Epilepsy with myoclonic-atonic seizures (EMAtS), historically termed Doose syndrome, is a developmental and epileptic encephalopathy characterized by the usually abrupt onset of multiple generalized seizure types, including myoclonic-atonic seizures, in early childhood. Advances in genetic diagnostics, antiseizure treatments, and precision therapies have reshaped understanding and management of EMAtS.

Spinal muscular atrophy (SMA) is a rare neuromuscular disorder characterized by progressive motor weakness with multisystem involvement. Type III SMA, also known as Kugelberg-Welander disease, typically presents in childhood and allows survival into adolescence and adulthood, during which cumulative complications may emerge. We report the case of a 19-year-old female patient with genetically confirmed SMA type III (zero copies of SMN1, two copies of SMN2) whose disease course was complicated by chronic respiratory failure with hypercapnia requiring non-invasive ventilation and intractable generalized epilepsy. She was born prematurely at seven and a half months via emergent cesarean section for placenta previa and maternal hemorrhage, requiring a one-month neonatal intensive care unit stay with supplemental oxygen. SMA was diagnosed at 28 months of age following early motor weakness. Over childhood, she developed choking with thin liquids, weak cough during viral illnesses, and recurrent respiratory infections, with progression to restrictive lung disease and impaired airway clearance. At age 11, she developed head-drop seizures and was diagnosed with intractable generalized idiopathic epilepsy. Orthopedic complications included neuromuscular scoliosis requiring spinal fusion. This case underscores how SMA type III evolves into a multisystem disorder with cumulative respiratory, neurologic, and orthopedic morbidity, highlighting the need for vigilant longitudinal surveillance, proactive respiratory support, individualized seizure management, and coordinated interdisciplinary care.

Cenobamate is a novel alkyl-carbamate antiseizure medication (ASM) that represents a major breakthrough in the treatment of drug-resistant epilepsy, particularly focal seizures. Unlike other ASMs, cenobamate achieves seizure freedom in up to one third of patients with focal drug-resistant epilepsy-a response not observed with other therapies. Herein, we describe the chemocentric and phenotypic screening strategy employed by one of us (Yong Moon Choi) while at SK Biopharmaceuticals and how cenobamate was developed by optimizing earlier alkyl-carbamates such as carisbamate and felbamate. We discuss how the incorporation of a tetrazole moiety likely played a significant role in its successful development. Cenobamate was found to display potent broad-spectrum activity in diverse disease-relevant rodent models, including maximal electroshock, pentylenetetrazole, kindling, and lithium-pilocarpine-induced status epilepticus. When compared to 12 other ASMs, it ranked highest across four models of difficult-to-treat focal seizures. We discuss how the two known molecular activities of cenobamate, i.e., positive allosteric modulation of GABAA receptors via a non-benzodiazepine site and inhibition of persistent sodium currents (INaP), may contribute to its clinical efficacy and how pharmacokinetic/pharmacodynamic modeling confirmed that the effective brain concentrations of cenobamate align with clinically relevant plasma concentrations observed in seizure-free patients. The discovery of cenobamate has significant implications for future ASM development. It validates phenotypic screening as a powerful tool for identifying first-in-class central nervous system therapeutics and highlights the value of chemocentric optimization using known scaffolds. The predictive utility of specific preclinical models-especially kindling and lithium-pilocarpine-suggests that future ASM discovery should prioritize models that better mimic pharmacoresistant epilepsy. The dual mechanisms of cenobamate may serve as a blueprint for designing ASMs with synergistic actions. Approval of cenobamate represents a paradigm shift in epilepsy treatment and offers a promising framework for discovering more effective therapies for drug-resistant epilepsy.

Epilepsy is the most common chronic neurological disorder and one of the leading causes of disability. We report a rare and clinically significant complication involving the inadvertent substitution of felbamate with carbamazepine in a 37-year-old man with refractory epilepsy. He developed drowsiness, ataxia, dysarthria, and vomiting, followed by hematological abnormalities and respiratory symptoms. Although carbamazepine levels were within the reference range, a probable diagnosis of acute carbamazepine toxicity was made in the setting of refractory epilepsy. Therapeutic interventions included discontinuation of carbamazepine, antimicrobial therapy, and supportive care. Inadvertent substitution of antiepileptic medications in patients with refractory epilepsy can lead to serious multisystem complications. Vigilant medication management and multidisciplinary care are essential to prevent adverse outcomes.

Felbamate is an anti-epileptic drug that was approved by the Food and Drug Administration for the management of focal seizures and Lennox-Gastaut syndrome. It should be a consideration for patients with drug-resistant epilepsy where the benefit of seizure control outweighs the risk of severe idiosyncratic reactions. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, monitoring, and toxicity of felbamate, so providers can direct patient therapy to optimal outcomes.

One of the accepted factors of antiseizure medication resistance is the action of P-glycoprotein (P-gp), limiting the access of drugs to the nervous system. But if we ask which antiseizure medications are substrates of P-gp and which are not, the available bibliography will not allow us to obtain a clear answer. In this review, we focus on clarifying this response. The reviewed studies have been conducted both in cell lines and in mice that have been administered a P-gp inhibitor, artificially induced with drug-resistant epilepsy, or had a P-gp gene knockout. A limited number of studies have been conducted in dogs, primates, brain sections of known epilepsies, or human volunteers, including pharmacokinetic studies in healthy volunteers and symptomatic response to treatment. Notably, in human cases, allele variation studies check if having one allele or another of P-gp varies the pharmacokinetics in question. As we see, the approach to P-gp and antiseizure medication can be done using very different methods, which undoubtedly complicates the interpretation of the findings. We cannot be categorical in our results, but we can mention probabilities. Regarding the weighting of studies, we will consider those conducted in humans as more important, followed by animal studies, and we will give less weight to studies showing contradictory results compared to the general bibliographic base. Based on the published bibliography, we propose that, among the anticrisis medications, the following are likely substrates of P-glycoprotein: Phenytoin, Phenobarbital, Oxcarbazepine, Lamotrigine, Topiramate, and Lacosamide (less evidence). The following are probably not substrates: Brivaracetam, Zonisamide, Valproic acid, Perampanel, Gabapentin, and Vigabatrin. We have not obtained enough information about: Carbamazepine, Eslicarbazepine, Levetiracetam, Tiagabine, Felbamate, Pregabalin, Rufinamide, Ezogabine, and Retigabine.

Lennox-Gastaut syndrome (LGS) is a severe childhood-onset developmental and epileptic encephalopathy characterized by multiple drug-resistant seizures, cognitive impairments, and distinctive EEG patterns. Given its profound impact on patients' quality of life, developing effective pharmacotherapies remains a critical clinical challenge.

Lennox-Gastaut Syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by multiple drug-resistant seizure types, presenting significant challenges for treatment. This comprehensive review examines seizure-type-specific response patterns to various therapeutic interventions in LGS. We conducted an extensive literature review of randomized controlled trials, observational studies, and real-world evidence, covering research up to February 2025. Our analysis shows that atonic seizures respond particularly well to corpus callosotomy (CC) and Vagus Nerve Stimulation (VNS), with CC demonstrating superior efficacy. Generalized tonic-clonic seizures (GTCS) show favorable responses to antiseizure medications (ASMs) such as felbamate, lamotrigine, topiramate, fenfluramine, lacosamide, and perampanel. Myoclonic seizures tend to respond better to clonazepam, topiramate, zonisamide, brivaracetam, and perampanel, but may show limited responsiveness to neuromodulation and CC. Atypical absence seizures may respond to valproate, topiramate, and rufinamide, but show poor responses to brivaracetam and perampanel. The ketogenic diet and resective epilepsy surgery demonstrate broad efficacy across seizure types, although specific data for each type remain limited. VNS is most effective for atonic and tonic seizures, with less consistent responses in GTCS and focal seizures. Emerging neuromodulation techniques, including deep brain stimulation (DBS) and responsive neurostimulation (RNS), show promise, particularly for tonic and GTCS, but further investigation is needed. This review underscores the importance of tailoring treatment to predominant seizure types and calls for more rigorous, seizure-type-specific outcome reporting in future clinical trials, along with the need for long-term studies. The findings advocate for a precision, network-based approach to treatment, where therapeutic decisions are guided by individual seizure patterns and supported by evidence-based, seizure-type-specific efficacy data.

Wound healing (WH) poses a significant socio-economic burden due to its high incidence and recurrence rates. Iron overload (IO) could be a factor leading to delayed WH. This study thus analyzed IO-related genes (IORGs) in WH, offering possibilities for developing new therapeutic strategies. Differential gene expression (DEGs) analysis was conducted between the WH group and intact skin (IS) group, intersected with IORGs to obtain differentially expressed IORGs (DE-IORGs). Functional enrichment analysis and potential drug screening were performed on DE-IORGs. A protein-protein interaction (PPI) network of DE-IORGs was constructed, and hub genes were identified using CytoHubba and MCODE methods. ROC curves of hub genes were plotted, and their expression levels in WH and IS groups as well as inter-gene correlations were analyzed. Additionally, immune infiltration variances in WH and IS groups, along with miRNA and TFs of hub genes, were examined. Finally, the effect of EGFR on skin wound healing was verified by scratch healing assay. 39 DE-IORGs were predominantly enriched in signaling pathways like HIF-1 signaling pathway and Th17 cell differentiation. Potential drugs for treating WH (e.g., felbamate, SA-94315, GANT-58, rucaparib) were identified. Three hub genes related to IO in WH were pinpointed (HIF1A, CDKN2A, EGFR) with diagnostic value. Immune infiltration analysis showed higher levels of immune cells like endothelial cells and macrophages in the WH group. Additionally, 55 miRNAs (e.g., hsa-mir-200a-3p, hsa-mir-218-5p) and 2 TFs (L3MBTL2, ZNF76) regulating the three hub genes were predicted. Cell experiments showed that EGFR could promote skin wound healing. The study suggested HIF1A, CDKN2A, and EGFR as potential diagnostic biomarkers for effective WH diagnosis, offering new insights into identifying potenti1al therapeutic targets for WH treatment.