Impact of seizure outcome and extent of neocortical resection on emotional well-being in patients with epilepsy one year after temporal lobe surgery.

BACKGROUND: Seizure frequency and cognitive function are common parameters in assessing epilepsy surgery outcomes. However, psychobehavioral outcomes, such as symptoms of depression and quality of life (QOL), have not found equal attention yet. OBJECTIVE: To assess the effect of seizure frequency, the extent of resection, and cognitive function on the psychobehavioral outcome of patients after temporal lobe surgery for pharmacoresistant epilepsy. METHODS: We retrospectively reviewed all consecutive patients who underwent surgery for intractable temporal lobe epilepsy between 09/2015 and 07/2019. We examined seizure outcome, surgical plan, resection volume, cognitive functions, and psychobehavioral outcome. RESULTS: This study included 77 patients (31 males, 46 females) who underwent temporal lobe surgery. One year after surgery, 53 patients (68.8 %) were completely seizure-free (Engel IA) and 92.2 % of patients showed a worthwhile improvement in seizure frequency (Engel I-III). Resection volume was significantly negatively correlated with QOL (r =  - 0.284, p = 0.041). However, after controlling for the effect of seizure outcome, no significant correlation remained. Patients with a worthwhile improvement in seizure frequency showed significantly fewer symptoms of depression (p = 0.024) and a significantly higher QOL (p = 0.012) one year after surgery. The differences in symptoms of depression (p = 0.044) and QOL (p = 0.030) between patients with and without improvements in seizure frequency remained significant after controlling for the effect of resection volume. After procedures sparing the amygdala and hippocampus (neocortical resection), patients presented significantly fewer symptoms of depression (p = 0.044) and significantly better QOL (p = 0.008) than patients after procedures involving mesial-temporal structures, independent of the resection volume, and after controlling for the side of the procedure (dominant vs. non-dominant). After also controlling for seizure outcome, the difference remained for QOL (p = 0.014) but not for symptoms of depression. CONCLUSIONS: A patient's emotional well-being one year after surgery for pharmacoresistant temporal lobe epilepsy strongly depends on their seizure outcome. As an individual factor, the extent of neocortical resection negatively affects postsurgical emotional well-being, but a favorable seizure outcome outweighs this effect, independent of the resection volume. A favorable seizure outcome even outweighs the negative effects of procedures involving mesial-temporal structures on symptoms of depression.

A multicenter randomized controlled feasibility trial of a digital self-management intervention for adults with epilepsy.

OBJECTIVE: Self-management interventions may enhance health-related quality of life (HRQoL) in epilepsy. However, several barriers often impair their implementation in the real world. Digital interventions may help to overcome some of these barriers. Considering this, the Helpilepsy Plus Prototype was developed as a prototype smartphone-delivered self-care treatment program for adults with epilepsy. METHODS: The 12-week Helpilepsy Plus Prototype was evaluated through a randomized controlled feasibility trial with a waiting-list control (WLC) group. Outcome measurement at baseline and at 12 weeks assessed adherence to the prototype intervention and changes in epilepsy-related outcomes. The primary endpoint was patient autonomy measured with EASE, and secondary endpoints included HRQoL measured with QOLIE-31, health literacy measured with HLQ, anxiety, and depression symptoms measured with HADS. Semi-structured interviews were conducted with a heterogeneous sample of participants to assess user-friendliness and usefulness. The prototype program was delivered through the Neuroventis Platform (Neuroventis, BV, Overijse, Belgium), a certified medical device (under EU/MDD Class I, and EU/MDR grace period). RESULTS: Ninety-two patients were included (46 in the intervention group, 46 in WLC). Most participants (63%, 58/92 women, median age 30 years) had pharmacoresistant epilepsy (61%, 56/92). Only 22% of participants (10/46) in the intervention group completed at least half of all intervention sessions. No significant differences between the intervention group and WLC were observed. Although there was a larger proportion of patients in the intervention group with meaningful improvements in HRQoL compared to WLC (19/46 versus 11/46), the difference was not significant (p = 0.119). Qualitative feedback showed that participants would appreciate more personalization, such as adaptation of the content to their current epilepsy knowledge level, a more interactive interface, shorter text sections, and interaction through reminders and notifications. SIGNIFICANCE: Digital interventions should allow sufficient scope for personalization and interaction to increase patient engagement and enable benefits from self-care apps. Feedback loops allow the participatory development of tailored interventions. PLAIN LANGUAGE SUMMARY: In this study, we investigated the effectiveness of an app-based self-help intervention. Study participants were either randomly assigned to a group that had access to the app or a group that received access to the app after the end of the study. Although a larger proportion of participants in the intervention group showed a relevant improvement in quality of life, the difference between the two groups was not statistically significant. Less than one-fifth of participants in the intervention group attended at least half of all intervention sessions; patient feedback showed that patients required more personalization and interactive options.

Consultation Requests and Satisfaction with a Telehealth Network for Epilepsy: Longitudinal Analysis of the Epilepsy Network Hessen Evaluation.

Background: Telemedicine improves access to specialized medical expertise, as required for paroxysmal disorders. The Epilepsy Network Hessen Evaluation (ENHE) is a pilot cross-sectoral teleconsultation network connecting primary neurologists and pediatricians with epilepsy centers in Hessen, a federal German state. Methods: We prospectively and longitudinally evaluated telehealthcare in the ENHE. Participating physicians rated each consultation for satisfaction and impact on further management. The survey was administered at each consultation and 3 months later. Results: We analyzed 129 consultations involving 114 adult and pediatric patients. Their mean age was 34 years (standard deviation: 26, range: 0.1-91 years), 48% were female, and 34% were children and adolescents. The most common consultation requests were co-evaluation of an electroencephalogram (electroencephalogram [EEG]; 76%) and therapeutic (33%) and differential diagnosis (24%) concerns. Physicians transmitted one paraclinical examination on average (range: 1-4), predominantly EEG (85%), followed by magnetic resonance imaging (17%) and written records (9%). Response rates were 72% for the initial and 67% for the follow-up survey. Across respondents, 99% (n = 92) were satisfied with the ENHE. Overall, 80% of the consultations contributed to the diagnosis, and 90% were considered helpful for treatment, influencing it in 71% of cases. Seizure frequency had decreased more often (96%) than increased (4%) at 3 months. The initial diagnosis was confirmed in 78% of patients. Discussion: In this pilot teleconsultation network for paroxysmal disorders, diagnostic and therapeutic advice was perceived as helpful. Clinical outcomes were largely positive, suggesting tele-epileptology is viable for paroxysmal (seizure) disorders.

Predictors for and use of rescue medication in adults with epilepsy: A multicentre cross-sectional study from Germany.

BACKGROUND: Seizure clusters, prolonged seizures, and status epilepticus are life-threatening neurological emergencies leading to irreversible neuronal damage. Benzodiazepines are current evidence-based rescue therapy options; however, recent investigations indicated the prescription of mainly unsuitable benzodiazepines and inappropriate use of rescue medication. OBJECTIVE: To examine current use, satisfaction, and adverse events concerning rescue medication in patients with epilepsy in Germany. PATIENTS AND METHODS: The study was conducted at epilepsy centres in Frankfurt am Main, Greifswald, Marburg, and Münster between 10/2020 and 12/2020. Patients with an epilepsy diagnosis were assessed based on a questionnaire examining a 12-month period. RESULTS: In total, 486 patients (mean age: 40.5, range 18-83, 58.2 % female) participated in this study, of which 125 (25.7 %) reported the use of rescue medication. The most frequently prescribed rescue medications were lorazepam tablets (56.8 %, n = 71 out of 125), buccal midazolam (19.2 %, n = 24), and rectal diazepam (10.4 %, n = 13). Seizures continuing for over several minutes (43.2 %, n = 54), seizure clusters (28.0 %, n = 35), and epileptic auras (28.0 %, n = 35) were named as indications, while 28.0 % (n = 35) stated they administered the rescue medication for every seizure. Of those continuing to have seizures, 46.0 % did not receive rescue medication. On average, rescue medication prescription occurred 7.1 years (SD 12.7, range 0-66) after an epilepsy diagnosis. CONCLUSIONS: Unsuitable oral benzodiazepines remain widely prescribed for epilepsy patients as rescue medication. Patients also reported inappropriate use of medication. A substantial proportion of patients who were not seizure-free did not receive rescue medication prescriptions. Offering each patient at risk for prolonged seizures or clusters of seizures an individual rescue treatment with instructions on using it may decrease mortality and morbidity and increase quality of life. .

Transient postictal dysphagia in older adults with focal structural epilepsy.

OBJECTIVE: Seizures can cause transient neurological symptoms, such as hemiparesis and aphasia. However, temporary swallowing changes leading to postictal dysphagia have not been previously described. Therefore, this study evaluated the presence of swallowing disorders following seizure. In addition, dysphagia severity and duration of any recovery from dysphagic symptoms were investigated. METHODS: The local clinical database of all fiberoptic endoscopic evaluation of swallowing (FEES) examinations performed from 2008 to 2019 was screened for patients diagnosed with seizures, but excluding patients with intensive care unit admission or intubation >24 h. Patient charts were evaluated to identify preexisting dysphagia or potential concurrent medical causes for dysphagia, including hyponatremia, increased intracranial pressure, sepsis, or other encephalopathies associated with infections, or other possible causes at the time of admission. Patients receiving >.5 defined daily doses of benzodiazepines or neuroleptics were also excluded. Age, sex, seizure semiology and etiology, comorbidities, concurrent pneumonia, and dysphagia course during hospitalization were evaluated as predictors of the occurrence of dysphagia or its potential duration. RESULTS: We identified 41 patients with dysphagia following a seizure, without evidence of any concurrent cause of swallowing dysfunction. These patients all presented with focal structural epilepsy, they had a mean age of 79 ± 11.3 years (range = 44-95 years), and 21 were women. The mean Elixhauser Comorbidity Score was 4.8. Hospital-acquired pneumonia was detected in 21 patients (51.2%). FEES diagnosed mild and severe dysphagia in 21 (51.2%) and 20 (48.8%) patients, respectively. Dysphagia improved significantly (p = .001) during hospitalization, persisting for an average of 3.9 days (median = 3 days, SD = 2.07 days, range = 1-8 days). SIGNIFICANCE: Dysphagia is a potential transient neurological deficit following seizure. Our findings suggest that older patients, with focal structural epilepsy, are at risk for postictal dysphagia. Further studies are needed to ascertain the prevalence, complications, and predictors of postictal dysphagia. Dysphagia screening may improve early detection in patients with relevant risk factors, as well as reduce the occurrence of aspiration pneumonia.

Fenfluramine for the treatment of status epilepticus: use in an adult with Lennox-Gastaut syndrome and literature review.

BACKGROUND: Novel treatments are needed to control refractory status epilepticus (SE). This study aimed to assess the potential effectiveness of fenfluramine (FFA) as an acute treatment option for SE. We present a summary of clinical cases where oral FFA was used in SE. METHODS: A case of an adult patient with Lennox-Gastaut syndrome (LGS) who was treated with FFA due to refractory SE is presented in detail. To identify studies that evaluated the use of FFA in SE, we performed a systematic literature search. RESULTS: Four case reports on the acute treatment with FFA of SE in children and adults with Dravet syndrome (DS) and LGS were available. We report in detail a 30-year-old woman with LGS of structural etiology, who presented with generalized tonic and dialeptic seizures manifesting at high frequencies without a return to clinical baseline constituting the diagnosis of SE. Treatment with anti-seizure medications up to lacosamide 600 mg/d, brivaracetam 300 mg/d, valproate 1,600 mg/d, and various benzodiazepines did not resolve the SE. Due to ongoing refractory SE and following an unremarkable echocardiography, treatment was initiated with FFA, with an initial dose of 10 mg/d (0.22 mg/kg body weight [bw]) and fast up-titration to 26 mg/d (0.58 mg/kg bw) within 10 days. Subsequently, the patient experienced a resolution of SE within 4 days, accompanied by a notable improvement in clinical presentation and regaining her mobility, walking with the assistance of physiotherapists. In the three cases reported in the literature, DS patients with SE were treated with FFA, and a cessation of SE was observed within a few days. No treatment-emergent adverse events were observed during FFA treatment in any of the four cases. CONCLUSIONS: Based on the reported cases, FFA might be a promising option for the acute treatment of SE in patients with DS and LGS. Observational data show a decreased SE frequency while on FFA, suggesting a potentially preventive role of FFA in these populations. KEY POINTS: We summarize four cases of refractory status epilepticus (SE) successfully treated with fenfluramine. Refractory SE resolved after 4-7 days on fenfluramine. Swift fenfluramine up-titration was well-tolerated during SE treatment. Treatment-emergent adverse events on fenfluramine were not observed. Fenfluramine might be a valuable acute treatment option for SE in Dravet and Lennox-Gastaut syndromes.

Management of status epilepticus in pregnancy: a clinician survey.

BACKGROUND: Status epilepticus in pregnancy (SEP) is rare and life-threatening for both mother and fetus. There are well-established guidelines for the management of women with epilepsy during pregnancy; however, there is little evidence guiding the management of SEP, leading to uncertainty among treating physicians. Therefore, this survey aims to investigate the real-world practices of physicians treating SEP to explore management approaches for improvements in care. METHODS: An anonymous, electronic survey was created and distributed to neurointensivists and neurologists between September and December 2021. RESULTS: One hundred physicians initiated the survey and 95 completed it in full: 87 (87%, 87/100) identified neurology as their primary specialty, 31 had subspecialty training in neurocritical care, and 48 had subspecialty training in epilepsy and/or clinical neurophysiology. Over half of the survey respondents (67%, 67/100) reported having participated in the management of SEP, with 48.9% (49/98) having done so in the past year. Most survey respondents (73%, 73/100) reported that their management approach to SEP is different than that of non-pregnant patients. Survey respondents were more likely to involve epilepsy consultants when treating SEP (58.5%, 58/99) and the vast majority involved Obstetrics/Maternal Fetal Medicine consultants (90.8%, 89/98). Survey respondents showed a clear preference for levetiracetam (89.7%, 87/97) in the treatment of benzodiazepine refractory status epilepticus followed by lacosamide (61%, 60/98) if an additional second line agent was needed. Valproate and phenobarbital were unlikely to be used. There was less agreement for the management of refractory and super-refractory SEP. CONCLUSIONS: Levetiracetam is the most frequently used anti-seizure medication (ASM) for benzodiazepine-refractory SEP. Survey participants tended to manage SEP differently than in non-pregnant patients including greater involvement of interdisciplinary teams as well as avoidance of ASMs associated with known teratogenicity.

The impact of referring patients with drug-resistant focal epilepsy to an epilepsy center for presurgical diagnosis.

BACKGROUND: Epilepsy surgery is an established treatment for drug-resistant focal epilepsy (DRFE) that results in seizure freedom in about 60% of patients. Correctly identifying an epileptogenic lesion in magnetic resonance imaging (MRI) is challenging but highly relevant since it improves the likelihood of being referred for presurgical diagnosis. The epileptogenic lesion's etiology directly relates to the surgical intervention's indication and outcome. Therefore, it is vital to correctly identify epileptogenic lesions and their etiology presurgically. METHODS: We compared the final histopathological diagnoses of all patients with DRFE undergoing epilepsy surgery at our center between 2015 and 2021 with their MRI diagnoses before and after presurgical diagnosis at our epilepsy center, including MRI evaluations by expert epilepsy neuroradiologists. Additionally, we analyzed the outcome of different subgroups. RESULTS: This study included 132 patients. The discordance between histopathology and MRI diagnoses significantly decreased from 61.3% for non-expert MRI evaluations (NEMRIs) to 22.1% for epilepsy center MRI evaluations (ECMRIs; p < 0.0001). The MRI-sensitivity improved significantly from 68.6% for NEMRIs to 97.7% for ECMRIs (p < 0.0001). Identifying focal cortical dysplasia (FCD) and amygdala dysplasia was the most challenging for both subgroups. 65.5% of patients with negative NEMRI were seizure-free 12 months postoperatively, no patient with negative ECMRI achieved seizure-freedom. The mean duration of epilepsy until surgical intervention was 13.6 years in patients with an initial negative NEMRI and 9.5 years in patients with a recognized lesion in NEMRI. CONCLUSIONS: This study provides evidence that for patients with DRFE-especially those with initial negative findings in a non-expert MRI-an early consultation at an epilepsy center, including an ECMRI, is important for identifying candidates for epilepsy surgery. NEMRI-negative findings preoperatively do not preclude seizure freedom postoperatively. Therefore, patients with DRFE that remain MRI-negative after initial NEMRI should be referred to an epilepsy center for presurgical evaluation. Nonreferral based on NEMRI negativity may harm such patients and delay surgical intervention. However, ECMRI-negative patients have a reduced chance of becoming seizure-free after epilepsy surgery. Further improvements in MRI technique and evaluation are needed and should be directed towards improving sensitivity for FCDs and amygdala dysplasias.

Supply problems of antiseizure medication are common among epilepsy patients in Germany.

OBJECTIVE: To evaluate the frequency of reported antiseizure medication (ASM) supply problems among patients with epilepsy (PWE) in Germany. METHODS: The Epi2020 study was a multicenter study focusing on different healthcare aspects of adult PWE in Germany. In addition to basic clinical and demographic characteristics, PWE were asked to answer a questionnaire regarding supply difficulties regarding their ASM, and if they had to discontinue ASM treatment due to supply problems. Generic switch of medication was recorded, and adverse effects were measured using the Liverpool Adverse Events Profile (LAEP) scale. Data were analyzed to detect predictors of supply problems. RESULTS: In total, 434 PWE with a mean age of 40 years (median 37 years, SD = 15.5, range: 18-83 years, 254 female) participated in this study. 53.7% of PWE (n = 233) reported that at least once in the past 12 months their ASM was not available at the pharmacy, and 24.9% (n = 108) reported having experienced ASM supply problems three times or more during the past 12 months. Patients with epilepsy treated with carbamazepine and zonisamide reported frequent problems with availability in 45.8% and 44.8% respectively, whereas those treated with lacosamide and valproate reported supply problems less frequently (17.0% and 16.4%, respectively). Nine patients (2.1%) were unable to take their ASM as prescribed at least once in the past 12 months due to supply problems. Forty-nine patients (11.3%) reported having to switch ASM due to supply difficulties with generic replacement occurring in 39.4% (n = 171) of patients. Those with supply problems were more likely to be treated with more ASMs and scored higher on the LAEP. CONCLUSION: Supply problems with ASM are frequent among PWE in Germany and are reported for older and newer ASMs. Supply problems contribute to ASM nonadherence and are positively correlated with the number of ASM taken and adverse events.

Status epilepticus in pregnancy.

Status epilepticus is a frequent neurological emergency associated with a case fatality of about 10-15% depending on age, cause, and other factors, and a high burden for patients, caregivers, and society. In pregnancy, it can occur in two different clinical constellations: (1) In women with a history of epilepsy and (2) as new onset status epilepticus in pregnancy (NOSEP). Both entities are relatively rare but differ in terms of etiology. Here we describe the epidemiology, etiologies, diagnosis, clinical course with the maternal and fetal outcome, and the suggested management strategies for either manifestation. This paper was presented at the 8th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures held in September 2022.