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Classic Toxic Epidermal Necrolysis (TEN) in Lupus Erythematosus (LE) is rare and that caused by oxcarbazepine is even rarer. It can be triggered/induced by various insults, the most prominent being drugs. Herein, we describe a young female, a diagnosed case of LE with lupus nephritis, with recent-onset central nervous system vasculitis (incidentally detected on neuroimaging while she was being evaluated for a recent-onset behavioural change), who within a month of exposure to the drug developed an extensive exfoliating skin rash with mucosal lesions, which on histopathological evaluation showed TEN in LE, triggered by Oxcarbazepine, which was commenced for seizure prophylaxis. She was managed with pulse methylprednisolone, followed by intravenous immunoglobulin (IVIg), after which she made a satisfactory recovery. It is highlighted that TEN in LE patterns must be recognized in an emergency and Acute Syndrome of Apoptotic Panepidermolysis (ASAP) concept applied promptly without awaiting diagnoses. Further, many common drugs possibly trigger this pathology making the rara-avis not rare anymore!

Oxcarbazepine (OXZ) and levetiracetam (LEV) are two new generation anti‐epileptic drugs, often co‐administered in children with enzyme‐inducing antiepileptic drugs (EIAEDs). The anti‐epileptic effect of OXZ and LEV are linked to the exposure of OXZ’s active metabolite 10‐monohydroxy derivative (MHD) and (the parent) LEV, respectively. However, little is known about the confounding effect of age and EIAEDs on the pharmacokinetics (PKs) of MHD and LEV. To address this knowledge gap, physiologically‐based pharmacokinetic (PBPK) modeling was performed in the PK‐Sim software using literature data from children greater than or equal to 2 years of age. Age‐related changes in clearance (CL) of MHD and LEV were characterized, both in the presence (group 1) and absence (group 2) of concomitant EIAEDs. The drug‐drug interaction effect of EIAEDs was estimated as the difference in CL estimates between groups 1 and 2. PBPK modeling suggests that bodyweight normalized CL (ml/min/kg) is higher in younger children than their older counterparts (i.e., due to an influence of age). Concomitant EIAEDs further increase MHD’s CL to a fixed extent of 25% at any age, but EIAEDs’ effect on LEV’s CL increases with age from 20% (at 2 years) to 30% (at adolescence). Simulations with the maximum recommended doses (MRDs) revealed that children between 2 and 4 years and greater than 4 years, who are not on EIAEDs, are at risk of exceeding the reference exposure range for OXZ and LEV, respectively. This analysis demonstrates the use of PBPK modeling in understanding the confounding effect of age and comedications on PKs in children and adolescents.

The article presents the key positions on the diagnosis and treatment of migraine. The structure of migraine attacks, complications, principles of treatment of different types of migraine attacks and preventive treatment are presented. Attention is paid to the use of anticonvulsants.

Aim Hypothyroxinemia might be easily ignored, due to attention is typically paid to individuals with elevated thyroid stimulating hormone (TSH). In this study, we aimed to evaluate the association of oxcarbazepine use as adjuvant for treatment of schizophrenia with hypothyroxinemia and central set point of thyroid homeostasis. Methods This retrospective cohort study was conducted in the "Second Affiliated Hospital of Xinxiang Medical University". Inpatients with a diagnosis of schizophrenia admitted between January 2016 and October 2019 with normal thyroid function at admission were included. Oxcarbazepine use was the exposure measure. Newly developed hypothyroxinemia was the primary outcome measure and parameters of thyroid homeostasis central set point as measured by "TSH index" and "thyroid feedback quantile-based index (TFQI)" were the secondary outcome measures. Results A total of 1,207 eligible patients were included. The occurrence of hypothyroxinemia in patients who received oxcarbazepine was higher (35/107, 32.7%) than in those patients who did not (152/1099, 13.8%), with adjusted relative risk of 2.24 and 95% confidence interval of 1.57 and 3.17. Oxcarbazepine use was associated with greater reduction in TSH index (adjusted β -0.33 and 95% confidence interval -0.48, -0.19) and TFQI (adjusted β -0.24 and 95% confidence interval -0.31, -0.16). Conclusion Oxcarbazepine use was independently associated with increased risk of developing hypothyroxinemia, and greater reduction in TSH index and TFQI, suggesting that impaired central set point of thyroid homeostasis might be involved in the mechanism of oxcarbazepine induced hypothyroxinemia.

Aim: The purpose of this study was to examine the effects of antiepileptics on thyroid function tests and to compare these effects among different antiepileptics. Materials and Methods: Two hundred and twenty patients (102 female and 118 male) aged 1-17 years indicated for antiepileptic drug (AED) therapy for epilepsy were enrolled in this study which was performed in a child neurology clinic between January 2014 and January 2018. Those patients using a single AED and with complete seizure control were included. In this study period, according to the local protocol, we measured free thyroxine (fT4) and thyroid-stimulating hormone (TSH) levels at the beginning of treatment and at the 12th month of AED therapy. Results: The mean age of the patients was 10.2 +/- 4.4 years. TSH elevation was observed in only eight patients. These eight patients' thyroid autoantibodies were negative and their thyroid ultrasonography were normal. Subclinical hypothyroidism (TSH: 5-10, fT4 normal) was present in three of these eight patients, and they were therefore not started on medication. The other five were started on L-thyroxine. Four of these were using valproic acid and one was using carbamazepine. We found no significant difference between TSH and fT4 levels measured before the start and at the 12th month of drug therapy, nor among the different AEDs used. Conclusion: AEDs have no marked effects on thyroid function, and may therefore be safely used from that perspective. WOS:000718894700005

Purpose To evaluate the current trends and factors associated with the first anti-seizure medications (ASMs) prescribed for epilepsy in Taiwan. Methods Data for patients with epilepsy were collected from the National Health Insurance Research Database, a population-based claims database. We selected patients with newly diagnosed epilepsy from 2013 to 2016. Multivariate logistic regression was used to examine the factors associated with the selection of newer ASMs for the first prescription. Results A total of 73,891 patients with newly diagnosed epilepsy were eligible for the study, and the annual incidence was approximately 0.79 per 1,000 people. The five ASMs most prescribed for monotherapy were valproic acid, phenytoin, levetiracetam, gabapentin, and oxcarbazepine, accounting for nearly 90% of all ASMs. Valproic acid was the most-prescribed ASM (more than 30%), and levetiracetam has replaced phenytoin as the second choice since 2015. Factors associated with the selection of newer ASMs for the first prescription were patients’ year of diagnosis, gender, socioeconomic level, and previous or existing comorbidities and the profiles of the care providers (accreditation level, service volume, geographic location, and degree of urbanization of the surrounding area). Conclusion The data indicated that the trends in ASMs first prescribed for patients in Taiwan accorded with most of the international epilepsy treatment guidelines. However, there were some differences between our results and those in developed countries. In addition, we observed a large urban-rural disparity in the administration of ASMs.

We aim to report the major congenital malformation (MCM) rates for new and old anti-epileptic drugs (AED) exposures during the first trimester of pregnancy in women with epilepsy (WWE).We extracted relevant data on drug exposure and malformation rate from the records of a prospective observational registry (Kerala Registry of Epilepsy and Pregnancy) for all completed pregnancies between 1998 and 2019. A comprehensive and uniform criterion with detailed guideline was used for assessment of malformations. We employed generalised linear model to generate adjusted incidence rate ratios (aIRR) of MCM in AED exposed group as compared to AED unexposed group, after adjustment for age and educational status of mothers' and epilepsy classification.The unadjusted MCM rate was 6.2% for all the infants included in the study (148/2328); 4.7% for the unexposed group (16/340), and 6.6% for the exposed group (132/1988). The aIRR of MCM as compared to unexposed group was similar for all monotherapies; lamotrigine (0.50; 95% CI 0.07-3.68), levetiracetam (1.16; 0.43-3.11), oxcarbazepine (1.61; 0.62-4.21) valproate (1.71, 0.93-3.19), phenytoin (1.21, 0.51-2.90), carbamazepine (0.99, 0.54-1.82), and phenobarbitone (1.20, 0.52-2.74). However, the point estimates suggest least risk with lamotrigine and highest risk with valproate. Polytherapy with high-dose valproate carried significantly higher risk of MCM as compared to the unexposed group (aIRR=4.12; 2.18-7.79, p0.001). The aIRR of GTCS during pregnancy was 1.63 (95% CI 1.12-2.37, p = 0.011) for monotherapy with new AEDs (lamotrigine, levetiracetam or oxcarbazepine) as compared to old AEDs (phenobarbitone, phenytoin, carbamazepine, or valproate).The MCM risk was significantly higher for polytherapy with high dose valproate. It did not differ substantially between different AED monotherapies although point estimate was lowest with lamotrigine. Pregnant women on new AEDs report higher likelihood of GTCS than women on old AEDs during pregnancy.

To study the world experience on the influence of antiepileptic drugs on sexual function and fertility in men and to find the drugs with the least negative impact on these functions, the search for the articles and abstracts in the MedLine, The Cochrane Library, Scopus, Google scholar databases was performed with such keywords as fertility, male fertility, men fertility, antiepileptic drugs, epilepsy, sex hormones, sperm parameters, sexual and reproductive health, sexual function. The analysis of the obtained data revealed that there is a relative lack of information on the effect of antiepileptic drugs on fertility in men, which necessitates further researches to study the influence of these drugs on the fertility of men, not just women. When prescribing antiepileptic drugs, in turn, it is desirable to give preference to drugs with the least negative impact on sexual function and fertility, such as levetiracetam, lamotrigine and oxcarbazepine., Для изучения мирового опыта влияния противоэпилептических препаратов на половые функции и фертильность у мужчин и отбора медикаментов с наименьшим отрицательным влиянием на эти функции проведен поиск статей и резюме в базах данных ресурсов MedLine, The Cochrane Library, Scopus, Google scholar с использованием таких ключевых слов, как fertility, male fertility, men fertility, antiepileptic drugs, epilepsy, sex hormones, sperm parameters, sexual and reproductive health, sexual function. В результате анализа полученных данных установлено, что существует относительная недостаточность информации о влиянии противоэпилептических препаратов на фертильность у мужчин, что обусловливает необходимость проведения дальнейших исследований, направленных на изучение влияния этих препаратов именно на фертильность мужчин, а не только женщин. При назначении противоэпилептических средств, в свою очередь, желательно отдавать предпочтение препаратам с минимальным негативным воздействием на половые функции и фертильность, таким как леветирацетам, ламотриджин или окскарбазепин., Для вивчення світового досвіду впливу протиепілептичних препаратів на статеві функції і фертильність у чоловіків і відбору медикаментів з найменшим негативним впливом на ці функції проведений пошук статей та резюме у базах даних ресурсів MedLine, The Cochrane Library, Scopus, Google scholar з використанням таких ключових слів, як fertility, male fertility, men fertility, antiepileptic drugs, epilepsy, sex hormones, sperm parameters, sexual and reproductive health, sexual function. У результаті аналізу отриманих даних встановлено, що існує відносна недостатність інформації щодо впливу протиепілептичних препаратів на фертильність у чоловіків, що обумовлює необхідність проведення подальших досліджень, спрямованих на вивчення впливу цих препаратів саме на фертильність чоловіків, а не тільки жінок. При призначенні протиепілептичних засобів, у свою чергу, бажано надавати перевагу препаратам з найменшим негативним впливом на статеві функції і фертильність на зразок леветирацетаму, ламотриджину й окскарбазепіну.

In this study, we performed a study on 106 children with epilepsy who were treated with sodium valproate (the VPA group, n = 37), oxcarbazepine (the OXC group, n = 34), or levetiracetam (the LEV group, n = 35). In addition, the clinical data of epileptic children who were newly diagnosed in the same period without antiepileptic drug (AED) treatment (the untreated group, n = 35) and normal children who received physical examination in our hospital (the healthy group, n = 35) were selected as controls. We analyzed the efficacy and safety of different AEDs, used blood ammonia and homocysteine levels as the observation indicators, and calculated the incidence of hyperammonemia (VAH) and hyperhomocysteinemia (HHcy) treated with different AEDs. And, based on the effect of epilepsy status on the cognitive function of patients, we also analyzed the effect of different AED treatments on children’s cognitive function. Our results show that sodium valproate, oxcarbazepine, and levetiracetam are all effective in the treatment of children with epilepsy and can be used as the first-line choice of antiepileptic treatment for children with epilepsy. However, compared with sodium valproate, levetiracetam and oxcarbazepine have a lower incidence of adverse drug reactions and do not cause an increase in blood ammonia and Hcy levels, so they have higher safety of drug treatment. In addition, compared with sodium valproate, levetiracetam and oxcarbazepine have better recovery of cognitive function in children with epilepsy and so they have better application value.

Introduction. Zoster is caused by the reactivation of a dormant viral infection, and is characterized by painful, vesicular lesions along a dermatome. Neuritic pain associated with zoster can be treated with anticonvulsant medications. Case Report. An immunocompetent adult physician developed prominent zoster lesions in the trigeminal nerve distribution. Treatment included antiviral therapy for the acute infection, and pharmacotherapy for neuritic pain. Pharmacotherapy included several anticonvulsant agents, with labial angioedema developing after initiation of oxcarbazepine. Discussion. The case is notable for the pictorial timeline of lesion development, as well as the marked incident angioedema following initiation of treatment for neuritis with oxcarbazepine. Conclusions. Clinicians should remain vigilant for drug-induced facial angioedema when treating patients with trigeminal zoster-related neuritis due to the potential for angioedema to aggravate a lesion, resulting in scarring. Angioedema of the head and neck should be closely monitored due to the potential for airway compromise.

Paroxysmal kinesigenic dyskinesia (PKD) is a rare condition characterized by abnormal involuntary movements that are precipitated by a sudden movement. PKD is often misdiagnosed with psychogenic movement disorders. Carbamazepine is usually the first choice of medication due to its well-established evidence but could induce Stevens-Johnson syndrome. We report a 21-year-old male patient with PKD referred to our movement disorders clinic after being misdiagnosed with conversion syndrome. PRRT2 gene testing using next-generation sequencing revealed a mutation in c.649dupC p. (Arg217fs). The patient responded well to carbamazepine but had to withdraw the treatment due to carbamazepine-induced Stevens-Johnson syndrome after 3 weeks of medication. Our patient did not respond to trials of levetiracetam and phenytoin but finally responded well to oxcarbazepine. The patient was followed up for 4 years, during which he had no attacks and no side effects. Here, we present a PKD case with carbamazepine-induced Stevens-Johnson syndrome successfully treated with oxcarbazepine despite the risk of cross-reactive skin eruption between these antiepileptics. Careful history taking and examining patient’s attacks are crucial to accurate diagnosis and treatment in PKD patients.

Shapiro syndrome (SS) is a rare disorder characterized by a triad of spontaneous periodic hypothermia, hyperhidrosis, and corpus callosum agenesis (CCA). Less than 80 cases have been reported so far. Its etiology and pathophysiology, however, are still unclear. In his original publication, Shapiro et al attributed these signs to dysregulation of encephalic pathways secondary to CCA. Nevertheless, since the syndrome was originally described, 19 patients have been reported with an intact corpus callosum, considering it a variant of the condition. In this article, we report the clinical outcome of a 20-month-old girl with SS without evidence of CCA, presenting an atypical onset in which sleep abnormalities were the most prominent complaints, with the classical episodic manifestations appearing afterward; the patient exhibited an optimal response to management with oxcarbazepine. To our understanding, this is fourth-youngest case ever reported of this SS variant, and the first to present sleep disturbances as the most prominent complaint.

AIM: To conduct a retrospective comparative analysis of the efficacy and safety of epilepsy therapy with antiepileptic drugs. MATERIALS AND METHODS: The analysis of the treatment of 428 patients with epilepsy at the Children’s City Hospital No. 8 in Kazan, receiving antiepileptic drugs. RESULTS: It was found that valproic acid is more effective in the treatment of idiopathic generalized epilepsies compared to focal epilepsies ( p = 0.0006). Valproate and carbamazepine were the most effective in the treatment of focal epilepsy with short- and long-term follow-up. Valproic acid is more effective than topiramate ( p = 0.02), oxcarbazepine ( p = 0.003), and levetiracetam ( p = 0.003) in the treatment of focal epilepsy in short- and long-term follow-up. Carbamazepine is more effective than topiramate ( p = 0.01), oxcarbazepine ( p = 0.02), and levetiracetam ( p = 0.001) in the treatment of focal epilepsy in long-term follow-up. It was revealed that more often they complained about side effects when using carbamazepine (63.2%). Levetiracetam was found to be better tolerated compared to valproate ( p = 0.0006) and carbamazepine ( p = 0.0006). Topiramate is better tolerated than carbamazepine ( p = 0.02) and valproate ( p = 0.03). Oxcarbazepine is better tolerated than carbamazepine in women ( p = 0.04). CONCLUSIONS: When choosing an antiepileptic drug, it is necessary to be guided by the principle: first the basic, and then the drugs of the next generations, in the future, rely on information about the tolerability of the drug. It is necessary to evaluate the therapeutic effect of antiepileptic drugs with long-term observation, and use the criterion of “complete absence of seizures” as an indicator of the effectiveness of drugs.

Introduction The present evidence indicates that approximately 70% of patients with epilepsy can be successfully treated with antiepileptic drugs (AEDs). A significant proportion of patients are not under sufficient control and pharmacoresistant epilepsy is clearly associated with poor quality of life and increased morbidity and mortality. There is a great need for newer therapeutic options able to reduce the percentage of drug-resistant patients. Areas covered A number of hypotheses trying to explain the development of pharmacoresistance have been put forward. These include: target hypothesis (altered AED targets), transporter (overexpression of brain efflux transporters), pharmacokinetic (overexpression of peripheral efflux transporters in the intestine or kidneys), intrinsic severity (initial high seizure frequency), neural network (aberrant networks) and gene variant hypothesis (genetic polymorphisms). Expert opinion A continuous search for newer AEDs or among non-AEDs (blockers of efflux transporters, interleukine antagonists, cyclooxygenase inhibitors, mTOR inhibitors, angiotensin II receptor antagonists) may provide efficacious drugs for the management of drug-resistant epilepsy. Also, combinations of AEDs exerting synergy in preclinical and clinical studies (for instance, lamotrigine + valproate, levetiracetam + valproate, topiramate + carbamazepine) might be of importance in this respect. Preclinically antagonistic combinations must be avoided (lamotrigine + carbamazepine, lamotrigine + oxcarbazepine).

Neurocysticercosis (NCC) is a significant problem in India and other developing countries; however, several aspects of this disease have no clear, practical guidelines. There is a need for pragmatic guidelines, summarizing the available evidence, and filling in the gaps in evidence with expert advice to manage children with neurocysticercosis. An expert group (16 members) and a writing group (8 members) was constituted, consisting of members with varied expertise. It included pediatric neurologists (18), neurologist (1), Neuroradiologists (4), and a parasitologist (1). The writing group divided the six topics and reviewed the literature on the topics individually to determine the clinical questions for which no clear guidance was available from the literature. The experts were then contacted and opinions were obtained online. The Delphi consensus method was adopted to arrive at a general consensus regarding various questions, with both the experts and the writing group members contributing. The final guidelines were then drafted by the writing group. Diagnosis of NCC should be based on clinical history and neuroimaging. Contrast-enhanced magnetic resonance imaging of the brain is the modality of choice. For single enhancing lesion, albendazole therapy for 10–14 days is recommended, and it should be combined with praziquantel for 10–14 days for more than one ring-enhancing lesions. For persistent lesion, the same dose and duration of albendazole or concurrent administration of albendazole and praziquantel should be given. Pulse intravenous steroids should be used to reduce the acute symptomatic edema in children with cysticercal encephalitis. Carbamazepine or oxcarbazepine are best suited for seizure prophylaxis for those who present with seizures; phenytoin and levetiracetam are the other alternatives. In the case of NCC presenting with symptoms other than seizures, there appears to be no role for routine anti-seizure medication prophylaxis. For a single ring-enhancing lesion, six months of anti-seizure medication is sufficient if the lesion resolves on follow-up. Those with persistent lesions, calcification, or multiple lesions, require a longer treatment duration of at least 24 months.

Pharmacodynamic aggravation (PA) is an unpredictable increase in the frequency, the severity of existing seizures, and/or development of new seizure types despite rational (adequate for seizure type and epilepsy form) antiepileptic drug (AED) prescription. Many mechanisms and predictors of its development are still poorly understood.Objective: to analyze PA of seizures in patients with newly diagnosed focal epilepsy receiving monotherapy with sodium channel blockers with epileptiform activity index (EAI) assessment.Patients and methods. We enrolled 201 patients with newly diagnosed focal epilepsy aged 16—81 years. In twelve months, patients had five follow-up visits. At each visit, treatment tolerability and efficacy were assessed, taking into account changes in the type, severity, and frequency of seizures. Additionally, at each visit, video-electroencephalographic monitoring was performed with EAI assessment. PA of seizures occurred in patients on oxcarbazepine, carbamazepine, and lacosamide therapy.Results and discussion. Five patients with PA of seizures had increased total EAI and EAI before sleep at the second follow-up visit after sodium channel blockers prescription. Electroencephalographic correlates of PA occurred earlier than clinical manifestations. In patients with PA, the absolute increase in EAI was minimal in patients receiving oxcarbazepine, and lacosamide therapy was associated with a minimal relative increase in EAI. At the end of the follow-up, total EAI decreased by 54—80% relative to its initial value in all five patients. The difference in the total index during the first and last visits was statistically significant.Conclusion. Due to the low level of knowledge about PA of seizures, it seems necessary to consider its possibility in all cases of increased frequency, aggravation, or change in the type of seizures after the AED treatment initiation or an increase in its dose. It is also possible to use changes in total EAI and EAI before sleep as an early objective marker of PA in adults with focal epilepsy.

Hyponatremia (HN) is the most common electrolyte imbalance (defined as a serum sodium concentration Na(S) of

Aromatic antiepileptic drugs (AEDs)-induced cutaneous adverse drug reactions (cADRs) add up to the limited use of the AEDs in the treatment and prevention of seizures. Human leukocyte antigen-B (HLA-B) alleles have been linked to AEDs-induced cADRs. We investigated the association between cADRs (including Stevens–Johnson syndrome; SJS/toxic epidermal necrolysis; TEN, drug reaction with eosinophilia and systemic symptoms; DRESS, and Maculopapular eruption; MPE) caused by AEDs (phenytoin, carbamazepine, lamotrigine, phenobarbital and oxcarbazepine) and HLA-B alleles in Thai population. Through the case-control study, 166 patients with AEDs-induced cADRs, 426 AEDs-tolerant patients (AEDs-tolerant controls), and 470 healthy subjects (Thai population) were collected. The HLA genotypes were detected using the polymerase chain reaction-sequence specific oligonucleotide probe (PCR-SSOP) method. We also performed a meta-analysis with these data and other populations. The carrier rate of HLA-B*15:02 was significantly different between AEDs-induced cADRs group and AEDs-tolerant group (Odds ratio; OR 4.28, 95% Confidence interval; CI 2.64–6.95, p p HLA-B*15:02 with AEDs-induced cADRs (OR 4.77, 95%CI 1.79–12.73, p HLA-B*15:02 was associated with SJS/TEN induced by AEDs (OR 10.28, 95%CI 6.50–16.28, p p = 0.001) and carbamazepine (OR 137.69, 95%CI 50.97–371.98, p HLA-B*15:02 and AEDs-induced SJS/TEN was demonstrated with an OR of 10.79 (95%CI 5.50–21.16, p HLA-B*08:01, HLA-B*13:01, and HLA-B*56:02 were significantly higher in the DRESS group compared with the AEDs-tolerant group (p = 0.029, 0.007, and 0.017, respectively). The HLA-B*15:02 allele may represent a risk factor for AEDs-induced cADRs.

Oxcarbazepine (OXC) is an antiepileptic drug (AED) used in children and adults as initial and adjunctive therapy for focal epilepsy (FE). It has been used in Russia since 2007; however, only a few studies have been published on its use in Russian patients to date.Objective: to assess the effectiveness and tolerability of OXC as initial therapy for FE in adults and adolescents, as well as to study epileptiform activity index (EAI) changes during treatment and its relationship with treatment effectiveness and tolerability.Patients and methods. We evaluated treatment effectiveness and tolerability and EAI in 89 adults with newly diagnosed FE aged 15–75 years for 12 months. Patients were divided into three subgroups according to the OXC treatment regimen. Side Effects of Anti-Epileptic Drugs (SIDAED) scale was used to assess treatment tolerability. Retention rate and seizure frequency changes were used to evaluate treatment effectiveness. EAI changes were assessed with video electroencephalography monitoring (4–24 h) during each visit (baseline, after 1, 3, 6, and 12 months).Results and discussion. The retention rate in patients on OXC monotherapy after 12 months was 71.9%, almost one-half of them (46.1%) achieved sustained remission. More than half of patients (52.9%) were prescribed 1200 mg/day of OXC, 12.3% – Conclusion. OXC, as the initial AED for FE, has demonstrated high treatment effectiveness and tolerability. In addition, total EAI 2.5-fold reduction allows its usage as an additional quantitative marker of OXC treatment effectiveness.

Trigeminal neuralgia (TN) is a highly disabling disorder characterised by very severe, brief and electric shock like recurrent episodes of facial pain. New diagnostic criteria, which subclassify TN on the basis of presence of trigeminal neurovascular conflict or an underlying neurological disorder, should be used as they allow better characterisation of patients and help in decision-making regarding medical and surgical treatments. MR imaging, including high-resolution trigeminal sequences, should be performed as part of the diagnostic work-up. Carbamazepine and oxcarbazepine are drugs of first choice. Lamotrigine, gabapentin, pregabalin, botulinum toxin type A and baclofen can be used either alone or as add-on therapy. Surgery should be considered if the pain is poorly controlled or the medical treatments are poorly tolerated. Trigeminal microvascular decompression is the first-line surgery in patients with trigeminal neurovascular conflict while neuroablative surgical treatments can be offered if MR imaging does not show any neurovascular contact or where patients are considered too frail for microvascular decompression or do not wish to take the risk.

Allergic reactions are common reasons for withdrawal of oxcarbazepine treatment in patients with epilepsy. However, some patients are not responsive to other antiseizure medications. Herein, two pediatric patients with epilepsy and allergic to oxcarbazepine to whom oxcarbazepine therapy was successfully reintroduced are described. The reintroduction strategy used in this study was simple, feasible, and suitable for the reintroduction of oxcarbazepine in pediatric patients with epilepsy.

OBJECTIVE To describe the clinical characteristics of cutaneous adverse reactions and cross-sensitivity induced by antiseizure medications and compare the pattern of use of antiseizure medications in patients with epilepsy according to skin rash history. METHODS We analysed patients with a history of skin rash presenting for up to 12 weeks after initiating antiseizure medication. The history of skin rash was verified by medical charts, interviews, and identification of skin lesions by patients based on illustrative images. The minimum follow-up period was eight months. The control group comprised epilepsy patients with regular antiseizure medication use for at least 12 weeks without skin rash. We included 109 cases and 99 controls. RESULTS The median (interquartile range) period from the index rash was six years (2-11). Carbamazepine was the trigger medication in 48% of cases and induced skin rashes in all patients with cross-sensitivity and carbamazepine exposure. Stevens-Johnson syndrome, toxic epidermal necrolysis, or drug reactions with eosinophilia and systemic symptoms affected 36% of cases. Carbamazepine- or oxcarbazepine-induced maculopapular exanthema occurred earlier (median: one week) than that induced by other antiseizure medications (median: three weeks) (p=0.006). Cross-sensitivity was more common in patients with at least one episode of Stevens-Johnson syndrome (29%) and Stevens-Johnson/toxic epidermal necrolysis overlap (50%) than in patients with maculopapular exanthema (8%) (p=0.01). Although most cases were mild, the pattern of antiseizure medication use differed from that of controls, with a lower proportion of antiseizure medication typically associated with severe cutaneous adverse reactions (carbamazepine, phenytoin, phenobarbital, primidone, oxcarbazepine, and lamotrigine) (p

Background Epilepsy is a severe chronic neurologic disease with a prevalence of 0.7% worldwide; anti-seizure medications (ASMs) are the mainstay of epilepsy treatment. The effects of sociodemographic factors on the characteristics of initial treatment in patients with newly diagnosed focal epilepsy in Western China are unknown. This study was conducted to explore sociodemographic factors associated with initial treatment characteristics. Methods Patients with focal epilepsy on continuous ASM treatment who visited to our epilepsy center at Sichuan Provincial People’s Hospital between January 2018 and December 2019 were recruited. Data on initial treatment status and sociodemographic variables were obtained from the patients with a questionnaire designed by our researchers. We examined whether sociodemographic factors were associated with epileptic patients’ access to neurologists and prescriptions of individual ASMs. Results A total of 569 patients completed this study. We found that patients with a higher education level, aged Conclusions This observation suggests that sociodemographic characteristics are associated with access to neurologists and prescriptions of individual antiepileptic drugs. These data may help public health officials establish guidelines for doctors and distribute resources according to the needs of different patient groups.

Introduction Visuospatial abilities are fundamental for good school achievements and good daily functioning. Previous studies showed an impairment of visuospatial skills in pediatric patients with epilepsy; pharmacological treatment, although indispensable for the seizure control, could further affect cognitive functions. The aim of our study was to evaluate the visuospatial skills in children and adolescents with different forms of epilepsy well-controlled by antiseizure monotherapy, both at baseline and after one year follow-up, through a standardized neuropsychological assessment. Methods We recruited 207 children and adolescents (mean age = 10.35 ± 2.39 years) with epilepsy, well controlled by monotherapy with levetiracetam, valproic acid, ethosuximide, oxcarbazepine or carbamazepine and 45 age/sex-matched controls. All the participants performed the Rey-Osterrieth Complex Figure, a standardized test for visuospatial perception and visuospatial memory assessment, at baseline and after 12 month of drug therapy. Age, sex, executive functions, non-verbal intelligence, age at onset of epilepsy, epilepsy duration, epilepsy type, lobe and side of seizure onset were considered in our analysis. EEG, seizure frequency, and drug dose were also recorded. Results At baseline, the epilepsy group performed significantly worse than controls in the Immediate Recall test but not the Direct Copy test, without differences between epilepsy subgroups. Immediate Recall scores were related to age of seizure onset and epilepsy duration and executive functions. The re-assessment after 1 year showed that the Immediate Recall mean scores were not significantly changed in the levetiracetam and oxcarbazepine group, while they significantly worsened in the valproic acid, ethosuximide and carbamazepine groups. The Immediate Recall scores were correlated to age, age at onset of epilepsy, epilepsy duration, and executive functions. Conclusions Children with epilepsy may exhibit visuospatial memory impairment compared to their peer, that may be correlated to some features of the epilepsy itself and to the impairment of executive functions. Different antiseizure medications can affect visuospatial memory differently, so it is important monitoring this aspect in pediatric patients.

Impairments in cognition are common in epilepsy and may be caused or exacerbated by antiseizure medications (ASMs). Positive effects on cognition may also be seen with some ASMs. Cognitive outcomes are of particular concern in children who may be at an increased risk of cognitive adverse effects of treatment. A comprehensive literature search was conducted in PubMed in order to evaluate the evidence for cognitive changes associated with treatment with ASMs in paediatric epilepsy patients. The ASMs considered were those in the current edition of the British National Formulary (BNF). For most ASMs, remarkably few studies providing robust data on cognitive effects in paediatric patients were identified. The available evidence suggests cognitive impairments may be associated with treatment with phenobarbital. Topiramate and phenytoin are also associated with negative effects on cognition, in particular word-finding difficulties and other language deficits with topiramate, but there are few data available specifically on children. Lamotrigine, levetiracetam and fenfluramine are associated with improvements in some cognitive domains, although it is unclear whether these effects are directly attributable to the medications or are a result of improvements in seizures. Neutral effects on cognition (no substantial evidence of worsening) were suggested for carbamazepine, everolimus, lacosamide, oxcarbazepine, perampanel and valproate. There is limited data for cannabidiol, clobazam, eslicarbazepine acetate, ethosuximide, rufinamide, vigabatrin and zonisamide, although the available evidence suggests these drugs are not associated with severe cognitive impairment. There was too little information to reach conclusions about the effects of brivaracetam, felbamate, gabapentin, pregabalin, retigabine, stiripentol or tiagabine.

Psychiatric pharmacogenetic testing is commonly used by providers in primary care and mental health settings. The purpose of this article is to describe the extent to which psychiatric pharmacogenetic testing supports clinical practice. human leukocyte antigen (HLA)-A and HLA-B should be tested before initiating carbamazepine and oxcarbazepine due to risk of serious skin reactions. For psychotropic medications metabolized through the liver, limited evidence suggests testing for variation in metabolism through CYP2D6 and CYP2D19. For specific medication and genotype-phenotype variations, guidance through the Clinical Pharmacogenetics Implementation Consortium (CPIC) or the International Society of Psychiatric Genetics (ISPG) should be reviewed. Commercial tests interpret this information differently and should not be used for broad guidance. Clinicians should follow current guidelines from professional bodies such as CPIC or ISPG and test for HLA-A or HLA-B before initiating carbamazepine or oxcarbazepine. Evidence is limited for psychiatric pharmacogenetic testing. Clinicians should continue to follow best practice and clinical practice guidelines.

The nonclinical branch of regulatory pharmacology has traditionally relied on the sensitivity and specificity of regulatorily recommended bioassays. Nonetheless, any predictive testing (eg, safety pharmacology) with less than 100% sensitivity or 100% specificity is prone to deliver false positive or negative results (namely, outcomes discordant to the clinical gold standard). It was recently suggested that the statistics-based and regulatory pertinent "predictive values approach" (PVA) might help to reach a more predictive use of preclinical testing data. To resolve the associated probability of carcinogenicity to humans, the PVA was applied to 37 pharmaceuticals bearing inadequate epidemiological evidence of carcinogenicity, but identifiable as unequivocal mutagens. According to current knowledge, a 98.9% (or more) probability of carcinogenicity to humans was reckoned for those 37 genotoxic drugs. Accordingly, these pharmaceutical drugs might be either scientifically or regulatorily regarded as "carcinogenic to humans." In the USA, European Union, or Canada as examples, the great majority of these 37 pharmaceuticals are authorized for medical use in humans. From the results of the present appraisal, the following is suggested (1) for the pharmaceuticals listed in this report, to include significant carcinogenicity warnings in their prescribing information; (2) to conduct pharmacoepidemiology studies or risk-benefit analyses (if warranted), and (3) based on the respective risk-benefit analyses, to re-evaluate the authorization of hydralazine and phenoxybenzamine as antihypertensives, oxcarbazepine as an anticonvulsant, and phenazopyridine as a urinary tract antimicrobial or analgesic. For the four latter drugs (eg, phenoxybenzamine), a 99.5% probability of carcinogenicity to humans was estimated.

OBJECTIVES: To investigate the interaction among the efficacy, tolerability and overall effectiveness of the first antiseizure medication in patients 16 years or older with newly diagnosed epilepsy. MATERIALS AND METHODS: The study included 584 patients who were referred to the Tampere University Hospital between 1 January 1995 and 31 December 2005 and were diagnosed with epilepsy. All individuals were retrospectively followed up until 31 December 2006, until reaching at least one year of seizure freedom, or until death if before the cut-off date. RESULTS: Overall, after thorough validation of the epilepsy diagnosis 459 patients comprised the study cohort; among these patients, 73% of males and 60% of females became seizure-free for at least one year with the first antiseizure medication. The seizure freedom rate for focal epilepsy was 67%. There was no significant difference in focal epilepsy to achieve seizure freedom between oxcarbazepine, carbamazepine or valproic acid. The seizure freedom rate among patients above 60 years of age was 67%. For patients with structural and unknown aetiology, seizure freedom rates were 61.5% and 75.3%, respectively. Additionally, epileptiform activity on EEG in patients with focal epilepsy decreased odds of seizure freedom in adjusted logistic regression models (OR 0.55, p=0.036). CONCLUSIONS: This study provides a more positive prediction of seizure freedom compared with previous studies with the onset of epilepsy at 16 years or older with an overall estimation that two-thirds of patients with new-onset epilepsy obtain seizure freedom with the first antiseizure medication. acceptedVersion

Epileptic encephalopathy is a condition resulting from extreme forms of intractable childhood epilepsy. The disease can cause severe delays in cognitive, sensory, and motor function development, in addition to being fatal in some cases. Missense mutations of SCN8A, which encodes Nav1.6, one of the main voltage-gated sodium channel subunits in neurons and muscles, have been linked to early infantile SCN8A encephalopathy. Herein, we report the case of a 5-month-old girl with SCN8A encephalopathy with a novel missense mutation. Apart from intractable seizures and autistic phenotypes, the results of blood and biochemical tests, electroencephalogram (EEG) results, and brain magnetic resonance imaging (MRI) results were all normal. As the phenotypes caused by these mutations cannot be identified by any clinical, neuroimaging, or electrophysiological features, genetic sequencing should be considered to identify the underlying genetic causes. Although phenytoin is recommended as a last-resort treatment for SCN8A encephalopathy, the administration of the oxcarbazepine, instead of phenytoin, mitigated this patient’s intractable seizures.

Perioral myoclonia with absences (POMA) is not recognized as a unique electro-clinical syndrome and studies suggest its inclusion under the genetic generalized epilepsy (GGE) spectrum. The aim of this study was to explore the prevalence and electro-clinical homogeneity of this disorder in an epilepsy monitoring unit. Between 2013 and 2019, among drug-resistant epilepsy patients who were referred for video-telemetry, those diagnosed with POMA based on the presence of documented absences with prominently observed peri-oral muscular contractions accompanied by generalized EEG features were included. Among 62 patients who were diagnosed with absence epilepsy, five finally met the criteria for POMA (8.1%) with late childhood or adolescent onset of epilepsy. Four (80%) had a referral diagnosis of focal epilepsy based on historical focal features with exacerbation of seizures on oxcarbazepine. All five patients demonstrated brief absences with orbicularis oris muscle contractions accompanied by subtle focal phenomenology. One patient had concurrent axial-appendicular myoclonic jerks precipitated by hyperventilation. While four patients had strikingly identical interictal and ictal characteristics of typical absence epilepsy, one patient demonstrated additional atypical generalized polyspike discharges without a "dart-dome" morphology. Therapeutic response to introduction of sodium valproate was noted in all five patients. Features that were not consistent with the diagnosis were apparent in one patient who was re-classified with combined focal and generalized epilepsy. Differentiating aspects in this patient included multifocal discharges, background slowing, fast-recruiting ictal rhythms and valproate resistance. This is one of the largest case series of POMA. This entity, which falls under the spectrum of GGE, remains under-diagnosed and its distinctive electro-clinical features need to be recorded in order to prevent misclassification as focal epilepsy of probable opercular origin. Background-slowing, atypical ictal rhythms and valproate unresponsiveness are not consistent with the diagnosis of this unique absence epilepsy. [Published with video sequences].

Oxcarbazepine is recommended for the first line treatment of focal seizures in monotherapy and add-on therapy in both children and adults. It is well tolerated and less frequently interacts with other drugs, possible side effects less often lead to the cessation of the therapy. An important feature of the drug is a positive effect on the sexual sphere of patients and a presumed positive effect on reducing depressive symptoms.

Neuropathic pain (NPP) is a kind of pain caused by disease or damage impacting the somatosensory system. Ion channel drugs are the main treatment for NPP; however, their irregular usage leads to unsatisfactory pain relief. To regulate the treatment of NPP with ion channel drugs in clinical practice, the Chinese Association for the Study of Pain organized first-line pain management experts from China to write an expert consensus as the reference for the use of ion channels drugs . Here, we reviewed the mechanism and characteristics of sodium and calcium channel drugs, and developed recommendations for the therapeutic principles and clinical practice for carbamazepine, oxcarbazepine, lidocaine, bulleyaconitine A, pregabalin, and gabapentin. We hope this guideline provides guidance to clinicians and patients on the use of ion channel drugs for the management of NPP.

Medication-related harm represents a significant issue for patient safety and quality of care. One strategy to avoid preventable adverse drug events is to utilize patient-specific factors such as pharmacogenomics (PGx) to individualize therapy. We measured the number of patients enrolled in a health-system biobank with actionable PGx results who received relevant medications and assessed the incidence of adverse drug events (ADEs) that might have been prevented had the PGx results been used to inform prescribing. Patients with actionable PGx results in the following four genes with Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines were identified: HLA-A*31:01, HLA-B*15:02, TPMT, and VKORC1. The patients who received interacting medications (carbamazepine, oxcarbazepine, thiopurines, or warfarin) were identified, and electronic health records were reviewed to determine the incidence of potentially preventable ADEs. Of 36,424 patients with PGx results, 2327 (6.4%) were HLA-A*31:01 positive; 3543 (9.7%) were HLA-B*15:02 positive; 2893 (7.9%) were TPMT intermediate metabolizers; and 4249 (11.7%) were homozygous for the VKORC1 c.1639 G>A variant. Among patients positive for one of the HLA variants who received carbamazepine or oxcarbazepine (n = 92), four (4.3%) experienced a rash that warranted drug discontinuation. Among the TPMT intermediate metabolizers who received a thiopurine (n = 56), 11 (19.6%) experienced severe myelosuppression that warranted drug discontinuation. Among patients homozygous for the VKORC1 c.1639 G>A variant who received warfarin (n = 379), 85 (22.4%) experienced active bleeding and/or international normalized ratio (INR) > 5 that warranted drug discontinuation or dose reduction. Patients with actionable PGx results from a health-system biobank who received relevant medications experienced predictable ADEs. These ADEs may have been prevented if the patients’ PGx results were available in the electronic health record with clinical decision support prior to prescribing.

Epilepsy is one of the most common chronic neurological diseases. About 12.5 million women of childbearing potential have this disease. Epilepsy is not a contraindication to pregnancy and most women with epilepsy give birth to healthy children. Women of childbearing potential often face many concerns when planning a pregnancy, one of them is the use of antiepileptic drugs during pregnancy. Both in the planning of pregnancy and during pregnancy, it is necessary to strive for the most effective and safer treatment for epilepsy. Has been observed that pregnant women and the fetus may be affected by uncontrolled seizures. Therefore, there should be a balanced risk between uncontrolled epileptic seizures and the risk of antiepileptic drugs to the fetus and mother. Women with epilepsy pregnancy should be planned. They should know details and comprehensive information. In women of childbearing potential with epilepsy, proper contraceptive selection is essential. Potential drug interactions have been identified that may lead to ineffective hormonal contraceptives and reduce the effectiveness of antiepileptic drugs. Planning pregnancy it is important to consider indications and variants for the treatment of antiepileptic drugs. If possible, the antiepileptic drugs used should be changed to safer drugs. However, changes of treatment should be done before pregnancy, with sufficient provision time to evaluate the effectiveness of the new antiepileptic drugs and to determine the minimum effective dose before conception. The risk to the fetus from the use of antiepileptic drugs is associated with intrauterine development deceleration, congenital malformations, increased neurological development, cognitive functions risk of disruption. The risk can be different to the fetus from different antiepileptic drugs. The largest fetal malformations are associated with the use of Valproate, the lowest with Lamotrigine, Levetiracetam and Oxcarbazepine. To reduce this risk, the first trimester of pregnancy consumption of folic acid 4–5 mg/day is recommended. The diagnosis of epilepsy is not a contraindication to give birth by natural routes. We all know about the benefits of breastfeeding for the mother and baby. Studies show that antiepileptic drugs used had any adverse effects for breastfeeding. So all mothers with epilepsy and those taking antiepileptic drugs should be encouraged to breastfeed, except in very rare cases.

OBJECTIVES The objective of this study was to evaluate seizure remission rates in patients with benign epilepsy of childhood with centrotemporal spikes (BECTS) receiving antiepileptic drugs. METHODS PubMed and Web of Science were searched for studies on pharmacotherapy in patients with BECTS using free search terms or Medical Subject Headings. Only studies that used seizure-freedom rates as an indicator for pharmaceutical efficacy were considered. Different antiepileptic drugs were compared using the Fisher exact test for seizure-freedom rates. RESULTS A total of 19 studies were included, 6 of them being randomized controlled trials. The randomized controlled trials included a total of 308 patients and covered sulthiame (n = 52), topiramate (n = 45), levetiracetam (n = 43), oxcarbazepine (n = 31), carbamazepine (n = 68), and clobazam (n = 18) as well as placebo (n = 35) and untreated control groups (n = 16). Treatment success rates were significantly higher in those children treated with sulthiame, levetiracetam, and clobazam compared with the children treated with carbamazepine, oxcarbazepine, or topiramate. CONCLUSIONS The available literature suggests the use of sulthiame, levetiracetam, or clobazam as first-line agents for the treatment of BECTS.

Levetiracetam (LEV) and oxcarbazepine (OXC) are commonly used in the treatment of epilepsy, but their efficacy and safety have seldom been compared for the treatment of children with benign epilepsy with centrotemporal spikes (BECTS). We thus assessed the efficacy of LEV and OXC monotherapy in the treatment of children with BECTS, and the effect of this treatment on children’s intelligence and cognitive development. This was a randomized, single-center trial. Children with BECTS were randomized (1:1) into LEV and OXC groups, and were assessed at 1, 3 and 6 months after treatment. The primary outcomes were the frequency of seizures and changes in intelligence and cognitive function. Secondary outcomes were electroencephalogram (EEG) results and safety. Seventy children were enrolled and randomized to the LEV group or the OXC group, and 32 of the 35 children in each group completed the study. After 6 months, the effective treatment rate of the OXC group was significantly higher than that of the LEV group (78.12 vs. 53.12%, p = 0.035). However, no significant inter-group difference was observed in EEG improvement (p = 0.211). In terms of intelligence and cognitive development, children in the OXC group exhibited significantly improved choice reaction time, mental rotation, and Wisconsin Card Sorting Test results (all p p = 0.756). OXC monotherapy was more effective than LEV for children with BECTS. In addition, children with OXC monotherapy had higher improvements in children’s intelligence and cognitive function than those with LEV monotherapy.

Therapeutic drug monitoring (TDM) of antiepileptic drugs (AED) using blood is well established but limited by its invasiveness, accessibility, cost, interpretation errors, and related disturbances in protein binding. TDM using oral fluid (OF) could overcome these limitations. This paper provides a summary of the current evidence for using OF as a matrix to perform TDM of AEDs, as well as practical considerations. A literature search of MEDLINE, EMBASE, and the Cochrane Library was conducted on April 9, 2018 (and then updated on May 20, 2020) using all AEDs as keywords along with "oral fluid," "saliva," "salivary," "seizure," "epilepsy," "antiepileptic," and "anticonvulsant." A total of 18 relevant articles were found and included in this review. There is evidence to suggest that AED TDM using OF is feasible and that reference ranges can be calculated for the following drugs: carbamazepine, ethosuximide, lacosamide, lamotrigine, levetiracetam, oxcarbazepine, phenobarbital, phenytoin, primidone, topiramate, and valproic acid. For all other AEDs, there is either a lack of evidence on the feasibility of TDM using OF or the evidence indicates that TDM using OF is not feasible. Practical considerations should include the timing and method of OF collection (stimulated or unstimulated) due to their probable impact on the reliability of AED TDM. Using OF may improve the acceptability and accessibility and reduce the cost of AED TDM. Clinical implementation requires standardized collection protocols, more rigorously defined OF reference ranges, and further studies to determine the relevance to clinically important outcomes.

Cutaneous adverse drug reactions (cADRs) are one of the most common, severe, and life-threatening types of adverse reactions following treatment with antiseizure medications (ASMs). Some studies have reported a higher incidence of ASM-induced cADRs in females than in males. This study sought to perform a systematic review, meta-analysis, and meta-regression to compare the ASM cADR risks between females and males. We searched the literature using three databases (EMBASE, PubMed, and Web of Science) between October 1998 and November 2018, later updated to October 2019. Studies were included in the meta-analysis if they met the following criteria: (1) observational studies that estimated the incidence of cADRs related to ASMs; (2) provided the risk or odds ratio (OR) for cADRs among female and male patients exposed to ASMs; and (3) provided information on patients’ characteristics. We assessed the impact of study characteristics, publication bias, and measures to reduce bias, and performed a DerSimonian and Laird random effects meta-analysis. We included 28 studies in this review. Of these, seven studies were eligible for inclusion in the meta-analysis, involving a total of 223,209 patients. Overall, females were more likely to develop cADRs to ASMs than males (OR 1.76, 95% confidence interval [CI] 1.55–1.99). The largest differences were observed in patients prescribed lamotrigine (OR 2.17, 95% CI 1.53–3.08, p < 0.001) and carbamazepine (OR 1.63, 95% CI 1.02–2.60, p = 0.042). Also, the OR trended higher for phenytoin (OR 2.46, 95% CI 0.79–7.65, p = 0.12), followed by oxcarbazepine (OR 1.91, 95% CI 0.75–4.85, p = 0.18) and sodium valproate (OR 0.60, 95% CI 0.12–2.99, p = 0.53), but the difference did not reach statistical significance. In the remaining 21 studies, 13 reported numerically higher risk of cADRs among females compared to male patients, and in five of these, the difference was statistically significant. Our findings confirmed that females are more susceptible to cADRs induced by ASMs than males. More research is needed to understand the pathophysiological mechanisms for this difference. PROSPERO (CRD42018111943).

Background Due to blocking β-receptors, and potassium KCNH2 channels, sotalol may influence seizure phenomena. In the previous study, we have shown that sotalol potentiated the antielectroshock action of phenytoin and valproate in mice. Materials and methods As a continuation of previous experiments, we examined the effect of sotalol on the action of four chosen second-generation antiepileptic drugs (oxcarbazepine, lamotrigine, pregabalin, and topiramate) against the maximal electroshock in mice. Undesired effects were evaluated in the chimney test (motor impairment) and step-through passive-avoidance task (long-term memory deficits). Finally, brain concentrations of antiepileptics were determined by fluorescence polarization immunoassay, while those of sotalol by liquid chromatography–mass spectrometry. Results Sotalol at doses of up to 100 mg/kg did not affect the electroconvulsive threshold. Applied at doses of 80–100 mg/kg, sotalol did not affect the antielectroshock action of oxcarbazepine, lamotrigine, pregabalin, or topiramate. Sotalol alone and in combinations with antiepileptics impaired neither motor performance nor long-term memory. Finally, sotalol significantly decreased the brain concentrations of lamotrigine and increased those of oxcarbazepine and topiramate. Pharmacokinetic interactions, however, did not influence the final antielectroshock effects of above-mentioned drug combinations. On the other hand, the brain concentrations of sotalol were not changed by second-generation antiepileptics used in this study. Conclusion Sotalol did not reduce the antielectroshock action of four second-generation antiepileptic drugs examined in this study. Therefore, this antidepressant drug should not interfere with antiseizure effects of lamotrigine, oxcarbazepine, pregabalin, and topiramate in patients with epilepsy. To draw final conclusions, our preclinical data should still be confirmed in other experimental models and clinical conditions.

Introduction: The epilepsy classification in under developed countries faces many difficulties in reporting, work-up and management strategies. Exploring local practice in general hospitals will positively add to the welfare of patients with epilepsy. The objectives of this study were to assess the current medical practice in epilepsy work up and to study the selection of AEDs as per ILAE guidelines. Methods: This was a cross sectional-retrospective hospital based study, conducted between April and September 2016 in Omdurman Teaching Hospital, Khartoum, Sudan. Patients aged 18 years old and above were enrolled. Epilepsy was defined as having at least two non-provoked seizures in the least 6 months in a patient who was assessed by clinical review and electroencephalogram (EEG). Epilepsy was classified as generalized, focal or unclassified. Medications refer to all internationally licensed antiepileptic medications (AEDs) in 2016. Results: One hundred adult Sudanese patients were enrolled for this study. The most common event described during the ictal phase was tongue biting in 50% of participants followed by body stiffness in 46%. Epilepsy was classified as generalized in 84%, focal in 11% and unclassified in 5% patients. In generalized epilepsy, the MRI detected 23.3% abnormal findings higher than the CT which detected 14.8% (4/27), p value = 0.032. In focal epilepsy, the CT detected 75% abnormal findings higher than the MRI which detected 33.3%, p value = 0.02. The AEDs used were as follows: Carbamazepine (CBZ) 48%, Na valproate (VP) 33%, Lamotrigine (LMT) 2%, Levetricetan (LVT) 1%, CBZ + VP 14% and CBZ + Oxcarbazepine (OXC) 2%. Conclusion: The current medical practice in Omdurman teaching hospital should be modified to match the international league against epilepsy (ILAE) guidelines in workup, management, AEDs selection and classification of epilepsy.

IntroductionThe management of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) remains challenging in view of the paucity of data and evidence-based treatment recommendations are missing.MethodsIn this single-centre, non-randomised, prospective open-label study, we evaluated and compared the efficacy of oral and parenteral treatments for SUNCT and SUNA in a real-world setting. Additionally, single-arm meta-analyses of the available reports of SUNCT and SUNA treatments were conducted.ResultsThe study cohort comprised 161 patients. Most patients responded to lamotrigine (56%), followed by oxcarbazepine (46%), duloxetine (30%), carbamazepine (26%), topiramate (25%), pregabalin and gabapentin (10%). Mexiletine and lacosamide were effective in a meaningful proportion of patients but poorly tolerated. Intravenous lidocaine given for 7–10 days led to improvement in 90% of patients, whereas only 27% of patients responded to a greater occipital nerve block. No statistically significant differences in responders were observed between SUNCT and SUNA. In the meta-analysis of the pooled data, topiramate was found to be significantly more effective in SUNCT than SUNA patients. However, a higher proportion of SUNA than SUNCT was considered refractory to medications at the time of the topiramate trial, possibly explaining this isolated difference.ConclusionsWe propose a treatment algorithm for SUNCT and SUNA for clinical practice. The response to sodium channel blockers indicates a therapeutic overlap with trigeminal neuralgia, suggesting that sodium channels dysfunction may be a key pathophysiological hallmark in these disorders. Furthermore, the therapeutic similarities between SUNCT and SUNA further support the hypothesis that these conditions are variants of the same disorder.

Objective Antiseizure medications (ASMs) can rarely result in severe, sometimes fatal, cutaneous adverse reactions. To date, few studies have reported on the incidence rates (IRs) of severe cutaneous adverse reactions (SCARs) due to ASM use. This study aimed to determine the IRs of SCAR resulting from the use of seven commonly prescribed ASMs, carbamazepine (CBZ), phenytoin (PHT), oxcarbazepine (OXC), lamotrigine (LMT), zonisamide (ZNS), levetiracetam (LVT), and topiramate (TPM), and to compare the associated risks among the drugs. Methods Using a nationwide health claims database, we selected all the patients prescribed with one of the target ASMs. We defined a SCAR case as the first hospitalization with one of three specific codes provided by the International Classification of Diseases, 10th revision (L511, L512, and L27). We then calculated the IR of SCARs according to each target ASM. Results The IR of SCARs for each ASM was as follows: 870/1 000 000 person-years (PYs) for CBZ, 5750/1 000 000 PYs for PHT, 1490/1 000 000 PYs for OXC, 3860/1 000 000 PYs for LMT, 1540/1 000 000 PYs for ZNS, 830/1 000 000 PYs for LVT, and 400/1 000 000 PYs for TPM. Concomitant use of antibiotics and nonsteroidal anti-inflammatory drugs significantly increased the risk of SCARs with OXC, LVT, or TPM use. Comorbid skin disease was associated with a significantly higher IR of SCARs from CBZ, PHT, OXC, LMT, or LVT use. Significance This is the first study in Asia to determine the IRs of SCARs for various ASMs and compare the rates across drugs using a large dataset. The results from this study should help clinicians select safer ASMs in practice.

Objective To evaluate the efficacy of drugs for patients with central mid-temporal (rolandic) discharges detected by electroencephalogram (EEG). Methods This retrospective study enrolled 430 patients with rolandic discharges, who were treated at the Neuroelectrophysiology Center of the Children’s Hospital of Nanjing Medical University from February 2015 to February 2018. Patients were divided into three groups according to medication: levetiracetam (LEV), oxcarbazepine (OXC) and sodium valproate (VPA). All patients were followed up for at least 2 years, and the seizure frequency, EEG results and side effects of drugs were recorded. Results Rolandic epilepsy (RE) occurred in 398/430 patients. Rolandic discharges were also found in those with febrile seizures, tic disorders, and attention deficit hyperactivity disorder. Thirty-one patients experienced only one seizure and no relapse, while 367 patients experienced more than two seizures (including 364 receiving drug treatment). The failure rate of LEV as initial therapy was significantly higher than those of OXC and VPA. The overall efficacy of OXC was higher than that of LEV. However, none of the three medications could control rolandic discharges. Moreover, the side effects of the three drugs were mild. Conclusions Rolandic discharges are common in children with RE and other diseases, such as febrile seizures, tic disorders, and attention deficit hyperactivity disorder. Patients with only one seizure need no treatment. Those with multiple seizures can be treated with OXC, LEV, and VPA. OXC serves as the initial antiepileptic drug with a lower failure rate and significant efficacy.

Introduction. Oxcarbazepine (OXC) is approved for initial and adjunctive therapy of focal epilepsy (FE), being also a drug of choice in case of pediatric FE. Despite that OXC has been used in the Russian Federation (RF) since 2007, studies assessing its efficacy and tolerability are scarce.Aim. To evaluate efficacy and tolerability of OXC therapy in patients with newly-diagnosed epilepsy.Patients and methods. There were enrolled 103 patients (56 (54.4%) into the study: males and 47 (45.6%) females with FE, aged 44.32±19.71 years. Depending on the OXC daily dose, all patients were divided into 3 subgroups: 1200 mg/day (n=16; 15.5%). Video-electroencephalographic (video-EEG) monitoring was performed at each visit (at baseline, 1, 3, 6 and 12 months after then onset of therapy). Treatment efficacy was assessed by using the criteria of retention on treatment, seizure absence, seizure rate decrease by >50%, seizure rate decrease by

Background Accurate estimation of conception is critical in the assessment of the effects of drugs used during pregnancy or to prevent pregnancy. In a novel application, we studied the effectiveness of oral contraceptives (OCs), where misclassification of conception relative to OC exposure may obscure effect estimates. Methods We studied OC failure, in a large claims database, among women who used antiepileptic drugs with metabolizing enzyme-inducing properties (carbamazepine or oxcarbazepine), which reduce OC's effectiveness or enzyme-neutral properties (lamotrigine or levetiracetam), with no expected impact on OC effectiveness. We compared conception rates in women 12-48 years of age concomitantly using OCs and enzyme-inducing drugs with rates in concomitant users of OCs and enzyme-neutral drugs. We measured conception with a validated algorithm that estimates gestational age based on pregnancy endpoints. We estimated relative and attributable risk using generalized estimating equation models after standardized mortality ratio weighting. Results We identified 89,777 concomitant use episodes with adjusted contraceptive failure rates of 1.6 (95% confidence interval (CI) = 1.4, 1.8) per 100 person-years among users of enzyme-neutral drugs and 18,964 episodes with a rate of 2.3 (1.9, 2.8) among users of enzyme-inducing drugs. The relative risk of conception for enzyme-inducing group was 1.4 (1.1, 1.8), and the rate difference was 0.7 (0.2, 1.2). Conclusions OCs in combination with antiepileptic drugs that interact with metabolic enzymes were associated with increased contraceptive failure rates. Measurement of conception in claims data had adequate accuracy to uncover a strong drug-drug interaction, offering promise for broader application in comparative effectiveness studies on hormonal contraceptives to inform clinical and regulatory decisionmaking.