Tertiary Epilepsy Center Research Articles

Impact of Genetic Testing on Therapeutic Decision-Making in Childhood-Onset Epilepsies-a Study in a Tertiary Epilepsy Center.

We assessed the frequency of pediatric monogenic epilepsies and precision therapies at a tertiary epilepsy center. We analyzed medical records of children, born in 2006-2011 and followed at the Danish Epilepsy Center from January to December 2015; 357 patients were identified, of whom 27 without epilepsy and 35 with acquired brain damage were excluded. Of the remaining 295 children, 188 were consented for study inclusion and genetic testing. At inclusion, 86/188 had a preexisting genetic diagnosis and did not undergo further genetic testing. The 102 genetically unsolved patients underwent WES, which identified a (likely) pathogenic variant in eight patients and a highly relevant variant of unknown significance (VUS) in seven additional patients. Single nucleotide polymorphism array was performed in the remaining 87 patients and revealed no (likely) pathogenic copy number variants (CNVs). Patients with a genetic diagnosis had a significantly lower median age at seizure onset and more often had febrile seizures, status epilepticus, or neurodevelopmental impairment compared to those who remained genetically unsolved. Most common epilepsies were focal or multifocal epilepsies and developmental and epileptic encephalopathies (DDEs). Fifty-three patients, with a putative genetic diagnosis, were potentially eligible for precision therapy approaches. Indeed, genetic diagnosis enabled treatment adjustment in 32/53 (60%); 30/32 (93%) patients experienced at least a 50% reduction in seizure burden while only 4/32 (12.5%) became seizure-free. In summary, a genetic diagnosis was achieved in approximately 50% of patients with non-acquired epilepsy enabling precision therapy approaches in half of the patients, a strategy that results in > 50% reduction in seizure burden, in the majority of the treated patients.

Imaging in medically refractory epilepsy at 3 Tesla: a 13-year tertiary adult epilepsy center experience

ObjectivesMRI negative epilepsy has evolved through increased usage of 3 T and insights from surgically correlated studies. The goal of this study is to describe dedicated 3 T epilepsy MRI findings in medically refractory epilepsy (MRE) patients at a tertiary epilepsy center to familiarize radiologists with an updated spectrum and frequency of potential imaging findings in the adult MRE population.MethodsIncluded were all patients with MRE admitted to the epilepsy monitoring unit who were discussed at weekly interdisciplinary imaging conferences at Toronto Western Hospital with MRI studies (3 T with dedicated epilepsy protocol) performed between January 2008 and January 2021. Lesion characterization was performed by two readers based on most likely imaging diagnosis in consensus. Lobes involved per case were recorded.ResultsA total of 738 patients (386 female; mean age 35 years, range 15–77) were included. A total of 262 patients (35.5%) were MRI negative. The most common imaging finding was mesial temporal sclerosis, seen in 132 patients (17.9%), followed by encephalomalacia and gliosis, either posttraumatic, postoperative, postischemic, or postinfectious in nature, in 79 patients (10.7%). The most common lobar involvement (either partially or uniquely) was temporal (341 cases, 58.6%). MRE patients not candidates for surgical resection were included in the study, as were newly described pathologies from surgically correlated studies revealing findings seen retrospectively on reported MRI negative exams (isolated enlargement of the amygdala, temporal pole white matter abnormality, temporal encephalocele).ConclusionThis study provides an updated description of the spectrum of 3 T MRI findings in adult MRE patients from a tertiary epilepsy center.

Long-term evolution and prognostic factors of epilepsy in limbic encephalitis with LGI1 antibodies.

To characterize the evolution of epilepsy in patients with leucine-rich glioma inactivated 1 antibody-associated (LGI1ab) limbic encephalitis, including factors associated with drug-resistant epilepsy (DRE). Retrospective analysis of patients with LGI1 encephalitis managed at two tertiary epilepsy centers between 2005 and 2019 and whose samples were confirmed by the French Reference Center of Paraneoplastic Neurological Syndromes. Raw clinical, biological, EEG, and MRI data were reviewed. Two endpoints were defined: (i) Epilepsy remission: patients seizure free and in whom anti-seizure medications (ASM) have been stopped for at least 1year at the last follow-up visit (ii) DRE: patients with persistent seizures at the last follow-up despite at least two ASM used at efficacious daily dose. 39 patients with LGI1 encephalitis were included with a median follow-up duration of 42months (range 13-169). All of them reported seizures at the acute phase, with faciobrachial dystonic seizures (FBDS) in 23 (59%) and other focal seizures in 38 (97%), including 4 patients (10%) with de novo status epilepticus. At the last follow-up visit, 11 patients (28%) achieved epilepsy remission. Among the 28 patients with persistent epilepsy, eight (29%) fulfilled criteria of DRE. The only factor significantly associated with epilepsy remission was the time from clinical onset of the encephalitis to initiation of the first immunomodulatory treatment, with longer delay in patients with persistent epilepsy (7.5 ± 8.9 vs 2.4 ± 1.7months, p = 0.006). Evolution to DRE was only driven by MRI evolution. Eight of the 15 patients (53%) who developed hippocampal atrophy (p = 0.007) also suffered from drug-resistant seizures at the last follow-up. In patients with LGI1 encephalitis, rapid initiation of immunomodulatory treatment favors long-term epilepsy remission. Evolution to DRE might primarily reflect the anatomical lesion of limbic structures. Determining what modalities of immune treatment may alter these outcomes requires prospective studies with long-term follow-up.

Clinical profile and outcomes of epilepsy surgery in children from a tertiary epilepsy care center in India

The present study aims to describe epilepsy surgery outcomes in the pediatric population from a tertiary center in India. Children less than 18 years who underwent epilepsy surgery between June 2015 and December 2019 for whom at least a 1-year follow-up was available, were retrospectively evaluated for clinical presentation, radiology, surgical intervention, and seizure outcomes. Out of a total of 355 epilepsy surgeries performed, 242 were in the pediatric group (140 males, 80 females). The mean age at surgery was 9.4 years±4.8 years (range 4 months-18 years). The mean duration of epilepsy was 5.64 years±3.91 (range 2 months-17 years). 126 patients experienced daily seizures, 45 weekly and 39 reported monthly seizures. Six had refractory status epilepticus. All the patients were on multiple anti-epileptic drugs (AEDs): the mean number of AEDs was 3.27±0.98 (range 2-7 AEDs). Focal seizure was the most common seizure type seen in 72.27% of children (159/220). The most frequent etiology was focal cortical dysplasia (70), followed by bilateral parieto-temporo-occipital gliosis (48). All the patients underwent standard pre-surgical evaluation. Eleven patients needed stage 2 evaluation (intracranial EEG). The different surgeries performed were electrocorticography (ECOG) and navigation-guided resection (65), anterior temporal lobectomy and hippocampectomy (ATLAH) (48), functional hemispherotomy (39), callosotomy (28), disconnection surgeries (16), and multilobar resection (12). Twelve patients underwent more than one surgery. The patients were followed up between a minimum of 12 months and a maximum of 66 months (median 32 months; IQR 20 months). Engel class 1 outcome was observed in 81.38% in definitive surgeries. Outcomes of temporal lobe (TL) surgeries (92.3%) were better compared to hemispheric (87.17%) and extratemporal lobe (ETL) surgeries (75.32%). We encountered unexpected transient motor deficits in 2 patients and culture-proven meningitis in 8 patients. Post-surgery drug freedom (P-value 0.003) was the most important factor for better developmental, cognitive and behavioral outcomes. Epilepsy surgeries are safe and seizure outcomes are excellent in properly selected cases with thorough presurgical evaluation. Early referral to a tertiary epilepsy center is needed for timely intervention.

Psychometric properties of the Lithuanian version of the patient-weighted inventory on quality of life in epilepsy

BackgroundWe aimed (1) to confirm that the Lithuanian version of the patient-weighted 31-item Quality of Life in Epilepsy Inventory (QOLIE-31-P) is a valid and reliable tool to be used among patients with epilepsy (PWE) in Lithuania and (2) to determine how the quality of life (QoL) is associated with demographic and clinical variables, adverse effects of antiseizure medication as well symptoms of depression and anxiety in this population. MethodsWe used a translated and adapted Lithuanian version of the patient-weighted 31-item Quality of Life in Epilepsy Inventory (QOLIE-31-P) and conducted a cross-sectional anonymous survey among 303 adult PWE at a tertiary epilepsy center at Vilnius University Hospital Santaros Klinikos. The questionnaire also included the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), the Generalized anxiety disorder scale-7 (GAD-7), and the Liverpool Adverse Events Profile scale (LAEP). Missing values were replaced after performing multiple imputation (MI). ResultsQOLIE-31-P had high internal consistency (Cronbach’s α = 0.933 for all items and α = 0.676 to 0.906 for individual subscales). Its factor structure (71.2% of variance explained) consisted of seven factors, some of which overlapped (“Emotional Well-Being” and “Overall QoL”) or were split (“Social Function”) in comparison to the pre-defined content of the subscales. Multitrait-scaling revealed that each item is better correlated with the subscale it is included in than other subscales, suggesting good convergent and discriminant validity. On average, PWE scored 69.9 ± 16.8 (n = 164, mean = 64.9 after MI) on the QOLIE-31-P. Results were higher among male PWE, those employed or studying and having a higher level of education. In a pooled multiple regression model (adjusted R¯2 = 0.700, p < 0.001), the NDDIE (βst = −0.230, p < 0.001), the GAD-7 (βst = −0.226, p < 0.001), the LAEP (βst = −0.406, p < 0.001), and seizure frequency (βst = −0.156, p < 0.001) were statistically significantly associated with total QOLIE-31-P scores. ConclusionThe Lithuanian version of the QOLIE-31-P demonstrates optimal reliability and construct validity to be applied in this population. It is strongly associated with seizure frequency as well as short instruments used to measure anxiety, depression, and adverse medication effects.

Epidemiology and specific features of shoulder injuries in patients affected by epileptic seizures

PurposeEpileptic seizures can cause multiple shoulder injuries, the most common of which are dislocations, recurrent instability, fractures, and isolated lesions of the rotator cuff. Currently, only limited literature exists which describes the frequency and types of lesions in cohorts of epileptic patients and the corresponding treatment outcome. This study aims to document the occurrence of shoulder lesions in patients affected by seizures and to provide detailed information on trauma dynamics, specific lesion characteristics and treatment complications.MethodsAll patients referring to a tertiary epilepsy center were screened for shoulder injuries and the clinical records of those sustaining them during a seizure were reviewed. Demographic information, lesions’ characteristics and trauma dynamics were analysed, as wells as—when carried out—the type of surgical intervention and any postoperative complications.ResultsThe average age at the time of injury of 106 included patients was 39.7 ± 17.5 years and a male predominance was recorded (65%). Bilateral injuries occurred in 29 patients, simultaneously in 17 cases. A younger age, bilateral shoulder injuries and shoulder dislocations were significantly associated with the occurrence of a shoulder injury solely by muscular activation (p = 0.0054, p = 0.011, p < 0.0001). The complication rate in 57 surgically treated patients with follow-up data was 38.7%, with recurring instability being the most frequently reported complication (62.5%).ConclusionsUncontrolled muscle activation during a seizure is a distinctive but not exclusive dynamic of injury in epileptic patients, accounting for more than the half of all shoulder lesions, especially in the younger. This can lead both to anterior and posterior dislocations or fracture-dislocations and is frequently cause of bilateral lesions and of instability recurrence after surgery. The high complication rates after surgical treatment in this selected subgroup of patients require that appropriate preventative measures are taken to increase the probability of treatment success.Level of evidenceCohort study, level III.

Naming-related spectral responses predict neuropsychological outcome after epilepsy surgery.

This prospective study determined the use of intracranially recorded spectral responses during naming tasks in predicting neuropsychological performance following epilepsy surgery. We recruited 65 patients with drug-resistant focal epilepsy who underwent preoperative neuropsychological assessment and intracranial EEG recording. The Clinical Evaluation of Language Fundamentals evaluated the baseline and postoperative language function. During extra-operative intracranial EEG recording, we assigned patients to undergo auditory and picture naming tasks. Time-frequency analysis determined the spatiotemporal characteristics of naming-related amplitude modulations, including high gamma augmentation at 70-110 Hz. We surgically removed the presumed epileptogenic zone based on the intracranial EEG and MRI abnormalities while maximally preserving the eloquent areas defined by electrical stimulation mapping. The multivariate regression model incorporating auditory naming-related high gamma augmentation predicted the postoperative changes in Core Language Score with r2 of 0.37 and in Expressive Language Index with r2 of 0.32. Independently of the effects of epilepsy and neuroimaging profiles, higher high gamma augmentation at the resected language-dominant hemispheric area predicted a more severe postoperative decline in Core Language Score and Expressive Language Index. Conversely, the model incorporating picture naming-related high gamma augmentation predicted the change in Receptive Language Index with an r2 of 0.50. Higher high gamma augmentation independently predicted a more severe postoperative decline in Receptive Language Index. Ancillary regression analysis indicated that naming-related low gamma augmentation and alpha/beta attenuation likewise independently predicted a more severe Core Language Score decline. The machine learning-based prediction model suggested that naming-related high gamma augmentation, among all spectral responses used as predictors, most strongly contributed to the improved prediction of patients showing a >5-point Core Language Score decline (reflecting the lower 25th percentile among patients). We generated the model-based atlas visualizing sites, which, if resected, would lead to such a language decline. With a 5-fold cross-validation procedure, the auditory naming-based model predicted patients who had such a postoperative language decline with an accuracy of 0.80. The model indicated that virtual resection of an electrical stimulation mapping-defined language site would have increased the relative risk of the Core Language Score decline by 5.28 (95% confidence interval: 3.47-8.02). Especially, that of an electrical stimulation mapping-defined receptive language site would have maximized it to 15.90 (95% confidence interval: 9.59-26.33). In summary, naming-related spectral responses predict neuropsychological outcomes after epilepsy surgery. We have provided our prediction model as an open-source material, which will indicate the postoperative language function of future patients and facilitate external validation at tertiary epilepsy centres.

Psychiatric and Behavioural Side Effects Associated With Perampanel in Patients With Temporal Lobe Epilepsy. A Real-World Experience.

Psychiatric and behavioural side effects are common, undesirable effects associated with antiseizure medication use. Temporal lobe epilepsy is the most common focal epilepsy in adults and it is frequently associated with drug resistance. Patients with intractable epilepsy are more likely to have psychiatric and behavioural side effects when taking antiseizure medications and seem to be at higher risk for psychiatric comorbidities. Perampanel is a novel anti-seizure medication approved for focal and generalised epilepsies as add-on therapy. This is a 12-week short-term observational prospective study on people with focal epilepsy consecutively recruited from an Italian tertiary epilepsy centre, aimed to compare incidence and severity of psychiatric and behavioural side effects associated with perampanel use in patients with temporal lobe epilepsy as compared to other focal epilepsies. All patients received add-on perampanel according to indication and clinical judgement. Incidence and severity of psychiatric and behavioural side effects were rated by Neuropsychiatric Inventory Questionnaire. All patients enrolled answered the questionnaire before starting perampanel and after 12 weeks of treatment. We found no significant difference in terms of incidence and severity of psychiatric and behavioural side effects associated with perampanel in patients with temporal lobe epilepsy as compared to other focal epilepsies. In line with the literature, the most common adverse effects were “irritability” for both groups and “aggression” for patients with other focal epilepsies.

Late-Onset Focal Epilepsy: Electroclinical Features and Prognostic Role of Leukoaraiosis.

The aim of this study was to describe the electroclinical and prognostic characteristics, and to investigate the role of leukoaraiosis in outpatients with new-onset elderly focal epilepsy aged ≥60 years, referred to a tertiary epilepsy center between 2005 and December 31, 2020. Among the 720 patients who were referred to the center, we retrospectively selected 162 consecutive outpatients, with a first referral for recent-onset focal epilepsy of unknown cause (UC) or structural cause (SC), and collected a clinical and standard-Electroencephalogram (S-EEG), 24-h ambulatory EEG (A-EEG), and neuroimaging data. We also analyzed the seizure prognosis after titration of the first antiseizure medication (ASM). One hundred and four UC and 58 SC patients, followed up for 5.8 ± 5.3 years (mean ± SD), were included. Compared with the SC group, the patients with UC showed a predominance of focal seizures with impaired awareness (51.9% of cases) and focal to bilateral tonic-clonic seizures during sleep (25%); conversely, the SC group, more frequently, had focal to bilateral tonic-clonic seizures during wakefulness (39.6%) and focal aware seizures (25.8%) (p < 0.0001). Oral or gestural automatisms were prevalent in UC epilepsy (20.2 vs. 6.9% in the SC group, p = 0.04). In UC compared to patients with SC, interictal epileptiform discharges showed a preferential temporal lobe localization (p = 0.0007), low expression on S-EEG, and marked activation during deep Non-Rapid Eye Movement (NREM) sleep (p = 0.003). An overall good treatment response was found in the whole sample, with a probability of seizure freedom of 68.9% for 1 year. The cumulative probability of seizure freedom was significantly higher in the UC compared with the SC group (p < 0.0001). The prognosis was worsened by leukoaraiosis (p = 0.012). In the late-onset focal epilepsy of unknown cause, electroclinical findings suggest a temporal lobe origin of the seizures. This group showed a better prognosis compared with the patients with structural epilepsy. Leukoaraiosis, per se, negatively impacted on seizure prognosis.

The Growing Need for a Transitional Age Program for Adolescents with Epilepsy in Korea

Epilepsy is one of the most common chronic neurological conditions in adolescents and young adults. The transition from the pediatric to the adult health care system can be a major challenge for most adolescents with epilepsy and their families. An unsuccessful transition can have a detrimental effect on them as individuals, as well as on their families. Generally speaking, pediatric epileptologists often feel uncomfortable when they deal with adolescents and young adults with epilepsy due to unfamiliarity with the common psychosocial problems and diseases of adulthood, while adult epileptologists are unfamiliar with childhood-specific epilepsy syndromes and, in many cases, patients’ previous history. Therefore, a transitional age program (TAP) is imperative to remediate the care gap and facilitate a smooth transition from the pediatric to the adult care system. A TAP is a set of processes that cover all the areas of the transition, including an assessment of transition readiness, rethinking the diagnosis using currently available tests, a reevaluation for neurobehavioral comorbidities, education, setting goals, and providing recommendations. Furthermore, the TAP should start as early as possible and must be comprehensive, flexible, and patient-centered. The cost-benefit effectiveness of TAPs requiring a multidisciplinary team has not been fully evaluated, but TAPs are becoming ubiquitous, especially in developed countries. I think that TAPs must be implemented in practical ways for adolescents and young adults with epilepsy at tertiary epilepsy centers as soon as possible in Korea. Key words: Epilepsy; Transitional care; Adolescent.

Predictors of postoperative long-term seizure outcome in pediatric patients with focal cortical dysplasia type II at a German tertiary epilepsy center.

Focal cortical dysplasia (FCD) is a common cause of early-onset intractable epilepsy, and resection is a highly sufficient treatment option. In this study, the authors aimed to provide a retrospective analysis of pre- and postoperative factors and their impact on postoperative long-term seizure outcome. The postoperative seizure outcomes of 50 patients with a mean age of 8 ± 4.49 years and histologically proven FCD type II were retrospectively analyzed. Furthermore, pre- and postoperative predictors of long-term seizure freedom were assessed. The seizure outcome was evaluated based on the International League Against Epilepsy (ILAE) classification. Complete resection of FCD according to MRI criteria was achieved in 74% (n = 37) of patients. ILAE class 1 at the last follow-up was achieved in 76% (n = 38) of patients. A reduction of antiepileptic drugs (AEDs) to monotherapy or complete withdrawal was achieved in 60% (n = 30) of patients. Twelve patients (24%) had a late seizure recurrence, 50% (n = 6) of which occurred after reduction of AEDs. A lower number of AEDs prior to surgery significantly predicted a favorable seizure outcome (p = 0.013, HR 7.63). Furthermore, younger age at the time of surgery, shorter duration of epilepsy prior to surgery, and complete resection were positive predictors for long-term seizure freedom. The duration of epilepsy, completeness of resection, number of AEDs prior to surgery, and younger age at the time of surgery served as predictors of postoperative long-term seizure outcome, and, as such, may improve clinical practice when selecting and counseling appropriate candidates for resective epilepsy surgery. The study results also underscored that epilepsy surgery should be considered early in the disease course of pediatric patients with FCD type II.

Correcting for physiological ripples improves epileptic focus identification and outcome prediction.

ObjectiveThe integration of high‐frequency oscillations (HFOs; ripples [80–250 Hz], fast ripples [250–500 Hz]) in epilepsy evaluation is hampered by physiological HFOs, which cannot be reliably differentiated from pathological HFOs. We evaluated whether defining abnormal HFO rates by statistical comparison to region‐specific physiological HFO rates observed in the healthy brain improves identification of the epileptic focus and surgical outcome prediction.MethodsWe detected HFOs in 151 consecutive patients who underwent stereo‐electroencephalography and subsequent resective epilepsy surgery at two tertiary epilepsy centers. We compared how HFOs identified the resection cavity and predicted seizure‐free outcome using two thresholds from the literature (HFO rate > 1/min; 50% of the total number of a patient's HFOs) and three thresholds based on normative rates from the Montreal Neurological Institute Open iEEG Atlas (https://mni‐open‐ieegatlas.research.mcgill.ca/): global Atlas threshold, regional Atlas threshold, and regional + 10% threshold after regional Atlas correction.ResultsUsing ripples, the regional + 10% threshold performed best for focus identification (77.3% accuracy, 27% sensitivity, 97.1% specificity, 80.6% positive predictive value [PPV], 78.2% negative predictive value [NPV]) and outcome prediction (69.5% accuracy, 58.6% sensitivity, 76.3% specificity, 60.7% PPV, 74.7% NPV). This was an improvement for focus identification (+1.1% accuracy, +17.0% PPV; p < .001) and outcome prediction (+12.0% sensitivity, +1.0% PPV; p = .05) compared to the 50% threshold. The improvement was particularly marked for foci in cortex, where physiological ripples are frequent (outcome: +35.3% sensitivity, +5.3% PPV; p = .014). In these cases, the regional + 10% threshold outperformed fast ripple rate > 1/min (+3.6% accuracy, +26.5% sensitivity, +21.6% PPV; p < .001) and seizure onset zone (+13.5% accuracy, +29.4% sensitivity, +17.0% PPV; p < .05–.01) for outcome prediction. Normalization did not improve the performance of fast ripples.SignificanceDefining abnormal HFO rates by statistical comparison to rates in healthy tissue overcomes an important weakness in the clinical use of ripples. It improves focus identification and outcome prediction compared to standard HFO measures, increasing their clinical applicability.

The Occurrence of Seizure Clusters in Patients With Epilepsy Is Partly Determined by Epilepsy Severity: A Single-Center Retrospective Observational Study.

Purpose: This retrospective observational study aimed to investigate the self-reported prevalence of seizure clusters (SCs) in patients with epilepsy (PWE) and its relationship with clinical characteristics.Methods: We retrospectively analyzed data from consecutive PWE from our hospital in northeastern China. Data were collected from the databank of a tertiary epilepsy center. Logistic regression models were employed to investigate the relationships between the individual patient demographic/clinical variables and the occurrence of SC.Results: In total, 606 consecutive PWE were included in the final analysis, and 268 (44.2%) patients experienced at least one seizure cluster. In multivariate logistic regression models, age (OR: 1.014; 95% CI: 1.002–1.027; p = 0.02), seizure frequency (OR: 2.08; 95% CI: 1.555–2.783; p < 0.001), multiple seizure types (OR: 5.111; 95% CI: 1.737–15.043; p = 0.003), number of current anti-seizure medications (ASM) (OR: 1.533; 95% CI: 1.15–2.042; p = 0.004), drug-resistant epilepsy (OR: 1.987; 95% CI: 1.159–3.407; p = 0.013), and a history of status epilepticus (OR: 1.903; 95% CI: 1.24–2.922; p = 0.003) were independent variables associated with a history of SC in PWE.Conclusion: Seizure clusters (SCs) are common occurrences at our study center. The occurrence of SC in individuals with epilepsy, to some extent, is determined by the epilepsy severity.

Parental experiences and perspectives on the value of seizure detection while caring for a child with epilepsy: A qualitative study

IntroductionCaring for a child with epilepsy has a significant impact on parental quality of life. Seizure unpredictability and complications, including sudden unexpected death in epilepsy (SUDEP), may cause high parental stress and increased anxiety. Nocturnal supervision with seizure detection devices may lower SUDEP risk and decrease parental burden of seizure monitoring, but little is known about their added value in family homes. MethodsWe conducted semi-structured in-depth interviews with parents of children with refractory epilepsy participating in the PROMISE trial (NCT03909984) to explore the value of seizure detection in the daily care of their child. Children were aged 4–16 years, treated at a tertiary epilepsy center, had at least one nocturnal major motor seizure per week, and used a wearable seizure detection device (NightWatch) for two months at home. Data were analyzed using inductive thematic analysis. ResultsTwenty three parents of nineteen children with refractory epilepsy were interviewed. All parents expressed their fear of missing a large seizure and the possible consequences of not intervening in time. Some parents felt the threat of child loss during every seizure, while others thought about it from time to time. The fear could fluctuate over time, mainly associated with fluctuations of seizure frequency. Most parents described how they developed a protective behavior, driven by this fear. The way parents handled the care of their child and experienced the burden of care influenced their perceptions on the added value of NightWatch. The experienced value of NightWatch depended on the amount of assurance it could offer to reduce their fear and the associated protective behavior as well as their resilience to handle the potential extra burden of care, due to false alarms or technical problems. ConclusionHealthcare professionals and device companies should be aware of parental protective behavior and the high parental burden of care and develop tailored strategies to optimize seizure detection device care.

Predictive semiology of psychogenic non-epileptic seizures in an epilepsy monitoring unit.

IntroductionThe diagnosis of psychogenic nonepileptic seizures (PNES) is a common clinical dilemma. We sought to assess the diagnostic value of four ictal signs commonly used in differentiating PNES from epileptic seizures (ES).MethodsWe retrospectively reviewed consecutive adult video-electroencephalogram (VEM) studies conducted at a single tertiary epilepsy center between May 2009 and August 2016. Each event was assessed by a blinded rater for the presence of four signs: fluctuating course, head shaking, hip thrusting, and back arching. The final diagnosis of PNES or ES was established for each event based on clinical and VEM characteristics. All ES were pooled regardless of focal or generalized onset. We analyzed the odds ratio of each sign in PNES in comparison to ES with adjustment for repeated measures using logistic regression. Additionally, we calculated the sensitivity, specificity, predictive values, and likelihood ratios of each sign to diagnose PNES.ResultsA total of 742 events from 140 VEM studies were assessed. Fluctuating course (odds ratio (OR) 37.37, 95% confidence interval (CI) 13.56–102.96, P < 0.0001), head shaking (OR 2.95, 95% CI 1.26–6.79, P = 0.012), and hip thrusting (OR 4.28, 95% CI 1.21–15.18, P = 0.02) were each significantly predictive of PNES. Fluctuating course had the highest sensitivity (76.16%). Back arching (OR 1.06, 95% CI 0.35–3.20, P = 0.92) was not significantly associated with PNES.ConclusionFluctuating course, head shaking, and hip thrusting are semiological features significantly more common in PNES than ES. Fluctuating course is the most reliable sign. Back arching does not appear to differentiate PNES from ES.

Depressive symptoms in patients with epilepsy and clinically associated features in a single tertiary center

Although depressive symptoms are the most common psychiatric comorbidity in epilepsy, they remain underestimated and untreated in a large proportion of patients. The purpose of this study was to evaluate depression severity and related clinical features in people with epilepsy using a well-reliable self-report index of mood, the Beck Depression Inventory-II (BDI-II). One-hundred seventeen adult patients with epilepsy were recruited from a tertiary epilepsy center and completed the BDI-II. A single-item analysis of the 21 questions of the BDI-II was computed and differences between women and men in each depressive symptom were evaluated. Correlation and regression analyses were used to identify clinical features associated with the severity of depression. Results showed gender differences in some items, with women reporting overall higher depression severity than men. The most common symptoms regarded domains of sleeping patterns, tiredness, and loss of energy. Regression evidence suggested that being female, having an epilepsy duration < 10 years, as well as being treated with psychotropic drugs and reporting generalized seizure, were associated with higher depression severity. Despite its cross-sectional nature, this study reinforces the importance of investigating and possibly treating depressive symptoms in adult patients with epilepsy, since they negatively impact well-being, daytime activities, and sleep. Further studies identifying pharmacological and non-pharmacological treatments for depression in epilepsy need to be planned.

Outcomes in the treatment of psychogenic nonepileptic seizures (PNES) with CBTip: Response in seizure frequency, depression, anxiety, and quality of life

RationalePsychogenic Nonepileptic Seizures (PNES) are seizure-like episodes without EEG abnormality, and are of psychological origin. Cognitive Behavioral Therapy (CBT), a type of psychological counseling, is known to be the best intervention to treat PNES and the underlying psychiatric symptoms. Yet, many remain untreated because of limited access to specialized counseling programs. In this study, first we intended to see if the positive outcomes of the CBTip can be replicated in our patient population using within-group comparison. We also aimed to examine the outcomes of patients who received a variable dose of treatment than the established treatment protocol. MethodWe obtained retrospective patient reported outcomes (PRO) data from patients treated with Cognitive Behavioral Therapy-informed psychotherapy (CBT-ip) from January 2015 to January 2020 in an outpatient tertiary care epilepsy center. The CBTip program is a 12-session intervention delivered weekly by a seizure counselor. Although the program comprises 12 sessions of treatment, we included patients who attended at least 7 sessions consistent with previous research that used a similar cutoff. We had a total of 160 patient PROs included in the analysis. Outcome variables including seizure frequency, depression, anxiety, and quality of life were examined using self-report outcome scores. Demographic and other clinical and psychosocial confounding variables were controlled. ResultsIn the first analysis in which we compared pre-treatment scores with 3-month posttreatment scores, there was no significant change in seizure frequency, depression, anxiety, and quality-of-life outcomes. In the second analysis when we compared pre- and posttreatment scores in patients who completed the treatment in longer than 3-month time, there were significant improvement in primary and secondary outcomes. For seizure frequency, 10 patients had data for “seizures per day in the last 6 months” and 5 participants (50%) improved by 50% or more in the number of seizures per day. There were also significant reductions in depression and anxiety scores but not in quality of life. Implication and conclusionsOur analysis showed that patients treated with CBTip with a minimum of 7 sessions in 3 months did not have significant improvement. However, attending at least 7 sessions of CBTip in longer than 3 months was effective for seizure control, depression, and anxiety. The observational and exploratory nature of our study, however, limits the generalizability of our findings outside of the single tertiary clinical care setting.

Late diagnoses of Dravet syndrome: How many individuals are we missing?

We report new genetic diagnoses of Dravet syndrome in a group of adults with complex epilepsy of unknown cause, under follow‐up at a tertiary epilepsy center. Individuals with epilepsy and other features of unknown cause from our unit underwent whole‐genome sequencing through the 100 000 Genomes Project. Virtual gene panels were applied to frequency‐filtered variants based on phenotype summary. Of 1078 individuals recruited, 8 (0.74%) were identified to have a pathogenic or likely pathogenic variant in SCN1A. Variant types were as follows: nonsense (stopgain) in five (62.5%) and missense in three (37.5%). Detailed review of childhood history confirmed a phenotype compatible with Dravet syndrome. Median age at genetic diagnosis was 44.5 years (range 28‐52 years). Tonic‐clonic seizures were ongoing in all despite polytherapy including valproate. All had a history of fever sensitivity and myoclonic seizures, which were ongoing in two (25%) and three (37.5%) individuals, respectively. Salient features of Dravet syndrome may be less apparent in adulthood, making clinical diagnosis difficult. Regardless of age, benefits of a genetic diagnosis include access to syndrome‐specific treatment options, avoidance of harmful drugs, and monitoring for common complications.

Post-traumatic stress disorder (PTSD) symptoms in children with severe epilepsy

ObjectivesTo assess symptoms of post-traumatic stress disorder (PTSD) in children with severe epilepsy and the associations of trauma symptoms across age, comorbid symptoms, epilepsy-specific factors, parental resources, and psychopathology. MethodsFifty children with severe epilepsy across three different age groups (0–5 yrs., 6–12 yrs., 13–18 yrs.) were assessed with developmental-sensitive and standardized PTSD assessment tools when hospitalized at the tertiary epilepsy center Filadelfia, Denmark. The Diagnostic Infant and Preschool Assessment (DIPA), the Darryl test, and the ITQ questionnaire were used to assess the three age groups, respectively. ResultsTwenty-two percent of the overall sample met the criteria for PTSD, with a prevalence of symptoms increasing with age (6%, 28%, and 40%). Comorbid psychiatric symptoms in preschoolers were present in 81% of the children witnessing a high level of distress in this group. Behavioral difficulties were elevated across all three age groups, and 40% of the children with trauma symptoms had a parent with concurrent psychopathology. ConclusionTo the authors’ knowledge, this study is the first to assess trauma symptoms with standardized tests in children with more complicated epilepsies. Trauma symptoms in the group are high; however, there is a need for larger scale studies and research into trauma symptoms in children with more severe epilepsy than those assessable with the included assessment tools. The trauma perspective in severe childhood epilepsy might further clarify the complex associations of biological and contextual variables that affect the children’s life quality and enable better preventative treatment options for this group.

Diagnostic challenges in patients with temporal lobe seizures and features of autoimmune limbic encephalitis.

Consensus criteria for autoimmune limbic encephalitis (ALE) allow for a diagnosis even without neuronal antibodies (Abs), but it remains unclear which clinical features should prompt neuronal Ab screening in temporal lobe epilepsy patients. The aim of the study was to investigate whether patients with temporal lobe seizures associated with additional symptoms or signs of limbic involvement may harbor neuronal Abs, and which clinical features should prompt neuronal Ab screening in these patients. We identified 47 patients from a tertiary epilepsy center with mediotemporal lobe seizures and additional features suggestive of limbic involvement, including either memory deficits, psychiatric symptoms, mediotemporal magnetic resonance imaging (MRI) hyperintensities or inflammatory cerebrospinal fluid (CSF). Neuronal Ab testing was carried out at two independent reference laboratories (Bielefeld-Bethel, Germany, and Barcelona, Spain). All brain MRI scans were assessed by two reviewers independently. Temporal lobe seizures were accompanied by memory deficits in 35/46 (76%), psychiatric symptoms in 27/42 (64%), and both in 19/42 patients (45%). Limbic T2/fluid-attenuated inversion recovery signal hyperintensities were found in 26/46 patients (57%; unilateral: n=22, bilateral: n=4). Standard CSF studies were abnormal in 2/37 patients (5%). Neuronal Abs were confirmed in serum and/or CSF in 8/47 patients (17%) and were directed against neuronal cell-surface targets (leucine-rich glioma inactivated protein 1: n=1, contactin-associated protein-2: n=1, undetermined target: n=3) or glutamic acid decarboxylase in its 65-kD isoform (n=3, all with high titers). Compared to Ab-negative patients, those who harbored neuronal Abs were more likely to have uni- or bilateral mediotemporal MRI changes (8/8, 100% vs. 18/38, 47%; p=0.01, Fisher's exact test). In patients with temporal lobe seizures and additional limbic signs, 17% had neuronal Abs affirming ALE diagnosis. Mediotemporal MRI changes were found in all Ab-positive cases and had a positive likelihood ratio of 2.11 (95% confidence interval 1.51-2.95).