Therapeutic drug monitoring of anti-seizure medications (ASMs) in pediatric patients presents unique challenges and considerations. In this article, the authors discuss pediatric physiology and developmental pharmacokinetics in the context of ASMs. Thirteen ASMs are discussed, including information on the history, mechanism of action and pharmacokinetics, relevant drug interactions, adverse effects, toxicity, and special considerations for monitoring tests. Specific drugs covered in this article are levetiracetam, brivaracetam, carbamazepine, oxcarbazepine, eslicarbazepine, clobazam, ethosuximide, lacosamide, lamotrigine, phenobarbital, valproic acid, zonisamide, and topiramate.

The paradoxical effect of levetiracetam (LEV) refers to the paradoxical aggravation of epileptic seizures during clinical application. In this case, we report for the first time a patient with MRI-negative drug-resistant frontal lobe epilepsy who developed nonconvulsive status epilepticus (NCSE) following LEV dose escalation, as documented by stereoelectroencephalography (SEEG). The SEEG findings suggested that paradoxical activation of mesial temporal structures may be involved in the occurrence of LEV-induced paradoxical effects.

This study addresses critical concerns in epilepsy management regarding generic drug substitution and the bioequivalence risks associated with switching antiepileptic drugs (AEDs). For patients undergoing long-term treatment, precise brand identification of levetiracetam (LEV) holds significant clinical value to ensure therapeutic consistency and safety. To meet this need, we developed a qualitative brand discrimination method based on surface-enhanced Raman spectroscopy (SERS) combined with machine learning. Silver sol was used as the SERS substrate, with potassium iodide as an aggregating agent and Rhodamine 6G (R6G) as an optimized probe. After validating LEV's characteristic Raman peaks through integrated theoretical and experimental approaches, spectra from three commercial LEV brands were analyzed using principal component analysis (PCA) and support vector machine (SVM) classification. The model achieved 100% accuracy, precision, and sensitivity in 10-fold stratified cross-validation, demonstrating robust brand-discrimination capability. Unlike conventional quantitative assays that verify API content but cannot distinguish between different manufacturers, this SERS-based approach detects formulation-specific differences(?)such as variations in crystal form and preparation process(?)through unique spectral fingerprints. It thus provides a rapid, label-independent tool for brand authentication, batch consistency evaluation, and on-site pharmaceutical screening, effectively complementing pharmacopeial methods. This work supports medication safety and offers a reliable strategy for drug quality control and market surveillance, particularly in preventing counterfeit drugs and ensuring formulation stability in long-term epilepsy therapy.

Levels of levetiracetam in milk can be relatively high in some women and can occasionally cause sedation and other adverse effects in their breastfed infants. If levetiracetam is required by the mother, it is not necessarily a reason to discontinue breastfeeding. However, the infant should be monitored for drowsiness, adequate weight gain, and developmental milestones, especially in younger, exclusively breastfed infants and when using combinations of anticonvulsants. Maternal serum level monitoring and dosage adjustment is advisable in the early postpartum period if the drug was taken throughout pregnancy and breastfeeding.[1] Some evidence suggests that levetiracetam might reduce the maternal breastmilk supply in some women.

Sudden unexpected death is a rare but clinically important event in pregnant women with epilepsy. This case report describes a fatal bathtub drowning in a pregnant woman with epilepsy secondary to pregnancy-related intracerebral hemorrhage. A 31-year-old woman at 6 months' gestation was found submerged in a bathtub filled with 41 °C water, and resuscitation attempts were unsuccessful. At age 29 years, she experienced intracerebral hemorrhage requiring hematoma evacuation during delivery of her first child and subsequently developed poststroke epilepsy. She had three nocturnal generalized tonic-clonic seizures before death. Autopsy revealed increased lung weight and frothy fluid in the airways, consistent with drowning. Neuropathological examination revealed a previous right frontal white matter hemorrhage involving the cortical surface, considered a potential epileptogenic focus. Microscopic examination revealed significant hemosiderin deposition and associated chronic inflammatory changes in the affected area, which may be linked to epileptogenesis. Despite treatment with the maximum dose of levetiracetam (3,000 mg/day), the postmortem blood concentration was near the lower limit of the therapeutic range. This case highlights the structural basis of epilepsy following pregnancy-related intracerebral hemorrhage, the difficulty in preventing fatal seizure-related events in pregnant women, and the potential role of hyperthermia during bathing as a seizure trigger.

In most patients who have Ebstein anomaly (EA), neurological symptoms are either associated with thromboembolic episodes or due to arrhythmic complications. Cerebral cavernous malformation (CCM) is a vascular anomaly made up of sinusoidally dilated blood vessels, often presenting with seizure activity or intracranial bleeding. There has never been any documented report regarding coexisting EA and CCM. Herein, we have reported a 32-year-old female with an established history of Ebstein anomaly diagnosed in 2013 who had a history of generalized tonic-clonic fits since 2020. Neuroimaging studies showed the presence of a right frontal lobe mass with typical "popcorn-like" appearance and hemosiderin ring on MRI, indicative of cerebral cavernous malformation. The patient declined surgery and was managed conservatively with levetiracetam. With the occurrence of further fits in 2025, neuroimaging showed similar findings but without the presence of intratumoral bleeding. Subsequently, she underwent a left frontoparietal craniotomy for GTE of the lesion with cavernoma on histopathology. The neurological status of the patient was stable during her discharge on the fourth postoperative day. This case documents a previously unreported coexistence of Ebstein anomaly and cerebral cavernous malformation in a single patient. Given the rarity of both conditions, coexistence is coincidental. This indicates the need for genetic and molecular studies to determine whether a real biological association exists.

Background Epilepsy affects millions of people worldwide, and drug-resistant epilepsy (DRE) poses significant challenges. This investigation examined the relationship between ABCB1 gene variations and the efficacy of levetiracetam (LEV) in patients with focal epilepsy. Materials and Methods We classified 360 focal epilepsy patients treated with LEV as responders to LEV (n=142), second ASM (n=92), or non-responders (n=126). Five ABCB1 polymorphisms (rs1128503, rs2032582, rs1045642, rs2235035, and rs1922242) were genotyped using TaqMan assays. ABCB1 gene expression was analyzed in whole blood samples from 73 patients. Statistical analyses compared genotype, allele, and haplotype distributions between the two groups using Fisher's exact test and evaluated mean ABCB1 gene expression levels across genotypes with a t-test or analysis of variance. Results Significant genetic associations were identified between the rs2235035 and rs1922242 polymorphisms and the response to LEV or followed by the second ASM. The minor alleles and mutant genotypes of both SNPs were more prevalent among responders, suggesting protective effects against DRE. The 'AAAAT' and GCGAT haplotypes were associated with improved treatment response. Blood samples investigation revealed increased ABCB1 expression in reference genotypes of rs2235035 and rs1922242 compared to heterozygotes. This study identified novel associations between ABCB1 polymorphisms (rs2235035, rs1922242) and LEV response in patients with focal epilepsy. Conclusions The findings suggest potential genetic markers for predicting treatment outcomes and provide insights into the functional implications of these polymorphisms. Additional studies are warranted to confirm these findings and investigate their potential use in individualized treatment of epilepsy.

Lhermitte-Duclos Disease is a rare, benign cerebellar tumour that is a manifestation of Cowden Syndrome, a hereditary tumour predisposition syndrome caused by germline mutations in the PTEN gene. Here, we report a 38-year-old female patient with no past medical history or family neurological history presenting to hospital with a new, unprovoked, bilateral tonic-clonic seizure with no apparent seizure focus. EEG showed no epileptiform activity, and 7T MRI demonstrated bilateral Lhermitte-Duclos Disease as well as several cortical meningoencephaloceles. Her seizures were controlled with levetiracetam, and given her cerebellar lesion was minimally symptomatic, no further interventions were pursued. PTEN germline testing identified a heterozygous c.1003C>T (p.Arg335*) variant known to be pathogenic for Cowden Syndrome, and we promptly referred this patient for cancer screening. She was diagnosed with ductal carcinoma in situ and thyroid atypia of undetermined significance, and she subsequently underwent bilateral mastectomy and total thyroidectomy respectively. Lhermitte-Duclos Disease and Cowden Syndrome may present initially in previously healthy patients with bilateral tonic-clonic seizures without clear epileptogenic foci. Recognition of the underlying hereditary cancer syndrome enables timely cancer detection, potentially improving treatment outcomes.