Pharmacotherapy Of Epilepsy Research Articles

Evaluation of thiopyrano[2,3-d]thiazole derivatives as potential anticonvulsant agents.

Anticonvulsant drug discovery has achieved significant progress; however, pharmacotherapy of epilepsy continues to be a challenge for modern medicine and pharmacy. To expand the chemical space of heterocycles as potential antiepileptic agents, herein we report on the synthesis and evaluation of anticonvulsant properties of a series of thiopyrano[2,3-d]thiazoles. The studied heterocycles are characterized by satisfactory drug-likeness and pharmacokinetics properties, calculated in silico using SwissADME. The anticonvulsant activity of thiopyrano[2,3-d]thiazole derivatives was evaluated in vivo using the subcutaneous pentylenetetrazole test. Three hits, that is, compounds 12, 14, and 16, that caused a pronounced anticonvulsant effect were identified. Derivatives 12, 14, and 16 positively affected the latent period of onset of clonic seizures, number of seizures, mortality rate, and duration of the seizure period of animals under experimental conditions. The anticonvulsant properties of compound 14 were equivalent to the effect of the reference drug, sodium valproate. All hit compounds are characterized by satisfying toxicity properties in the human lymphocytes and HEK293 cell line. The most active hit 14 possesses a potential affinity with the GABAA receptor in the molecular docking study and forms a stable complex in the molecular dynamics experiments equal to diazepam. Preliminary SAR results were obtained and discussed based on screening data.

Subthreshold Cannabidiol Potentiates Levetiracetam in the Kainic Acid Model of Temporal Lobe Epilepsy: A Pilot Study.

Refractoriness to antiseizure medications is still a major concern in the pharmacotherapy of epilepsy. For this reason, we decided to evaluate the combination of levetiracetam and cannabidiol, administered at a subthreshold dose, to limit the possible adverse effects of this phytocannabinoid. We administered levetiracetam (300 mg/kg/day, via osmotic minipumps), cannabidiol (120 mg/kg/day, injected once a day subcutaneously), or their combination for one week in epileptic rats. Saline-treated epileptic rats were the control group. Animals were monitored with video electroencephalography the week before and after the treatment. No changes were found in the controls. Levetiracetam did not significantly reduce the total seizure number or the overall seizure duration. Still, the overall number of seizures (p < 0.001, Duncan's new multiple range test) and their total duration (p < 0.01) increased in the week following treatment withdrawal. Cannabidiol did not change seizures when administered as a single drug. Instead, levetiracetam combined with cannabidiol resulted in a significant reduction in the overall number and duration of seizures (p < 0.05), when comparing values measured during treatment with both pre- and post-treatment values. These findings depended on changes in convulsive seizures, while non-convulsive seizures were stable. These results suggest that cannabidiol determined a remarkable potentiation of levetiracetam antiseizure effects at a subthreshold dose.

The Frequency and Structure of Adverse Drug Reactions in the Pharmacotherapy of Epilepsy

The problem of the safety of antiepileptic therapy due to the duration of treatment and the need for regular intake of antiepileptic drugs (AEDs) is extremely significant. Adverse reactions (ADRs) may outweigh any positive effect of therapy associated with seizure reduction. The purpose of the study: to analyze the frequency and structure of ADRs of AEDs. Materials and Methods: The work was carried out within the framework of comprehensive research on the topic No. 210-16 "Epidemiological, genetic and neurophysiological aspects of diseases of the nervous system (central, peripheral and vegetative) and preventive medicine" (registration number 0120.0807480). Results: The frequency of ADRs against the background of third-generation AEDs was not inferior to that against the background of receiving second-generation AEDs, while the structure of ADRs was different: third-generation AEDs had a higher incidence of ADRs from the central nervous system, including a worsening of the course of epilepsy. The ratio of the chances of valproic acid accumulation with the achievement of toxic concentration in the blood and the development of un-desirable side effects in poor metabolizers (carriers of the polymorphism of CYP2C9*2 or CYP2C9*3) the gene encoding the cytochrome P450 isoenzyme 2C9 of the liver is 5.94 and 4.27, respectively. Conclusion: A personalized approach to ensuring the safety of valproic acid preparations based on taking into account the carriage of polymorphisms of the CYP2C9 gene allows to reduce the incidence of ADRs in patients receiving valproic acid preparations from 59.28% to 10.78%. The introduction of a personalized approach to the administration of valproates to patients suffering from epilepsy in the Krasnoyarsk Territory did not lead to an increase in direct costs.

Established and emerging GABAA receptor pharmacotherapy for epilepsy.

Drugs that modulate the GABAA receptor are widely used in clinical practice for both the long-term management of epilepsy and emergency seizure control. In addition to older medications that have well-defined roles for the treatment of epilepsy, recent discoveries into the structure and function of the GABAA receptor have led to the development of newer compounds designed to maximise therapeutic benefit whilst minimising adverse effects, and whose position within the epilepsy pharmacologic armamentarium is still emerging. Drugs that modulate the GABAA receptor will remain a cornerstone of epilepsy management for the foreseeable future and, in this article, we provide an overview of the mechanisms and clinical efficacy of both established and emerging pharmacotherapies.

Advancement in Epilepsy Pharmacotherapy: An Insight into the Pharmacophoric Approaches of Recent Drugs.

Epilepsy is the most general, extensive, and severe neurological disorder, affecting more than 50 million individuals globally. Initially, conventional medicines and simple salts like potassium bromide were employed as antiepileptic medication candidates. Nowadays, many anticonvulsant drugs have been discovered as first-generation and second-generation and newer drugs and are still in development phases. The pharmacophore-based drug design process includes pharmacophore modeling and validation, pharmacophore-based virtual screening, virtual hits profiling, and lead identification with special reference. This comprehensive article reviews recently developed anticonvulsant derivatives on the basis of pharmacophoric approaches. A literature survey was performed using various search engines like Google Scholar, Scopus, Sci Finder, ScienceDirect, Science gate, Scilit, PubMed, NINDS database of NIH, Bentham Sciences, and other online and print journals and scientific databases. The presented review discusses such kinds of newer drugs that are in the market as well as in clinical trial phases. Detailed outcomes of pharmacophoric modeling have been discussed for newly derived derivatives like targets involved in Epilepsy, lead molecules etc., for the treatment of epilepsy. This exhaustive review will assist the researchers in the further development of potential antiepileptic agents.

MiR-134 And MiR-106b Are Circulating Biomarkers For Temporal Lobe Epilepsy: Pilot Study Results

Temporal lobe epilepsy (TLE) is among the most common forms of focal epilepsy in adults. Currently, scientists search for microRNAs as noninvasive epilepsy biomarkers. MicroRNAs constitute a class of short (or small) non-coding RNAs that control the level of gene expression affecting the stability of mRNA. They are key regulators and therapeutic targets in epilepsy. Considering the role of miRNA-134 and miRNA-106b in the processes of epileptogenesis, the goal of our study was the clinical evaluation of their circulation as novel noninvasive molecular diagnostic markers of TLE. Material and Methods — Our pilot study involved 59 participants. The main group included 33 patients with mesial temporal lobe epilepsy, the control group encompassed 26 healthy volunteers. The ranking of patients was carried out depending on the disease duration, presence of epileptiform activity on the electroencephalogram (EEG) and hippocampal sclerosis on MRI, the number of taken antiepileptic drugs (AEDs), and patient response to the pharmacotherapy of epilepsy. The isolation of circulating microRNAs from blood plasma was accomplished via the sorption method, and the analysis of microRNA expression was performed by real-time PCR. Results — The expression levels of miR-134 and miR-106b in blood plasma in patients with TLE were reduced. Therefore, these microRNAs can be diagnostic biomarkers of patients with TLE, compared with the control group. The results of receiver operating characteristic (ROC) analysis yielded high sensitivity and specificity values of this biomarker for the diagnosis of TLE. Conclusion — Circulating miR-134 and miR-106b concentrations were significantly reduced in patients with mesial TLE (MTLE), compared with healthy controls. At the same time, the level of microRNA expression did not depend on the presence of hippocampal sclerosis and the response to antiepileptic therapy.

The evolution of antiseizure medication therapy selection in adults: Is artificial intelligence -assisted antiseizure medication selection ready for prime time?

Antiseizure medications (ASMs) are the mainstay of symptomatic epilepsy treatment. The primary goal of pharmacotherapy with ASMs in epilepsy is to achieve complete seizure remission while minimizing therapy-related adverse events. Over the years, more ASMs have been introduced, with approximately 30 now in everyday use. With such a wide variety, much guidance is needed in choosing ASMs for initial therapy, subsequent replacement monotherapy, or adjunctive therapy. The specific ASMs are typically tailored by the patient's related factors, including epilepsy syndrome, age, sex, comorbidities, and ASM characteristics, including the spectrum of efficacy, pharmacokinetic properties, safety, and tolerability. Weighing these key clinical variables requires experience and expertise that may be limited. Furthermore, with this approach, patients may endure multiple trials of ineffective treatments before the most appropriate ASM is found. A more reliable way to predict response to different ASMs is needed so that the most effective and tolerated ASM can be selected. Soon, alternative approaches, such as deep machine learning (ML), could aid the individualized selection of the first and subsequent ASMs. The recognition of epilepsy as a network disorder and the integration of personalized epilepsy networks in future ML platforms can also facilitate the prediction of ASM response. Augmenting the conventional approach with artificial intelligence (AI) opens the door to personalized pharmacotherapy in epilepsy. However, more work is needed before these models are ready for primetime clinical practice.

Of the Mechanisms of Paroxysmal Depolarization Shifts: Generation and Maintenance of Bicuculline-Induced Paroxysmal Activity in Rat Hippocampal Cell Cultures.

Abnormal depolarization of neuronal membranes called paroxysmal depolarization shift (PDS) represents a cellular correlate of interictal spikes. The mechanisms underlying the generation of PDSs or PDS clusters remain obscure. This study aimed to investigate the role of ionotropic glutamate receptors (iGluRs) in the generation of PDS and dependence of the PDS pattern on neuronal membrane potential. We have shown that significant depolarization or hyperpolarization (by more than ±50 mV) of a single neuron does not change the number of individual PDSs in the cluster, indicating the involvement of an external stimulus in PDS induction. Based on this data, we have suggested reliable protocols for stimulating single PDS or PDS clusters. Furthermore, we have found that AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors are necessary for PDS generation since AMPAR antagonist NBQX completely suppresses bicuculline-induced paroxysmal activity. In turn, antagonists of NMDA (N-methyl-D-aspartate) and kainate receptors (D-AP5 and UBP310, respectively) caused a decrease in the amplitude of the first action potential in PDSs and in the amplitude of the oscillations of intracellular Ca2+ concentration occurring alongside the PDS cluster generation. The effects of the NMDAR (NMDA receptor) and KAR (kainate receptor) antagonists indicate that these receptors are involved only in the modulation of paroxysmal activity. We have also shown that agonists of some Gi-coupled receptors, such as A1 adenosine (A1Rs) or cannabinoid receptors (CBRs) (N6-cyclohexyladenosine and WIN 55,212-2, respectively), completely suppressed PDS generation, while the A1R agonist even prevented it. We hypothesized that the dynamics of extracellular glutamate concentration govern paroxysmal activity. Fine-tuning of neuronal activity via action on Gi-coupled receptors or iGluRs paves the way for the development of new approaches for epilepsy pharmacotherapy.

Pharmacotherapy of epilepsy: new solutions to old problems

The literature review provides an update on recent advances in antiepileptic pharmacotherapy. The article considers the mechanisms of action of the drugs, the range of efficacy, side effects and enzyme-inducing properties, potential teratogenicity.&#x0D; A review of the literature revealed some of the problems of patients with epilepsy remaining unresolved to this day. Despite an increase in the number of anticonvulsants in recent years, one-third of patients are pharmacoresistant to antiepileptic therapy and continue to suffer from seizures. The hope for reducing the proportion of patients with uncontrolled seizures rests on future therapeutic developments, including targeted therapies aimed at the molecular mechanisms underlying the epilepsy pathogenesis. Clinical outcomes in patients with epilepsy could also significantly improve with advances in the development of new highly accurate diagnostic and treatment methods, the identification of biomarkers for drug development, as well as routine clinical follow-up and the introduction of truly innovative disease-modifying therapies.

(+)-Borneol enantiomer ameliorates epileptic seizure via decreasing the excitability of glutamatergic transmission.

Epilepsy is one common brain disorder, which is not well controlled by current pharmacotherapy. In this study we characterized the therapeutic potential of borneol, a plant-derived bicyclic monoterpene compound, in the treatment of epilepsy and elucidated the underlying mechanisms. The anti-seizure potency and properties of borneol were assessed in both acute and chronic mouse epilepsy models. Administration of (+)-borneol (10, 30, 100 mg/kg, i.p.) dose-dependently attenuated acute epileptic seizure in maximal-electroshock seizure (MES) and pentylenetetrazol (PTZ)-induced seizure models without obvious side-effect on motor function. Meanwhile, (+)-borneol administration retarded kindling-induced epileptogenesis and relieved fully kindled seizures. Importantly, (+)-borneol administration also showed therapeutic potential in kainic acid-induced chronic spontaneous seizure model, which was considered as a drug-resistant model. We compared the anti-seizure efficacy of 3 borneol enantiomers in the acute seizure models, and found (+)-borneol being the most satisfying one with long-term anti-seizure effect. In electrophysiological study conducted in mouse brain slices containing the subiculum region, we revealed that borneol enantiomers displayed different anti-seizure mechanisms, (+)-borneol (10 μM) markedly suppressed the high frequency burst firing of subicular neurons and decreased glutamatergic synaptic transmission. In vivo calcium fiber photometry analysis further verified that administration of (+)-borneol (100 mg/kg) inhibited the enhanced glutamatergic synaptic transmission in epilepsy mice. We conclude that (+)-borneol displays broad-spectrum anti-seizure potential in different experimental models via decreasing the glutamatergic synaptic transmission without obvious side-effect, suggesting (+)-borneol as a promising anti-seizure compound for pharmacotherapy in epilepsy.

Therapeutic developments in the surgical treatments of epilepsy: a review

In the 21st century, neurological disease is more complicated with the enhancement of technology; epilepsy is one of them. Currently, 1%-5% prevalence was observed, and 0.5%-1% were in chronic neurological disease. The involuntary spontaneous stimulation and inhibition in the brain caused seizures. The seizures are life-threatening episodes in which inelastic starching of lumber muscles and whole-body trimmers were observed. The period of episodic attack is directly proportional to the severity of the disease. This systemic review is based on developing therapeutic surgeries for epilepsy in the 21st century. The data was collected from Medline, PubMed, Embase, Cochrane library, and Web of Science. Surgical treatment, therapeutic methods, developmental approach in treatment, epilepsy, neurological disorders, and seizure attack words were used as the keywords. A total of 120 articles and reviews were selected, of which 11 were included based on exclusion criteria. The pharmacotherapy of epilepsy is set to undergo significant changes in the following 10 years due to the large quantity of continuing epilepsy and more general neuroscience research and the numerous novel compounds that are now being developed.

Results of clinical and economic analysis of pharmacotherapy of patients epilepts

Epilepsy is one of the most common serious diseases of the central nervous system in the world. The effective system of pharmaceutical care for epileptic patients requires the involvement of appreciable budgetary financial resources. In order to determine the actual state of pharmaceutical care to the population, clinical and economic studies are used, the results of which allow to optimize the cost of pharmacotherapy and ensure the implementation of the constitutional rights of Ukrainian citizens to available medical and pharmaceutical care.&#x0D; The aim of the study was to conduct a clinical and economic analysis of pharmacotherapy of epilepsy.&#x0D; The object of the study was the data of 118 medical records of patients diagnosed with epilepsy, who were treating at specialized healthcare facilities. Evaluation of the degree of pharmacotherapy rationality in epileptic patients was taken using frequency, VEN, ABC analysis.&#x0D; The results of the investigation of patients’ medical records showed that 87 trade names of medications (76 international non-proprietary names of medications) were prescribed for epileptic patients. The total number of prescriptions is 918. The average number of prescriptions per patient is 7, which indicates polypragmasy. It was found that the leader in the number of appointments were carbamazepine – 11.11% of the total number of prescriptions and valproic acid – 3.49%. It is proved that in the structure of prescriptions for epileptic patients the part of medication with index V was 7.89%, which indicates a low degree of prescriptions compliance with healthcare standards. According to the results of the integrated ABC and VEN analysis, it was proved that among the groups A/V, A/E, A/N, the group A/V has the largest amount of expenditures – 36.38% of total cost. In general, group N accounts for 41.97% of total costs, which may indicate the irrational use of drugs in the provision of pharmaceutical care to epileptic patients.&#x0D; The results of clinical and economic analysis of medical records of epileptic patients allowed to identify features in the organization of pharmaceutical care, as well as to substantiate the main directions of improving pharmacotherapy of epileptic patients with limited budget funding for healthcare.

Caring for women with epilepsy in Palestine: A qualitative study of the current status

ObjectiveThis qualitative study was conducted to explore the current status of caring for women with epilepsy (WWE) in the Palestinian healthcare system. MethodsThis study used an explorative qualitative design. A purposive sampling technique was used to recruit the participants. Semi-structured in-depth interviews were conducted with neurologists (n = 6), gynecologists (n = 5), psychiatrists (n = 3), an internist (n = 1), and clinical pharmacists (n = 5). The interpretive description methodology was used to thematically analyze the qualitative data. ResultsA total of 745 min (12.4 h) of interview time were analyzed. The qualitative data collected in this study were categorized under 3 major themes and multiple subthemes. The 3 major themes were: (1) diagnosis and care for patients with epilepsy, (2) general issues in caring for patients with epilepsy, and (3) consideration of women’s issues in the pharmacotherapy of epilepsy. Formally adopted protocols/criteria for the diagnosis and care for WWE were lacking. ConclusionFindings of this qualitative study showed a need to formally adopt uniform guidelines that can guide the diagnosis and care of WWE in the Palestinian healthcare system. The findings of this study might be informative to healthcare providers, decision-makers in healthcare authorities, WWE, and patient advocacy groups who could be interested in improving and benchmarking healthcare services provided to WWE. Future studies are still needed to quantitatively measure adherence to the international guidelines in caring for WWE.

ABCG2, SCN1A and CYP3A5 genes polymorphism and drug-resistant epilepsy in children: A case-control study

Drug Resistant -Epilepsy is still a major challenge in pharmacotherapy of epilepsy. Pharmacogenetic pathways are one of the most important elements that can help clinicians determine medication response and provide more efficient drug therapy, especially in cases of drug resistance. Genetic alterations in drug target and transporter proteins, in part, could explain the development of drug-resistant epilepsy. We sought to assess the association of CYP3A5 (rs776746), SCN1A (rs2298771) and ABCG2 (rs2231137) candidate polymorphisms with drug-resistant epilepsy among Iranian children with epilepsy. In a hospital-based case-control study, 93 participants, including 45 men and 48 women aged 1.5 to 14 years old were recruited. Genotyping of CYP3A5 (rs776746), SCN1A (rs2298771) and ABCG2 (rs2231137) polymorphisms using the high-resolution melting (HRM) method were measured in 46 children with drug-resistant epilepsy and 47 healthy control subjects. The binary logistic regression model was used to estimate the odds ratio (OR) for each polymorphism per effect allele increase. The mean (standard deviation [SD]) age of the drug-resistant patients was 10.7 (9.0) years versus 7.3 (3.6) in the control group. In the case group, most of the patients with epilepsy were diagnosed with generalized seizure (about 87%) and negative epileptic history status (63%). Furthermore, idiopathic epilepsy was dominant in the case group (69%). There was a clinically meaningful increase in the chance of drug-resistant epilepsy in participants with candidate polymorphism in ABCG2 gene (per allele T increase, adjusted odds ratio [OR] 2.41, confidence interval [CI] 0.99 to 5.87, P=0.05). No significant association was found between CYP3A5 (per allele C increase, OR 0.92, CI 0.33 to 2.60, P= 0.88) and SCN1A (per allele *1 increase, OR 0.65, 95% CI 0.34 to 1.23, P= 0.19) with drug-resistant epilepsy. We found evidence for the relationship between the ABCG2 gene polymorphism and a higher chance of drug-resistant epilepsy in children. This finding may have important implications for understanding the role of ABCG2 gene polymorphism in children with drug-resistant epilepsy.

Якість життя як показник ефективності комбінованої терапії з використанням транскраніальної магнітної стимуляції при епілепсії

У статті наводиться аналіз якості життя згідно з опитувальником QOLIE‑31 у 48 пацієнтів з епілепсією, яким здійснювалася ритмічна транскраніальна магнітна стимуляція (рТМС). Аналіз результатів проведеного дослідження з використанням рТМС і мінімальних терапевтичних доз антиепілептичних препаратів показав, що подібна комбінація фармакологічних і фізичних чинників дозволяє контролювати перебіг епілепсії та забезпечує досить високу протисудомну дію. Отримані результати дозволили обгрунтовано доповнити медикаментозне лікування епілепсії проведенням курсу рТМС, домогтися оптимального терапевтичного результату в кожного пацієнта з мінімальним ризиком побічних ефектів, а також поліпшити якість його життя.

Nanoengineered on-demand drug delivery system improves efficacy of pharmacotherapy for epilepsy.

Long-term pharmacotherapy, serving as the main therapeutic approach for epilepsy prophylaxis, has suffered from limited efficacy and potential side effects because of the blood-brain barrier (BBB) and untimely medication. Here, we reported a nanoengineered drug delivery system for synergistic brain-targeting delivery and on-demand drug release of antiepileptic drugs (AEDs). The dopamine-pyrrole hybrid system can improve delivery efficiency through a combination of receptor-mediated transcytosis and BBB disruption–enabled transport induced by photothermal conversion of near-infrared light. Incorporation of polydopamine endowed the delivery system with enhanced conductivity and sensitivity, giving sustained (2 hours) and rapid (30 s) drug release in response to epileptiform discharges. Acute, continuous, and spontaneous seizure models validated that the delivery system could inhibit seizures upon epileptiform abnormalities, treated by one-fifth of the conventional dosage. Complemented with satisfactory biosafety results, this “smart” modality is promising to be an effective and safe strategy to improve the therapeutic index of AEDs for epilepsy.

Is It Time to Test the Antiseizure Potential of Palmitoylethanolamide in Human Studies? A Systematic Review of Preclinical Evidence.

Antiseizure medications are the cornerstone pharmacotherapy for epilepsy. They are not devoid of side effects. In search for better-tolerated antiseizure agents, cannabinoid compounds and other N-acylethanolamines not directly binding cannabinoid receptors have drawn significant attention. Among these, palmitoylethanolamide (PEA) has shown neuroprotective, anti-inflammatory, and analgesic properties. All studies examining PEA’s role in epilepsy and acute seizures were systematically reviewed. Preclinical studies indicated a systematically reduced PEA tone accompanied by alterations of endocannabinoid levels. PEA supplementation reduced seizure frequency and severity in animal models of epilepsy and acute seizures, in some cases, similarly to available antiseizure medications but with a better safety profile. The peripheral-brain immune system seemed to be more effectively modulated by subchronic pretreatment with PEA, with positive consequences in terms of better responding to subsequent epileptogenic insults. PEA treatment restored the endocannabinoid level changes that occur in a seizure episode, with potential preventive implications in terms of neural damage. Neurobiological mechanisms for PEA antiseizure effect seemed to include the activation of the endocannabinoid system and the modulation of neuroinflammation and excitotoxicity. Although no human study was identified, there is ground for testing the antiseizure potential of PEA and its safety profile in human studies of epilepsy.

Barbiturates and valproates in the pharmacotherapy of epilepsy: clinical and psychological interactions

Barbiturates and valproates in the pharmacotherapy of epilepsy: clinical and psychological interactions

The effect of weight reduction surgery on the efficacy and tolerability of epilepsy pharmacotherapy

BackgroundBariatric surgery is an increasingly utilized procedure among patients with obesity-related medical complications. The impact of bariatric surgery on seizure frequency and antiseizure drug (ASD) levels are not well described. MethodsWe conducted a retrospective chart review of adult patients with a history of epilepsy or seizures undergoing bariatric surgery for morbid obesity from September 1997–September 2019. The median follow-up was 60 months [range 9–220 months]. ResultsForty-six patients with a history of seizures were identified (38 female); 44 patients had recurrent and unprovoked seizures. Seventeen sets of pre- and post-surgery drug concentrations from 14 patients were reviewed. The median age at surgery was 44 years (range, 19–68). Thirty-three patients were prescribed ASDs at the time of bariatric surgery (median 1 drug [range, 1–3]). Laparoscopic Roux-en-Y was performed in 40 patients, and sleeve gastrectomy in 6 patients. Median pre-surgery weight was 120.75 kg (range, 71–230) and BMI 44.4 kg/m2 (range, 34–77.6). Six months following surgery the median weight was 89.5 kg (range, 58.2–202) and BMI 34.2 kg/m2 (range, 24.5–61.9).Nine patients (19.6%) had a worsening of seizure control on long-term follow-up (median 60, range 9–220 months) following bariatric surgery, including five (10.8%) who suffered seizures within 6 months of bariatric surgery. Five patients developed ASD-associated side effects following bariatric surgery including irritability in two patients (levetiracetam and phenytoin) and one patient each suffering from somnolence (phenytoin), hyperammonemic encephalopathy (sodium valproate), and nausea and vomiting (carbamazepine). Subtherapeutic post-surgery drug concentrations were identified in 5 patients and supratherapeutic concentrations in one patient. In the initial 6 months following surgery, ASD doses were increased in five patients and reduced in five. ConclusionsThe majority of patients with epilepsy who undergo bariatric surgery have no change in seizure frequency. However, a significant minority of patients may experience medication side effects or an increase in seizure tendency due to the impact of bariatric surgery on ASD drug absorption and metabolism leading. Pre- and post-surgical serum concentrations should be measured in patients with seizures or epilepsy receiving ASDs.

Benefits of multi-day supplementation with probiotic kefir in Rasmussen encephalitis: the first case report

ABSTRACT Introduction Rasmussen encephalitis (RE) is a rare inflammatory disease, characterized by unilateral hemispheric atrophy, focal intractable seizures, progressive hemiparesis, and neurological deficits. Case report The patient is a young man under pharmacotherapy for epilepsy, exhibiting classical abnormal movements, which are consider typical hallmarks of RE. During clinical care sessions, he presented many episodes of tonic-clonic seizures involving sudden loss of consciousness followed by a post-ictal phase with weakness and interaction difficulty. During the kefir supplementation, the patient presented only short-term absence seizures, quickly returning to activities. Additionally, he presented cognitive and language improvement, being more responsive to commands. The daily diary control of patient’s mother and caregiver at school reported an impressive reduction in number and severity of seizures, becoming less aggressive and more involved in school activities. The serum biochemical markers showed that kefir administration caused a significant decrease of pro-inflammatory and a simultaneous increase of anti-inflammatory cytokine levels. In parallel, after treatment, this probiotic reduced reactive oxygen species levels, increased NO bioavailability, revealing antiapoptotic and antigenotoxic effects. Regarding the microbiological analysis, kefir increased Lactobacillus and Bifidobacterium species. Conclusion To our knowledge, this is the first case reporting remarkable beneficial effects of the probiotic kefir in RE. This case report strongly suggests kefir supplementation as a potential and safe-effective adjuvant therapeutic strategy in the control and treatment of RE.