The first ER-targeting flavone-based fluorescent probe for Cys: Applications in real-time tracking in an epilepsy model and food analysis.

Epilepsy is one of the most commonly-seen neurological disorders, and both endoplasmic reticulum stress (ERS) and oxidative stress (OS) have been demonstrated to be associated with epileptic seizures. As one of the three endogenous thiol-containing amino acids, cysteine (Cys) is recognized not only as an important biomarker of various biological processes but also widely used as a significant additive in the food industry. However, the exact role that Cys plays in ERS has not been well answered up to now. In this paper, we reported the first flavone-based fluorescent probe (namely BFC) with nice endoplasmic reticulum (ER)-targeting ability, which was capable of monitoring Cys in a fast response (3.0 min), large stokes shift (130 nm) and low detection limit (10.4 nM). The recognition mechanism of Cys could be attributed to the addition-cyclization reaction involving a Cys residue and an acrylate group, resulting in the release of the strong excited-state intramolecular proton transfer (ESIPT) emission molecule of benzoflavonol (BF). The low cytotoxicity and good biocompatibility of the probe BFC allowed for monitoring the fluctuation of endogenous Cys levels under both ERS and OS processes, as well as in zebrafish models of epilepsy. Quantitative determination of Cys with the probe BFC was also achieved in three different food samples. Additionally, a probe-immersed test strips integrated with a smartphone device was successfully constructed for on-site colorimetric detection of Cys. Undoubtedly, our work provided a valuable tool for tracking Cys levels in both an epilepsy model and real food samples.

SCN1A intronic variants impact on Nav1.1 protein expression and sodium channel function, and associated with epilepsy phenotypic severity.

High-throughput sequencing has identified numerous intronic variants in the SCN1A gene in epilepsy patients. Abnormal mRNA splicing caused by these variants can lead to significant phenotypic differences, but the mechanisms of epileptogenicity and phenotypic differences remain unknown. Two variants, c.4853-1 G>C and c.4853-25 T>A, were identified in intron 25 of SCN1A, which were associated with severe Dravet syndrome (DS) and mild focal epilepsy with febrile seizures plus (FEFS+), respectively. The impact of these variants on protein expression, electrophysiological properties of sodium channels and their correlation with epilepsy severity was investigated through plasmid construction and transfection based on the aberrant spliced mRNA. We found that the expression of truncated mutant proteins was significantly reduced on the cell membrane, and retained in the cytoplasmic endoplasmic reticulum. The mutants caused a decrease in current density, voltage sensitivity, and an increased vulnerability of channel, leading to a partial impairment of sodium channel function. Notably, the expression of DS-related mutant protein on the cell membrane was higher compared to that of FEFS+-related mutant, whereas the sodium channel function impairment caused by DS-related mutant was comparatively milder than that caused by FEFS+-related mutant. Our study suggests that differences in protein expression levels and altered electrophysiological properties of sodium channels play important roles in the manifestation of diverse epileptic phenotypes. The presence of intronic splice site variants may result in severe phenotypes due to the dominant-negative effects, whereas non-canonical splice site variants leading to haploinsufficiency could potentially cause milder phenotypes.

Genotype-driven therapeutics in DEE and metabolic epilepsy: navigating treatment efficacy and drug resistance.

Neonatal intensive care unit (NICU), particularly in treating developmental and epileptic encephalopathy (DEE) and metabolic epilepsy (ME), requires a deep understanding of their complex etiologies and treatment responses. After excluding treatable cases such as infectious or autoimmune encephalitis, our focus shifted to a more challenging subgroup of 59 patients for in-depth genetic analysis using exome sequencing (ES). The ES analysis identified 40 genetic abnormalities, significantly including de novo variants. Notably, we found structural variation as duplications in regions 2q24.3, including SCN1A and SCN2A were observed in 7 cases. These genetic variants, impacting ion channels, glucose transport, transcription regulation, and kinases, play a crucial role in determining medication efficacy. More than one-third (34.2%) of patients with DEE had an unfavorable response to anti-seizure medications (ASMs) in the chronic phase. However, since the ketogenic supplementary diet showed a positive effect, more than three-quarters (80%) of these drug-resistant patients improved during a 3-month follow-up. In contrast, the ME had a lower adverse reaction rate of 9.1% (2/22) to specialized medications, yet there were 5 fatalities and 10 cases with unidentified genetic etiologies. This study suggests the potential of categorizing drug-resistant variants and that a ketogenic diet could be beneficial in managing DEE and ME. It also opens new perspectives on the mechanisms of the ketogenic diet on the discovered genetic variants.

Pediatric peri-insular hemispherotomy and functional hemispherectomy for severe medically refractory epilepsy: comparison of two techniques.

PURPOSE: Since it was first described in the 1970s, functional hemispherotomy has been an essential tool in treating disabling, medically refractory epilepsy resulting from diffuse unilateral hemispheric disease. We report our experience with 23 patients who underwent hemispherotomy, both using the functional hemispherotomy (FH) as well as a modified peri-insular hemispherotomy (PIH) technique. We present the surgical technique for the latter, review outcomes following disconnection surgery and discuss the differences between the techniques when it comes to complications and postoperative results. METHODS: A retrospective study of 23 patients with refractory seizures who underwent cerebral hemispherectomy. A thorough analysis of the clinical, imaging, surgical features and postoperative results was performed. We also present the surgical technique for a modified PIH technique. RESULTS: Between 2000 and 2020, 23 pediatric patients with refractory seizures underwent hemispherotomy (12 FHs, 11 modified PIHs). 91.3% of patients were seizure free at 6 months, 87% at 1 year, and 78.3% at last follow-up. None of the 23 patients presented Engel IV outcome. FH was found to have statistically longer surgical duration (5 ± 1.5 vs. 3.83 ± 0.5 h; p = <0.001). Neurocognition was improved in two thirds of the patients (66.9%). Our study also shows improvement of motor activity in the majority of the patients, regardless of the pathology and surgical technique. In the present report we modified the Cook et al. technique by implementing an amygdalohippocampectomy with resection of the tail of the hippocampus posteriorly and medially, to achieve temporo-occipital disconnection, instead of a complete temporal lobectomy. CONCLUSION: When patients are wisely selected, the hemispherectomy procedure should be considered as a most attractive and curative treatment for children with refractory seizures, not only giving the patient a high chance of seizure freedom but also providing an improvement in motor and cognitive skills. In our particular case and based on the present study, the modified PIH proves to be a highly effective technique. It not only has a shorter surgical time but also a very low complication rate.

Novel technique of switching TIVA and sevoflurane during epilepsy surgery for combined intraoperative motor evoked potentials monitoring and electrocorticography: an illustrative case report.

BACKGROUND: During epilepsy surgery, it is equally important to record electrocorticography (ECoG) for detecting epileptogenic activity and guiding brain resection, and to evaluate neuromonitoring data, particularly motor evoked potentials (MEP), for avoidance of postoperative neurological complications. However, sevoflurane, which is commonly used during recording of ECoG, may attenuate the MEP response. It enforces anesthesiologists and neurosurgeons to select one anesthetic agent over another, facilitating either ECoG or MEP monitoring. CASE PRESENTATION: In the presented case of a 20-year-old man, who underwent surgery for temporal lobe epilepsy, a novel technique of neuroanesthesia was introduced, integrating initial induction of the total intravenous anesthesia (TIVA) with propofol (effect-site concentration, 2.3-3.0 µg/ml), its subsequent switching to sevoflurane (end-tidal concentration, 2.5%) for ECoG recording, and further change back to TIVA for MEP monitoring during brain resection. CONCLUSIONS: Intraoperative switch of anesthetic agents according to specific intraoperative requirements may be useful for cases of brain surgery requiring both ECoG recordings and MEP monitoring.

Impact of being a relative of a patient with epilepsy on the association of attitudes toward epilepsy and disease knowledge levels.

OBJECTIVE: The social prognosis for individuals with epilepsy is often poorer than their clinical prognosis, highlighting the significant influence of social factors on the progression of the disease. Relatives of patients with epilepsy (RPEs) generally have more positive attitudes towards epilepsy compared to the general population. This study aimed to examine the effect of being an RPE on the relationship between attitudes toward epilepsy and levels of disease knowledge. METHODS: This cross-sectional analytical study included 217 adult participants, comprising 93 RPEs and 124 controls (non-RPEs), selected through convenience sampling. Data were collected via face-to-face interviews using a questionnaire that included sections on socio-demographic characteristics, the Epilepsy Knowledge Scale, and the Public Attitudes Toward Epilepsy (PATE) Scale. Path analysis was conducted using the Maximum Likelihood method. Due to the non-normal distribution of exogenous variables, the robust Huber/White/sandwich estimator method was used to calculate confidence intervals and fit indices. RESULTS: The mean age of the participants was 34.7 ± 11.5 years, with 128 (59.0 %) being female. RPEs scored an average of 26.8 ± 9.9 on the PATE Scale, which was significantly lower than the average score of 29.7 ± 11.0 for non-RPEs (p = 0.047). Path analysis indicated that being an RPE indirectly fosters a positive attitude through increased knowledge levels. While the direct effect of being an RPE on attitudes was not statistically significant, the indirect effect mediated by knowledge was significant. SIGNIFICANCE: This study highlights that the level of knowledge about epilepsy, a key predictor of positive attitudes, remains important even among RPEs. In kinship contexts where neurobiological and psychosocial factors are at play, the primary determinant of attitudes toward epilepsy is still the level of knowledge about the condition. Consequently, focusing on increasing knowledge about epilepsy should be the main strategy to promote positive attitudes, providing a more promising avenue for future research and interventions.

Modification of pre-ictal cortico-hippocampal oscillations by medial ganglionic eminence precursor cells grafting in the pilocarpine model of epilepsy.

Cell replacement therapies using medial ganglionic eminence (MGE)-derived GABAergic precursors reduce seizures by restoring inhibition in animal models of epilepsy. However, how MGE-derived cells affect abnormal neuronal networks and consequently brain oscillations to reduce ictogenesis is still under investigation. We performed quantitative analysis of pre-ictal local field potentials (LFP) of cortical and hippocampal CA1 areas recorded in vivo in the pilocarpine rat model of epilepsy, with or without intrahippocampal MGE-precursor grafts (PILO and PILO+MGE groups, respectively). The PILO+MGE animals had a significant reduction in the number of seizures. The quantitative analysis of pre-ictal LFP showed decreased power of cortical and hippocampal delta, theta and beta oscillations from the 5 min. interictal baseline to the 20 s. pre-ictal period in both groups. However, PILO+MGE animals had higher power of slow and fast oscillations in the cortex and lower power of slow and fast oscillations in the hippocampus compared to the PILO group. Additionally, PILO+MGE animals exhibited decreased cortico-hippocampal synchrony for theta and gamma oscillations at seizure onset and lower hippocampal CA1 synchrony between delta and theta with slow gamma oscillations compared to PILO animals. These findings suggest that MGE-derived cell integration into the abnormally rewired network may help control ictogenesis.

Aprepitant's roles in abating seizures, behavioral, and cognitive deficits in mice model of epilepsy.

BACKGROUND: Aprepitant (APR), a neurokinin 1 receptor antagonist, is an approved drug for treating chemotherapy-induced nausea and vomiting. OBJECTIVES: Investigate the beneficial roles of APR alone or in combination with sodium valproate (VPA) against lithium pilocarpine [li-pilo]-induced seizures, behavioral changes, and cognitive deficits. METHODS: Thirty male mice were divided into five groups, each containing 6. "Vehicle Group I," "Control Group II "li-pilo, " Valproate (VPA) group III (400 mg/kg/i.p.), "APR group IV, " and "Combination Group V." Videos of mice were recorded, and they were watched for episodes of spontaneous recurring seizures (SRS). Behavioral Tests were performed. At the end of the study, animal brains were taken for biochemical assays and gene expression studies. RESULTS: APR partially protected against SRS with partial restoration of average behavioral and standard cognitive skills associated with a significant increase in brain SOD activity and a significant decrease in MDA, IL-1ß, NF-КB, and SP-3 levels in relation to the control group. Interestingly, a combination of APR with VPA in epileptic mice showed complete protection against li-pilo-induced behavioral changes and cognitive deficits, a significant increase in brain SOD activity, and a considerable decrease in MDA, IL-1ß, NF-ΚB, and SP levels to normal. CONCLUSION: Using APR as an adjuvant to VPA is more effective in protecting against li-pilo-induced seizures, behavioral changes, and cognitive deficits due to its antioxidant, anti-inflammatory, and NK1 antagonist effects than using APR alone as drug therapy.

Association of reductions in rescue medication requirements with vagus nerve stimulation: Results of long-term community collected data from a seizure diary app.

OBJECTIVE: To assess the impact of vagus nerve stimulation (VNS) on quality of life contributors such as rescue medications. METHODS: Using the seizure diary application SeizureTracker™ database, we examined trends in rescue administration frequency before and after the first recorded VNS magnet swipe in patients with drug-resistant epilepsy who had 1) At least one VNS magnet swipe recorded in the diary, and 2) Recorded usage of a benzodiazepine rescue medication (RM) within 90 days prior to the first swipe. A paired Wilcoxon rank-sum test was used to assess changes in RM usage frequency between 30-, 60-, 90-, 180- and 360-day intervals beginning 30 days after first magnet swipe. Longitudinal changes in RM usage frequency were assessed with a generalized estimating equation model. RESULTS: We analyzed data of 95 patients who met the inclusion criteria. Median baseline seizure frequency was 8.3 seizures per month, with median baseline rescue medication usage frequency of 2.1 administrations per month (SD 3.3). Significant reductions in rescue medication usage were observed in the 91 to 180 day interval after first VNS magnet swipe, and at 181 to 360 days and at 361 to 720 days, with the magnitude of reduction increasing over time. Decreases in rescue medication usage were sustained when controlling for patients who did not record rescue medication use after the first VNS magnet swipe (N=91). Significant predictors of reductions in rescue medication included baseline frequency of rescue medication usage and time after first VNS magnet swipe. SIGNIFICANCE: This retrospective analysis suggests that usage of rescue medications is reduced following the start of VNS treatment in patients with epilepsy, and that the magnitude of reduction may progressively increase over time.

Ayurveda therapy in the management of epilepsy.

Epilepsy, a chronic non-communicable disease of the brain, is one of the most common neurological diseases globally that affects people of all ages. The existence of medical, neurological, psychiatric, and cognitive comorbidities has always undermined the available advanced treatment strategies for epilepsy. New-generation antiepileptic drugs being less successful in completely controlling the seizures and observance of complex diseases, including drug-resistant cases, have provided scope for integrating and incorporating the therapeutic modalities of Ayurveda, the ancient Indian art of holistic medicine, in the effective management of epilepsy. Epilepsy can be correlated to Apasmara, described in the classics of Ayurveda as the transient appearance of unconsciousness with loathsome expression due to derangement of memory, intelligence, and mind. The multifaceted therapeutic approach of Ayurveda, which involves pharmacologic and nonpharmacologic measures, purificatory and pacifying procedures, herbal and herbo-mineral formulations, disease, and host-specific approaches, have enhanced the potential of not only relieving symptoms but also modifying the pathophysiology of the disease. Newer paradigms of research in Ayurveda, along with holistic and integrative approaches with contemporary medicine, can not only benefit the existing healthcare system but also impact future healthcare management in epileptology research. This cursory literature review is an earnest attempt to identify, evaluate, and summarize various studies and provide a comprehensive insight into the potential of Ayurveda in understanding and treating epilepsy.

Unravelling the critical role of neuroinflammation in epilepsy-associated neuropsychiatric comorbidities: A review.

Epilepsy is a complex neurological disorder characterized not only by seizures but also by significant neuropsychiatric comorbidities, affecting approximately one-third of those diagnosed. This review explores the intricate relationship between epilepsy and its associated psychiatric and cognitive disturbances, with a focus on the role of inflammation. Recent definitions of epilepsy emphasize its multifaceted nature, linking it to neurobiological, psychiatric, cognitive, and social deficits. Inflammation has emerged as a critical factor influencing both seizure activity and neuropsychiatric outcomes in epilepsy patients. This paper critically examines how dysregulated inflammatory pathways disrupt neurotransmitter transmission and contribute to depression, mood disorders, and anxiety prevalent among individuals with epilepsy. It also evaluates current therapeutic approaches and underscores the potential of anti-inflammatory therapies in managing epilepsy and related neuropsychiatric conditions. Additionally, the review highlights the importance of the anti-inflammatory effects of anti-seizure medications, antidepressants, and antipsychotics and their therapeutic implications for mood disorders. Also, the role of ketogenic diet in managing epilepsy and its psychiatric comorbidities is briefly presented. Furthermore, it briefly discusses the role of the gut-brain axis in maintaining neurological health and how its dysregulation is associated with epilepsy. The review concludes that inflammation plays a pivotal role in linking epilepsy with its neuropsychiatric comorbidities, suggesting that targeted anti-inflammatory interventions may offer promising therapeutic strategies. Future research should focus on longitudinal studies comparing outcomes between epileptic patients with and without neuropsychiatric comorbidities, the development of diagnostic tools, and the exploration of novel anti-inflammatory treatments to better manage these complex interactions.

Pervasive expostulation of p53 gene promoting the precipitation of neurogenic convulsions: A journey in therapeutic advancements.

Epilepsy, a neurological disorder characterized by prolonged and excessive seizures, has been linked to elevated levels of the tumor suppressor gene p53, which contributes to neuronal dysfunction. This review explores the molecular mechanisms of p53 in epilepsy and discusses potential future therapeutic strategies. Research indicates that changes in p53 expression during neuronal apoptosis, neuroinflammation, and oxidative stress play a significant role in the pathogenesis of epilepsy. Elevated p53 disrupts glutamatergic neurotransmission and hyperactivates NMDA and AMPA receptors, leading to increased neuronal calcium influx, mitochondrial oxidative stress, and activation of apoptotic pathways mediated neuronal dysfunction, exacerbating epileptogenesis. The involvement of p53 in epilepsy suggests that targeting this protein could be beneficial in mitigating neuronal damage and preventing seizure recurrence. Pharmacological agents like pifithrin-α have shown promise in reducing p53-mediated apoptosis and seizure severity. Gene therapy approaches, such as viral vector-mediated delivery of wild-type p53 or RNA interference targeting mutant p53, have also been effective in restoring normal p53 function and reducing seizure susceptibility. Despite these advances, the heterogeneous nature of epilepsy and potential long-term side effects of p53 modulation present challenges. Future research should focus on elucidating the precise molecular mechanisms of p53 and developing personalized therapeutic strategies. Modulating p53 activity holds promise for reducing seizure susceptibility and improving the quality of life for individuals with epilepsy. The current review provides the understanding the intricate role of p53 in neuroinflammatory pathways, including JAK-STAT, JNK, NF-κB, Sonic Hedgehog, and Wnt, is crucial for developing targeted therapies.

Structural brain characteristics of epilepsy patients with comorbid migraine without aura.

Migraine is a common bi-directional comorbidity of epilepsy, indicating potential complex interactions between the two conditions. However, no previous studies have used brain morphology analysis to assess possible interactions between epilepsy and migraine. Voxel-based morphometry (VBM), surface-based morphometry (SBM), and structural covariance networks (SCNs) can be used to detect morphological changes with high accuracy. We recruited 30 individuals with epilepsy and comorbid migraine without aura (EM), along with 20 healthy controls (HC) and 30 epilepsy controls (EC) without migraine. We used VBM, SBM, and SCN analysis to compare differences in gray matter volume, cortical thickness, and global level and local level graph theory indexes between the EM, EC, and HC groups to investigate structural brain changes in the EM patients. VBM analysis showed that the EM group had gray matter atrophy in the right temporal pole compared with the HC group (p < 0.001, false discovery rate correction [FDR]). Furthermore, the headache duration in the EM group was negatively correlated with the gray matter volume of the right temporal pole (p < 0.05). SBM analysis showed cortical atrophy in the left insula, left posterior cingulate gyrus, left postcentral gyrus, left middle temporal gyrus, and left fusiform gyrus in the EM compared with the HC group (p < 0.001, family wise error correction). We found a positive correlation between headache frequency and the cortical thickness of the left middle temporal gyrus (p < 0.05). SCN analysis revealed no differences in global parameters between the three groups. The area under the curve (AUC) of the nodal betweenness centrality in the right postcentral gyrus was lower in the EM group compared with the HC group (p < 0.001, FDR correction), and the AUC of the nodal degree in the right fusiform gyrus was lower in the EM group compared with the EC group (p < 0.001, FDR correction). We found clear differences in brain structure in the EM patients compared with the HC group. Accordingly, migraine episodes may influence brain structure in epilepsy patients. Conversely, abnormal brain structure may be an important factor in the development of epilepsy with comorbid migraine without aura. Further studies are needed to investigate the role of brain structure in individuals with epilepsy and comorbid migraine without aura.

Rate of Breastfeeding Initiation and Continuation in Patients with Epilepsy: Study from a Tertiary Care Center in Makkah.

Objective: The aim of this study was to assess the rate of breastfeeding initiation and continuation among women with epilepsy treated in a tertiary care center in the Makkah region. Methods: All women with epilepsy treated in the epilepsy clinic at King Abdullah Medical City from 2019 to June 2023 were interviewed by phone. Data collected included patients' demographics, type and control of epilepsy, number of antiseizure medications (ASMs), and obstetric history. Results: Forty-eight patients were included in the study. A total of 32 (66.7%) were more than 30 years old, and 41 (85.4%) were from urban areas. A total of 22 (45.8%) received only one antiepileptic drug, 18 (37.5%) received two drugs, and 8 (16.7%) received three or more drugs. The majority (68.6%) of patients practiced breastfeeding. Breastfeeding lasted 6 months or longer for 12.1% of mothers. Bottle feeding was needed for 72.9% of patients. Breastfeeding was reported by significantly more patients (73.2%) from urban areas versus 42.9% of those from rural areas (P = 0.043). Also, 81.8% of patients on one ASM practiced breastfeeding, compared to 62.5% on more than two ASMs (P = 0.048). Other significant factors related to breastfeeding were not having a seizure during pregnancy (81.8%-57.7%, P = 0.049) and a normal vaginal delivery (81.3%-43.8%, P = 0.008). Conclusion: The rate of breastfeeding among women with epilepsy in the Makkah region is low. Several factors, including the number of ASMs, seizure control during pregnancy, spontaneous vaginal delivery, and being from an urban area, were significantly related to breastfeeding behavior among these women.

Evaluating depression in Indonesian adolescents with epilepsy: Comprehensive validation and reliability assessment of the neurological disorders depression inventory-epilepsy for youth Indonesian version (NDDI-E-Y[ID]).

OBJECTIVES: Epilepsy is a common chronic neurological disorder in pediatrics. Depression is an often underdetected comorbidity in childhood epilepsy. This study aimed to adapt the Neurological Disorders Depression Inventory-Epilepsy for Youth (NDDI-E-Y) to the Indonesian language and population, as well as to validate the Indonesian version of NDDI-E-Y (NDDI-E-Y[ID]). METHODS: This three-stage study comprised instrument translation, cultural verification, and content validity testing (first stage), pilot testing (second stage), followed by concurrent validity and reliability testing (third stage) of the NDDI-E-Y(ID). Validation was done against the Centre for Epidemiologic Studies Depression Scale - Revised (CESD-R). Content validity, assessed by six experts, was quantified using the content validity index for items (I-CVI) and scale (S-CVI). Participants were adolescents aged 12-17 years diagnosed with any type of epilepsy who completed both instruments. Concurrent validity was evaluated using Spearman's correlation and reliability was measured using Cronbach's alpha. RESULTS: The first stage produced a culturally appropriate NDDI-E-Y(ID). Thirty healthy adolescents and 10 adolescents with epilepsy participated in the second stage. In the third stage, another group of 30 adolescents with epilepsy took part. We obtained I-CVI and S-CVI values averaging 1. The NDDI-E-Y(ID) showed a positive and significant correlation with CESD-R (Spearman's rho = 0.671, p < 0.001). A Cronbach's alpha of 0.928 reflected a high internal consistency. SIGNIFICANCE: Based on the results, the NDDI-E-Y(ID) was found to be a valid and reliable screening instrument for detecting depression in youth with epilepsy. PLAIN LANGUAGE SUMMARY: Depression is an under-recognized problem in youth with epilepsy. Currently available depression screening tools are in English, making it less suitable for detection purposes in Indonesia. This study developed and validated the Indonesian version of the NDDI-E-Y, a depression screening tool for youth with epilepsy.

User involvement in the design and development of medical devices in epilepsy: A systematic review.

OBJECTIVE: This systematic review aims to describe the involvement of persons with epilepsy (PWE), healthcare professionals (HP) and caregivers (CG) in the design and development of medical devices is epilepsy. METHODS: A systematic review was conducted, adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eligibility criteria included peer-reviewed research focusing on medical devices for epilepsy management, involving users (PWE, CG, and HP) during the MDD process. Searches were performed on PubMed, Web of Science, and Scopus, and a total of 55 relevant articles were identified and reviewed. RESULTS: From 1999 to 2023, there was a gradual increase in the number of publications related to user involvement in epilepsy medical device development (MDD), highlighting the growing interest in this field. The medical devices involved in these studies encompassed a range of seizure detection tools, healthcare information systems, vagus nerve stimulation (VNS) and electroencephalogram (EEG) technologies reflecting the emphasis on seizure detection, prediction, and prevention. PWE and CG were the primary users involved, underscoring the importance of their perspectives. Surveys, usability testing, interviews, and focus groups were the methods used for capturing user perspectives. User involvement occurs in four out of the five stages of MDD, with production being the exception. SIGNIFICANCE: User involvement in the MDD process for epilepsy management is an emerging area of interest holding a significant promise for improving device quality and patient outcomes. This review highlights the need for broader and more effective user involvement, as it currently lags in the development of commercially available medical devices for epilepsy management. Future research should explore the benefits and barriers of user involvement to enhance medical device technologies for epilepsy. PLAIN LANGUAGE SUMMARY: This review covers studies that have involved users in the development process of medical devices for epilepsy. The studies reported here have focused on getting input from people with epilepsy, their caregivers, and healthcare providers. These devices include tools for detecting seizures, stimulating nerves, and tracking brain activity. Most user feedback was gathered through surveys, usability tests, interviews, and focus groups. Users were involved in nearly every stage of device development except production. The review highlights that involving users can improve device quality and patient outcomes, but more effective involvement is needed in commercial device development. Future research should focus on the benefits and challenges of user involvement.

Limited cerebellar gradient extension in temporal lobe epilepsy with dystonic posturing.

OBJECTIVE: Dystonic posturing (DP) is a common semiology in temporal lobe epilepsy (TLE). We aimed to explore cerebellar gradient alterations in functional connectivity in TLE patients with and without DP. METHODS: Resting-state functional MRI data were obtained in 60 TLE patients and 32 matched healthy controls. Patients were further divided into two groups: TLE with DP (TLE + DP, 31 patients) and TLE without DP (TLP-DP, 29 patients). We explored functional gradient alterations in the cerebellum based on cerebellar-cerebral functional connectivity and combined with independent component analysis to evaluate cerebellar-cerebral functional integration and reveal the contribution of the motor components to the gradient. RESULTS: There were no obvious differences in clinical features and postoperative seizure outcomes between TLE + DP and TLE-DP patients. Patients and controls all showed a clear unimodal-to-transmodal gradient transition in the cerebellum, while TLE patients demonstrated an extended principal gradient in functional connectivity compared to healthy controls, which was more limited in TLE + DP patients. Gradient alterations were more widespread in TLE-DP patients, involving bilateral cerebellum, while gradient alterations in TLE + DP patients were limited in the cerebellum ipsilateral to the seizure focus. In addition, more cerebellar motor components contributed to the gradient alterations in TLE + DP patients, mainly in ipsilateral cerebellum. SIGNIFICANCE: Extended cerebellar principal gradients in functional connectivity revealed excessive functional segregation between unimodal and transmodal systems in TLE. The functional connectivity gradients were more limited in TLE + DP patients. Functional connectivity in TLE patients with dystonic posturing involved more contribution of cerebellar motor function to ipsilateral cerebellar gradient. PLAIN LANGUAGE SUMMARY: Dystonic posturing contralateral to epileptic focus is a common symptom in temporal lobe epilepsy, and the cerebellum may be involved in its generation. In this study, we found cerebellar gradients alterations in functional connectivity in temporal lobe epilepsy patients with and without contralateral dystonic posturing. In particular, we found that TLE patients with dystonic posturing may have more limited cerebellar gradient in functional connectivity, involving more contribution of cerebellar motor function to ipsilateral cerebellar gradient. Our study suggests a close relationship between ipsilateral cerebellum and contralateral dystonic posturing.

A multicultural comparative study of self-stigma in epilepsy: Differences across four cultures.

OBJECTIVE: Epilepsy is a neurological disorder characterized by recurrent seizures, exhibiting variance in prevalence and treatment availability across diverse geopolitical contexts and cultural milieus. The stigma associated with epilepsy is a significant global issue affecting the quality of life (QOL) of people with epilepsy (PWE). This study aims to examine the relationship between self-stigma and depressive symptoms in PWE, with a particular emphasis on understanding the manifestations of these across different cultural contexts. We aim to enhance the provision of customized care to diverse cultural settings, fostering the adoption of healthier lifestyles for PWE. METHODS: We recruited PWE who received treatment at specialized medical facilities for epilepsy in Japan, Malaysia (Chinese, Malay), and Turkey from February to October 2023. The Epilepsy Self-Stigma Scales (ESSS), Neurological Disorders Depression Inventory for Epilepsy (NDDI-E), and Generalized Anxiety Disorder 7 (GAD-7) in local languages were used to assess self-stigma, depressive symptoms, and anxiety. RESULTS: The ESSS total scores were significantly higher among the Turkish and Japanese cohorts (F [3, 406] = 6.57, p < 0.001, η2 = 0.05). In addition, the self-stigma observed moderate positive correlations for depressive symptoms (rs = 0.41-0.50, Ps < 0.001) and anxiety (rs = 0.42-0.44, Ps < 0.001). The ANCOVA findings suggested that the notable variations in self-stigma, as found in the one-way ANOVA conducted across four cultures, were reduced when taking into consideration depressed symptoms. Our finding highlights the potential influence of mental health factors over cultural factors concerning self-stigma. SIGNIFICANCE: The manifestation of self-stigmatization within epilepsy exhibits distinctions across diverse cultural cohorts, regardless of the demographic and clinical variation, yet demonstrates a significant correlation with psychological factors. In subsequent research endeavors, we should comprehensively investigate these subtle differences, their potential impact on patient care, and the development of supportive approaches. PLAIN LANGUAGE SUMMARY: This cross-cultural study reveals significant variations in self-stigma among people with epilepsy across different cultural contexts, with Turkish and Japanese cohorts showing higher levels. Self-stigma demonstrated moderate positive correlations with depressive symptoms and anxiety across all cultures. Notably, differences in self-stigma were reduced when accounting for depressive symptoms, suggesting that mental health factors may have a stronger influence than cultural factors. These findings underscore the importance of considering both cultural and psychological aspects in developing targeted interventions to address self-stigma in epilepsy care.