Antiepilepsy Drugs Research Articles

Formulation and Evaluation of Extended Release Matrix Tablets of Lamotrigine

For extended release drug delivery systems, the oral route of drug administration has, by far received more attention as it is natural uncomplicated, convenient and safer route. Matrix tablets composed of drug and release retarding material (e.g. polymer) offer the simplest approach in designing the extended release system. Long-term adherence to anti-epilepsy drug (AED) regimens is frequently suboptimal. Poor adherence to therapy is associated with a number of negative consequences, including an increase in patient seizures and mortality. The present study was aimed to study the effect of Chitosan and Sodium Alginate on the release rate Lamotrigine for the preparation of extended release formulations. Matrix Tablets were prepared by wet granulation method and subjected for Physiochemical and in-vitro evaluation tests. The results were shown that the prepared were found to be within the pharmacopeial limit and with good release characteristics.

Modulation of keap-1/Nrf2/HO-1 and NF-ĸb/caspase-3 signaling pathways by dihydromyricetin ameliorates sodium valproate-induced liver injury

Nuclear factor erythroid factor 2 (Nrf2) is the key regulatory of the antioxidant response elements. Also, Nrf2 interacts with nuclear factor kappa B (NF-ĸB) to inhibit subsequent inflammatory cascade. Activation of Nrf2 signaling ameliorates drug-induced liver injury. Sodium valproate (SVP) is an anti-epilepsy drug with a hepatotoxic adverse effect that restricts its clinical use. In this study, coadministration of Dihydromyricetin (DHM), a natural flavonoid, with SVP to rats upregulated gene expression of Nrf2 and its downstream gene, heme oxygenase 1 (HO-1), while suppressed the Nrf2 repressor, Keap-1. Additionally, DHM led to downregulation of proinflammatory factors in liver tissues, including NF-ĸB, interleukin 1 beta (IL-1β), and tumor necrosis factor alpha (TNF-α). This was accompanied by a decrease in the proapoptotic protein (cleaved caspase-3) expression level. Furthermore, biochemical and histopathological studies showed that DHM treatment improved liver function and lipid profile while decreased inflammatory cell infiltration, congestion, and hepatocellular damage. According to our knowledge, prior research has not examined the protective effect of DHM on the liver injury induced by SVP. Consequently, this study provides DHM as a promising herbal medication that, when used with SVP, can prevent its induced hepatotoxicity owing to its potential anti-oxidative, anti-inflammatory, and anti-apoptotic properties.

Audit to assess if children who have a feeding tube and take anti-epilepsy drugs (AED’s) can maintain normal serum vitamin D levels with national recommendations of vitamin D supplementation

Audit to assess if children who have a feeding tube and take anti-epilepsy drugs (AED’s) can maintain normal serum vitamin D levels with national recommendations of vitamin D supplementation

Treatment compliance, treatment patterns, and healthcare utilization in epilepsy patients with first add-on antiepileptic drugs: A nationwide cohort study

ObjectiveThis study aimed to assess the treatment compliance, patterns, healthcare resource utilization (HCRU), and costs of anti-epilepsy drugs (AEDs) as the first add-on therapy in patients with epilepsy. MethodsWe conducted a retrospective population-based cohort study using Korean National Health Insurance claims data from 2016 to 2020. Patients with epilepsy who newly received AED add-on therapy were identified and followed for up to 12 months to evaluate persistence, adherence, treatment patterns, HCRU, and costs. ResultsAmong 6,746 patients who initiated AED add-on therapy, 65.5% were persistent on their index AED add-on from the index date until the end of the follow-up period, and the mean persistent time on the index add-on was 307.3 ± 92.3 days. A total of 76.8% patients were adherent, with a medication possession ratio (MPR) ≥80%, and the mean MPR was 88.9 ± 25.4%. Persistence and adherence to the index AED add-on were relatively higher among patients prescribed lamotrigine, levetiracetam, oxcarbazepine, and perampanel than those prescribed carbamazepine, topiramate, or valproate. A total of 41.0% of the patients changed their index AED add-on during the follow-up period. The carbamazepine, topiramate, and valproate groups had higher rates of change than the other AED groups. HCRU and costs tended to be lower in the lamotrigine, levetiracetam, oxcarbazepine, and perampanel groups. Furthermore, perampanel showed the lowest HCRU and costs for all-cause cases as well as the lowest length of stay and outpatient visits for epilepsy-related cases. ConclusionIn this population-based study, the use of lamotrigine, levetiracetam, oxcarbazepine, or perampanel as the first add-on therapy in patients with epilepsy contributed to better treatment compliance and lower HCRU and costs than that of carbamazepine, topiramate, or valproate.

Long-term Rapamycin Treatment Inhibit AKT Activity and Lower Intracellular Calcium Expression in Organotypic Hippocampal Slice Cultures Model of Epilepsy

Despite the development of anti-epilepsy drugs, drug-refractory epilepsy still becomes a challenging problem along with an increased incidence of epilepsy. To face that challenge and increase patients’ quality of life, treatment of epilepsy must effectively prevent epileptogenesis, not only symptomatic treatment. AKT signaling pathway was proven to have important roles in epilepsy through its function in the synaptic plasticity, neurogenesis, axon guidance, modulation of the glutamate transporter, and activation of the Ca2+ channel. AKT also activated mTOR signaling pathway as activator of mTORC1 and also effector of mTORC2. Several studies showed the ability of long-term rapamycin treatment to inhibit mTORC2. This study used organotypic hippocampal slice cultures (OHSC) and long-term rapamycin treatment was administered for 3, 5, 8, and 10 days at a dose of 20 nM after induction of epilepsy by low-Mg2+ medium administration for 40 minutes. Low-Mg2+ medium administration induced seizure activity in OHSC showed by significant increase in intracellular Ca2+expressionand also significantly increase AKT activity. After administration of long-term rapamycin treatment AKT activity and intracellular Ca2+expression were significantly reduced. The longer the treatment of rapamycin, the lower the AKT activity and intracellular Ca2+expression. Long-term rapamycin treatment has the potential to become a novel epilepsy drug through its ability to attenuate AKT activity and suppress the seizures proven by lower intracellular Ca2+expression.

Vitamin d levels in pediatric epilepsy patients on the anti-epileptic drugs at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia

Background: Epilepsy is a common neurological disorder of childhood repeatedly necessitating prolonged use of anticonvulsants. This study was done to evaluate the status of vitamin D in epileptic children. We targeted to describe the prevalence and risk factors for vitamin D deficiency among children with epilepsy. 
 Methods: A hospital-based descriptive cross-sectional study design with prospective data collection was used among children with epilepsy on anti-epileptic drugs attending the Pediatric Neurology Clinic and their primary caretakers. For this study, a sample of 226 children and adolescents were included in the study and a blood sample for the determination of serum vitamin D was taken. The participants were interviewed, and medical records were thoroughly reviewed. Descriptive statistics and binary logistic regression analysis was done to assess determinants of vitamin D deficiency. . 
 Results: In this study, the prevalence of vitamin D deficiency was found to be 42%. Children on polytherapy (AOR = 4.3 (1.2 - 16)), 3 or more AEDs (AOR = 0.1 (0.0 - 0.8)), female sex (AOR = 1.8 (1.7 - 2.6)), age >15 years (AOR = 2.12 (1.0 - 1.5)), 4 months of exclusive breastfeeding (AOR = 5.6 (4.9 - 36)), family diet (AOR = 0.3 (0.1 - 0.8)) and non-ambulation (AOR = 1.7 (1.8 - 3.6)) were factors associated with being in the vitamin D deficiency group.
 Conclusion: According to this study patients who take Anti-Epilepsy drugs are at a higher risk of a poor vitamin D status. Based on this finding, the need for timely and appropriate vitamin D supplementation and periodic follow-up seems to be very evident.

Classification System for Predicting Emergent Epilepsy Phenotype in the Intra-amygdala Kainic Acid Mouse Model of Epilepsy.

Animal models of drug-resistant epilepsy represent an important resource for discovering new drug targets and testing experimental medicines. Intra-amygdala microinjection of kainic acid in mice is one of the most widely regarded models of drug-resistant epilepsy. Mice develop acute status epilepticus, which diminishes after a few hours and then, within a few days, mice display spontaneous seizures (epilepsy). The frequency of spontaneous seizures varies between mice, with some developing low or high seizure rates. The ability to predict soon after status epilepticus, which mice will go on to develop a normal frequency of seizures, would enable a significant reduction in resources and EEG reviewing time and lead to humane early end-points for the mice with low or high seizure rates. In this study, we developed two machine learning models, a feature-based and transfer learning-based approach, for predicting the emergent spontaneous seizure rates in the intra-amygdala kainic acid model based on the acute EEGs recorded in mice during status epilepticus lasting 40 minutes. The method was trained on data from 28 mice and subsequently tested on data from 16 mice. The feature-based and transfer learning-based models achieved accuracies of 69% and 75%, respectively on the test set in classifying emergent epilepsy as normal or outlier (i.e. low-frequency or high-frequency seizure rate). A limitation of the intra-amygdala kainic acid model has been the loss of time and resources from generating mice with low or high rates of spontaneous seizures. To date, no other research has attempted to predict emergent spontaneous seizure rates. The feature-based and transfer learning-based models will assist researchers in identifying mice with a normal frequency of seizures before the onset of spontaneous seizures. We have implemented this approach as a web server, which can potentially reduce the time and resources spent analysing the EEGs of mice who develop low-frequency or high-frequency seizure rates. This will enable the early humane endpoint of outlier mice, which aligns with the principles of the responsible use of animals in research and simultaneously speeds up preclinical anti-epilepsy drug discovery.

QSAR, molecular docking, and molecular designs of some anti-epilepsy compounds

Epilepsy is a non-communicable central nervous system (CNS) disease that accounts for approximately 0.8–1.2 % of the global population at any time. The hyper-activities of gamma butyric acid aminotransferase (GABAAT) enzyme have been confirmed to be largely responsible for seizure/epilepsy. Because of this special function, the GABAAT enzyme has been the main target of many anti-epilepsy drugs (AEDs). To date, many discovered AEDs have not eradicated this neurological disease. Since experimental determinations of modern drugs are usually costly and sometimes non-eco-friendly, in-silco quantitative structure–activity relationship (QSAR)-machine learning, docking and pharmacokinetics (PMK) techniques were used to design and test the oral bio-availabilities of all the designed AEDs. QSAR models were generated, and the predictive properties of R2int = 0.9827, R2ext = 0.9407, and R2adj of 0.9667 indicate the evidence that the developed model was not by chance. Six (6) new AEDs were newly designed, and they were found to have better anti-epileptic activities values of 2.146799, 2.224866, 2.31479, 2.450313, 2.301474, and 2.618303 than the standard AED, Vigabatrin (0.40672). Also, the docked new compounds shows excellent binding energies of −127.001, −129.071, −130.515, −126.881, −130.771, and −126.974 kcal/mol compared to the referenced AED (−76.9173 kcal/mol). The PMK and absorption, distribution, metabolism, excretion, and toxicity (ADMET) investigations also revealed that all the designed compounds were found to be bio-available for human administration. 'Therefore, the newly designed analogues (AEDs) could be considered as potential drug candidates for the treatment of epilepsy.

The TSC2 c.2742+5G>A variant causes variable splicing changes and clinical manifestations in a family with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a genetic, variably expressed, multisystem disease characterized by benign tumors. It is caused by pathogenic variants of the TSC complex subunit 1 gene (TSC1) and the TSC complex subunit 2 gene (TSC2). Genetic testing allows for early diagnosis, genetic counseling, and improved outcomes, but it did not identify a pathogenic variant in up to 25% of all TSC patients. This study aimed to identify the disease-causing variant in a Han-Chinese family with TSC. A six-member, three-generation Han-Chinese family with TSC and three unrelated healthy women were recruited. A comprehensive medical examination, a 3-year follow-up, whole exome sequencing, Sanger sequencing, and segregation analysis were performed in the family. The splicing analysis results obtained from six in silico tools, minigene assay, and patients' lymphocyte messenger RNA were compared, and quantitative reverse transcription PCR was used to confirm the pathogenicity of the variant. Two affected family members had variable clinical manifestations including a rare bilateral cerebellar ataxia symptom. The 3-year follow-up results suggest the effects of a combined treatment of anti-epilepsy drugs and sirolimus for TSC-related epilepsy and cognitive deficits. Whole exome sequencing, Sanger sequencing, segregation analysis, splicing analysis, and quantitative reverse transcription PCR identified the TSC2 gene c.2742+5G>A variant as the genetic cause. This variant inactivated the donor splice site, a cryptic non-canonical splice site was used for different splicing changes in two affected subjects, and the resulting mutant messenger RNA may be degraded by nonsense-mediated decay. The defects of in silico tools and minigene assay in predicting cryptic splice sites were suggested. This study identified a TSC2 c.2742+5G>A variant as the genetic cause of a Han-Chinese family with TSC and first confirmed its pathogenicity. These findings expand the phenotypic and genetic spectrum of TSC and may contribute to its diagnosis and treatment, as well as a better understanding of the splicing mechanism.

Microglia PKM2 Mediates Neuroinflammation and Neuron Loss in Mice Epilepsy through the Astrocyte C3-Neuron C3R Signaling Pathway

Epilepsy is a neurological disease and approximately 30% of patients have failed to respond to current anti-epilepsy drugs. The neuroinflammation mechanism has raised increasing concerns and been regarded as the novel treatment strategy in epilepsy, but the target molecules require further research. Pyruvate kinase isoform 2 (PKM2) is well studied in peripheral inflammation, but its role in epilepsy neuroinflammation remains unclear. We knocked down microglia PKM2 in the hippocampus using a stereotaxic adeno-associated virus (AAV) microinjection and established a pilocarpine-induced status epilepticus (PISE) model. Racine score was used to evaluate the seizure grade. Next, we used WB, Multiplex tyramide signal amplification (TSA) staining and other methods to determine neuroinflammation and the complement component 3 (C3)-C3aR interaction in primary microglia. Results showed that microglia PKM2 knockdown reduced epilepsy grade and rescued neuron loss. Mechanistically, PKM2 knockdown inhibited microglia activation and inflammation factor secretion through suppressing p65 expression and phosphorylation. The reduced microglia C1q, TNF-α, and IL-1α were responsible for the decreased astrocyte C3 expression and the following neuron damage caused by the C3-C3aR interaction. Our data suggest that microglia PKM2 inhibition ameliorates neuroinflammation and neuron loss through C3-C3aR interaction in epilepsy, which provides an attractive target for the intervention of damaged neuron-glia crosstalk in epilepsy.

Phenotypes of a female patient with novel de novo frameshift ARX variant identified by whole-exome sequencing: a case report.

A 2-year-old girl with frequent seizures, global developmental delay, and autistic features was referred to our hospital. She was the second child of consanguineous non-affected parents. She had a high forehead, mildly prominent ears, and prominent nasal root. A generalized epileptiform discharge was noted in her electroencephalography. Brain MRI revealed corpus callosum agenesis, cerebral atrophy, and a left parafalcine cyst. The WES result showed a likely pathogenic variant identified as a novel de novo deletion in exon 4 of the ARX gene, which creates a frameshift variant. The patient is on dual therapy of antiepilepsy drugs, physiotherapy, speech therapy, occupational therapy, and oral motor exercises. Variants in the ARX gene can result in various phenotypes in males transmitted from asymptomatic carrier females. However, several reports showed that the ARX variants might cause phenotypes in females with milder symptoms than affected males. We report a novel de novo ARX variant in an affected female with a NDD. Our study confirms that the ARX variant might cause remarkable pleiotropy phenotypes in females. Moreover, WES could help to identify the pathogenic variant in NDD patients with diverse phenotypes.

Evaluation of P-glycoprotein-targeting circulating microRNAs as peripheral biomarkers for medically intractable epilepsy

BackgroundEarly diagnosis of medically intractable epilepsy is challenging in clinical work. P-glycoprotein (P-gp) is one of the most important multidrug efflux transporters, which has been demonstrated to contribute to the drug resistance of intractable epilepsy. The present study was aimed to explore the diagnostic value of microRNAs (miRNAs) targeting P-gp for medically intractable epilepsy.MethodsThirty-six patients with intractable epilepsy and 36 epilepsy patients responsive to anti-epilepsy drugs, who visited Jinshan Hospital of Fudan University from September 2014 to September 2016, were enrolled in this study. Clinical information of the patients was obtained by retrospectively reviewing medical records. MiRNAs with differential serum expression between the two groups of patients were detected by microarray assay. Meanwhile, miRNAs that were confirmed to regulate P-gp in vitro by western blot were selected for further validation. In the validation phase, reverse transcription quantitative PCR (RT-qPCR) was conducted to confirm the differential expression of the candidate miRNAs in the epilepsy cohorts. Receiver operating characteristic (ROC) curve analysis was carried out to evaluate the diagnostic value of the miRNAs for intractable epilepsy.ResultsThree miRNAs including miR-6514-3p, miR-6076-5p, and miR-6855-3p were identified to be candidate miRNAs by microarray assay. The results of western blotting validated that miR-146a-5p and miR-138-5p could regulate P-gp expression in vitro, so they were included in the candidate miRNAs for further validation. In the validation phase, the results of RT-qPCR indicated that compared with drug-responsive patients, the patients with intractable epilepsy showed decreased level of miR-138-5p and increased level of miR-146a-5p. The results of ROC curve analysis indicated that miR-138-5p (AUC = 0.877) and miR-146a-5p (AUC = 0.866) had high diagnostic value for intractable epilepsy. In addition, the miR-panel composed of miR-138-5p and miR-146a-5p showed higher diagnostic value (AUC = 0.926) than the miRNAs selected by microarray assay.ConclusionsOur results indicated that the dysregulated miR-138-5p and miR-146a-5p which target P-gp expression have high potential as peripheral biomarkers for medically intractable epilepsy.

A pain fired from brain: Abdominal Epilepsy

Introduction: Abdominal pain is a nonspecific symptom which can be caused by a constellation of pathologies. It can be related sometimes to pathologies that affect the brain and mind. Among pathological conditions that can cause paroxysmal gastrointestinal symptoms are porphyria, abdominal migraine, cyclical vomiting, intestinal malrotation and peritoneal bands. Among them, rare, but important to recognize is abdominal epilepsy. Abdominal epilepsy is more a diagnosis of exclusion, and it is considered to be part of the group of temporal lobe epilepsies, which usually occur in children. However rare, there is recorded documentation of its occurrence even in adults. Method: We present two adult case reports with abdominal symptoms who have undergone several investigations before the diagnosis. Results: In these patients the pellicular combination of the irregular paroxysm of abdominal pain, combined with symptoms involving the central nervous system and the exclusion of pathologies that can produce similar symptoms can guide the physician to the diagnosis of abdominal epilepsy. Discussion: It should be suspected abdominal epilepsy when we encounter unexplained and recurrent gastrointestinal symptoms such as severe paroxysmal pain, hunger, flatulence, nausea and sometimes diarrhea. Symptoms are associated with central nervous system symptoms such as lethargy, confusion or alteration of consciousness and are improved with antiepileptic therapy. This diagnosis is usually associated with electroencephalography changes. The symptoms are quite vague and for this reason, it is difficult to make a diagnosis. Keywords: abdominal epilepsy, unexplained abdominal pain, EEG, adults, antiepilepsy drug therapy, case report

Medication use during pregnancy and birth defects in Hunan province, China, during 2016-2019: A cross-sectional study.

Safety of drug use during pregnancy attracts attentions from clinicians, pregnant woman, and even the total society. However, the studies about medication use during pregnancy and the followed birth defects (BDs) are rare in Chinese. To study condition about medication use during pregnancy and the followed BDs in Hunan province of China, here a cross-sectional study was carried out. All women using medication during pregnancy and delivering fetuses with BDs in Hunan province, China, during 2016 to 2019 were employed in this study. The descriptive analysis was carried out with Excel 2010, and the data analyses were performed by using Chi-Squared test in SPSS 16.0. After filtering, a total of 752 cases were included. In these fetuses, the males are more than females (P < .05). The severe BDs, leading to death or uncorrectable lifelong deformity, were observed for 346 times, and the other (minor) BDs were observed for 593 times. The most used drugs, categorized into pregnancy C, D, or X degrees by food and drug administration (FDA) or pharmaceutical manufacturers, mainly included anti-hyperthyroidism drugs, anti-epilepsy drugs, preventing miscarriage drugs, etc. This population-based data highlight the potential high risks for BDs from the aspect of drug use during pregnancy in Hunan province of China, and drugs with more safety, less kinds, and lower doses should be the better choice for pregnant women.

Reducing the shock factor with new anti-epilepsy drugs

Epilepsy is one of the most common serious neurological conditions, affecting 1 in 131 people in the UK. Patients with epilepsy suffer recurrent spontaneous seizures when neuronal activity elevates beyond physiological limits. Although current anti-epileptic drugs can effectively prevent seizures in some patients, up to 20% of paediatric and 40% of adult patients are refractory to treatment. One therapeutic avenue that has not yet been pursued for epilepsy is targeting neuronal homeostasis. PUMILIO (PUM) is a transcriptional repressor that maintains neuron action potentials within physiological limits and, importantly, is abnormally reduced in patients with epilepsy. In their recent article, Richard Baines and colleagues, therefore, investigated PUM as a therapeutic target for epilepsy.The authors identified a new compound, 4-tert-butyl-benzaldehyde (4-TBB), which could increase expression and stability of PUM in Drosophila and mice, and had physiochemical properties compatible with clinical use. They pre-treated diverse Drosophila and mouse models of epilepsy with 4-TBB prior to electrical or chemical induction of seizures. The team found that 4-TBB acts as an anticonvulsant, significantly reducing behavioural and physiological signs of seizure. The authors also confirmed that 4-TBB acts – at least in part – through modulation of PUM, as protein levels of downstream targets of PUM were reduced in treated mouse brains and because RNAi-induced reduction of PUM significantly diminished the anticonvulsant activity of 4-TBB in Drosophila.The authors then identified RAB216, a more-potent analogue of 4-TBB, which also increased PUM expression, and induced anticonvulsant activity in Drosophila and mice, at significantly lower concentrations than 4-TBB. Moreover, RAB216 also reduced the duration of seizures in an electrically induced seizure assay within a murine model that recapitulates drug-refractory epilepsy.The Baines lab identified two anticonvulsant compounds that modulate PUM expression and activity to oppose the high neuronal activity associated with seizures. This approach modulates neuronal homeostasis, which may incur fewer side effects, as these mechanisms are tightly controlled to avoid under- or over-activation. Interestingly, although mice were pre-treated with 4-TBB for 3 days prior to seizure induction, there were no overt signs of side effects. However, future work is required to investigate the full mode of action of the new compounds, beyond the modulation of PUM activity. Moreover, as PUM is expressed systemically, the development of compounds targeting central nervous system-specific downstream targets or co-factors of PUM could further minimise potential side effects. Nevertheless, the authors have demonstrated the potential of a novel approach to treating epilepsy, which may reduce the proportion of drug-refractory patients.

A Systematic Review of the Cost-effectiveness of Perampanel in the Treatment of Epilepsy

A Systematic Review of the Cost-effectiveness of Perampanel in the Treatment of Epilepsy

Keeping your gums healthy

If you do not take care of your gums (Box), you can develop gum disease. Gum disease can develop when a thin layer of bacteria, called plaque, is allowed to collect along the gumline and between the teeth. This can cause your gums to swell and bleed and, if left untreated, can even cause tooth loss. There are mild forms of gum disease that may be reversed if caught early and more severe forms that involve specialized treatment from a dentist.Box.Caring for your gums.Here are some things you can do at home to help prevent gum disease:▪Brush your teeth twice a day for 2 minutes each time. Using a toothpaste with fluoride will help reduce your risk of cavities, too.▪Clean between your teeth once a day with floss, floss holders, water flossers, or special sticks, brushes, or picks designed for cleaning between your teeth.▪Avoid tobacco.▪Visit your dentist regularly for professional cleanings and an examination. Here are some things you can do at home to help prevent gum disease:▪Brush your teeth twice a day for 2 minutes each time. Using a toothpaste with fluoride will help reduce your risk of cavities, too.▪Clean between your teeth once a day with floss, floss holders, water flossers, or special sticks, brushes, or picks designed for cleaning between your teeth.▪Avoid tobacco.▪Visit your dentist regularly for professional cleanings and an examination. Mild gum disease is called gingivitis. It may cause your gums to become red and swell. They may even bleed. Fortunately, this form of gum disease can often be stopped in its tracks with a professional dental cleaning followed by improved care of your teeth and gums at home. More severe cases of gum disease are called periodontitis (pare-ee-oh-DON-tie-tis). Periodontitis develops when plaque builds up under the gumline and between the teeth. Sometimes this plaque hardens into a substance called tartar, which traps plaque beneath the gumline. The bacteria in the plaque produce acid and toxins that cause the gum tissue to become infected and inflamed. Your body reacts to this swelling, and the connection of the gum tissue to the supporting bone can break down. This forms pockets where plaque can collect further, and, if left untreated, the bone that holds your teeth can start to break down. Only a dentist can treat periodontitis. He or she uses a special tool that scrapes the tartar off your teeth and then smooths the bone, which allows your gum tissue to reattach. Once you have had periodontitis, you are at risk of developing it again. For this reason, you may need to schedule more frequent dental visits. In addition to red, swollen, and bleeding gums, other signs of gum disease may include the following:▪gums that have pulled away from the teeth, causing teeth to look longer▪bad breath or bad taste that will not go away▪permanent teeth that are loose or separating▪a change in the way your teeth fit together when you bite▪a change in the fit of partial dentures Some things increase the risk of developing gum disease. In addition to poor care of your mouth at home, examples include the following:▪smoking or chewing tobacco▪crooked teeth that are hard to keep clean▪diabetes▪hormonal changes, like pregnancy▪medications, including steroids, certain types of antiepilepsy drugs, cancer therapy drugs, some calcium channel blockers, and oral contraceptives Gum disease is caused by plaque that builds up along your gumline, which can break down the tissues (including bone) that help hold your teeth in place. Left untreated, gum disease can cause teeth to become loose and fall out or to have to be removed. Taking care of your teeth and making regular visits to your dentist can help prevent gum disease.

Management of Psychiatric and Neurological Comorbidities in Epilepsy

People with epilepsy often have between 30 and 50% of their patients with neuropsychiatric disorders. The major neurological comorbidities linked with epilepsy, such as migraine, dementia, traumatic brain injury, and autism spectrum disorder, have relative effects on some of the psychiatric disorders, such as mood and anxiety disorders. The current research objective was to report the usage of pharmacologic drugs in the treatment of a neuropsychiatric disorder in epilepsy. A total of 630 patients of different aged groups (9-18 years, between 19-64 years and Elderly &gt; 65 years) were included in our research. The study was carried out at Qazi Hussain Ahmed Medical Complex Nowshera from September 2021 to Jan 2022. Epilepsy patients in rural areas had a substantially lower incidence of neuropsychiatric disorders than those in urban areas, and most of the patients were men. The most often used Anti epilepsy drugs (AEDs) for treating epilepsy were lamotrigine, valproate, and levetiracetam, which were used by 50% of participants. Carbamazepine was only used by adults and was least frequently utilized by older people. In order to effectively manage neuro-psychiatric comorbidities in epilepsy, it is important to consider both possible iatrogenic and therapeutic consequences.

CRMP2 modulates mossy fiber sprouting in dentate gyrus of pilocarpine induced rat model of epilepsy

As a hallmark of epilepsy, mossy fiber sprouting was regarded as an ideal mode to study neural rewiring upon injury. The process of mossy fiber sprouting constitutes key steps for neural circuit formation, including axon collateral formation and outgrowth, reversed pathfinding and synapse connection. The canonical function of CRMP2 is to promote neurite/axon outgrowth via binding to tubulin heterodimers, which is mainly regulated by its phosphorylation state. CRMP2 expression and phosphorylation were reported to change in medial temporal epilepsy patients and animal modes of epilepsy. As a novel anti-epilepsy drug, Lacosamide is able to impair CRMP2 mediated tubulin polymerization. Previous studies suggested possible roles of CRMP2 in mossy fiber sprouting. Here, we provide direct evidence to support the role of CRMP2 in the process of mossy fiber sprouting in an animal model of epilepsy. We found that CRMP2 phosphorylation was downregulated specifically in the hippocampus during latent phase of epileptic rats. In addition, with the reduction of CRMP2 expression levels in dentate gyrus by CRMP2 shRNA, we observed decreased mossy fiber sprouting in these CRMP2 knockdown rats. Our results demonstrated that CRMP2 modulates mossy fiber sprouting in dentate gyrus of pilocarpine induced rat model of epilepsy.

Safety and Efficacy of Clonazepam in the Treatment of Juvenile Myoclonic Epilepsy: A Meta-Analysis.

Juvenile myoclonic epilepsy (JME) is referred to as one of the most common epileptic syndromes. Several anti-epilepsy drugs (AEDs) have been developed and remain part of clinical intervention with varying safety and efficacy profiles. Comprehensive synthesis of the scientific evidence examining the safety and efficacy of clonazepam toward the treatment of JME was carried out in the study. A detailed scientific literature search was made utilizing the most relevant scientific studies published to date on the intervention of clonazepam in the management of JME. In this study, a detailed search was made in multiple databases, including PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Scielo databases. Confidence intervals among the studies and continuous measures, proportion, and risk factor analysis were determined using the MedCalC tool (Version 20.110) as per PRISMA guidelines. A total of 6 studies out of 70 were found eligible for meta-analysis, where 186 JME patients were subjected to clonazepam intervention with controls. Clonazepam was reported effective in comparative analysis among six studies where P < 0.001. The result also shows a higher prevalence of JME in the female population compared to males (male versus female; 86/110). Efficacy and safety of clonazepam were reported significant as well. Clonazepam is effective AEDs for the management of JME. However, more clinical evidence requires for statistical validation of clinical efficacy.