Long-term effects of vagus nerve stimulation therapy on cognitive functioning in patients with drug-resistant epilepsy.

BACKGROUND: Despite the increasing use of vagus nerve stimulation (VNS) for drug-resistant epilepsy, its impact on cognitive functioning remains insufficiently investigated. OBJECTIVE: We aimed to comprehensively assess changes in cognition after long-term VNS therapy in a prospective sample of adults with epilepsy. METHODS: Between December 2019 and March 2023, patients scheduled for VNS implantation were invited for neuropsychological assessment, including tests of executive functions, working and short-term memory (recall of a verbal logical story and the Rey-Osterrieth complex figure (ROCF)), and social cognition. Participants were re-evaluated after a year of VNS therapy and the pre- and postoperative scores were compared by means of the Student's t or Wilcoxon's signed rank tests for paired samples. Patients available only after a longer follow-up (more than 24 months) were also re-examined and included in a secondary analysis. RESULTS: The study included 28 PWE (16, 57.1% female, average age 33.7 ± 10.0 years). Twenty-two PWE followed-up at 14.5 ± 4.8 months had worse categorical verbal fluency than preoperatively (t = 2.613, p = 0.016). After including patients with long follow-up (n = 28, 21.6 ± 11.4 months), the group scored better on the delayed recall of the ROCF (17.09 ± 8.84 to 20.65 ± 8.32 points, t(22) = - 2.618, p = 0.016) and the Happé strange stories test (5.0 ± 2.6 to 6.1 ± 2.1 points, t(14) = - 3.281, p = 0.005). No significant changes were observed in other cognitive domains (p > 0.05). CONCLUSION: We suggest improvements in a task of social cognition and short-term visual memory after longer use of VNS therapy. Such findings should be confirmed in larger trials after controlling for changes in ictal or interictal activity.

Quality of Sleep and Work Productivity among White-Collar Workers during the COVID-19 Pandemic.

Background and Objectives: The COVID-19 pandemic has disrupted routine sleep and work patterns in the general population. We conducted an anonymous online survey among white-collar workers from various finance, IT and technology companies in Lithuania to define factors associated with worse sleep quality and diminished productivity during a COVID-19 lockdown. Materials and Methods: Employees of selected companies in Lithuania completed an anonymous questionnaire online that included the Pittsburgh Sleep Quality Index (PSQI), The Sleep Locus of Control (SLOC), the Generalized Anxiety Disorder Scale-7 (GAD-7), and the World Health Organization's Health and Work Performance Questionnaire (WHO-HPQ). Respondents also provided information about their sleep hygiene, physical activity and alcohol use. Results: Data of 114 respondents (56, 49.1% male) were used for analysis. Among them, 49 (43.0%) suffered from poor sleep and 29 (25.4%) had clinically relevant levels of anxiety. However, there were only negligible levels of absenteeism in the sample (a median of zero hours of work lost over the past month). In a stepwise linear regression model (F(5,108) = 11.457, p < 0.001, R2adj = 0.316), high levels of anxiety, daily hours spent using the screen, use of electronic devices in the bedroom, smoking in the evening, and COVID-19-related changes in appetite were associated with worse sleep quality. Absenteeism was associated with physical activity of moderate intensity and decreased self-reported productivity during the pandemic (F(2,111) = 7.570, p = 0.001, R2adj = 0.104). However, there was no strong relationship between sleep-related variables (i.e., sleep hygiene, sleep locus of control, quality of sleep) or levels of anxiety and measures of work productivity. Conclusions: Our findings suggest that while bad sleep hygiene, anxiety, and changes in appetite are associated with worse sleep quality among white-collar workers during the pandemic, work productivity may remain high irrespective of disrupted sleep.

Mortality among People with Epilepsy: A Retrospective Nationwide Analysis from 2016 to 2019.

We estimated age-adjusted mortality and investigated the dominant causes of death as well as comorbidities among people with epilepsy (PWE) in Lithuania, a country with frequent deaths from external causes. From 2016 to 2019, the age-adjusted rate of death among PWE in Lithuania was compared with mortality data in the general population. Each year of analysis, individuals who were diagnosed with epilepsy comprised a retrospective cohort. The standardized mortality ratio (SMR) of PWE varied from 2.93 (95% CI 2.78 to 3.07) to 3.18 (95% CI 3.02 to 3.34). PWE died at least one decade earlier than expected in the general population. The dominant causes of death were cardiovascular diseases (their proportion ranged from 44.8% to 49.3%), cancer (16.7% to 21.3%) and external causes of death (8.5% to 10.9%). The proportion of the latter decreased over time (r = -0.99, p = 0.01), whereas the SMR for external causes of death remained relatively constant. Epilepsy was the underlying cause of death in 163 cases (2.6%), and noted as a condition contributing to death in 1010 cases (15.9%). Cerebrovascular and cardiological conditions and dementia were the most frequent comorbidities among PWE before their death. Epilepsy-unrelated causes of death are relevant contributors to mortality among PWE. There is a need for PWE-oriented societal interventions to reduce the frequency of external deaths beyond the trend in the general population.

Does Epilepsy Have an Impact on Locus of Control?

Many chronic diseases impair patients' quality of life and may also affect their control perceptions. This could particularly happen for patients with epilepsy whose seizures often imply loss of control as a deeply disturbing experience. In 1980, a study on learned helplessness in epilepsy found a highly significant reduction of internal general locus of control (GLOC) and an increase of chance and powerful others health-related LOC (HLOC). In consequence, LOC became a frequent target of investigations relating to depression and anxiety, quality of life, coping, compliance, and other psychosocial aspects of epilepsy. Both GLOC and HLOC were investigated, and special groups like children, elderly, mentally handicapped persons, and those with psychogenic non-epileptic seizures were addressed. Most studies attempted to relate in-group differences of LOC to other parameters. Seizure-free patients were found to have a more internal HLOC, and patients with severe epilepsies have a more external HLOC. Patients with a high external HLOC seem to have more difficulties with coping and to be more anxious. Whereas external GLOC was correlated with learned helplessness, internal GLOC was associated with high self-efficacy and better life quality. An association of external LOC with depression seemed not to be a stable co-relation as clinical improvement following epilepsy surgery dissociated the two. A hypothesis was confirmed that the ability of some patients to counteract seizures at their onset, thus preserving control, was correlated with a higher internal HLOC. Some other theoretically well-founded hypotheses were not supported. Absolute figures as reported in several papers are of limited use because the only normative data for comparison come from a local sample of 1976 from Tennessee, whereas LOC scores may differ largely dependent on cultural and societal conditions. Very few controlled studies exist, and the early finding of a generally externalized LOC in epilepsy was confirmed only in one study performed in a South Indian community known for strong stigma against epilepsy. A recent transcultural investigation conducted in Brazil and Lithuania found no differences from healthy controls and between countries. It seems worthwhile to further investigate relations of LOC with epilepsy stigma.

Use of cannabis and its products among patients in a tertiary epilepsy center: A cross-sectional survey.

PURPOSE: The purpose of this study was to evaluate whether the topic of using cannabis as a treatment option for epilepsy is relevant among adult patients with the disorder and assess the possible determinant attitudes for having a history of cannabis consumption or being inclined to try it for medical purposes. MATERIAL AND METHODS: Willing adult (≥18 years) patients with diagnosed epilepsy participated in a cross-sectional survey study at a tertiary epilepsy center. The questions were related to cannabis use and opinions towards the safety and efficacy profile of cannabis for treating epilepsy. RESULTS: From 250 respondents, 41 (16.4%) reported prior use of cannabis or its preparations (15 [36.6%] for self-treatment). There were 81 (32.4%) participants further interested in cannabis use for treating epilepsy. In a binary regression model (Nagelkerke R2¯â€¯= 0.331), the opinion that cannabis is safer because of its natural origin (ß = 0.749, p = 0.027) and the premise of understanding its legal status (ß = 0.418, p = 0.024) positively predicted which participants have reported cannabis use. These patients were also more likely to consult internet sources (p = 0.004) and agree that cannabis as an epilepsy treatment option is effective (U = 2231.5, p < 0.001), safe (U = 1822.0, p < 0.001) and has no side effects (U = 2470.5, p = 0.004). Patients who had not tried cannabis were more likely to envision the products as potentially addictive (p = 0.012) and presumably be deterred from using them due to beliefs in harmful effects (ß = -0.632, p = 0.025). In general, nonusers were not inclined to try cannabis for treating epilepsy (Md = 2, range 1 to 7). However, those interested in the possibility of using cannabis to treat epilepsy would be more willing to try the respective preparations (p < 0.001). CONCLUSION: Among adult patients with epilepsy, we report no particularly high rate of cannabis use or interest in applying cannabis for medical purposes. In order to clarify the scientific and legal status of the preparations, treating neurologists should consult prior users and patients interested in the possibility of trying cannabis as an epilepsy remedy.

European trends in epilepsy surgery.

OBJECTIVE: Resective surgery is effective in treating drug-resistant focal epilepsy, but it remains unclear whether improved diagnostics influence postsurgical outcomes. Here, we compared practice and outcomes over 2 periods 15 years apart. METHODS: Sixteen European centers retrospectively identified 2 cohorts of children and adults who underwent epilepsy surgery in the period of 1997 to 1998 (n = 562) or 2012 to 2013 (n = 736). Data collected included patient (sex, age) and disease (duration, localization and diagnosis) characteristics, type of surgery, histopathology, Engel postsurgical outcome, and complications, as well as imaging and electrophysiologic tests performed for each case. Postsurgical outcome predictors were included in a multivariate logistic regression to assess the strength of date of surgery as an independent predictor. RESULTS: Over time, the number of operated cases per center increased from a median of 31 to 50 per 2-year period (p = 0.02). Mean disease duration at surgery decreased by 5.2 years (p < 0.001). Overall seizure freedom (Engel class 1) increased from 66.7% to 70.9% (adjusted p = 0.04), despite an increase in complex surgeries (extratemporal and/or MRI negative). Surgeries performed during the later period were 1.34 times (adjusted odds ratio; 95% confidence interval 1.02-1.77) more likely to yield a favorable outcome (Engel class I) than earlier surgeries, and improvement was more marked in extratemporal and MRI-negative temporal epilepsy. The rate of persistent neurologic complications remained stable (4.6%-5.3%, p = 0.7). CONCLUSION: Improvements in European epilepsy surgery over time are modest but significant, including higher surgical volume, shorter disease duration, and improved postsurgical seizure outcomes. Early referral for evaluation is required to continue on this encouraging trend.

Current standards of neuropsychological assessment in epilepsy surgery centers across Europe.

We explored the current practice with respect to the neuropsychological assessment of surgical epilepsy patients in European epilepsy centers, with the aim of harmonizing and establishing common standards. Twenty-six epilepsy centers and members of "E-PILEPSY" (a European pilot network of reference centers in refractory epilepsy and epilepsy surgery), were asked to report the status of neuropsychological assessment in adults and children via two different surveys. There was a consensus among these centers regarding the role of neuropsychology in the presurgical workup. Strong agreement was found on indications (localization, epileptic dysfunctions, adverse drugs effects, and postoperative monitoring) and the domains to be evaluated (memory, attention, executive functions, language, visuospatial skills, intelligence, depression, anxiety, and quality of life). Although 186 different tests are in use throughout these European centers, a core group of tests reflecting a moderate level of agreement could be discerned. Variability exists with regard to indications, protocols, and paradigms for the assessment of hemispheric language dominance. For the tests in use, little published evidence of clinical validity in epilepsy was provided. Participants in the survey reported a need for improvement concerning the validity of the tests, tools for the assessment of everyday functioning and accelerated forgetting, national norms, and test co-normalization. Based on the present survey, we documented a consensus regarding the indications and principles of neuropsychological testing. Despite the variety of tests in use, the survey indicated that there may be a core set of tests chosen based on experience, as well as on published evidence. By combining these findings with the results of an ongoing systematic literature review, we aim for a battery that can be recommended for the use across epilepsy surgical centers in Europe.

Epilepsia partialis continua: A review.

Epilepsia partialis contina (EPC) in a narrow definition is a variant of simple focal motor status epilepticus in which frequent repetitive muscle jerks, usually arrhythmic, continue over prolonged periods of time. In a broader definition (used in this review) it also includes non-motor manifestations otherwise known as aura continua. EPC may occur as a single episode, repetitive episodes, it may be chronic progressive or non-progressive. It appears as an unusual manifestation of epilepsy in which more typical paroxysmal events are partly or entirely replaced by the sustained repetition of seizure fragments in rapid succession. The minimum duration is defined as one hour but EPC may continue for up to many years. There are multiple possible etiologies which can be local or systemic, including two disease entities, Rasmussen encephalitis and Russian tick-borne spring-summer encephalitis. Among systemic brain disorders, mitochondrial diseases and non-ketotic hyperglycemia are particularly likely to cause EPC whereas stroke is a frequent cause of acute EPC. The symptoms of motor EPC have been interpreted as cortical reflex myocloni but the pathophysiology is probably not uniform for all cases. In pathophysiological terms, EPC seems to represent an oscillation of excitation and inhibition in a feedback loop whose mechanisms are still poorly understood. However, EPC only seems to occur rarely in an otherwise healthy brain. Treatment has to take account of the etiology but, in general, EPC tends to be drug-resistant. Epilepsy surgery is often indicated in Rasmussen encephalitis.

Current practices in long-term video-EEG monitoring services: A survey among partners of the E-PILEPSY pilot network of reference for refractory epilepsy and epilepsy surgery.

PURPOSE: The European Union-funded E-PILEPSY network aims to improve awareness of, and accessibility to, epilepsy surgery across Europe. In this study we assessed current clinical practices in epilepsy monitoring units (EMUs) in the participating centers. METHOD: A 60-item web-based survey was distributed to 25 centers (27 EMUs) of the E-PILEPSY network across 22 European countries. The questionnaire was designed to evaluate the characteristics of EMUs, including organizational aspects, admission, and observation of patients, procedures performed, safety issues, cost, and reimbursement. RESULTS: Complete responses were received from all (100%) EMUs surveyed. Continuous observation of patients was performed in 22 (81%) EMUs during regular working hours, and in 17 EMUs (63%) outside of regular working hours. Fifteen (56%) EMUs requested a signed informed consent before admission. All EMUs performed tapering/withdrawal of antiepileptic drugs, 14 (52%) prior to admission to an EMU. Specific protocols on antiepileptic drugs (AED) tapering were available in four (15%) EMUs. Standardized Operating Procedures (SOP) for the treatment of seizure clusters and status epilepticus were available in 16 (59%). Safety measures implemented by EMUs were: alarm seizure buttons in 21 (78%), restricted patient's ambulation in 19 (70%), guard rails in 16 (59%), and specially designated bathrooms in 7 (26%). Average costs for one inpatient day in EMU ranged between 100 and 2200 Euros. CONCLUSION: This study shows a considerable diversity in the organization and practice patterns across European epilepsy monitoring units. The collected data may contribute to the development and implementation of evidence-based recommended practices in LTM services across Europe.

Current use of imaging and electromagnetic source localization procedures in epilepsy surgery centers across Europe.

OBJECTIVE: In 2014 the European Union-funded E-PILEPSY project was launched to improve awareness of, and accessibility to, epilepsy surgery across Europe. We aimed to investigate the current use of neuroimaging, electromagnetic source localization, and imaging postprocessing procedures in participating centers. METHODS: A survey on the clinical use of imaging, electromagnetic source localization, and postprocessing methods in epilepsy surgery candidates was distributed among the 25 centers of the consortium. A descriptive analysis was performed, and results were compared to existing guidelines and recommendations. RESULTS: Response rate was 96%. Standard epilepsy magnetic resonance imaging (MRI) protocols are acquired at 3 Tesla by 15 centers and at 1.5 Tesla by 9 centers. Three centers perform 3T MRI only if indicated. Twenty-six different MRI sequences were reported. Six centers follow all guideline-recommended MRI sequences with the proposed slice orientation and slice thickness or voxel size. Additional sequences are used by 22 centers. MRI postprocessing methods are used in 16 centers. Interictal positron emission tomography (PET) is available in 22 centers; all using 18F-fluorodeoxyglucose (FDG). Seventeen centers perform PET postprocessing. Single-photon emission computed tomography (SPECT) is used by 19 centers, of which 15 perform postprocessing. Four centers perform neither PET nor SPECT in children. Seven centers apply magnetoencephalography (MEG) source localization, and nine apply electroencephalography (EEG) source localization. Fourteen combinations of inverse methods and volume conduction models are used. SIGNIFICANCE: We report a large variation in the presurgical diagnostic workup among epilepsy surgery centers across Europe. This diversity underscores the need for high-quality systematic reviews, evidence-based recommendations, and harmonization of available diagnostic presurgical methods.

Current status of epilepsy health care for adult patients from central and eastern European Union countries--a survey of members of the Central Europe Epilepsy Experts Working Group.

PURPOSE: The aim of this survey was to review and compare the current approaches to epilepsy management in central and eastern EU (CEEU) countries. METHOD: The questionnaire was sent to ten invited experts from Bulgaria, Czech Republic, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia, and Slovenia. It focused on the treatment of adults. RESULTS: The number of neurologists and epilepsy reference centers is highly variable in CEEU countries. None of the analyzed states has a formal specialization in epileptology. No universal state-approved criteria for reference centers exist in Czech Republic, Estonia, Hungary, Latvia, and Slovenia. Generally, the protocols for epilepsy treatment in CEEU countries, including drug-resistant epilepsy, are in accordance with international guidelines; however, most countries have their own national standards of care and some have local clinical guidelines. Also, the reimbursement systems for antiepileptic drugs in CEEU countries are highly variable. Seven countries have epilepsy surgery centers. The costs of epilepsy surgeries are fully reimbursed, procedures performed abroad may also be covered. The length of time spent on waiting lists for surgery following the completion of preoperative investigations varies from two weeks to three years. The fraction of patients who qualified and were operated on within 12 months ranges from 20% to 100%. CONCLUSION: The lack of unified procedures pertaining to the evaluation and therapy of epilepsy is reflected by marked differences in access to treatment modalities for patients from CEEU countries.