Low Seizure Frequency Research Articles

Quality of life in SCN1A-related seizure disorders across the lifespan.

This cohort study aims to describe the evolution of disease features and health-related quality of life per life stage in Dravet syndrome and other SCN1A-related non-Dravet seizure disorders which will enable treating physicians to provide tailored care. Health-related quality of life and disease features were assessed cross-sectionally in participants with a SCN1A-related seizure disorder, categorized per age group for Dravet syndrome, and longitudinally over seven years follow-up (2015-2022). Data were collected from questionnaires, medical records, and semi-structured telephonic interviews. Health-related quality of life was measured with the Paediatric Quality of Life Inventory, proxy-reported for participants with Dravet syndrome and for participants with non-Dravet aged younger than 18 years old and self-reported for participants with non-Dravet over 18 years old. Associations between health-related quality of life and disease features were explored with multivariable regression analyses, cross-sectionally in a cohort of 115 patients with Dravet and 48 patients with generalized epilepsy with febrile seizures plus and febrile seizures (non-Dravet) and longitudinally in a cohort of 52 Dravet patients and 13 non-Dravet patients. In the cross-sectional assessment in 2022, health-related quality of life was significantly lower in Dravet syndrome, compared to non-Dravet and normative controls. Health-related quality of life in the School and Psychosocial domain was significantly higher in older Dravet age groups. A higher health-related quality of life was associated with fewer behavioural problems [β = -1.1; 95% confidence interval (CI), (-1.4 to -0.8)], independent walking (β = 8.5; 95%CI (4.2-12.8)), compared to the use of a wheelchair), and fewer symptoms of autonomic dysfunction (β = -2.1, 95%CI (-3.2 to -1.0)). Longitudinally, health-related quality of life was significantly higher seven years later in the course of disease in Dravet participants (Δ8.9 standard deviation (SD) 18.0, P < 0.05), mediated by a lower prevalence of behavioural problems (β = -1.2, 95%CI (-2.0 to -0.4)), lower seizure frequency (β = -0.1, 95%CI (-0.2 to -0.0)) and older age (β = 0.03, 95%CI (0.01-0.04)). In summary, health-related quality of life was significantly higher at older age in Dravet syndrome. This finding may reflect the benefits of an advanced care strategy in recent years and a ceiling of severity of disease symptoms, possibly resulting in an increased wellbeing of parents and patients. The strong association with behavioural problems reinforces the need to incorporate a multidisciplinary approach, tailored to the age-specific needs of this patient group, into standard care.

The spectrum of indications for ultralong-term EEG monitoring

PurposeWe assessed clinical cases to investigate the spectrum of indications for ultra-longterm EEG monitoring using a subcutaneous implantable device in adult patients with focal epilepsy. MethodsElectronic charts were reviewed from patients undergoing ultra-longterm recordings at the European Epilepsy centers Barcelona, Freiburg and Vienna. Specific patient settings approached in the three centers were analyzed, and the main clinical question was extracted. Results from recordings were analyzed based on the specific results and information obtained. Results24 patients in whom ultra-longterm recordings were available were analyzed. A total of 11 main indications for subcutaneous long-term EEG recordings were identified, including the identification of active epilepsy in patients with low seizure frequency, under- and overreporting of patients, differentiation of non-epileptic from epileptic events, assessment of seizure severity, circadian and multidian rhythms of seizure occurrence, validation of treatment efficacy, improvement of patient-based reporting and medicolegal evidence for seizure freedom. This is reported with patient-specific case vignettes. ConclusionUltra-longterm monitoring using subcutaneous implantable EEG devices can provide relevant diagnostic and treatment information in a large spectrum of clinical situations. This is discussed considering the intrinsic limitations of the method related to spatial coverage, sensitivity and validity as a biomarker of ongoing seizures.

Trends, outcomes, and complications of surgery for lesional epilepsy in infants and toddlers: A multicenter study.

To assess seizure and developmental outcomes, their predictors, and complications in 160 children who, between 1998 and 2022, underwent surgery for lesional epilepsy with curative intent before the age of 3 years. To compare trends in epilepsy surgery in this age group before and after the year 2014. Retrospective multicenter study. Descriptive and univariate analyses, and multivariable models for all outcomes. These 160 patients (76 F; 47.5%) underwent 169 surgeries (age at surgery 20.4 ± 9.4 months). At the last follow-up (77 ± 57.4 months), 121 patients (75.6%) were in Engel class I, 106 (66.2%) of whom were in Engel class Ia. Antiseizure medications were stopped in 84 patients (52.5%). Complications requiring reoperations were observed in 16 patients (10%; 9.5% of surgeries) and unexpected permanent deficits in 12 (7.5%; 7.1% of surgeries). Postoperative cognitive functions remained unchanged in 56 patients (44.4%), improved in 51 (40.5%), and worsened in 19 (15.1%). Multivariable analyses showed that the probability of achieving Engel class Ia was lower when the duration of epilepsy was longer, patients underwent preoperative video-EEG, and unexpected postoperative permanent deficits occurred. Cognitive improvement after surgery was associated with lower preoperative seizure frequency, better preoperative developmental level, and a longer postoperative follow-up. FCDII and tumors were the histopathologies carrying a higher probability of achieving seizure freedom, while polymicrogyria was associated with a lower probability of cognitive improvement. The number of patients operated on after 2014 was higher than before (61.3% vs. 38.7%), with stable outcomes. Epilepsy surgery is effective and safe in infants and toddlers, although the complication rate is higher than seen in older patients. Shorter duration of epilepsy, lower seizure frequency, no need for video-EEG, tumors, and some malformations of cortical development are robust predictors of seizure and cognitive outcome that may be exploited to increase earlier referral. This study analyzed the results of epilepsy surgery in 160 children who had been operated on before the age of 3 years at four Italian centers between 1998 and 2022. At the last follow-up (77 ± 57.4 months), 121 patients (75.6%) were free from disabling seizures, of which 106 (66.2%) were completely seizure-free since surgery. Major surgical complications occurred in 28 patients (17.5%), which is higher than observed with epilepsy surgery in general, but similar to hemispheric/multilobar surgery. Postoperative cognitive function remained unchanged in 56 patients (44.4%), improved in 51 (40.5%), and worsened in 19 (15.1%). Epilepsy surgery is effective and safe in infants and toddlers.

Rat strain differences in seizure frequency and hilar neuron loss after systemic treatment with pilocarpine

At least 3 months after systemic treatment with pilocarpine to induce status epilepticus, Long-Evans and Sprague-Dawley rats were video-EEG monitored for seizures continuously for 1 month. Rats were then perfused, hippocampi were processed for Nissl staining, and hilar neurons were quantified. Seizure frequency in Long-Evans rats was 1/10th of that in Sprague-Dawley rats, and more variable. Hilar neuron loss was also less severe in Long-Evans rats. However, there was no correlation between hilar neuron loss and seizure frequency in either strain. The low and variable seizure frequency suggests limited usefulness of pilocarpine-treated Long-Evans rats for some epilepsy experiments.

Evaluation of social inclusion in Brazilian adult women with epilepsy: Perception of stigma and quality of life

Epilepsy is a chronic disease characterized by recurrent epileptic seizures that can affect the perception of stigma and compromise the quality of life of those living with it. In addition, sociodemographic factors such as employment and maintaining a job, education, and the autonomy to drive vehicles are often impaired. ObjectiveTo assess the social inclusion of adult women with epilepsy in relation to the perception of stigma and quality of life, and the clinical aspects of the disease. MethodologyData from 70 adult Brazilian women with epilepsy regarding aspects related to their social inclusion were verified. Such data were linked to clinical aspects and scores from the questionnaires: Quality of Life in Epilepsy Inventory 31 (QOLIE-31) and the Epilepsy Stigma Scale (ESS), with a significance level of p < 0.05. ResultsAverage age of 45.5 years, 40 (57.1 %) women were divorced/single/widowed, 31 (44.3 %) women had less than 10 years of formal education, 32 (45.7 %) women had no income, and 57 (81.4 %) did not have a driver's license. The age at the time of the first seizure was 18 years, the seizures were focal in 46 (65.7 %) cases, and 26 (37.1 %) cases were seizure-free in the last year. A high number of women reported that the diagnosis of epilepsy negatively influenced aspects of autonomy such as the possession of a driver's license and going out alone. Longer duration of epilepsy was associated with lower education, not having children, and lower scores on the QOLIE-31. Higher scores on the QOLIE-31 were correlated with lower frequency of seizures and with the age at the time of the first seizure. Values in the dimension − energy and fatigue of the QOLIE-31 were significantly lower in the group with less independence compared to the other two groups with more independence, in latent class analyses (ANOVA, adjusted for age 42.1 ± 35.6 vs 57.2 ± 28.4 vs 73.9 ± 23.8, p = 0.0295). DiscussionClinical aspects of epilepsy and having a partner, autonomy, and independence such as driving vehicles are factors that contribute to social inclusion and to the perception of a better quality of life for adult women with epilepsy. ConclusionIt was observed that having a partner, autonomy, and independence such as driving vehicles are factors that contribute to social inclusion and to the perception of a better quality of life for adult women with epilepsy.

Connectome reorganization associated with temporal lobe pathology and its surgical resection.

Network neuroscience offers a unique framework to understand the organizational principles of the human brain. Despite recent progress, our understanding of how the brain is modulated by focal lesions remains incomplete. Resection of the temporal lobe is the most effective treatment to control seizures in pharmaco-resistant temporal lobe epilepsy (TLE), making this syndrome a powerful model to study lesional effects on network organization in young and middle-aged adults. Here, we assessed the downstream consequences of a focal lesion and its surgical resection on the brain's structural connectome, and explored how this reorganization relates to clinical variables at the individual patient level. We included adults with pharmaco-resistant TLE (n = 37) who underwent anterior temporal lobectomy between two imaging time points, as well as age- and sex-matched healthy controls who underwent comparable imaging (n = 31). Core to our analysis was the projection of high-dimensional structural connectome data-derived from diffusion MRI tractography from each subject-into lower-dimensional gradients. We then compared connectome gradients in patients relative to controls before surgery, tracked surgically-induced connectome reconfiguration from pre- to postoperative time points, and examined associations to patient-specific clinical and imaging phenotypes. Before surgery, individuals with TLE presented with marked connectome changes in bilateral temporo-parietal regions, reflecting an increased segregation of the ipsilateral anterior temporal lobe from the rest of the brain. Surgery-induced connectome reorganization was localized to this temporo-parietal subnetwork, but primarily involved postoperative integration of contralateral regions with the rest of the brain. Using a partial least-squares analysis, we uncovered a latent clinical imaging signature underlying this pre- to postoperative connectome reorganization, showing that patients who displayed postoperative integration in bilateral fronto-occipital cortices also had greater preoperative ipsilateral hippocampal atrophy, lower seizure frequency and secondarily generalized seizures. Our results bridge the effects of focal brain lesions and their surgical resections with large-scale network reorganization and interindividual clinical variability, thus offering new avenues to examine the fundamental malleability of the human brain.

Leukocyte differential gene expression prognostic value for high versus low seizure frequency in temporal lobe epilepsy

BackgroundThis study was performed to test the hypothesis that systemic leukocyte gene expression has prognostic value differentiating low from high seizure frequency refractory temporal lobe epilepsy (TLE).MethodsA consecutive series of patients with refractory temporal lobe epilepsy was studied. Based on a median baseline seizure frequency of 2.0 seizures per month, low versus high seizure frequency was defined as ≤ 2 seizures/month and > 2 seizures/month, respectively. Systemic leukocyte gene expression was analyzed for prognostic value for TLE seizure frequency. All differentially expressed genes were analyzed, with Ingenuity® Pathway Analysis (IPA®) and Reactome, to identify leukocyte gene expression and biological pathways with prognostic value for seizure frequency.ResultsThere were ten males and six females with a mean age of 39.4 years (range: 16 to 62 years, standard error of mean: 3.6 years). There were five patients in the high and eleven patients in the low seizure frequency cohorts, respectively. Based on a threshold of twofold change (p < 0.001, FC > 2.0, FDR < 0.05) and expression within at least two pathways from both Reactome and Ingenuity® Pathway Analysis (IPA®), 13 differentially expressed leukocyte genes were identified which were all over-expressed in the low when compared to the high seizure frequency groups, including NCF2, HMOX1, RHOB, FCGR2A, PRKCD, RAC2, TLR1, CHP1, TNFRSF1A, IFNGR1, LYN, MYD88, and CASP1. Similar analysis identified four differentially expressed genes which were all over-expressed in the high when compared to the low seizure frequency groups, including AK1, F2R, GNB5, and TYMS.ConclusionsLow and high seizure frequency TLE are predicted by the respective upregulation and downregulation of specific leukocyte genes involved in canonical pathways of neuroinflammation, oxidative stress and lipid peroxidation, GABA (γ-aminobutyric acid) inhibition, and AMPA and NMDA receptor signaling. Furthermore, high seizure frequency-TLE is distinguished prognostically from low seizure frequency-TLE by differentially increased specific leukocyte gene expression involved in GABA inhibition and NMDA receptor signaling. High and low seizure frequency patients appear to represent two mechanistically different forms of temporal lobe epilepsy based on leukocyte gene expression.

Perampanel outcomes at different stages of treatment in people with focal and generalized epilepsy treated in clinical practice: Evidence from the PERMIT study.

The PERMIT study is the largest pooled analysis of perampanel (PER) clinical practice data conducted to date. This post-hoc analysis of PERMIT investigated the effectiveness, safety and tolerability of PER when used as early add-on therapy (after failure of one or two previous antiseizure medications) in comparison with late add-on therapy (after failure of three or more previous antiseizure medications). Retention and effectiveness were assessed after 3, 6, and 12 months, and at the last visit (last observation carried forward). Effectiveness was assessed by seizure type (total seizures, focal seizures, generalized tonic-clonic seizures [GTCS]) and assessments included seizure freedom rate and responder rate. Safety and tolerability were assessed by evaluating adverse events (AEs) and discontinuation due to AEs. The Full Analysis Set included 1184 and 2861 PWE treated with PER as early and late add-on therapy, respectively. Compared to the late add-on subgroup, the early add-on subgroup was characterized by later mean age at epilepsy onset, shorter mean duration of epilepsy, lower rates of intellectual disability and psychiatric comorbidity, and lower frequency of seizures per month, suggesting a less severe form of epilepsy in this subgroup. After 12 months, retention was significantly higher in the early versus late add-on subgroup (67.7% vs. 62.4%; p = 0.004). At the last visit, responder rates in the early versus late add-on subgroup were significantly higher for total seizures (68.2% vs. 39.3%; p < 0.001), focal seizures (65.0% vs. 36.8%; p < 0.001) and GTCS (83.7% vs. 67.2%; p < 0.001), as were seizure freedom rates (total seizures, 35.9% vs. 11.9% [p < 0.001]; focal seizures, 29.4% vs. 8.7% [p < 0.001]; GTCS, 69.0% vs. 48.1% [p < 0.001]). Incidence of AEs was significantly lower in the early versus late add-on subgroup (42.1% vs. 54.7%; p < 0.001), as was the rate of discontinuation due to AEs over 12 months (15.0% vs. 18.1%; p = 0.031). This study demonstrated that PER was effective and generally well tolerated when initiated as early or late add-on therapy, but it was significantly more effective and better tolerated when initiated early. These findings support PER's use as a broad-spectrum, early add-on therapy for use in PWE with focal and generalized seizures.

Clinical characteristics of 80 subjects with KCNQ2-related encephalopathy: Results from a family-driven survey

Variants of KCNQ2 are associated with a wide spectrum of disorders, ranging from Self-limiting Neonatal Epilepsy (SelNE) to Early Onset Developmental and Epileptic Encephalopathy (KCNQ2-DEE). Comorbidities associated with this end of the spectrum have been seldomly described and their impact on the life of patients and their families is yet to be investigated.Collaborating with caregivers from different European family associations, we have developed a questionnaire aimed at investigating the onset and frequency of epileptic seizures, anti-seizure medications (ASM), hospitalizations, stages of development, and comorbidities.Responses from 80 patients, 40 males, from 14 countries have been collected. Median age 7.6 years (4 months – 43.6 years). Of 76 epileptic patients (93.6%), 55.3% were seizure-free with a mean age at last seizure of 26.7 months. Among patients with active epilepsy, those older have a lower frequency of seizures (p > 0.05). We were able to identify three different clusters of varying severity (Mild, Severe, Profound), based on neurodevelopmental features and symptoms, excluding epilepsy. Patients in a higher severity cluster had a higher mean number of comorbidities, which had a higher impact on families. Notably, patients in different clusters presented different epilepsy onset and courses.This study constitutes the most extensive data collection of patients with KCNQ2-DEE, with a focus on comorbidities in a wide age group. The participation of caregivers helps to define the impact of the disease on the lives of patients and families and can help identify new primary and secondary outcomes beyond seizures in future studies.

Semiology characteristics and location of epileptogenic zone in motor seizures of axial and shoulder girdle muscles assessed by video stereoelectroencephalography study in 65 patients.

To study the semiology characteristics of motor seizures of axial and shoulder girdle muscles (ASMs) by stereoelectroencephalography (SEEG) and its value in determining location of epileptogenic zone. A total of 598 patients underwent SEEG assessment in Sanbo Brain Hospital were reviewed; 65 patients with ASMs selected. Thirteen semiology feature items were extracted according to the location and symmetry of involved axial muscles, direction of movement, etc. Seizures were grouped with items, and the k-means was used to analyze association between ASMs semiology characteristics and seizure-onset zone (SOZ). The SOZs of ASMs involved 23 combinations of seven different brain regions: 31 patients (47.7%) had one brain region, 19 (29.2%) had two, 14 (21.5%) had three, and one patient (1.5%) had four. One hundred and fifteen brain regions were analyzed. Seven brain regions accounted for a significant difference in chi-square test, χ2 = 62.79, p < 0.0001, with the highest proportion of insular and perisylvian. The k-means method identified two clusters: cluster 1 had a high degree of agreement with temporal lobe epilepsy (12/15), characterized by less shrug-like movement, later involvement of axial shoulder girdle muscles, longer duration, and lower seizure frequency; cluster 2 had a high degree of agreement with posterior cortex epilepsy (14/18), characterized by earlier involvement of axial shoulder girdle muscles, shorter duration, and higher seizure frequency. In frontal lobe, insular and perisylvian, anterior and middle cingulate gyrus, are the two categories accounted for similar proportion. Seizure-onset lateralized at the contralateral of unilateral cervical tonic, with rate of seizure-free was 73.7%. The incidence of ASMs is high in insular and perisylvian. Unilateral cervical tonic seizures have good lateralizing value. Based on semiology characteristics, ASMs can be roughly clustered into two categories, which can only effectively distinguish the origins of temporal lobe and posterior cortex, with low discrimination for the seizure-onset of other lobes.

Brivaracetam add-on treatment in pediatric patients with severe drug-resistant epilepsy: Italian real-world evidence

Purpose: To report the efficacy and tolerability of brivaracetam (BRV) in add-on therapy in pediatric patients with severe drug-resistant epilepsy. Prognostic factors of clinical outcome were also analyzed. Methods: This Italian multicenter retrospective observational study was conducted on 45 pediatric patients with severe drug-resistant epilepsy, treated with BRV for at least 1 month and with a follow-up >6 months. Demographic, clinical, and treatment variables were assessed at T0 (baseline, BRV introduction) and T1 (6 months after BRV introduction). The response was defined as ≥50% seizure frequency reduction; responders and non-responders were then compared to assess potential prognostic factors. Results: Forty-five patients (M = 28, mean age 12.4+/-4.4 years) were enrolled (focal epilepsy=14; generalized epilepsy=2; epileptic encephalopathy=29). At T1, 19/45 patients (42.2%) were responders (≥50% seizure frequency reduction), with 4 patients (8.9%) achieving a ≥ 75% seizure reduction and 2 patients (4.4%) becoming seizure free. Epilepsy onset at >12 months of age (p = 0.001), disease duration ≤6 years (p = 0.036), and lower seizure frequency at baseline (p = 0.008) were the prognostic factors significantly associated with a better prognosis. No significant difference emerged for demographics, epilepsy types/etiology, intellectual disability, or therapy variables. At T1, 21 patients (46.6%) discontinued BRV, mainly due to lack of efficacy (13 subjects; 28.9%) and adverse events in 8 patients (17.8%). Conclusion: Brivaracetam was an effective and tolerated treatment in pediatric patients with severe drug-resistant epilepsy, especially when the seizure onset was at >12 months of age, the epilepsy duration ≤6 years, and the seizure frequency before BRV treatment was low. Further and controlled studies are needed.

Factors Associated With New-Onset Seizures Following Stereotactic Radiosurgery for Newly Diagnosed Brain Metastases

PurposeStereotactic radiosurgery (SRS) is a highly effective therapy for newly diagnosed brain metastases. Prophylactic antiepileptic drugs are no longer routinely used in current SRS practice, owing to a perceived low overall frequency of new-onset seizures and potential side effects of medications. It is nonetheless desirable to prevent unwanted side effects following SRS. Risk factors for new-onset seizures after SRS have not been well established. As such, we aimed to characterize variables associated with increased seizure risk. Methods and MaterialsPatients treated with SRS for newly diagnosed brain metastases between 2013 and 2016 were retrospectively reviewed at a single institution. Data on baseline demographics, radiation parameters, and clinical courses were collected. ResultsThe cohort consisted of 305 patients treated with SRS without prior seizure history. Median age and baseline Karnofsky Performance Scale score were 64 years (interquartile range, 55-70) and 80 (interquartile range, 80-90), respectively. Twenty-six (8.5%) patients developed new-onset seizures within 3 months of SRS. There was no association between new-onset seizures and median baseline Karnofsky Performance Scale score, prior resection, or prior whole brain radiation therapy. There were significant differences in the combined total irradiated volume (12.5 vs 3.7 cm3, P < .001), maximum single lesion volume (8.8 vs 2.8 cm3, P = .003), lesion diameter (3.2 vs 2.0 cm, P = .003), and number of lesions treated (3 vs 1, P = .018) between patients with and without new-onset seizures, respectively. On multivariate logistic regression, total irradiated volume (odds ratio, 1.09 for every 1-cm1 increase in total volume; confidence interval, 1.02-1.17; P = .016) and pre-SRS neurologic symptoms (odds ratio, 3.08; 95% confidence interval, 1.19-7.99; P = .020) were both significantly correlated with odds of seizures following SRS. ConclusionsOur data suggest that larger total treatment volume and the presence of focal neurologic deficits at presentation are associated with new-onset seizures within 3 months of SRS. High-risk patients undergoing SRS may benefit from counseling or prophylactic antiseizure therapy.

Perampanel as adjuvant treatment in epileptic encephalopathies: A multicenter study in routine clinical practice

ObjectiveDevelopmental and epileptic encephalopathies (DEEs) are a heterogeneous group of syndromes, including Lennox–Gastaut syndrome (LGS), which are refractory to multiple therapies. Perampanel efficacy has been reported in LGS but further real-world evidence is needed in DEEs. MethodsA multicenter, retrospective, 1-year observational study in patients with DEEs on adjuvant perampanel treatment was conducted to assess perampanel safety and effectiveness in this type of patients in a real-world setting. Seizure types [focal onset seizures (FOS), generalized tonic-clonic seizures (GTCS), tonic seizures (TS), atonic seizures (AtS), atypical absences (AA), and myoclonic seizures (MS)] and seizure clusters were divided in different frequency groups: daily, weekly, and monthly seizures, and absent or seizure freedom. Patients could have more than one seizure type. For each frequency group, group change and seizure freedom were analyzed. ResultsEighty-seven patients diagnosed with DEEs (45 males) of median age 22 [1–70] years were included. The most frequent DEEs were LGS (35.6%) and Lennox-like syndrome (37.9%). At baseline 20 patients had three to five types of seizures, 36 patients had two types of seizures and 31 patients had one predominant type of seizure. The mean number of seizure types per patient at baseline was 2.12 ± 0.97 which was reduced to 1.62 ± 0.91 at 12 months (p < 0.001). Overall, 51.7% of patients had a significant improvement in at least one seizure type. At baseline, 45 patients had GTCS, 42 FOS, 41 TS, 18 AA, 16 AtS, 11 MS, and 30 seizures clusters. Seizure freedom for each specific type at 12 months was significantly achieved by 35% of patients with GTCS (p < 0.001), 17% (p = 0.016) with TS and 37% with seizure clusters (p < 0.001). Patients achieved seizure freedom from other seizure types but with no statistical significance: 7% FOS-free, 28% AA-free, 6% Ats-free, and 18% MS-free. Regarding changes of group at 12 months, 22% of TS and 19% of FOS improved significantly to a group with lower seizure frequency (p = 0.004 and p = 0.02, respectively). In remaining groups (4% of GTCS, 11% of AA, 18% of Ats, 18% of MS, and 13% of seizure clusters), the improvement was not statistically significant. Twenty-nine patients discontinued perampanel: 18 (21%) due to AEs, 8 (9%) due to lack of efficacy, and 3 (3%) due to seizure worsening. Adverse events, mostly mild or moderate, were reported in 53% of patients, and irritability/mood changes (22%) and somnolence (17%) were the most frequent. ConclusionThis is the first large-scale real-world study with perampanel across different seizure types in patients with DEEs. Perampanel was effective, especially in GTCS, TS, and FOS, as well as in seizure clusters. Perampanel was generally well-tolerated without unexpected AEs.

Long-term Outcome of Epilepsy and Cortical Malformations Due to Abnormal Migration and Postmigrational Development: A Cohort Study.

To evaluate the long-term outcomes of patients with epilepsy and malformations of cortical development (MCD). We conducted a historical cohort study of patients with epilepsy and MCD due to impaired neuronal migration and postmigration organization with a follow-up period of ≥5 years. For each patient, MCD was classified after accurate neuroimaging reappraisal by an expert neuroradiologist. The primary outcome was remission, defined as a period of seizure freedom ≥5 years at any time from epilepsy onset. We used Kaplan-Meier estimates for survival analysis and univariate and multivariate Cox regression analyses to evaluate baseline variables as possible factors associated with remission. The cohort included 71 patients (M/F 31/40) with a 17-year median follow-up (1,506 person-years). About half (49.3%) had heterotopia, 35.2% polymicrogyria, 7% lissencephaly, and 8.5% the combination of 2 MCD. The mean age at seizure onset was 12.4 ± 7.2 years. Intellectual disability and neurologic deficits were observed in 30.4% and 40.9%, respectively. More than 60% of patients had refractory epilepsy. In 3 patients who underwent epilepsy surgery, MCD diagnosis was confirmed by histology. At the last visit, 44% of patients had been seizure-free during the previous year, but none of them had stopped antiseizure medication. Thirty patients achieved remission (42.2%) at some point in their disease history, whereas 41 individuals (57.8%) had never been in remission for ≥5 years. The cumulative remission rate was 38% by 20 years from inclusion. In the Cox model, unilateral distribution of MCD (hazard ratio [HR] 2.68, 95% CI 1.04-6.92) and a low seizure frequency at onset (HR 5.01, 95% CI 1.12-22.5) were significantly associated with remission. Patients with epilepsy and MCD showed a remission rate of 38% by 20 years from onset. Unilateral distribution of the MCD is associated with a 3-fold probability of achieving remission. About 40% of patients showed a drug-sensitive condition with risk of relapse during their epilepsy course. This study provides Class II evidence that in patients with epilepsy and MCD, unilateral MCD and low seizure frequency at onset are associated with achieving epilepsy remission.

Parental preferences for seizure detection devices: Adiscrete choice experiment.

ObjectivePrevious studies identified essential user preferences for seizure detection devices (SDDs), without addressing their relative strength. We performed a discrete choice experiment (DCE) to quantify attributes' strength, and to identify the determinants of user SDD preferences.MethodsWe designed an online questionnaire targeting parents of children with epilepsy to define the optimal balance between SDD sensitivity and positive predictive value (PPV) while accounting for individual seizure frequency. We selected five DCE attributes from a recent study. Using a Bayesian design, we constructed 11 unique choice tasks and analyzed these using a mixed multinomial logit model.ResultsOne hundred parents responded to the online questionnaire link; 49 completed all tasks, whereas 28 completed the questions, but not the DCE. Most parents preferred a relatively high sensitivity (80%–90%) over a high PPV (>50%). The preferred sensitivity‐to‐PPV ratio correlated with seizure frequency (r = −.32), with a preference for relative high sensitivity and low PPV among those with relative low seizure frequency (p = .04). All DCE attributes significantly impacted parental choices. Parents expressed preferences for consulting a neurologist before device use, personally training the device's algorithm, interaction with their child via audio and video, alarms for all seizure types, and an interface detailing measurements during an alarm. Preferences varied between subgroups (learning disability or not, SDD experience, relative low vs. high seizure frequency based on the population median).SignificanceVarious attributes impact parental SDD preferences and may explain why preferences vary among users. Tailored approaches may help to meet the contrasting needs among SDD users.

Quantification of brain age using high-resolution 7 tesla MR imaging and implications for patients with epilepsy.

Epilepsy patients exhibit morphological differences on neuroimaging compared to age-matched healthy controls, including cortical and sub-cortical volume loss and altered gray-white matter ratios. The objective was to develop a model of normal aging using the 7T MRIs of healthy controls. This model can then be used to determine if the changes in epilepsy patients resemble the changes seen in aging, and potentially give a marker for the severity of those changes. Sixty-nine healthy controls (24F/45M, mean age 36.5±10.5years) and forty-four epilepsy patients (24F/20M, 33.2±9.9years) non-lesional at 3T were scanned with volumetric T1-MPRAGE at 7T. These images were segmented and quantified using FreeSurfer. A linear regression-based model trained on healthy controls was developed to predict ages using derived imaging features among the epilepsy patient cohort. The model used 114 features with significant linear correlation with age. The regression-based model estimated brain age with mean absolute error (MAE) of 6.6years among controls. Comparable prediction accuracy of 6.9years MAE was seen epilepsy patients. T-test of mean absolute error showed no difference in the prediction accuracy with controls and epilepsy patients (p=0.68). However, average signed error showed elevated (+5.0years, p=0.0007) predicted age differences (PAD; brain-PAD=, predicted minus biological age) among epilepsy patients. Morphological metrics in the medial temporal lobe were major contributors to PAD. Additionally, patients with seizure frequency greater than once a week showed significantly elevated brain-PAD (+8.2±5.3years, n=13) compared to patients with lower seizure frequency (3.7±6.5years, n=31, p=0.033). Morphological patterns suggestive of premature aging were observed in non-lesional epilepsy patients vs. controls and in high seizure frequency patients vs. low frequency patients. Modeling brain age with 7T MRI may provide a sensitive imaging marker to assess the differential effects of the aging process in diseases such as epilepsy.

Clinical and electroencephalogram characteristics and treatment outcomes in children with benign epilepsy and centrotemporal spikes.

BACKGROUNDEpilepsy is a syndrome characterized by transient, rigid, paroxysmal, and repetitive central nervous system dysfunction. Prevention, control, and improvement of cognitive and behavioral dysfunction are of great significance for improving the patients’ intellectual development and quality of life. Electroencephalograms (EEG) can predict an accelerated decline in cognitive function.AIMTo determine the clinical and EEG characteristics and treatment results of benign epilepsy in spiking children.METHODSA total of 106 cases of benign epilepsy in children with myocardial spines treated at our hospital from January 2017 to January 2020 were selected. Differences in clinical data and EGG characteristics between treatment-effective/-ineffective patients were analyzed, and children’s intellectual development before and after treatment evaluated using the Gesell Development Diagnostic Scale.RESULTSEEG showed that the discharge proportion in the awake and sleep periods was 66.04%, and the peak/peak discharge was mainly single-sided, accounting for 81.13%, while the discharge generalization accounted for 31.13%. There was no significant difference in any of these variables between sexes and ages (P > 0.05). The proportion of patients with early onset (< 5 years old) and seizure frequency > 3 times/half a year was 40.00% and 60.00%, respectively; the incidence rate and seizure frequency in the younger age group (< 5 years old) were significantly higher than those in the treatment-effective group (P < 0.05), while the discharge index was significantly lower than that in the treatment-effective group (P < 0.05). The discharge index was negatively correlated with fine motor skill and language development (r = -0.274 and -0.247, respectively; P < 0.05), but not with the rest (P > 0.05). Logistic regression analysis showed that low age onset (< 5 years old) and seizure frequency were the factors affecting ineffective-treatment of benign epilepsy in children (odds ratio = 11.304 and 5.784, respectively; P < 0.05). The discharge index of the responsive group after treatment was significantly lower than that of the unresponsive group (P < 0.05). However, there was no significant difference between groups after treatment in gross and fine motor skills, adaptability, language, and personal social development (P > 0.05).CONCLUSIONThe EEG of children with benign epilepsy due to spinal wave in central time zone has characteristic changes, and the therapeutic effect is influenced by age of onset and attack frequency.

Religious Experience and Clinical-EEG Aspects in Adult People with Epilepsy.

Spirituality and religiosity are complex cognitive phenomena; however, the relationship between spiritual experiences and epilepsy continues to be debated. Methods. Data from the daily spiritual experience scale (DSES) were related to EEG data and clinical variables of 100 adult people with epilepsy (PWEs). DSES scores were compared to 51 normal individuals (control group [CG]), with a significance level of P < .05. Results. The total score in the DSES was 36.1 ± 14 and 37.6 ± 13.2, respectively, in the PWEs and in the CG. In the PWEs, there was a correlation between DSES and age (Pearson's correlation; -0.22; P = .027) and educational level (0.207; P = .039). PWEs with ≥one seizure/month have a lower frequency of daily spiritual experiences than those with better controlled seizures (T-test; 39.2 ± 16.2 vs 31.7 ± 7.6; P = .038). EEG epileptiform activity (EA) in the right hemisphere was associated with a higher frequency of spiritual experiences than those with left-hemisphere EA (29.8 ± 9.0 vs 38.5 ± 17.5; P = .010). Conclusion. Demographic aspects, EA in the right hemisphere, and lower seizure frequency are associated with daily spiritual experiences in epilepsy, suggesting an association between aspects of spirituality, epilepsy, and neurobiological correlates.

Association between the Serum Coenzyme Q10 Level and Seizure Control in Patients with Drug-Resistant Epilepsy.

Drug-resistant epilepsy (DRE) is a chronic neurological disorder with somatic impacts and increased risk of metabolic comorbidities. Oxidative stress might play an important role in metabolic effects and as a regulator of seizure control, while coenzyme Q10 (CoQ10) could improve insulin sensitivity through antioxidant effects. We aimed to investigate the association between CoQ10 level and clinical outcome, represented by the seizure frequency and quality of life, in DRE patients. DRE patients (N = 33) had significantly higher serum insulin levels and lower scores on the physical domain of the World Health Organization Quality of Life questionnaire (WHOQoL) than gender-age matched controls. The serum CoQ10 level (2910.4 ± 1163.7 ng/mL) was much higher in DRE patients than the normal range. Moreover, the serum CoQ10 level was significantly correlated with the seizure frequency (r = −0.412, p = 0.037) and insulin level (r = 0.409, p = 0.038). Based on stratification by insulin resistance (HOMA-IR > 2.4), the subgroup analysis showed that patients with a greater HOMA-IR had higher CoQ10 levels and lower seizure frequency, and had a significantly worse quality of life. In summary, CoQ10 could be a mediator involved in the mechanism of epilepsy and serve as a biomarker of the clinical outcome in DER patients.

Comparative assessment of health-related quality of life with and without anticonvulsant therapy in patients with childhood epilepsy with centrotemporal spikes.

ObjectiveTo estimate anti-seizure medication (ASM) treatment burden and its effects on health-related quality of life (HRQOL) in new-onset childhood epilepsy with centrotemporal spikes (CECTS) using different treatment approaches in Kazakhstan.MethodsForty-three patients were followed prospectively during 2015 to 2020 for at least 2 years. Patients were divided into three groups: (1) history of ≤3 seizures (n = 32); (2) ≥4 seizures (n = 6); (3) cerebral palsy coexisting with CECTS (n = 5). The first group was subdivided into treated (n = 8) and observed (n = 24) subgroups. The shortened Quality of Life in Childhood Epilepsy Questionnaire (QOLCE-55) was completed by parents after 6 months of follow-up.ResultsAt the end of the study, all children had a sustained remission from seizures for at least 2 years. Differences were identified in emotional, social, and physical subscales between patients in the low seizure frequency group. Signs of low self-esteem, anxiety, depression, limited social interaction owing to pharmacotherapy, painful medical procedures, and stigma were reasons for decreased HRQOL in the treated subgroup. Overall HRQOL in treated (89.2 ± 5.2) patients was significantly decreased compared with observed children with low seizure frequency (98.0 ± 3.0).ConclusionASM therapy does not necessarily improve and may decrease HRQOL in children with low seizure frequency CECTS.