Generation Antiepileptic Drugs Research Articles

Bone Mineral Density Screening in People With Epilepsy and Intellectual Disability.

Vitamin D measurements and dual energy x-ray absorptiometry (DXA) scans are recommended in people with intellectual disability and/or epilepsy in order to prevent bone-linked harm. The prevalence of vitamin D supplementation and bone mineral density screening were evaluated in 68 people with epilepsy and intellectual disability (EID) and 68 matched controls with epilepsy without intellectual disability. DXA scans were not performed in any of the people with EID but were performed in 11.8% of the people in the control group. People with EID had a higher vitamin D supplementation rate and were treated with more antiepileptic drugs (AEDs) and more AED combinations, including first generation AEDs. Increased awareness of bone health screening in people with epilepsy and especially EID is warranted.

Prospects for the use of perampanel in the treatment of epilepsy in patients with malignant gliomas of the brain

Epilepsy occurs in 35-95% of patients with malignant cerebral gliomas of low malignancy and in 29-71% of patients with gliomas of high malignancy. Seizures can be both the first manifestation of malignant cerebral glioma and appear in the postoperative period and during chemoradiotherapy. This requires the use of antiepileptic drugs, which should control the seizure syndrome, provide control and secondary prevention of seizures, without reducing the response of anti-tumour therapy and the the patient QoL. The processes of epileptogenesis and oncogenesis are closely interrelated through common developmental mechanisms in which glutamate plays a key role. Hypersecretion of glutamate is accompanied by increased expression and activation of its receptors, which increases convulsive readiness. This is accompanied by increased level of brain neurotrophic growth factor, the number of synapses between peritumoral neurons and glioma cells, and increased expression of a number of growth factors, which contributes to tumourous proliferation. In this regard, special attention when treating epilepsy in patients with malignant cerebral gliomas is given to perampanel, a glutamate receptor blocker, a 3rd generation antiepileptic drug. The findings show that perampanel not only effectively controls seizures in patients with malignant cerebral gliomas, but also suppresses tumourous proliferation. Perampanel is able to dose-dependently enhance apoptosis and disrupt cell migration in malignant glioma cell lines. The findings have revealed synergistic effect of perampanel in combination with temozolamide. In conditions of chemoradiation therapy perampanel has a protective effect on healthy peritumoral tissues. Undesirable drug reactions during the use of perampanel are infrequent and insignificant. Additional studies are needed to further research the anticonvulsant and antitumour efficacy of perampanel to treat epilepsy in patients with malignant brain tumours.

An Retrospective Study of Commonly Prescribed Antiepileptic Drugs and it’s Interaction with Other Drugs which are Already in use Respect to Other Disease

Antiepileptic drugs (AED) are increasingly used in the treatment of some non-epileptic neurological diseases and psychiatric diseases. Most of the available data on the use of these agents in clinical conditions other than epilepsy are from case series, uncontrolled studies, or small randomized clinical trials, and their apparent efficacy requires confirmation in well-designed large phase III trials. Interactions between antiepileptic drugs or between antiepileptic drugs and other drugs can be pharmacokinetic or pharmacodynamic. Pharmacokinetic interactions include changes in absorption, distribution ,or eliminate , while pharmacodynamic interactions include synergism and antagonism at the site ,of action. Most clinically significant antiepileptic drug interactions are due to induction or inhibition of drug metabolism. Carbamazepine, phenytoin, phenobarbital and primidone are strong inducers of cytochrome P450 and glucuronide enzymes (as well as P-glycoprotein) and may reduce the effectiveness of concomitantly administered drugs such as oral anticoagulants, calcium antagonists, antimicrobial steroids. Mechanism Oxcarbazepine, eslicarbazepine acetate, felbamate, rufinamide, topiramate (at doses ≥ 200 mg/day) and perampanel (at doses ≥ 8 mg/day) have weaker inducing properties and less tendency to produce interactions mediated by enzyme induction. In contrast to enzyme induction, enzyme inhibition results in decreased metabolic clearance of the affected drug, which can increase serum concentrations leading to toxic effects. Examples of important interactions mediated by enzyme inhibition include valproic-induced increases in serum concentrations of phenobarbital and lamotrigine. There are also interactions where other drugs induce or inhibit the metabolism of antiepileptic drugs. Examples include an increase in serum carbamazepine concentration due to erythromycin and a decrease in serum lamotrigine concentration due to estrogen-containing contraceptives. Pharmacodynamic interactions between antiepileptic drugs may also be clinically important. These interactions can have potentially beneficial effects, such as the combined therapeutic synergy of valproic acid and lamotrigine, or adverse effects, such as the mutual potentiation of neurotoxicity in patients treated with a combination of sodium channel blocking antiepileptic drugs. AEDs are also used to treat psychiatric conditions, particularly bipolar disorder. To date, the AEDs most commonly used to treat this disorder have been carbamazepine and valproic acid, which have shown manic efficacy and likely long-term mood-stabilizing effects in many bipolar patients, including those who are lithium-intolerant. . The availability of new generation AEDs has expanded treatment options for bipolar disorder. Lamotrigine, oxcarbazepine, gabapentin, and topiramate appear to show promise in the treatment of bipolar disorder, both as monotherapy and in combination with traditional mood stabilizers. In addition, newer AEDs appear to have a more favorable tolerability and drug interaction profile than older compounds, thus improving compliance

A Review of the Association between Infections, Seizures, and Drugs.

Seizures are a common presenting symptom of the central nervous system (CNS) and could occur from infections (such as toxins) or drugs. The aim of this study was to present a systematic review of the association between infections, seizures, and drugs. Through February 18, 2024, according to the PRISMA guidelines and based on the PICO standard format, relevant, in-depth consequent guide approach and evidence-based options were selected associated with a knowledgeable collection of current, high-quality manuscripts. Imbalance between inhibitory and excitatory neurotransmitters due to infections, drugs such as ticarcillin, amoxicillin, oxacillin, penicillin G, ampicillin, tramadol, venlafaxine, cyclosporine, tacrolimus, acyclovir, cellcept, the old generation of antiepileptic drugs, such as carbamazepine, phenytoin, and many other drugs could cause different stages of CNS disturbances ranging from seizure to encephalopathy. Infections could cause life-threatening status epilepticus by continuous unremitting seizures lasting longer than 5 minutes or recurrent seizures. Meningitis, tuberculosis, herpes simplex, cerebral toxoplasmosis, and many others could lead to status epilepticus. In fact, confusion, encephalopathy, and myoclonus were reported with drugs, such as ticarcillin, amoxicillin, oxacillin, penicillin G, ampicillin, and others. Penicillin G was reported as having the greatest epileptogenic potential. A high dose, in addition to prolonged use of metronidazole, was reported with seizure infection. Meropenem could decrease the concentration of valproic acid. Due to the inhibition of cytochrome P450 3A4, the combination of clarithromycin and erythromycin with carbamazepine needs vigilant monitoring. Due to changes in drug metabolism, co-administration of antiseizure drugs and antibiotics may lead to an enhanced risk of seizures. In patients with neurocysticercosis, cerebral malaria, viral encephalitis, bacterial meningitis, tuberculosis, and human immunodeficiency virus, the evidence-based study recommended different mechanisms mediating epileptogenic properties of toxins and drugs.

Ketogenic Diet in the Treatment of Epilepsy.

Epilepsy is one of the most disabling neurological diseases. Despite proper pharmacotherapy and the availability of 2nd and 3rd generation antiepileptic drugs, deep brain stimulation, and surgery, up to 30-40% of epilepsy patients remain drug-resistant. Consequences of this phenomenon include not only decreased a quality of life, and cognitive, behavioral, and personal disorders, but also an increased risk of death, i.e., in the mechanism of sudden unexpected death in epilepsy patients (SUDEP). The main goals of epilepsy treatment include three basic issues: achieving the best possible seizure control, avoiding the undesired effects of treatment, and maintaining/improving the quality of patients' lives. Therefore, numerous attempts are made to offer alternative treatments for drug-resistant seizures, an example of which is the ketogenic diet. It is a long-known but rarely used dietary therapy for intractable seizures. One of the reasons for this is the unpalatability of the classic ketogenic diet, which reduces patient compliance and adherence rates. However, its antiseizure effects are often considered to be worth the effort. Until recently, the diet was considered the last-resort treatment. Currently, it is believed that a ketogenic diet should be used much earlier in patients with well-defined indications. In correctly qualified patients, seizure activity may be reduced by over 90% or even abolished for long periods after the diet is stopped. A ketogenic diet can be used in all age groups, although most of the available literature addresses pediatric epilepsy. In this article, we focus on the mechanisms of action, effectiveness, and adverse effects of different variants of the ketogenic diet, including its classic version, a medium-chain triglyceride diet, a modified Atkins diet, and a low glycemic index treatment.

Effect of valproic acid monotherapy on serum leptin and ghrelin levels in epileptic children (literature review)

The incidence of epilepsy varies between industrialized countries and developing ones. Anti-epileptic drugs are the standard of care for epilepsy management with sodium valproate being the most commonly prescribed anti-epileptic drug in children with epilepsy. Valproic acid (VPA) is a first generation anti-epileptic drug used widely as a monotherapy or part of polytherapy for a variety of seizures in children more than two years of age. It is stated that long-term treatment with VPA is associated with risks such as weight gain, hyperinsulinemia, metabolic syndrome, and cardiovascular disease. However,the exact pathogenesis of weight gain has not been clearly identified pathogenetically. Studying the effect of VPA monotherapy on possible causative factors (leptin and ghrelin levels) of weight gain would help in undertaking appropriate preventive actions alongside VPA therapy. We review the available literature on the research carried out on this subject in the following sections.

Study comparing the effect of topiramate and pregabalin on learning and memory with phenytoin in albino rats using morris water maze and elevated plus maze

Epilepsy is a chronic neurological disorder characterized by repeated seizures. Neurocognitive impairment is one of the adverse drug reactions (ADRs) in the case of antiepileptic drugs (AEDs). Phenytoin (PHT), an effective older generation AED, shows decline in cognitive functions such as memory, concentration and motor speed in both healthy volunteers and epileptic patients. Topiramate, has cognitive complaints among the adverse effects reported and include impaired concentration and memory, slowing of thought process, and difficulties in word finding. Another antiepileptic Pregabalin shows that it’s negative effects on cognitive functions are mild. Hence, a comparative assessment of the above group of drugs along with a control group was done using morris water maze and elevated plus maze. Effects on learning and memory was assessed using parameters such as escape latency and transfer latency. Albino rats were taken (24 in number) and assigned into 4 groups with three drug groups and one control group. They were given the respective drugs for a period of 15 days and then checked for escape latency and transfer latency times to assess the effect on “learning”. Thereafter the rats received the drugs for another 5 days after which they were assessed for “memory”. It was seen that phenytoin and topiramate do affect learning in comparison to pregabalin but the result about affecting memory was not conclusive.

Third generation antiepileptic drugs: mechanism of action, pharmacokinetics, interaction and use in childhood

The review considers pharmacological characteristics of new antiepileptic drugs (AEDs) of the third generation such as eslicarbazepine, lacosamide, retigabine, perampanel, everolimus, brivaracetam, zonisamide. The data on the mechanisms of action, pharmacokinetics, drug interactions, indications for use and side effects are presented. The drugs are recognized as superior in safety and efficacy to previously known AEDs of the first and second generations. The majority of new AEDs is used to control focal seizures, as well as in specific epileptic syndromes (Lennox–Gastaut syndrome, Dravet syndrome), and tuberous sclerosis. The drugs differ in the mechanism of action, pharmacokinetic properties, effectiveness and profile of side effects, which account for an opportunity to apply a personalized approach to patient treatment. Properly selected therapy allows to achieve good control over epileptic seizures as well as lower a risk of disease-related complications. While prescribing AEDs, it is necessary to take into account their pharmacokinetic and pharmacodynamic features.

Simultaneous determination of 24 antiepileptic drugs and their active metabolites in human plasma by UHPLC-MS/MS

Antiepileptic drugs (AEDs) have narrow therapeutic ranges with large individual variability. Routine therapeutic drug monitoring of AEDs was useful for dose optimization, but the common immunoassays could not meet the detection requirements of AEDs, especially for new generation AEDs. The aim of this study was to validate an ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method for simultaneously quantification of 24 AEDs and their active metabolites in human plasma and comparison with a chemiluminescent immunoassay (Simens ADVIA Centaur). The method validation was performed according to FDA and EMEA guidelines. A one-step protein precipitation by acetonitrile followed a five-fold dilution was performed for sample pretreatment. A 5.2 min gradient separation by methanol and 10 mM ammonium acetate was used for separation at 0.6 mL/min under 45 °C. Both positive and negative electrospray ionization were used. Isotopic internal standard was used for all analytes. The inter-day (36 days) accuracy and precision of quality control samples were − 1.07–13.69% and < 6.70% for all analytes. The stability was acceptable for all analytes under routine storing conditions. A total of 436 valproic acid, 118 carbamazepine, and 65 phenobarbital samples were determined twice by each of the UHPLC-MS/MS and immunoassay. Evaluated by Bland-Altman plot, the mean overestimation of the immunoassay compared to UHPLC-MS/MS was 16.5% for valproic acid, 5.6% for carbamazepine, and 40.3% for phenobarbital.

A retrospective comparative fractal and radiomorphometric analysis of the effect of 3 generations of anti-epileptic drugs on the mandible

The present study investigated the possible impacts of anti-epileptic drugs (AEDs) on trabecular and cortical bone in the mandible. Fractal dimension (FD) and the radiomorphometric parameters of mandibular cortical width (MCW), panoramic mandibular index (PMI), and mandibular cortical index (MCI) were assessed on 497 dental panoramic radiographs (DPRs) of patients in the case group and controls. AEDs were compared according to 3 generations, duration of use, and patient age and sex. FD of the angle and body of the mandible and MCW were significantly lower in the case group than in the control group (P < .001). FD values in the ramus and angle were lower in first-generation and third-generation AEDs than in second-generation drugs (P ≤ .011). FD in the mandibular body was lower in first-generation and second-generation AED users than in third-generation drugs (P=.017). Drug use for at least 1 year resulted in significantly lower values for all FDs and MCW values and more class 3 MCI assessments than short-duration use, but PMI was higher with more than 1 year of AED use (P ≤ .020). Age and sex had no significant effects. AEDs caused significant changes in bone compared with controls in some FD values, MCW, and MCI. The effect of drug generation is pronounced in trabecular bone. Anti-epileptic drug use for more than 1 year had a greater effect than short-term use.

Clinical side-effects based drug repositioning for anti-epileptic activity

Several generations of anti-epileptic drugs (AEDs) are available but have several associated side effects apart from a limited success rate. Drug repositioning strategies have gained importance in the last two decades owing to lower failure rates and economic burden. Drugs with similar side effect profiles may share a common mechanism of action and thus can be linked to other disease treatments. The present study was carried out to identify the newly approved drug candidate(s) as AEDs using clinical side-effects drug repositioning strategy. The clinical side effect similarity of drugs available in the SIDER v4.1 database was estimated against common side effects of 5 major marketed AEDs, using the ‘dplyr’ package library in the R. Further drugs were filtered based on Blood Brain Barrier permeability prediction and FDA-approval status. Molecular docking studies were performed for selected 26 hits (drugs) against previously identified epilepsy target receptors: Voltage-gated sodium channel α2 (Nav1.2), GABA receptor α1-β1 (GABAr α1-β1), and Voltage-gated calcium channel α-1 G (Cav3.1). Only 2 drugs (Ziprasidone and Paroxetine) showed better binding affinities against studied epilepsy receptors Nav1.2, GABAr α1-β1, and Cav3.1, than their corresponding standard AEDs, i.e. Carbamazepine, Clonazepam, and Pregabalin, respectively. Ziprasidone reportedly showed seizure-like symptoms in ∼3% of patients and was hence omitted from further study. The MDS study of docked complexes of Paroxetine with selected epilepsy target receptors showed stable RMSD values and better interaction energies. The study reveals Paroxetine as a potential candidate to be repurposed for 1st line epileptic seizure medication. Communicated by Ramaswamy H. Sarma

Investigating anti-inflammatory and immunomodulatory properties of brivaracetam and lacosamide in experimental autoimmune encephalomyelitis (EAE)

PurposeInflammation plays a role in drug-resistant epilepsy (DRE). We have previously reported an increased proportion of CD4 T cells displaying a pro-inflammatory profile in the peripheral blood of adults with DRE. Specific anti-epileptic drugs (AEDs) exhibit immunomodulatory properties that could increase the risk of infections but also contribute to their beneficial impact on DRE and other neurological diseases. The impact of novel generation AEDs on the profile of immune cells and on neuroinflammatory processes remains unclear. MethodsWe compared the influence of brivaracetam and lacosamide on the activation of human and murine peripheral immune cells in vitro and in vivo in active experimental autoimmune encephalomyelitis (EAE), a common mouse model of central nervous system inflammation. ResultsWe found that brivaracetam and lacosamide at 2.5 μg/ml did not impair the survival and activation of human immune cells, but a higher dose of 25 μg/ml decreased mitogen-induced proliferation of CD8 T cells in vitro. Exposure to high doses of brivaracetam, and to a lesser extent lacosamide, reduced the proportion of CD25+ and CD107a+ CD8+ human T cells in vitro, and the frequency of CNS-infiltrating CD8+ T cells at EAE onset and CD11b+ myeloid cells at peak in vivo. Prophylactic administration of brivaracetam or lacosamide did not delay EAE onset but significantly improved the clinical course in the chronic phase of EAE compared to control. ConclusionNovel generation AEDs do not impair the response to immunization with MOG peptide but improve the course of EAE, possibly through a reduction of neuroaxonal damage.

Second Generation of Antiepileptic Drugs and Oxidative Stress

Epilepsy is a chronic disease of the central nervous system characterized by recurrent epileptic seizures. As a result of epileptic seizure or status epilepticus oxidants are excessively formed, which may be one of the causes of neuronal death. Given the role of oxidative stress in epileptogenesis, as well as the participation of this process in other neurological conditions, we decided to review the latest state of knowledge regarding the relationship between selected newer antiepileptic drugs (AEDs), also known as antiseizure drugs, and oxidative stress. The literature review indicates that drugs enhancing GABA-ergic transmission (e.g., vigabatrin, tiagabine, gabapentin, topiramate) or other antiepileptics (e.g., lamotrigine, levetiracetam) reduce neuronal oxidation markers. In particular, levetiracetam may produce ambiguous effects in this regard. However, when a GABA-enhancing drug was applied to the healthy tissue, it tended to increase oxidative stress markers in a dose-dependent manner. Studies on diazepam have shown that it exerts a neuroprotective effect in a "U-shaped" dose-dependent manner after excitotoxic or oxidative stress. Its lower concentrations are insufficient to protect against neuronal damage, while higher concentrations produce neurodegeneration. Therefore, a conclusion follows that newer AEDs, enhancing GABA-ergic neurotransmission, may act similarly to diazepam, causing neurodegeneration and oxidative stress when used in high doses.

Metabolic Derangements with Anticonvulsants in Children with Generalised Tonic-clonic Epilepsy: A Cross-sectional Study

Introduction: Epilepsy is one of the most prevalent noncommunicable neurologic conditions, accounting for significant disability and mortality. The effects of Antiepileptic Drugs (AEDs) on total cholesterol, triglycerides, High-Density Lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and apolipoprotein levels have been demonstrated in many studies, mainly conducted with adults. However, there have been very few studies in children. Derangement of lipid profile and other metabolic abnormalities could lead to the development of metabolic syndrome in children. The adverse metabolic effects of anti-epileptics are underestimated, as only a few studies have been done in this area, which is a legitimate concern. Aim: To assess the impact of AEDs on metabolic parameters in children with epilepsy. Materials and Methods: This was a descriptive, crosssectional study conducted in the Department of Paediatrics and Pharmacology at Pt. BD Sharma PGIMS, Rohtak, Haryana, India. The study included 100 children with epilepsy from May 2022 to October 2022. A predefined case record form, including demographic and clinical characteristics, was filled for each participant. The parameters recorded were age, gender, outpatient number, type of epilepsy, history of duration of epilepsy, current AED history, and seizure frequency over the preceding six months, as per the case record form. Guidelines from the International Diabetes Federation were used for diagnosing metabolic syndrome in children. The data was entered into Microsoft excel and presented using descriptive statistics. The chi-square test was used to differentiate between categorical variables. Results: The mean age of the study participants was 10.2±2.97 years. There were more males (62%) than females (38%). A 48% of the patients received monotherapy, while 52% received polytherapy. A total of 24% of the patients had derangement in lipid profile (increased triglycerides and decreased HDL), with 14% of patients on monotherapy and 10% on polytherapy. The difference in metabolic derangements between monotherapy and polytherapy was not statistically significant (p=0.25). Out of 100 participants, 3% fulfilled the criteria for metabolic syndrome, with a predominance in males. Conclusion: Metabolic derangements are known with 1st generation AEDs, but 2nd generation AEDs can also lead to significant metabolic abnormalities.

Levetiracetam Protects Against Glutamate-Induced Excitotoxicity in SH-SY5Y Cell Line

The latest research has shown that the new generation of antiepileptic drugs has neuroprotective on nervous system. On the other hand, the effect of levetiracetam, a new generation antiepileptic drug, on GIC in SH-SY5Y cells remains uncertain. This research aims to investigate the effect of levetiracetam on GIC and oxidant and antioxidant levels in SH-SY5Y cells. It is utilized SH-SY5Y cell line at this research. Four groups were formed to assess the impact of levetiracetam on SH-SY5Y cell death following GIC. While no treatment was administered to the control group, 10 mM glutamate was administered to the glutamate group for 24 hours (10, 25, 50 and 100 μg/ml). LEV at different concentrations was given to the levetiracetam for 24 hours. The levetiracetam + glutamate was pretreated with levetiracetam at several concentrations for 1 hour (10, 25, 50, and 100 μg/ml), which was followed by a 24-hour exposure to 10 mM glutamate. TAS and TOS levels in cells and cell viability were examined. Following the GIC, a 25 μg/ml-Levetiracetam improved cell viability in neuroblastoma cells dramatically (p &amp;lt; 0.05). LEV (25 ug/ml) + glutamate while enhanced TAS levels in neuroblastoma cells in comparison to the glutamate (p &amp;lt; 0.05), significantly reduced TOS levels (p &amp;lt; 0.05 Levetiracetam improves cell survival by reducing cell death following GIC in neuroblastoma cells. In the acute process, levetiracetam exerts a protective effect.

Acute bilateral glaucoma related to uveal effusion syndrome associated with topiramate

AbstractPurpose: Drugs mostly sulfa‐related compounds, have produced uveal effusions, forward rotation of the iris‐lens diaphragm, transient myopia, and secondary angle closure. It has been recently encountered one case in which uveal effusions have occurred after administration of topiramate, a new anticonvulsant medication.Methods: A 54‐year‐old woman was seen in our emergency department with severe headaches, progressively blurry vision and photophobia in both eyes starting that morning. On examination, her visual acuity was hand movement in both eyes. Central corneal edema was observed, narrow chamber and anterior lens‐iris complex displacement with an unreactive middle pupil in both eyes. The funduscopic examination was difficult to assess due to the media opacity. Intraocular pressure measured with an applanation tonometer was 45 mm of mercury (mmHg) in the right eye and 50 mmHg in the left eye. Her medications included topiramate which she had started 2 weeks prior to initial examination due to headaches followed by neurology.Results: Topiramate‐induced angle closure has even been described as an idiosyncratic reaction in patients with normal depth of anterior chamber. The drug causes a prostaglandins increasement that trigger ciliary body edema at the local level but without acting at the systemic level. Ultrasound biomicroscopy shows the presence of a ciliochoroidal effusion syndrome, edema and the ciliary body anterolateral rotation, with zonular relaxation, changes that lead to iris‐lens diaphragm anterior displacement and, as a consequence, narrowing of the responsible anterior chamber with an acute glaucoma crisis.Conclusions: Topiramate is a sulfamate monosaccharide and belongs to a new generation of antiepileptic drugs, widely prescribed throughout the world as treatment of generalized tonic–clonic seizures and partial seizures. Prophylaxis of migraine, bipolar disorder, depression and neuropathic pain are other recent indications of its use. Bilateral acute glaucoma due to uveal effusion syndrome should be considered as an infrequent complication of topiramate use.References.1. Prithvi S. Sankar, MD; Louis R. Pasquale et al. Uveal Effusion and Secondary Angle‐Closure Glaucoma Associated With Topiramate Use. Arch Ophthalmol. 2001;119(8):1210–1211.

Poststroke Seizure and Epilepsy: A Review of Incidence, Risk Factors, Diagnosis, Pathophysiology, and Pharmacological Therapies

Stroke is the most common cause of epilepsy and ultimately leads to a decrease in the quality of life of those affected. Ischemic and hemorrhagic strokes can both lead to poststroke epilepsy (PSE). Significant risk factors for PSE include age < 65age less than 65 years, stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS), cortical involvement, and genetic factors such as TRPM6 polymorphism. The diagnosis of PSE is made by using imaging modalities, blood biomarkers, and prognostic criteria. Electroencephalography (EEG) is currently the gold standard to diagnose PSE, while new combinations of modalities are being tested to increase diagnostic specificity. This literature review uncovers a newly found mechanism for the pathology of poststroke epilepsy. The pathogenesis of early-onset and late-onset is characterized by sequelae of neuronal cellular hypoxia and disruption of the blood-brain barrier, respectively. Interleukin-6 is responsible for increasing the activity of glial cells, causing gliosis and hyperexcitability of neurons. Epinephrine, high-mobility group protein B1, downregulation of CD32, and upregulation of HLA-DR impact the pathology of poststroke epilepsy by inhibiting the normal neuronal immune response. Decreased levels of neuropeptide Y, a neurotransmitter, act through multiple unique mechanisms, such as inhibiting intracellular Ca2+ accumulation and acting as an anti-inflammatory, also implemented in the worsening progression of poststroke epilepsy. Additionally, CA1 hippocampal resonant neurons that increase theta oscillation are associated with poststroke epilepsy. Hypertensive small vessel disease may also have an implication in the temporal lobe epilepsy by causing occult microinfarctions. Furthermore, this review highlights the potential use of statins as primary prophylaxis against PSE, with multiple studies demonstrating a reduction in incidence using statins alone, statins in combination with antiepileptic drugs (AEDs), and statins with aspirin. The evidence strongly suggests that the second generation AEDs are a superior treatment method for PSE. Data from numerous studies demonstrate their relative lack of significant drug interactions, increased tolerability, and potential superiority in maintaining seizure-free status.

Drug Utilization and Evaluation of Antiepileptic Drugs in a Tertiary Care Hospital

Abstract: Aim: Drug utilization and evaluation (DUE) study of antiepileptic drugs in a tertiary care hospital. Methods: A total of 110 case records of patients were included in a prospective observational study which was conducted for duration of 6 months. The prescription pattern was analyzed based on age, gender, route of administration, indication, duration of therapy, type of seizures, generation of Anti-Epileptic Drugs (AEDs), and rationality. Results: AEDs were prescribed more for patients between the ages of 51-60 years. The majority of patients receiving AEDs were males and AEDs were mostly used in the neurology department followed by neurosurgery and general medicine. Levetiracetam was prescribed most commonly as monotherapy. Lorazepam and midazolam were the most common add-on drugs. Gabapentin was mostly prescribed for severe neuropathic pain. The oral route was the common route of administration of AEDs. AEDs were highly prescribed for prophylaxis of seizures. Second-generation AEDs were highly used compared to other drugs. Conclusion: Second-generation AEDs were used as monotherapy and were found to be effective in reducing seizures and economically affordable for patients. As monotherapy, levetiracetam was the drug of choice followed by lorazepam. Keywords: Drug Utilization Evaluation (DUE), Epilepsy, Antiepileptic drugs, Levetiracetam, Phenytoin, Seizures.

Seizure after surgical treatment of chronic subdural hematoma-Associated factors and effect on outcome.

IntroductionChronic subdural hematoma (cSDH) is becoming more prevalent due to population aging and the increasing use of antithrombotic drugs. Postoperative seizure in cSDH have a negative effect on outcome, and there currently no consensus regarding prophylactic anti-epileptic drug (AED) treatment. The objective of this study was to evaluate predisposing and triggering factors associated with postoperative epileptic seizure in patients with cSDH.MethodsAll patients, who were surgically treated for cSDH in a single tertiary care center between 2015 and 2019, were considered for inclusion. Relevant patient- and hematoma-specific characteristics were retrospectively extracted from hospital records. Paroxysmal events categorized by the treating physician as suspected postoperative seizures were noted. The clinical outcome was extracted from the last available follow-up visit and classified according to the Glasgow outcome scale (GOS).ResultsOf the included 349 patients, 54 (15.5%) developed suspected postoperative epileptic complications in the form of early seizure (≤ 7 days) in 11 patients (3.2%) and late seizure (>7 days) in 43 patients (12.3%). In the logistic regression analysis, solely depressed brain volume (supratentorial volume (ml) not filled with re-expanded brain) was independently associated with postoperative seizure (odds ratio [OR] 1.006, 95% CI: 1.001–1.011; p = 0.034). The occurrence of postoperative seizure (OR 6.210, 95% CI: 2.704–14.258; p < 0.001) and preoperative Markwalder grading (OR 2.919, 95% CI: 1.538–5.543; p = 0.001) were independently associated with unfavorable (GOS1−3) outcome.ConclusionLarger postoperative depressed brain volume was the only factor independently associated with suspected postoperative seizure, and it could help identify a subgroup of patients with higher susceptibility to epileptic events. Based on our data, no formal recommendation can be made regarding the prophylactic use of anti-epileptic drugs. Nevertheless, the relative safety of new generation AEDs and the detrimental effect of postoperative seizure on outcome may justify its use in a selected patient population.

Eslicarbazepine acetate is porphyrogenic and should be used with caution in patients with the acute hepatic porphyrias.

Eslicarbazepine acetate, a third-generation antiepileptic drug (AED), has shown improved clinical response and safety in comparison to older generation AEDs for patients with partial-onset seizures. It is currently not known whether eslicarbazepine acetate is safe to use in patients with the acute hepatic porphyrias (AHPs) since a few first-generation AEDs, such as phenobarbital and carbamazepine, are known porphyrogenic agents. In this study, we used a recently published in vitro fluorescence-based screening assay to screen for porphyrogenicity in various agents. The assay confirmed that among the tested compounds used, allyl isopropyl acetamide, carbamazepine, eslicarbazepine acetate, and phenobarbital were porphyrogenic. Thus, eslicarbazepine acetate should be avoided if possible in patients with the AHPs, but if initiated, patients should be closely monitored and the drug should be discontinued if a porphyric exacerbation occurs.