Taiwan Chingguan Yihau (NRICM101) prevents kainic acid-induced seizures in rats by modulating neuroinflammation and the glutamatergic system (preprint)

Taiwan Chingguan Yihau (NRICM101) is a Traditional Chinese medicine (TCM) formula used to treat coronavirus disease 2019; however, its impact on epilepsy has not been revealed. Therefore, the present study evaluated the anti-epileptogenic effect of orally administered NRICM101 on kainic acid (KA)-induced seizures in rats and investigated its possible mechanisms of action. Sprague‒Dawley rats were administered NRICM101 (300 mg/kg) by oral gavage for 7 consecutive days before receiving an intraperitoneal injection of KA (15 mg/kg). NRICM101 considerably reduced the seizure behavior and electroencephalographic seizures induced by KA in rats. NRICM101 also significantly decreased the neuronal loss and glutamate increase and increased GLAST, GLT-1, GAD67, GDH and GS levels in the cortex and hippocampus of KA-treated rats. In addition, NRICM101 significantly suppressed astrogliosis (as determined by decreased GFAP expression); neuroinflammatory signaling (as determined by reduced HMGB1, TLR-4, IL-1β, IL-1R, IL-6, p-JAK2, p-STAT3, TNF-α, TNFR1 and p-IκB levels, and increased cytosolic p65-NFκB levels); and necroptosis (as determined by decreased p-RIPK3 and p-MLKL levels) in the cortex and hippocampus of KA-treated rats. The effects of NRICM101 were similar to those of carbamazepine, a well-recognized antiseizure drug. Furthermore, no toxic effects of NRICM101 on the liver and kidney were observed in NRICM101-treated rats. The results indicate that NRICM101 has antiepileptogenic and neuroprotective effects through the suppression of the inflammatory cues (HMGB1/TLR4, Il-1β/IL-1R1, IL-6/p-JAK2/p-STAT3, and TNF-α/TNFR1/NF-κB) and necroptosis signaling pathways (TNF-α/TNFR1/RIP3/MLKL) associated with glutamate level regulation in the brain and is innocuous. Our findings highlight the promising role of NRICM101 in the management of epilepsy.

The Human Microglia Atlas (HuMicA) Unravels Changes in Homeostatic and Disease-Associated Microglia Subsets across Neurodegenerative Conditions (preprint)

Dysregulated microglia activation, leading to neuroinflammation, is currently considered to be of major relevance in the development and progression of neurodegenerative diseases. The initial M1/M2 dual activation classification for microglia is now considered outdated. Even the "disease-associated microglia" (DAM) phenotype, firstly described in mice, has proven insufficient to precisely represent the multitude of microglia phenotypes in pathology. In this study, we have constructed a transcriptomic atlas of human brain immune cells by integrating single-nucleus (sn)RNA-seq datasets from multiple neurodegenerative conditions. Sixteen datasets were included, comprising 295 samples from patients with Alzheimer's disease, autism spectrum disorder, epilepsy, multiple sclerosis, Lewy body diseases, COVID-19, and healthy controls. The integrated Human Microglia Atlas (HuMicA) dataset included 60,557 nuclei and revealed 11 microglial subpopulations distributed across all pathological and healthy conditions. Among these, we identified four different homeostatic clusters as well as pathological phenotypes. These included two stages of early and late activation of the DAM phenotype and the disease-inflammatory macrophage (DIM) phenotype, which was recently described in mice, and is also present in human microglia, as indicated by our analysis. The high versatility of microglia is evident through changes in subset distribution across various pathologies, suggesting their contribution to the establishment of pathological phenotypes. Our analysis showed overall depletion of four substates of homeostatic microglia, and expansion of niche subpopulations within the DAM and DIM spectrum across distinct neurodegenerative pathologies. The HuMicA is an invaluable resource tool used to support further advances in the study of microglia biology through healthy and disease settings.

Epileptic seizure and electroencephalographic characteristics of adult COVID-19 inpatients during the Omicron outbreak in China: a single center retrospective study (preprint)

Background This retrospective analysis assessed the characteristics of epileptic seizure and continuous electroencephalogram (CEEG) data in hospitalized patients diagnosed with COVID-19 during the Omicron outbreak.Methods CEEG was performed in 28 patients, with 17 showing unexplained altered mental status and 11 suspected of having seizures. Demographic and clinical variables, imaging results, outcomes, and comorbidities were collected.Results In total, 1,405 patients with COVID-19 infection were admitted during the study period. The proportion of patients who required intensive care unit (ICU) care and the in-hospital mortality was 16.3% and 7.8%, respectively. Among patients who underwent CEEG monitoring, 11 were in ICU, and 17 were in regular wards. Of these, 8 patients (28.5%) had severe COVID-19, whereas 6 had acute neuroimaging findings. EEG findings were not specific, with 7 patients (25%) having normal EEG results. Furthermore, 11 (39.3%) had benign EEG alterations, 6 (21.4%) had malignant, and 4 (14.3%) had highly malignant. Six patients exhibited epileptiform abnormalities, including 1 with a prior epilepsy history. Moreover, 4 patients experienced electrographic seizures, with 2 manifesting as epilepsia partialis continua and 2 as nonconvulsive status epilepticus. Periodic and rhythmic patterns were observed in 2 patients, spike-and-wave in 1 patient and generalized rhythmic delta activity in another patient. EEG attenuation without reactivity was seen in 4 patients.Conclusions Seizures can manifest as early symptoms in individuals infected with the Omicron variant of COVID-19. Despite the increased contagiousness associated with Omicron, we observed a higher prevalence of normal EEG results. This suggested that the Omicron variant may be associated with a lower likelihood of causing encephalitis or encephalopathy compared to other variants.

Determining the role and responsibilities of the community epilepsy nurse in the management of epilepsy.

AIMS AND OBJECTIVES: The aim of this study is to enhance the understanding of the core elements and influencing factors on the community-based epilepsy nurse's role and responsibilities. BACKGROUND: Internationally, epilepsy nurse specialists play a key role in providing person-centred care and management of epilepsy but there is a gap in understanding of their role in the community. DESIGN: A national three-stage, mixed-method study was conducted. METHODS: One-on-one, in-depth semi-structured qualitative interviews were conducted online with 12 community-based epilepsy nurses (Stage 1); retrospective analysis of data collected from the National Epilepsy Line, a nurse-led community helpline (Stage 2); and focus group conducted with four epilepsy nurses, to delve further into emerging findings (Stage 3). A thematic analysis was conducted in Stages 1 and 3, and a descriptive statistical analysis of Stage 2 data. Consolidated Criteria for Reporting Qualitative studies checklist was followed for reporting. RESULTS: Three key themes emerged: (1) The epilepsy nurse career trajectory highlighted a lack of standardised qualifications, competencies, and career opportunities. (2) The key components of the epilepsy nurse role explored role diversity, responsibilities, and models of practice in the management of living with epilepsy, and experiences navigating complex fragmented systems and practices. (3) Shifting work practices detailed the adapting work practices, impacted by changing service demands, including COVID-19 pandemic experiences, role boundaries, funding, and resource availability. CONCLUSION: Community epilepsy nurses play a pivotal role in providing holistic, person-centred epilepsy management They contribute to identifying and addressing service gaps through innovating and implementing change in service design and delivery. RELEVANCE TO CLINICAL PRACTICE: Epilepsy nurses' person-centred approach to epilepsy management is influenced by the limited investment in epilepsy-specific integrated care initiatives, and their perceived value is impacted by the lack of national standardisation of their role and scope of practice. NO PATIENT OR PUBLIC CONTRIBUTION: Only epilepsy nurses' perspectives were sought.

Impacts of COVID-19 Pandemic on Seizure Control in Children with Epilepsy (preprint)

The coronavirus disease 2019 (COVID-19) pandemic has disrupted health care worldwide. As the pandemic has been prolonged, quarantine restrictions have been lightened gradu-ally, which can influence outcomes of pediatric patients with chronic disease such as epi-lepsy by increase of susceptibility of the COVID-19 infection. The aim of this study was to determine impacts of COVID-19 pandemic on seizure control and identify potential risk factors that might worsen seizure attacks during the pandemic in children with epilepsy. We performed a retrospective chart review of 48 pediatric patients with epilepsy during the COVID-19 pandemic from January 2016 to July 2022. During the COVID-19 pandemic period, 25% of pediatric patients experienced sei-zure worsening, showing an increase in seizure frequency or duration or both. Factors associated with worsening seizures during pandemic were: diagnosis of epi-lepsy less than one year, comorbid conditions with cerebral palsy or having a tracheosto-my or a PEG, and infection with other viruses (respiratory syncytial virus, influenza virus A, influenza virus B) rather than COVID-19 infection. Our finding highlights the need to proactively monitor and regularly follow up (es-pecially short period of time) patients after they are diagnosed with epilepsy. It is also important to properly manage those who are susceptible to serious illness and keep sea-sonal viral infections under surveillance to manage exacerbated seizure in children with epilepsy. Furthermore, pediatric physicians should not overlook surveillance of seasonal respiratory viruses since quarantine restrictions are getting eased.

Association of Seizure with COVID-19 Vaccines in Persons with Epilepsy: A Systematic Review and Meta-analysis (preprint)

Objective: Seizure following immunization, especially in persons with epilepsy (PwE), has long been a concern, and seizure aggravation followed by Coronavirus Disease 2019 (COVID-19) vaccines is a serious issue for PwE. The immunization rate in PwE has been lower compared to same-age controls due to vaccine hesitancy and concerns about seizure control. Herein, we systematically reviewed the seizure activity-related events in PwE following COVID-19 vaccination. Methods: Four search engines were searched from inception until January 31, 2023, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses was followed. Random- and fixed-effect models using the logit transformation method were used for meta-analysis. The quality of the studies was evaluated by the Newcastle-Ottawa scale. Outcomes of interest included (a) pooled proportion of increased seizure frequency and (b) pooled incidence proportion of status epilepticus (SE) in PwE receiving COVID-19 vaccines. Results: Of the 2207 studies identified, 18 met eligibility criteria, of which 16 entered the meta-analysis. The pooled proportion of increased seizure frequency (16 studies-4197 PwE) was 5% (95CI: 3%-6%, I2 =57%), further subcategorized into viral vector (3%, 95CI: 2%-7%, I2 =0%), mRNA (5%, 95CI: 4%-7%, I2 =48%), and inactivated (4%, 95CI: 2%-8%, I2 =77%) vaccines. The pooled incidence proportion of SE (15 studies-2480 PwE) was 0.08% (95CI: 0.02%-0.32%, I2 =0%), further subcategorized into the viral vector (0.00%, 95CI: 0.00%-1.00%, I2 =0%), mRNA (0.09%, 95CI: 0.01%-0.62%, I2 =0%), and inactivated (0.00%, 95CI: 0.00%-1.00%, I2 =0%) vaccines. No significant difference was observed between mRNA and viral vector vaccines (5 studies, 1122 vs. 198 PwE, respectively) regarding increased seizure frequency (OR: 1.10, 95CI: 0.49-2.50, p-value=0.81, I2 =0%). Significance: The meta-analysis proposed a 5% increased seizure frequency following COVID-19 vaccination in PwE, with no difference between mRNA and viral vector vaccines. Furthermore, we found a 0.08% incidence proportion for SE. While this safety evidence is noteworthy, this cost should be weighed against vaccination benefits.

Predictors of objective treatment adherence in adolescents with epilepsy: The important role of motivation.

OBJECTIVE: Adolescents with epilepsy are at heightened risk for suboptimal anti-seizure medication (ASM) adherence; however, there is a paucity of adherence interventions for this age group. The current study aimed to identify a comprehensive and novel set of predictors of objective, electronically-monitored ASM adherence in adolescents with epilepsy. METHODS: Participants included 104 adolescents (13-17 years old; M = 15.36 ± 1.40), diagnosed with epilepsy and their caregivers. Cross-sectional data were collected from adolescents, caregivers, healthcare providers, and medical chart reviews, including demographics (i.e., age, race/ethnicity, sex, insurance status), the COVID-19 pandemic (i.e., participation before versus during), seizure characteristics (i.e., presence and severity), ASM side effects (Pediatric Epilepsy Side Effects Questionnaire), adherence motivation (1-item 6-point Likert scale item), and adherence barriers (Pediatric Epilepsy Medication Self-Management Questionnaire). Electronically-monitored adherence data was collected via the AdhereTechTM pill bottle or the Vaica SimpleMedTM pillbox over 30 days. RESULTS: Adolescents demonstrated suboptimal adherence at 78 ± 31.6%, despite high ASM adherence motivation (M = 4.43 ± .94) and minimal adherence barriers (M = 35.64 ± 3.78). Hierarchical multiple regression, which included non-modifiable sociodemographic and medical variables (Block 1) and behaviorally modifiable psychosocial variables (Block 2) was significant, F(12,87) = 3.69, p < .001. Specifically, having private insurance (versus Medicaid or public insurance; t = -2.11, p = .038) and higher adherence motivation (t = 2.91, p = .005) predicted higher objective ASM adherence. CONCLUSION: Routine assessment of adherence predictors is vital for the promotion of adherence among adolescents with epilepsy. Adolescent adherence motivation may be an important element of multi-component interventions focused on improving ASM adherence in adolescents with epilepsy.

COVID-19 vaccination status and related process of care outcomes among U.S. adults with active epilepsy-National Health Interview Survey, United States, 2021.

Growing research has examined the effects of the COVID-19 pandemic on people with epilepsy. There are no published national estimates of COVID-19 vaccination status among U.S. adults with active epilepsy. The purpose of this study is to use 2021 National Health Interview Survey (NHIS) data to examine select COVID-19-related outcomes by epilepsy status in a nationally representative sample of US adults. The study sample met the criteria for operationalization of epilepsy status (i.e., active epilepsy vs. no epilepsy history) and select questions related to COVID-19 testing, vaccination, delays in care, or experience with virtual care during the COVID-19 pandemic. All analyses accounted for the NHIS complex sample design and response sampling weights. Our study found that in 2021 receipt of one COVID-19 vaccination among U.S. adults with active epilepsy was generally similar to that among adults without a history of epilepsy. By age, adults aged 18-44 years with active epilepsy (27.0%) were significantly less likely to have reported receiving two COVID-19 vaccinations compared with their peers with no epilepsy history (39.1%). Compared to adults with no epilepsy history, adults with active epilepsy reported similar experiences and outcomes regarding COVID-19 testing and obtaining health care during the COVID-19 pandemic. This study provides baseline estimates of select COVID-19 outcomes among US adults with active epilepsy to guide interventions and additional studies.

On-scene time delays for epileptic seizures in emergencies during a social pandemic: A population-based study.

OBJECTIVES: The on-scene time of Emergency Medical Services (EMS), including time for hospital selection, is critical for people in an emergency. However, the outbreak of the novel coronavirus disease 2019 (COVID-19) led to longer delays in providing immediate care for individuals with non-COVID-19-related emergencies, such as epileptic seizures. This study aimed to examine factors associated with on-scene time delays for people with epilepsy (PWE) with seizures needing immediate amelioration. MATERIALS & METHODS: We conducted a population-based retrospective cohort study for PWE transported by EMS between 2016 and 2021. We used data from the Hiroshima City Fire Service Bureau database, divided into three study periods: "Pre period", the period before the COVID pandemic (2016-2019); "Early period", the early period of the COVID pandemic (2020); and "Middle period", the middle period of the COVID pandemic (2021). We performed linear regression modeling to identify factors associated with changes in EMS on-scene time for PWE during each period. In addition, we estimated the rate of total EMS call volume required to maintain the same on-scene time for PWE transported by EMS during the pandemic expansion. RESULTS: Among 2,205 PWE transported by EMS, significant differences in mean age and prevalence of impaired consciousness were found between pandemic periods. Total EMS call volume per month for all causes during the same month <5,000 (-0.55 min, 95% confidence interval [CI] -1.02 - -0.08, p = 0.022) and transport during the Early period (-1.88 min, 95%CI -2.75 - -1.00, p < 0.001) decreased on-scene time, whereas transport during the Middle period (1.58 min, 95%CI 0.70 - 2.46, p < 0.001) increased on-scene time for PWE transported by EMS. The rate of total EMS call volume was estimated as 0.81 (95%CI -0.04 - 1.07) during the expansion phase of the pandemic to maintain the same degree of on-scene time for PWE transported by EMS before the pandemic. CONCLUSIONS: On-scene time delays on PWE in critical care settings were observed during the Middle period. When the pandemic expanded, the EMS system required resource allocation to maintain EMS for time-sensitive illnesses such as epileptic seizures. Timely system changes are critical to meet dramatic social changes.

Case definitions for onchocerciasis-associated epilepsy and nodding syndrome: A focused review.

Onchocerciasis-associated epilepsy (OAE) is an important but neglected public health problem in onchocerciasis-endemic areas with insufficient or inadequate onchocerciasis control. Hence, there is a need for an internationally accepted, easy-to-use epidemiological case definition of OAE to identify areas of high Onchocerca volvulus transmission and disease burden requiring treatment and prevention interventions. By including OAE as a manifestation of onchocerciasis, we will considerably improve the accuracy of the overall onchocerciasis disease burden, which is currently underestimated. Hopefully, this will lead to increased interest and funding for onchocerciasis research and control interventions, notably the implementation of more effective elimination measures and treatment and support for affected individuals and their families.

COVID-19 vaccination uptake in people with epilepsy in wales.

PURPOSE: People with epilepsy (PWE) are at increased risk of severe COVID-19. Assessing COVID-19 vaccine uptake is therefore important. We compared COVID-19 vaccination uptake for PWE in Wales with a matched control cohort. METHODS: We performed a retrospective, population, cohort study using linked, anonymised, Welsh electronic health records within the Secure Anonymised Information Linkage (SAIL) Databank (Welsh population=3.1 million).We identified PWE in Wales between 1st March 2020 and 31st December 2021 and created a control cohort using exact 5:1 matching (sex, age and socioeconomic status). We recorded 1st, 2nd and booster COVID-19 vaccinations. RESULTS: There were 25,404 adults with epilepsy (127,020 controls). 23,454 (92.3%) had a first vaccination, 22,826 (89.9%) a second, and 17,797 (70.1%) a booster. Comparative figures for controls were: 112,334 (87.8%), 109,057 (85.2%) and 79,980 (62.4%).PWE had higher vaccination rates in all age, sex and socioeconomic subgroups apart from booster uptake in older subgroups. Vaccination rates were higher in older subgroups, women and less deprived areas for both cohorts. People with intellectual disability and epilepsy had higher vaccination rates when compared with controls with intellectual disability. CONCLUSIONS: COVID-19 vaccination uptake for PWE in Wales was higher than that for a matched control group.

Living with epilepsy during COVID-19 pandemic restrictions: A longitudinal perspective.

The purpose of our study was to explore how people with epilepsy fared during two of the most stringent 4-month society-wide COVID-19-related pandemic restrictions in Ireland, in 2020 and one year later in 2021. This was in the context of their seizure control, lifestyle factors, and access to epilepsy-related healthcare services. A 14-part questionnaire was administered to adults with epilepsy during virtual specialist epilepsy clinics in a University Hospital in Dublin, Ireland at the end of the two lockdowns. People with epilepsy were questioned on their epilepsy control, lifestyle factors, and quality of epilepsy-related medical care, compared to pre-COVID times. The study sample consisted of two separate cohorts of those diagnosed with epilepsy (100 (51.8%) in 2020, and 93 (48.2%) in 2021, with similar baseline characteristics. There was no significant change in seizure control or lifestyle factors from 2020 to 2021, except for deterioration in anti-seizure medication (ASM) adherence in 2021 compared to 2020 (p = 0.028). There was no correlation between ASM adherence and other lifestyle factors. Over the two years, poor seizure control was significantly associated with poor sleep (p < 0.001) and average seizure frequency in a month (p = 0.007). We concluded that there was no significant difference between seizure control or lifestyle factors between the two most stringent lockdowns in Ireland, in 2020 and 2021. Furthermore, people with epilepsy reported that throughout the lockdowns access to services was well maintained, and they felt well supported by their services. Contrary to the popular opinion that COVID lockdowns greatly affected patients with chronic diseases, we found that those with epilepsy attending our service remained largely stable, optimistic, and healthy during this time.

Neurological and Neuropsychiatric Impacts of COVID-19 Pandemic.

BACKGROUND: Albeit primarily a disease of respiratory tract, the 2019 coronavirus infectious disease (COVID-19) has been found to have causal association with a plethora of neurological, neuropsychiatric and psychological effects. This review aims to analyze them with a discussion of evolving therapeutic recommendations. METHODS: PubMed and Google Scholar were searched from 1 January 2020 to 30 May 2020 with the following key terms: "COVID-19", "SARS-CoV-2", "pandemic", "neuro-COVID", "stroke-COVID", "epilepsy-COVID", "COVID-encephalopathy", "SARS-CoV-2-encephalitis", "SARS-CoV-2-rhabdomyolysis", "COVID-demyelinating disease", "neurological manifestations", "psychosocial manifestations", "treatment recommendations", "COVID-19 and therapeutic changes", "psychiatry", "marginalised", "telemedicine", "mental health", "quarantine", "infodemic" and "social media". A few newspaper reports related to COVID-19 and psychosocial impacts have also been added as per context. RESULTS: Neurological and neuropsychiatric manifestations of COVID-19 are abundant. Clinical features of both central and peripheral nervous system involvement are evident. These have been categorically analyzed briefly with literature support. Most of the psychological effects are secondary to pandemic-associated regulatory, socioeconomic and psychosocial changes. CONCLUSION: Neurological and neuropsychiatric manifestations of this disease are only beginning to unravel. This demands a wide index of suspicion for prompt diagnosis of SARS-CoV-2 to prevent further complications and mortality.

Les impacts neurologiques et neuropsychiatriques d'une infection à la COVID-19. CONTEXTE: Bien qu'il s'agisse principalement d'une maladie des voies respiratoires, la maladie infectieuse à coronavirus apparue en 2019 (COVID-19) s'est avérée avoir un lien de causalité avec une pléthore d'impacts d'ordre neurologique, neuropsychiatrique et psychologique. Cette étude entend donc analyser ces impacts tout en discutant l'évolution des recommandations thérapeutiques se rapportant à cette maladie. MÉTHODES: Les bases de données PubMed et Google Scholar ont été interrogées entre les 1er janvier et 30 mai 2020. Les termes clés suivants ont été utilisés : « COVID-19 ¼, « SRAS ­ CoV-2 ¼, « Pandémie ¼, « Neuro ­ COVID ¼, « AVC ­ COVID ¼, « Épilepsie ­ COVID ¼, « COVID ­ encéphalopathie ¼, « SRAS ­ CoV-2 ­ encéphalite ¼, « SRAS ­ CoV-2 ­ rhabdomyolyse ¼, « COVID ­ maladie démyélinisante ¼, « Manifestations neurologiques ¼, « Manifestations psychosociales ¼, « Recommandations thérapeutiques ¼, « COVID-19 et changement thérapeutiques ¼, « Psychiatrie ¼, « Marginalisés ¼, « Télémédecine ¼, « Santé mentale ¼, « Quarantaine ¼, « Infodémique ¼ et « Médias sociaux ¼. De plus, quelques articles de journaux relatifs à la pandémie de COVID-19 et à ses impacts psychosociaux ont également été ajoutés en fonction du contexte. RÉSULTATS: Il appert que les manifestations neurologiques et neuropsychiatriques des infections à la COVID-19 sont nombreuses. Les caractéristiques cliniques d'une implication des systèmes nerveux central et périphérique sautent désormais aux yeux. Ces caractéristiques ont fait l'objet d'une brève analyse systématique à l'aide de publications scientifiques. En outre, la plupart des impacts d'ordre psychologique de cette pandémie se sont révélés moins apparents que les changements réglementaires, socioéconomiques et psychosociaux. CONCLUSION: Les manifestations neurologiques et neuropsychiatriques de cette maladie ne font que commencer à être élucidées. Cela exige donc une capacité accrue de vigilance en vue d'un diagnostic rapide, et ce, afin de prévenir des complications additionnelles et une mortalité accrue.

COVID-19 and parents of children with epilepsy: Experiences and positive changes.

Introduction: The aim of this study is to explore the ways that parents with children or adolescents with epilepsy (CAWE) experienced the restrictive measures, as well as the stressors and challenges that they had to face. Methods: We employed an experiential approach and fifteen Greek-speaking parents answered to an in-depth semi-structured interview, during the second lockdown period. Data were analyzed through the Thematic Analysis (TA). Results: The emerging themes were the challenges encountered in terms of medical monitoring, the "stay-home" impact on their everyday lives as a family, their psycho-emotional responses. More specifically, parents identified the irregular doctor appointments and their struggle to access the hospital services as the most important challenges. Moreover, parents reported that the "stay-home" impact has disrupted their children's daily routines among others. Finally, parents highlighted their emotional strain and worries experienced during the lockdown along with the positive changes that occurred.

Investigation of the low glutamate diet as an adjunct treatment for pediatric epilepsy: A pilot randomized controlled trial.

INTRODUCTION: Current dietary therapies for epilepsy have side effects and are low in nutrients, which would make an alternative dietary treatment, which addresses these issues, advantageous. One potential option is the low glutamate diet (LGD). Glutamate is implicated in seizure activity. Blood brain barrier permeability in epilepsy could enable dietary glutamate to reach the brain and contribute to ictogenesis. OBJECTIVE: to assess the LGD as an adjunct treatment for pediatric epilepsy. METHODS: This study was a nonblinded, parallel, randomized clinical trial. The study was conducted virtually due to COVID-19 and registered on clinicaltrials.gov (NCT04545346). Participants were eligible if they were between the ages of 2 and 21 with ≥4 seizures per month. Baseline seizures were assessed for 1-month, then participants were allocated via block randomization to the intervention month (N=18), or a wait-listed control month followed by the intervention month (N=15). Outcome measures included seizure frequency, caregiver global impression of change (CGIC), non-seizure improvements, nutrient intake, and adverse events. RESULTS: Nutrient intake significantly increased during the intervention. No significant differences in seizure frequency were observed between intervention and control groups. However, efficacy was assessed at 1-month compared to the standard 3-months in diet research. Additionally, 21% of participants were observed to be clinical responders to the diet. Overall health (CGIC) significantly improved in 31%, 63% experienced ≥1 non-seizure improvements, and 53% experienced adverse events. Clinical response likelihood decreased with increasing age (0.71 [0.50-0.99], p=0.04), as did the likelihood of overall health improvement (0.71 [0.54-0.92], p=0.01). DISCUSSION: This study provides preliminary support for the LGD as an adjunct treatment before epilepsy becomes drug resistant, which is in contrast to the role of current dietary therapies in drug resistant epilepsy.

[Possibilities of optimizing therapy in COVID-19 survivors with focal epilepsy]. / Vozmozhnosti optimizatsii terapii u patsientov s fokal'noi epilepsiei, perenesshikh COVID-19.

OBJECTIVE: To study the effect of phenosanoic acid therapy on the frequency of seizures, asthenia and quality of life of adult patients with focal epilepsy who had a new coronavirus infection caused by SARS-CoV-2. MATERIAL AND METHODS: The data of 20 patients with focal epilepsy who suffered COVID-19 and received therapy with phenosanic acid (Dibufelon) were studied. The frequency of epileptic seizures, the severity of asthenia and the quality of life were evaluated according to clinical scales. RESULTS: Significant decrease in the frequency of bilateral tonic-clonic seizures and focal seizures with loss of consciousness was recorded. There was a significant improvement in the quality of life. There was no significant dynamics of asthenia against the background of taking the drug phenosanic acid in patients. CONCLUSION: The preparation of phenosanic acid can be an effective means of add-on therapy in patients with epilepsy who have undergone COVID-19.

Effects of coronavirus disease 2019 vaccination on seizures in patients with epilepsy.

BACKGROUND: Given that seizures may be triggered by vaccination, this study aimed to evaluate the risk and correlative factors of seizures in patients with epilepsy (PWE) after being vaccinated against coronavirus disease 2019 (COVID-19). METHODS: This study retrospectively enrolled PWE who were vaccinated against COVID-19 in the epilepsy centers of 11 hospitals in China. We divided the PWE into two groups as follows: (1) patients who developed seizures within 14 days of vaccination were assigned to the SAV (with seizures after vaccination) group; (2) patients who were seizure-free within 14 days of vaccination were assigned to the SFAV (seizure-free after vaccination) group. To identify potential risk factors for seizure reccurence, the binary logistic regression analysis was performed. Besides, 67 PWE who had not been vaccinated were also included for elucidating the effects of vaccination on seizures recurrence, and binary logistic regression analysis was performed to determine whether vaccination would affect the recurrence rate of PWE who had drug reduction or withdrawal. RESULTS: The study included a total of 407 patients; of which, 48 (11.8%) developed seizures within 14 days after vaccination (SAV group), whereas 359 (88.2%) remained seizure-free (SFAV group). The binary logistic regression analysis revealed that duration of seizure freedom ( P  < 0.001) and withdrawal from anti-seizure medications (ASMs) or reduction in their dosage during the peri-vaccination period were significantly associated with the recurrence of seizures (odds ratio = 7.384, 95% confidence interval = 1.732-31.488, P  = 0.007). In addition, 32 of 33 patients (97.0%) who were seizure-free for more than three months before vaccination and had a normal electroencephalogram before vaccination did not have any seizures within 14 days of vaccination. A total of 92 (22.6%) patients experienced non-epileptic adverse reactions after vaccination. Binary logistic regression analysis results showed that vaccine did not significantly affect the recurrence rate of PWE who had the behavior of ASMs dose reduction or withdrawal ( P  = 0.143). CONCLUSIONS: PWE need protection from the COVID-19 vaccine. PWE who are seizure-free for >3 months before vaccination should be vaccinated. Whether the remaining PWE should be vaccinated depends on the local prevalence of COVID-19. Finally, PWE should avoid discontinuing ASMs or reducing their dosage during the peri-vaccination period.