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Fulltext Flumazenil Pretreatment Reduces Mefenamic Acid-Induced Central Nervous System Toxicity in Mice

Jarrar Q, Ayoub R, Jarrar Y, Aburass H, Goh KW, Ardianto C, et al.

J Integr Neurosci, 2023 Jul 26;22(4):104.
PMID: 37519168 DOI: 10.31083/j.jin2204104

BACKGROUND: Mefenamic acid (MFA), a common analgesic, causes central nervous system (CNS) toxicity at high doses with a proposed activity on the Gamma-aminobutyric acid (GABA) system. However, it remains unknown whether flumazenil (FMZ), a GABA type A receptor (GABAAR) antagonist, can reverse MFA toxicity.
METHODS: The behavioral and neurophysiological effects of MFA were investigated in mice with and without FMZ pre-treatment. The elevated zero maze (EZM) and marble burying tests were used to assess anxiety-like behaviors and burying activities, respectively. The standard bar test was used to evaluate catalepsy, while the actophotometer test was used to measure locomotor activity. Seizure intensity was scored, and fatalities were counted.
RESULTS: Without FMZ pre-treatment, MFA induced behavioral and neurophysiological effects in a dose-dependent manner as follows: At a dose of 20 mg/kg, i.p, MFA-treated mice exhibited anxiety-like behaviors, which was determined by a significant increase in the time spent in the closed areas and a significant decrease in the number of entries to the open areas of the EZM apparatus. These mice also showed a significant decrease in the burying activity, manifested as a significant decrease in the number of buried marbles. At 40 mg/kg, i.p., MFA-treated mice showed catalepsy that was associated with a significant decrease in locomotor activity. At a dose of 80 mg/kg, i.p., mice developed fatal tonic-clonic seizures (seizure score = 4). Pre-treatment with FMZ (5 mg/kg, i.p.) significantly reversed the anxiety-like behaviors and restored marble-burying activity. Additionally, FMZ prevented catalepsy, significantly restored locomotor activity, reduced seizure intensity (seizure score = 0.3) and significantly reduced mortalities.
CONCLUSIONS: The present study's findings indicate that activation of the GABAAR is involved in the CNS toxicity of MFA, and FMZ reverses MFA toxicity by interfering with this receptor.

Matched MeSH terms: Seizures/drug therapy
Possible interplay between the theories of pharmacoresistant epilepsy

Juvale IIA, Che Has AT

Eur J Neurosci, 2021 03;53(6):1998-2026.
PMID: 33306252 DOI: 10.1111/ejn.15079

Epilepsy is one of the oldest known neurological disorders and is characterized by recurrent seizure activity. It has a high incidence rate, affecting a broad demographic in both developed and developing countries. Comorbid conditions are frequent in patients with epilepsy and have detrimental effects on their quality of life. Current management options for epilepsy include the use of anti-epileptic drugs, surgery, or a ketogenic diet. However, more than 30% of patients diagnosed with epilepsy exhibit drug resistance to anti-epileptic drugs. Further, surgery and ketogenic diets do little to alleviate the symptoms of patients with pharmacoresistant epilepsy. Thus, there is an urgent need to understand the underlying mechanisms of pharmacoresistant epilepsy to design newer and more effective anti-epileptic drugs. Several theories of pharmacoresistant epilepsy have been suggested over the years, the most common being the gene variant hypothesis, network hypothesis, multidrug transporter hypothesis, and target hypothesis. In our review, we discuss the main theories of pharmacoresistant epilepsy and highlight a possible interconnection between their mechanisms that could lead to the development of novel therapies for pharmacoresistant epilepsy.

Matched MeSH terms: Seizures/drug therapy
Cerebral infarction in juvenile rheumatoid arthritis

Gururaj AK, Chand RP, Chuah SP

Clin Neurol Neurosurg, 1988;90(3):261-3.
PMID: 3197355

Cerebral involvement associated with juvenile rheumatoid arthritis is rare. It is not influenced by treatment and the presentation can be varied. We describe a case of cerebral infarction secondary to vasculitis in a child with juvenile rheumatoid arthritis.

Matched MeSH terms: Seizures/drug therapy
Fulltext A post hoc analysis of the long-term safety and efficacy of perampanel in Asian patients with epilepsy

Inoue Y, Kaneko S, Hsieh PF, Meshram C, Lee SA, Aziz ZA, et al.

Epilepsia, 2019 03;60 Suppl 1:60-67.
PMID: 30869167 DOI: 10.1111/epi.14645

This post hoc analysis assessed the long-term safety, tolerability, and efficacy of perampanel in Asian patients with refractory focal seizures; an additional analysis assessed the effect of perampanel on focal impaired awareness seizures (FIAS) with focal to bilateral tonic-clonic (FBTC) seizures. In this subanalysis, data from Asian patients ≥12 years of age who had focal seizures with FBTC seizures despite taking one to 3 concomitant antiepileptic drugs at baseline, and who had entered either the long-term extension phase of 3 phase-3 perampanel trials (study 307) or the 10-week extension phase of study 335, were analyzed for the effect of perampanel on duration of exposure, safety, and seizure outcomes. Of 874 Asian patients included in the analysis, 205 had previously received placebo during the double-blind phase-3 trials and 669 had previously received perampanel 2-12 mg/day; 313 had FIAS with FBTC seizures at core study baseline. The median duration of exposure to perampanel was 385.0 days, and the retention rate at one year was 62.6%. Overall, during the first 52 weeks of perampanel treatment, 777 patients (88.9%) had treatment-emergent adverse events (TEAEs), most of which were mild to moderate in severity. The most frequent TEAEs were dizziness (47.1%), somnolence (22.3%), and nasopharyngitis (17.4%). During the first 52 weeks of perampanel treatment, median percent change in seizure frequency per 28 days from pre-perampanel baseline for all focal seizures was -28.1%, and -51.7% for FIAS with FBTC seizures. The 50% responder rate relative to pre-perampanel baseline for all focal seizures was 33.8%, and 51.1% for FIAS with FBTC seizures. Long-term treatment with perampanel in Asian patients had safety, tolerability, and efficacy similar to that of the global population in the phase-3 trials and extension study 307. The safety profile and response rate suggest benefit for an Asian population of patients with refractory epilepsy.

Matched MeSH terms: Seizures/drug therapy
Perampanel, an AMPA receptor antagonist: From clinical research to practice in clinical settings

Tsai JJ, Wu T, Leung H, Desudchit T, Tiamkao S, Lim KS, et al.

Acta Neurol. Scand., 2018 Apr;137(4):378-391.
PMID: 29214650 DOI: 10.1111/ane.12879

Epileptic seizures are refractory to treatment in approximately one-third of patients despite the recent introduction of many newer antiepileptic drugs (AEDs). Development of novel AEDs therefore remains a high priority. Perampanel is a first-in-class non-competitive selective AMPA receptor antagonist with a unique mechanism of action. Clinical efficacy and safety of perampanel as adjunctive treatment for focal seizures with/without secondary generalization (±SG) and primary generalized tonic-clonic (PGTC) seizures have been established in five phase 3 randomized controlled trials (RCTs), and a long-term extension study, and perampanel is approved as monotherapy for focal seizures ±SG in the USA. In patients with focal seizures ±SG, add-on perampanel resulted in median percent reduction in seizure frequency 23.3%-34.5% and ≥50% responder rate 28.5%-37.6%; in PGTC seizures, these results were 76.5% and 64.2%, respectively. Efficacy among adolescents (reduction in seizure frequency 34.8%-35.6%; ≥50% responder rate 40.9%-45.0%) and elderly people (reduction in seizure frequency 12.5%-16.9%; ≥50% responder rate 22.2%-42.9%) is similar to those in adults, and results remain comparable between Asian (reduction in seizure frequency 17.3%-38.0%) and global populations. Perampanel has been extensively studied in real-world clinical practice, with similar efficacy and safety results to the RCTs (≥50% responder rate 12.8%-75.0%; adverse events of somnolence/sedation, dizziness, ataxia, and behavioral changes). Real-world observational studies suggest that perampanel tolerability can be improved by slow titration (2 mg every 2-4 weeks), and bedtime administration can mitigate somnolence and dizziness. Counseling about the potential for behavioral changes and close monitoring are recommended.

Matched MeSH terms: Seizures/drug therapy*
Fulltext Antiepileptic drug utilisation and seizure outcome among paediatric patients in a Malaysian public hospital

Hasan SS, Bahari MB, Babar ZU, Ganesan V

Singapore Med J, 2010 Jan;51(1):21-7.
PMID: 20200771

INTRODUCTION: The primary purpose of this study was to evaluate the utilisation pattern and seizure outcome of newer and older antiepileptic drugs in paediatric clinical practice in a Malaysian hospital setting.
METHODS: Over a two-month period, all paediatric epilepsy patients from Penang General Hospital, Malaysia who were diagnosed according to the classification of the International League Against Epilepsy were followed up prospectively, and the patients' information was gathered with the help of a validated data collection form. This included demographic characteristics, monotherapy and polytherapy of antiepileptic drugs, as well as the number of seizures experienced.
RESULTS: Partial seizures, including complex and simple partial seizures (47.2 percent), followed by generalised seizures (40 percent), were the most common seizure types found in this study. An average of 1.51 antiepileptic drugs per patient was prescribed, with 54.3 percent of the patients on monotherapy and 45.7 percent on polytherapy. Overall, sodium valproate was the most frequently prescribed antiepileptic drug (36.8 percent), followed by carbamazepine (30.2 percent) and lamotrigine (10.4 percent). Carbamazepine was the most frequently prescribed monotherapy (28.6 percent), followed by sodium valproate (17.1 percent). The newer antiepileptic drugs were also found to be used as monotherapy in 7.2 percent of the cases. Moreover, a significant difference was observed between the older and newer antiepileptic drugs in terms of the number of seizures experienced (p=0.027). Most (75 percent) of the seizure-free patients were on carbamazepine monotherapy.
CONCLUSION: Monotherapy was the most frequently used remedy in all forms of epilepsy. Overall, sodium valproate was the most commonly used drug, while carbamazepine was found to be more frequently used as monotherapy. There was a significant difference found between the older and newer antiepileptic drugs, with 87.5 percent of seizure-free patients on older antiepileptic drugs.

Study site: all paediatric epilepsy patients from Penang General Hospital

Matched MeSH terms: Seizures/drug therapy*
The complexity of achieving anticoagulation control in the face of warfarin-phenytoin interaction: an Asian case report

Hassan Y, Awaisu A, Aziz NA, Ismail O

Pharm World Sci, 2005 Feb;27(1):16-9.
PMID: 15861930

Phenytoin has been reported to have major interactions with warfarin. Phenytoin induces warfarin's metabolism. However, there are many case reports which provide conflicting conclusions. Here, we report a case of a 65-year-old man with mechanical heart valve on chronic warfarin therapy who experienced persistent fluctuations of INR and bleeding secondary to probable warfarin-phenytoin interactions. The patient's anticoagulation clinic visits prior to hospitalization were thoroughly evaluated and we continued to follow-up the case for 3 months post-hospitalization. The reported interaction could be reasonably explained from the chronology of events and the pattern of INR fluctuations whenever phenytoin was either added or discontinued from his drug regimen.

Matched MeSH terms: Seizures/drug therapy
Schaftoside Suppresses Pentylenetetrazol-Induced Seizures in Zebrafish via Suppressing Apoptosis, Modulating Inflammation, and Oxidative Stress

Dang J, Paudel YN, Yang X, Ren Q, Zhang S, Ji X, et al.

ACS Chem Neurosci, 2021 07 07;12(13):2542-2552.
PMID: 34128378 DOI: 10.1021/acschemneuro.1c00314

The lack of disease-modifying therapeutic strategies against epileptic seizures has caused a surge in preclinical research focused on exploring and developing novel therapeutic candidates for epilepsy. Compounds from traditional Chinese medicines (TCMs) have gained much attention for a plethora of neurological diseases, including epilepsy. Herein, for the first time, we evaluated the anticonvulsive effects of schaftoside (SS), a TCM, on pentylenetetrazol (PTZ)-induced epileptic seizures in zebrafish and examined the underlying mechanisms. We observed that SS pretreatments significantly suppressed seizure-like behavior and prolonged the onset of seizures. Zebrafish larvae pretreated with SS demonstrated downregulation of c-fos expression during seizures. PTZ-induced upregulation of apoptotic cells was decreased upon pretreatment with SS. Inflammatory phenomena during seizure progression including the upregulation of interleukin 6 (IL-6), interleukin 1 beta (IL-1β), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were downregulated upon pretreatment with SS. The PTZ-induced recruitment of immunocytes was in turn reduced upon SS pretreatment. Moreover, SS pretreatment modulated oxidative stress, as demonstrated by decreased levels of catalase (CAT) and increased levels of glutathione peroxidase-1a (GPx1a) and manganese superoxide dismutase (Mn-SOD). However, pretreatment with SS modulated the PTZ-induced downregulation of the relative enzyme activity of CAT, GPx, and SOD. Hence, our findings suggest that SS pretreatment ameliorates PTZ-induced seizures, suppresses apoptosis, and downregulates the inflammatory response and oxidative stress, which potentially protect against further seizures in zebrafish.

Matched MeSH terms: Seizures/drug therapy
Comparison between the effects of propofol and etomidate on motor and electroencephalogram seizure duration during electroconvulsive therapy

Tan HL, Lee CY

Anaesth Intensive Care, 2009 Sep;37(5):807-14.
PMID: 19775046

An ideal anaesthetic for electroconvulsive therapy (ECT) should have rapid onset and offset with no effect on seizure duration, and provide cardiovascular stability during the procedure. Propofol is commonly used, even though it has been shown to shorten seizure duration which might affect the efficacy of ECT Etomidate has been advocated as an alternative. This prospective, randomised, single-blind, crossover study was conducted to compare the effects of etomidate (Etomidate-Lipuro, B. Braun Ltd, Melsungen, Germany) and propofol (Diprivan, AstraZeneca, UK) on seizure duration as well as haemodynamic parameters in patients undergoing ECT Twenty patients aged between 18 and 70 years were recruited. Group I received etomidate 0.3 mg/kg for the first course of ECT (Group IA) and propofol 1.5 mg/kg for the second ECT (Group IB), while Group II received propofol for the first ECT (Group IIA) and etomidate for the second ECT (Group IIB). There was a washout period of two to three days in between procedures. Parameters recorded included motor seizure duration, electroencephalogram seizure duration, blood pressure and heart rate. Analysis demonstrated neither period effect nor treatment period interaction. Etomidate was associated with a significantly longer motor and electroencephalogram seizure duration compared with propofol (P < 0.01). Neither drug demonstrated consistent effects in suppressing the rise in heart rate or blood pressure during ECT Myoclonus and pain on injection were the most common adverse effects in etomidate group and propofol group respectively. Etomidate is a useful anaesthetic agent for ECT and should be considered in patients with inadequate seizure duration with propofol.

Matched MeSH terms: Seizures/drug therapy*
What are the effects of intravenous immunoglobulins on seizures and quality of life of people with epilepsy? A Cochrane Review summary with commentary

Ahmad Fauzi A, Patrick Engkasan J

Dev Med Child Neurol, 2021 05;63(5):501-502.
PMID: 33559130 DOI: 10.1111/dmcn.14835
Matched MeSH terms: Seizures/drug therapy
Does rapid withdrawal of antiseizure medication increase risk of seizure recurrence in epilepsy? A Cochrane Review summary with commentary

Patrick Engkasan J

Dev Med Child Neurol, 2021 08;63(8):897-898.
PMID: 33904198 DOI: 10.1111/dmcn.14906
Matched MeSH terms: Seizures/drug therapy
Effect of fluoxetine on maximal electroshock seizures in mice: acute vs chronic administration

Raju SS, Noor AR, Gurthu S, Giriyappanavar CR, Acharya SB, Low HC, et al.

Pharmacol Res, 1999 Jun;39(6):451-4.
PMID: 10373242

There are no definite reports regarding the effects of chronic fluoxetine on animal models of epilepsy. Since chronically administered fluoxetine, in comparison to acutely administered fluoxetine has different effects on CNS, the present study was undertaken to investigate the effect of acute and chronic fluoxetine pretreatment, on a median anticonvulsant dose (ED50) of phenytoin in male ICR albino mice. Additionally, the effects of fluoxetine pretreatment on median convulsive current (CC50) in the presence and absence of phenytoin were investigated and results were compared. The maximal electroshock seizure (MES) test was used to estimate the ED50of phenytoin. The electroshock threshold test was used to estimate CC50. ED50and CC50values were calculated by probit analysis. The effects of the chronic and acute fluoxetine groups on the ED50of phenytoin were significantly different (P<0.05), and on CC50this difference was not statistically significant. Chronic fluoxetine insignificantly increased the ED50of phenytoin and decreased the CC50while acute fluoxetine decreased the ED50of phenytoin and increased the CC50. Our results indicate that chronic fluoxetine does not have an antiepileptic property and it may have dubious proconvulsant properties, contrary to acute fluoxetine.

Matched MeSH terms: Seizures/drug therapy*
Fulltext Identification of curcumin analogues with anti-seizure potential in vivo using chemical and genetic zebrafish larva seizure models

Choo BKM, Kundap UP, Faudzi SMM, Abas F, Shaikh MF, Samarut É

Biomed Pharmacother, 2021 Oct;142:112035.
PMID: 34411917 DOI: 10.1016/j.biopha.2021.112035

Seizures are the outward manifestation of abnormally excessive or synchronous brain activity. While seizures can be somewhat symptomatically managed with anti-epileptic drugs (AEDs), many patients are still refractory to the currently available AEDs. As a result, there is a need to identify new molecules with anti-seizure properties. Curcumin is the principle curcuminoid of Curcuma longa, or colloquially turmeric, and has been experimentally proven to have anti-convulsive properties, but its poor bioavailability has dampened further therapeutic interest. Hence, this study aimed to ask if structural analogues of curcumin with an adequate bioavailability could have an anti-seizure effect in vivo. To do so, we tested these analogues following a multipronged approach combining the use of several zebrafish seizure models (chemically-induced and genetic) and complementary assays (behavioural and brain activity). Overall, from the 68 analogues tested, we found 15 different derivatives that were able to significantly decrease the behavioural hyperactivity induced by pentylenetetrazol. Of those, only a few showed an effect on the hyperactivity phenotype of two genetic models of brain seizures that are the gabra1 and gabrg2 knockouts. Two analogues, CA 80(1) and CA 74(1), were able to significantly alleviate brain seizures of gabrg2-mutant larvae. As a result, these analogues are good candidates as novel anti-seizure agents.

Matched MeSH terms: Seizures/drug therapy*
Effect of newer anti-epileptic drugs (AEDs) on the cognitive status in pentylenetetrazol induced seizures in a zebrafish model

Choo BKM, Kundap UP, Johan Arief MFB, Kumari Y, Yap JL, Wong CP, et al.

Prog Neuropsychopharmacol Biol Psychiatry, 2019 06 08;92:483-493.
PMID: 30844417 DOI: 10.1016/j.pnpbp.2019.02.014

Epilepsy is marked by seizures that are a manifestation of excessive brain activity and is symptomatically treatable by anti-epileptic drugs (AEDs). Unfortunately, the older AEDs have many side effects, with cognitive impairment being a major side effect that affects the daily lives of people with epilepsy. Thus, this study aimed to determine if newer AEDs (Zonisamide, Levetiracetam, Perampanel, Lamotrigine and Valproic Acid) also cause cognitive impairment, using a zebrafish model. Acute seizures were induced in zebrafish using pentylenetetrazol (PTZ) and cognitive function was assessed using the T-maze test of learning and memory. Neurotransmitter and gene expression levels related to epilepsy as well as learning and memory were also studied to provide a better understanding of the underlying processes. Ultimately, impaired cognitive function was seen in AED treated zebrafish, regardless of whether seizures were induced. A highly significant decrease in γ-Aminobutyric Acid (GABA) and glutamate levels was also discovered, although acetylcholine levels were more variable. The gene expression levels of Brain-Derived Neurotrophic Factor (BDNF), Neuropeptide Y (NPY) and Cyclic Adenosine Monophosphate (CAMP) Responsive Element Binding Protein 1 (CREB-1) were not found to be significantly different in AED treated zebrafish. Based on the experimental results, a decrease in brain glutamate levels due to AED treatment appears to be at least one of the major factors behind the observed cognitive impairment in the treated zebrafish.

Matched MeSH terms: Seizures/drug therapy*
Tumor Necrosis Factor-α, the Pathological Key to Post-Traumatic Epilepsy: A Comprehensive Systematic Review

Arulsamy A, Shaikh MF

ACS Chem Neurosci, 2020 07 01;11(13):1900-1908.
PMID: 32479057 DOI: 10.1021/acschemneuro.0c00301

Post-traumatic epilepsy (PTE) is one of the detrimental outcomes of traumatic brain injury (TBI), resulting in recurrent seizures that impact daily life. However, the pathological relationship between PTE and TBI remains unclear, and commonly prescribed antiepileptic drugs (AED) are ineffective against PTE. Fortunately, emerging research implicates neuroinflammation, particularly, tumor necrosis factor-α (TNF-α), as the key mediator for PTE development. Thus, this review aims to examine the available literature regarding the role of TNF-α in PTE pathology and, subsequently, evaluate TNF-α as a possible target for its treatment. A comprehensive literature search was conducted on four databases including PubMed, CINAHL, Embase, and Scopus. Articles with relevance in investigating TNF-α expression in PTE were considered in this review. Critical evaluation of four articles that met the inclusion criteria suggests a proportional relationship between TNF-α expression and seizure susceptibilit and that neutralization or suppression of TNF-α release results in reduced susceptibility to seizures. In conclusion, this review elucidates the importance of TNF-α expression in epileptogenesis postinjury and urges future research to focus more on clinical studies involving TNF-α, which may provide clearer insight into PTE prevention, therefore improving the lives of PTE patients.

Matched MeSH terms: Seizures/drug therapy
Naturally Occurring HMGB1 Inhibitor, Glycyrrhizin, Modulates Chronic Seizures-Induced Memory Dysfunction in Zebrafish Model

Paudel YN, Khan SU, Othman I, Shaikh MF

ACS Chem Neurosci, 2021 09 15;12(18):3288-3302.
PMID: 34463468 DOI: 10.1021/acschemneuro.0c00825

Glycyrrhizin (GL) is a well-known pharmacological inhibitor of high mobility group box 1 (HMGB1) and is abundantly present in the licorice root (Glycyrrhiza radix). HMGB1 protein, a key mediator of neuroinflammation, has been implicated in several neurological disorders, including epilepsy. Epilepsy is a devastating neurological disorder with no effective disease-modifying treatment strategies yet, suggesting a pressing need for exploring novel therapeutic options. In the current investigation, using a second hit pentylenetetrazol (PTZ) induced chronic seizure model in adult zebrafish, regulated mRNA expression of HMGB1 was inhibited by pretreatment with GL (25, 50, and 100 mg/kg, ip). A molecular docking study suggests that GL establishes different binding interactions with the various amino acid chains of HMGB1 and Toll-like receptor-4 (TLR4). Our finding suggests that GL pretreatment reduces/suppresses second hit PTZ induced seizure, as shown by the reduction in the seizure score. GL also regulates the second hit PTZ induced behavioral impairment and rescued second hit PTZ related memory impairment as demonstrated by an increase in the inflection ratio (IR) at the 3 h and 24 h T-maze trial. GL inhibited seizure-induced neuronal activity as demonstrated by reduced C-fos mRNA expression. GL also modulated mRNA expression of BDNF, CREB-1, and NPY. The possible mechanism underlying the anticonvulsive effect of GL could be attributed to its anti-inflammatory activity, as demonstrated by the downregulated mRNA expression level of HMGB1, TLR4, NF-kB, and TNF-α. Overall, our finding suggests that GL exerts an anticonvulsive effect and ameliorates seizure-related memory disruption plausibly through regulating of the HMGB1-TLR4-NF-kB axis.

Matched MeSH terms: Seizures/drug therapy
Elucidating the Potential Side Effects of Current Anti-Seizure Drugs for Epilepsy

Akyüz E, Köklü B, Ozenen C, Arulsamy A, Shaikh MF

Curr Neuropharmacol, 2021;19(11):1865-1883.
PMID: 34525933 DOI: 10.2174/1570159X19666210826125341

Over the decades, various interventions have been developed and utilized to treat epilepsy. However, the majority of epileptic patients are often first prescribed anti-epileptic drugs (AED), now known as anti-seizure drugs (ASD), as the first line of defense to suppress their seizures and regain their quality of life. ASDs exert their anti-convulsant effects through various mechanisms of action, including regulation of ion channels, blocking glutamate-mediated stimulating neurotransmitter interaction, and enhancing the inhibitory GABA transmission. About one-third of epileptic patients are often resistant to anti-convulsant drugs, while others develop numerous side effects, which may lead to treatment discontinuation and further deterioration of quality of life. Common side effects of ASDs include headache, nausea and dizziness. However, more adverse effects, such as auditory and visual problems, skin problems, liver dysfunction, pancreatitis and kidney disorders may also be witnessed. Some ASDs may even result in life-threatening conditions as well as serious abnormalities, especially in patients with comorbidities and in pregnant women. Nevertheless, some clinicians had observed a reduction in the development of side effects post individualized ASD treatment. This suggests that a careful and well-informed ASD recommendation to patients may be crucial for an effective and side-effect-free control of their seizures. Therefore, this review aimed to elucidate the anticonvulsant effects of ASDs as well as their side effect profile by discussing their mechanism of action and reported adverse effects based on clinical and preclinical studies, thereby providing clinicians with a greater understanding of the safety of current ASDs.

Matched MeSH terms: Seizures/drug therapy
Fulltext Fruits for Seizures? A Systematic Review on the Potential Anti-Convulsant Effects of Fruits and their Phytochemicals

Siang LH, Arulsamy A, Yoon YK, Shaikh MF

Curr Neuropharmacol, 2022;20(10):1925-1940.
PMID: 34517803 DOI: 10.2174/1570159X19666210913120637

Epilepsy is a devastating neurological disorder. Current anti-convulsant drugs are only effective in about 70% of patients, while the rest remain drug-resistant. Thus, alternative methods have been explored to control seizures in these drug-resistant patients. One such method may be through the utilization of fruit phytochemicals. These phytochemicals have been reported to have beneficial properties such as anti-convulsant, anti-oxidant, and anti-inflammatory activities. However, some fruits may also elicit harmful effects. This review aims to summarize and elucidate the anti- or pro-convulsant effects of fruits used in relation to seizures in hopes of providing a good therapeutic reference to epileptic patients and their carers. Three databases, SCOPUS, ScienceDirect, and PubMed, were utilized for the literature search. Based on the PRISMA guidelines, a total of 40 articles were selected for critical appraisal in this review. Overall, the extracts and phytochemicals of fruits managed to effectively reduce seizure activities in various preclinical seizure models, acting mainly through the activation of the inhibitory neurotransmission and blocking the excitatory neurotransmission. Only star fruit has been identified as a pro-convulsant fruit due to its caramboxin and oxalate compounds. Future studies should focus more on utilizing these fruits as possible treatment strategies for epilepsy.

Matched MeSH terms: Seizures/drug therapy
Fulltext Effect of tualang honey against KA-induced oxidative stress and neurodegeneration in the cortex of rats

Mohd Sairazi NS, K N S S, Asari MA, Mummedy S, Muzaimi M, Sulaiman SA

BMC Complement Altern Med, 2017 Jan 09;17(1):31.
PMID: 28068984 DOI: 10.1186/s12906-016-1534-x

Administration of KA on rodents has resulted in seizures, behavioral changes, oxidative stress, and neuronal degeneration on selective population of neurons in the brain. The present study was undertaken to investigate the extent of neuroprotective effect conferred by Malaysian Tualang Honey (TH), an antioxidant agent, in the cerebral cortex of rats against KA-induced oxidative stress and neurodegeneration in an animal model of KA-induced excitotoxicity.

Matched MeSH terms: Seizures/drug therapy*
Periodic lateralized epileptiform discharges in neuropsychiatric lupus: association with cerebritis in magnetic resonance imaging and resolution after intravenous immunoglobulin

Lim KS, Cheong KL, Tan CT

Lupus, 2010 May;19(6):748-52.
PMID: 20133346 DOI: 10.1177/0961203309351539

A 13-year-old girl with a known diagnosis of systemic lupus erythematosus presented with seizures and psychosis. An electroencephalogram (EEG) revealed continuous, non-evolving periodic lateralized epileptiform discharges (PLEDs) in the left temporal region, which did not resolve with benzodiazepine. A magnetic resonance imaging (MRI) brain scan demonstrated a focal hyperintensity in the left medial temporal and left occipital lobes, left thalamus and bilateral cerebellar white matter, with evidence of vasculitis in the magnetic resonance angiography. Intravenous immunoglobulin was given because of failed steroid therapy, which resulted in a full resolution of clinical, EEG and MRI abnormalities. Lupus cerebritis should be considered as a possible aetiology in PLEDs, and immunoglobulin can be effective in neuropsychiatric lupus.

Matched MeSH terms: Seizures/drug therapy

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