Use Of Antiepileptic Medications Research Articles

Threshold-dependent association between non-rapid eye movement obstructive sleep apnea and interictal epileptiform discharges: A hospital study.

Obstructive sleep apnea frequently coexists with epilepsy, potentially influencing its pathophysiology. However, the effect of obstructive sleep apnea severity on interictal epileptiform discharges is not well understood. To explore this, we studied 108 Asian patients with epilepsy who underwent single-night polysomnography. We utilized generalized linear models, adjusting for age, sex, epilepsy type (focal versus generalized), antiepileptic medication use and disease duration, to analyse the relationship between obstructive sleep apnea severity, as measured by the apnea-hypopnea index, and interictal epileptiform discharge frequency during non-rapid eye movement and rapid eye movement sleep. Our analysis revealed that severe obstructive sleep apnea (apnea-hypopnea index ≥ 30) was associated with a higher frequency of interictal epileptiform discharges during non-rapid eye movement sleep (p = 0.04), but no such association was observed during rapid eye movement sleep. Additionally, the frequency of interictal epileptiform discharges in non-rapid eye movement sleep was positively correlated with the wake time between sleep onset and offset (p = 0.03). Further studies are warranted to validate our findings across diverse ethnicities, and over multiple nights of sleep and interictal epileptiform discharge recordings.

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.

Seizure Duration and Electroconvulsive Therapy in Major Depressive Disorder

Electroconvulsive therapy (ECT), wherein a generalized epileptic seizure is induced, is a treatment for major depressive disorder (MDD). Currently, it is unclear whether there is an association between seizure length and treatment outcome. To explore the association between seizure duration, potential confounding variables, and ECT treatment outcome. This population-based cohort study obtained data from the Swedish National Quality Register for ECT. Patients treated for unipolar MDD with unilateral electrode placement between January 1, 2012, and December 31, 2019, were included. The electroencephalographic (EEG) seizure duration from the first ECT treatment session for each patient was used for analysis. Data analyses were performed between March 2021 and May 2024. The primary outcome was remission, defined as a cutoff score of less than 10 points on the self-assessment version of the Montgomery-Åsberg Depression Rating Scale within 1 week after ECT. Multivariate logistic regression analysis was performed to calculate odds ratios (ORs) between different seizure duration groups. Furthermore, the associations between concomitant use of pharmacological treatments, seizure duration, and remission rate were explored. Among the 6998 patients included, 4229 (60.4%) were female and the mean (SD) age was 55.2 (18.6) years. Overall, 2749 patients (39.3%) achieved remission after ECT. Patients with EEG seizure duration of 60 to 69 seconds had the highest remission rates compared with patients with seizure duration of less than 20 seconds (OR, 2.17; 95% CI, 1.63-2.88; P < .001). Anticonvulsant medications were associated with shorter seizure duration (eg, lamotrigine: β coefficient [SE], -6.02 [1.08]; P < .001) and lower remission rates (eg, lamotrigine: adjusted OR, 0.67; 95% CI, 0.53-0.84; P < .001). This study found an association between seizure length and remission from MDD. Use of anticonvulsant medication during ECT was associated with shorter seizure duration and lower remission rates after ECT.

Antiepileptic Medication-induced Severe Cutaneous Adverse Reactions in Hospitalized Children: A Retrospective Study.

There are limited data on severe cutaneous adverse reactions (SCARs) associated with antiepileptic medications. The current study aims to investigate the clinical and epidemiological characteristics of antiepileptic medication-induced SCARs in hospitalized children. The current five-year retrospective study was conducted at Isfahan University of Medical Sciences, Iran. This study included all children with a definite diagnosis of SCARs secondary to the use of antiepileptic medications based on the world health organization (WHO) definition. In our study SCARs were categorized into three fields: Hypersensitivity syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS), and Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Among 259 children with SCARs induced by antiepileptic medications, 199 (76.83%), 42 (16.22%), and 18 (6.95%) had hypersensitivity syndrome, DRESS, and SJS/TEN, respectively. Phenobarbital was the most common offending drug in all types of SCARs. The multinomial logistic regression model revealed that lymphadenopathy increased the occurrence of DRESS by 35 times compared to hypersensitivity syndrome (P < 0.001). Girls were at risk of SJS/TEN approximately 6 times more than boys (P = 0.027). Age (P = 0.021), weight (P = 0.036), and mucosal involvement (P < 0.001) affected the hospitalization duration in children with SCARs related to antiepileptic medication. There are some similarities and differences in the clinical and epidemiological features of Iranian children suffering from antiepileptic medication-induced SCARs.

Developing an Online Interactive Volumetric Surface Viewer for Visualizing Spatial Distribution of Intracranial Lesions.

The exact location of intracranial neoplasms and metastatic lesions within the cortex may provide key insights into predicting treatment effectiveness and toxicities. Modern neuroimaging approaches have enabled precise, rapid diffeomorphic alignment from individual brains to an atlas, allowing the registration of contours and dose distributions onto a common template. However, there is a paucity of intuitive tools to perform such functions. Here, we developed an online interactive volumetric surface viewer that displays distribution of brain lesions of specific clinical features within the context of prior radiation treatment in populations of patients on a common atlas. Data from 647 patients treated at our institution with radiotherapy for intracranial lesions were analyzed with FreeSurfer to perform intensity normalization, skull-stripping, and affine registration to Talairach coordinates. A custom-built VoxelMorph model was trained to register T1 MRIs to a common atlas. Radiation dose maps and contours on underlying CT simulation scans were rigidly aligned to the T1 MRIs. The diffeomorphic warps were then applied to the radiation dose maps and contours, including the gross tumor volumes. Surface rendering of the template atlas was performed using FreeSurfer and visualized using PyCortex. Clinical information including primary sites for brain metastases, lesion size, survival, recurrence, use of anti-epileptic medications, radiation necrosis, and neuro-cognitive toxicity was embedded into the PyCortex viewer. The custom-trained VoxelMorph model enabled rapid normalization of the T1MRIs to the atlas brain. PyCortex allows for interactive visualization of the spatial distribution of lesions on the cortical surface across a rich array of clinical parameters. Initial maps have qualitatively revealed a predilection for metastases in the right hemisphere. This WebGL viewer allows intuitive clinical interrogation on a visual surface enabling population inferences. For example, one can visualize the distribution of brain metastases of a large patient cohort based on their primary tumor sites, propensity for seizure and risk for radionecrosis. We successfully built an online interactive viewer to visualize the spatial distribution of intracranial lesions on a common reference. Our approach extends prior work allowing visual interaction of lesions and real-time generation of inference maps by combining a front-end viewer and back-end database of clinical data. This viewer may represent a critical step towards uncovering the location-dependent breakdown of the blood-brain-barrier, differentiating the propensity of primary lesions metastasizing to brain regions, and allowing the discovery of associations of previously understudied spatial neighborhoods. We plan to release a publicly available web-based viewer to further explore, interrogate, and inform future radiation treatments.

A Multicenter Study on the Clinical Characteristics and Outcomes Among Children With Moderate to Severe Abusive Head Trauma

IntroductionWe aimed to identify clinical characteristics, risk factors for diagnosis, and describe outcomes among children with AHT. MethodsWe performed an observational cohort study in tertiary care hospitals from 14 countries across Asia and Ibero-America. We included patients <5 years old who were admitted to participating pediatric intensive care units (PICUs) with moderate to severe traumatic brain injury (TBI). We performed descriptive analysis and multivariable logistic regression for risk factors of AHT. Results47 (12%) out of 392 patients were diagnosed with AHT. Compared to those with accidental injuries, children with AHT were more frequently < 2 years old (42, 89.4% vs 133, 38.6%, p < 0.001), more likely to arrive by private transportation (25, 53.2%, vs 88, 25.7%, p < 0.001), but less likely to have multiple injuries (14, 29.8% vs 158, 45.8%, p = 0.038). The AHT group was more likely to suffer subdural hemorrhage (SDH) (39, 83.0% vs 89, 25.8%, p < 0.001), require antiepileptic medications (41, 87.2% vs 209, 60.6%, p < 0.001), and neurosurgical interventions (27, 57.40% vs 143, 41.40%, p = 0.038). Mortality, PICU length of stay, and functional outcomes at 3 months were similar in both groups. In the multivariable logistic regression, age <2 years old (aOR 8.44, 95%CI 3.07-23.2), presence of seizures (aOR 3.43, 95%CI 1.60-7.36), and presence of SDH (aOR 9.58, 95%CI 4.10-22.39) were independently associated with AHT. ConclusionsAHT diagnosis represented 12% of our TBI cohort. Overall, children with AHT required more neurosurgical interventions and the use of anti-epileptic medications. Children younger than 2 years and with SDH were independently associated with a diagnosis of AHT. Type of StudyObservational cohort study. Level of EvidenceIII.

Antiepileptic Drugs and the Relationship with the Intestinal Microbiota

This review of the literature examines the use of antiepileptic medications and how they relate to gut microbiota. Relationships exist between the makeup of the intestinal microbiota and the development and execution of the most fundamental physiological processes. Additionally, it affects the functioning of the central nervous system (CNS) by interacting with the microbiota-intestine-brain axis. The use of pharmaceutical medication is one of the factors that can alter the composition of the gut microbiota. When treating epilepsy, various drug types are used, each with a different mechanism of action. Among the medications in question are to piramate, primidone, phenytoin, carbamazepine, and phenobarbital. The similarity in structure and function between enteric and nerve cells establishes the connection between the brain and the gut. Valproic acid significantly reduced intestinal inflammation in research involving rats with colitis. Its limited ability to treat seizures in these circumstances may be due to the enterocytes limited ability to absorb this medicine. The study came to the conclusion that colitis patients and people with healthy gut, brain, and microbiota interactions typically respond better to antiepileptics and anticonvulsants than people with imbalances in this axis. These imbalances can result in a lower seizure threshold and an increased frequency of epileptic seizures.

Liver enzyme inducing anticonvulsant drug use is associated with prevalent vertebral fracture.

It is unclear whether prevalent vertebral fractures are associated with use of anticonvulsant drugs, especially those that induce liver enzymes (LEI) that metabolize drugs and vitamin D. Our purpose was to estimate the prevalence of vertebral fracture on densitometric lateral spine images according to duration of prior anticonvulsant medication use. Our study population was 11,822 individuals (mean [sd] age 76.1 [6.8] years, 94% female) who had bone densitometry with VFA between 2010 and 2018. Cumulative prior exposure to LEI anticonvulsants (carbamazepine, phenobarbital, phenytoin, valproic acid, n = 538), non-LEI anticonvulsants (clonazepam, gabapentin, levetiracetam, others, n = 2786), and other non-clonazepam benzodiazepines (n = 5082) was determined using linked pharmacy records. Prevalent vertebral fractures were identified on VFA images using the modified ABQ method. Logistic regression models were used to estimate the association of anticonvulsant drug exposure with prevalent vertebral fractures. Prevalence of one or more vertebral fractures was 16.1% for the entire analytic cohort, and 27.0%, 19.0%, and 18.5% for those with ≥ 2years of prior LEI anticonvulsant use, non-LEI anticonvulsant use, and other benzodiazepine use, respectively. Adjusted for multiple covariates, use of prior LEI anticonvulsant medication for ≥ 2years was associated with prevalent fracture on VFA (OR 1.48 [95% CI 1.04, 2.10]). LEI anticonvulsant use for ≥ 2years is associated with higher vertebral fracture prevalence. Lateral spine VFA imaging at the time of bone densitometry may be appropriate for older individuals who have used LEI anticonvulsant medications for ≥ 2years.

When the Brain and the Heart Collide: A Complex Diagnostic and Management Dilemma of Coexisting Psychogenic Nonepileptic Seizures and Takotsubo Cardiomyopathy - A Case Report

Epilepsy is a prevalent neurological disorder affecting around one percent of the global population. Accurate diagnosis is paramount for effective treatment, but challenging-to-diagnose seizures require a comprehensive evaluation to exclude other conditions. Psychogenic nonepileptic seizures (PNES) or pseudoseizures are sudden episodes resembling epileptic seizures, but not arising from abnormal cerebral electrical activity. PNES are often misdiagnosed as epilepsy, leading to delayed appropriate psychological therapy and unwarranted antiepileptic medication use. We report a unique case of a patient initially diagnosed and treated as epilepsy, who was later diagnosed with PNES during hospitalization. Additionally, the patient presented Takotsubo cardiomyopathy (TCM), a rare stress-induced cardiomyopathy, posing a diagnostic and management challenge alongside PNES. To the best of our knowledge, this is the first case of coexisting PNES and TCM, which warrants further investigation.

Study on MRI evaluation of various etiologies of seizures

Introduction: Epilepsy describes a condition in which a person has unprovoked, recurrent seizures due to a chronic, underlying process. Several studies have estimated the prevalence of epilepsy ranging from 5-30 persons per 1000 population. Most of the patients suffering from epilepsy have good control on seizures with the use of antiepileptic medications, however most of the patients with intractable epilepsy have seizures that are focal and can be potentially treated. Objectives of our study: The objective of our study to find out the role of MRI in evaluating the aetiologies of seizures in subjects with seizure disorder. Methodology: We included a total of 150 subjects after taking voluntary consent from the study subjects based on inclusion and exclusion criteria. A detailed proforma was recorded which included subject’s socio demographic data, medical history, personal history, past-history, family history and general physical examination, blood pressure measurement, systemic examination etc. The points noted were duration of illness, type of seizures, and any associated illness. Detailed clinical and neurological examination were done to find out any neurological deficit. Based on the history and examination, a clinic etiological diagnosis was made. Follow up of subjects were done until the completion of treatment (maximum 6 months).

Association between CACNA1C gene rs100737 polymorphism and glutamatergic neurometabolites in bipolar disorder

Abnormalities in Ca2+ homeostasis in Bipolar Disorders (BD) have been associated with impairments in glutamatergic receptors and voltage-gated calcium channels. Increased anterior cingulate cortex (ACC) glutamatergic neurometabolites have been consistently disclosed in BD by proton magnetic resonance spectroscopy (1H-MRS). A single nucleotide polymorphism (SNP) in the CACNA1C gene (rs1006737), which encodes the alpha 1-C subunit of the L-type calcium channel, has been associated with BD and is reported to modulate intra-cellular Ca2+. Thus, this study aimed to explore the association of the CACNA1C genotype with ACC glutamatergic metabolites measured by 1H-MRS in both BD and HC subjects. A total of 194 subjects (121 euthymic BD type I patients and 73 healthy controls (HC) were genotyped for CACNA1C rs1006737, underwent a 3-Tesla 1H-MRS imaging examination and ACC glutamatergic metabolite were assessed. We found overall increased glutamatergic metabolites in AA carriers in BD. Specifically, higher Glx/Cr was observed in subjects with the AA genotype compared to both AG and GG in the overall sample (BD + HC). Also, female individuals in the BD group with AA genotype were found to have higher Glx/Cr compared to those with other genotypes. CACNA1C AA carriers in use of anticonvulsant medication had higher estimated Glutamine (Glx-Glu) than the other genotypes. Thus, this study suggest an association between calcium channel genetics and increased glutamatergic metabolites in BD, possibly playing a synergic role in intracellular Ca2+ overload and excitotoxicity.

A Review of the Prevalence, Etiology, Diagnosis, and Management of Pediatric Epilepsies in India

AbstractPediatric seizures are one of the most common neurological manifestations seen in pediatrics. Unravelling the etiology, timely and appropriate investigations followed by suitable therapies are essential for improving quality of life. During the pandemic, focused group discussions were conducted among 50 pediatric neurologists across five cities in India to gather insights on treatment practices in pediatric epilepsy and to optimize therapeutic strategies and alternative approaches for rational use of antiepileptic medications. These discussions were mainly aimed at reviewing current literature on prevalence, etiology, diagnosis, and management of epilepsy in children and subsequently rationalizing diagnostic and treatment approaches in routine clinical practice. Epileptic encephalopathies comprise of childhood epilepsy with progressive cerebral dysfunction. Genomics plays a vital role in identifying the underlying genetic associations, empowering precision therapy. Currently, the ketogenic diet has become a well-recognized modality for reducing severity of seizures. To overcome the high incidence of adverse effects due to older antiepileptic drugs, newer drugs are being developed to improve ease of use, diminish drug interactions, decrease adverse effects, and identify drugs with unique mechanisms of action. Common lacunae in practice include information gaps, educating parents, or caregivers about rational drug use and ensuring compliance to antiepileptic medications. This article discussed the consensus clinical viewpoint of expert clinicians, as well as insights on optimized treatment of pediatric epilepsies in both infancy and childhood. It also discusses aspects, like reducing drug burden, emerging therapies in the identification of the genetic basis of epilepsies, and targeted therapy alternatives, for pediatric populations in the Indian scenario.

Abstract 76: Alteration in bone metabolism and bone mineral density with chronic anti-epileptic drug therapy in North Indian population

Objective: Anti-epileptic drugs are the mainstay of treatment of epilepsy. Prolong use of anti-epileptic medicines can lead to reduction in bone mineral density (BMD), resulting in 2-6-fold increase in fracture risk. This study was carried out to assess the impact of AEDs on the markers of bone turnover and BMD in North Indian patients.Methods: In this hospital based observational study sixty adult patients with epilepsy, on antiepileptic drugs were included. Serum calcium, phosphorus, alkaline phosphatase (ALP), albumin, 25 (OH) vitamin D and intact Parathyroid hormone (iPTH) and BMD (at lumbar spine with DEXA) were measured in all study subjects.Results: The serum level of calcium, phosphorus and 25(OH) Vitamin D was significantly decreased and iPTH and ALP levels were increased in patients taking anti-epileptic drugs for > 5 years. There was a significant negative correlation between serum calcium, phosphorus and vitamin D levels and significant positive correlation with ALP and iPTH levels with duration anti-epileptic therapy. There was negative correlation between the T-score and anti-duration of anti-epileptic therapy.Conclusions: Use of anti-epileptic (both old and new) medication in adults is associated with decline in BMD, calcium, vitamin D and phosphorus levels and elevation in iPTH and ALP levels.

Lipomyelomeningocele: Epidemiological Studies in a Pediatric Neurosurgery Department of Bangladesh

Background: Spinal dysraphism, one of the most common birth defects, has been estimated to occur annually in more than 320,000 infants worldwide. Lipomyelomeningocele (LipoMMC) is a closed neural tube defect in which the surface lipomatous tissue is attached to the spinal cord. LipoMMC results from premature disjunction of the epithelial ectoderm from the neural ectoderm at a gestational age of 18–28 postovulatory days.Both genetic and environmental factors are suggested to have important roles in the occurrence of neural tube defects. In addition, variables such as vitamin B 12 deficiency, maternal hyperinsulinemia,maternal dietary glycemic intake, maternal obesity and use of antiepileptic medications during pregnancy have been suggested as risk factors for spinal dysraphism. Objective:The aims and objectives of this study was to see the epidemiology of Lipomyelomeningocelein our population. We shall also compare our result with other previous study result. Materials and method: It is a retrospective study. Cases were obtained from a NINS Pediatrics neurosurgery electronic registry (emrbd.com). The study was carried out at Department of Paediatrics Neurosurgery, NINS&amp;H, and DhakafromNovember 2017 to till date.Subjects was included from a NINS Pediatrics neurosurgery electronic registry.Structured questionnaire was used to collect the necessary information. Risks and benefits of this study were explained to the patient and patient’s legal guardian/ parents in an easily understandable local language. Conclusion: In this study the majority of cases were female. Environmental factors also appear to be associated with lipomyelomeningocele risk factor. Additional studies needed to establish the environmental risk factor associated with LipoMMC. Bang. J Neurosurgery 2021; 11(1): 25-29

Prevalence and correlates of depression in patients with epilepsy in Sri Lanka.

Depression is one of the most common psychiatric disorders in patients with epilepsy and it is often associated with poor quality of life, increased risk of suicide and poor seizure control, yet remains underdiagnosed and undertreated. The prevalence and associations for depression in patients with epilepsy vary between studies reflecting regional and cultural influences. Therefore, it is important to identify unique attributes within a community on this phenomenon This is the first study from Sri Lanka on the prevalence and correlates of depression in patients with epilepsy. We conducted this cross-sectional study at the Epilepsy clinic, Colombo North Teaching Hospital, Ragama. All consenting patients with a diagnosis of epilepsy followed up at the clinic, during study period, were enrolled. Symptoms of depression were screened with Beck Depression Inventory II and diagnosis was confirmed with a clinical assessment by psychiatrist. Of 150 participants, majority were female 63.3%. (95) and 36.7% (55) of the sample were between 26-45 years. The prevalence of depressive disorder was 22% (33). The prevalence of depression was significantly associated with the recent diagnosis of epilepsy, use of multiple antiepileptic medications and duration of seizure free period (p<0.05). There is a statistically significant association between prevalence of depression with the use of carbamazepine, topiramate, clobazam and phenobarbitone. Regression analysis revealed higher the duration individuals suffering from epilepsy were at lower odds of having depression compared with that of individuals suffering from lower duration of epilepsy. For each year in increase of duration of epilepsy, the odds of depression decreased by 2% (95% CI 0.3% to 5.1%). The prevalence of depression is high in patients with epilepsy. Risk of having depression is higher during the early phase of the illness. Therefore, it is important to screen patients with epilepsy for depressive disorder during the early course of the illness.

The efficacy of homoeopathy on enhancement in quality of life in children with epilepsy

Objectives: To study the improvement in the Quality of Life in Epilepsy affected Children’s with Homoeopathic medicines. To find the Homoeopathic remedies in the treatment of Epilepsy from complete repertory.Background: Children with epilepsy particularly suffer from the Problems with Chronic antiepileptic medication use which is associated with possible side effects and have an influence on a child´s overall health and quality of life. Homeopathy system of medicine which not only relieves the symptom of the disease but also improve the quality of life in chronic diseases, as the medicine selection is based on the individuality of the patient. Materials and Methods: Random selection of 15 cases presenting with similar symptoms of Epilepsy from the OPD, and peripheral centres of Sarada Krishna Homoeopathic Medical College are taken. Pre and post treatment analysis was done using Quality of Life in Childhood Epilepsy scale score (QOLCE-55).Remedies prescribed based on the rubrics selected from the complete repertory.Result and Conclusion: Comparing the before and after scores based on Quality of life scale 55 for epilepsy of all the 15 cases taken for this study, 7 cases showed marked improvement, 5 cases showed moderate improvement, 1 case showed mild improvement and 2 case did not show any improvement. The study concludes that individualistic approach of Homoeopathy on epilepsy affected children’s found effective in the management of epilepsy as well as improvement in the quality of life.

The perceived effects of cannabis products in the management of seizures in CDKL5 Deficiency Disorder

IntroductionCDKL5 Deficiency Disorder (CDD) is a severe treatment-resistant form of early-onset epilepsy. Current treatment options are often ineffective and associated with adverse effects, forcing families to seek alternative therapies for their children including products derived from cannabis. Reportsof miraculous cures and a public preferencefor ‘natural’ therapies have resulted in considerable public interest, and so this study aimed to characterize the use of cannabis in these individuals, as well as compare caregiver perceptions of efficacy and safety to objective evidence of seizure control and number of antiepileptic drugs used. MethodsFamilies from the International CDKL5 Disorder Database were invited to complete questionnaires which included data relating to their child’s current and past treatments, including use of any cannabis-derived preparations. Perceived effects on seizure control, as well as additional benefits and adverse effects were reported. Seizure frequency and number of antiepileptic drugs were compared between those actively using cannabis products and those who were not. Longitudinal analysis was performed on a subset of the study population to compare these same variables at pre-treatment and post-treatment time points. ResultsThree hundred and twelve caregivers answered questions regarding their child’s use of antiepileptic medications. Of these, 82 (26%) described use of cannabis preparations either at present, or in the past, with the most common being cannabidiol. Of 70 caregivers that described their perceived effect on seizure control, more than two thirds reported an improvement in seizure control, either temporary (16%) or lasting (54%). Additional benefits included improvements in attention, cognition, and sleep. The majority of responses (78%) described adverse effects as ‘none’, though some reported an increase in sedation and gastrointestinal upset. There was no reduction in the median seizure frequency nor the number of different antiepileptic drugs, for those who were actively using cannabis products compared to those who were not. Similarly, individuals who were not using cannabis products at an initial time point had no differences in seizure frequency nor number of antiepileptic drugs at a second timepoint when they had started using this treatment. ConclusionsAlthough this is an observational study, limited by potential participation bias and the unreliable nature of unblinded self-assessment, it suggests that caregivers perceive cannabis products, especially cannabidiol, to have a tolerable adverse effect profile and adequate efficacy. Despite this, cannabis was not associated with a reduction in seizure frequency nor number of antiepileptic drugs when compared to non-users or when compared to pre-treatment. Randomized controlled trials are urgently needed to more reliably assess this treatment’s safety and efficacy.

Transcranial magnetic stimulation for the treatment of epilepsy.

Epilepsy is a highly prevalent neurological condition characterised by repeated unprovoked seizures with various aetiologies. Although antiepileptic medications produce clinical improvement in many individuals, nearly a third of individuals have drug-resistant epilepsy that carries significant morbidity and mortality, and even individuals who have clinical improvement from antiepileptic medications often report iatrogenic symptoms. There remains a need for non-invasive and more effective therapies for this population. Transcranial magnetic stimulation (TMS) uses electromagnetic coils to excite or inhibit neurons, with repetitive pulses at low-frequency producing an inhibitory effect that could conceivably reduce cortical excitability associated with epilepsy. This is an updated version of the original Cochrane Review published in 2016. To assess the evidence for the use of TMS in individuals with drug-resistant epilepsy compared with other available treatments in reducing seizure frequency, improving quality of life, reducing epileptiform discharges, antiepileptic medication use, and side effects. For the latest update, we searched the Cochrane Register of Studies (CRS Web) and MEDLINE (Ovid 1946 to 2 June 2020). CRS Web includes randomised or quasi-randomised controlled trials from PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP), the Cochrane Central Register of Controlled Trials (CENTRAL), and the specialised registers of Cochrane Review Groups including Epilepsy. We included randomised controlled trials that were double-blinded, single-blinded, or unblinded, and placebo controlled, no treatment, or active controlled, which used repetitive transcranial magnetic stimulation (rTMS) without restriction of frequency, coil, duration or intensity on participants with drug-resistant epilepsy. We extracted information from each trial including methodological data; participant demographics including baseline seizure frequency, type of epileptic drugs taken; intervention details and intervention groups for comparison; potential biases; and outcomes and time points, primarily change in seizure frequency or responder rates, as well as quality of life and epileptiform discharges, adverse effects, and changes in medication use. The original search revealed 274 records from the databases that after selection provided seven full-text relevant studies for inclusion. The latest search identified 179 new records from the databases that after evaluation against the inclusion and exclusion criteria provided one additional full-text relevant study. The eight included studies (241 participants) were all randomised trials; seven of the studies were blinded. Methodological and design information in the included studies was unclear, particularly relating to randomisation and allocation concealment methods. We were not able to combine the results of the trials in analysis due to differences in the studies' designs. For the current update, two of the eight studies analysed showed a statistically significant reduction in seizure rate from baseline (72% and 78.9% reduction of seizures per week from the baseline rate, respectively), whilst the other six studies showed no statistically significant difference in seizure frequency following rTMS treatment compared with controls (low-certainty evidence). One study assessed quality of life and found that more participants showed improvement in quality of life scores with active treatments compared to the sham treatment, but this only involved seven participants (very low-certainty evidence). Four studies evaluated our secondary endpoint of mean number of epileptic discharges, three of which showed a statistically significant reduction in discharges after active rTMS treatment. Adverse effects were uncommon in the studies and typically involved headache, dizziness, and tinnitus; however increased seizure frequency did occur in a small number of individuals. The included trials reported no significant changes in medication use. Overall the risk of bias was either low or unclear, and the certainty of the evidence was low to very low. Overall, we judged the certainty of evidence for the primary outcomes of this review to be low to very low. We found some evidence to suggest that rTMS is safe but some adverse events were experienced. The variability in technique and outcome reporting prevented meta-analysis, and the evidence for efficacy of rTMS for seizure reduction is still lacking, despite reasonable evidence that it is effective at reducing epileptiform discharges.

Antiepileptic drugs and prostate cancer risk in the Finnish Randomized Study of Screening for Prostate Cancer.

Antiepileptic drugs (AEDs) with histone deacetylase (HDAC) inhibitor properties decrease prostate cancer (PCa) cell proliferation in vitro. A population-based cohort of 78 615 men was used to evaluate the risk of PCa among users of AEDs. Study population was linked to the Finnish national prescription database to obtain information on individual medication reimbursements in 1996 to 2015. Cox regression with antiepileptic medication use as a time-dependent variable was used to analyze PCa risk overall, and low, medium and high-risk PCa separately. The analysis was adjusted for age, screening trial arm, and other drugs in use, including statins, antidiabetic drugs, antihypertensive drugs, aspirin, and nonsteroidal anti-inflammatory drugs. Compared to the nonusers of AEDs, overall PCa risk was decreased among AED users (hazard ratio [HR]=0.86, 95%confidence interval [CI]=0.76-0.96). A similar PCa risk decrease was observed among users of HDACi AEDs (HR=0.87, 95%CI=0.76-1.01), but no risk difference was found when comparing HDACi AED users to users of other AEDs (HR=0.98, 95%CI=0.76-1.27). Our study showed a decrease in overall PCa risk among men using AEDs compared to nonusers. The risk associations were similar for HDAC inhibitors as for AEDs in general.

Brain-derived neurotrophic factor levels in newly diagnosed patients with bipolar disorder, their unaffected first-degree relatives and healthy controls.

Brain-derived neurotrophic factor (BDNF), which facilitates neuroplasticity and synaptogenesis, may be decreased in bipolar disorder, but has not been systematically investigated in people with newly diagnosed bipolar disorder and unaffected first-degree relatives. To compare BDNF levels in patients with newly diagnosed bipolar disorder, their unaffected first-degree relatives and healthy controls. The study investigated plasma BDNF levels in patients (n = 371) with newly diagnosed bipolar disorder, their unaffected first-degree relatives (n = 98) and healthy controls (n = 200) using enzyme-linked immunosorbent assay. We further investigated associations between BDNF levels and illness-related variables and medication status. BDNF levels were found to be 22.0% (95% CI 1.107-1.343) higher in patients with bipolar disorder compared with healthy controls (P < 0.001) and 15.6% higher in unaffected first-degree relatives compared with healthy controls (95% CI 1.007-1.327, P = 0.04), when adjusting for age and gender. Further, BDNF levels were positively associated with duration of illness at a trend level (P = 0.05), age (P = 0.001) and use of anti-epileptic medication (P = 0.05). These findings suggest that BDNF levels are not decreased in the early stages of bipolar disorder and in unaffected first-degree relatives contrasting with prior findings during later stages of the illness.