Lennox-Gastaut syndrome (LGS) is a refractory epileptic encephalopathy that mainly affects children, but can also involve adults, and is characterized by multiple seizure types, electroencephalographic (EEG) abnormalities, and mental retardation. This review focuses on the etiology, pathogenesis, diagnostic criteria, and treatment of LGS. In terms of etiology, LGS may be caused by a variety of factors such as abnormal brain development, perinatal brain injury, inherited metabolic diseases, and gene mutations. The pathogenesis involves multiple gene mutations that affect the balance of neuronal excitability and inhibition.LGS is diagnosed on the basis of multiple seizure types with an age of onset of less than 18 years, an EEG that shows widespread slow (1.5~2.5 Hz) spiking slow complex waves, and a triad of intellectual and psychosocial dysfunction. Therapeutically, LGS is treated with antiepileptic seizure medications (ASMs) , including valproate, lamotrigine, and rufinamide, but patients often develop resistance to ASMs. Non-pharmacological treatments include ketogenic diet, vagus nerve stimulation (VNS) , and corpus callosotomy (CC) , which provide palliative treatment options for patients who have difficulty controlling seizures. Despite the variety of therapeutic options, the prognosis for LGS is usually poor, with patients often experiencing intellectual disability and seizures persisting into adulthood. This review emphasizes the importance of further research into the etiology and pathogenesis of LGS and the need to develop new therapeutic approaches to improve patients' quality of life and reduce the burden of disease.
Drug-resistant epilepsy (DRE) not only have disruption of the patients by seizure, but also influence the quality of life, cognitive function and social association, as well as development delay even retrogression for children. Epilepsy surgery is the only curative treatment currently available for focal lesional pharmacoresistant epilepsy, five years complete seizure freedom rates was around 60% after surgery. The criterion of surgical intervention at present is achievement for the diagnosis of DRE, thereafter consideration of early epilepsy surgery, but these maybe a long-term duration. Recent advance in examine methods and surgical techniques have improved the surgical treatment of epilepsy, to such patient with focal lesional structure abnormality, before the DRE emergence, under the discussion of the multidisciplinary team. Children under 3 years old, the brain have greater neural plasticity, early surgical treatment is expected at allow the healthy brain to recover and develop the language function and quality of life. Numerous cause may pose abstracts to the delay of surgical intervention: (1) diagnosis delay; (2) patient himself and their familiar recognize that there have same risk of surgical treatment; (3) the primary doctor firmly believe that epilepsy surgery is the ultimate methods; (4) special problems of the patient, such including: age, comorbidity, and the location of symptom, EEG as well as imaging non-conformation.
Objective To explore the clinical characteristics of patients with combined use of ≥2 kinds of anti-seizure medications in Tibetan plateau. Methods Epilepsy patients who were hospitalized in the People’s Hospital of Tibet Autonomous Region from September 2018 to September 2023 and used ≥2 kinds of anti-seizure medications in combination were selected. Their demographic data such as gender, age, and ethnicity, as well as diagnostic information, medication and other clinical data were collected, and relevant demographic and clinical characteristics were analyzed. In the later stage, telephone follow-up was used to record medication and epileptic seizure control. Results A total of 2295 patients with epilepsy were included, of which 142 (6.2%) met the inclusion criteria, of which 133 (93.7%) were Tibetans. There were more males than females (86 vs. 56, P<0.05), and more minors and young patients than middle-aged and elderly patients (106 vs. 36, P<0.05). 87.3% of the patients underwent magnetic resonance imaging (MRI) or computed tomography (CT), and 71.1% of the patients were abnormal. The main cause of epilepsy was structural etiology (84/142, 59.2%). The most common combination was two drugs (127/142, 89.4%). The largest proportion of combination was sodium valproate and levetiracetam (46/142, 32.4%). After standardized multi-drug combination therapy, the average frequency of epilepsy seizures was significantly reduced compared with the baseline, and the difference was statistically significant (P<0.05). Among the 98 patients aged ≥14 years, 15 cases (15.3%) had drug-refractory epilepsy, 18 cases (18.4%) had seizures controlled by standardized combination medication, 16 cases (16.3%) had seizures controlled by reducing combination medication to a single drug, 5 cases (5.1%) had good control and had stopped medication, 3 cases (3.1%) had frequent epileptic seizures due to poor medication compliance, 15 cases (15.3%) had irregular medication, 17 cases (17.3%) died, and 9 cases (9.2%) were lost. Conclusion The proportion of epilepsy treated with multiple drugs and refractory to drugs was lower than the conclusion of previous studies, and the anti-epileptic effect of multiple drugs was positive. Structural causes (stroke, etc.) are the main causes of epilepsy, and brain parasitic infection is a unique factor of high-altitude epilepsy. Strengthening the standardized use of drugs will help improve the treatment status and prognosis of patients.
Objective To systematically evaluate the safety profiles of anti-seizure medications (ASMs) regarding metabolic adverse events in the pediatric population, identify risk signals across different age stages, and provide evidence-based support for clinical individualized medication and pharmacovigilance. MethodsData from the Food and Drug Administration (FDA) adverse event reporting system (FAERS) spanning Q1 2013 to Q3 2024 were analyzed. Reports involving metabolic adverse events in patients aged 0~18 years after ASMs use were screened. Data mining methods, including Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), and Bayesian Confidence Propagation Neural Network (BCPNN), were applied. Standardized classification was performed using the Medical Dictionary for Regulatory Activities (MedDRA) v26.1 to analyze adverse reaction signals across metabolic pathways, including glucose, lipids, proteins/amino acids, and bone/calcium/phosphorus/magnesium, as well as trace metals. Stratified safety evaluations were conducted across four age groups: infants (0~2 years), toddlers (2~6 years), children (6~2 years), and adolescents (12~18 years). ResultsA total of 2,356 metabolic adverse event reports were included. Significant signals were observed for protein and amino acid metabolism disorders (ROR=5.44), bone/calcium/magnesium/phosphorus metabolism disorders (ROR=1.59), and iron/trace metal metabolism disorders (ROR=1.83), with some signals being specific to the pediatric population. Several drugs, including valproate, topiramate, levetiracetam, and gabapentin, showed strong risk signals across multiple metabolic pathways, primarily manifesting as hyperammonemia, hypocalcemia, and hypomagnesemia. Risk profiles varied significantly by age group: lacosamide showed prominent signals for bone metabolism disorders in the 0~2 years group; perampanel showed significant signals for amino acid metabolism disorders in the 2~6 years group; and in the 12~18 years group, clonazepam and gabapentin showed extremely high ROR values (>48) for iron/trace metal metabolism disorders. The median onset time for metabolic adverse events associated with novel ASMs was significantly later than that of traditional ASMs (38 days vs. 8 days), suggesting a relatively delayed but prolonged metabolic toxicity for newer agents. ConclusionThe use of ASMs in minors can trigger multi-system metabolic disturbances, with significant differences in risk profiles across different drugs and age groups. We recommend strengthening the dynamic monitoring of metabolic parameters during treatment, with particular attention to the potential toxicity of high-risk drugs within specific age windows, thereby promoting the establishment of precision dosing and early intervention strategies.
Epilepsy is a common chronic disease of the nervous system, which has certain adverse effects on the cognitive, psychological and social functions of the patients. To date, anti-seizure medications (ASMs) remain the first-line treatment option for epilepsy, but many patients with epilepsy still do not have effective seizure control when multiple ASMs are used in combination. Therefore, there is an urgent need for a new target and mechanism ASMs to bring about new treatment options and hope for patients with intractable epilepsy. Perampanel, a new third-generation ASMs, whereas second-generation ASMs tend to exert anti-seizure effects mainly by regulating ion channels or enhancing related mechanisms such as gamma-aminobutyric acid (GABA) effects, perampanel exerts its effects mainly by targeting the excitatory neurotransmitter glutamate. Perampanel is the first selective α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptor antagonist and the first selective inhibitory ASMs for excitatory postsynaptic function. Because of its unique target and mechanism, it has been approved by many countries in the world for adjuvant additive therapy and monotherapy for patients with focal and general epilepsy. In addition, with the discovery of the neuroprotective, antioxidant, neurotransmitter regulation effects of perampanel, it also provides a new potential choice for the treatment of other diseases. This article mainly reviews the mechanism of action, pharmacokinetics, clinical trials and treatment of other diseases other than epilepsy of perampanel.
