s, p < 0.01); the ipsilateral head turning in the two groups did not differ (3.0 vs. 2.9 s) in duration. The angular speed of head turning did not differ for ipsilateral and for contralateral head turning in FLE and TLE. SIGNIFICANCE: Quantitative analysis of head turning demonstrates significant differences between patients with FLE and TLE. These differences likely represent differences in spread of epileptic activity. This information may be useful in the seizure evaluation of patients considered for resective epilepsy surgery.

A longitudinal study of surgical outcome and its determinants following posterior cortex epilepsy surgery.

PURPOSE: To investigate the longitudinal seizure outcome and identify potential prognostic indicators following posterior cortex epilepsy (PCE) surgery. METHODS: We reviewed patients who underwent a parietal, occipital, or parietooccipital resections between 1994 and 2006, using survival analysis and multivariate regression with Cox proportional hazard modeling. A favorable outcome was defined as Engel Class I at last follow-up. RESULTS: Fifty-seven patients were identified with a mean follow-up of 3.3 years (range 1-12 years). The estimated chance of seizure freedom (SF) was 73.1% at 6 postoperative months, 68.5% at 1 year, 65.8% at between 2 and 5 years, and 54.8% at 6 years and beyond. Most recurrences (75%) occurred within the first 6 postoperative months. Parietal resections had a worse outcome than occipital or parietooccipital resections (52% SF vs. 89% and 93%, respectively, at 5 years). Independent predictors of recurrence included an epilepsy etiology other than tumor or dysplasia [risk ratio (RR) 2.29], limiting resection to a lesionectomy (RR 2.10), having ipsilateral temporal spiking on preoperative scalp electroencephalography (EEG) (RR 2.06), or any ipsilateral spiking on postoperative EEG (RR 2.70) (Log likelihood-ratio test p < 0.0001). Only 40-50% of patients with a poor outcome predictor were SF at 5 postoperative years as opposed to about 80% otherwise. In surgical failures, recurrent seizure frequency was related directly to baseline seizure frequency and to the presence of ipsilateral spiking on postoperative EEG. DISCUSSION: These data highlight favorable long-term outcomes following PCE surgery. Limited surgical resection and diffuse baseline epileptogenicity may be important predictors of seizure recurrence.

Lateralizing significance of quantitative analysis of head movements before secondary generalization of seizures of patients with temporal lobe epilepsy.

PURPOSE: To quantitatively evaluate the lateralizing significance of ictal head movements of patients with temporal lobe epilepsy (TLE). METHODS: We investigated EEG-video recorded seizures of patients with TLE, in which the camera position was perpendicular to the head facing the camera in an upright position and bilateral head movement was recorded. Thirty-eight seizures (31 patients) with head movement in both directions were investigated. Ipsilateral and contralateral head movements were defined according to ictal EEG. Head movements were quantified by selecting the movement of the nose in relation to a defined point on the thorax (25/s) in a defined plane facing the camera. The duration of the head version was determined independently of the camera angle. The angle, duration, and angular speed of the head movements were computed and inter and intrasubject analyses were performed (Wilcoxon rank sum). RESULTS: Ipsilateral movement always preceded contralateral movement. The positive predictive value was 100% for movement in both directions. The duration of contralateral head version was significantly longer than ipsilateral head movement (6.4 +/- 4.1 s vs. 3.9 +/- 3.1 s, p<0.001). The angular speed of both movements was similar (15.5 +/- 12.1 deg/s vs. 17.3 +/- 13.0 deg/s). CONCLUSION: The quantitative analysis shows the importance of sequence in the seizure's evolution and duration, but not angular speed for correct lateralization of versive head movement. This quantitative method shows the high lateralizing value of ictal lateral head movements in TLE.