レノックス・ガストー症候群他

OBJECTIVE: To systematically review the current research progress on clobazam in pediatric antiepileptic therapy, focusing on its pharmacological mechanisms, pharmacokinetic properties, clinical efficacy, safety profile, and approaches to individualized treatment, with particular emphasis on the influence of CYP2C19 genetic polymorphisms on pharmacokinetics and therapeutic outcomes, and to provide a comprehensive reference for the rational clinical use of clobazam. METHODS: This article comprehensively reviews the current research progress on clobazam in pediatric antiepileptic therapy, including evidence of efficacy across different epilepsy syndromes, strategies for managing drug-drug interactions, and individualized dosing regimens based on genotyping and therapeutic drug monitoring. RESULTS: Clobazam is a 1,5-benzodiazepine used as an antiseizure medication. Compared with classical 1,4-benzodiazepines, it demonstrates greater efficacy and fewer sedative adverse effects. Clobazam was approved by the U.S. Food and Drug Administration (FDA) in 2011 as an adjunctive therapy for seizures associated with Lennox-Gastaut syndrome (LGS) in patients aged ≥2 years. Since then, it has been increasingly used as adjunctive therapy for several pediatric epilepsy syndromes, including Dravet syndrome (DS), epilepsy with myoclonic-atonic seizures (EMAS), and epileptic encephalopathy with spike-wave activation during sleep. CYP2C19 genetic polymorphisms significantly influence its pharmacokinetics and therapeutic outcomes. Across the reviewed studies, adjunctive clobazam achieved ≥50% seizure reduction in approximately 53% of children and seizure freedom in approximately 24%. Efficacy was highest in LGS, supported by randomized controlled trials, while evidence for other syndromes was largely observational. CYP2C19 poor metabolizer status significantly increased N-desmethylclobazam exposure, supporting genotype-guided dose initiation. CONCLUSION: Clobazam demonstrates consistent efficacy as adjunctive therapy in pediatric drug-resistant epilepsy, with the strongest evidence supporting its use in LGS. Individualized treatment informed by CYP2C19 genotyping and therapeutic drug monitoring can optimize clinical outcomes. This review provides a comprehensive reference for the rational clinical use of clobazam.

BACKGROUND: This study evaluates the efficacy and safety of Vagus Nerve Stimulation (VNS) in the treatment of refractory Lennox-Gastaut Syndrome (LGS) in pediatric patients. METHODS: A systematic literature review was conducted based on observational studies and case series analyses, followed by assessment of risk of bias using the ROBINS-I tool. RESULTS: The results demonstrated that, among the combined sample of 527 patients included in the selected studies, 375 achieved a reduction greater than 50% in seizure frequency after VNS therapy, with some cases reporting complete seizure remission. The analysis suggests greater effectiveness for atonic seizures (drop attacks), followed by tonic and absence seizures. Regarding secondary outcomes, significant qualitative improvements were reported in alertness, attention, and sleep quality. Although the intervention appears to be relatively safe, the included studies presented a high risk of bias in the outcome measurement domain, mainly due to the impracticality of blinding in surgical procedures and the subjective nature of caregiver-reported outcomes. The heterogeneity of clinical responses appears to be associated with differences in stimulation parameters and variability in baseline clinical conditions. CONCLUSION: VNS yields results that suggest potential utility in the management of LGS. While the ideal scenario would require randomized clinical trials with representative and exclusive samples for the syndrome, as well as standardized stimulation protocols, it is understood that methodological limitations exist when dealing with a rare syndrome. Therefore, the importance of this systematic review is highlighted in order to encourage individualized and assertive clinical decisions in the management of these patients.

This article offers a critical overview of the therapeutic role of cannabis and cannabinoids following their recent regulation in Spain through Royal Decree 903/2025 for the use of standardized compounded formulations. In chronic pain, cannabis is not considered a high-potency analgesic, but rather a third-line option for refractory cases, especially neuropathic pain. Its benefit is modest and acts mainly on the affective-emotional dimension of suffering rather than on the nociceptive signal itself. Regarding chemotherapy-induced nausea and vomiting, it is reserved for refractory cases; although it shows benefits compared with placebo, its efficacy is comparable to that of conventional antiemetics and it presents a less favorable toxicity profile. For spasticity in multiple sclerosis, preparations such as nabiximols reduce patients' perception of symptoms, although there is a high discontinuation rate due to lack of efficacy or adverse effects. In contrast, the use of cannabidiol in refractory pediatric epilepsy (Dravet syndrome, Lennox-Gastaut syndrome, and tuberous sclerosis complex) is supported by the strongest evidence. The BECOME study highlights improvements that go beyond seizure reduction, positively impacting alertness, sleep, and family quality of life. Its role in other indications with weak or inconsistent evidence, such as fibromyalgia, glaucoma, anorexia, and anxiety, is also reviewed. In conclusion, although cannabis may offer certain benefits, its integration into modern clinical practice should be cautious, individualized, and carried out under strict clinical supervision. The analysis of real-world use data will undoubtedly provide valuable insights.

RATIONALE: Hormones such as estrogen and progesterone influence seizure thresholds resulting in catamenial epilepsy in a subset of women with epilepsy. While prior studies assessing the correlation between menarche and seizure onset have found mixed results, little is known about the effects of puberty on seizure burden in patients with developmental and epileptic encephalopathies, such as Lennox-Gastaut syndrome (LGS). Determining whether seizure burden in LGS is affected by pubertal changes such as menarche will inform prognosis and anticipatory guidance for caregivers of patients. METHODS: A single-center retrospective chart review of female patients with LGS who had a documented age of menarche and who had been evaluated at a single tertiary care children's hospital between 2013-2023 was performed. Menarche was used as a proxy for puberty. Seizure type, frequency, number of anti-seizure medications, and change in anti-seizure medications were recorded yearly between the ages of 5-21 years. Statistical analysis with cumulative logit mixed models was used to estimate the odds of a patient having higher seizure frequency by seizure type. A linear mixed model was used to assess change in antiseizure medications. RESULTS: A total of 22 patients met inclusion criteria. Menarche was not independently statistically significantly associated with increased overall seizure when controlling for age (OR 0.58, p = 0.195). However, age was independently positively associated with seizure frequency (OR 1.16 per year, p = 0.002). When controlling for age, most individual seizure types (non-motor, atonic, tonic, myoclonic, clonic, status epilepticus) did not significantly increase with menarche. Total number of antiseizure medications (ASMs) used significantly increased after menarche by an estimated 0.43 ASMs (p = 0.026), when controlling for age. CONCLUSIONS: After controlling for age, menarche in patients with LGS did not correlate with increased seizure frequency in total or if stratified by specific seizure types. However, overall seizure frequency and anti-seizure medication usage increased with age, suggesting a gradual worsening of epilepsy over adolescence. These data provide important information regarding the clinical course of LGS which may aid in both medical management and in anticipatory guidance for families as their children enter adolescence. Further study is needed for deeper understanding of long-term outcomes of LGS, and how age and puberty may affect seizures in males with LGS.

OBJECTIVE: Interictal electroencephalographic (EEG) activities are generally considered asymptomatic. Pulse wave amplitude drop (PWAD) is a marker of autonomic nervous system (ANS) reactivity linked to cardiovascular risk. Generalized paroxysmal fast activity (GPFA) is a major EEG pattern in different epileptic conditions. We investigated whether GPFA, even when clinically silent, triggers ANS activation measured by PWAD. METHODS: We retrospectively analyzed 511 GPFA events during sleep from 21 patients undergoing polysomnography. We characterized GPFA events and their association with PWAD. RESULTS: Among 511 GPFA events, 26.4% were clinically asymptomatic without PWAD (Group 1), 40.5% were clinically silent with PWAD ≥ 30% as the only detected sign (Group 2), and 33.1% were clinically symptomatic (Group 3). Compared to Groups 1 and 2, Group 3 events had longer duration (p = .007 and p < .0001), had higher heart rate variation (p < .001), and were more often symmetric (p < .001). Group 3 GPFA occurred more often in N1 sleep compared to Group 2 (32.1 vs. 18.1%, p = .004). Unexpectedly, PWAD was poorly correlated with GPFA duration (r = .068). Finally, Group 2 GPFA-associated PWADs more closely resembled microarousal-associated PWADs than apnea/hypopnea-associated PWADs in temporal profile. SIGNIFICANCE: PWAD uncovers autonomic responses in most GPFA, challenging the concept that "interictal" implies asymptomatic. This repetitive ANS activation raises questions about its potential long-term clinical consequences. These findings support the use of pulse oximetry during video-EEG to detect subclinical autonomic changes, although further studies are needed to determine their clinical significance and whether they should influence the management of interictal activities.