Bilateral Tonic-clonic Seizures Research Articles

Forgetting to take antiseizure medications is associated with focal to bilateral tonic-clonic seizures, as revealed by a cross-sectional study.

ObjectivesTo evaluate the effects of nonadherence to antiseizure medications (ASMs) and clinical characteristics on seizure control, we employed a prospective cohort cross-sectional study using self-reports and medical records of patients with epilepsy (PWEs).MethodsEight hundred and fifty-five PWEs taking ASMs were enrolled from fourteen collaborative outpatient clinics from January 2018 to March 2019. Questions from the Morisky Medication Adherence Scale were used as adherence self-reports. If a PWE’s questionnaire indicated that they had missed doses of their ASMs, outpatient physicians asked them directly about the details of their compliance, including the timing of intentionally or unintentionally missed doses. The association between lack of seizure control and utilization outcomes, such as missed doses, demographics, and clinical characteristics of the PWEs, were assessed by univariate and multivariate analyses.ResultsMultivariate analysis revealed that forgetting to take ASMs was associated with lack of seizure control and the existence of focal to bilateral tonic–clonic seizures. Dementia, younger age, use of three or more antiepileptic agents, and living in a one-person household were associated with the risk of forgetting to take ASMs.SignificanceFor PWEs with poor drug management or a high incidence of missed doses of ASMs, efforts to improve adherence could facilitate better seizure control and decrease focal to bilateral tonic–clonic propagation.

Conversational analysis of consciousness during seizures

ObjectiveThe objectives of the study were to 1) investigate how patients with epilepsy describe the subjective, conscious experience of having a seizure and 2) determine whether certain themes and descriptions correspond to specific types of epilepsy. MethodsWe interviewed thirteen patients with electroencephalographically confirmed epilepsy about their subjective experience of having a seizure and used conversational analysis (CA) to analyze the language they used to describe this experience. ResultsSeven patients had focal to bilateral tonic–clonic seizures (FBTCS), 7 had focal impaired awareness seizures (FIAS), 1 had focal aware seizures (FAS), and one had generalized onset tonic–clonic (GTC) seizures. Three had multiple types of seizures. Focal seizure origin was frontal in 2 patients, right hemisphere in 1, parieto-occipital in 1, and temporal in 8. Focal to bilateral tonic–clonic and GTC seizures were most frequently associated with descriptions of a total loss of consciousness (n = 8), whereas FIAS were most frequently associated with a perceived loss of consciousness but able to describe some aspects of being unconscious (n = 5). Temporal seizures most frequently accompanied reports of memory loss/impairment (n = 4). Ten patients provided specific descriptions of the transition between the interictal and ictal state or auras. Descriptions consciousness and unconsciousness ranged significantly, resembling a continuum rather than corresponding to distinct levels. ConclusionThe subjective experience of consciousness for patients with epilepsy may differ by seizure type and origin. These may reflect different involvement of brain regions involved in producing consciousness and arousal. Conversational analysis and narrative approaches can significantly aid clinicians in the diagnosis and management of epilepsy.

Electroclinical Phenotype-Genotype Homogeneity in Drug-Resistant "Generalized" Tonic-Clonic Seizures of Early Childhood.

Children with refractory focal to bilateral tonic-clonic seizures, despite normal high-resolution imaging, are often not subjected to genetic tests due to the costs involved and instead undergo multimodality presurgical evaluation targeted at delineating a focal onset. The objective of this study was to ascertain genotype-phenotype correlations in this group of patients. An online hospital database search was conducted for children who presented in 2019 with drug-resistant epilepsy dominated by nonlateralizing focal-onset/rapid generalized (bilateral) tonic-clonic seizures (GTCS), subjected to presurgical evaluation and subsequent genetic testing due to absence of a clear focus hypothesis. Phenotypic homogeneity was apparent in 3 children who had onset in infancy with drug-resistant GTCS (predominantly unprovoked and occasionally fever provoked) and subsequent delayed development. 3-Tesla magnetic resonance imaging (MRI) scans were negative and video EEG documented a homogeneous pattern of multifocal and/or generalized epileptiform discharges with phenomenology favoring probable focal-onset/generalized-onset bilateral tonic-clonic seizures. All 3 tested positive for SCN1A gene variants (heterozygous missense substitution variants in 2 children, one of which was novel and a novel duplication in one that led to frameshift and premature truncation of the protein), suggestive of SCN1A-mediated epilepsy. This electroclinical profile constituted 3 out of 25 patients with SCN1A-epilepsy phenotypes at our center. These cases suggest that children with early-onset drug-resistant "generalized" epilepsy are likely to have a genetic basis although the presentation may not be typical of Dravet syndrome. Hence, genetic testing for SCN1A variants is recommended in children with drug-resistant MRI negative focal-onset/generalized-onset bilateral tonic-clonic seizures before subjecting them to exhaustive presurgical workup and to guide appropriate treatment and prognostication.

Thalamus and focal to bilateral seizures: A multiscale cognitive imaging study.

ObjectiveTo investigate the functional correlates of recurrent secondarily generalized seizures in temporal lobe epilepsy (TLE) using task-based fMRI as a framework to test for epilepsy-specific network rearrangements. Because the thalamus modulates propagation of temporal lobe onset seizures and promotes cortical synchronization during cognition, we hypothesized that occurrence of secondarily generalized seizures, i.e., focal to bilateral tonic-clonic seizures (FBTCS), would relate to thalamic dysfunction, altered connectivity, and whole-brain network centrality.MethodsFBTCS occur in a third of patients with TLE and are a major determinant of disease severity. In this cross-sectional study, we analyzed 113 patients with drug-resistant TLE (55 left/58 right), who performed a verbal fluency fMRI task that elicited robust thalamic activation. Thirty-three patients (29%) had experienced at least one FBTCS in the year preceding the investigation. We compared patients with TLE-FBTCS to those without FBTCS via a multiscale approach, entailing analysis of statistical parametric mapping (SPM) 12–derived measures of activation, task-modulated thalamic functional connectivity (psychophysiologic interaction), and graph-theoretical metrics of centrality.ResultsIndividuals with TLE-FBTCS had less task-related activation of bilateral thalamus, with left-sided emphasis, and left hippocampus than those without FBTCS. In TLE-FBTCS, we also found greater task-related thalamotemporal and thalamomotor connectivity, and higher thalamic degree and betweenness centrality. Receiver operating characteristic curves, based on a combined thalamic functional marker, accurately discriminated individuals with and without FBTCS.ConclusionsIn TLE-FBTCS, impaired task-related thalamic recruitment coexists with enhanced thalamotemporal connectivity and whole-brain thalamic network embedding. Altered thalamic functional profiles are proposed as imaging biomarkers of active secondary generalization.

Disrupted alertness and related functional connectivity in patients with focal impaired awareness seizures in temporal lobe epilepsy

ObjectiveFocal impaired awareness seizures are common in temporal lobe epilepsy (TLE). The cognitive impairment associated with this type of seizure is unclear. Alertness is a fundamental aspect of cognition. The locus coeruleus (LC) is closely related to alertness. We aimed to assess the impairment in alertness and LC-related alertness network in patients with focal impaired awareness seizures. MethodsPatients with unilateral TLE were grouped into the only focal impaired awareness seizure group (focal group, n = 19) and the focal impaired awareness seizure with focal to bilateral tonic–clonic seizure (FBTCS) group (FBTCS group, n = 19) and compared with matched healthy controls (HC, n = 19). Alertness was assessed with the attention network test. Functional magnetic resonance imaging (fMRI) was used to construct an alertness-related LC-based functional connectivity (FC) network. ResultsThe focal group exhibited impaired tonic and phasic alertness and exhibited a decreased trend of LC-based FC to the left superior frontal gyrus (SFG). The FBTCS group exhibited impaired tonic alertness, phasic alertness, and alertness efficiency. No significant difference or trend in LC-based FC was found in the FBTCS group. SignificanceThis study reveals disrupted alertness and alertness-related LC-based FC in patients with focal impaired awareness seizures. Our results further demonstrate that the patterns of impaired alertness and of changed LC-based FC were not significantly different between focal impaired awareness seizures and FBTCS.

Effect of Brivaracetam on Efficacy and Tolerability in Patients With Brain Tumor-Related Epilepsy: A Retrospective Multicenter Study.

Background: Epilepsy is a common symptom of brain tumors and is often pharmacoresistent. Among new antiseizure medications (ASMs) Brivaracetam (BRV) has been approved as adjunctive treatment for focal seizures and it was tested in non-oncological patient populations. This is the first study that retrospectively explored efficacy and tolerability of BRV as add-on therapy in brain tumor-related epilepsy (BTRE) patients.Materials and Methods: We reviewed the medical records of 33 BTRE patients from six Italian epilepsy centers; charts included tumor history, diagnosis of BTRE, BRV added as first or second add-on for uncontrolled seizures and/or adverse events (AEs) of the previous ASMs, at least 1-month follow-up, seizure frequency, and AEs assessment.Results: Thirty-three patients (19 males, mean age: 57.6 years; 14 females, mean age: 42.4 years): 11 low grade gliomas, five high grade gliomas, six meningiomas, 10 glioblastomas, one primary cerebral lymphoma. Fourteen patients had focal aware seizures, nine focal unaware, seven focal to bilateral tonic-clonic seizures, three patients presented more than one seizure type: focal unaware with focal to bilateral tonic clonic seizures (two patients) and focal aware and unaware seizures (one patient). Mean seizure frequency in the month preceding BRV introduction: 7.0; at last follow-up: 2.0 (p = 0.001). Seven patients (21.2%) reported AEs (anxiety, agitation, fatigue, vertigo) and three of them (9.0%) required drug withdrawal due to psychiatric adverse events (PAEs). Three other patients withdrew BRV: one for scarce compliance (3.0%), two for uncontrolled seizures (6.0%).Conclusion: Our results showed that BRV could be a new therapeutic option effective in reducing seizures in BTRE patients, taking into account the incidence of PAEs in this particular population. Future and larger prospective studies are needed.

Improving the effectiveness of ANT DBS therapy for epilepsy with optimal current targeting.

ObjectiveDeep brain stimulation of the ANT is a novel treatment option in refractory epilepsy with an established efficacy at the group level. However, data on the effect of individualized programming are currently lacking. We report the effect of programming changes on outcome in deep brain stimulation of anterior nucleus of thalamus (ANT DBS). Secondly, we investigated whether the effect differs between seizure types. Thirdly, we compared the response status between patients with stimulation contacts verified inside the ANT with patients with contacts located outside of ANT.MethodsThe participants were 27 consecutive patients with ANT DBS implantation with at least two‐year follow‐up. Seizures were subdivided into focal aware (FAS), focal impaired awareness (FIAS), and focal to bilateral tonic‐clonic seizures (FBTCS). The patients’ seizure diaries were analyzed retrospectively to assess changes in different seizure types. Active contact locations for each patient were verified from preoperative MRI and postoperative CT fusion images using SureTune III (Medtronic Inc, Minneapolis, MN) software.ResultsA significant reduction in monthly mean seizure frequency occurred in FIAS: 56% at two‐year and 65% at five‐year follow‐up. The effects on FAS and FBTCS were less pronounced. Patients with contacts inside the ANT or on the anterolateral border of ANT experienced a greater reduction in seizure frequency than patients with outside‐ANT contacts. Ultimately, seven patients became responders due to changes in DBS programming or repositioning of contacts, increasing our responder rate from 44% to 70% as measured by a seizure reduction of at least 50%.SignificanceANT DBS appears to be especially effective in reducing FIAS, when the appropriately chosen contacts are activated.

Postictal brainstem hypoperfusion and risk factors for sudden unexpected death in epilepsy.

Since the strongest risk factor for sudden unexpected death in epilepsy (SUDEP) is frequent bilateral tonic-clonic seizures (BTCS), our aim was to determine whether postictal hypoperfusion in brainstem respiratory centers (BRCs) is more common following tonic-clonic seizures. We studied 21 patients with focal epilepsies who underwent perfusion imaging with arterial spin labeling MRI. Subtraction maps of cerebral blood flow were obtained from the postictal and baseline scans. We identified 6 regions of interest in the brainstem that contain key BRCs. Patients were considered to have postictal BRC hypoperfusion if any of the 6 regions of interest were significantly hypoperfused. All 6 patients who experienced BTCS during the study had significant clusters of postictal hypoperfusion in BRCs compared to 7 who had focal impaired awareness seizures (7/15). The association between seizure type studied and the presence of BRC hypoperfusion was significant. Duration of epilepsy and frequency of BTCS were not associated with postictal brainstem hypoperfusion despite also being associated with risk for SUDEP. Postictal hypoperfusion in brainstem respiratory centers occurs more often following BTCS than other seizure types, providing a possible explanation for the increased risk of SUDEP in patients who regularly experience BTCS.

Etiology and Types of Seizures in Patients Presenting to a Tertiary Care Hospital in Karachi: A Cross-Sectional Study.

IntroductionEpilepsy is a burdensome disorder for affected individuals and community. There is limited data available on the epidemiological aspects of seizures in Pakistan and further research is necessary. We aimed to fill this gap by studying this information in epilepsy patients presenting to our neurology department. The purpose of this study is to evaluate the causes and types of seizures among the target population.MethodThis is a cross-sectional study conducted at the Department of Neurology, Dr. Ruth K.M. Pfau Civil Hospital Karachi. In this study we evaluated the causes and types of seizures among patients presenting to our department during the two-year study duration (January 2018-December 2019). Informed consent was taken. Detailed history was taken including features of seizure episodes, age at first seizure, family history and comorbid conditions. Relevant investigations were carried out. The data was compiled to deduce the relevant information using SPSS v20.0. T-test and Chi-square were used for analyzing the data.ResultsA total of 996 patients presented during the study duration. Primary seizures were found in 58% cases while secondary seizures were found in 42% cases. This distribution was more equal in children with 49.6% primary seizures and 50.4% secondary seizures; the gap widened in adults with 64.3% primary seizures and 35.7% secondary seizures. The most common cause of secondary seizures was neonatal encephalopathy which was present in 18.7% patients, followed by traumatic head injury in 18.2% patients. Central nervous system (CNS) infection was the cause in 17.9% patients, cerebral tumors in 14.1% patients, stroke in 11.5%, metabolic encephalopathy in 7.4%, febrile seizures in 6.5% and CNS malformations in 5.7% patients. The top three causes in children were neonatal encephalopathy (28.3%), CNS infections (19.3%) and febrile seizures (12.7%). Adults with secondary seizures were diagnosed most often with head trauma (25.2%), cerebral tumors (19.9%) and stroke (18.4%) as causative factors. The most common type of seizures was generalized onset tonic-clonic seizures which was found in 73.0% patients followed by focal to bilateral tonic-clonic seizures in 8.9% patients. Other types of seizures included focal aware seizures in 5.0%, mixed seizure types in 4.2%, focal impaired awareness seizures in 3.1%, absence seizures in 2.7%, myoclonic seizures in 2.0% and atonic seizures in 1.0% patients. Seizures in children were mostly generalized onset tonic-clonic seizures (75.4%), mixed seizure types (5.7%) and focal to bilateral tonic-clonic seizures (5.2%). In adults the three most common types corresponded to the overall result: generalized onset tonic-clonic seizures (71.2%), focal to bilateral tonic-clonic seizures (11.6%) and focal aware seizures (6.6%).ConclusionWe found that the most common cause of seizures overall in our study population was primary seizures, though primary and secondary seizures were more evenly present in children. Among secondary causes neonatal encephalopathy stood out as the most common cause in children; head trauma was the predominant cause in adults. Most common type of seizures overall and in adults was generalized onset tonic-clonic seizures, followed by focal to bilateral tonic-clonic and focal aware seizure types. Pediatric patients presented most often with generalized onset tonic-clonic seizures, followed by mixed seizure types and focal to bilateral tonic-clonic seizures.

Epilepsy in NF1: a systematic review of the literature.

Epilepsy is one of the possible neurological manifestations of the neurofibromatosis type 1 (NF1) that represents the most common neurocutaneous disorder. We performed a systematic review of the literature on epilepsy associated with NF1 since 1995 in order to better define prevalence and describe type and causes of seizures. Data on type, nature of studies, number of patients, gender, and inheritance of NF1 were recorded as well as data on causes, type, EEGs, brain imaging, intellectual disability (ID), surgical treatment, and outcome of epilepsy. We identified a total of 141 references through the literature search of Pubmed and Embase. After screening, 42 records were identified, including 11617 individuals with NF1 (53% of males). Overall prevalence was estimated at 5.4% lifelong with values that seemed to be slightly lower in children, 3.7% (p 0.0016). Neither gender differences nor correlation with NF1 inheritance was found. Focal with or without bilateral tonic-clonic seizures were the most common seizure type encountered (60.9%). Structural causes were identified in half of cases (114/226). Low-grade gliomas were the most frequent associated lesions followed by mesial temporal sclerosis, malformation of cortical development, dysembryoplastic neuroepithelial tumor, and cerebrovascular lesions. In these cases, the surgical approach improved the epileptic outcome. Prevalence of epilepsy is higher in subjects with NF1 respect of the general population, with values apparently significantly lower in pediatric age. Brain tumors and cytoarchitectural abnormalities are the most frequent causes of epilepsy in this population, although many other brain complications should be taken in account.

A Russian retrospective multicenter open-label observational study based on medical documentation on the use of perampanel in everyday clinical practice

Objective : to retrospectively assess the Russian experience with perampanel (PER) in everyday clinical practice as an adjunctive medication for the treatment of patients aged 12 years or older with focal epilepsy (FE). Patients and methods . A multicenter retrospective study was conducted, during which the physicians filled out standard questionnaires assessing the characteristics of the disease and the therapy performed. The maximum follow-up period was 12 months. Each patient was included in the study only once for the duration of the study. A total of 164 cases of pharmacoresistant FE were analyzed. The patients' mean age was 37.7 years; the male to female ratio was 1:1. The disease duration over 10 years was in 68.7% of patients; structural epilepsy was present in 68.2% (temporal and frontal lesions in 53.4 and 39.1%, respectively) Results and discussion . Most (26.6%) patients were prescribed PER after three previous lines of therapy; before PEP administration, there was a maximum of 2 (50.9%) and 3 (29.6%) drugs, respectively, in the combination. The initial frequency of all seizure types reached 9 [3; 34] per month; that of focal-onset bilateral tonic-clonic seizures was 3 [2; 6] per month. Combined therapy including PER could lead to the disappearance of seizures in 22.7% of cases; the responders (by all seizure types) were 52.8%, whereas the remission rate of bilateral tonic-clonic seizures was 60.8% of patients, the responder rate was 27,8%. At 12 months of follow-up, the therapy retention rate reached 80.7% (95% confidence interval, 72.3—89.1). Adverse events (AEs) were noted in 31.3% of patients; the most frequent AEs were drowsiness (10.4%), aggression (9.8%), irritability (6.7%); other AEs were observed in individual cases. The average dose of PER was 8 mg. Conclusion . PER was effective in patients with resistant PEs at a maximum follow-up of 12 months in routine clinical practice. Remission of all seizure types was achieved in 22.7% of cases, the decrease in the number of seizures >50% was seen in 52.8% of cases; the therapy retention rate was 80.7%. The drug had a therapeutic effect in all types of focal seizures and was most effective in focal-onset bilateral tonic-clonic seizures. Along with its good clinical effect, PER demonstrated a predictable safety profile.

The Sensitivity of Scalp EEG at Detecting Seizures-A Simultaneous Scalp and Stereo EEG Study.

Compare the detection rate of seizures on scalp EEG with simultaneous intracranial stereo EEG (SEEG) recordings. Twenty-seven drug-resistant epilepsy patients undergoing SEEG with simultaneous scalp EEG as part of their surgical work-up were included. A total of 172 seizures were captured. Of the 172 seizures detected on SEEG, 100 demonstrated scalp ictal patterns. Focal aware and subclinical seizures were less likely to be seen on scalp, with 33% of each observed when compared with focal impaired aware (97%) and focal to bilateral tonic-clonic seizures (100%) (P < 0.001). Of the 72 seizures without ictal scalp correlate, 32 demonstrated an abnormality during the SEEG seizure that was identical to an interictal abnormality. Seizures from patients with MRI lesions were statistically less likely to be seen on scalp than seizures from nonlesional patients (P = 0.0162). Stereo EEG seizures not seen on scalp were shorter in duration (49 seconds) compared with SEEG seizures seen on scalp (108.6 seconds) (P < 0.001). Scalp EEG is not a sensitive tool for the detection of focal aware and subclinical seizures but is highly sensitive for the detection of focal impaired aware and focal to bilateral tonic-clonic seizures. Longer duration of seizure and seizures from patients without MRI lesions were more likely to be apparent on scalp. Abnormalities seen interictally may at times represent an underlying seizure. The cognitive, affective, and behavioral long-term effects of ongoing difficult-to-detect seizures are not known.

Who seizes longest? Impact of clinical and demographic factors.

To investigate the impact of clinical and demographic parameters on the duration of focal onset seizures with and without secondary generalization using precise duration measurements from intracranial electroencephalographic (iEEG) recordings. Patients with unifocal epilepsy syndromes and iEEG recording were retrospectively identified from the database of the local epilepsy center (2006-2016). Seizure duration was defined as time difference of iEEG seizure pattern onset and cessation. The seizure semiology was classified based on video recordings. Clinical and demographic data were extracted from patient reports. In total, 69 adults were included, and 654 focal onset seizures were analyzed. Focal to bilateral tonic-clonic seizures (FBTCSs; 98/654) were significantly longer than focal seizures (FSs) without generalization (FS-BTCs; 556/654, P<.001), and most FSs (545/654, 83.3%) terminated within 2 minutes. The duration of FSs was prolonged with increasing age of the patients (P=.003) and was significantly shortened (P<.001) by evolution into an FBTCS. FBTCSs with lateralizing semiologies like version (P=.015) and sign of four (P=.043) were associated with longer bilateral tonic-clonic manifestations. Furthermore, FBTCSs with preceding aura, frontal origin, or onset during sleep were by trend shorter. Age (P<.001) and disease duration (P=.028) were essential for prediction of FS-BTC duration, whereas the vigilance state (P=.085) was the main prediction factor for the duration of FBTCSs. The identified modifiers of seizure duration are of great relevance for clinical risk evaluation, especially in the aging epilepsy patient suffering from temporal lobe epilepsy with secondary generalized seizures.

Cardiogenic cerebral infarction in the parietal lobe predicts the development of post-stroke epilepsy

PurposePost-stroke epilepsy (PSE) is a major late complication of cardioembolic cerebral infarction. However, few studies have examined the epileptogenicity and characteristics of first-occurrence cardioembolic cerebral infarctions. MethodsThis retrospective study included 93 consecutive patients with old cardioembolic cerebral infarctions who were classified into two groups based on their epileptic history: patients presenting with PSE or stroke without seizure (SWS). Each patient was diagnosed with an epileptic seizure subtype and treated with appropriate anti-epileptic therapy after admission. We evaluated clinical characteristics, laboratory results, and intracranial infarct areas. The sizes of these areas were measured using MRI diffusion-weighted image (DWI) of each patient after their first stroke. The volume was calculated by multiplying the total slice area with the slice thickness. ResultsPSE was diagnosed in 43 (46.2 %) of 93 patients. The mean (± SD) time from infarction onset to the first seizure in the PSE group was 22.5 ± 31.6 months. The PSE group exhibited significantly more atrial fibrillation (p = 0.022) and higher glucose levels (p < 0.001) compared with the SWS group. The most common PSE seizure type was focal to bilateral tonic-clonic seizure (61.0 %). Although DWI did not reveal any significant differences in the volume of infarctions between the two groups, the involvement of the parietal lobe in infarction of the PSE group (69.8 %) upon first admission was significantly higher (p = 0.006) than that of the SWS group (40.0 %). Multiple logistic regression analysis revealed that parietal lobe involvement in infarction (OR 4.95; 95 % CI 1.25–19.60; p = 0.023) was a significant independent predictor of PSE. ConclusionThe involvement of the parietal lobe in infarction was a significant independent predictor of PSE. Dysfunction of the parietal lobe might play a critical role in the epileptogenesis of PSE.

Time course of 75%-100% efficacy response of adjunctive brivaracetam.

BackgroundTime to sustained seizure frequency reduction can provide clinically meaningful epilepsy outcomes.Aims of the StudyTo examine the time course of brivaracetam (BRV) efficacy in adults with focal seizures and focal to bilateral tonic‐clonic seizures (FBTCS).MethodsPost hoc analysis of data pooled from three randomized controlled trials of oral adjunctive BRV in adults with epilepsy. Patients with focal epilepsy and a subpopulation with FBTCS receiving BRV 50, 100, or 200 mg/d (initiated without up‐titration) or placebo for 12 weeks were analyzed for time to sustained ≥75%, ≥90%, and 100% seizure reduction without interruption from first day until trial ends.ResultsEvaluation included 1160 patients with focal seizures, including 352 patients with FBTCS. Sustained ≥75%, ≥90%, and 100% response in focal seizures was higher from day 1 for BRV 100 and 200 mg/d vs placebo (P < .01). Sustained ≥75% and 100% FBTCS reduction from day 1 was higher for BRV 100 and 200‐mg/d groups vs placebo (P < .01).ConclusionsThe majority of patients achieving 75%‐100% sustained seizure frequency reduction (all focal seizure types and the subpopulation with FBTCS) with oral BRV (100 or 200 mg/d) achieved this response on the first‐treatment day.

CTnI, BNP and CRP profiling after seizures in patients with drug-resistant epilepsy

PurposeTo profile serum levels of high sensitivity Troponin I (hs-cTnI), B-Type Natriuretic Peptide (BNP), and high sensitivity C Reactive Protein (hs-CRP), after epileptic seizures in patients with focal drug-resistant epilepsy, relating the results to the revised SUDEP-7 inventory. MethodsWe prospectively evaluated patients admitted to our Epilepsy Monitoring Unit. hs-cTnI, BNP, and hs-CRP were measured at admission and after the first seizure. The revised SUDEP-7 Risk Inventory was calculated. The statistical significance level was set at 0.05. ResultsFifty-eight patients were included (53.4 % female). The index seizure was a focal to bilateral tonic-clonic seizure (FBTCS) in 25.9 % of the patients, and 17.5 % had post-ictal generalized EEG suppression (PGES). After the seizure, 25.9 % had a significant (above 50 %) increase in hs-cTnI, 23.3 % in BNP, and 4.3 % in hs-CRP. About 40 % had cardiovascular risk factors (CRF), without known cardiac disease. The elevation of one biomarker did not compel the elevation of another. hs-cTnI increase was associated with FBTCS, PGES, longer seizures, maximal ictal heart rate, and HR change. Increases in BNP were associated with CRF. hs-CRP increase was associated with PGES. We found no significant association between SUDEP-7 and any biomarker increase. SignificanceSeveral patients had increases in biomarkers of myocardial necrosis/dysfunction after seizures, without significant association with the SUDEP-7 inventory. Different patterns of biomarkers’ elevations point to multifactorial pathophysiologies hypothetically associated with incipient myocardial lesions. A larger cohort with follow-up data could help to clarify the clinical relevance of these findings.

Efficacy and safety of perampanel monotherapy in patients with focal-onset seizures with newly diagnosed epilepsy or recurrence of epilepsy after a period of remission: The open-label Study 342 (FREEDOM Study).

ObjectiveOur study assessed perampanel monotherapy in patients (aged ≥12 years) with focal‐onset seizures (FOS) with or without focal to bilateral tonic‐clonic seizures (FBTCS) in Japan and South Korea.MethodsStudy 342 (NCT03201900; FREEDOM) is a single‐arm, open‐label, Phase III study. Patients initially received perampanel in a 32‐week 4‐mg/d Treatment Phase (6‐week Titration; 26‐week Maintenance Periods). If they experienced a seizure during the 4‐mg/d Maintenance Period, they could be up‐titrated to 8 mg/d across an additional 30‐week Treatment Phase (4‐week Titration; 26‐week Maintenance Periods). Primary endpoint was the seizure‐freedom rate during the Maintenance Period (4 mg/d and last evaluated dose [4 or 8 mg/d]). Secondary endpoints included time to first seizure onset and to withdrawal during Maintenance. Treatment‐emergent adverse events (TEAEs) were monitored.ResultsAt data cutoff (February 28, 2019), 89 patients with FOS (84 [94.4%] with newly diagnosed epilepsy and 5 [5.6%] with recurrence of epilepsy after a period of remission) had received ≥1 perampanel dose; 16 patients discontinued during the 4‐mg/d Titration Period, meaning 73 patients entered the 4‐mg/d Maintenance Period and were included in the primary analysis set for efficacy. Seizure‐freedom rate in the 26‐week Maintenance Period was 46/73 (63.0%; 95% confidence interval [CI]: 50.9‐74.0) at 4 mg/d and 54/73 (74.0%; 95% CI: 62.4‐83.5) at 4 or 8 mg/d. Cumulative probability of seizure‐onset and withdrawal rates during Maintenance was 30.8% (95% CI: 21.5‐43.0) and 23.7% (95% CI: 15.4‐35.3) at 4 mg/d, and 18.2% (95% CI: 11.0‐29.3) and 23.3% (95% CI: 15.2‐34.8) at 4 or 8 mg/d. Perampanel was generally well tolerated, and the most common TEAE was dizziness.SignificancePerampanel monotherapy (4 to 8 mg/d) was efficacious and consistent with the known safety profile up to 26 weeks in patients (≥12 years) with primarily newly diagnosed FOS with or without FBTCS.

Altered gray matter volume in MRI-negative focal to bilateral tonic-clonic seizures.

To investigate cortical changes in MRI-negative patients with focal to bilateral tonic-clonic seizures (FBTCS). High-resolution three-dimensional T1-weighted MRI were collected with a GE 3.0-T MRI scanner from 26 patients with FBTCS and 21 healthy volunteers at Nanjing Brain Hospital. Voxel-based morphometry was performed on T1-weighted MRI of all subjects. A two-sample t test was performed to compare the GMV of two groups. Age and gender were taken as covariables, so that brain regions with significant differences, as compared by two-sample t test, between the two group were obtained. These regions were extracted as the regions of interest (ROIs) used for correlation analysis between ROIs and clinical variables. There is no significant difference in GMF between two groups. In FBTCS, regions with decreased GMV are bilateral thalamus, bilateral orbitofrontal cortex, left medical cingulate gyrus, and right supplementary motor area. GMV is increased within the bilateral para-hippocampal regions (voxel-wise FDR-corrected, P < 0.05). The GMVs are significantly negatively correlated with disease duration in the left thalamus and the left para-hippocampal region (P < 0.05). Seizures may lead to the loss of neurons and the decrease of GMV in FBTCS. The increase of GMV in some regions might be due to inflammatory responses in the early stages of epileptic seizures.

Characterization and Outcomes of Epileptic Seizures in Mexican Pediatric Patients With Anti-N-Methyl-D-Aspartate Receptor Encephalitis.

IntroductionAnti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is one of the most common autoimmune encephalitides. The frequency of anti-NMDAR encephalitis is known to exceed the frequency of any individual viral encephalitis in young subjects. Epileptic seizures are a cardinal symptom in anti-NMDAR encephalitis; a significant amount of pediatric patients exhibit seizures as the first symptom of the disease, and most of them will develop them during the acute phase. The use of antiepileptic drugs (AEDs) is a cornerstone of the treatment of these patients, but the choice of agent and duration of treatment is currently unknown.Materials and methodsThis was a single-center retrospective review case series of all pediatric patients with a confirmed diagnosis of anti-NMDAR encephalitis and epileptic seizures admitted to the National Institute of Pediatrics in Mexico City from January 2012 to July 2019.ResultsWe included a total of 31 patients (males 64.5%, median age: 10 years). No patient showed evidence of teratoma; only 38% of cases had a viral prodrome. Most patients initially exhibited psychiatric symptoms (51%), but the leading cause in soliciting medical assistance was the presence of epileptic seizures (71%). About 85% of patients presented epileptic seizures during the course of the illness, predominantly focal onset seizures (42% focal to bilateral tonic-clonic seizures, 32% focal seizures with impaired awareness). Electroencephalogram (EEG) was abnormal in 97% of patients; the characteristic extreme delta brush pattern was found in 9% of patients. Two AEDs on average were required to control seizures during the acute stage. In six (19%) patients, human herpesvirus (HHV) was detected in cerebrospinal fluid (CSF); all of them had epileptic seizures, which were more resistant to pharmacological treatment during the acute phase, requiring a higher number of AED (median 2.5 vs. 2). The development of epilepsy after acute encephalitis was uncommon; at 24 months, only one patient continued to have epileptic seizures. One of the factors most closely related to the persistence of epileptic seizures was the inadequate response to immunotherapy after four weeks. The functional prognosis was generally good; at a two-year follow-up, only two (10%) patients had a significant disability [modified Rankin Scale (mRS) score: 3-5]; both patients had seizures at a one-year follow-up.ConclusionsSustained use of AEDs after the acute phase of anti-NMDAR encephalitis is controversial. We found that the continuation of AEDs after the acute phase could be considered in the following scenarios: status epilepticus (SE), inadequate response to immunotherapy at four weeks, and a high mRS score at discharge and during follow-up. In other cases, discontinuation of AED may be warranted. More studies are needed in our country to replicate these results.

Antiepileptic drug withdrawal and seizure severity in the epilepsy monitoring unit

ObjectiveThe goal of this study was to identify a strategy for antiepileptic drug (AED) reduction to allow efficient recording of focal seizures (FS) in patients undergoing video-electroencephalography (EEG) in an epilepsy monitoring unit (EMU) while avoiding the risk of complications associated with more severe seizure types. MethodsWe retrospectively reviewed consecutive patients admitted to our institution's EMU from July 1, 2016 to December 31, 2017. We included 114 presurgical patients who had AEDs reduced and at least one seizure during the admission. We compared AED dosages at which FS versus focal to bilateral tonic–clonic seizures (f-BTCS), seizure clusters, and lorazepam administration occurred. We also examined rate of AED reduction and seizure types. We used a receiver-operating characteristic (ROC) curve to identify a dose maximizing FS and minimizing other seizure types. ResultsAntiepileptic drug withdrawal rates ranged from 0 to 100% in the first 24 h (mean: 20%, standard deviation: 20%). Focal to bilateral tonic–clonic seizures and lorazepam administration occurred at a lower median AED dose than did FS (0%, 7.2%, and 43.8%, respectively, expressed as a percentage of the patient's outpatient daily AED dose; p < 0.001). A daily EMU-administered dose of one-third of the patient's outpatient AED dose allowed 55.0% of FS to occur while avoiding 82.0% of more severe seizure types. The seizure types had no difference in rate of AED withdrawal in the first 24 h of EMU stay. ConclusionsFocal seizures occurred at a higher AED dose than did f-BTCS. This may imply that a low minimally effective dose of AED could allow FS to be recorded while providing protection against f-BTCS. This strategy could improve efficacy and safety in the EMU.