Focal Awareness Research Articles

Focal epilepsies: update on diagnosis and classification.

Correctly diagnosing and classifying seizures and epilepsies is paramount to ensure the delivery of optimal care to patients with epilepsy. Focal seizures, defined as those that originate within networks limited to one hemisphere, are primarily subdivided into focal aware, focal impaired awareness, and focal to bilateral tonic-clonic seizures. Focal epilepsies account for most epilepsy cases both in children and adults. In children, focal epilepsies are typically subdivided in three groups: self-limited focal epilepsy syndromes (e.g., self-limited epilepsy with centrotemporal spikes), focal epilepsy of unknown cause but which do not meet criteria for a self-limited focal epilepsy syndrome, and focal epilepsy of known cause (e.g., structural lesions - developmental or acquired). In adults, focal epilepsies are often acquired and may be caused by a structural lesion such as stroke, infection and traumatic brain injury, or brain tumors, vascular malformations, metabolic disorders, autoimmune, and/or genetic causes. In addition to seizure semiology, neuroimaging, neurophysiology, and neuropathology constitute the cornerstones of a diagnostic evaluation. Patients with focal epilepsy who become drug-resistant should promptly undergo assessment in an epilepsy center. After excluding pseudo-resistance, these patients should be considered for presurgical evaluation as a means to identify the location and extent of the epileptogenic zone and assess their candidacy for a surgical procedure. The goal of this seminar in epileptology is to summarize clinically relevant information concerning focal epilepsies. This contributes to the ILAE's mission to ensure that worldwide healthcare professionals, patients, and caregivers continue to have access to high-quality educational resources concerning epilepsy.

The city as an information system: Urban agency, experiential inputs and planning measures

From the point of view of urban agents, the city can be seen as an information system. In this article, we focus on the city as an information structure insofar as it is an experiential context. Therefore, we will not deal with the “analytical information” about city X that is available while being elsewhere. We will instead deal with the “experiential information” which is accessible while being/acting in city X. A large part of urban experiential information reaches individuals without any specific conscious focal awareness. For the individuals operating in the city and using the city (residents, shopkeepers, entrepreneurs, developers, consumers, tourists, etc.), experiential information is crucial. At the personal level, experiential inputs help to positively regulate an individual's psycho-physical state. On an interpersonal level, experiential inputs help to structure and coordinate agency among human agents, and between them and physical elements of the environment. In discussing experiential information, the attention is not merely on human senses, but, first of all, on the vehicles that convey such information: images, sounds, smells, artifacts, behaviours. Taking experiential information seriously implies new ways to interpret the functioning of cities and modes of urban intervention (e.g. planning and urban design).

Duration of epileptic seizure types: A data-driven approach.

To determine the duration of epileptic seizure types in patients who did not undergo withdrawal of antiseizure medication. From a large, structured database of 11 919 consecutive, routine video-electroencephalograpy (EEG) recordings, labeled using the SCORE (Standardized Computer-Based Organized Reporting of EEG) system, we extracted and analyzed 2742 seizures. For each seizure type we determined median duration and range after removal of outliers (2.5-97.5 percentile). We used surface electromyography (EMG) for accurate measurement of short motor seizures. Myoclonic seizures last <150 ms, epileptic spasms 0.4-2s, tonic seizures 1.5-36 s, atonic seizures 0.1-12,5s, when measured using surface EMG. Generalized clonic seizures last 1-24 s. Typical absence seizures are rarely longer than 30 s (2.75-26.5s) and atypical absences last 2-100 s. In our patients, the duration of focal aware (median: 27 s; 1.25-166 s) and impaired awareness seizures (median: 42.5s; 9.5-271 s) was shorter than reported previously in patients undergoing withdrawal of antiseizure medication. All focal seizures terminated within 10 min. Median duration of generalized tonic-clonic seizures was 79.5s (57-102 s) and of focal-to-bilateral tonic-clonic seizures was 103.5 (77.5-237 s). All tonic-clonic seizures terminated within 5 min. This comprehensive list of seizure durations provides important information for characterizing seizures and diagnosing patients with epilepsy. The upper limits of seizure durations are helpful in early recognition of imminent status epilepticus.

Glioma features and seizure control during long-term follow-up.

An epileptic seizure is a common presenting symptom of glioma, or epilepsy may develop later during the disease. Epileptic seizures affect the quality of life in patients with glioma. Good seizure control during 6-12months follow-up has been associated with gross total resection, radiation therapy and chemotherapy of gliomas. Little is known about seizure control during long-term follow-up and about factors which may affect the prognosis of epilepsy in glioma patients. We identified retrospectively all adult patients with diffuse glioma (grade 2-4) associated epilepsy (n=123) living in Helsinki, who received treatment at Helsinki University Hospital neuro-oncology center during 2013-2015. We excluded patients with histopathological diagnosis prior to 2005. Data was collected from medical records for five years after diagnosis of glioma, or until death. In this patient cohort 49 (39.8%) had grade 2 glioma, 19 (15.4%) had grade 3 glioma and 55 (44.7%) had grade 4 glioma. 29 (23.6%) of tumors were astrocytomas, 24 (19.5%) were oligoastrocytomas, 15 (12.2%) were oligodendrogliomas and 55 (44.7%) were glioblastomas. A seizure was the presenting symptom in 87 (70.7%) of the patients. The majority, 68 (57.6%) patients were seizure-free for at least 12months at some point during follow-up and 47 (39.8%) patients were seizure-free during the last year of follow-up. Survival for five years from glioma diagnosis (p<0.001), lower grade of tumor (p<0.001), IDH mutation (p<0.001), epilepsy as first symptom (p<0.001), younger age (p<0.001) and lack of progression (p = 0.021) correlated with seizure freedom at the end of follow-up. When the results were analyzed separately in survivors and deceased patients, only progression correlated negatively with seizure freedom at the end of follow-up in surviving patients (p = 0.008). In 5-year survivors, longer seizure-free periods were achieved by patients without progression of glioma (p = 0.040) vs patients with progression, or without focal aware (p 0.003) or focal impaired awareness seizures (p = 0.002) vs patients with only focal to bilateral tonic-clonic seizures. In deceased patients, progression (p<0.001) and lower grade of glioma (p = 0.003) correlated positively and focal aware seizures negatively (p = 0.021) with a longer seizure-free period. In all patients, freedom of seizures at the end of follow-up was less likely for patients who had focal aware (p = 0.015) than for patients without focal aware seizures. There are differences in seizure-free times in patients with grade 2-4 glioma and epilepsy. The results suggest that the prognosis of glioma may be the most important factor influencing the prognosis of epilepsy.

Prevalence of mesial temporal sclerosis in patients with epilepsy who underwent magnetic resonance imaging in Gondar university hospital, North-West Ethiopia 2020

Background- Mesial temporal lobe sclerosis is commonly associated with intractable temporal lobe epilepsy and is seen in about 60% to 80% of cases. This study is aimed at determining the prevalence of mesial temporal sclerosis on MRI among all epilepsy patients. Methods- Hospital based retrospective cross-sectional study in adult patients referred for MRI of the brain from January 2019 - September 2020 were conducted. The study is carried out at the University of Gondar Referral Hospital with a 1.5T Philips MRI machine, in Gondar town located 741 k.m. northwest of Addis Ababa. Results - A total of 77 patients were included, out of which 61 had generalized tonic clonic epilepsy, 7 had focal impaired awareness seizures, 6 had focal to bilateral tonic clonic and 2 had focal aware. Features of mesial temporal sclerosis were identified in 8 of 77 (10.4 %) of the cases, all of them had generalized tonic-clonic epilepsy &amp; none of our participants with mesial temporal sclerosis had focal impaired awareness seizures. Mesial temporal sclerosis in our study is found to equally involve the right (50 %) and left (50 %) sides and none of our patients have bilateral involvement, and the most common findings are hippocampal atrophy in 6 out of 8 (75 %) of the cases and increased hippocampal signal intensity in 5 of 8 (62.5 %). Conclusion - The prevalence of mesial temporal sclerosis in patients with epilepsy is found to be less than what is documented in most literatures.

Real-world evaluation of perampanel effectiveness in Japanese adolescents with epilepsy

Real-world data from adolescents treated with perampanel in a routine clinical setting are lacking in Japan. We evaluated the safety and efficacy of perampanel for adolescent patients (aged 12-17 years) with drug-resistant, refractory epilepsy in real-world settings. This was a large-scale, prospective, observational post-marketing study, with a 104-week observation period. Safety was assessed by monitoring adverse effects (adverse drug reactions). For efficacy assessments, seizure frequency was compared between the four weeks immediately prior to the last observation and the four weeks before the commencement of perampanel. In total, 519 patients were enrolled; 505 and 484 patients were included in the safety and efficacy analysis sets, respectively. The mean age was 14.4 years. The mean daily dose of perampanel was 4.4 mg/day. The main reasons for discontinuation at 104 weeks were adverse events (48.4%) and inadequate efficacy (46.8%). The retention rate at 104 weeks was 50.5%. Adverse effect and severe adverse effect incidences were 42.2% and 1.8%, respectively. The most common adverse effects were somnolence (13.5%), irritability (8.5%), dizziness (5.1%), and agitation (4.8%). There were significant differences in the occurrence of adverse effects between the initial titration interval of <2 weeks and 2-4 weeks (odds ratio=0.441, p=0.029) and 4-8 weeks (odds ratio=0.462, p=0.027). The median percent change in seizure frequency at the last observation carried forward was −50.0 for focal aware seizures with motor signs, −73.3 for focal aware seizures without motor signs, −28.6 for focal impaired awareness seizures, −62.6 for focal to bilateral tonic-clonic seizures, and −20.0 for generalized tonic-clonic seizures. In adolescent patients, perampanel was well tolerated and efficacious in reducing seizure frequency. No unexpected safety issues were observed, and slow titration may reduce the incidence of adverse effects.

Optimizing deep brain stimulation for the treatment of drug-resistant temporal lobe epilepsy: a pilot study.

The authors sought to determine the antiseizure effects of deep brain stimulation (DBS) of the parahippocampal cortex (PHC) for treatment of drug-resistant mesial temporal lobe epilepsy (MTLE). After a 3-month baseline period, 6 adult patients with drug-resistant MTLE and hippocampal sclerosis (HS) had stereoelectroencephalography (SEEG)-DBS electrodes implanted at the PHC for identification of the seizure onset zone (SOZ). Patients entered an 8-month, randomized, double-blind protocol for DBS, followed by a 12-month open-phase study. Monthly reports of seizure frequency were collected, with separate counting of focal seizures with or without awareness impairment (focal impaired awareness seizures [FIAS] or focal aware seizures [FAS], respectively) and focal evolving to bilateral generalized tonic clonic seizures (GTCS). Stimulation parameters were 130 Hz, 450 μsec, 2.5-3 V, and cyclic stimulation 1 minute on/4 minutes off. The total seizure rate decrement during follow-up was 41% (CI 25%-56%), with better seizure control for GTCS (IQR 19%-20%) and FIAS (IQR 0%-16%), with FAS being less responsive (IQR 67%-236%). No neuropsychological deterioration was observed. PHC DBS induced important antiseizure effects in patients with incapacitating FIAS and GTCS, most likely through blocking the propagation of hippocampal-onset seizures. The PHC target can be easily and safely approached due to positioning away from vascular structures, and there was no evidence of DBS-induced cognitive deterioration.

Polanyi and the Revised Taxonomy: Teaching Technology for High-Level Creative Thinking and Risk Taking

This paper presents a model for mastery learning. The framework for this model overlays the cognitive and knowledge dimensions from Krathwohl’s revision of Bloom’s Taxonomy, the Revised Taxonomy, with Polanyi's theory of personal knowledge. A simplified framework integrates Polanyi's concepts of subsidiary and focal awareness with the Revised Taxonomy levels of knowledge acquisition to form a new model consisting of two dynamic parts: base thought and elevated thought. The base/elevated thought framework serves as a model for mastery learning with regards to the usefulness, application, and integration of technology into the creative problem-solving process. Allocating base knowledge to other means of instruction (for example, online tutorials or flipped classroom techniques) frees up the instructor's time and allows the expert (teacher) to engage novices (students) in more direct student-instructor contextual learning requiring higher levels of cognitive thinking. While this paper proposes the use of the framework within the context of a technology-focused model, its application has potential for other learning scenarios.

Epidemiological and clinical features of epileptic patients in Goma, Democratic Republic of the Congo

Introduction: Epilepsy is one of the most common neurological conditions but the majority of epileptic patients in sub-Saharan African countries do not receive appropriate treatment. In the Democratic Republic of the Congo (DRC), very few epidemiological studies have been conducted on epilepsy. The objective of this study was to describe socio-demographic characteristics, the type of epileptic seizures, and etiological factors of these seizures in a hospital cohort of epileptic patients followed at the Neuropsychiatric Hospital Center in Goma (in the DRC). Materials and methods: This was a cross-sectional study of 917 epileptic patients received in neurology consultation at the Neuropsychiatric Hospital Center in Goma (in the DRC) from January 1st, 2017 to December 31st, 2021. Results: The median age of patients was 16 years, the median age of the patients at onset of seizures was 13 years and the median time between onset of seizures and consultation was 8.0 months; 14.2% of had a family history of epilepsy. Generalized tonic-clonic seizures were the most frequent (76.7%), followed by motor focal impaired awareness seizures (5.2%) and non-motor focal aware seizures (3.6%). The etiologic factor was found in 444 (48.4%) patients and was dominated by chronic alcoholism (20.9%), neurocysticercosis (17.6%), meningitis (14.6%), malnutrition (11.3%), cerebral malaria (8.3%), and head injury (7.7%). Conclusion: This study provides an epidemiological overview of epilepsy in Goma city. The etiological factors and types of seizures will dictate the best possible treatment options.

Seizure underreporting in LGI1 and CASPR2 antibody encephalitis.

Patients with anti-leucine-rich glioma-inactivated 1 protein (LGI1) or anti-contactin-associated protein 2 (CASPR2) antibody encephalitis typically present with frequent epileptic seizures. The seizures generally respond well to immunosuppressive therapy, and the long-term seizure outcome seems to be favorable. Consequentially, diagnosing acute symptomatic seizures secondary to autoimmune encephalitis instead of autoimmune epilepsy was proposed. However, published data on long-term seizure outcomes in CASPR2 and LGI1 antibody encephalitis are mostly based on patient reports, and seizure underreporting is a recognized issue. Clinical records from our tertiary epilepsy center were screened retrospectively for patients with LGI1 and CASPR2 antibody encephalitis who reported seizure freedom for at least 3 months and received video-electroencephalography (EEG) for >24 h at follow-up visits. Twenty (LGI1, n=15; CASPR2, n=5) of 32 patients with LGI1 (n=24) and CASPR2 (n=8) antibody encephalitis fulfilled these criteria. We recorded focal aware and impaired awareness seizures in four of these patients (20%) with reported seizure-free intervals ranging from 3 to 27 months. Our results question the favorable seizure outcome in patients with CASPR2 and LGI1 antibody encephalitis and suggest that the proportion of patients who have persistent seizures may be greater. Our findings underline the importance of prolonged video-EEG telemetry in this population.

Optimal timing of interictal FDG-PET for epilepsy surgery: A systematic review on time since last seizure.

Interictal 18F‐Fluorodeoxyglucose positron emission tomography (FDG‐PET) is used in the workup for epilepsy surgery when MRI and EEG video monitoring are not conclusive. Timing of FDG‐PET is crucial to avoid the metabolically dynamic (post)ictal state that complicates interpretation, but the exact time window is unclear. We performed a systematic review to provide an evidence‐based recommendation for the minimal time interval between last seizure and FDG‐PET acquisition. We searched PubMed and Embase for articles on the effect of time since last seizure on FDG‐PET outcome. Quality assessment was conducted with the Critical Appraisal Skills Programme Cohort Study Checklist. We identified five studies. Three studies were classified as of low to moderate quality, mainly due to undocumented data or insufficient statistical measurements. Two high‐quality studies included only adults with Temporal Lobe Epilepsy (TLE). The metabolic interictal phase is 24 or 48 hours after the last seizure, depending on seizure type. The recommendation is based on the best available evidence from two small study populations for TLE. If clinically possible, interictal FDG‐PET in adults should be performed at least 24 hours after focal aware seizures and 48 hours after focal impaired awareness and focal to bilateral tonic–clonic seizures.

Efficacy of cenobamate by focal seizure subtypes: Post-hoc analysis of a phase 3, multicenter, open-label study

PurposeTo report post-hoc efficacy data by focal seizure subtypes from 10 US study sites from a large, global, open-label, phase 3 study of adjunctive cenobamate. MethodsPatients 18–70 years old with uncontrolled focal seizures taking stable doses of 1–3 antiseizure medications were administered increasing daily doses of cenobamate (12.5, 25, 50, 100, 150, 200 mg/day) at 2-week intervals (target dose 200 mg/day). Further increases to 400 mg/day by 50-mg/day increments every other week were allowed. Results240 patients were evaluated; 27 (11.3%), 224 (93.3%), and 56 (23.3%) patients had focal aware motor (FAM), focal impaired awareness (FIA), and focal to bilateral tonic-clonic (FBTC) seizures, respectively (patients may have had ≥ 1 seizure subtype). Median baseline seizure frequencies/28 days were 10.5, 2.3, and 0.9 for FAM, FIA, and FBTC seizure subtypes. Reductions in median percent seizure frequency/28 days from baseline were observed during Months 1–3 (55.0%, 52.4%, and 94.1% for FAM, FIA, and FBTC). Greater reductions were observed during Months 4–5 (88.2%, 81.0%, and 100%) and during Months 25–27 (98.1%, 100%, and 100%). The percentage of patients achieving 100% seizure reduction in the FAM, FIA, and FBTC seizure subtypes was 22.2% (6/27), 21.5% (48/223), and 50% (28/56) during Months 1–3 and increased to 47.8% (11/23), 54.3% (88/162), and 90.5% (38/42) during Months 25–27, respectively. The most common treatment-emergent adverse events (≥ 20%) were fatigue, dizziness, and somnolence. No cases of DRESS were reported. ConclusionsSeizure reductions occurred in all focal seizure subtypes with cenobamate over time through Months 25–27, with the earliest onset in the FBTC group. Results from this subset analysis of the phase 3 study support the long-term efficacy of cenobamate across focal seizure types.

Seizure types associated with negative arterial spin labeling and positive diffusion-weighted imaging on peri-ictal magnetic resonance imaging

PurposeArterial spin labeling (ASL) and diffusion-weighted imaging (DWI) are useful for assessing hyperperfusion and cytotoxic edema, respectively, caused by acute seizures. This study investigated the clinical characteristics associated with normal ASL findings and DWI abnormalities in patients with acute seizures. MethodsOverall, 41 patients with ASL and DWI images that were obtained within 48 h of focal onset seizure diagnosis, due to epilepsy or acute symptomatic seizures, were divided into groups based on initial ASL findings (ASL-negative vs. ASL-positive), and DWI abnormalities (DWI-negative vs. DWI-positive). The diagnosis was made based on seizure semiology, electroencephalography, and conventional imaging modalities. ASL and DWI abnormalities were based on visual assessment. ResultsOf the 41 patients, eight (19.5%) displayed normal ASL findings. The proportion of patients with focal aware seizures (FAS) was significantly higher among ASL-negative patients (62.5%) than that in ASL-positive patients (15.2%); the proportion of patients with focal impaired awareness seizures (FIAS) was significantly lower among ASL-negative patients (12.5%) than that among ASL-positive patients (57.6%). Hyperintensity findings on DWI were observed in 12 patients (29.3%, DWI-positive). The proportion of patients with FIAS was significantly higher among DWI-positive patients (75.0%) than that among DWI-negative patients (37.9%). Multivariate analysis revealed that FAS and FIAS were associated with normal ASL findings (odds ratio [OR]: 21.37, P = 0.010) and DWI abnormalities (OR = 6.11, P = 0.028). ConclusionA diagnosis of seizures should not be excluded based on normal ASL findings, especially in patients with FAS. FIAS may be a risk factor for neuronal damage caused by seizure activity.

Evaluation of real‐world effectiveness of perampanel in Japanese adults and older adults with epilepsy

While previous studies have demonstrated the safety and effectiveness of perampanel (PER) in combination with other anti-seizure medications in adult patients, data for older patients are limited. This study aimed to confirm real-world safety and effectiveness of combination treatment with PER in Japanese patients with focal seizures with or without focal to bilateral tonic-clonic seizures (FBTCS) or generalised tonic-clonic seizures (GTCS) according to age subgroups (<65 and ≥65 years of age). This large-sample prospective post-marketing observational study included a 24-52-week observation period after the first PER treatment. Safety was assessed according to adverse drug reactions (ADRs) and efficacy was evaluated based on the 50% responder rate and rates of overall symptom improvement. Among the 3,808 patients who were enrolled, 3,716 (3,026 patients aged <65 years and 690 patients aged ≥65 years) and 3,272 were included in the safety and efficacy analysis datasets, respectively. ADRs were reported for 1,247 patients (33.6%) in the safety analysis dataset. Of these, 36.2% and 22.2% were aged <65 years and ≥65 years, respectively, and the most common ADRs were somnolence (11.6%, 5.5%) and dizziness (9.7%, 5.4%). The 50% responder rates in patients aged <65 years and those ≥65 years were 60.1% and 89.0% for those with focal aware seizures (FAS) with motor signs; 48.0% and 60.0% for FAS without motor signs; 47.4% and 80.2% for focal impaired awareness seizures; 70.8% and 93.4% for FBTCS; and 63.6% and 88.9% for GTCS, respectively. The improvement rates of symptoms/conditions were also higher in patients aged ≥65 years than those <65 years. PER was effective in reducing seizure frequency and was safe, especially in older patients. PER may be a clinical treatment option for older patients with seizure disorders.

The Development of Pedagogical Competence in Tacit Knowing

Polanyi’s theory of personal knowledge provides a paradigmatic conceptual framework for the empirical analysis of tacit knowing and learning. We use this framework to analyze the development of pedagogical competence. Drawing on Polanyi, we regard pedagogical competence as a particular field of professional tacit knowing that relates subsidiary and focal awareness of events in class, effects situated appraisal, and relates events to teaching intentions. The development of pedagogical competence takes place when a teacher struggles to relate teaching intentions to ongoing events in tacit knowing and engages in situated experimentation. Based on Polanyi’s conception of subsidiary awareness, focal awareness, and appraisal, we present an empirical vignette from a case study. In it, a teacher engages in situated experimentation to resolve two opposing semantic fields in class: an intended field of interaction, which focuses on the lesson topic, and the field of student peer relations. Based on our analysis, we argue that the teacher’s competence development is focused on the educative task of managing students’ peer culture, while the teacher’s focal awareness remains on the didactical task of teaching a subject.

Focal impaired awareness seizures in a rodent model: A functional anatomy.

ObjectivePatients with temporal lobe epilepsy (TLE) frequently report debilitating comorbidities such as memory impairments, anxiety, and depression. An extensive neuronal network generates epileptic seizures and associated comorbidities, but a detailed description of this network is unavailable, which requires the generation of neuronal activation maps in experimental animals.MethodsWe recorded electrographic seizures from the hippocampi during a kindling‐evoked focal impaired awareness seizure with observed freezing, facial twitching, and involuntary head bobbing. We mapped seizure circuits activated during these seizures by permanently tagging neurons through activity‐induced immediate early genes, combined with immunohistochemical approaches.ResultsThere was bilateral activation of circuits necessary for memory consolidation, including the hippocampal complex, entorhinal cortex, cingulate gyrus, retrosplenial cortex, piriform cortex, and septohippocampal complex in kindled animals compared with unstimulated awake behaving mice. Neuronal circuits in the ventral hippocampus, amygdala, and anterior cingulate cortex, which regulate the stress response of hypothalamic‐pituitary‐adrenal axis, were also markedly activated during a focal impaired awareness seizure.SignificanceThis study highlights neuronal circuits preferentially activated during a focal awareness impaired seizure in a rodent model. Many of the seizure‐activated neuronal circuits are critical modulators of memory consolidation and long‐term stress/depression response. The hijack of these memory and depression regulatory systems by a focal seizure could account for the frequent reports of comorbidities such as memory impairment and depression in many TLE patients.

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

ObjectiveTo 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).MethodsPatients 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.ResultsOf 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%).SignificanceThis 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.

New-onset seizures in older people: Clinical features, course and outcomes

ObjectiveThe incidence of epilepsy increases with age. With current demographic trends, this presents a healthcare challenge. We investigated the clinical spectrum of first seizures, evaluated neuroimaging and EEG findings, and determined clinical outcomes, including anti-seizure medication (ASM) response in older people. In addition, we sought to understand the relative effects of age and frailty on ASM response. MethodsA retrospective single centre cohort study of 207 cases ≥60 years' old, 113 of whom were eventually diagnosed with a first seizure in a specialist epilepsy clinic. Results65/113 (57.5%) presented with either focal aware or focal impaired awareness seizures. Stroke was the most common aetiological association (31.9%, 36/113), and odds of seizure recurrence did not significantly differ between aetiologies. 55/86 (64.0%) who started an ASM had no seizure recurrence. 14/48 (29.2%) who underwent EEG had epileptiform abnormalities, however EEG result directly affected management in only 4/48 (8.3%). The most common MRI findings were small vessel disease (37/93, 39.8%), stroke (27/93, 29.0%) and global atrophy (14/93, 15.1%). Increasing age and frailty did not affect the odds of seizure recurrence or of experiencing ASM side effects. Severity of small vessel disease or atrophy did not affect odds of seizure recurrence. ConclusionOur data inform the management of first seizures in older people and provisionally support the use of ASMs in patients with increasing age and frailty, despite concerns over polypharmacy and comorbidity. Our findings should be replicated in larger cohorts.

Autoimmune Encephalitis–Related Seizures and Epilepsy: Diagnostic and Therapeutic Approaches

Autoimmune Encephalitis–Related Seizures and Epilepsy: Diagnostic and Therapeutic Approaches

Recognition of seizure semiology and semiquantitative FDG-PET analysis of anti-LGI1 encephalitis.

AimsAnti‐leucine‐rich glioma‐inactivated 1 (LGI1) autoimmune encephalitis (AE) is characterized by complex manifestations of seizures. Here, we report a new seizure semiology, attempt to classify the disease by semiology type, and explore the metabolic pattern of each group.MethodsAnti‐LGI1 AE patients were retrospectively screened between May 2014 and September 2019 in our tertiary epilepsy center. All enrolled patients had seizures during long‐range video electroencephalogram (EEG) recordings, and all patients (except one) underwent [18F] fluoro‐2‐deoxyglucose (FDG) positron emission tomography (PET) scans. Voxel‐based metabolic analysis and z‐distribution analysis were carried out to determine the metabolic pattern.ResultsThirty‐three patients were enrolled. According to the patients’ seizure semiology, we divided the patients into four groups: focal impaired awareness seizures (FIAS, n = 17), faciobrachial dystonic seizures (FBDS)‐only (n = 6), FBDS‐plus (n = 8), and focal aware motor seizures (FAMS) (n = 2). No significant differences were found in the clinical manifestations or accessory tests except for the onset age (FIAS < FBDS‐plus) and seizure semiology. This was the first study to extensively describe the clinical manifestations and EEG of FAMS in anti‐LGI1 AE patients. In addition, we found that the patients with different semiologies all showed a wide range of abnormal metabolism, which is not limited to the temporal regions and basal ganglia, and extends far beyond our previous interpretation of FDG‐PET data.ConclusionOur results showed that FAMS can serve as a rare indicative seizure semiology of anti‐LGI1 AE and that individuals with this disease exhibited widespread functional network alterations.