Use Of Antiepileptic Drugs Research Articles

Study of Antiepileptic Drug use Patterns in Epilepsy Patients at the Neurology Polyclinic of Dr. M. Djamil Hospital, Padang

Epilepsy is a neurological disorder with high prevalence worldwide. It is characterized by recurrent seizures due to abnormal electrical activity in the brain. Treatment involves the use of antiepileptic drugs (AEDs) to control seizures. Suboptimal use of AEDs can have negative impacts on seizure management in patients. This study aims to identify the most frequently used AEDs, the patterns of monotherapy and polytherapy use, and the factors influencing AED selection. This study is a descriptive research with prospective data collection. The data used are medical records of epilepsy patients at the Neurology Polyclinic of Dr. M. Djamil Hospital Padang. The research sample was obtained using the consecutive sampling technique. Data analysis was conducted descriptively and presented in the form of descriptions and percentages from the collected medical record data regarding the use of antiepileptic drugs. In this study, 24 out of a total of 45 patients (53.3%) received single-agent antiepileptic therapy (monotherapy), while 21 other patients (46.7%) received combination antiepileptic therapy. The most common single-agent therapy was phenytoin, used by 17 patients, followed by carbamazepine used by 4 patients, and phenobarbital used by 3 patients. As for combination therapy, 14 patients received a combination of phenytoin and phenobarbital, 6 patients received a combination of carbamazepine and phenobarbital, and 1 patient received a combination of valproic acid and phenobarbital.

Antiepileptic Drugs as Prophylaxis for Seizures after Excision of Brain Tumors

Abstract Background Seizures are the most common & most serious side effect of cranial surgery. The latter condition requires chronic treatment with Antiepileptic drugs (AEDs) and comes with relevant socioeconomic sequelae. The routine prophylactic use of AEDs for people undergoing tumor resection has remained controversial due to the risk of postoperative seizures. Some Neurosurgeons are advocates to the use of AEDs to reduce the risk of these seizures. Objective To evaluate the efficacy of prophylactic AEDs routinely in brain tumor patients without previous history of seizures. Primary objective has been to identify the efficacy of AEDs in perioperative seizure prophylaxis. Secondary objective has been to highlight the most common type of post-operative AEDs. Methods All available studies from 2000-2021 including randomized or non-randomized clinical trials, prospective or retrospective observational cohort studies, and case series of six or more cases that address these criteria have been collected. Results Our search concluded that the most common type of post-operative seizure is the Early seizure which is of total 87 patients representing 12.3% of seizure reported patients, yet when comparing the P-value between the Early & late seizure it has a P-value of 0.415 which is nonsignificant rendering the comparison redundant. The Most common types of AED used are Phenytoin (PHT) 89 (71.8%) & Levetiracetam (LEV) 109 (81.8%). To measure the efficacy of AEDs two groups of patients with no history of AED administration or seizures preoperatively were created, one the control group of 268 participants were not administered AEDs postoperatively only 32 (11.94%) of them suffered from seizures postoperatively. The other group of 171 participants were administered the AEDs postoperatively only 25 (14.62%) of these participants suffered from postoperative seizure. Comparing both of these results statistically it had a P-value of 0.416 which is non-Significant statistically. On interpreting these results was that the AED have no influence in controlling the seizures. Conclusion Postoperative seizures are one of the main complications of brain tumor surgery. Neurosurgeons have a strong belief more of tradition that preventing seizures with Anti-Epileptic Drugs (AEDs) as a sort of seizure prophylaxis is not only effective but also necessary. Finally, there is not enough evidence of sufficient quality available to suggest that antiepileptic drugs AEDs treatment can or cannot be recommended to reduce Post-craniotomy seizures.

Anti-epileptic drug use and subsequent degenerative dementia occurrence.

The use of anti-epileptic drugs (AEDs) in degenerative dementia (DD) remains uncertain. We aimed to evaluate the association of early AED administration with subsequent DD occurrence. Using a large nationwide database, we enrolled patients newly diagnosed with epilepsy from 2014 to 2019 (n = 104,225), and using propensity score matching, we divided them into treatment (those prescribed AEDs in 2014) and control groups. The primary outcome was subsequent DD occurrence in 2019. Overall, 4489 pairs of patients (2156 women) were matched. The odds ratio (treatment/control) for DD occurrence was 0.533 (95% confidence interval: 0.459-0.617). The DD proportions significantly differed between the treatment (340/4489 = 0.076) and control (577/4489 = 0.129) groups. Among patients newly diagnosed with epilepsy, compared to non-use, early AED use was associated with a lower occurrence of subsequent DD. Further investigations into and optimization of early intervention for epilepsy in DD are warranted. Anti-epileptic drug (AED) use before epilepsy diagnosis was linked with a lower subsequent degenerative dementia (DD) occurrence.Identifying the epileptic phenotype was crucial for justifying early AED use in DD.AED use with an epilepsy diagnosis did not pose an additional risk of DD.The potential contribution of combination drug therapy to the strategy was noted.

Annual trends in pain management modalities in patients with newly diagnosed autoimmune rheumatic diseases in the USA from 2007 to 2021: an administrative claims-based study

Autoimmune rheumatic diseases have distinct pathogenic mechanisms and are causes of disability and increased mortality worldwide. In this study, we aimed to examine annual trends in pain management modalities among patients with autoimmune rheumatic diseases. We identified newly diagnosed patients with ankylosing spondylitis, psoriatic arthritis, rheumatoid arthritis, Sjögren's syndrome, systemic sclerosis, or systemic lupus erythematosus (SLE) in the Merative Marketscan Research Databases from 2007 to 2021. The database includes deidentified inpatient and outpatient health encounters with employment-sponsored health insurance claims in the USA. We found minimal occurrences of multiple overlapping conditions and included only the initial recorded diagnosis for each patient. We determined the annual incidence of patients treated with opioids, anticonvulsants, antidepressants, skeletal muscle relaxants, non-steroidal anti-inflammatory drugs (NSAIDs), topical analgesics, and physical therapy in the year following diagnosis. Logistic regression was used to estimate the association between calendar year and outcomes, adjusted for age, sex, and region. We included 141 962 patients: 10 927 with ankylosing spondylitis, 21 438 with psoriatic arthritis, 71 393 with rheumatoid arthritis, 16 718 with Sjögren's syndrome, 18 018 with SLE, and 3468 with systemic sclerosis. 107 475 (75·7%) were women and 34 487 (24·3%) were men. Overall, the incidence of opioid use increased annually until 2014 by 4% (adjusted odds ratio [aOR] 1·04 [95% CI 1·03-1·04]) and decreased annually by 15% after 2014 (0·85 [0·84-0·86]). The incidence of physical therapy use increased annually by 5% until 2014 (aOR 1·05 [95% CI 1·04-1·06]), with a slight decrease annually by 1% after 2014 (0·99 [0·98-1·00]). The incidence of anticonvulsant use increased annually by 7% until 2014 (aOR 1·07 [95% CI 1·07-1·08]) and did not significantly change after 2014 (1·00 [0·99-1·00]). Before 2014, the incidence of NSAIDs use increased by 2% annually (aOR 1·02 [95% CI 1·02-1·03]); however, after 2014, the incidence decreased annually by 5% (0·95 [0·95-0·96]). These trends did not differ by sex except for NSAID use before 2014 (pinteraction=0·02) and topical analgesic use after 2014 (pinteraction=0·0100). Since 2014, the use of non-opioid pain management modalities has increased or stabilised, whereas opioid and NSAID use has declined. Future studies are needed to evaluate the effectiveness of these changes, and the effects they have had on outcomes such as quality of life, disability, and function. National Institute of Arthritis and Musculoskeletal and Skin Diseases.

Children with ADHD and EEG abnormalities at baseline assessment, risk of epileptic seizures and maintenance on methylphenidate three years later

PurposeThis study aimed to assess the incidence of EEG abnormalities (EEG-ab) in children diagnosed with ADHD, investigate the risk of epileptic seizures (SZ) and maintenance on methylphenidate (MPH) over a three-year period.MethodsA total of 517 ADHD children aged 6–14 years were included. Baseline assessments included the identification of EEG-ab, ADHD inattentive subtype (ADHD-I), comorbid epilepsy, the use of antiepileptic drugs (AEDs) and the use of MPH. At the 3-year follow-up, assessments included the presence of EEG-ab, maintenance on MPH, AED usage, SZ risk in cases with EEG-epileptiform abnormalities (EEG-epi-ab), compared with control ADHD cases without EEG-epi-ab matched for age and gender.ResultsEEG-ab were identified in 273 (52.8%) cases. No statistically significant differences were observed between the EEG-ab and EEG-non-ab groups in terms of age, gender, ADHD-I type or initial use of MPH. EEG non-epileptiform abnormalities (EEG-non-epi-ab) were found in 234 out of 478 (49%) cases without EEG-epi-ab. Notably, EEG-non-epi-ab occurred more frequently in the group of 39 cases with EEG-epi-ab (30/39 (76.9%) vs. 9/39, (21.3%), a subset selected for 3-year follow-up. At 3-year-follow-up no statistically significant difference was found in maintenance on MPH in ADHD cases with and without EEG-epi-ab. Nobody of ADHD cases without comorbid epilepsy or with comorbid epilepsy with achieved SZ freedom developed new SZ. Only 3 children with drug resistant epilepsy experienced SZs, without increase in SZ frequency. The disappearance rate of EEG-epi-ab was higher than that EEG-non-epi-ab (71.8% vs. 33.3%).ConclusionsChildren with and without EEG-ab exhibited similar patterns of MPH use (initial use, positive response, and maintenance on MPH). The presence of comorbid epilepsy and EEG-ab, with or without EEG-epi-ab, was not associated with an increased risk of SZ despite the use of MPH.

Periventricular Heterotopias: Neuroependymal Abnormalities

AbstractPeriventricular nodular heterotopia (PVNH) is a group of malformation of cortical development characterized by ectopic neuronal nodules, located along the lateral ventricles. Magnetic resonance imaging can identify gray matter nodules located in wall of ventricles, which appear as island having the same signal of gray matter within white matter. The symptomatological spectrum is various, but the most common clinical presentation is with epileptic seizures, often a drug-resistant type. Features as severity, age of presentation, and associated malformations depend on the underlying etiology. From a genetic point of view, FLNA1 and ERMARD are acknowledged to be the main target of mutations that cause PVNH, although recently many other genes have shown a clear pathogenetic involvement. PVNH may manifest as a solitary discovery in brain imaging or present in conjunction with various other brain or systemic abnormalities. The diagnosis of PVNH is mainly carried out with electroneurophysiological and neuroimaging examinations, while the etiological diagnosis is made with genetic investigations. Treatment consists of use of anticonvulsant drugs, but no significant difference exists among them. In addition, frequently, PVNH-related seizures show poor response to drug, leading to requirement for surgical treatment, performed taking advantages from stereotactic ablative techniques that have a meaningful impact on surgical outcome.

Epileptogenesis and neuroinflammation

Progress in the treatment of epilepsy in recent years has been determined mainly by the development and use of new anticonvulsants, as well as the search for new alternative methods for reducing epileptic seizures. The issue of pharmacoresistance remains relevant. This paper presents an analysis of information about neuroinflammation as a pathophysiological phenomenon, its possible role in epileptogenesis and the prospects for influencing the pathological process in epilepsy by influencing its elements. General data on epileptogenesis, the role of neuroinflammation in its formation and maintenance, the main cellular and humoral effectors of the neuroinflammatory process and the prospects for the development of new therapeutic approaches are presented.

Psychiatric symptoms, associated pharmacological treatments and cognitive function: A population-based study of men

BackgroundPsychiatric symptomatology and medications used in their treatment may be modifiable risk factors associated with cognitive function, although findings from population-based studies spanning the full adult age range are lacking. This study aimed to investigate associations between psychiatric symptomatology, psychotropic medication use and cognitive function in a population-based sample of men. MethodsData for 537 men were drawn from the Geelong Osteoporosis Study. Cognitive function (psychomotor function, attention, working memory and visual learning) was determined using the Cog-State Brief Battery. Current depressive and anxiety symptomatology was determined using the Hospital Anxiety and Depression Scale, and psychotropic medication use was self-reported. Linear regression models were developed to determine associations between psychiatric symptomatology and psychotropic medication use with each cognitive measure. ResultsDepressive symptomatology was associated with lower overall cognitive function (b-0.037 ± 0.010, η2 = 0.025, p < 0.001), psychomotor function (b 0.006 ± 0.002, η2 = 0.028 p < 0.001) and attention (b 0.004 ± 0.001, η2 = 0.021, p < 0.001), whereas psychotropic use was associated with lower overall cognitive function (b − 0.174 ± 0.075, η2 = 0.010, p = 0.021), attention (b 0.017 ± 0.008, η2 = 0.008, p = 0.038 and working memory (b 0.031 ± 0.012, η2 = 0.010, p = 0.010). Anticonvulsant use was associated with lower overall cognitive function (b − 0.723 ± 0.172, η2 = 0.032, p < 0.001), attention (b 0.065 ± 0.018, η2 = 0.029, p < 0.001) and working memory (b 0.088 ± 0.026, η2 = 0.022, p < 0.001). All relationships were found to have a small effect. There were no significant associations between anxiety symptomatology and antidepressant and anxiolytic use with any of the cognitive domains. ConclusionDepressive symptomatology and anticonvulsant use were associated with lower cognitive function. Understanding the underlying mechanisms involved in these relationships can advance knowledge on the heterogeneity in cognitive ageing and aid in prevention initiatives.

Anticonvulsants in Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a complex neurological syndrome that arises as a complication of liver dysfunction. The primary focus in HE management has traditionally been on ammonia detoxification, but recent research has paved light on the potential role of anticonvulsant medications in improving the cognitive impairment and preventing seizures associated with HE. This review mainly aims to provide a comprehensive analysis of the use of anticonvulsants in hepatic encephalopathy, by taking a looking at their mechanisms of action, efficacy, and safety profiles.&#x0D; Keywords: Hepatic encephalopathy, Anticonvulsants, Cognitive impairment

Effect of a Declined Plasma Concentration of Valproic Acid Induced by Meropenem on the Antiepileptic Efficacy of Valproic Acid.

This study aimed to indicate whether a declined plasma concentration of valproic acid (VPA) induced by co-administration of meropenem (MEPM) could affect the antiepileptic efficacy of VPA. We retrospectively reviewed data of hospitalized patients who were diagnosed with status epilepticus or epilepsy between 2010 and 2019. Patients co-administered VPA and MEPM during hospitalization were screened and assigned to the exposure group, while those co-administerd VPA and other broad-spectrum antibiotics were allocated to the control group. The exposure group and control group included 50 and 11 patients, respectively. With a similar dosage of VPA, the plasma concentration of VPA significantly decreased during co-administration (24.6 ± 4.3 μg/mL) compared with that before co-administration (88.8 ± 13.6 μg/mL, p < 0.0001), and it was partly recovered with the termination of co-administration (39.8 ± 13.2 μg/mL, p = 0.163) in the exposure group. The inverse probability of treatment weighting estimated the treatment efficacy via changes in seizure frequency, seizure duration, and concomitant use of antiepileptic drugs, which were not significantly different between the exposure and control groups. In the exposure group, there was no significant differences in seizure frequency between the periods of before-during and before-after (p = 0.074 and 0.153, respectively). Seizure duration during VPA-MEPM co-administration was not significantly different from that before co-administration (p = 0.291). In this study, the reduced plasma concentration of VPA induced by the co-administration of MEPM did not affect the antiepileptic efficacy of VPA. This conclusion should be interpreted with caution, and more research is warranted. Chinese Clinical Trial Registry: ChiCTR2000034567. Registered on 10 July 2020.

Changes in Immunoreactivity of Vimentin and GFAP in the Hippocampus of Patients with Drug-Resistant Epilepsy

Epilepsy is a serious neurological disorder that can greatly impact a person’s quality of life and even result in disability. Unfortunately, despite the use of various antiepileptic drugs, more than 30% of patients develop a form of the disease that is resistant to medication, leaving surgery as the only treatment option. In order to better understand and potentially treat epilepsy, there has been a focus on the role of glial mechanisms and the potential for pathogenetic treatment. Specifically, researchers have looked at the expression of cytoskeletal proteins, such as Glial Fibrillary Acidic Protein (GFAP) and vimentin, in nervous tissue. Our study examined the expression of these proteins in the hippocampus of patients with different types of hippocampal sclerosis and Drug-Resistant Epilepsy (DRE). We found a significant increase in the expression of GFAP and vimentin in these structures, suggesting a potential role in the development of reactive gliosis. However, we did not find any correlations between these proteins in all areas studied. This suggests that the activation of these cytoskeletal proteins may occur independently and ultimately contribute to the development of reactive gliosis. These findings provide valuable insights into the mechanisms of epilepsy and may help improve diagnostic and treatment approaches.

Does Size Really Matter? Incidence of Periprosthetic Fractures After Femoral Osteotomy in Patients With Cerebral Palsy.

Of children, 30% to 35% with cerebral palsy (CP) develop hip subluxation or dislocation and often require reconstructive hip surgery, including varus derotation osteotomy (VDRO). A recent literature review identified postoperative fractures as the most common complication (9.4%) of VDROs. This study aimed to assess risk factors for periprosthetic fracture after VDRO in children with CP. A total of 347 patients (644 hips, 526 bilateral hips) with CP and hip subluxation or dislocation (129 females; mean age at index VDRO: 8.6 y, SD 3.4, range: 1.5 to 17.7; 2 Gross Motor Function Classification System (GMFCS) I, 35 GMFCS II, 39 GMFCS III, 119 GMFCS IV, 133 GMFCS V, 21 unavailable) were included in this retrospective, single-group intervention (VDRO) study at a tertiary referral center. Imaging and clinical documentation for patients age 18 years or younger at index surgery, treated with VDRO were reviewed to determine demographic data, GMFCS level, surgeon, type of hardware implanted, use of anticonvulsants and steroids, type of postoperative immobilization, presence of periprosthetic fractures, fracture location and mechanism, and time from surgery to fracture. Potential determinants of periprosthetic fractures were assessed using mixed effects logistic regression. Of 644 hips, 14 (2.2%, 95% CI: 1.3%, 3.6%) sustained a periprosthetic fracture, at a median of 2.1 years postoperatively (interquartile range: 4.6 y, range: 1.2 mo to 7.8 y). Patients with a fracture had a median age at index surgery of 7.3 years (interquartile range: 4.3, range: 2.8 to 17.8; 1 GMFCS II, 6 GMFCS IV, 7 GMFCS V). Periprosthetic fractures were not significantly related to age at index surgery ( P = 0.18), sex ( P = 0.30), body mass index percentile ( P = 0.87), surgery side ( P = 0.16), anticonvulsant use ( P = 0.35), type of postoperative immobilization ( P = 0.40), GMFCS level ( P = 0.31), or blade plate size ( P = 0.17). Only surgeon volume significantly related to periprosthetic fracture (odds ratio = 5.03, 95% CI: 1.53, 16.56, P = 0.008), with the highest-volume surgeon also using smaller blade plates ( P < 0.01). Periprosthetic fractures after VDRO surgery in children with CP are uncommon, and routine hardware removal appears unnecessary. The data suggest that the common dogma of putting in the largest blade plate possible to maximize fixation may increase the risk of periprosthetic fracture. Due to the overall low fracture rate, especially when contextualized relative to the risk of hardware removal, a reactive approach to hardware removal appears warranted. Level III-retrospective study (targeting varus derotational osteotomies in children with cerebral palsy).

Abstract A030: The Montreal Cognitive Assessment (MoCA) administered virtually or via Duo APP in primary brain tumor patients: a preliminary analysis

Abstract Background: Primary brain tumor (PBT) patients experience cognitive dysfunction (CD) because of both their tumor and its treatment. Evaluating CD in PBT populations may inform patient outcomes and clinical management and allow exploration of biologic underpinnings associated with its occurrence. The Montreal Cognitive Assessment (MoCA) is a brief assessment of objective measures of cognition that evaluates 8 specific cognitive domains. Our group has previously reported the feasibility of MoCA, and this study includes using the newly developed MoCA Duo APP to evaluate and report the cognitive function of patients with PBT. Associations between total MoCA scores and clinical and demographic characteristics were explored. Methods: This cohort consisted of adult PBT patients (n=172) enrolled in the NCI-NOB Natural History Study (NCT02851706: PI T. Armstrong). Assessments were performed between February 2020 and July 2023 by MoCA certified assessors and administered in the clinic or via telehealth. MoCA scores range from 0 to 30 (normal cognition ≥ 26). Healthcare providers collected demographic and clinical characteristics, with Karnofsky performance status (KPS) scores categorized as poor (≤ 80) or good (≥ 90). Descriptive statistics, independent t-tests, one-way ANOVAs, and Pearson’s correlation were conducted using IBM SPSS Statistics software. Results: The majority of patients were male (58%), white (81%), had ≥12 years of education (87%), had high-grade (3/4) tumors (65%), and a good KPS score (68%). The mean MoCA score was 25 (median: 26; range: 6-30) with a mean completion time of 10.7 minutes (median: 10; range: 6.1-41.1). Forty-two percent (n=73) were classified as abnormal. The median scores were lowest in the visuospatial/executive (4/5; range: 0-5), abstraction (2/3; range: 0-3) and delayed recall (4/5; range: 0-5) domains. A univariate analysis identified lower MoCA scores in patients with high-grade tumors (p&amp;lt;0.001), poor KPS scores (p&amp;lt;0.001), who underwent two or more surgeries (p=0.004) or treatments (p=0.038), had recurrence (p=0.002), had progression on current imaging (p=0.017), and had current anticonvulsant (p=0.014) and corticosteroid use (p=0.036). Age at diagnosis (r=-0.157, p=0.021) and at visit (r=-0.193, p=0.005) had a weak negative correlation with MoCA scores. Conclusions: Our results indicate that patient age, tumor progression, treatment, and concomitant medications are associated with MoCA scores. Further analysis will evaluate tumor methylation status and blood-based biomarkers associated with occurrence to develop prediction models that can be evaluated in larger cohorts. Future investigations should compare MoCA scores to other forms of cognitive assessment, including patient-reported outcomes, incorporating multiple timepoints to monitor CD in patients throughout their treatment and survivorship care. Citation Format: McKenzie C. Kauss, Elizabeth Vera, Kimberly Reinhart, Hope Miller, Jaime Garcia, Morgan Johnson, Madhura V. Managoli, Maeve Pascoe, Kaitlynn Slattery, Alex R. Wollet, Mark R. Gilbert, Alvina Acquaye-Mallory, Terri S. Armstrong, Vivian A. Guedes. The Montreal Cognitive Assessment (MoCA) administered virtually or via Duo APP in primary brain tumor patients: a preliminary analysis [abstract]. In: Proceedings of the AACR Special Conference on Brain Cancer; 2023 Oct 19-22; Minneapolis, Minnesota. Philadelphia (PA): AACR; Cancer Res 2024;84(5 Suppl_1):Abstract nr A030.

Ventricular Septal Defect And Maternal History Of Epilepsy: A Case Report

Pregnancy with epilepsy can cause major risks for both the mother and the offspring. It is known that the use of antiepileptic drugs (AEDs) during pregnancy can increase the risk of cardiac malformations. This journal reports a 19-day-old male infant who came with complaints of shortness of breath and a blue lip 2 days before admission. The mother had a history of epilepsy and had regularly taken epilepsy medication since before pregnancy. Physical examination revealed cyanotic lips, chest wall retraction, coarse crackles, and murmurs. The patient's symptoms and signs were associated with congenital heart disease, so he was further observed in the NICU. After bedside echocardiography, the results showed a patent foramen ovale and perimembranous ventricular septal defect. The teratogenic effect of AED is thought to be one of the major causative factors of congenital heart disease. A ventricular septal defect is the most common cardiac malformation found in population-based studies. The long-term effects of AED exposure during pregnancy require further investigation, both in terms of the type of AED (old or new) and the duration of AED consumption. It is important to educate mothers-to-be about this, especially to avoid the risk of congenital heart disease in their offspring. Keywords: epilepsy, ventricular septal defect, cardiac malformation.

Quality of life, adherence and knowledge of epileptic patients and the impact of a pharmacist‐led educational intervention: A review

AbstractAround 65 million individuals suffer from epilepsy worldwide, and when it is not properly treated, it is linked to higher rates of physical harm and mortality. Due to the requirement for long‐term therapy and the side effects of many medications, medication compliance is a significant issue. The purpose of this review was to summarize the findings of previous studies examining the quality of life (QOL), adherence, patient education, and medication knowledge, as well as the impact of a pharmacist‐led educational intervention. Additionally, to find out if these studies benefit epileptic patients, to find the appropriate method used to help them in all aspects of their lives, and to use these in future studies. A systematic and comprehensive search was conducted using specific keywords from PubMed, Google Scholar, and Research Gate. A significantly poorer QOL was linked to prolonged antiepileptic drug use or poor adherence as well as psychiatric problems. Neglect was the most frequent reason for nonadherence. The frequency of seizures was greatly reduced, and the adherence was significantly increased by patient education and medication understanding. Patient awareness, adherence, QOL, and seizure frequency were dramatically improved following the intervention. In the absence of optimal treatment, epilepsy is associated with increased rates of bodily injuries and mortality. It is crucial to increase patient education and knowledge about disease and treatment in order to improve adherence, and QOL. Intervention by a chemist is required to achieve these results.

Efficacy of Melatonin as a Sleep Inducer in EEG Procedures in the Pediatric Population: A Cross-Sectional Study.

Introduction Melatonin has been used as an alternative to sleep deprivation for EEGsleep induction in the pediatric population. Our study aims to describe the efficacy of the currently used doses of melatonin for sleep induction among the pediatric age group. Methods A retrospective cross-sectional study included allpatients who underwent an EEG after receiving melatonin over the period of one year. A total of 126 patients have been included in the study. Patients aged one year to three yearsreceived oral melatonin in doses between 2 mg and 6 mg. Patients in the age of three years and above received 10 mg of melatonin. Patients' success rate in achieving sleep and the exact time required for the patients to fall asleep were obtained using the readings of their EEG. The percentage of patients who have achieved sleep and the time required for those patients to sleep were calculated and correlated with the patient'sgender, the presence of any associated neurobehavioral disorders, and their use of antiepileptic drugs (AED). Results Successful sleep was achieved in 84.9% (n:107) of the patients, with a mean time of 24 minutes to fall asleep(SD =14.36). Patients with neurobehavioral disorders were 20% less likely to fall asleep when compared to other patients without neurobehavioral disorders (p: 0.003). However, there was not a statistically significant difference among different genders and among patients who received AED. Conclusion Melatonin is an effective sleep inducer for patients undergoing EEG procedures. It should be considered in the majority of patients. However, in patients with neurobehavioral disorders, a lower success rate is expected.

Inflammation and oxidative stress in epileptic children: from molecular mechanisms to clinical application of ketogenic diet.

Childhood epilepsy affects up to 1 % of children. It has been shown that 30 % of patients are resistant to drug treatments, making further investigation of other potential treatment strategies necessary. One such approach is the ketogenic diet (KD) showing promising results and potential benefits beyond the use of current antiepileptic drugs. This study aims to investigate the effects of KD on inflammation and oxidative stress, as one of the main suggested mechanisms of neuroprotection, in children with epilepsy. This narrative review was conducted using the Medline and Google Scholar databases, and by searching epilepsy, drug-resistant epilepsy, child, children, ketogenic, ketogenic diet, diet, ketogenic, keto, ketone bodies (BHB), PUFA, gut microbiota, inflammation, inflammation mediators, neurogenic inflammation, neuroinflammation, inflammatory marker, adenosine modulation, mitochondrial function, MTOR pathway, Nrf2 pathway, mitochondrial dysfunction, PPARɣ, oxidative stress, ROS/RNS, and stress oxidative as keywords. Compelling evidence underscores inflammation and oxidative stress as pivotal factors in epilepsy, even in cases with genetic origins. The ketogenic diet effectively addresses these factors by reducing ROS and RNS, enhancing antioxidant defenses, improving mitochondrial function, and regulating inflammatory genes. Additionally, KD curbs pro-inflammatory cytokine and chemokine production by dampening NF-κB activation, inhibiting the NLRP3 inflammasome, increasing brain adenosine levels, mTOR pathway inhibition, upregulating PPARɣ expression, and promoting a healthy gut microbiota while emphasizing the consumption of healthy fats. KD could be considered a promising therapeutic intervention in patients with epilepsy particularly in drug-resistant epilepsy cases, due to its targeted approach addressing oxidative stress and inflammatory mechanisms.

Differences in clinical outcomes and resource utilization in pediatric traumatic brain injury between countries of different sociodemographic indices.

The burden of traumatic brain injury (TBI) is disproportionately high in low- and middle-income countries (LMICs). This study aimed to compare clinical outcomes and healthcare utilization for children with moderate to severe TBIs between LMICs and non-LMICs in Asia and Latin America. The authors performed an observational multicenter study from January 2014 to February 2023 among children with moderate to severe TBIs admitted to participating pediatric intensive care units (PICUs) in the Pediatric Acute and Critical Care Medicine Asian Network (PACCMAN) and Red Colaborativa Pediátrica de Latinoamérica (LARed Network). They classified sites according to their 2019 sociodemographic index (SDI). Low, low-middle, and middle SDI sites were considered LMICs, while high-middle and high SDI sites were considered non-LMICs. The authors documented patient demographics and TBI management. Accounting for death, they recorded 14-day PICU-free and 28-day hospital-free days, with fewer free days indicating poorer outcome. The authors compared children who died and those who had poor functional outcomes (defined as Pediatric Cerebral Performance Category [PCPC] level of moderate disability, severe disability, or vegetative state or coma) between LMICs and non-LMICs and performed a multivariable logistic regression analysis for predicting poor functional outcomes. In total, 771 children with TBIs were analyzed. Mortality was comparable between LMICs and non-LMICs (9.6% vs 12.9%, p = 0.146). Children with TBIs from LMICs were more likely to have a poor PCPC outcome (31.0% vs 21.3%, p = 0.004) and had fewer ICU-free days (median [IQR] 6 [0-10] days vs 8 [0-11] days, p = 0.004) and hospital-free days (median [IQR] 9 [0-18] days vs 13 [0-20] days, p = 0.007). Poor functional outcomes were associated with LMIC status (adjusted OR [aOR] 1.53, 95% CI 1.04-2.26), a lower Glasgow Coma Scale score (aOR 0.83, 95% CI 0.78-0.88), and the presence of multiple trauma (aOR 1.49, 95% CI 1.01-2.19). Children with TBIs in LMICs required greater resource utilization in the form of early intubation and mechanical ventilation (81.6% vs 73.2%, p = 0.006), use of hyperosmolar therapy (77.7% vs 63.6%, p < 0.001), and use of antiepileptic drugs (73.9% vs 53.1%, p < 0.001). Within Asia and Latin America, children with TBIs in LMICs were more likely to have poor functional outcomes and required greater resource utilization. Further research should focus on investigating causal factors and developing targeted interventions to mitigate these disparities.

Anti-epileptic Drugs Use and Increased Risk of Stroke: A Systematic Review

Background: Antiepileptic drugs (AEDs), the predominant treatment for epilepsy, are also utilised for migraine, neuropathic pain, and bipolar disorders, accounting for 1% of usage among the common population. There is a greater risk of stroke, heart attack, and arrhythmia among AED users particularly those with enzyme-inducing properties. Summary: This systematic review aimed to look into the ischemic stroke risk among AED users, particularly in patients who had never had a cerebrovascular accident before. English-language literature was searched in the databases of PubMed, EMBASE, and Google Scholar between 2000 and 2021. Studies should report the association between AEDs and the ischemic stroke risk. The outcomes for assessing efficacy and safety were: event ratio, hazard ratio, odds ratio, and risk ratio. Seven of the eight studies showed an increased risk of ischemic stroke associated with AEDs among individuals without a history of cardiovascular accidents Phenytoin, sodium valproate, oxcarbamazepine, levetiracetam, phenobarbital, and carbamazepine were all linked to an increased risk of stroke. Adequate data on the association between the duration of AED exposure and stroke was missing. Key message: Not all AEDs are enzyme inducers. We conclude significant stroke risk with AEDs (mainly enzyme inducers), and dose dependency need to be assessed. The risks and benefits of AEDs should be weighed among the patients, especially with vascular risk factors to limit the risk of ischemic stroke.

A phase Ib/II randomized, open-label drug repurposing trial of glutamate signaling inhibitors in combination with chemoradiotherapy in patients with newly diagnosed glioblastoma: the GLUGLIO trial protocol

BackgroundGlioblastoma is the most common and most aggressive malignant primary brain tumor in adults. Glioblastoma cells synthesize and secrete large quantities of the excitatory neurotransmitter glutamate, driving epilepsy, neuronal death, tumor growth and invasion. Moreover, neuronal networks interconnect with glioblastoma cell networks through glutamatergic neuroglial synapses, activation of which induces oncogenic calcium oscillations that are propagated via gap junctions between tumor cells. The primary objective of this study is to explore the efficacy of brain-penetrating anti-glutamatergic drugs to standard chemoradiotherapy in patients with glioblastoma.Methods/designGLUGLIO is a 1:1 randomized phase Ib/II, parallel-group, open-label, multicenter trial of gabapentin, sulfasalazine, memantine and chemoradiotherapy (Arm A) versus chemoradiotherapy alone (Arm B) in patients with newly diagnosed glioblastoma. Planned accrual is 120 patients. The primary endpoint is progression-free survival at 6 months. Secondary endpoints include overall and seizure-free survival, quality of life of patients and caregivers, symptom burden and cognitive functioning. Glutamate levels will be assessed longitudinally by magnetic resonance spectroscopy. Other outcomes of interest include imaging response rate, neuronal hyperexcitability determined by longitudinal electroencephalography, Karnofsky performance status as a global measure of overall performance, anticonvulsant drug use and steroid use. Tumor tissue and blood will be collected for translational research. Subgroup survival analyses by baseline parameters include segregation by age, extent of resection, Karnofsky performance status, O6-methylguanine DNA methyltransferase (MGMT) promotor methylation status, steroid intake, presence or absence of seizures, tumor volume and glutamate levels determined by MR spectroscopy. The trial is currently recruiting in seven centers in Switzerland.Trial registrationNCT05664464. Registered 23 December 2022.