Use Of Antiepileptic Drugs Research Articles

In utero antidepressant exposure not associated with ADHD in the offspring: A case control sibling design.

Recent studies have reported an association between antidepressant (AD) use during pregnancy and the risk to develop attention-deficit/hyperactivity disorder (ADHD) in the offspring. However, the association might be confounded by risk factors in the pregnant parent. To control for unmeasured factors between pregnancies carried by the same parent, we set up a case-control sibling study using the University of Groningen prescription database IADB.nl. Children receiving medication for ADHD (cases) before the age of 16 years were matched to siblings not receiving such medication (controls). Exposure was defined as at least two prescriptions for any AD during pregnancy, i.e., the period of 39weeks before the birth date of the offspring. Secondary analyses were performed to assess the effects of the degree of exposure (the amount of Defined Daily Doses) and the type of AD exposed to. Univariate and multivariate logistic regression was used to estimate odds ratios (ORs) with corresponding 95% confidence intervals (CI). In total, 2,833 children (1,304 cases and 1,529 controls) were included in the analysis. Exposure rate to ADs among cases and controls was 2.2% and 2.4%, respectively. After adjusting for the birth date of the child (as a proxy for the date of pregnancy), age of the pregnant parent at birth, use of psychostimulants, opioids, and antiepileptic drugs by the pregnant parent in the 15 months before birth of the child, an adjusted OR of 1.11 (95% CI 0.67-1.83) was found for the risk of ADHD in the offspring when exposed in utero to ADs. This indicates no increased risk of ADHD in offspring following in utero exposure to ADs. The secondary analyses revealed no statistically significant associations either. The present study provides further evidence that an association between in utero AD exposure and ADHD in offspring might not exist. This perceived association may be caused (at least partially) by confounding by indication. The extent to which depression in the pregnant parent could cause mental disorders such as ADHD in offspring, and the mechanisms involved, should be investigated in further studies.

Adherence to Prophylactic Anticonvulsant Guidelines for Newly Diagnosed Brain Tumor Patients: A Quality Improvement Study.

Clinical guidelines suggest that prophylactic antiepileptic drugs (AEDs) should be given to newly diagnosed seizure-naive brain tumor patients for up to 1 week after craniotomy. Yet, data suggest that prophylactic AEDs are used up to 12 months after surgery. A quality improvement project was implemented to improve adherence to evidence-based prophylactic AED guidelines. A quasi-experimental, pre- and post-test intervention design was used to assess the effect of a multiphase intervention on guideline adherence and prophylactic anticonvulsant prescription rates. The 16-week intervention consisted of provider education sessions, provider alerts, documentation templates, and a weekly audit and feedback. Participants included four providers and newly diagnosed seizure-naive brain tumor patients. Measures included guideline adherence rates and AED prescription rates extracted from chart review, and a provider attitude and knowledge survey. Analyses included descriptive statistics, Wilcoxon signed-rank tests, and Chi-square tests. Guideline adherence increased significantly (p < .01) from 4 months before implementation (15.8%) to 1 year before implementation (27.8%) and then to 93.3% after implementation. Provider knowledge showed clinically meaningful decreases in the likelihood to prescribe prophylactic AEDs (-.5 point) and increased understanding of prophylactic AED side effects (+0.5 point), although these were not statistically significant (p = .083). Finally, prophylactic AED prescription rates decreased by 2.2% (p = .119) compared with 4 months and 1 year before implementation (2.6%; p = .072). This project highlights the important role of provider education, provider alerts, a documentation template, and audit and feedback in improving guideline adherence rate. Findings suggest that the combination intervention and weekly audit and feedback strategy can improve guideline adherence to prophylactic anticonvulsant use in seizure-naive newly diagnosed brain tumor patients. By following prophylactic AED guideline recommendations, clinicians can avoid the potential side effects of anticonvulsant-induced cognitive, behavioral, and psychiatric issues that can impair patients' quality of life.

Hyponatremia after craniotomy in children: a single-institution review.

Hyponatremia after craniotomy can be associated with increased morbidity. However, the incidence of and factors associated with post-craniotomy hyponatremia in children are not known. We performed a retrospective cohort study of patients aged 0-21years who underwent craniotomy in 2017-2019 at a single center to determine the incidence of and to identify risk factors for hyponatremia after craniotomy. Indications for craniotomy included tumors (excluding craniopharyngioma), epilepsy, intracranial infection, trauma, craniofacial, suboccipital decompression for the treatment of Chiari malformation, and cerebrovascular disease. Hyponatremia was defined as a serum sodium level ≤ 135mEq/L any time during the postoperative hospital stay. Statistical significance was defined a priori at p < 0.05. Postoperative hyponatremia occurred in 61 (25%) of 240 children. On univariate analysis, hyponatremia was associated with younger age (8.5 vs 6.3years, p = 0.01), use of preoperative anti-epileptic drugs (p = 0.02), need for blood transfusion (p = 0.02), government/private insurance (p = 0.04), and pre-existing hydrocephalus, defined as the requirement for permanent cerebrospinal fluid (CSF) diversion (p = 0.04). On multivariate analysis, only hydrocephalus (OR 2.95, 95% CI 1.03-8.40) remained statistically significant. Hyponatremia most occurred on the first postoperative day, with normonatremia achieved in a median of 14 (IQR 9.8-24.3) h. Hyponatremia was significantly associated with longer length of stay (median 8 vs 3days, p < 0.01). Hyponatremia was present in 25% of children after craniotomy. Preoperative hydrocephalus as an independent risk factor for hyponatremia after craniotomy.

Prevalence of anticonvulsant-induced vitamin D deficiency

Background. Epilepsy is a common disease in children and adults, requiring long-term or lifelong use of antiepileptic drugs (AEDs) in 60% of cases. Enzyme-inducing and enzyme-inhibiting AEDs may have a negative effect on vitamin D metabolism. However, at present, standard treatment protocols for patients with epilepsy include no nutrients and vitamin-mineral vitamin D containing complexes.Objective: to analyze studies on the prevalence of vitamin D deficiency induced by AEDs intake in patients with epilepsy.Material and methods. The search for full-text publications in Russian and English was carried out in еLibrary, PubMed/ MEDLINE, ClinicalKey, Google Scholar databases, covering the last five years. The analysis included 9 domestic and 54 foreign epidemiological studies assessing prevalence of AED-induced vitamin D deficiency and, consequently, altered bone mineralization and osteomalacia/osteoporosis.Results. Both in children and adults, the prevalence of AED-induced vitamin D deficiency reaches 40% and even higher. The region of residence of patients with epilepsy does not significantly affect this indicator. Impaired bone mineralization is associated with AED-induced vitamin D deficiency and requires the inclusion of vitamin D in the protocols of disease-modifying epilepsy therapy in children and adults.Conclusion. The results of the review showed high relevance of the discussed interdisciplinary problem and need to introduce laboratory screening of vitamin D deficiency among pediatric and adult patients with epilepsy.

Research Progress of Febrile Seizures in Children

Febrile seizures (FS) are common neurological diseases in childhood. It is age-dependent and often occurs in children from 6 months to 5 years old. The etiology of FS is diverse and the mechanism is complex, which is not completely clear, but most children have a good prognosis. Through timely identification, symptomatic treatment and health guidance to patients’ families, we can get a good prognosis. In the treatment of FS, we should pay attention to finding the cause, and do a good job in the health education and guidance for children's families. At present, the long-term use of antiepileptic drugs is not recommended to prevent the recurrence and secondary epilepsy of FS. In the future, through the development of traditional Chinese medicine, the combination of Chinese and Western medicine can be considered in order to improve the therapeutic effect of FS. This paper reviews the relevant literature about the research progress of FS in recent years in China and abroad, to provide new ideas for the diagnosis and treatment of FS in children.

Serum folate levels in children with epilepsy seen in a tertiary health care facility in north central Nigeria.

Children suffering from epilepsy are maintained on antiepileptic drugs (AED) to ensure a reasonable quality of life. These drugs, however, are not without side effects. Notable among which is interference with the metabolism of folate with its attendant clinical implications such as megaloblastic anemia and bleeding diathesis. This study was carried out to determine the serum folate levels of children with epilepsy, compare the folate levels of these children with that of controls, the levels in subjects on different AED, and to investigate the possible effect of duration of AED use on serum folate levels. It was a comparative cross-sectional study involving children with epilepsy aged 2-14 years attending the paediatric neurology clinic of University of Ilorin Teaching Hospital (UITH), Ilorin. A total of 140 epileptic and 140 age-and-sex-matched nonepileptic children as controls were recruited into the study. Mean serum folate levels in subjects of 6.3 ± 1.6 ng/mL was significantly lower than 7.5 ± 1.5 ng/mL in controls (P = 0.001). The mean serum folate level in subjects on AED was comparable with the value in AED naïve subjects. The mean serum folate level was also comparable among subjects on carbamazepine, phenobarbitone, and valproate as monotherapy. There was no correlation between the duration of AED use and the mean serum folate levels (r = -0.180; P = 0.069). The mean serum folate level in subjects was significantly lower than the value in controls; but was comparable in subjects on carbamazepine, phenobarbitone, and valproate as monotherapy. There was no correlation between the duration of AED use and mean serum folate levels.

A Novel Radiographic and Clinical Assessment Scoring Tool for Seizure Risk Stratification in the Acute Phase of Cerebral Venous Sinus Thrombosis: A Systematic Review and Meta-Analysis

Background: Nearly 40% of cerebral venous sinus thrombosis (CVST) cases experience a seizure. A plethora of problems may arise from seizures. Many of these are well recognized in literature as well as in clinical practice. These include the risk for acute respiratory failure, acute renal injury, demand ischemia of myocardium, aspiration pneumonia, and a variety of musculoskeletal injury. Given the lack of a validated tool to predict seizure in the acute phase of CVST, the use of prophylactic anti-epileptic drugs (AEDs) is controversial. A systematic review and meta-analysis of observational studies was conducted to identify risk factors to construct a clinical prediction tool for seizure in acute CVST. Methods: Systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Observational studies that investigated the risk factors for seizure in acute CVST were retrieved from MEDLINE, EBSCO, Web of Science, and Pro-Quest. The summary odds ratios (ORs) were calculated from the pool of data under the random effects model. A point value of 1, 2, or 3 was assigned to each risk factor based on their β-coefficient in the predictive model. Discriminative ability of this model was evaluated on the receiver operating characteristic curve. Results: Initial literature search revealed 1,046 articles discussing seizure as a complication of acute CVST. Through a robust systematic review process with two independent reviewers, 14 studies fully meeting the inclusion criteria were selected. Data elements extracted from the studies were analyzed and re-synthesized. Anatomical involvement of frontal lobe (OR: 4.85; 95% confidence interval (CI): 3.52 - 6.68), parietal lobe (OR: 2.52, 95% CI: 1.41 - 4.52), cortical vein thrombosis (OR: 3.16, 95% CI: 2.18 - 4.58), hemorrhagic venous ischemia (OR: 3.85; 95% CI: 3.20 - 4.64), and clinical presentation of motor deficit (OR: 3.07; 95% CI: 2.66 - 3.55) or confusion (OR: 2.15; 95% CI: 1.57 - 2.94) showed a strong association with increased risk for seizure in the setting of acute CVST. We developed a novel Radiographic and Clinical Assessment (RC) scoring system, consisting of the significant six risk factors. RC score yielded a calculated area under the curve of 0.89, with probabilities for seizure ranging from 40% with a score of 0 to 92% for score of 6. Conclusions: RC scoring tool can be used to stratify the seizure risk based on radiographic findings and the clinical presentation in the acute phase of CVST. This predictive tool may be helpful in identifying patients whose seizure risk is high and can potentially further be used as a clinical decision support tool for prophylactic AED treatment. J Neurol Res. 2022;12(3):114-120 doi: https://doi.org/10.14740/jnr731

Inflammatory Surrogate Parameters for Predicting Ifosfamide-Induced Neurotoxicity in Sarcoma Patients.

Sarcomas compromise a heterogenous group of tumors of a mesenchymal origin. Although treatment options in many solid tumors have evolved over the past decades, the treatment of advanced sarcoma is still based on conventional chemotherapeutic agents. Beside anthracyclines, alkylating agents such as ifosfamide are frequently used in sarcoma treatment. However, treatment with ifosfamide can cause severe dose- and treatment-limiting side effects, such as ifosfamide-induced neurotoxicity (IIN). Especially in sarcoma, consecutive risk assessment analyses investigating the individual factors associated with the increased incidence in IIN, remain insufficient so far. In this retrospective analysis, we investigated 172 sarcoma patients treated with ifosfamide. Out of 172 patients, 49 patients (28.5%) developed IIN. While gender, age, histologic origin, and tumor stage were not associated with the occurrence of IIN, infusion times, simultaneous radiotherapy, and concomitant use of opioids or anticonvulsants affected the risk of developing IIN. Sarcoma patients with IIN showed an alteration in several inflammatory markers, including a lower lymphocyte count, hemoglobin levels, and calcium levels, as well as elevated GGT, sodium, and CRP levels. Remarkably, the occurrence of IIN was associated with a worse prognosis regarding progression free and overall survival. In addition, high CTCAE grades were negatively associated with overall survival in sarcoma. The observation that an inflammatory state is associated with an increased risk of IIN in sarcoma patients can be used prospectively to further investigate the relationship of inflammation and IIN. In addition, the easily accessible blood markers used in our study to predict IIN can be incorporated into clinical decision making.

Association of injury after prescription opioid initiation with risk for opioid-related adverse events among older Medicare beneficiaries in the United States: A nested case-control study.

BackgroundInjury, prevalent and potentially associated with prescription opioid use among older adults, has been implicated as a warning sign of serious opioid-related adverse events (ORAEs) including opioid misuse, dependence, and poisoning, but this association has not been empirically tested. The study aims to examine the association between incident injury after prescription opioid initiation and subsequent risk of ORAEs and to assess whether the association differs by recency of injury among older patients.Methods and findingsThis nested case-control study was conducted within a cohort of 126,752 individuals aged 65 years or older selected from a 5% sample of Medicare beneficiaries in the United States between 2011 and 2018. Cohort participants were newly prescribed opioid users with chronic noncancer pain who had no injury or ORAEs in the year before opioid initiation, had 30 days or more of observation, and had at least 1 additional opioid prescription dispensed during follow-up. We identified ORAE cases as patients who had an inpatient or outpatient encounter with diagnosis codes for opioid misuse, dependence, or poisoning. During a mean follow-up of 1.8 years, we identified 2,734 patients who were newly diagnosed with ORAEs and 10,936 controls matched on the year of cohort entry date and a disease risk score (DRS), a summary score derived from the probability of an ORAE outcome based on covariates measured prior to cohort entry and in the absence of injury. Multivariate conditional logistic regression was used to estimate ORAE risk associated with any and recency of injury, defined based on the primary diagnosis code of inpatient and outpatient encounters. Among the cases and controls, 68.0% (n = 1,859 for cases and n = 7,436 for controls) were women and the mean (SD) age was 74.5 (6.9) years. Overall, 54.0% (n = 1,475) of cases and 46.0% (n = 1,259) of controls experienced incident injury after opioid initiation. Patients with (versus without) injury after opioid therapy had higher risk of ORAEs after adjustment for time-varying confounders, including diagnosis of tobacco or alcohol use disorder, drug use disorder, chronic pain diagnosis, mental health disorder, pain-related comorbidities, frailty index, emergency department visit, skilled nursing facility stay, anticonvulsant use, and patterns of prescription opioid use (adjusted odds ratio [aOR] = 1.4; 95% confidence interval (CI) 1.2 to 1.5; P < 0.001). Increased risk of ORAEs was associated with current (≤30 days) injury (aOR = 2.8; 95% CI 2.3 to 3.4; P < 0.001), whereas risk of ORAEs was not significantly associated with recent (31 to 90 days; aOR = 0.93; 95% CI 0.73 to 1.17; P = 0.48), past (91 to 180 days; aOR = 1.08; 95% CI 0.88 to 1.33; P = 0.51), and remote (181 to 365 days; aOR = 0.88; 95% CI 0.73 to 1.1; P = 0.18) injury preceding the incident diagnosis of ORAE or matched date. Patients with injury and prescription opioid use versus those with neither in the month before the ORAE or matched date were at greater risk of ORAEs (aOR = 5.0; 95% CI 4.1 to 6.1; P < 0.001). Major limitations are that the study findings can only be generalized to older Medicare fee-for-service beneficiaries and that unknown or unmeasured confounders have the potential to bias the observed association toward or away from the null.ConclusionsIn this study, we observed that incident diagnosis of injury following opioid initiation was associated with subsequent increased risk of ORAEs, and the risk was only significant among patients with injury in the month before the index date. Regular monitoring for injury may help identify older opioid users at high risk for ORAEs.

Use of Anti-epileptic Drugs for Post Traumatic Seizure: A Global Survey.

Post traumatic seizures (PTS) and post traumatic epilepsy (PTE) are potential consequences of traumatic brain injury (TBI). There is no consensus regarding its management among treating doctors. We have undertaken a global survey to assess the variability of management practices of PTS and PTE and highlight the pressing need to formulate uniform practice guidelines. A questionnaire consisting of sixteen questions were developed with the help of Google survey and sent through e-mail, or social media platforms like WhatsApp, Facebook messenger or Telegram, to practicing Neurologists and Neurosurgeons round the world. There were a total of 220 responses. Majority of our responders (n = 202; 91.8%) would start an anti-epileptic (AED) prophylaxis to prevent PTS; 18 people (8.18%) told that they would not start AED prophylaxis for TBI. Phenytoin (n = 98; 48.5%) followed by Levetiracetam (n = 78; 38.6%) was the preferred drug, although the latter was significantly preferred by high and upper middle-income countries (p<.001). Majority (n = 99; 49%) would not use it beyond two weeks. Most clinicians would manage PTE with a single drug (n = 160; 72.7%) either Phenytoin (n = 69; 31.3%) or levetiracetam (n = 67; 30.4%). Most of them (n = 174; 86%) would treat for less than one year. Practices in the management of PTS and PTE vary widely among clinicians. Our study point towards the need for the development of a more robust and comprehensive practice guidelines for the management of the same.

Quantitative measurement of peritumoral concentrations of glutamate, N-acetyl aspartate, and lactate on magnetic resonance spectroscopy predicts glioblastoma-related refractory epilepsy.

Increased extracellular glutamate is known to cause epileptic seizures in patients with glioblastoma (GBM). However, predicting whether the seizure will be refractory is difficult. The present study investigated whether evaluation of the levels of various metabolites, including glutamate, can predict the occurrence of refractory seizure in GBM by quantitative measurement of metabolite concentrations on magnetic resonance spectroscopy (MRS). Forty patients were treated according to the same treatment protocol for primary GBM at Ehime University Hospital between April 2017 and July 2021. Of these patients, 23 underwent MRS to determine concentrations of metabolites, including glutamate, N-acetylaspartate, creatine, and lactate, in the tumor periphery by applying LC-Model. The concentration of each metabolite was expressed as a ratio to creatine concentration. Patients were divided into three groups: Type A, patients with no seizures; Type B, patients with seizures that disappeared after treatment; and Type C, patients with seizures that remained unrelieved or appeared after treatment (refractory seizures). Relationships between concentrations of metabolites and seizure types were investigated. In 23 GBMs, seizures were confirmed in 11 patients, including Type B in four and Type C in seven. Patients with epilepsy (Type B or C) showed significantly higher glutamate and N-acetylaspartate values than did non-epilepsy patients (Type A) (p < 0.05). No significant differences in glutamate or N-acetylaspartate levels were seen between Types B and C. Conversely, Type C showed significantly higher concentrations of lactate than did Type B (p = 0.001). Cutoff values of lactate-to-creatine, glutamate-to-creatine, and N-acetylaspartate-to-creatine ratios for refractory seizure were > 1.25, > 1.09, and > 0.88, respectively. Extracellular concentrations of glutamate, N-acetylaspartate, and lactate in the tumor periphery were significantly elevated in patients with GBM with refractory seizures. Measurement of these metabolites on MRS may predict refractory epilepsy in such patients and could be an indicator for continuing the use of antiepileptic drugs.

CORRELATION BETWEEN THE DURATION OF ANTI-EPILEPTIC DRUGS THERAPY AND VITAMIN D LEVEL IN EPILEPTIC CHILDREN

Long-term use of antiepileptic drugs (AEDs) for epilepsy causes a decrease in vitamin D levels due to the activation of liver cytochrome P450 enzymes. The novelty of this study is due to researching about correlation between the duration of anti-epileptic drugs therapy and vitamin d level in epileptic children This cross-sectional study was conducted from October - December 2021in children with epilepsy aged 1 month to 18 years admitted to pediatric neurology polyclinic of DR Wahidin Sudirohusodo. They were divided into two groups: epileptic children receiving AEDs treatment ≤ 1 year and epileptic children receiving AEDs treatment 1 year. Statistical analysis showed no significant relationship between the duration of AEDs use and the incidence of vitamin D deficiency in children with epilepsy.Keywords: Vitamin D Deficiency; Antiepileptic Drugs; Epilepsy

Seizure after surgical treatment of chronic subdural hematoma-Associated factors and effect on outcome.

IntroductionChronic subdural hematoma (cSDH) is becoming more prevalent due to population aging and the increasing use of antithrombotic drugs. Postoperative seizure in cSDH have a negative effect on outcome, and there currently no consensus regarding prophylactic anti-epileptic drug (AED) treatment. The objective of this study was to evaluate predisposing and triggering factors associated with postoperative epileptic seizure in patients with cSDH.MethodsAll patients, who were surgically treated for cSDH in a single tertiary care center between 2015 and 2019, were considered for inclusion. Relevant patient- and hematoma-specific characteristics were retrospectively extracted from hospital records. Paroxysmal events categorized by the treating physician as suspected postoperative seizures were noted. The clinical outcome was extracted from the last available follow-up visit and classified according to the Glasgow outcome scale (GOS).ResultsOf the included 349 patients, 54 (15.5%) developed suspected postoperative epileptic complications in the form of early seizure (≤ 7 days) in 11 patients (3.2%) and late seizure (>7 days) in 43 patients (12.3%). In the logistic regression analysis, solely depressed brain volume (supratentorial volume (ml) not filled with re-expanded brain) was independently associated with postoperative seizure (odds ratio [OR] 1.006, 95% CI: 1.001–1.011; p = 0.034). The occurrence of postoperative seizure (OR 6.210, 95% CI: 2.704–14.258; p < 0.001) and preoperative Markwalder grading (OR 2.919, 95% CI: 1.538–5.543; p = 0.001) were independently associated with unfavorable (GOS1−3) outcome.ConclusionLarger postoperative depressed brain volume was the only factor independently associated with suspected postoperative seizure, and it could help identify a subgroup of patients with higher susceptibility to epileptic events. Based on our data, no formal recommendation can be made regarding the prophylactic use of anti-epileptic drugs. Nevertheless, the relative safety of new generation AEDs and the detrimental effect of postoperative seizure on outcome may justify its use in a selected patient population.

P09.03.A Associations of levetiracetam use with the safety and tolerability of chemoradiotherapy for patients with newly diagnosed glioblastoma

Abstract Background Levetiracetam (LEV) is one of the most frequently used antiepileptic drugs (AED) for brain tumor patients with seizures. We hypothesized that toxicity of LEV and temozolomide-based chemoradiotherapy may overlap. Patients and Methods In a retrospective analysis of individual patient data using a pooled cohort of patients with newly diagnosed glioblastoma included in clinical trials prior to chemoradiotherapy (CENTRIC, CORE, AVAglio) or prior to maintenance therapy (ACT-IV), we tested associations of hematologic toxicity, nausea or emesis, fatigue, and psychiatric adverse events during concomitant and maintenance treatment with the use of LEV alone or with other AED versus other AED alone or in combination versus no AED use at the start of chemoradiotherapy and of maintenance treatment. Results Of 1681 and 2020 patients who started concomitant chemoradiotherapy and maintenance temozolomide, respectively, 473 and 714 patients (28.1% and 35.3%) were treated with a LEV-containing regimen, 538 and 475 patients (32.0% and 23.5%) with other AED, and 670 and 831 patients (39.9% and 41.1%) had no AED. LEV was associated with higher risk of psychiatric adverse events during concomitant treatment in univariable and multivariable analyses (RR 1.86 and 1.88, p&amp;lt;0.001) while there were no associations with hematologic toxicity, nausea or emesis, or fatigue. LEV was associated with reduced risk of nausea or emesis during maintenance treatment in multivariable analysis (HR=0.80, p=0.017) while there were no associations with hematologic toxicity, fatigue, or psychiatric adverse events. Conclusion Any association of psychiatric adverse events with LEV did not persist beyond the concomitant treatment phase. Antiemetic properties of LEV may be beneficial during the maintenance temozolomide.

Impact of medications, mood state, and electrode placement on ECT outcomes in treatment-refractory psychosis

BackgroundTreatment-refractory psychosis (TRP) is a significant clinical challenge. While clozapine is frequently effective, alternate or augmentation strategies are often necessary. Evidence supports effectiveness of electroconvulsive therapy (ECT), but questions remain about optimal treatment parameters and impacts of concomitant pharmacotherapy. Objective/Hypothesis: To analyze the impact of clozapine, anticonvulsant medication, mood state, and ECT electrode placement on outcomes in TRP. We hypothesized that ECT would lead to greater reduction in positive symptoms, particularly in patients receiving clozapine. MethodsRetrospective study in a tertiary TRP program. The Positive and Negative Syndrome Scale (PANSS) was used for clinical outcomes, with positive subscore as primary outcome. Clinical and ECT data were analyzed using a linear modelling approach, controlling for relevant covariates. ResultsA total of 309 patients were included. ECT plus clozapine associated with greater improvement in positive, general, and total symptoms than ECT alone. ECT associated with greater improvement in negative symptoms in depressed patients. Bifrontal placement was mostly equivalent to bitemporal, with greater reduction of positive symptoms in patients receiving clozapine, and associated with lower electrical dose in patients on anticonvulsants. Clozapine increased seizure duration, while anticonvulsants decreased it. Anticonvulsant use in ECT patients associated with equivalent to slightly improved symptom reduction. ConclusionsECT's benefit in TRP may be greatest in patients receiving clozapine. ECT can improve negative symptoms in depressed TRP patients. Bifrontal placement is effective in TRP. Clozapine and anticonvulsants have opposite effects on seizure duration, but anticonvulsants may not adversely affect clinical outcomes of ECT for TRP.

Evaluation of the risk factors for recurrence and the development of epilepsy in patients with febrile seizure.

Although febrile seizure (FS) is generally considered benign and self-limiting, there are differences regarding the risk factors, the prognosis, and the development of epilepsy. To examine the clinical and sociodemographic characteristics of patients diagnosed with FS, and to determine the risks of recurrence and the development of epilepsy. Between 2015 and 2019, we performed a retrospective evaluation of 300 patients with FS followed for at least 24 months. The first episode of FS was simple in 72.7% of the patients and complex in 27.3%, and it recurred in 40%. Age under 12 months in the first FS, complex FS, and neurodevelopmental delay were found to statistically increase the risk of recurrence (p < 0.05). A total of 7% of the patients developed epilepsy, and this rate was found to be higher in patients with neurodevelopmental delay and long-term use of antiepileptic drugs (p < 0.001). The development of epilepsy was also observed in 77.8% of the patients with abnormal electroencephalogram (EEG). Epilepsy developed more frequently in those with abnormal EEG (p<0.001). Neurodevelopmental delay was an important risk factor for FS recurrence and the development of epilepsy. Abnormality in the EEG is an important risk factor for the development of epilepsy. We found that the long-term prophylactic treatment did not cause decreases in the recurrence of FS nor in the development of epilepsy.

Molecular Insights on the Therapeutic Effect of Selected Flavonoids on Diabetic Neuropathy.

One of the common clinical complications of diabetes is diabetic neuropathy affecting the nervous system. Painful diabetic neuropathy is widespread and highly prevalent. At least 50% of diabetes patients eventually develop diabetic neuropathy. The four main types of diabetic neuropathy are peripheral neuropathy, autonomic neuropathy, proximal neuropathy (diabetic polyradiculopathy), and mononeuropathy (Focal neuropathy). Glucose control remains the common therapy for diabetic neuropathy due to limited knowledge on early biomarkers that are expressed during nerve damage, thereby limiting the cure through pharmacotherapy. Glucose control dramatically reduces the onset of neuropathy in type 1 diabetes but proves to be less effective in type 2 diabetes. Therefore, the focus is on various herbal remedies for prevention and treatment. There is numerous research on the use of anticonvulsants and antidepressants for the management of pain in diabetic neuropathy. Extensive research is being conducted on natural products, including the isolation of pure compounds like flavonoids from plants and their effect on diabetic neuropathy. This review focuses on the use of important flavonoids such as flavanols (e.g., quercetin, rutin, kaempferol, and isorhamnetin), flavanones (e.g., hesperidin, naringenin and class eriodictyol), and flavones (e.g., apigenin, luteolin, tangeretin, chrysin, and diosmin) for the prevention and treatment of diabetic neuropathy. The mechanisms of action of flavonoids against diabetic neuropathy by their antioxidant, anti-inflammation, anti-glycation properties, etc., are also covered in this review article.

Folic acid and methotrexate use and their association with COVID-19 diagnosis and mortality: a case–control analysis from the UK Biobank

ObjectiveTo determine if methotrexate or folic acid prescription was associated with differential risk for COVID-19 diagnosis or mortality.DesignCase–control analysis.SettingThe population-based UK Biobank (UKBB) cohort.ParticipantsData from 380 380 UKBB participants with...

Coping drinking motives, neural functional coupling during emotion processing, and alcohol use in young adults with bipolar disorder.

Rates of alcohol use disorders in individuals with bipolar disorder are 3 to 5 times greater than in the general population and exceed rates of alcohol use disorders reported in other affective and anxiety disorders. Despite this high rate of comorbidity, our understanding of the psychosocial and neural mechanisms that underlie the initiation of alcohol misuse in young adults with bipolar disorder remains limited. Prior work suggests that individuals with bipolar disorder may misuse alcohol as a coping mechanism, yet the neural correlates of coping drinking motives and associated alcohol use have not been previously investigated in this population. Forty-eight young adults (22 bipolar disorder type I, 26 typically developing; 71% women; average age ± standard deviation=22 ± 2 years) completed the Drinking Motives and Daily Drinking Questionnaires, and a Continuous Performance Functional magnetic resonance imaging (fMRI) Task with Emotional and Neutral Distracters. We calculated the relative difference in anterior cingulate cortex (ACC) functional coupling with the anterior insula and amygdala in response to emotional distracters compared with neutral stimuli and investigated the relations with coping drinking motives and alcohol use. Across all participants, coping drinking motives were associated with greater quantity of recent alcohol use. In individuals with bipolar disorder, greater ACC-anterior insula functional coupling was associated with greater coping drinking motives, and greater quantity and frequency of recent alcohol use. The relative difference in ACC-anterior insula functional coupling was not associated with coping drinking motives or alcohol use in the typically developing group. Greater ACC-anterior insula functional coupling in individuals with bipolar disorder was also associated with greater anxiety symptoms and recent perceived psychological stress. Exploratory analyses suggest that the relations between ACC-anterior insula functional coupling and coping drinking motives may be confounded by anticonvulsant use. Results suggest that a difference in ACC-anterior insula functional coupling during emotion processing may underlie alcohol use as a maladaptive coping mechanism in young adults with bipolar disorder.

Incidence and risk factors of epilepsy following brain arteriovenous malformation rupture in adult patients.

Little is known about incidence, time of onset, clinical presentation, and risk factors of epileptic seizure following brain arteriovenous malformation (bAVM) rupture. We performed a monocentric retrospective cohort study from January 2003 to March 2021. The main objective of this study was to determine the incidence of seizures after spontaneous bAVM rupture in nonepileptic adult patients and describe the corresponding clinical features. The secondary objective was to identify clinical, radiological, or biological predictors for the occurrence of de novo seizures after bAVM rupture. Of the 296 cases of bAVM rupture registered during the study period, 247 nonepileptic patients (male 53%, median age 40) were included in the study. Fifty-nine patients (23.9%) had at least one seizure after bAVM rupture. The use of preventive antiepileptic drugs (10.3 [1.5-74.1]; P = 0.02) and decompressive craniectomy (15.4 [2.0-125]; P < 0.009) were independently associated with the occurrence of epilepsy after the bAVM rupture. The factors independently associated with the absence of any seizure after the rupture were isolated intraventricular hemorrhage (0.3 [0.1-0.99]; P = 0.04) and infratentorial location of the bAVM (0.2 [0.1-0.5]; P = 0.09). The first seizure occurred within the first year or within 5years in, respectively, 83.1% and 98.3% of the patients. Epilepsy affects nearly a quarter of patients after bAVM rupture. Decompressive craniectomy represents an independent risk factor significantly associated with the occurrence of epilepsy after bAVM rupture. The introduction of preventive AEDs after rupture could be considered in these most severe patients who have a decompressive craniectomy.