RESUMEN
PURPOSE: Postoperative seizures are a significant complication following glioma surgery. While prophylactic antiseizure medications (ASMs) are widely prescribed, the optimal duration of prophylaxis remains unclear. Current guidelines lack specificity regarding high-risk subgroups that may benefit from extended ASM therapy. Here, we aimed to determine whether ASM duration affects postoperative seizure occurrence and to identify patient subgroups in whom longer ASM prophylaxis significantly reduces seizure risk. METHODS: We conducted a retrospective cohort study of 206 adult high-grade glioma patients who underwent resection. Postoperative seizure occurrence was the primary outcome. ASM duration was modeled using logistic regression with cubic splines to detect non-linear effects, and a classification decision tree was trained to identify high-risk subgroups. Observed seizure rates were compared across data-driven ASM duration thresholds. Time-to-event analysis was also performed. RESULTS: Mean age was 48.1 years (SD 15.9); 48.5% were male. Most tumors were located in the frontal (43.3%) and temporal lobes (29.6%), with glioblastoma being the most common histology (65%). Spline regression revealed no statistically significant association between ASM duration and seizure occurrence (pseudo R² = 0.0066; p = 0.69). However, decision tree analysis suggested a clinically meaningful subgroup: patients aged > 52.5 years with subtotal resection had increased seizure risk when ASM duration was ≤ 135 days. In this group, extending ASM prophylaxis was associated with a lower seizure rate. CONCLUSION: While extended ASM prophylaxis was not broadly associated with reduced seizure risk, tree-based analysis suggested an older, incompletely resected subgroup that may benefit from prolonged ASM use. REGISTRATION NUMBER: IR.TUMS.SINAHOSPITAL.REC.1402.091 retrospectively registered.
Asunto(s)
Anticonvulsivantes , Neoplasias Encefálicas , Glioma , Procedimientos Neuroquirúrgicos , Complicaciones Posoperatorias , Convulsiones , Neoplasias Supratentoriales , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Convulsiones/etiología , Convulsiones/prevención & control , Convulsiones/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/administración & dosificación , Glioma/cirugía , Glioma/patología , Árboles de Decisión , Adulto , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/tratamiento farmacológico , Anciano , Procedimientos Neuroquirúrgicos/efectos adversos , Neoplasias Supratentoriales/cirugía , Neoplasias Encefálicas/cirugía , Estudios de SeguimientoRESUMEN
PURPOSE: Tuberous sclerosis complex (TSC) is associated with early-onset epilepsy, often leading to drug-resistant epilepsy (DRE) and developmental impairment. Preventive therapy with vigabatrin (VGB) has been proposed as a strategy to modify disease progression, but its efficacy and safety remain uncertain. This systematic review and meta-analysis aimed to evaluate the impact of preventive VGB therapy on seizure occurrence [including infantile epileptic spasms syndrome (IESS) and DRE], neurocognitive outcomes, and adverse events in infants with TSC. METHODS: We performed a systematic search of MEDLINE, EMBASE, Scopus, and Web of Science. Studies were eligible if they enrolled infants with TSC without prior seizures and compared preventive VGB to standard treatment. Risk of bias was assessed using the ROB 2.0 tool for randomized trials and the Newcastle-Ottawa Scale for observational studies. Meta-analyses were performed using a random-effects model, with results expressed as risk ratios (RR) or standardized mean differences (SMD) and 95 % confidence intervals (CI). RESULTS: Three studies with 149 children were included. There was reduced occurrence of seizures (including IESS and DRE) in the preventive therapy group (39/68 vs 64/81). However, the risk ratios were not statistically significant for occurrence of seizures (RR: 0.72; 95 % CI: 0.47-1.10), IESS (RR: 0.23; 95 % CI: 0.04-1.25), and DRE (RR: 0.74; 95 % CI: 0.49-1.12). Neurocognitive outcomes did not differ significantly between the two groups (SMD: 0.35; 95 % CI: -0.21- 0.91). Preventive vigabatrin was generally well-tolerated, with few adverse events and rare treatment discontinuation reported. CONCLUSION: Preventive vigabatrin therapy may prevent the development of epilepsy, including IESS and DRE, in children with TSC, with an acceptable safety profile. Although statistical significance was not achieved, the favorable trend highlights the potential clinical benefits of early intervention with VGB. Larger, high-quality randomized trials are warranted to confirm these findings and explore the long-term neurodevelopmental outcomes.
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Anticonvulsivantes , Esclerosis Tuberosa , Vigabatrin , Humanos , Vigabatrin/uso terapéutico , Vigabatrin/efectos adversos , Esclerosis Tuberosa/complicaciones , Esclerosis Tuberosa/tratamiento farmacológico , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/efectos adversos , Niño , Espasmos Infantiles/prevención & control , Convulsiones/prevención & control , LactanteRESUMEN
OBJECTIVE: To review the literature regarding the management of Lambert Eaton Myasthenic Syndrome (LEMS) in pregnancy, with a focus on the clinical challenges posed by coexisting hypertensive disorders, including preeclampsia and the routine use of magnesium sulfate for seizure prophylaxis. DATA SOURCES: A systematic search of PubMed, Embase, Web of Science, and Scopus was conducted through May 2024 using combinations of keywords and MeSH terms including "Lambert Eaton Myasthenic Syndrome," "LEMS," "pregnancy," "preeclampsia," "magnesium sulfate," and "hypertensive disorders of pregnancy." STUDY ELIGIBILITY CRITERIA: Studies were included if they reported pregnancy outcomes, maternal complications, or management considerations in patients with LEMS or related myasthenic syndromes. Exclusion criteria included non-English language publications, animal studies, and review articles without case-level data. Study appraisal and synthesis methods Studies were appraised based on relevance to Lambert-Eaton Myasthenic Syndrome in pregnancy, with particular attention to hypertensive complications and seizure prophylaxis strategies. Due to the rarity of this condition, included articles were primarily case reports and case series. Data were synthesized using a qualitative narrative approach, focusing on clinical presentation, interventions, and maternal-neonatal outcomes. Studies involving myasthenia gravis were also reviewed for comparison, given overlapping neuromuscular risks. No formal risk-of-bias assessment or statistical pooling was conducted due to heterogeneity and limited sample size. RESULTS: Twenty-four citations were included, encompassing case reports, case series, and retrospective analyses. Of these, 5 (21%) specifically involved LEMS during pregnancy, and 2 (8%) reported transient neonatal LEMS. Magnesium sulfate was discussed in 3 (13%) studies, with at least one case documenting exacerbation of neuromuscular symptoms. Two cases involved the co-occurrence of preeclampsia and LEMS, highlighting the dilemma of balancing seizure prophylaxis with neuromuscular safety. No standardized treatment protocols were identified. Multidisciplinary care and individualized decision-making were emphasized across reports. CONCLUSIONS: The intersection of LEMS and hypertensive disorders of pregnancy is clinically complex and underreported. The use of magnesium sulfate-a cornerstone of preeclampsia management-poses a potential risk for patients with LEMS, underscoring the need for heightened awareness, individualized treatment plans, and multidisciplinary collaboration. Further research is needed to establish safe, evidence-based guidelines for managing this rare but high-risk patient population.
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Anticonvulsivantes , Hipertensión Inducida en el Embarazo , Síndrome Miasténico de Lambert-Eaton , Sulfato de Magnesio , Preeclampsia , Humanos , Embarazo , Femenino , Síndrome Miasténico de Lambert-Eaton/complicaciones , Síndrome Miasténico de Lambert-Eaton/terapia , Síndrome Miasténico de Lambert-Eaton/tratamiento farmacológico , Sulfato de Magnesio/uso terapéutico , Anticonvulsivantes/uso terapéutico , Convulsiones/prevención & controlRESUMEN
Early postoperative seizures, defined as occurring within 7 days after surgery, are a significant complication that occurs following neurosurgical procedures involving cerebral manipulation. As a result, short-term antiseizure medication is typically administered in Japan despite the lack of consensus regarding its prophylactic use. Perampanel hydrate, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, was recently introduced in an intravenous formulation in Japan, providing new potential for early postoperative seizures prevention during the perioperative period. This study aimed to evaluate the safety and feasibility of a single-dose intravenous infusion of perampanel hydrate during brain tumor surgery. We conducted a single-arm, open-label, exploratory safety trial involving 10 adult patients undergoing brain tumor resection. Each participant received a 6 mg intravenous dose of perampanel hydrate during surgery, with no additional antiseizure medication administered postoperatively unless clinically indicated. The primary endpoint was the incidence of grade 3 or higher adverse events related to the study drug. Secondary endpoints included hematological toxicity, the incidence of early postoperative seizures, anesthetic recovery time, and perampanel hydrate blood concentration profiles. No grade 3 or higher adverse events were observed. Minor adverse events included transient grade 2 liver enzyme elevations and postoperative restlessness, both of which resolved within a week. Notably, no cases of early postoperative seizures occurred, and perampanel hydrate blood levels remained high even 7 days after a single administration. Intravenous perampanel hydrate appears safe and well tolerated in the perioperative setting and may effectively prevent early postoperative seizures. Further studies are planned to evaluate its efficacy in larger patient cohorts.
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Anticonvulsivantes , Neoplasias Encefálicas , Complicaciones Posoperatorias , Piridonas , Convulsiones , Humanos , Piridonas/administración & dosificación , Piridonas/efectos adversos , Piridonas/uso terapéutico , Masculino , Nitrilos , Femenino , Persona de Mediana Edad , Convulsiones/prevención & control , Convulsiones/etiología , Neoplasias Encefálicas/cirugía , Complicaciones Posoperatorias/prevención & control , Infusiones Intravenosas , Anciano , Adulto , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Anticonvulsivantes/uso terapéuticoRESUMEN
BACKGROUND: Awake craniotomy with direct cortical stimulation (DCS) mapping is the gold standard for resection of pathology in eloquent regions. Prophylactic anti-seizure medications (ASMs) are commonly used to prevent intraoperative seizure. There is a preference for levetiracetam (LEV), due to its low side effect profile. We investigated whether a prophylactic dose of fosphenytoin (FOS) compared to LEV reduced the risk of intraoperative complications. METHODS: We performed a retrospective analysis of consecutive adult and pediatric awake craniotomy cases from 2018 to 2024 who received either 1 g LEV or 10 mg/kg FOS at the start of surgery. Data was collected on intraoperative events including seizure and new neurologic deficits during mapping, aborted stimulation mapping, and 24-hour neurologic deficits and seizures. A composite outcome was counted if one or more of the complications occurred. RESULTS: 112 patients met inclusion criteria; 61 (55 %) were included in the LEV group and 51 (45 %) were included in the FOS group. There was no significant difference in number of recorded or clinical intraoperative seizure between treatment groups (p = 0.925). There were no observed side effects from FOS or LEV prophylaxis. FOS was the factor most associated with all the outcomes of interest, followed by home ASM regimen (other and LEV), year of surgery, GBM, and preoperative seizures. In a multivariable model of these top variables, only prophylactic FOS was significantly associated with lower odds of composite events (OR = 0.20, 95 % CI 0.05-0.65, p = 0.011), intraoperative events (OR = 0.26, 95 % CI 0.06-0.91, p = 0.045) and 24-hour deficits (OR = 0.25, 95 % CI 0.07-0.79, p = 0.024). FOS prophylaxis was significantly associated with reduced risk of transient neurologic deficits (OR = 0.20, 95 % CI 0.04-0.82, p = 0.036). CONCLUSION: Though there was no difference in rate of intraoperative and postoperative seizure, the lower rate of transient neurologic deficit and intraoperative events suggests prophylactic fosphenytoin may improve safety of awake craniotomy with DCS compared to levetiracetam.
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Anticonvulsivantes , Craneotomía , Complicaciones Intraoperatorias , Levetiracetam , Fenitoína , Convulsiones , Humanos , Levetiracetam/uso terapéutico , Levetiracetam/administración & dosificación , Estudios Retrospectivos , Craneotomía/métodos , Craneotomía/efectos adversos , Masculino , Femenino , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/administración & dosificación , Adulto , Convulsiones/prevención & control , Persona de Mediana Edad , Fenitoína/análogos & derivados , Fenitoína/uso terapéutico , Fenitoína/administración & dosificación , Vigilia , Niño , Complicaciones Intraoperatorias/prevención & control , Adolescente , Anciano , Adulto Joven , PreescolarRESUMEN
Cranial meningioma are the most common type of primary brain tumor, and focal onset, tumor-related seizures affect a significant proportion of patients. Seizures affect 30% of symptomatic preoperative patients and a further 12% of postoperative patients. Although most patients may be cured of their oncological disease by surgery, seizures confer disability, reduced quality-of-life, delayed return to driving and work, and increase the risk of sudden death. Tumor-associated seizures are also more likely to be resistant to antiseizure medications (ASMs). ASMs are limited to treating the symptoms of epilepsy-seizures-but have no disease-modifying effect on the mechanisms that cause or maintain seizure susceptibility. There is a need to be able to predict who is at risk of developing postoperative seizures for targeted prevention or closer monitoring of those at greater risk. Mechanisms underpinning brain tumor-related seizures are most likely multifactorial and related to morphological, biochemical, and metabolic causes. Brain tumors likely cause cortical hyperexcitability due to irritation caused by mass effect, brain invasion, and peritumoral brain edema. Inflammatory mediators are involved in epileptogenesis in animal models and human seizure syndromes and there are experimental data to support the development of inflammatory mediators as biomarkers for epileptogenesis. Meningioma-associated seizures are incompletely understood and consequently unpredictable with current knowledge. In this review, we discuss the proposed mechanisms of epileptogenesis in brain tumors and putative neuroinflammatory mechanisms for meningioma-associated seizures. Ultimately, we evaluate the potential of neuroinflammatory biomarkers of epileptogenesis in meningioma and the current challenges with extrapolating from current literature, which primarily consider epilepsy and intrinsic brain tumors. A prospective randomized controlled trial (STOP'EM: ISRCTN14381346) is open in the UK and will determine the role of two weeks of prophylactic levetiracetam in seizure-naïve patients undergoing meningioma surgery and provide an opportunity to obtain serial blood measurements from patients to assist with biomarker discovery.
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Epilepsia , Meningioma , Complicaciones Posoperatorias , Medición de Riesgo , Convulsiones , Humanos , Meningioma/complicaciones , Meningioma/cirugía , Convulsiones/diagnóstico , Convulsiones/etiología , Convulsiones/prevención & control , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Medición de Riesgo/métodos , Biomarcadores/análisis , Epilepsia/diagnóstico , Epilepsia/etiología , Epilepsia/prevención & control , Factores de Riesgo , Encéfalo/fisiopatologíaRESUMEN
OBJECTIVES: This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the efficacy and tolerability of antiseizure medications (ASMs) in preventing a first seizure in people with brain tumours compared with placebo or no active treatment.
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Anticonvulsivantes , Neoplasias Encefálicas , Convulsiones , Adulto , Humanos , Anticonvulsivantes/uso terapéutico , Neoplasias Encefálicas/complicaciones , Ensayos Clínicos Controlados Aleatorios como Asunto , Convulsiones/prevención & control , Convulsiones/etiología , Revisiones Sistemáticas como Asunto , Metaanálisis como AsuntoRESUMEN
Chronic epilepsy is mainly characterized by spontaneous recurrent seizures (SRS). The peroxisome proliferator activated receptor gamma/phosphatase and tensin homolog/protein kinase B (PPARγ/PTEN/Akt) pathway is involved in the pathogenesis of SRS and neuronal loss. Curcumin is a natural compound, and previous studies have shown it provides neuroprotection via anti-inflammation and anti-oxidant effects in many central nervous system (CNS) diseases. In the present study, we show that curcumin regulates the abnormal expression of PTEN and Akt in the SRS phase, improves the neuronal loss in the hippocampus, and suppresses SRS development and seizure spike activity in epileptic rats. More importantly, these effects are reversed by the PPARγ antagonist, T0070907, suggesting that curcumin exerts neuroprotective and anti-epileptic effects through the PPARγ/PTEN/Akt signaling pathway. Other studies have shown that curcumin can cross the BBB and has a safety profiles and pleiotropic pharmacological effects. Thus, our data support the proposition that curcumin might be a potential neuroprotective and anti-epileptic agent for chronic epilepsy.
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Anticonvulsivantes , Curcumina , Epilepsia , Neuronas , Fármacos Neuroprotectores , Convulsiones , Transducción de Señal , Animales , Curcumina/farmacología , Curcumina/uso terapéutico , Fosfohidrolasa PTEN/metabolismo , PPAR gamma/metabolismo , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Masculino , Ratas , Neuronas/efectos de los fármacos , Neuronas/patología , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Ratas Sprague-Dawley , Epilepsia/tratamiento farmacológico , Epilepsia/patología , Epilepsia/metabolismo , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , Hipocampo/efectos de los fármacos , Hipocampo/patología , Hipocampo/metabolismo , Convulsiones/metabolismo , Convulsiones/tratamiento farmacológico , Convulsiones/prevención & control , Convulsiones/patología , Modelos Animales de Enfermedad , Enfermedad CrónicaRESUMEN
BACKGROUND: Awake craniotomy (AC) has become the standard technique for eloquent region tumor resection. However, concerns remain regarding perioperative seizure and other complications requiring conversion to general anesthesia or operation termination. To prevent such events, antiseizure medications (ASMs) are commonly used but the effectiveness of their combinations is still debated. MATERIAL AND METHOD: This study is a retrospective cohort study of patients who underwent awake craniotomy for glioma resection. Patients were divided into two groups based on their seizure control medication: Group S (N = 29) received one ASM, while Group D (N = 26) received dual ASM. We conducted a comparative analysis of intraoperative seizure (IOS) and postoperative seizure (POS) rates between the two groups. Additionally, we evaluated the risk factors associated with POS and the 1-month postoperative Karnofsky Performance Scale (1 M-KPS). RESULT: A total of 55 patients (41.8% female) with a median age of 39.0 (interquartile range [IQR] 33.0-51.0) were included. The rate of IOS was 27.6% in Group S and 11.5% in Group D, with no statistically significant difference (p = 0.14). POS occurred in 24.1% of group S and 7.7% of group D (p = 0.10), demonstrating comparable rates. Moreover, the length of hospital stay (p = 0.61), the length of ICU stay (p = 0.14), postoperative KPS (p = 0.13), and 1 M-KPS (p = 0.22) were comparable between the two cohorts. The occurrence of POS was not associated with adjuvant therapy or the Isocitrate Dehydrogenase 1 (IDH1) mutation. Univariate and multivariate regression models found preoperative KPS and the extent of resection to have a significant association with 1 M-KPS. CONCLUSION: Adding a second ASM does not have a significant effect on preventing POS and IOS or improving 1 M-KPS. Accordingly, we recommend against the routine use of dual ASM due to their potential for increased adverse events.
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Anticonvulsivantes , Neoplasias Encefálicas , Craneotomía , Glioma , Complicaciones Intraoperatorias , Complicaciones Posoperatorias , Convulsiones , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/efectos adversos , Quimioterapia Combinada/efectos adversos , Craneotomía/efectos adversos , Craneotomía/métodos , Complicaciones Intraoperatorias/epidemiología , Complicaciones Intraoperatorias/etiología , Complicaciones Intraoperatorias/fisiopatología , Complicaciones Intraoperatorias/prevención & control , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/fisiopatología , Complicaciones Posoperatorias/prevención & control , Vigilia/fisiología , Convulsiones/etiología , Convulsiones/fisiopatología , Convulsiones/prevención & control , Factores de Riesgo , Estado de Ejecución de Karnofsky , Humanos , Masculino , Femenino , Neoplasias Encefálicas/cirugía , Glioma/cirugía , Estudios de Seguimiento , Resultado del Tratamiento , Estudios Retrospectivos , Levetiracetam/administración & dosificación , Levetiracetam/efectos adversos , Fenitoína/administración & dosificación , Fenitoína/efectos adversos , Adulto Joven , Adulto , Persona de Mediana Edad , AncianoRESUMEN
High dose busulfan (Bu) is widely used in conditioning regimens for patients undergoing hematopoietic stem cell transplantation. Like all alkylating agents, it has significant inter-patient pharmacokinetic (PK) variability. The influence of Bu plasma exposure on treatment outcomes and toxicities have led to the continued use of therapeutic drug monitoring of Bu. We investigated Bu PK in a unique myeloablative fractionated Bu regimen, designed to lower nonrelapse mortality in older patients and those with comorbidities. Intravenous (IV) Bu was administered once daily for 6 days, with a 7-day break after the first 2 Bu doses. Since seizures are a major risk of high-dose Bu, phenytoin was given as seizure prophylaxis. In an interim analysis, we noted a substantially increased (14.7%) Bu clearance on day -6 compared with day -13. When phenytoin was replaced by levetiracetam, Bu clearance increased by only 4.9% between days -13 and -6, significantly lower than that observed with phenytoin (P = .00001). These results indicate the presence of a drug-drug interaction (DDI) between Bu and phenytoin. There was no difference in efficacy of seizure prophylaxis between phenytoin and levetiracetam, and there were no experienced adverse events related to levetiracetam. Our results indicate that levetiracetam is a safe and efficacious alternative to phenytoin for seizure prophylaxis in Bu-based conditioning regimens in stem cell transplantation, notably without the significant drug-drug interaction observed with phenytoin.
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Anticonvulsivantes , Busulfano , Trasplante de Células Madre Hematopoyéticas , Convulsiones , Acondicionamiento Pretrasplante , Humanos , Busulfano/farmacocinética , Busulfano/administración & dosificación , Busulfano/efectos adversos , Busulfano/uso terapéutico , Convulsiones/prevención & control , Convulsiones/etiología , Masculino , Femenino , Persona de Mediana Edad , Anticonvulsivantes/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Fenitoína/uso terapéutico , Anciano , Adulto , Acondicionamiento Pretrasplante/métodos , Acondicionamiento Pretrasplante/efectos adversos , Interacciones Farmacológicas , LevetiracetamRESUMEN
BACKGROUND: The use of monopolar electrocautery in vagal nerve stimulator (VNS) revision surgeries has been debated due to concerns about device interference. Thus, herein, we aimed to evaluate the safety and efficacy of monopolar electrocautery during VNS generator replacement surgeries, particularly its impact on seizure control and battery performance. METHODS: A retrospective observational study was conducted on 30 patients who underwent VNS generator revision at a tertiary care center. Patients were divided into two groups: those in whom monopolar electrocautery was used (nâ¯=â¯18) and those in whom it was not used (n=â¯=â¯12). Pre- and postoperative data were collected, including seizure frequency, VNS settings, and operative time. The McHugh Outcome Classification was used to assess seizure control. RESULTS: The surgeries were significantly shorter in the electrocautery group than in the nonelectrocautery group (20.06⯱â¯2.29 vs. 51.83⯱â¯12.76â¯min, pâ¯<â¯0.001). Furthermore, there was no significant difference in seizure control between the two groups (pâ¯>â¯0.05). In two patients, a decline in seizure control classification was noted. However, this did not reach statistical significance. No lead damage or major complications developed in either group. CONCLUSION: Monopolar electrocautery significantly reduces the operative time during VNS generator revisions without compromising seizure control or increasing the risk of complications. Thus, monopolar electrocautery can be safely used in VNS revision surgeries, potentially streamlining the procedure and improving patient outcomes. However, further studies with larger populations are needed to confirm these findings.
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Electrocoagulación , Reoperación , Estimulación del Nervio Vago , Humanos , Electrocoagulación/métodos , Electrocoagulación/efectos adversos , Estudios Retrospectivos , Estimulación del Nervio Vago/instrumentación , Estimulación del Nervio Vago/métodos , Estimulación del Nervio Vago/efectos adversos , Masculino , Femenino , Reoperación/métodos , Reoperación/efectos adversos , Persona de Mediana Edad , Adulto , Convulsiones/prevención & control , Tiempo Operativo , AncianoRESUMEN
OBJECTIVES: Brain tumor-related epilepsy management poses significant challenge in clinical practice. Healthcare providers must tailor treatment based on each patient's unique circumstances. Different antiepileptic drugs can be used, including oxcarbazepine. Several studies show this drug's efficacy and safety in brain tumor-related epilepsy. METHODS: Observational, prospective study, monitoring the efficacy and safety of the drug oxcarbazepine in the prevention of epileptic seizures, included adult patients of both sexes with a supratentorial tumor and a risk of epileptic seizures after neurosurgery. RESULTS: The study included 153 hospitalized patients. The percentages of amplified waves, sharp waves, and spike waves decreased in the second and third compared with the first visit. Significantly lower percentages of sharp waves ( P = 0.028) on the second compared with the first measurement and spike waves ( P = 0.002) on the third compared with the first measurement were determined. Deterioration from normal to low hemoglobin concentration was observed in 40 (26%) patients at the second visit and 17 (12%) at the third visit, compared with the first visit. However, mean corpuscular volume, mean corpuscular hemoglobin, and mean corpuscular hemoglobin concentration values did not change significantly during the 6 months of follow-up. A transient drop in the number of thrombocytes was observed on the second visit. Adverse reactions to the drug were mild. Therapeutic adherence was low, as measured by the Morisky Medication Adherence Scale (MMAS-4). CONCLUSIONS: The drug oxcarbazepine has shown good efficacy and safety in the prevention of epileptic attacks after neurosurgery in patients with supratentorial tumors. Additional education of patients on the importance of taking regular therapy is crucial.
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Anticonvulsivantes , Carbamazepina , Epilepsia , Convulsiones , Neoplasias Supratentoriales , Humanos , Femenino , Oxcarbazepina/uso terapéutico , Masculino , Persona de Mediana Edad , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/efectos adversos , Estudios Prospectivos , Neoplasias Supratentoriales/complicaciones , Neoplasias Supratentoriales/cirugía , Adulto , Carbamazepina/análogos & derivados , Carbamazepina/uso terapéutico , Carbamazepina/efectos adversos , Anciano , Epilepsia/etiología , Epilepsia/prevención & control , Resultado del Tratamiento , Convulsiones/prevención & control , Convulsiones/etiología , Adulto JovenRESUMEN
This column presents the case example of a patient who was prescribed 3 different brand name drugs, all of which contain bupropion, which has a dose-dependent seizure risk. This case illustrates how such prescribing can result in a patient exceeding the recommended maximum daily dose of bupropion and having a seizure. This column also explains why prescribers should advise their patients to get their prescriptions filled by the same pharmacy or pharmacy chain.
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Antidepresivos de Segunda Generación , Bupropión , Medicamentos Genéricos , Convulsiones , Humanos , Antidepresivos de Segunda Generación/efectos adversos , Bupropión/efectos adversos , Bupropión/administración & dosificación , Medicamentos Genéricos/efectos adversos , Convulsiones/inducido químicamente , Convulsiones/prevención & controlRESUMEN
BACKGROUND: Seizures are common in patients with brain tumors, impacting daily life and healthcare burden. In contemporary neuro-oncology practice, levetiracetam is the most commonly prescribed anti-seizure medication (ASM). Although the practice is widely variable, levetiracetam is usually used for 2-3 years following surgery to prevent further seizures. However, the incidence of seizures post antitumoral treatment is relatively low, and the duration of use is not well defined. To address this knowledge gap, the current randomized controlled non-inferiority trial will be conducted comparing a shorter regimen of levetiracetam with the standard long-term schedule. METHODS AND ANALYSIS: Patients with newly diagnosed primary brain tumors (brain metastasis excluded) in the supratentorial compartment with a prior history of seizure will be eligible for the study. Adults (> 18 years), within 1 year from surgery, and controlled on levetiracetam monotherapy for 6 months will be randomized in a 1:1 ratio to either standard arm (long course: additional 2 years levetiracetam) or experimental arm (short course: tapered of levetiracetam and stopped). Stratification factors include tumor location, seizure type, histology, grade, and adjuvant therapy. The primary endpoint is 2-year seizure-free survival (SFS); secondary endpoints include seizure impact, quality of life, progression-free survival (PFS), and overall survival (OS). Assuming a 2-year SFS rate of 80%, a total of 431 patients (167 events) will be needed to prove the non-inferiority of the experimental arm (non-inferiority margin of 8%, α = 0.05, power = 80%). Considering an attrition rate of 40% (25% accounting for death and 15% lost to follow-up), the final sample size is 604. DISCUSSION: The trial will provide level 1 evidence on the optimal duration of ASM use in primary brain tumors with a history of seizures. If short-term ASM use is non-inferior, it will reduce drug utilization, lower neurotoxicity, improve quality of life, and optimize resource usage. ETHICS AND DISSEMINATION: The trial has been approved by the Institutional Ethics Committee of Tata Memorial Centre, Mumbai. REGISTRATION: Registered with CTRI/2024/06/069498, Clinicaltrials.gov: NCT06442748.
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Anticonvulsivantes , Neoplasias Encefálicas , Levetiracetam , Convulsiones , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Anticonvulsivantes/administración & dosificación , Anticonvulsivantes/uso terapéutico , Anticonvulsivantes/efectos adversos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/complicaciones , Ensayos Clínicos Fase III como Asunto , Esquema de Medicación , Levetiracetam/administración & dosificación , Levetiracetam/efectos adversos , Levetiracetam/uso terapéutico , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Convulsiones/etiología , Convulsiones/prevención & control , Convulsiones/tratamiento farmacológico , Estudios de Equivalencia como AsuntoRESUMEN
INTRODUCTION AND OBJECTIVE: Epilepsy is one of the most common chronic brain disorders worldwide. This study aimed to determine the effect of Galbanic acid on seizures. MATERIALS AND METHODS: In this study, 40 NMRI mice were used and divided into 4 groups. The control group received 10 mg/kg normal saline. Three groups received Galbanic acid at doses of 10, 20, and 40 mg/kg. The positive control group received diazepam with a dose of 10 mg/kg. All injections were made intraperitoneally for one week. Seizures were induced in all mice by injection of 90 mg/kg Pentylenetetrazole (PTZ). Then the latency of seizure onset in each of the experimental groups was recorded. After anesthesia with Ketamine 100 mg/kg and Xylazine 10 mg/kg, blood samples were taken and after decapitation, the hippocampus was isolated and the expression of αTNF-, IL1ß, and TLR4 genes in this region was measured. RESULTS: Galbanic acid increased the delay in seizure onset, decreased brain and serum nitrite levels, and decreased the expression of αTNF-, IL1ß, and TLR4 genes in brain tissue compared to the control group (P < 0.01, p < 0.001). CONCLUSION: Galbanic acid reduced nitrite and the expression of αTNF-, IL1ß, and TLR4, leading to a decrease in neuroinflammation and, as a result, a delay in seizure onset in mice.
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Anticonvulsivantes , Epilepsia , Hipocampo , Interleucina-1beta , Nitritos , Convulsiones , Receptor Toll-Like 4 , Factor de Necrosis Tumoral alfa , Animales , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-1beta/biosíntesis , Ratones , Convulsiones/metabolismo , Convulsiones/tratamiento farmacológico , Convulsiones/inducido químicamente , Convulsiones/prevención & control , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/biosíntesis , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/biosíntesis , Masculino , Nitritos/metabolismo , Epilepsia/tratamiento farmacológico , Epilepsia/metabolismo , Anticonvulsivantes/farmacología , Anticonvulsivantes/uso terapéutico , PentilenotetrazolRESUMEN
This study examined the prevalence, risk factors, and prognosis of epilepsy in patients with primary central nervous system lymphoma (PCNSL) and explored the necessity of prophylactic antiepileptic treatment in this population. In this retrospective, observational, single-center study, we analyzed clinical data from PCNSL patients who were diagnosed at our institution between January 2018 and April 2023. The cohort comprised 214 patients with PCNSL (with a median age of 62 years), of which 128 (47.6%) patients were male. Epilepsy was observed in 16.82% (36/214) of the patients, with 9.35% (20/214) presenting with seizures as the initial symptom. Cortical involvement was significantly associated with seizures (OR = 9.512, 95% CI 3.870-23.381; p = 0.036). Other potential risk factors included an edema zone > 1 cm around the lesion and PIM1 wild-type status. Antiepileptic drugs (AEDs) neither reduced seizure incidence (8.11% with AEDs vs. 8.43% with no AEDs, p = 0.970) nor improved PFS (HR = 0.613, 95% CI 0.338-1.109; p = 0.106). Therefore, AEDs should not be used as preventive measures in this population.
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Anticonvulsivantes , Neoplasias del Sistema Nervioso Central , Epilepsia , Linfoma , Convulsiones , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anticonvulsivantes/uso terapéutico , Neoplasias del Sistema Nervioso Central/complicaciones , Neoplasias del Sistema Nervioso Central/mortalidad , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Convulsiones/prevención & control , Convulsiones/tratamiento farmacológico , Convulsiones/etiología , Anciano , Estudios Retrospectivos , Adulto , Linfoma/complicaciones , Linfoma/mortalidad , Pronóstico , Factores de Riesgo , Anciano de 80 o más Años , Epilepsia/tratamiento farmacológico , Epilepsia/etiologíaRESUMEN
BACKGROUND: Pentylenetetrazole (PTZ) is a commonly used chemical to induce epileptic seizures in experimental animals. AIM: To investigate the neuroprotective effects of erucic acid against PTZ-induced seizures in mice and explore its underlying mechanisms. METHODOLOGY: The mice were randomly allocated into four groups: normal control, PTZ-treated (35â mg/kg via intraperitoneal injection), and PTZ + erucic acid (at doses of 10 and 20â mg/kg). Various parameters were assessed, including the percentage of animals experiencing convulsions, latency to death, percentage of deaths, levels of neurotransmitters, pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1 beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), nuclear factor kappa B (NF-κB), oxidative stress marker malondialdehyde (MDA), antioxidant enzymes catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), and caspase-3. The docking analysis was performed using AutoDock Vina software. RESULTS: Erucic acid markedly reduced the severity and frequency of PTZ-induced seizures, significantly decreased mortality rates, and restored altered neurotransmitter levels in mice. It alleviated oxidative stress by increasing the activity of antioxidant enzymes and reducing malondialdehyde (MDA) levels. Additionally, erucic acid mitigated neuroinflammation by downregulating pro-inflammatory cytokine production and inhibiting NF-κB activation. Molecular docking studies demonstrated that erucic acid exhibited strong binding affinities toward key molecular targets, including GABA (-4.546), NF-κB (-5.982), and caspase-3 (-5.22), suggesting its potential as a neuroprotective agent. CONCLUSION: Erucic acid may be an effective natural compound in PTZ-induced seizures in mice by restoring neurotransmitters, oxidative stress and neuroinflammatory mediators. It could prove to be a better alternative in the treatment of epilepsy.
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Fármacos Neuroprotectores , Neurotransmisores , Estrés Oxidativo , Convulsiones , Animales , Pentilenotetrazol , Estrés Oxidativo/efectos de los fármacos , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Convulsiones/metabolismo , Convulsiones/prevención & control , Ratones , Neurotransmisores/metabolismo , Masculino , Fármacos Neuroprotectores/farmacología , Simulación del Acoplamiento Molecular , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Biomarcadores/sangre , Citocinas/metabolismo , Simulación por ComputadorRESUMEN
Patients with seizure-induced shoulder instability endure significant hardship before ultimately undergoing surgical stabilization. These patients often present with significant bony lesions, causing recurring and frequent dislocations, not necessarily occurring during a seizure. Despite the increased surgical risks in this population, surgery-whether a bony procedure such as the Latarjet or, less commonly, a soft-tissue procedure-can result in positive outcomes. Surgery should be postponed until adequate seizure control is achieved, as seizures in the immediate postoperative period could be catastrophic.
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Epilepsia , Inestabilidad de la Articulación , Convulsiones , Luxación del Hombro , Articulación del Hombro , Humanos , Inestabilidad de la Articulación/cirugía , Inestabilidad de la Articulación/etiología , Inestabilidad de la Articulación/complicaciones , Luxación del Hombro/cirugía , Luxación del Hombro/etiología , Epilepsia/complicaciones , Epilepsia/tratamiento farmacológico , Convulsiones/prevención & control , Convulsiones/complicaciones , Articulación del Hombro/cirugíaRESUMEN
The potential therapeutic value of cynarin, a phenolic compound derived from artichoke, in treating epilepsy has not yet been reported. The present study evaluated the effects of cynarin on a kainic acid (KA)-induced seizure rat model and its potential mechanism. Cynarin was administered through oral gavage at a dosage of 10 mg kg-1 daily for 7 days before the induction of seizures with KA (15 mg kg-1) via intraperitoneal injection. The results showed that pretreatment with cynarin effectively attenuated the KA-induced seizure score and electroencephalogram (EEG) changes and prevented neuronal loss and glial cell activation in the hippocampi of KA-treated rats. In addition, pretreatment with cynarin dramatically prevented the aberrant levels of high mobility group box 1 (HMGB1), toll-like receptor-4 (TLR4), p-IκB, p65-NFκB, interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) induced by KA administration in hippocampal tissues. Additionally, KA substantially increased hippocampal glutamate levels and decreased cerebral blood flow, which were significantly alleviated by pretreatment with cynarin. The observed effects of cynarin were comparable to those of the antiepileptic drug carbamazepine (CBZ). Furthermore, there was no significant difference in the serum AST, ALT, creatinine, or bilirubin levels between the cynarin-treated rats and the control rats. Cynarin has a neuroprotective effect on a rat model of seizures induced by KA, reducing seizures, gliosis, inflammatory cytokines, and glutamate elevation and increasing cerebral blood flow. Thus, cynarin has therapeutic potential for preventing epilepsy.
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Cumarinas , Neuronas , Fármacos Neuroprotectores , Convulsiones , Animales , Ácido Kaínico/efectos adversos , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Convulsiones/prevención & control , Masculino , Ratas , Neuronas/efectos de los fármacos , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Fármacos Neuroprotectores/administración & dosificación , Cumarinas/administración & dosificación , Muerte Celular/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Anticonvulsivantes , Proteína HMGB1/metabolismo , Proteína HMGB1/genética , Interleucina-6/genética , Interleucina-6/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/genética , FN-kappa B/metabolismo , FN-kappa B/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismoRESUMEN
BACKGROUND: Busulfan at high doses has been associated with a risk of seizures. Phenytoin has been used traditionally as anti-seizure prophylaxis, and benzodiazepines and levetiracetam have been introduced more recently, providing data from retrospective series. The main purpose of this study was to evaluate the effectiveness of oral clonazepam as anti-seizure prophylaxis in adult patients receiving high doses of intravenous busulfan as part of the conditioning regimen for hematopoietic stem cell transplantation. The secondary objectives were to determine the feasibility of this regimen and to analyze the adverse events associated with the use of clonazepam. METHODS: This prospective, single-center study included 64 adult patients who received conditioning regimens with high doses of intravenous busulfan and anti-seizure prophylaxis with oral clonazepam, at a dose of 1 mg/8 h, from 12 h before starting treatment with busulfan until 48 h after ending administration. RESULTS: The effectiveness of the prophylaxis was 100%, with no episodes of seizures during busulfan treatment or in the 72 h afterwards. Treatment was feasible, and oral scheduled administration was completed in all patients. Adverse events that could be associated with clonazepam included the onset of somnolence, dizziness, and confusion, mostly mild. CONCLUSION: The oral clonazepam regimen described in this study has been prospectively shown to be an effective, feasible anti-seizure prophylaxis option with manageable toxicity.