Use Of Antiepileptic Drugs Research Articles

Anticonvulsants impacting bone metabolism: interim results from a cross-sectional study

Background. Despite a wide range of antiepileptic drugs (AEDs) with an improved pharmacological profile, patients often experience a variety of side effects during long-trem anticonvulsant therapy, among which are osteoporotic disorders. Currently, the mechanisms of AED effect on bone metabolism remain poorly understood, which creates certain difficulties in prevention and treatment of AED-induced osteoporosis.Objective: to study bone mineral density and laboratory parameters of bone metabolism in patients with epilepsy and longterm AED administration.Material and methods. A cross-sectional study included two comparison groups: 100 adult patients with epilepsy receiving AEDs for more than 12 months and 58 healthy volunteers without taking AEDs. All participants underwent general clinical examination, computed tomography (CT) densitometry at three time points (L1, L2 and femoral neck) and laboratory tests of mineral metabolism.Results. According to CT-densitometry results, a decrease in bone mineral density was detected in the majority of participants from both study groups. While assessing an impact of osteoporosis risk factors on bone tissue in epileptic patients, low motor activity and duration of AED therapy were the most significant, which was associated with lower bone mineral density indices. The study of laboratory mineral metabolism indicators revealed significant inter-group differences in indicators such as ionized calcium, 25-hydroxy-calciferol, free thyroxine and prolactin (p(U)=0.044, p(U)=0.040, p(U)=0.001, p(U)=0.003, respectively).Conclusion. The intermediate study results showed that long-term anticonvulsant use negatively affected bone metabolism in patients suffering from epilepsy. The data obtained point at need for further in-depth study of AED therapy effect on mineral metabolism.

P18.39.A SEIZURE PROPHYLAXIS IN GLIOMA SURGERY (SPRING): A MULTI-CENTRE, UNBLINDED, RANDOMISED TRIAL

Abstract BACKGROUND 50-80% of all glioma patients will suffer from seizures during their lifetime. Over half of these patients will have drug resistant seizures. Seizure risk is increased peri-operatively, at tumour progression, and shortly before death. Current guidelines do not support routine use of prophylactic peri-operative anti-epileptic drugs (AED) in seizure naïve patients; despite this, levetiracetam is frequently prescribed for this indication. The aim of this trial was to determine the clinical and cost effectiveness of prophylactic levetiracetam in seizure naïve patients undergoing surgery for a glioma at reducing the risk of seizures. MATERIAL AND METHODS Seizure naïve patients with newly diagnosed glioma undergoing surgery (biopsy or resection) were randomised (1:1) to receive 12 months prophylactic levetiracetam or no prophylaxis at 14 neurosurgery and neuro-oncology units in the UK. Participants received standard of care neurosurgery and neuro-oncology treatment and were followed until death or for a maximum of one year. The primary outcome was one year risk of first seizure analyzed using a logistic regression model and intention to treat analysis. Outcomes were analyzed by intention-to-treat. The target accrual was 804 participants. This trial was registered with ISRCTN 49474281. RESULTS Between Oct 10, 2019 and Aug 30, 2022, we randomised 96 patients, from 24 to 79 years of age, to levetiracetam (n=49) or no prophylaxis (n=47). Due to slow accrual during the Covid-19 pandemic the trial closed early. In the levetiracetam group there were 43 high grade glioma (HGG) and 6 low grade glioma (LGG), and in the no prophylaxis group there were 43 HGG and 4 LGG. Seventeen (35%) of 49 patients randomised to levetiracetam had a seizure, compared to 15 (32%) of 47 patients randomised to no prophylaxis (OR 1.25, 95%CI 0.49-3.21, p=0.64). Median time to first seizure was 4.8 months in the levetiracetam group and 3.0 months in the no prophylaxis group. In the levetiracetam group 20 (41%) of 49 patients died within 12 months (median overall survival 6.8 months; range 0.2-11.9), and in the no prophylaxis group 15 (32%) of 47 patients died within 12 months (median 4.7 months; range 0.1-12.0). There were no serious adverse events or suspected unexpected serious adverse events related to levetiracetam. CONCLUSION Due to poor accrual caused by the Covid-19 pandemic the SPRING trial closed early and is therefore underpowered. Based on the limited data there was no difference in the 12 month seizure risk in the prophylaxis and no prophylaxis patients undergoing surgery for newly diagnosed glioma. The role of prophylactic anti-epileptic drugs remains undefined.

Pattern and Predictors of Neurologic Comorbidities Among African Children with Epilepsy

Abstract Background Epilepsy is the most common neurologic disorder affecting children in Nigeria. It is often associated with other neurologic comorbidities in addition to epileptic seizures, such as attention deficit hyperactivity disorder (ADHD) and cognitive, visual, and hearing impairments, which can be unrecognized while focusing on the seizures. Methods This cross-sectional study assessed the prevalence, pattern, and predictors of neurologic comorbidities among 100 children with epilepsy (CWE) attending the pediatric neurology clinic of Jos University Teaching Hospital, Jos, Nigeria, and age- and sex-matched controls selected consecutively. Data were summarized using frequencies and proportions. Chi-squared and Mann–Whitney U tests were used to test the categorical values, while logistic regression was used to determine the predictive factors for neurologic comorbidities. Results The prevalence of neurologic comorbidities among CWE versus controls was 65 vs. 15% (p < 0.001). Factors associated with neurologic comorbidities in CWE include younger age at onset of epileptic seizures (p < 0.003), severity of seizures (p < 0.001), history of status epilepticus (p < 0.044), background history of intracranial infections (p < 0.029), and the use of combination antiepileptic drugs (p < 0.001). Predictors of comorbidities in CWE were treatment with sodium valproate and polytherapy. Conclusion Neurologic comorbidities are more frequent among CWE than controls; therefore, screening for neurologic comorbidities should be routine when assessing and managing CWE.

Acute Symptomatic Epileptic Seizures After Microsurgical Removal of Supratentorial Meningiomas

RELEVANCE. One of the problems complicating the early postoperative period in patients with supratentorial meningiomas is epileptic seizures, which in 9-16% of cases first develop within the first 7 days after tumor removal (acute symptomatic epileptic seizures).AIM OF THE STUDY. To identify risk factors for the occurrence of acute symptomatic epileptic seizures in the early postoperative period in patients with supratentorial meningiomas and to evaluate the effectiveness of prophylactic antiepileptic therapy.MATERIAL AND METHODS. A prospective, single-blind, randomized, placebo-controlled study was conducted using the sequential, alternate-arm randomization method. The treatment of 102 patients with supratentorial meningiomas was analyzed, in whom the tumor was removed between 01.01.2021 and 30.09.2023 at the N.V. Sklifosovsky Research Institute for Emergency Medicine. To identify risk factors for the development of acute symptomatic epileptic seizures in patients, we assessed the data of the anamnesis, examination of the patient, electroencephalography before surgery, neuroimaging before and after tumor resection, as well as the characteristics of the intraoperative period, duration and outcomes of hospitalization. To evaluate the effectiveness of the prophylactic use of antiepileptic drugs, patients were divided into two groups. The first group consisted of 49 patients who took an antiepileptic drug as a prophylaxis of early epileptic seizures. The second group consisted of 53 patients who took a placebo drug. Both groups were divided into two subgroups each depending on the development of an epileptic seizure or its absence after surgery. In the first group, patients with epileptic seizures were considered the main subgroup, the patients without seizures were considered the control. We assessed the placebo group similarly.RESULTS. In the placebo group, a risk factor for the development of acute symptomatic epileptic seizures was the transection of one or more veins, which was necessary to achieve sufficient surgical access, leading to a change in cerebral venous blood flow (p=0.013, odds ratio (OR)=11.43; 95% CI [1.75–74.73]). In both the antiepileptic drug group and the placebo group, risk factors included an increase in the volume of cerebral edema according to postoperative CT scan data compared with preoperative (p=0.05, OR=18.8; 95% CI [2.0–182.7] and p=0.01, OR=12.6; 95% CI [2.36–68.0], respectively), as well as hemorrhagic transformation of the perifocal edema zone (p=0.03, OR=8.75; 95% CI [1.36–56.4] and p=0.02, OR=9.7; 95% CI [2.1–44.6], respectively). The efficacy of prophylactic use of antiepileptic drugs in reducing the incidence of acute symptomatic epileptic seizures in the first 7 days after surgery was not established (p=0.295, OR=0.533; 95% CI [0.181–1.572]).CONCLUSION. We have identified the following risk factors for the development of acute symptomatic epileptic seizures: an increase in the volume of cerebral edema compared to the preoperative level according to postoperative computed tomography, the development of hemorrhagic transformation of cerebral edema in both groups, and the intersection of one or more veins during surgery (in the placebo group). Confirmation of the efficacy of routine use of antiepileptic drugs for the prevention of acute symptomatic epileptic seizures not received.

Real-World Assessment of Psychotropic and Antiepileptic Drug Use During Pregnancy in Belgium: Trends, Predictors, and Comparative Risk of Congenital Anomalies (2010-2016).

To analyze the prescription patterns and sociodemographic factors associated with the use of antipsychotic, antidepressant, and antiepileptic drugs during pregnancy in Belgium, and to investigate their potential association with congenital anomalies. Using a nationwide linked database, we identified antidepressants, antipsychotics, and antiepileptics via the Anatomical Therapeutic and Chemical Classification (ATC) codes. For each medication group, we calculated the overall prevalence and prevalence for the three most used medications at the fifth ATC level. Sociodemographic factors influencing medication use during pregnancy were analyzed, and potential associations with congenital anomalies were investigated through logistic regression models based on generalized estimating equations. Overall, 828 016 live births pregnancies associated with 611 094 mothers were identified. We found that the use of antidepressants, antipsychotics, and antiepileptics was decreasing with the arrival of pregnancy. Mothers with a less favorable sociodemographic status were more likely to be exposed to these medications. Antiepileptics used in the first trimester were associated with an increased risk of congenital anomalies (aOR = 1.65, 95% CI 1.11-2.45) compared with unexposed women. The three most used antiepileptics were lamotrigine, valproate, and levetiracetam, among them, we found an association with congenital anomalies only for valproate (aOR = 3.92, 95% CI 2.30-6.67). Psychotropic and antiepileptic drug use decreased during pregnancy. Pregnant women with a less favorable sociodemographic status were more likely to be exposed to psychotropics and antiepileptics during pregnancy. The elevated risk of congenital anomalies associated with antiepileptics use, particularly valproate, underscores the need for targeted interventions and increased awareness to improve maternal and fetal health outcomes.

Sida corymbosa prevents seizures and memory deficit via inhibition of oxidative stress and neuronal loss in the hippocampus

Mesiotemporal lobe epilepsy is the most refractory form of epilepsy. The management of this condition relies on the use of antiepileptic drugs known to provide symptomatic relief. Herbal remedies are therefore an alternative to finding a cure for epilepsy. The present study aimed to assess the antiepileptic and anti-amnesic effects of Sida corymbosa aqueous extract using the pentylenetetrazole (PTZ) kindling model in rats. For this, 48 rats were divided into 6 groups of 8 animals each and treated as follows: normal and negative controls received per os (p.o) distilled water (10 mL/kg); experimental groups received S. corymbosa extract (17.14, 34.28, and 68.56 mg/kg, p.o); and positive control group received levetiracetam (250 mg/kg, p.o). One hour after the treatments, animals intraperitoneally (i.p) received a subconvulsive dose of PTZ (25 mg/kg), except the normal control group. The animals were treated once daily until the onset of the first tonic-clonic seizure (stage 5) in the negative control group. Twenty-four hours following the onset of the first seizure, memory impairment was assessed. Twenty-four hours later, the animals were sacrificed, and the hippocampus and prefrontal cortex were collected for biochemical analyses. The extract (68.56 mg/kg) prevented (p < 0.001) seizures from day 1 to day 12 compared to the negative control group. The extract (17.14 and 34.28 mg/kg) increased the recognition index by 80 % (p < 0.05) and 60 % (p < 0.01), respectively, compared with the negative control group. Moreover, the extract (17.14 mg/kg) increased by 68 % (p < 0.001) the concentration of GABA in the hippocampus. The extract (17.14 and 34.28 mg/kg) increased the acetylcholine level by 51 % (p < 0.001) and 69 % (p < 0.001) in the hippocampus, respectively. The extract at a dose of 17.14 mg/kg decreased the concentration of MDA in the hippocampus by 43 % (p < 0.001). These findings suggest that the extract has antiepileptic and anti-amnesic potentials that could justify its empirical use.

Drug-induced hypersensitivity syndrome due to phenytoin: Case report and review of the literature.

Drug hypersensitivity syndrome (DIHS) is a rare but potentially fatal adverse drug reaction characterized by fever, rash, and visceral organ damage, particularly affecting the liver. Early recognition and appropriate management are crucial to prevent serious complications. However, there is limited information on the clinical presentation and management of DIHS, especially in the context of antiepileptic drugs. This case report aims to highlight the importance of recognizing subtle clinical signs and symptoms of DIHS, which can be easily overlooked, particularly in the context of antiepileptic drug use. We report a case of a 15-year-old male patient who developed DIHS after being prescribed phenytoin sodium for epilepsy. The patient presented with symptoms of fever, sore throat, rash, jaundice, and liver dysfunction. Initially, the patient did not receive glucocorticoids and experienced additional reactions to cefoxitin and phosphatidylcholine, likely due to cross-reactivity. The diagnosis of DIHS was made based on the patient's clinical presentation, including fever, extensive rash, organ involvement, and hematological abnormalities. The temporal association with the use of phenytoin sodium, along with the exclusion of other causes of fever and rash, supported the diagnosis. Upon initiation of glucocorticoid therapy with dexamethasone, the patient's symptoms significantly improved. The rash and pruritus decreased, and laboratory values showed improvement, with a decrease in liver enzymes and normalization of white blood cell counts. The patient's fever resolved within 48 hours of starting corticosteroids, and there was no evidence of ongoing inflammation as indicated by a decrease in C-reactive protein levels. Furthermore, the patient's 30-month follow-up revealed no recurrence of rash, liver dysfunction, or organic damage, indicating the long-term effectiveness of the treatment administered. This case highlights the importance of recognizing the subtle clinical signs and symptoms of DIHS, especially in the context of antiepileptic drug use. It underscores the potential benefits of early initiation of glucocorticoid therapy in managing DIHS. The case also serves as a reminder of the potential for drug cross-reactivity in DIHS and the need for cautious drug selection during the acute phase of the syndrome.

Clinical Spectrum and EEG Findings in Patients with Suspected Non-Convulsive Status Epilepticus

This study looked at the clinical spectrum as well as EEG results to help diagnose and treat patients with probable non-convulsive status epilepticus (NCSE). Patients were classified into two groups based on the degree of NCSE: mild to moderate and severe and their medical records revealed evidence of epilepsy in the form of rhythmic delta activity and localized slowing or widespread spike-and-wave (WSW) discharges in EEG. Severe NCSE was associated with increased antiepileptic drug use (90 vs 80%), longer treatment duration (10 vs 7days), and higher critical care unit admissions (40vs25%) (p&lt;0.05). EEG data showed a significant increase in the frequency of generalized spike-and-wave discharges (45 vs 30%) and localized slowing (32vs20%) (p&lt;0.05). Furthermore, these patients' neurological recovery was worse and they remained in the hospital longer. Finally, the severity of the NCSE and poor clinical outcomes were substantially linked to specific EEG patterns, especially localized slowing and WSW discharges.

Prescribing Trends and Associated Outcomes of Antiepileptic Drugs and Other Psychotropic Medications in US Nursing Homes: Proposal for a Mixed Methods Investigation.

Pilot data suggest that off-label, unmonitored antiepileptic drug prescribing for behavioral and psychological symptoms of dementia is increasing, replacing other psychotropic medications targeted by purposeful reduction efforts. This trend accelerated during the COVID-19 pandemic. Although adverse outcomes related to this trend remain unknown, preliminary results hint that harms may be increasing and concentrated in vulnerable populations. Using a mixed methods approach including both a retrospective secondary data analysis and a national clinician survey, this study aims to describe appropriate and potentially inappropriate antiepileptic and other psychoactive drug prescribing in US nursing homes (NHs), characteristics and patient-oriented outcomes associated with this prescribing, and how these phenomena may be changing under the combined stressors of the COVID-19 pandemic and the pressure of reduction initiatives. To accomplish the objective, resident-level, mixed-effects regression models and interrupted time-series analyses will draw on cohort elements linked at an individual level from the Centers for Medicare and Medicaid Services' (CMS) Minimum Data Set, Medicare Part D, Medicare Provider Analysis and Review, and Outpatient and Public Use Files. Quarterly cohorts of NH residents (2009-2021) will incorporate individual-level data, including demographics; health status; disease variables; psychotropic medication claims; comprehensive NH health outcomes; hospital and emergency department adverse events; and NH details, including staffing resources and COVID-19 statistics. To help explain and validate findings, we will conduct a national qualitative survey of NH prescribers regarding their knowledge and beliefs surrounding changing approaches to dementia care and associated outcomes. Funding was obtained in September 2022. Institutional review board exemption approval was obtained in January 2023. The CMS Data Use Agreement was submitted in May 2023 and signed in March 2024. Data access was obtained in June 2024. Cohort creation is anticipated by January 2025, with crosswalks finalized by July 2025. The first survey was fielded in October 2023 and published in July 2024. The second survey was fielded in March 2024. The results are in review as of July 2024. Iterative survey cycles will continue biannually until December 2026. Multidisciplinary dissemination of survey analysis results began in July 2023, and dissemination of secondary data findings is anticipated to begin January 2025. These processes are ongoing, with investigation to wrap up by June 2027. This study will detail appropriate and inappropriate antiepileptic drug use and related outcomes in NHs and describe disparities in long-stay subpopulations treated or not treated with psychotropics. It will delineate the impact of the pandemic in combination with national policies on dementia management and outcomes. We believe this mixed methods approach, including processes that link multiple CMS data sets at an individual level and survey-relevant stakeholders, can be replicated and applied to evaluate a variety of patient-oriented questions in diverse clinical populations. DERR1-10.2196/64446.

Danish population based study of familial epilepsy and childhood cancer.

Results from studies investigating the association between maternal or child epilepsy, use of anticonvulsants in pregnancy, and childhood cancer are inconsistent and at times contradictory. Linking Danish national databases, we obtained epilepsy and childhood cancer diagnoses, and anticonvulsant use data. We estimated adjusted odds ratios of all or specific childhood cancers in relation to maternal or child epilepsy and anticonvulsant therapies using conditional logistic regression. Maternal epilepsy was positively associated with all childhood cancers in offspring, specifically, with acute lymphoblastic leukemia (Odds Ratio (OR) = 1.68, 95% Confidence Interval (CI) = 1.16, 2.43) and Wilms tumor (OR = 2.13, 95% CI = 0.97, 4.68). When considering maternal ever (lifetime) ingestion of anticonvulsants, a positive association was found with all cancers (OR = 1.14, 95% CI = 1.00, 1.30), and central nervous system tumors (CNS) (OR = 1.36, 95% CI = 1.04, 1.76) as well as neuroblastoma (OR = 1.76, 95% CI = 1.06, 2.90) among offspring. Maternal anticonvulsant use before or during the index pregnancy was related to CNS tumors in offspring (OR = 1.99, 95% CI = 0.99, 4.00).

Characteristics of Patients Hospitalized to Community Hospitals With Malignant Brain Tumors and Factors Associated With Discharge Destination.

Our main objective was to compare the characteristics and hospital outcomes of patients with primary and metastatic brain malignancies and to investigate the associated factors related to hospital outcomes. We conducted a retrospective, cross-sectional study of 1628 patients with brain malignancies from 8 community hospitals between 2017 and 2022 who were identified using International Classification of Disease codes. A stepwise logistic regression was used to identify demographics and clinical characteristics associated with in-hospital mortality and home discharge. The median age was 65 years old, with 72.5% of patients having metastatic brain malignancies. After 7.2 days of hospital stay, 49.2% were discharged home, and 102 patients expired during hospitalization. Increased age, medical coverage by Medicare, hemiplegia or paraplegia, lower initial hemoglobin level, increased length of stay, and the use of electrolyte replacement, antibiotics, laxatives, heparin, and anticonvulsants were associated with a decreased likelihood of discharge to home. No medical insurance, Medicaid insurance coverage, comorbidities of cerebrovascular disorder, the need to stay in the intensive care unit, patient safety indicator events, and the use of antibiotics, oral analgesics, and ipratropium-albuterol were associated with increased odds of in-hospital mortality. We identified several predictor variables that delineate differences between both mortality risk and home discharge in patients with primary and metastatic brain tumors. Understanding these predictor variables can be helpful in improving the acute and post-acute care of this population.

Emerging suicidal ideation in a bipolar patient after taking pregabalin: a case report

Bipolar disorder is a severe mental illness and often occurs with comorbidities like anxiety or alcohol abuse. Thus pregabalin could be a promising drug. We present a case report of a 37-year-old woman with bipolar II disorder suffering from a depressive episode with features of anxiety and increased alcohol consumption. The patient was started on quetiapine as monotherapy. After a few days of add-on pregabalin, we observed suicidal ideations and self-harming behaviour, although expression of anxiety as well as alcohol consumption showed a decrease. When we stopped pregabalin and increased the dosage of quetiapine, suicidal behaviour almost disappeared. In the relevant literature, there is disagreement on the use of pregabalin. On the one hand, pregabalin is described as a safe and well-tolerated drug, and on the other hand, there are also concerns about the suicidal effect of anticonvulsants. In conclusion, we recommend the cautious use of pregabalin and other anticonvulsant drugs in patients with affective disorder. There could be a promising effect on the comorbidities but the effect on mood remains still unclear.

Prospects for the use of perampanel in the treatment of epilepsy in patients with malignant gliomas of the brain

Epilepsy occurs in 35-95% of patients with malignant cerebral gliomas of low malignancy and in 29-71% of patients with gliomas of high malignancy. Seizures can be both the first manifestation of malignant cerebral glioma and appear in the postoperative period and during chemoradiotherapy. This requires the use of antiepileptic drugs, which should control the seizure syndrome, provide control and secondary prevention of seizures, without reducing the response of anti-tumour therapy and the the patient QoL. The processes of epileptogenesis and oncogenesis are closely interrelated through common developmental mechanisms in which glutamate plays a key role. Hypersecretion of glutamate is accompanied by increased expression and activation of its receptors, which increases convulsive readiness. This is accompanied by increased level of brain neurotrophic growth factor, the number of synapses between peritumoral neurons and glioma cells, and increased expression of a number of growth factors, which contributes to tumourous proliferation. In this regard, special attention when treating epilepsy in patients with malignant cerebral gliomas is given to perampanel, a glutamate receptor blocker, a 3rd generation antiepileptic drug. The findings show that perampanel not only effectively controls seizures in patients with malignant cerebral gliomas, but also suppresses tumourous proliferation. Perampanel is able to dose-dependently enhance apoptosis and disrupt cell migration in malignant glioma cell lines. The findings have revealed synergistic effect of perampanel in combination with temozolamide. In conditions of chemoradiation therapy perampanel has a protective effect on healthy peritumoral tissues. Undesirable drug reactions during the use of perampanel are infrequent and insignificant. Additional studies are needed to further research the anticonvulsant and antitumour efficacy of perampanel to treat epilepsy in patients with malignant brain tumours.

Associations between specialized dementia care, COVID-19 and central nervous system medication use in assisted living: a population-based repeated cross-sectional study

BackgroundAssisted living (AL) is an increasingly common residential setting for persons with dementia; yet concerns exist about sub-optimal care of this population in AL given its lower levels of staffing and services. Our objectives were to (i) examine associations between AL setting (dementia care vs. other), COVID-19 pandemic waves, and prevalent antipsychotic, antidepressant, anti-dementia, benzodiazepine, and anticonvulsant drug use among residents with dementia/cognitive impairment, and (ii) explore associations between resident and home characteristics and prevalent medication use.MethodsWe conducted a population-based, repeated cross-sectional study using linked clinical and health administrative databases for all publicly funded AL homes in Alberta, Canada, examined between January 2018 - December 2021. The quarterly proportion of residents dispensed a study medication was examined for each setting and period (pandemic vs. comparable historical [2018/2019 combined]) focusing on four pandemic waves (March-May 2020, September 2020-February 2021, March-May 2021, September-December 2021). Log-binomial GEE models estimated prevalence ratios (PR) for period (pandemic vs. historical periods), setting (dementia care vs. other) and period-setting interactions, adjusting for resident (age, sex) and home (COVID-19 cases, health region, ownership) characteristics.ResultsOn March 1, 2020, there were 2,779 dementia care and 3,013 other AL residents (mean age 83, 69% female) with dementia/cognitive impairment. Antipsychotic use increased during waves 2–4 in both settings, but this was more pronounced in dementia care than other AL during waves 3 and 4 (e.g., adjusted [adj]PR 1.20, 95% CI 1.14–1.27 vs. adjPR 1.09, 95% CI 1.02–1.17, interaction p = 0.023, wave 3). Both settings showed a statistically significant but modest increase in antidepressant use and decrease in benzodiazepine use. For dementia care AL residents only, there was a statistically significant increase in gabapentinoid use during several waves (e.g., adjPR 1.32, 95% CI 1.10–1.59, wave 3). Other than a modest decrease in prevalent anti-dementia drug use for both settings in wave 2, no other significant pandemic effects were observed.ConclusionsThe persistence of the pandemic-associated increase in antipsychotic and antidepressant use in AL residents coupled with a greater increase in antipsychotic and gabapentinoid use for dementia care settings raises concerns about the attendant risks for residents with cognitive impairment.

Bipolar disorder is characterized by chronotype instability: A longitudinal investigation of circadian typology and mood

BackgroundChronotype is associated with circadian rhythmicity, a core etiological factor underlying bipolar disorder (BD). Given converging evidence linking late chronotype with poor mental health, the goal of the present study was to examine chronotype (in)stability and its relation to mood symptoms over time. MethodsParticipants with BD I (n = 271), BD II (n = 88), and healthy controls (n = 217) were included (follow-upM=10 years, Range=5–15) from the Prechter Longitudinal Study. Chronotype category and midpoint of sleep, corrected for weekend sleep-debt (MSFsc), were measured with the Munich Chronotype Questionnaire administered every 12 months alongside clinician-rated mood and medication usage. Self-reported mood was measured bi-monthly. Mixed effects models tested whether mood was associated with (in)stability of chronotype category and MSFsc covarying for age, sex, age, and medication. ResultsCompared to HC, individuals with BD self-reported having a later chronotype that significantly fluctuated over time. Individuals with BDI showed significantly less stability in MSFsc than HC. Anticonvulsant use was associated with more stability in MSFsc whereas antidepressant use was associated with less stability in MSFsc. ConclusionsIn a large longitudinal cohort, individuals with BD displayed significant instability in circadian typology. Psychopharmacology in BD may have differential impacts on circadian timing that is important to monitor.

AB083. Epilepsy and low-grade glioma-seizure control after surgical resection: a retrospective cohort study.

Seizures are a common manifestation in patients with low grade glioma (60-75%), and 60-90% patients attain seizure freedom after resection. Seizure control varies with histopathology, extent of resection and type of seizures. There is inconsistency in literature regarding utility of anti-epileptic drugs (AEDs) after tumor resection. We aimed to determine factors associated with seizure control in patients after low-grade glioma (LGG) resection. It was a retrospective cohort study. Medical record of all patients who underwent LGG resection at our center from 2019 to 2021 were reviewed; 77 patients fulfilled the selection criteria. Patients were also contacted via phone calls to collect information about their seizure control as per Engel Classification. Data was analyzed using SPSSv21. The mean age was 34.9±11.3 years, and there was male predominance (62; 80.5%). Generalized seizures were the most common type (54; 70%), and Levetiracetam was the most commonly prescribed AED (60; 77.9%). The median duration of pre-operative AED use was 4 [interquartile range (IQR): 1-24] months. Frontal lobe was the most common location of tumor (36; 46.8%). Most of the patients had their surgery under general anesthesia (51; 61.4%), while 29 (37.7%) underwent awake craniotomy. Nearly half of the patients had a gross total resection (31; 40.3%), and another 15 (19.5%) had near-total resection. Sixteen patients (20.8%) had their AEDs stopped within first 6 months post-operatively (at variable intervals), and all of them had Engel Class IA to ID control at time of follow-up (P=0.008). The 12 patients with grade I glioma also had optimum seizure control (P=0.03). Patients with grade I glioma have better seizure control after surgery. Tumor biopsy is associated with worse seizure outcome, though not statistically significant. Larger studies are needed to determine the ideal time and patient group for discontinuing AED after surgery.

A Review of Concordance and Quality in Clinical Guidelines for Hormonal Contraceptives to Mitigate Drug-Drug Interactions in Women With Epilepsy.

Concomitant use of hormonal contraceptive agents (HCAs) and enzyme-inducting antiepileptic drugs (EIAEDs) may lead to contraceptive failure and unintended pregnancy. This review identified and evaluated concordance and quality of clinical treatment guidelines related to the use of HCAs in women with epilepsy (WWE) receiving EIAEDs. Relevant clinical guidelines were identified across four databases and were independently evaluated for quality utilizing the AGREE-II protocol instrument. Quality in this context is defined as the rigor and transparency of the methodologies used to develop the guideline. Guidelines were further assessed in terms of concordance and discordance with the latest body of knowledge concerning the use of hormonal contraception in the presence of EIAEDs. A total of n = 5 guidelines were retrieved and evaluated. Overall guideline scores ranged from 17% to 92%, while individual domain scores ranged from 0% to 100%. Contraceptive guidelines consistently recommended the use of intrauterine systems and long-acting injectables in the presence of EIAEDs, recommended against the use of oral, transdermal, and vaginal ring contraceptives, and differed regarding recommendations related to implants. Guidelines agreed regarding recommendations that women treated with EIAEDs should receive intrauterine systems and long-acting injectables; however, the suggested frequency of administration of injectable contraceptives differed. The use of intrauterine systems in this population is supported by evidence, but there is uncertainty surrounding the use of long-acting injectables and contraceptive implants. To mitigate the risk of unintended pregnancy and its consequences, recommendations related to implants and long-acting injectable contraceptives should be evidence-based.

The impact of valproic acid administration: Effects on the growth of tongue cancer cells

Background: Tongue cancer represents the predominant malignancy within the oral cavity (25-40% of squamous cell carcinoma), necessitating treatment modalities such as surgery, radiotherapy, and chemotherapy. Valproic acid, an antiepileptic medication, functions as a histone deacetylase inhibitor or activator of anti-tumor signaling pathways. Objective: To deepen our understanding of the effects of valproic acid on the viability, cytotoxicity, proliferation, and migration capabilities of HSC-3 cells. Method: This study employed an in vitro laboratory approach, exposing HSC-3 cells to valproic acid. The experimental groups included a negative control with culture media devoid of valproic acid, and treatment groups exposed to valproic acid at concentrations of 145 ppm, 180 ppm, and 355 ppm, respectively. Results: Significant differences (p-value &lt;0.05) were observed between HSC-3 cells treated with valproic acid (145 ppm, 180 ppm, and 355 ppm) and the control group in terms of viability, cytotoxicity, proliferation, and migration. Reduced cell viability, increased cytotoxicity, and decreased proliferation were noted. Migration assays indicated suppressed migration of HSC-3 cells. Conclusion: In summary, this study reveals that valproic acid exerts substantial effects on various aspects of HSC-3 cell behavior. It decreases cell viability, enhances cytotoxicity, suppresses proliferation, and inhibits cell migration. These findings highlight the potential of valproic acid as a therapeutic agent for tongue cancer by targeting crucial cellular processes involved in cancer progression. Further research and clinical trials are essential to confirm these effects and explore their application in cancer treatment strategies. Novelty/Originality of this article:: This study shows valproic acid has potential as a therapeutic agent for tongue cancer by decreasing cell viability, increasing cytotoxicity, suppressing proliferation, and inhibiting migration of HSC-3 cells. These findings introduce a new application of valproic acid as an anticancer agent, expanding the use of antiepileptic drugs. This study opens up opportunities for developing more effective tongue cancer therapies and encourages further research and clinical trials to validate these findings

Use of antiepileptic medications for seizures' prevention during subarachnoid hemorrhage: A retrospective observational study.

The use of prophylactic antiepileptic drugs (AEDs) post-subarachnoid hemorrhage (SAH), particularly aneurysmal SAH, is controversial, with limited data available. This has led the new American Heart Association/American Stroke Association (AHA/ASA) guidelines to recommend against using AEDs. This study is aimed at determining whether the use of AEDs for primary prophylaxis is effective in reducing the incidence of seizures post-SAH. A retrospective observational study was conducted utilizing a reviewing chart for the period starting from June 2015 to the end of 2021. The reviews were conducted in the acute care areas of 2 tertiary hospitals primarily to assess the efficacy of AEDs against seizures in patients with SAH (particularly aneurysmal SAH). This was done by comparing the occurrence of early, late, and overall incidence of seizures between patients who received AEDs versus those who did not. Of the 62 patients, who mostly presented with aneurysmal SAH (71%), 42 received AEDs and 20 did not. Mostly, the baseline characteristics between the 2 groups were comparable. A few patients on AEDs developed early (n = 4/38), late (n = 3/29), and overall seizures (n = 6/33), whereas no early, late, or overall incidence of seizures was presented in the group who did not receive AEDs. However, this difference showed no significance (P > .05). The subjects who were given AEDs showed significantly longer hospital stays (42.11 ± 51.43 vs 14.10 ± 7.17; P = .002) and higher mortality rates (7/11 vs 0/11; P = .026). For all patients who received AEDs for prophylaxis, the overall incidence of seizures was negatively associated with the Glasgow coma scale (OR: 0.798; 95% CI 0.657-0.978; P = .022). Our findings support the 2023 AHA/ASA guideline recommendation to avoid using routine AEDs for prophylaxis for all SAH patients. Proper and careful stratification methods should be implemented in each given scenario.

Comparison of Postoperative Seizures Between Burr-Hole Evacuation and Craniotomy in Patients With Nonacute Subdural Hematomas: A Bi-Institutional Propensity Score-Matched Analysis.

Postoperative seizures are a common complication after surgical drainage of nonacute chronic subdural hematomas (SDHs). The literature increasingly supports the use of prophylactic antiepileptic drugs for craniotomy, a procedure that is often associated with larger collections and worse clinical status at admission. This study aimed to compare the incidence of postoperative seizures in patients treated with burr-hole drainage and those treated with craniotomy through propensity score matching (PSM). A retrospective cohort analysis was conducted on patients with surgical drainage of nonacute SDHs (burr-holes and craniotomies) between January 2017 to December 2021 at 2 academic institutions in the United States. PSM was performed by controlling for age, subdural thickness, subacute component, and preoperative Glasgow Coma Scale. Seizure rates and accompanying abnormalities on electroencephalographic tracing were evaluated postmatching. A total of 467 patients with 510 nonacute SDHs underwent 474 procedures, with 242 burr-hole evacuations (51.0%) and 232 craniotomies (49.0%). PSM resulted in 62 matched pairs. After matching, univariate analysis revealed that burr-hole evacuations exhibited lower rates of seizures (1.6% vs 11.3%; P = .03) and abnormal electroencephalographic findings (0.0% vs 4.8%; P = .03) compared with craniotomies. No significant differences were observed in postoperative Glasgow Coma Scale (P = .77) and length of hospital stay (P = .61). Burr-hole evacuation demonstrated significantly lower seizure rates than craniotomy using a propensity score-matched analysis controlling for significant variables.