Clinical effectiveness of the psychological therapy Mental Health Intervention for Children with Epilepsy in addition to usual care compared with assessment-enhanced usual care alone: a multicentre, randomised controlled clinical trial in the UK.

BACKGROUND: Mental health difficulties are common in children and young people with chronic health conditions, but many of those in need do not access evidence-based psychological treatments. The study aim was to evaluate the clinical effectiveness of integrated mental health treatment for children and young people with epilepsy, a common chronic health condition known to be associated with a particularly high rate of co-occurring mental health difficulties. METHODS: We conducted a parallel group, multicentre, open-label, randomised controlled trial of participants aged 3-18 years, attending epilepsy clinics across England and Northern Ireland who met diagnostic criteria for a common mental health disorder. Participants were randomised (1:1; using an independent web-based system) to receive the Mental Health Intervention for Children with Epilepsy (MICE) in addition to usual care, or assessment-enhanced usual care alone (control). Children and young people in both groups received a full diagnostic mental health assessment. MICE was a modular psychological intervention designed to treat common mental health conditions in children and young people using evidence-based approaches such as cognitive behaviour therapy and behavioural parenting strategies. Usual care for mental health disorders varied by site but typically included referral to appropriate services. Participants, along with their caregivers, and clinicians were not masked to treatment allocation but statisticians were masked until the point of analysis. The primary outcome, analysed by modified intention-to-treat, was the parent-report Strengths and Difficulties Questionnaire (SDQ) at 6 months post-randomisation. The study is complete and registered with ISRCTN (57823197). FINDINGS: 1401 young people were potentially deemed eligible for study inclusion. Following the exclusion of 531 young people, 870 participants were assessed for eligibility and completed the SDQ, and 480 caregivers provided consent for study inclusion between May 20, 2019, and Jan 31, 2022. Between Aug 28, 2019, and Feb 21, 2022, 334 participants (mean ages 10·5 years [SD 3·6] in the MICE group vs 10·3 [4·0] in control group at baseline) were randomly assigned to an intervention using minimisation balanced by age, primary mental health disorder, diagnosis of intellectual disability, and autistic spectrum disorder at baseline. 168 (50%) of the participants were female and 166 (50%) were male. 166 participants were randomly assigned to the MICE group and 168 were randomly assigned to the control group. At 6 months, the mean SDQ difficulties for the 148 participants in the MICE group was 17·6 (SD 6·3) and 19·6 (6·1) for the 148 participants in the control group. The adjusted effect of MICE was -1·7 (95% CI -2·8 to -0·5; p=0·0040; Cohen's d, 0·3). 14 (8%) patients in the MICE group experienced at least one serious adverse event compared with 24 (14%) in the control group. 68% percent of serious adverse events (50 events) were admission due to seizures. INTERPRETATION: MICE was superior to assessment-enhanced usual care in improving symptoms of emotional and behavioural difficulties in young people with epilepsy and common mental health disorders. The trial therefore shows that mental health comorbidities can be effectively and safely treated by a variety of clinicians, utilising an integrated intervention across ages and in the context of intellectual disability and autism. The evidence from this trial suggests that such a model should be fully embedded in epilepsy services and serves as a model for other chronic health conditions in young people. FUNDING: UK National Institute for Health Research Programme Grants for Applied Research programme and Epilepsy Research UK Endeavour Project Grant.

Health and Healthcare Disparities in Pediatric Epilepsy in the United States: A Scoping Review.

OBJECTIVES: Health disparities impact epilepsy care in children. Previous efforts to summarize data in this population have been limited. This study sought to understand how this information exists in the literature and identify gaps in knowledge. METHODS: A scoping review of peer-reviewed articles and gray literature was conducted using PRISMA guidelines. Disparity populations (e.g., Sex, Race/Ethnicity, Socioeconomic Status) and disparity outcomes (e.g., Quality of Life (QOL)/Psychological, Utilization, Mortality/Sudden Unexpected Death in Epilepsy) were identified. A finding was defined as a single result from a discrete statistical analysis of a specific clinical outcome by disparity population. Data extraction identified where this information existed in the literature and how it was reported. RESULTS: A total of 307 publications revealed 769 unique disparity/equity findings. Disparity populations were unequally represented (p < 0.0001). Sex and Race/Ethnicity had the most findings while Language/Immigration had the fewest. Nearly a quarter of findings (23%) addressed QOL/Psychological outcomes. The highest percentages of disparities were found in the Utilization, Mortality/SUDEP, and Economic categories. Of the 204 publications reporting disparity findings, fewer than half actually intended to investigate disparities as one of their original objectives. Of the disparity findings identified in peer-reviewed articles, a third were not mentioned in the abstract and 20% were not addressed in the discussion. INTERPRETATION: A comprehensive scoping review of health disparities in pediatric epilepsy found that specific disparity populations like Sex and Race/Ethnicity were robustly explored, while Language/Immigration was under-represented, despite a high rate of disparities. Health-related outcome categories were also unequally investigated. Disparity findings were often difficult to access within publications. ANN NEUROL 2024;95:733-742.

Long-Term Downregulation of the Sodium Channel Gene Scn8a Is Therapeutic in Mouse Models of SCN8A Epilepsy.

OBJECTIVE: De novo mutations of the voltage-gated sodium channel gene SCN8A cause developmental and epileptic encephalopathy (DEE). Most pathogenic variants result in gain-of-function changes in activity of the sodium channel Nav1.6, poorly controlled seizures, and significant comorbidities. In previous work, an antisense oligonucleotide (ASO) reduced Scn8a transcripts and increased lifespan after neonatal administration to a mouse model. Here, we tested long-term ASO treatment initiated after seizure onset, as required for clinical application. METHODS: ASO treatment was initiated after observation of a convulsive seizure and repeated at 4 to 6 week intervals for 1 year. We also tested the long-term efficacy of an AAV10-short hairpin RNA (shRNA) virus administered on P1. RESULTS: Repeated treatment with the Scn8a ASO initiated after seizure onset provided long-term survival and reduced seizure frequency during a 12 month observation period. A single treatment with viral shRNA was also protective during 12 months of observation. INTERPRETATION: Downregulation of Scn8a expression that is initiated after the onset of seizures is effective for long-term treatment in a model of SCN8A-DEE. Repeated ASO administration or a single dose of viral shRNA prevented seizures and extended survival through 12 months of observation. ANN NEUROL 2024;95:754-759.

Closed-loop stimulation in periods with less epileptiform activity drives improved epilepsy outcomes.

In patients with drug-resistant epilepsy, electrical stimulation of the brain in response to epileptiform activity can make seizures less frequent and debilitating. This therapy, known as closed-loop responsive neurostimulation (RNS), aims to directly halt seizure activity via targeted stimulation of a burgeoning seizure. Rather than immediately stopping seizures as they start, many RNS implants produce slower, long-lasting changes in brain dynamics that better predict clinical outcomes. Here we hypothesize that stimulation during brain states with less epileptiform activity drives long-term changes that restore healthy brain networks. To test this, we quantified stimulation episodes during low- and high-risk brain states-that is, stimulation during periods with a lower or higher risk of generating epileptiform activity-in a cohort of 40 patients treated with RNS. More frequent stimulation in tonic low-risk states and out of rhythmic high-risk states predicted seizure reduction. Additionally, stimulation events were more likely to be phase-locked to prolonged episodes of abnormal activity for intermediate and poor responders when compared to super-responders, consistent with the hypothesis that improved outcomes are driven by stimulation during low-risk states. These results support the hypothesis that stimulation during low-risk periods might underlie the mechanisms of RNS, suggesting a relationship between temporal patterns of neuromodulation and plasticity that facilitates long-term seizure reduction.

Anti-seizure gene therapy for focal cortical dysplasia.

Focal cortical dysplasias are a common subtype of malformation of cortical development, which frequently presents with a spectrum of cognitive and behavioural abnormalities as well as pharmacoresistant epilepsy. Focal cortical dysplasia type II is typically caused by somatic mutations resulting in mammalian target of rapamycin (mTOR) hyperactivity, and is the commonest pathology found in children undergoing epilepsy surgery. However, surgical resection does not always result in seizure freedom, and is often precluded by proximity to eloquent brain regions. Gene therapy is a promising potential alternative treatment and may be appropriate in cases that represent an unacceptable surgical risk. Here, we evaluated a gene therapy based on overexpression of the Kv1.1 potassium channel in a mouse model of frontal lobe focal cortical dysplasia. An engineered potassium channel (EKC) transgene was placed under control of a human promoter that biases expression towards principal neurons (CAMK2A) and packaged in an adeno-associated viral vector (AAV9). We used an established focal cortical dysplasia model generated by in utero electroporation of frontal lobe neural progenitors with a constitutively active human Ras homolog enriched in brain (RHEB) plasmid, an activator of mTOR complex 1. We characterized the model by quantifying electrocorticographic and behavioural abnormalities, both in mice developing spontaneous generalized seizures and in mice only exhibiting interictal discharges. Injection of AAV9-CAMK2A-EKC in the dysplastic region resulted in a robust decrease (∼64%) in the frequency of seizures. Despite the robust anti-epileptic effect of the treatment, there was neither an improvement nor a worsening of performance in behavioural tests sensitive to frontal lobe function. AAV9-CAMK2A-EKC had no effect on interictal discharges or behaviour in mice without generalized seizures. AAV9-CAMK2A-EKC gene therapy is a promising therapy with translational potential to treat the epileptic phenotype of mTOR-related malformations of cortical development. Cognitive and behavioural co-morbidities may, however, resist an intervention aimed at reducing circuit excitability.

A tool for monitoring cell type-specific focused ultrasound neuromodulation and control of chronic epilepsy.

Focused ultrasound (FUS) is a powerful tool for noninvasive modulation of deep brain activity with promising therapeutic potential for refractory epilepsy; however, tools for examining FUS effects on specific cell types within the deep brain do not yet exist. Consequently, how cell types within heterogeneous networks can be modulated and whether parameters can be identified to bias these networks in the context of complex behaviors remains unknown. To address this, we developed a fiber Photometry Coupled focused Ultrasound System (PhoCUS) for simultaneously monitoring FUS effects on neural activity of subcortical genetically targeted cell types in freely behaving animals. We identified a parameter set that selectively increases activity of parvalbumin interneurons while suppressing excitatory neurons in the hippocampus. A net inhibitory effect localized to the hippocampus was further confirmed through whole brain metabolic imaging. Finally, these inhibitory selective parameters achieved significant spike suppression in the kainate model of chronic temporal lobe epilepsy, opening the door for future noninvasive therapies.

Black Phosphorus Flake-Enabled Wireless Neuromodulation for Epilepsy Treatment.

Epilepsy is a prevalent and severe neurological disorder and generally requires prolonged electrode implantation and tether brain stimulation in refractory cases. However, implants may cause potential chronic immune inflammation and permanent tissue damage due to material property mismatches with soft brain tissue. Here, we demonstrated a nanomaterial-enabled near-infrared (NIR) neuromodulation approach to provide nongenetic and nonimplantable therapeutic benefits in epilepsy mouse models. Our study showed that crystal-exfoliated photothermal black phosphorus (BP) flakes could enhance neural activity by altering the membrane capacitive currents in hippocampus neurons through NIR photothermal neuromodulation. Optical stimulation facilitated by BP flakes in hippocampal slices evoked action potentials with a high spatiotemporal resolution. Furthermore, BP flake-enabled NIR neuromodulation of hippocampus neural circuits can suppress epileptic signals in epilepsy model mice with minimal invasiveness and high biocompatibility. Consequently, nanomaterial-enabled NIR neuromodulation may open up opportunities for nonimplantable optical therapy of epilepsy in nontransgenic organisms.

Low-frequency stimulation in the zona incerta attenuates seizure via driving GABAergic neuronal activity.

BACKGROUND: Managing refractory epilepsy presents a significant a substantial clinical challenge. Deep brain stimulation (DBS) has emerged as a promising avenue for addressing refractory epilepsy. However, the optimal stimulation targets and effective parameters of DBS to reduce seizures remian unidentified. OBJECTIVES: This study endeavors to scrutinize the therapeutic potential of DBS within the zona incerta (ZI) across diverse seizure models and elucidate the associated underlying mechanisms. METHODS: We evaluated the therapeutic potential of DBS with different frequencies in the ZI on kainic acid (KA)-induced TLE model or M1-cortical seizures model, pilocarpine-induced M1-cortical seizure models, and KA-induced epilepsy model. Further, employing calcium fiber photometry combined with cell-specific ablation, we sought to clarified the causal role of ZI GABAergic neurons in mediating the therapeutic effects of DBS. RESULTS: Our findings reveal that DBS in the ZI alleviated the severity of seizure activities in the KA-induced TLE model. Meanwhile, DBS attenuated seizure activities in KA- or pilocarpine-induced M1-cortical seizure model. In addition, DBS exerts a mitigating influence on KA induced epilepsy model. DBS in the ZI showed anti-seizure effects at low frequency spectrum, with 5 Hz exhibiting optimal efficacy. The low-frequency DBS significantly increased the calcium activities of ZI GABAergic neurons. Furthermore, selective ablation of ZI GABAergic neurons with taCasp3 blocked the anti-seizure effect of low-frequency DBS, indicating the anti-seizure effect of DBS is mediated by the activation of ZI GABAergic neurons. CONCLUSION: Our results demonstrate that low-frequency DBS in the ZI attenuates seizure via driving GABAergic neuronal activity. This suggests that the ZI represents a potential DBS target for treating both hippocampal and cortical seizure through the activation of GABAergic neurons, thereby holding therapeutic significance for seizure treatment.

Association between care experience and mental health hospitalisation among children in Scotland, with a focus on chronic conditions (CHiCS): a population-wide longitudinal study using administrative data.

BACKGROUND: Chronic conditions in children are associated with an increased risk of mental health problems. However, not much is known about the nature of this association among care experienced children. We explore the association between three chronic conditions (epilepsy, asthma, and diabetes) and mental health hospitalisation in children with or without care experience. METHODS: The Children's Health in Care in Scotland (CHiCS) is a population-wide longitudinal study that links health and social care data for 13 830 care-experienced children (6274 [45%] female, 7556 [55%] male) and 649 771 general population children (319 438 [49%] female, 330 333 [51%] male). Hospitalisations were followed up from birth between 1990 and 2004, up to July 31, 2016 (when children were aged 12-27 years). We used Cox proportional hazards models with age as timescale to estimate hazard ratios (HR) and 95% CIs for first mental health hospitalisation separately among care-experienced children and general population children. FINDINGS: Among general population children, 3152 (0·49%) children had epilepsy, 94 700 (14·57%) had asthma, and 5501 (0·85%) had diabetes. In comparison, among care-experienced children, 160 (1·16%) children had epilepsy, 2242 (16·21%) had asthma, and 142 (1·03%) had diabetes. Care-experienced children were more likely to have mental health hospitalisations than general population children, with 701 cases (5·1%) versus 5225 cases (0·8%), respectively. Among general population children, out of all three chronic conditions, epilepsy showed the highest risk (HR 2·61, 95% CI 2·20-3·09) for first mental health hospitalisation, followed by diabetes (1·93, 1·62-2·31), and asthma (1·25, 1·16-1·34). Among care-experienced children, asthma showed an HR of 1·43 (1·17-1·74) for first mental health hospitalisation, whereas epilepsy (1·33, 0·70-2·52) and diabetes (1·71, 0·96-3·05) had no association with first mental health hospitalisation in this subgroup. INTERPRETATION: The study highlights the associations between chronic conditions and risk of mental health hospitalisation among children with or without care experience. One limitation of the study is the small number of care experienced children with a chronic condition and mental health hospitalisation, which might have contributed to the lack of association found among care-experienced children between epilepsy and mental health, and diabetes and mental health. Nevertheless, one of its strengths is contributing to the limited knowledge regarding this association. FUNDING: Economic and Social Research Council, Medical Research Council, Scottish Government Chief Scientist Office.

Adult epilepsy.

Epilepsy is a common medical condition that affects people of all ages, races, social classes, and geographical regions. Diagnosis of epilepsy remains clinical, and ancillary investigations (electroencephalography, imaging, etc) are of aid to determine the type, cause, and prognosis. Antiseizure medications represent the mainstay of epilepsy treatment: they aim to suppress seizures without adverse events, but they do not affect the underlying predisposition to generate seizures. Currently available antiseizure medications are effective in around two-thirds of patients with epilepsy. Neurosurgical resection is an effective strategy to reach seizure control in selected individuals with drug-resistant focal epilepsy. Non-pharmacological treatments such as palliative surgery (eg, corpus callosotomy), neuromodulation techniques (eg, vagus nerve stimulation), and dietary interventions represent therapeutic options for patients with drug-resistant epilepsy who are not suitable for resective brain surgery.

Unraveling the Neural Circuits: Techniques, Opportunities and Challenges in Epilepsy Research.

Epilepsy, a prevalent neurological disorder characterized by high morbidity, frequent recurrence, and potential drug resistance, profoundly affects millions of people globally. Understanding the microscopic mechanisms underlying seizures is crucial for effective epilepsy treatment, and a thorough understanding of the intricate neural circuits underlying epilepsy is vital for the development of targeted therapies and the enhancement of clinical outcomes. This review begins with an exploration of the historical evolution of techniques used in studying neural circuits related to epilepsy. It then provides an extensive overview of diverse techniques employed in this domain, discussing their fundamental principles, strengths, limitations, as well as their application. Additionally, the synthesis of multiple techniques to unveil the complexity of neural circuits is summarized. Finally, this review also presents targeted drug therapies associated with epileptic neural circuits. By providing a critical assessment of methodologies used in the study of epileptic neural circuits, this review seeks to enhance the understanding of these techniques, stimulate innovative approaches for unraveling epilepsy's complexities, and ultimately facilitate improved treatment and clinical translation for epilepsy.

Potential merits and flaws of large language models in epilepsy care: A critical review.

The current pace of development and applications of large language models (LLMs) is unprecedented and will impact future medical care significantly. In this critical review, we provide the background to better understand these novel artificial intelligence (AI) models and how LLMs can be of future use in the daily care of people with epilepsy. Considering the importance of clinical history taking in diagnosing and monitoring epilepsy-combined with the established use of electronic health records-a great potential exists to integrate LLMs in epilepsy care. We present the current available LLM studies in epilepsy. Furthermore, we highlight and compare the most commonly used LLMs and elaborate on how these models can be applied in epilepsy. We further discuss important drawbacks and risks of LLMs, and we provide recommendations for overcoming these limitations.

Long-term physical and psychiatric morbidities and mortality of untreated, deferred, and immediately treated epilepsy.

OBJECTIVE: In Australia, 30% of newly diagnosed epilepsy patients were not immediately treated at diagnosis. We explored health outcomes between patients receiving immediate, deferred, or no treatment, and compared them to the general population. METHODS: Adults with newly diagnosed epilepsy in Western Australia between 1999 and 2016 were linked with statewide health care data collections. Health care utilization, comorbidity, and mortality at up to 10 years postdiagnosis were compared between patients receiving immediate, deferred, and no treatment, as well as with age- and sex-matched population controls. RESULTS: Of 603 epilepsy patients (61% male, median age = 40 years) were included, 422 (70%) were treated immediately at diagnosis, 110 (18%) received deferred treatment, and 71 (12%) were untreated at the end of follow-up (median = 6.8 years). Immediately treated patients had a higher 10-year rate of all-cause admissions or emergency department presentations than the untreated (incidence rate ratio [IRR] = 2.0, 95% confidence interval [CI] = 1.4-2.9) and deferred treatment groups (IRR = 1.7, 95% CI = 1.0-2.8). They had similar 10-year risks of mortality and developing new physical and psychiatric comorbidities compared with the deferred and untreated groups. Compared to population controls, epilepsy patients had higher 10-year mortality (hazard ratio = 2.6, 95% CI = 2.1-3.3), hospital admissions (IRR = 2.3, 95% CI = 1.6-3.3), and psychiatric outpatient visits (IRR = 3.2, 95% CI = 1.6-6.3). Patients with epilepsy were also 2.5 (95% CI = 2.1-3.1) and 3.9 (95% CI = 2.6-5.8) times more likely to develop a new physical and psychiatric comorbidity, respectively. SIGNIFICANCE: Newly diagnosed epilepsy patients with deferred or no treatment did not have worse outcomes than those immediately treated. Instead, immediately treated patients had greater health care utilization, likely reflecting more severe underlying epilepsy etiology. Our findings emphasize the importance of individualizing epilepsy treatment and recognition and management of the significant comorbidities, particularly psychiatric, that ensue following a diagnosis of epilepsy.

Development of an International Standard Set of Outcomes and Measurement Methods for Routine Practice for Adults with Epilepsy: The International Consortium for Health Outcomes Measurement Consensus Recommendations.

At present, there is no internationally accepted set of core outcomes or measurement methods for epilepsy clinical practice. Therefore, the International Consortium for Health Outcomes Measurement (ICHOM) convened an international working group of experts in epilepsy, people with epilepsy and their representatives to develop minimum sets of standardized outcomes and outcomes measurement methods for clinical practice that support patient-clinician decision-making and quality improvement. Consensus methods identified 20 core outcomes. Measurement tools were recommended based on their evidence of strong clinical measurement properties, feasibility, and cross-cultural applicability. The essential outcomes included many non-seizure outcomes: anxiety, depression, suicidality, memory and attention, sleep quality, functional status, and the social impact of epilepsy. The proposed set will facilitate the implementation of the use of patient-centered outcomes in daily practice, ensuring holistic care. They also encourage harmonization of outcome measurement, and if widely implemented should reduce the heterogeneity of outcome measurement, accelerate comparative research, and facilitate quality improvement efforts.

Global modified Delphi consensus on diagnosis, phenotypes, and treatment of SCN8A-related epilepsy and/or neurodevelopmental disorders.

OBJECTIVE: We aimed to develop consensus for diagnosis/management of SCN8A-related disorders. Utilizing a modified Delphi process, a global cohort of experienced clinicians and caregivers provided input on diagnosis, phenotypes, treatment, and management of SCN8A-related disorders. METHODS: A Core Panel (13 clinicians, one researcher, six caregivers), divided into three subgroups (diagnosis/phenotypes, treatment, comorbidities/prognosis), performed a literature review and developed questions for the modified Delphi process. Twenty-eight expert clinicians, one researcher, and 13 caregivers from 16 countries participated in the subsequent three survey rounds. We defined consensus as follows: strong consensus, ≥80% fully agree; moderate consensus, ≥80% fully/partially agree, <10% disagree; and modest consensus, 67%-79% fully/partially agree, <10% disagree. RESULTS: Early diagnosis is important for long-term clinical outcomes in SCN8A-related disorders. There are five phenotypes: three with early seizure onset (severe developmental and epileptic encephalopathy [DEE], mild/moderate DEE, self-limited (familial) infantile epilepsy [SeL(F)IE]) and two with later/no seizure onset (neurodevelopmental delay with generalized epilepsy [NDDwGE], NDD without epilepsy [NDDwoE]). Caregivers represented six patients with severe DEE, five mild/moderate DEE, one NDDwGE, and one NDDwoE. Phenotypes vary by age at seizures/developmental delay onset, seizure type, electroencephalographic/magnetic resonance imaging findings, and first-line treatment. Gain of function (GOF) versus loss of function (LOF) is valuable for informing treatment. Sodium channel blockers are optimal first-line treatment for GOF, severe DEE, mild/moderate DEE, and SeL(F)IE; levetiracetam is relatively contraindicated in GOF patients. First-line treatment for NDDwGE is valproate, ethosuximide, or lamotrigine; sodium channel blockers are relatively contraindicated in LOF patients. SIGNIFICANCE: This is the first-ever global consensus for the diagnosis and treatment of SCN8A-related disorders. This consensus will reduce knowledge gaps in disease recognition and inform preferred treatment across this heterogeneous disorder. Consensus of this type allows more clinicians to provide evidence-based care and empowers SCN8A families to advocate for their children.

Health care utilization of Hispanic/Latino veterans with epilepsy: A national population-based study.

OBJECTIVE: Hispanic/Latino people with epilepsy are a growing population that has been understudied in clinical epilepsy research. U.S. veterans are at a higher risk of epilepsy due to greater exposures including traumatic brain injury. Hispanic/Latino Veterans with Epilepsy (HL-VWEs) represent a growing population; however the treatment utilization patterns of this population have been vastly understudied. METHODS: HL-VWE were identified from administrative databases during fiscal year 2019. Variables compared between Hispanic and non-Hispanic VWEs included demographics, rurality, service era, utilization of clinical services/investigations, and service-connected injury. Chi-square and Student's t tests were used for comparisons. RESULTS: Among 56 556 VWEs, 3247 (5.7%) were HL. HL-VWEs were younger (59.2 vs 63.2 years; p < .01) and more commonly urban-dwelling (81.6% vs 63.2%, p < .01) compared to non-HL-VWEs. They were also more likely to have served in recent missions such as the Persian Gulf War and post- 9/11 wars (p < .01). HL-VWEs had a higher utilization of all neurology services examined including neurology clinic visits, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, electroencephalography (EEG), epilepsy monitoring, and comprehensive epilepsy care (p < .01 for all). HL-VWEs were more likely to visit an emergency room or have seizure-related hospitalizations (p < .01). HL-VWEs were more likely to have a service-connected disability greater or equal to 50% (p < .01). SIGNIFICANCE: This study is one of the largest cohorts examining HL-VWEs. We found higher utilization of services in neurology, epilepsy, and neuroimaging by HL-VWEs. HL-VWE are younger, more commonly urban-dwelling, and more likely to have served during recent combat periods and have higher amounts of service-connected disability. Given that the proportion of Hispanic veterans is projected to rise over time, more research is needed to provide the best interventions and mitigate the long-term impact of epilepsy on this diverse patient group.

Management of seizures in patients with primary mitochondrial diseases: consensus statement from the InterERNs Mitochondrial Working Group.

BACKGROUND AND PURPOSE: Primary mitochondrial diseases (PMDs) are common inborn errors of energy metabolism, with an estimated prevalence of one in 4300. These disorders typically affect tissues with high energy requirements, including heart, muscle and brain. Epilepsy may be the presenting feature of PMD, can be difficult to treat and often represents a poor prognostic feature. The aim of this study was to develop guidelines and consensus recommendations on safe medication use and seizure management in mitochondrial epilepsy. METHODS: A panel of 24 experts in mitochondrial medicine, pharmacology and epilepsy management of adults and/or children and two patient representatives from seven countries was established. Experts were members of five different European Reference Networks, known as the Mito InterERN Working Group. A Delphi technique was used to allow the panellists to consider draft recommendations on safe medication use and seizure management in mitochondrial epilepsy, using two rounds with predetermined levels of agreement. RESULTS: A high level of consensus was reached regarding the safety of 14 out of all 25 drugs reviewed, resulting in endorsement of National Institute for Health and Care Excellence guidelines for seizure management, with some modifications. Exceptions including valproic acid in POLG disease, vigabatrin in patients with γ-aminobutyric acid transaminase deficiency and topiramate in patients at risk for renal tubular acidosis were highlighted. CONCLUSIONS: These consensus recommendations describe our intent to improve seizure control and reduce the risk of drug-related adverse events in individuals living with PMD-related epilepsy.

Vagus nerve stimulation: Potential for treating chronic wounds.

Vagus nerve stimulation (VNS) has been approved as a treatment for various conditions, including drug-resistant epilepsy, migraines, chronic cluster headaches and treatment-resistant depression. It is known to have anti-inflammatory, anti-nociceptive and anti-adrenergic effects, and its therapeutic potential for diverse pathologies is being investigated. VNS can be achieved through invasive (iVNS) or non-invasive (niVNS) means, targeting different branches of the vagus nerve. iVNS devices require surgical implantation and have associated risks, while niVNS devices are generally better tolerated and have a better safety profile. Studies have shown that both iVNS and niVNS can reduce inflammation and pain perception in patients with acute and chronic conditions. VNS devices, such as the VNS Therapy System and MicroTransponder Vivistim, have received Food and Drug Administration approval for specific indications. Other niVNS devices, like NEMOS and gammaCore, have shown effectiveness in managing epilepsy, pain and migraines. VNS has also demonstrated potential in autoimmune disorders, such as rheumatoid arthritis and Crohn's disease, as well as neurological disorders like epilepsy and migraines. In addition, VNS has been explored in cardiovascular disorders, including post-operative atrial fibrillation and myocardial ischemia-reperfusion injury, and has shown positive outcomes. The mechanisms behind VNS's effects include the cholinergic anti-inflammatory pathway, modulation of cytokines and activation of specialised pro-resolving mediators. The modulation of inflammation by VNS presents a promising avenue for investigating its potential to improve the healing of chronic wounds. However, more research is needed to understand the specific mechanisms and optimise the use of VNS in wound healing. Ongoing clinical trials may support the use of this modality as an adjunct to improve healing.

Efficacy of rTMS for poststroke epilepsy and its effects on patients' cognitive function and depressive status.

OBJECTIVE: This study aimed to investigate the efficacy of rTMS in the treatment of poststroke epilepsy and the effect of rTMS on patients' cognitive function and depressive status. METHODS: One hundred and twenty-one poststroke epilepsy patients with mild cognitive impairment and depressive status admitted to the Department of Neurology of the Second People's Hospital of Nanning from January 1, 2017, to April 31, 2023, were selected and divided into the rTMS treatment group (treated group) and the control group. MMSE scores and HAMD scores were recorded before and after treatment. The frequency of EEG spiky waves recorded before and after treatment within 24 h and the frequency of any clinical seizure form (the number of clinical seizures within 1 month after treatment) and changes in observed indices before and after treatment were calculated. The differences between the data of the two groups were analyzed, to further assess the efficacy of rTMS in the treatment of poststroke epilepsy and the rTMS' effects on cognition and depression. RESULTS: Compared with drug treatment alone, rTMS significantly decreased clinical seizures and epileptiform discharges after stroke, especially in patients with lesions in the frontal, temporal, and parietal lobes. Compared with drug treatment alone, rTMS treatment can effectively reduce cognitive impairment and mood disorders, such as depression, especially for patients with lesions in the frontal and temporal lobes. The results of this experiment suggest that rTMS treatment does not increase adverse effects. CONCLUSION: rTMS reduces clinical seizures while improving cognitive impairment and depression in patients with epilepsy. Therefore, we suggest that low-frequency rTMS can be used as an adjunctive treatment for patients with epilepsy and provide some ideas and references for the treatment of epilepsy with cognitive impairment and depression.

Knowledge, attitudes, and practices of caregivers with children diagnosed with epilepsy attending a pediatric outpatient clinic: a descriptive, cross-sectional, questionnaire-based study in Addis Ababa, Ethiopia.

BACKGROUND: Caregivers' knowledge and attitudes influence help-seeking behavior and treatment decisions of patients with epilepsy, which in turn significantly impacts epilepsy care. In Ethiopia, epilepsy is often misunderstood, associated with misconceptions and accompanied by persistent negative attitudes. The objective of this study is to assess the knowledge, attitude, and practice of caregivers of children with epilepsy. METHODS: We conducted a hospital-based survey at the Yekatit 12 Hospital Pediatric Neurology Clinic, Addis Ababa, Ethiopia, between May and July 2022. We invited caregivers of children with epilepsy taking one or more daily anti-seizure medications to participate. Caregivers were invited to complete a structured questionnaire with guidance from a trained nurse to estimate knowledge and attitudes towards epilepsy and its treatment. Knowledge and attitudes were categorized as "good" and "favorable" (correct answers to ≥ 50% of questions) or "bad" and "unfavorable" (< 50% correct answers), respectively. Attitudes towards standard care versus non-standard (e.g., spiritual) care were also estimated. RESULTS: A total of 120 caregivers completed the questionnaire. Many caregivers were familiar with the term 'epilepsy', with more than half (51.7%) having heard or read about it previously. The reported causes of epilepsy varied, with birth injury being the most common cause (44 out of 120 caregivers). Notably, there was association between the caregiver's gender and their knowledge score, with a p-value = 0.05. Caregivers exposed to information about epilepsy through hearing or reading demonstrated significantly higher levels of knowledge, with a p-value < 0.001. Additionally, knowing someone with epilepsy other than the index child was significantly associated with higher knowledge scores (p-value < 0.001). The study also revealed negative attitudes toward epilepsy: for example, 56.7% of surveyed caregivers believed it is unlikely that a child with epilepsy has normal cognitive abilities and 39.1% believed they should never be allowed to attend regular school. Additionally, a high proportion of caregivers (70%) sought alternative treatments (e.g., spiritual help) alongside standard medical care. CONCLUSIONS: A significant knowledge gap was identified among caregivers, revealing prevalent misconceptions and negative attitudes. Improving epilepsy awareness, attitudes, and practices among caregivers will potentially contribute to overall improved quality of life for children with epilepsy.