Neurocognitive performance in functional neurological disorder: A systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Cognitive complaints are common in functional neurological disorder (FND), but it is unclear whether objective neurocognitive deficits are present. This systematic review summarized validated/standardized cognitive test performance in FND samples across cognitive domains. METHODS: Embase, PsycInfo and MEDLINE were searched from inception to 15 May 2023, combining terms for FND and cognitive domains (e.g., attention, memory, executive functioning). Studies included a range of FND phenotypes (seizures, motor, cognitive disorder, mixed), compared to healthy or clinical controls. Risk of bias was assessed with the modified Newcastle-Ottawa Scale and a qualitative synthesis/narrative review of cognitive performance in FND was conducted. Test performance scores were extracted, and random effects meta-analyses were run where appropriate. This review was registered on PROSPERO, CRD42023423139. RESULTS: Fifty-six studies including 2260 individuals with FND were eligible. Although evidence for some impairments emerged across domains of executive functioning, attention, memory and psychomotor/processing speed, this was inconsistent across studies and FND phenotypes. Common confounds included group differences in demographics, medication and intellectual functioning. Only 24% of studies objectively assessed performance validity. Meta-analyses revealed higher scores on tests of naming (g = 0.67, 95% confidence interval [CI] 0.50, 0.84) and long-term memory (g = 0.43, 95% CI 0.13, 0.74) in functional seizures versus epilepsy, but no significant differences in working (g = -0.08, 95% CI -0.44, 0.29) or immediate (g = 0.25, 95% CI -0.02, 0.53) memory and cognitive flexibility (g = -0.01, 95% CI -0.29, 0.28). CONCLUSIONS: There is mixed evidence for objective cognitive deficits in FND. Future research should control for confounds, include tests of performance validity, and assess relationships between objective and subjective neurocognitive functioning.

Distinct signatures of loss of consciousness in focal impaired awareness versus tonic-clonic seizures.

Loss of consciousness is a hallmark of many epileptic seizures and carries risks of serious injury and sudden death. While cortical sleep-like activities accompany loss of consciousness during focal impaired awareness seizures, the mechanisms of loss of consciousness during focal to bilateral tonic-clonic seizures remain unclear. Quantifying differences in markers of cortical activation and ictal recruitment between focal impaired awareness and focal to bilateral tonic-clonic seizures may also help us to understand their different consequences for clinical outcomes and to optimize neuromodulation therapies. We quantified clinical signs of loss of consciousness and intracranial EEG activity during 129 focal impaired awareness and 50 focal to bilateral tonic-clonic from 41 patients. We characterized intracranial EEG changes both in the seizure onset zone and in areas remote from the seizure onset zone with a total of 3386 electrodes distributed across brain areas. First, we compared the dynamics of intracranial EEG sleep-like activities: slow-wave activity (1-4 Hz) and beta/delta ratio (a validated marker of cortical activation) during focal impaired awareness versus focal to bilateral tonic-clonic. Second, we quantified differences between focal to bilateral tonic-clonic and focal impaired awareness for a marker validated to detect ictal cross-frequency coupling: phase-locked high gamma (high-gamma phased-locked to low frequencies) and a marker of ictal recruitment: the epileptogenicity index. Third, we assessed changes in intracranial EEG activity preceding and accompanying behavioural generalization onset and their correlation with electromyogram channels. In addition, we analysed human cortical multi-unit activity recorded with Utah arrays during three focal to bilateral tonic-clonic seizures. Compared to focal impaired awareness, focal to bilateral tonic-clonic seizures were characterized by deeper loss of consciousness, even before generalization occurred. Unlike during focal impaired awareness, early loss of consciousness before generalization was accompanied by paradoxical decreases in slow-wave activity and by increases in high-gamma activity in parieto-occipital and temporal cortex. After generalization, when all patients displayed loss of consciousness, stronger increases in slow-wave activity were observed in parieto-occipital cortex, while more widespread increases in cortical activation (beta/delta ratio), ictal cross-frequency coupling (phase-locked high gamma) and ictal recruitment (epileptogenicity index). Behavioural generalization coincided with a whole-brain increase in high-gamma activity, which was especially synchronous in deep sources and could not be explained by EMG. Similarly, multi-unit activity analysis of focal to bilateral tonic-clonic revealed sustained increases in cortical firing rates during and after generalization onset in areas remote from the seizure onset zone. Overall, these results indicate that unlike during focal impaired awareness, the neural signatures of loss of consciousness during focal to bilateral tonic-clonic consist of paradoxical increases in cortical activation and neuronal firing found most consistently in posterior brain regions. These findings suggest differences in the mechanisms of ictal loss of consciousness between focal impaired awareness and focal to bilateral tonic-clonic and may account for the more negative prognostic consequences of focal to bilateral tonic-clonic.

Glycolysis regulates neuronal excitability via lactate receptor, HCA1R.

Repetitively firing neurons during seizures accelerate glycolysis to meet energy demand, which leads to the accumulation of extracellular glycolytic by-product lactate. Here, we demonstrate that lactate rapidly modulates neuronal excitability in times of metabolic stress via the hydroxycarboxylic acid receptor type 1 (HCA1R) to modify seizure activity. The extracellular lactate concentration, measured by a biosensor, rose quickly during brief and prolonged seizures. In two epilepsy models, mice lacking HCA1R (lactate receptor) were more susceptible to developing seizures. Moreover, HCA1R deficient (knockout) mice developed longer and more severe seizures than wild-type littermates. Lactate perfusion decreased tonic and phasic activity of CA1 pyramidal neurons in genetically encoded calcium indicator 7 imaging experiments. HCA1R agonist 3-chloro-5-hydroxybenzoic acid (3CL-HBA) reduced the activity of CA1 neurons in HCA1R WT but not in knockout mice. In patch-clamp recordings, both lactate and 3CL-HBA hyperpolarized CA1 pyramidal neurons. HCA1R activation reduced the spontaneous excitatory postsynaptic current frequency and altered the paired-pulse ratio of evoked excitatory postsynaptic currents in HCA1R wild-type but not in knockout mice, suggesting it diminished presynaptic release of excitatory neurotransmitters. Overall, our studies demonstrate that excessive neuronal activity accelerates glycolysis to generate lactate, which translocates to the extracellular space to slow neuronal firing and inhibit excitatory transmission via HCA1R. These studies may identify novel anticonvulsant target and seizure termination mechanisms.

Clinical characteristics of patients with refractory non-epileptic seizures.

OBJECTIVES: This incidence of non-epileptic seizures (NES) is estimated at 1-35 per 100,000 population. While many patients achieve remission, a significant fraction of patients have a poor prognosis despite optimal interventions. This study reports on the characteristics of patients with refractory NES diagnosed and treated at a comprehensive epilepsy centre. METHODS: A retrospective review of admissions to the Epilepsy Monitoring Unit identified patients diagnosed with NES over a 6-year period. Patients with refractory NES were identified through review of medical files. A diagnosis of refractory NES was assigned when patients experienced ongoing NES at least 1 year after diagnostic video-EEG monitoring. Data pertaining to predisposing, precipitating and perpetuating factors was collected on all patients and a comparative analysis was conducted between refractory and non-refractory cases. RESULTS: 66 patients with NES were identified, 35% were deemed refractory. There was no significant difference amongst predisposing factors between the groups. Psychosocial adversity and a clear precipitant proximate to the onset of NES were significantly more common in the refractory cohort. Unemployment at time of diagnosis was a significant perpetuating factor associated with poor outcome. CONCLUSION: This study provides insight into the features associated with refractory NES and may serve to improve prognostication and management in this disabling condition.

Breathing control training for functional seizures: A multi-site, open-label pilot study.

There are no well-validated treatments for functional seizures. While specialist psychotherapy is usually recommended, the evidence for its benefit is qualified, and it can be difficult to obtain. Given the association between hyperventilation and functional seizures we explored an alternative modality, breathing control training, in a multi-site open label pilot trial. Participants with functional seizures over the age of 16 received an hour of breathing training from a respiratory physiotherapist, with a half-hour booster session a month later. Seizure frequency and Nijmegen scores (a measure of hyperventilation) were reported at baseline and follow-up, 3-4 months later. Eighteen subjects were recruited, and 10 completed follow-up. Seven of these 10 had improved seizure frequency, and 3 did not (Wilcoxon signed rank test, p = 0.09), with seizure frequency correlating with Nijmegen score (Spearman's rank correlation = 0.75, p = 0.034). The intervention was well tolerated, with no adverse events reported. These preliminary results support a potentially new approach to treating functional seizures that should prove cost-effective and acceptable, though require confirmation by a randomised controlled trial.

Impact of the COVID-19 pandemic, its related social restriction measures and vaccination campaign on emergency department attendances for epileptic seizures: An interrupted time-series analysis.

AIM: To investigate the impact of the outbreak of the COVID-19 pandemic, its related social restriction measure (national lockdown) and vaccination campaign on emergency department (ED) accesses for epileptic seizures. METHODS: Retrospective observational analysis conducted on a consecutive cohort of patients who sought medical care at the ED of the General Hospital of Merano, Italy, from January 1, 2015, to December 31, 2021. We investigated the monthly ED attendances for epileptic seizures between the periods before and after the outbreak of the COVID-19 pandemic and the national lockdown (March 2020) using an interrupted time-series analysis with data standardized for 1000 accesses/month. As a further temporal cutoff, we used the start of the national vaccination campaign. RESULTS: Between January 1, 2015, and December 31, 2021, a total of 415,005 ED attendances were recorded; 1,254 (0.3 %) were due to epileptic seizures. No significant difference was found in the rate of standardized ED accesses for epileptic seizures in March 2020 (time point of interest) to the pre-pandemic trend (0.33/1000; 95 %CI: -1.05 to 1.71; p = 0.637). Similarly, there was no difference between the pre- and post-pandemic trends (-0.02/1000; 95 %CI: -0.11 to 0.06; p = 0.600). When adopting January 2021 as time point of interest, we found no difference to the pre-vaccination trend (0.83/1000; 95 %CI: -0.48 to 2.15), and no difference in the pre- and post-vaccination trends (-0.12/1000; 95 %CI: -0.27 to 0.04). CONCLUSIONS: The COVID-19 pandemic and its related social restrictions (lockdown), as well as the COVID-19 national vaccination campaign, had little impact on ED accesses for epileptic seizures.

Testing the diagnostic accuracy of common questions for seizure diagnosis: Challenges and future directions.

OBJECTIVE: The aim of this study was to evaluate the diagnostic accuracy of common interview questions used to distinguish a diagnosis of epilepsy from seizure mimics including non-epileptic seizures (NES), migraine, and syncope. METHODS: 200 outpatients were recruited with an established diagnosis of focal epilepsy (n = 50), NES (n = 50), migraine (n = 50), and syncope (n = 50). Patients completed an eight-item, yes-or-no online questionnaire about symptoms related to their events. Sensitivity and specificity were calculated. Using a weighted scoring for the questions alone with baseline characteristics, the overall questionnaire was tested for diagnostic accuracy. RESULTS: Of individual questions, the most sensitive one asked if events are sudden in onset (98 % sensitive for epilepsy (95 % CI: 89 %, 100 %)). The least sensitive question asked if events are stereotyped (46 % sensitive for epilepsy (95 % CI: 32 %, 60 %)). Overall, three of the eight questions showed an association with epilepsy as opposed to mimics. These included questions about "sudden onset" (OR 10.76, 95 % CI: (1.66, 449.21) p = 0.0047), "duration < 5 min" (OR 3.34, 95 % CI: (1.62, 6.89), p = 0.0008), and "duration not > 30 min" (OR 4.44, 95 % CI: (1.94, 11.05), p = <0.0001). When individual seizure mimics were compared to epilepsy, differences in responses were most notable between the epilepsy and migraine patients. Syncope and NES were most similar in responses to epilepsy. The overall weighted questionnaire incorporating patient age and sex produced an area under the ROC curve of 0.80 (95 % CI: 0.74, 0.87)). CONCLUSION: In this study, we examined the ability of common interview questions used by physicians to distinguish between epilepsy and prevalent epilepsy mimics, specifically NES, migraines, and syncope. Using a weighted scoring system for questions, and including age and sex, produced a sensitive and specific predictive model for the diagnosis of epilepsy. In contrast to many prior studies which evaluated either a large number of questions or used methods with difficult practical application, our study is unique in that we tested a small number of easy-to-understand "yes" or "no" questions that can be implemented in most clinical settings by non-specialists.

Attention-based deep convolutional neural network for classification of generalized and focal epileptic seizures.

Epilepsy affects over 50 million people globally. Electroencephalography is critical for epilepsy diagnosis, but manual seizure classification is time-consuming and requires extensive expertise. This paper presents an automated multi-class seizure classification model using EEG signals from the Temple University Hospital Seizure Corpus ver. 1.5.2. 11 features including time-based correlation, time-based eigenvalues, power spectral density, frequency-based correlation, frequency-based eigenvalues, sample entropy, spectral entropy, logarithmic sum, standard deviation, absolute mean, and ratio of Daubechies D4 wavelet transformed coefficients were extracted from 10-second sliding windows across channels. The model combines multi-head self-attention mechanism with a deep convolutional neural network (CNN) to classify seven subtypes of generalized and focal epileptic seizures. The model achieved 0.921 weighted accuracy and 0.902 weighted F1 score in classifying focal onset non-motor, generalized onset non-motor, simple partial, complex partial, absence, tonic, and tonic-clonic seizures. In comparison, a CNN model without multi-head attention achieved 0.767 weighted accuracy. Ablation studies were conducted to validate the importance of transformer encoders and attention. The promising classification results demonstrate the potential of deep learning for handling EEG complexity and improving epilepsy diagnosis. This seizure classification model could enable timely interventions when translated into clinical practice.

Cognitive behavioral therapy in adults with functional seizures: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Randomized controlled clinical trials (RCTs) investigating cognitive-behavioral therapy (CBT) among adults with functional seizures (FS) have become increasingly available, prompting the opportunity to critically appraise the efficacy and safety of CBT in this population. METHODS: We conducted a systematic review and meta-analysis including RCTs comparing CBT in addition to standardized medical treatment (SMT) versus SMT alone for adults with FS. The primary outcome was seizure freedom at the end of treatment. Secondary outcomes included measures of quality of life, anxiety and depression assessed via standardized clinical questionnaires. RESULTS: Three RCTs were included comprising 228 participants treated with CBT and 222 with SMT. The intervention was significantly associated with seizure freedom (Odds Ratio [OR] 1.98; 95 % confidence interval [CI] 1.14, 3.46; p = 0.02; I2 = 0 %), reductions in anxiety (standardized mean difference [SMD] -0.21; 95 % CI -0.41, -0.003; p = 0.047; I2 = 0 %) and improvements in quality of life (SMD 0.34; 95 % CI 0.12, 0.57; p = 0.003; I2 = 0 %) at the end of treatment. Conversely, no significant differences between groups were observed in depression symptoms (SMD -0.19; 95 % CI -0.39, 0.02; p = 0.08; I2 = 0 %). There was no statistically significant increase in the risk of suicidal ideation and self-harm with CBT (OR 2.11; 95 % CI 0.81, 5.48; p = 0.13; I2 = 0 %) nor were there differences in terms of discontinuation rates during follow-up (OR 0.92; 95 % CI 0.49, 1.72; p = 0.79; I2 = 7 %). CONCLUSIONS: There is high-quality evidence supporting the efficacy and safety of CBT in treating FS. Future research should investigate whether combining CBT with other therapeutic methods could potentially enhance treatment efficacy.

Emergency management of pediatric epileptic seizures in non-hospital settings in Japan.

OBJECTIVE: To assess the current management of pediatric epileptic seizures in non-hospital settings and the efficacy of early therapeutic intervention with rescue medication in Japan. METHODS: This descriptive cross-sectional study was based on an online survey of caregivers of pediatric patients with epilepsy. The survey consisted of questions regarding seizure frequency and symptoms, the use of rescue medication, and emergency medical care. Statistical analyses were performed to evaluate the association between the time to rescue medication administration and seizure resolution. RESULTS: Responses were obtained from 1147 caregivers of pediatric patients with epilepsy. Of the patients described in the study, 98.5 % had been prescribed anti-seizure medication, 95.3 % had more than a few seizures per year, and 90.3 % used rescue medication. The time to seizure resolution was significantly reduced when rescue medication was administered early. Overall, 28.4 % of the patients required emergency transport to hospital, which increased disruption to the lives of caregivers, who returned to their normal activities after an average of 17.2 h. CONCLUSION: Emergency transport of patients places a significant burden on caregivers. Earlier administration of rescue medications is associated with a reduction in the need for emergency room visits, which reduces the burden on the patient as well as the caregiver.

Hypertension and other vascular risk factors in patients with functional seizures.

OBJECTIVE: Recent literature has suggested that functional seizures are associated with an elevated risk for vascular disease and mortality. We investigated the prevalence of risk factors for vascular disease in patients who were admitted to the epilepsy monitoring unit. METHODS: Patients who were admitted to the epilepsy monitoring unit and received a definitive diagnosis of either functional seizures or epilepsy were identified. Data collected included demographic, clinical characteristics, medication list, comorbidities, and scheduled blood pressure measurements that occurred every 12 h during the admission. The mean blood pressures were calculated and if they were above the American College of Cardiology and the American Heart Association guideline cutoff of 130/80 mm Hg or the patient had a documented history of hypertension the patient was counted as having the condition. A multiple logistic regression model was developed to evaluate the independent association of the patient's diagnosis (i.e., epilepsy or functional seizures) and vascular risk factors that controlled for the number of blood pressure measurements, age, sex, and if the patient was taking antihypertensive medications. RESULTS: 270 patients were included in this study of which 147 patients had epilepsy and 123 had functional seizures. Among those with functional seizures, 57.72 % had either a history of hypertension or a mean blood pressure above 130/80 compared to 38.78 % of those with epilepsy (p = 0.0022). In addition, 30.89 % of functional seizures patients had hyperlipidemia and 63.41 % were obese. The logistic regression model indicated that functional seizures were independently associated with high blood pressure (OR: 2.47, 95 % CI 1.10-5.69), hyperlipidemia (OR: 3.38, 95 % CI 1.35-8.86), and obesity (OR: 4.25, 95 % CI 2.22-8.36) compared to those with epilepsy. There was no significant difference in the prevalence of diabetes (OR: 0.81, 95 % CI 0.24-2.77) or current tobacco use (OR: 1.04, 95 % CI 0.48-2.25) between the groups. SIGNIFICANCE: Patients with functional seizures had an elevated prevalence of several vascular risk factors. These findings may partially account for complications associated with functional seizures and have implications related to their pathophysiology.

"This is real", "this is hard" and "I'm not making it up": Experience of diagnosis and living with non-epileptic attack disorder.

PURPOSE: To use a qualitative research approach to explore adults' experience of living with non-epileptic attack disorder. OBJECTIVE: The objective was to explore the experience of adults (18 years+) with a confirmed diagnosis of non-epileptic attack disorder (NEAD) across the trajectory of the disorder. The topics investigated included the onset of symptoms, the experience of non-epileptic attacks, the diagnostic process and living with NEAD. METHOD: Twelve people diagnosed with NEAD who attended a tertiary hospital neurology department took part in semi-structured interviews. The data generated were analysed using reflexive thematic analysis. RESULTS: Eleven women and one man with median age of 25 years took part. Three themes were developed: mind-body (dis)connect, a stigmatised diagnosis and a role for containment. Adults spoke about their experience of nonepileptic attacks, the diagnostic and management process and the impact of both nonepileptic attacks and the NEAD diagnosis on their lives. CONCLUSIONS: Adults' experience's within the healthcare system across the trajectory of NEAD influenced their own understanding and trust in their NEAD experience, how they shared this with others in their social and work lives and how they managed their NEAD symptoms on a daily basis. The research suggests the need for a consistent, timely implementation of a rule-in diagnostic approach and multi-disciplinary management of NEAD. It is recommended that lessons be taken from theoretical models including the common-sense model and a modified version of the reattribution model to support the de-stigmatisation of this diagnosis to inform psychoeducation and professionally facilitated peer-support groups.

Gaps in treatment of epileptic seizures in a Zambian rural area.

BACKGROUND: Epilepsy is a multifactorial neurological disorder, including parasitic infections of the brain such as neurocysticercosis (NCC). People with epileptic seizures (PWES) in low and middle-income countries often do not receive appropriate treatment, which besides epileptic seizures, may also lead to reduced quality of life and possibly death. The objective of this study was to describe gaps in treatment of epileptic seizures in a Zambian rural area. METHODS: A cross-sectional study was conducted in Sinda district of Zambia between August and October 2018. PWES identified from clinic records and with the help of community healthcare workers were recruited. Two questionnaires, one to PWES and the other to local healthcare workers, were administered to describe the treatment gap. RESULTS: A total of 146 PWES and 43 healthcare workers were interviewed. Of the 146 PWES, 131 had taken anti-seizure medication (ASM) at some point since their seizure onset, of which 49.6% were on current treatment. Only 18.3% were on continuous ASM, an overall treatment gap of 83.6%. Over 55% of healthcare workers did not know the relationship between epilepsy and NCC. The risk factors associated with lack of appropriate treatment were stock-outs of ASMs, lack of diagnostic equipment, poor patient follow-up, and PWES opting for traditional medicine. CONCLUSION: The treatment gap is substantial in Sinda district. The causes are multifactorial, involving shortcomings at the level of healthcare facilities, communities, and individuals. Directed training of healthcare workers and significant improvements in the supply and dispensing of ASMs will be key in substantially reducing the gap.

Short-term effects of ambient nitrogen dioxide on medical emergency calls for epileptic seizures: A time-series study.

Short-term exposure to air pollution has previously been studied in relation to certain neurological disorders, but there is still a lack of convincing data linking air pollution to epileptic seizures. The study's goal was to investigate how exposure to ambient nitrogen dioxide (NO2) affected the number of patients seeking assistance at the Wuhan Emergency Medical Center due to epileptic seizures. We gathered data on medical emergency calls (MECs), daily ambient air pollution concentrations (SO2, NO2, PM2.5, PM10, CO, and O3), and meteorological variables in Wuhan, China, spanning from January 1, 2017, to November 30, 2019. To investigate the potential influence of ambient nitrogen dioxide on MECs for epileptic seizures, we carried out a time-series investigation using the general additive model (GAM). Additionally, analyses stratified by season, age, and gender were performed. A total of 8989 records of MECs for epileptic seizures were enrolled in our study during the period. Statistical analysis indicates that a rise of 10 µg/m3 in NO2 concentration is linked to a 0.17% increase in daily MECs for epileptic seizures (95% confidence interval [CI]: 0.02%, 0.32%). Furthermore, people aged 14-59 years were more susceptible(2.25%, P < 0.05). The short-term effects of NO2 exposure on daily MECs for epileptic seizures were stronger in warm seasons than in cool seasons (0.55% vs. -0.10%, P < 0.0001). Our findings suggests that short-term exposure to ambient NO2 was positively correlated with daily MECs for epileptic seizures in Wuhan, China. Additionally, we observed that these associations were stronger in patients aged above 14 but under 60 years and the warmer seasons (from April to September).

Dissimilar Changes in Serum Cortisol after Epileptic and Psychogenic Non-Epileptic Seizures: A Promising Biomarker in the Differential Diagnosis of Paroxysmal Events?

The hypothalamic-pituitary-adrenal axis is known to be involved in the pathogenesis of epilepsy and psychiatric disorders. Epileptic seizures (ESs) and psychogenic non-epileptic seizures (PNESs) are frequently differentially misdiagnosed. This study aimed to evaluate changes in serum cortisol and prolactin levels after ESs and PNESs as possible differential diagnostic biomarkers. Patients over 18 years with ESs (n = 29) and PNESs with motor manifestations (n = 45), captured on video-EEG monitoring, were included. Serum cortisol and prolactin levels as well as hemograms were assessed in blood samples taken at admission, during the first hour after the seizure, and after 6, 12, and 24 h. Cortisol and prolactine response were evident in the ES group (but not the PNES group) as an acute significant increase within the first hour after seizure. The occurrence of seizures in patients with ESs and PNESs demonstrated different circadian patterns. ROC analysis confirmed the accuracy of discrimination between paroxysmal events based on cortisol response: the AUC equals 0.865, with a prediction accuracy at the cutoff point of 376.5 nmol/L 0.811 (sensitivity 86.7%, specificity 72.4%). Thus, assessments of acute serum cortisol response to a paroxysmal event may be regarded as a simple, fast, and minimally invasive laboratory test contributing to differential diagnosis of ESs and PNESs.

The Association of Epileptic Seizures after Acute Ischemic Stroke with Cerebral Cortical Involvement and Electroencephalographic Changes.

Background and objectives: while acute ischemic stroke is the leading cause of epilepsy in the elderly population, data about its risk factors have been conflicting. Therefore, the aim of our study is to determine the association of early and late epileptic seizures after acute ischemic stroke with cerebral cortical involvement and electroencephalographic changes. Materials and methods: a prospective cohort study in the Hospital of the Lithuanian University of Health Sciences Kaunas Clinics Department of Neurology was conducted and enrolled 376 acute ischemic stroke patients. Data about the demographical, clinical, radiological, and encephalographic changes was gathered. Patients were followed for 1 year after stroke and assessed for late ES. Results: the incidence of ES was 4.5%, the incidence of early ES was 2.7% and the incidence of late ES was 2.4%. The occurrence of early ES increased the probability of developing late ES. There was no association between acute cerebral cortical damage and the occurrence of ES, including both early and late ES. However, interictal epileptiform discharges were associated with the occurrence of ES, including both early and late ES.

Factors affecting long-term prognosis in adult patients with psychogenic non-epileptic seizures.

Background and purpose:

Among epileptic patients who are monitored using the video-electroencephalography monitoring (VEM) technique, in some patients a psychogenic non-epileptic seizure (PNES) can be identified as a definitive diagnosis. The long-term prognosis of these patients is not well known. In this study, we aimed to determine the factors that affect the prognosis of PNES.

Forty-one PNES patients diagnosed using VEM between 2012 and 2022 were questioned about their PNES frequencies in the last 12 months. According to their semiological characteristics, PNES types were divided into motor and non-motor seizures. The effects of clinical characteristics (e.g. age, gender, marital status, education level and PNES type) on the prognoses were identified. 

Twenty-one PNES patients (51.2%) had long-term seizure freedom after VEM. Thirteen of them (31.7%) entered the seizure-free period immediately after VEM, and the other eight (19.5%) continued suffering from PNES for several years and became seizure free in the last 12 months. In the poor-prognosis group, female cases showed worse prognoses than male cases. The prognoses of motor and non-motor PNES types did not show significant differences. 

This study showed that 51.2% of the PNES patients examined had long-term seizure freedom and that female patients had worse prognoses than male patients.

Astrocyte-derived SerpinA3N promotes neuroinflammation and epileptic seizures by activating the NF-κB signaling pathway in mice with temporal lobe epilepsy.

Impaired activation and regulation of the extinction of inflammatory cells and molecules in injured neuronal tissues are key factors in the development of epilepsy. SerpinA3N is mainly associated with the acute phase response and inflammatory response. In our current study, transcriptomics analysis, proteomics analysis, and Western blotting showed that the expression level of Serpin clade A member 3N (SerpinA3N) is significantly increased in the hippocampus of mice with kainic acid (KA)-induced temporal lobe epilepsy, and this molecule is mainly expressed in astrocytes. Notably, in vivo studies using gain- and loss-of-function approaches revealed that SerpinA3N in astrocytes promoted the release of proinflammatory factors and aggravated seizures. Mechanistically, RNA sequencing and Western blotting showed that SerpinA3N promoted KA-induced neuroinflammation by activating the NF-κB signaling pathway. In addition, co-immunoprecipitation revealed that SerpinA3N interacts with ryanodine receptor type 2 (RYR2) and promotes RYR2 phosphorylation. Overall, our study reveals a novel SerpinA3N-mediated mechanism in seizure-induced neuroinflammation and provides a new target for developing neuroinflammation-based strategies to reduce seizure-induced brain injury.

A meta-analytic review of the effectiveness of psychological treatment of functional/dissociative seizures on non-seizure outcomes in adults.

Psychological therapies are considered the treatment of choice for functional/dissociative seizures (FDSs). Although most previous studies have focused on seizure persistence or frequency, it has been argued that well-being or health-related quality of life outcomes may actually be more meaningful. This study contributes by summarizing and meta-analyzing non-seizure outcomes to quantify the effectiveness of psychological treatment in this patient group. A pre-registered systematic search identified treatment studies (e.g., cohort studies, controlled trials) in FDSs. Data from these studies were synthesized using multi-variate random-effects meta-analysis. Moderators of treatment effect were examined using treatment characteristics, sample characteristics, and risk of bias. A total of 171 non-seizure outcomes across 32 studies with a pooled sample size of N = 898 yielded a pooled effect-size of d = .51 (moderate effect size). The outcome domain assessed and the type of psychological treatment were significant moderators of reported outcomes. Greater rates of improvement were demonstrated for outcomes assessing general functioning. Behavioral treatments emerged as particularly effective interventions. Psychological interventions are associated with clinical improvements across a broad array of non-seizure outcomes, over and above seizure frequency, in adults with FDSs.

The effect of lacosamide monotherapy on sleep architecture in patients with epilepsy: a preliminary evidence.

Lacosamide (LCM) is a third-generation antiseizure medication (ASM), and its effect on sleep architecture was supported by a few studies in patients with drug-resistant epilepsy in which LCM was used as an add-on treatment. To gather knowledge on ASMs effects on sleep, this study aimed at evaluating the effects of LCM monotherapy on sleep in patients with focal epilepsy. Ten patients diagnosed with epilepsy (mean age 58.00 ± 14.77, 60.0% female, mean monthly seizure frequency 1.20 ± 2.48) starting LCM as monotherapy were included. Sleep architecture was assessed through polysomnography at baseline and at the 6-month follow-up visit. A significant decrease was observed in seizure frequency (p = 0.004), being all patients seizure-free at follow-up. At baseline, eight patients had poor sleep efficiency (< 85%). Sleep efficiency increased at follow-up, with only three patients having an index < 85% (p = 0.022). From baseline to follow-up, a significant decrease was observed in sleep latency (p = 0.022) and wakefulness after sleep onset (p = 0.047). Moreover, a significant decrease was observed in the percentage of stage 1 (Md = 6.70 vs Md = 3.85, p = 0.005) and stage 3 (Md = 27.70 vs Md = 22.35, p = 0.01) of Non-REM sleep. This study suggests that LCM monotherapy may positively impact sleep architecture in patients with epilepsy. The sleep efficiency improvement and the decrease of sleep latency and wakefulness after sleep onset observed at follow-up highlight better sleep stability and continuity in patients treated with LCM. Notably, all patients were seizure-free at follow-up, and seizure freedom may also concur to sleep structure improvement.