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Neurology May 2024Levetiracetam is a widely used antiseizure medication. Recent concerns have been raised regarding the potential prolongation of the QT interval by levetiracetam and...
BACKGROUND AND OBJECTIVES
Levetiracetam is a widely used antiseizure medication. Recent concerns have been raised regarding the potential prolongation of the QT interval by levetiracetam and increased risk of sudden cardiac death. This could have profound implications for patient safety and for prescribing practice. This study assessed the potential association of levetiracetam with cardiac outcomes related to QT interval prolongation. We compared outcomes of patients taking levetiracetam with those taking oxcarbazepine as a comparator medication that has not been associated with prolongation of the QT interval.
METHODS
The sample included patients who were newly prescribed levetiracetam or oxcarbazepine from January 31, 2010, to December 31, 2019, using administrative claims data from the OptumLabs Data Warehouse (OLDW). The analysis focused on a combined endpoint of sudden cardiac death or ventricular arrythmia, which are both linked to QT interval prolongation. We used a new user design and selected oxcarbazepine as an active comparator with levetiracetam to minimize bias. We used propensity score weighting to balance the levetiracetam and oxcarbazepine cohorts and then performed weighted Cox regressions to evaluate the association of levetiracetam with the combined endpoint.
RESULTS
We identified 104,655 enrollees taking levetiracetam and 39,596 enrollees taking oxcarbazepine. At baseline, enrollees taking levetiracetam were older, more likely to have diagnosed epilepsy, and more likely to have diagnosed comorbidities including hypertension, cerebrovascular disease, and coronary artery disease. In the main analysis, we found no significant difference between levetiracetam and oxcarbazepine in the rate of the combined endpoint for the Cox proportional hazards model (hazard ratio [HR] 0.79, 95% CI 0.42-1.47) or Cox regression with time-varying characteristics (HR 0.78, 95% CI 0.41-1.50).
DISCUSSION
When compared with oxcarbazepine, levetiracetam does not correlate with increased risk of ventricular arrythmia and sudden cardiac death. Our finding does not support the concern for cardiac risk to indicate restriction of levetiracetam use nor the requirement of cardiac monitoring when using it.
CLASSIFICATION OF EVIDENCE
This study provides Class II evidence that sudden cardiac death and ventricular arrythmia are not more frequent in patients older than 17 years newly prescribed levetiracetam, compared with those prescribed oxcarbazepine.
Topics: Humans; Levetiracetam; Oxcarbazepine; Anticonvulsants; Death, Sudden, Cardiac; Arrhythmias, Cardiac
PubMed: 38560823
DOI: 10.1212/WNL.0000000000209177 -
Cephalalgia : An International Journal... Feb 2024Short-lasting unilateral neuralgiform headache attacks (SUNHA) have the features of both short-lasting unilateral neuralgiform pain, such as trigeminal neuralgia or... (Review)
Review
BACKGROUND
Short-lasting unilateral neuralgiform headache attacks (SUNHA) have the features of both short-lasting unilateral neuralgiform pain, such as trigeminal neuralgia or stabbing headache, and associated trigeminal autonomic symptoms, such as paroxysmal hemicrania or cluster headache. Recognizing and adequately treating SUNHA is essential but current treatment methods are ineffective in treating SUNHA.
METHODS
We reviewed the changes in the concept of short-lasting unilateral neuralgiform headache attacks and provide a narrative review of the current medical and surgical treatment options, from the first choice of treatment for patients to treatments for selective intractable cases.
RESULTS
Unlike the initial impression of an intractable primary headache disorder affecting older men, SUNHA affects both sexes throughout their lifespan. One striking feature of SUNHA is that the attacks are triggered by cutaneous or intraoral stimulation. The efficacy of conventional treatments is disappointing and challenging, and preventive therapy is the mainstay of treatment because of highly frequent attacks of a very brief duration. Amongst them, lamotrigine is effective in approximately two-third of the patients with SUNHA, and intravenous lidocaine is essential for the management of acute exacerbation of intractable pain. Topiramate, oxcarbazepine and gabapentin are considered good secondary options for SUNHA, and botulinum toxin can be used in selective cases. Neurovascular compression is commonly observed in SUNHA, and surgical approaches, such as neurovascular compression, have been reported to be effective for intractable cases.
CONCLUSIONS
Recent advances in the understanding of SUNHA have improved the recognition and treatment approaches for this unique condition.
Topics: Male; Female; Humans; Aged; SUNCT Syndrome; Headache; Anticonvulsants; Gabapentin; Lamotrigine; Neuralgia; Trigeminal Autonomic Cephalalgias
PubMed: 38415675
DOI: 10.1177/03331024241232256 -
Epilepsy Research Nov 2023The neonatal and infantile period is the age group with the highest incidence of epilepsy, in which gene variants in sodium and potassium channels are an important...
OBJECTIVE
The neonatal and infantile period is the age group with the highest incidence of epilepsy, in which gene variants in sodium and potassium channels are an important etiology, so the sodium channel blocker class of antiseizure medications may be effective in the treatment of early onset epilepsy. This study aimed to summarize the efficacy and tolerability of oxcarbazepine (OXC) in the treatment of focal epilepsy in neonates and infants under 3 months of age.
METHODS
A retrospective analysis of children with focal epilepsy onset within 3 months of age and treated with OXC in a tertiary pediatric epilepsy center in China was conducted. The efficacy, tolerability and influencing factors of OXC were evaluated.
RESULTS
A total of 50 patients were enrolled, with a median age of epilepsy onset of 11.5 (2, 42) days. There were 32 cases of early infantile developmental and epileptic encephalopathy, 10 cases of self-limited neonatal or neonatal-infantile epilepsy, and 8 cases of focal epilepsy that could not be classified as epileptic syndrome. The median age of application of OXC was 47 (31, 66) days. The median follow-up time was 16.5 (10, 25) months, with 7 deaths. Thirty-eight cases (76.0 %) were effective with OXC treatment, including 28 cases (56.0 %) achieved seizure freedom. Of the 34 cases whose pathogenesis involved genetic factors, 19 cases with sodium/ potassium channel gene variants had higher effective and seizure-free rates than those with other gene variants. The most common adverse event was transient hyponatremia. 2 cases had rash and 2 cases had abnormal electrocardiogram, 3 of which discontinued OXC.
SIGNIFICANCE
This single-center retrospective study suggests that OXC is effective and tolerable for the treatment of focal epilepsy in neonates and infants under 3 months of age. The efficacy of OXC is better in patients with sodium/ potassium channel gene variants.
Topics: Child; Infant, Newborn; Humans; Infant; Oxcarbazepine; Retrospective Studies; Anticonvulsants; Carbamazepine; Epilepsies, Partial; Epilepsy; Sodium; Potassium Channels
PubMed: 37852019
DOI: 10.1016/j.eplepsyres.2023.107240 -
Pediatric Neurology Jul 2023Knowledge on antiseizure medication (ASM) use and retention for children with epilepsy is limited, partly because of extensive off-label use of newer drugs with limited...
BACKGROUND
Knowledge on antiseizure medication (ASM) use and retention for children with epilepsy is limited, partly because of extensive off-label use of newer drugs with limited registration. We used prescription data to study prescription patterns on a population-wide scale and compared the proportion of patients remaining on monotherapy of ASMs with and without formal indication for different age groups.
METHODS
A total of 14,681 individuals aged <18 years were included, using cross-referenced Swedish registers from 2007 to 2020. Kaplan-Meier retention rates were calculated for all ASMs. The most common pathways of the first three medications per patient were analyzed.
RESULTS
In children older than one month and up to age one year, monotherapy retention rates were the highest for oxcarbazepine, valproic acid, and carbamazepine. Among children aged one to five years, oxcarbazepine and levetiracetam were among ASMs that do not have a monotherapy indication in Sweden but still had high retention rates. In the age group five to 12 years, lamotrigine and oxcarbazepine had the highest retention rate. In males aged 12 to 18 years, valproic acid was the most common choice followed by lamotrigine, whereas lamotrigine was the first choice of ASM for females, exceeding the second and third most common options levetiracetam and oxcarbazepine by a factor of two and three, respectively.
CONCLUSION
Off-label medication is common in children with epilepsy but does not seem to be associated with lower retention. The restrictions regarding valproic acid for females of childbearing age seem to have been well implemented in Swedish neuropediatric care.
Topics: Male; Female; Humans; Child; Infant; Child, Preschool; Lamotrigine; Oxcarbazepine; Levetiracetam; Sweden; Valproic Acid; Triazines; Epilepsy; Anticonvulsants
PubMed: 37116405
DOI: 10.1016/j.pediatrneurol.2023.03.016 -
European Journal of Clinical... Oct 2023Topiramate, a broad-spectrum antiepileptic drug, exhibits substantial inter-individual variability in both its pharmacokinetics and therapeutic response. The aim of this...
OBJECTIVE
Topiramate, a broad-spectrum antiepileptic drug, exhibits substantial inter-individual variability in both its pharmacokinetics and therapeutic response. The aim of this study was to investigate the influence of patient characteristics and genetic variants on topiramate clearance using population pharmacokinetic (PPK) models in a cohort of Chinese pediatric patients with epilepsy.
METHOD
The PPK model was constructed using a nonlinear mixed-effects modeling approach, utilizing a dataset comprising 236 plasma concentrations of topiramate obtained from 181 pediatric patients with epilepsy. A one-compartment model combined with a proportional residual model was employed to characterize the pharmacokinetics of topiramate. Covariate analysis was performed using forward addition and backward elimination to assess the influence of covariates on the model parameters. The model was thoroughly evaluated through goodness-of-fit analysis, bootstrap, visual predictive checks, and normalized prediction distribution errors. Monte Carlo simulations were utilized to devise topiramate dosing strategies.
RESULT
In the final PPK models of topiramate, body weight, co-administration with oxcarbazepine, and a combined genotype of GKIR1-UGT (GRIK1 rs2832407, UGT2B7 rs7439366, and UGT1A1 rs4148324) were identified as significant covariates affecting the clearance (CL). The clearance was estimated using the formulas CL (L/h) = 0.44 × (BW⁄11.7) × e for the model without genetic variants and CL (L/h) = 0.49 × (BW⁄11.7) × e × e for the model incorporating genetic variants. The volume of distribution (Vd) was estimated using the formulas Vd (L) = 6.6 × (BW⁄11.7). The precision of all estimated parameters was acceptable. Furthermore, the model demonstrated good predictability, exhibiting stability and effectiveness in describing the pharmacokinetics of topiramate.
CONCLUSION
The clearance of topiramate in pediatric patients with epilepsy may be subject to the influence of factors such as body weight, co-administration with oxcarbazepine, and genetic polymorphism. In this study, PPK models were developed to better understand and account for these factors, thereby improving the precision and individualization of topiramate therapy in children with epilepsy.
Topics: Humans; Child; Topiramate; Oxcarbazepine; East Asian People; Epilepsy; Body Weight
PubMed: 37597080
DOI: 10.1007/s00228-023-03549-6 -
Frontiers in Neurology 2023No interventional study has been conducted in China to assess efficacy and safety of perampanel in treating Chinese patients with epilepsy, nor has there been any study...
BACKGROUND
No interventional study has been conducted in China to assess efficacy and safety of perampanel in treating Chinese patients with epilepsy, nor has there been any study on perampanel early add-on therapy in China. This interventional study aimed to assess efficacy and safety of perampanel as an early add-on treatment of focal-onset seizures (FOS) with or without focal-to-bilateral tonic-clonic seizures (FBTCS) in Chinese patients.
METHODS
In this multicenter, open-label, single-arm, phase 4 interventional study, Chinese patients ≥ 12 years old with FOS with or without FBTCS who failed anti-seizure medication (ASM) monotherapy from 15 hospitals in China were enrolled and treated with perampanel add-on therapy (8-week titration followed by 24-week maintenance). The primary endpoint was 50% responder rate. Secondary endpoints included seizure-freedom rate and changes in seizure frequency from baseline. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were recorded.
RESULTS
The full analysis set included 150 patients. The mean maintenance perampanel dose was 5.9 ± 1.5 mg/day and the 8-month retention rate was 72%. The 50% responder rate and seizure-freedom rate for all patients during maintenance were 67.9 and 30.5%, respectively. Patients with FBTCS had higher 50% responder rate (96.0%) and seizure-freedom rate (76.0%) during maintenance. Patients on concomitant sodium valproate had a significantly higher seizure-freedom rate than those on concomitant oxcarbazepine. Eight-six (55.1%) patients experienced treatment-related TEAEs, and the most common TEAEs were dizziness (36.5%), hypersomnia (11.5%), headache (3.9%), somnolence (3.2%), and irritability (3.2%). Withdrawal due to TEAEs occurred to 14.7% of the patients.
CONCLUSION
Perampanel early add-on was effective and safe in treating Chinese patients≥12 years old with FOS with or without FBTCS.www.chictr.org.cn, Identifier ChiCTR2000039510.
PubMed: 37712083
DOI: 10.3389/fneur.2023.1236046 -
Frontiers in Medicine 2023Stevens-Johnson syndrome (SJS) is considered a hypersensitivity syndrome affecting the skin and mucous membranes. It has been reported that an anticonvulsant drug,...
BACKGROUND
Stevens-Johnson syndrome (SJS) is considered a hypersensitivity syndrome affecting the skin and mucous membranes. It has been reported that an anticonvulsant drug, oxcarbazepine, may cause Stevens-Johnson syndrome and toxic epidermal necrolysis (TEN). However, the clinical features of oxcarbazepine-induced Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) remain ambiguous. This article aims to explore the clinical features of SJS/TEN.
METHODS
Systematic searches of several Chinese and English databases were conducted for case reports published on PubMed, EMBASE, Web of Science, MEDLINE, CNKI from January 1, 2007 to March 1, 2023.
RESULTS
A total of seventeen patients (10 males and 7 females) were included in this study, including nine adult patients and eight pediatric patients. The results showed that males seem to have a higher prevalence of SJS/TEN than females, and SJS/TEN usually occurs within 2 weeks after administration of oxcarbazepine (OXC). The main clinical manifestations among the included patients were rashes or maculopapules (17 cases, 100%), fever (11 cases, 64.7%), mucosal lesions (15 cases, 88.2%), conjunctivitis with/without ocular discharge (12 cases, 70.6%), and blisters (12 cases, 70.6%). After stopping OXC or switching to other drugs that treat primary disease as well as treatment with IVIG, glucocorticoid, anti-allergy, and fluid replacement, eight of the included patients recovered completely, and another eight of the included patients reported symptomatic improvement, while the prognosis of one of the included patients was not reported.
CONCLUSION
Diverse clinical signs and symptoms of SJS/TEN might result in misinterpretation and delayed diagnosis. It should be identified and treated immediately to avoid significant consequences and potentially jeopardize patients' lives.
PubMed: 37881633
DOI: 10.3389/fmed.2023.1232969 -
Therapeutic Advances in Neurological... 2024Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder, characterized by attacks of involuntary movements triggered by sudden action. Variants in...
BACKGROUND
Paroxysmal kinesigenic dyskinesia (PKD) is a rare neurological disorder, characterized by attacks of involuntary movements triggered by sudden action. Variants in proline-rich transmembrane protein 2 () are the most common genetic cause of PKD.
OBJECTIVE
The objective was to investigate the clinical and genetic characteristics of PKD and to establish genotype-phenotype correlations.
METHODS
We enrolled 219 PKD patients, documented their clinical information and performed screening using Sanger sequencing. Whole exome sequencing was performed on 49 PKD probands without variants. Genotype-phenotype correlation analyses were conducted on the probands.
RESULTS
Among 219 PKD patients (99 cases from 39 families and 120 sporadic cases), 16 variants were identified. Nine variants (c.879+4A>G, c.879+5G>A, c.856G>A, c.955G>T, c.884G>C, c.649C>T, c.649dupC, c.649delC and c.696_697delCA) were previously known, while seven were novel (c.367_403del, c.347_348delAA, c.835C>T, c.116dupC, c.837_838insC, c.916_937del and c.902G>A). The mean interval from onset to diagnosis was 7.94 years. Compared to patients without variants, patients with the variants were more likely to have a positive family history, an earlier age of onset and a higher prevalence of falls during pre-treatment attacks (27.14% 8.99%, respectively). Patients with truncated variants tend to have bilateral attacks. We identified two transmembrane protein 151A () variants including a novel variant (c.368G>C) and a reported variant (c.203C>T) in two PRRT2-negative probands with PKD.
CONCLUSION
These findings provide insights on the clinical characteristics, diagnostic timeline and treatment response of PKD patients. PKD patients with truncated variants may tend to have more severe paroxysmal symptoms. This study expands the spectrum of and variants. Carbamazepine and oxcarbazepine are both used as a first-line treatment choice for PKD patients.
PubMed: 38250317
DOI: 10.1177/17562864231224110 -
International Journal of Biological... Jun 2024A stable Madhuca indica oil-in-water nanoemulsion (99-210 nm, zeta potential: > - 30 mV) was produced employing Tween 20 (surfactant) and Transcutol P...
A stable Madhuca indica oil-in-water nanoemulsion (99-210 nm, zeta potential: > - 30 mV) was produced employing Tween 20 (surfactant) and Transcutol P (co-surfactant) (3:1). The nanoemulsion (oil: S = 3:7, 5:5, and 7:3) were subsequently incorporated into oxcarbazepine-loaded carboxymethylxanthan gum (DS = 1.23) dispersion. The hydrogel microspheres were formed using the ionic gelation process. Higher oil concentration had a considerable impact on particle size, drug entrapment efficiency, and buoyancy. The maximum 92 % drug entrapment efficiency was achieved with the microspheres having oil: S ratio 5:5. FESEM study revealed that the microspheres were spherical in shape and had an orange peel-like surface roughness. FTIR analysis revealed a hydrogen bonding interaction between drug and polymer. Thermal and x-ray examinations revealed the transformation of crystalline oxcarbazepine into an amorphous form. The microspheres had a buoyancy period of 7.5 h with corresponding release of around 83 % drug in 8 h in simulated stomach fluid, governed by supercase-II transport mechanism. In vivo neurobehavioral studies on PTZ-induced rats demonstrated that the microspheres outperformed drug suspension in terms of rotarod retention, number of crossings, and rearing activity in open field. Thus, Madhuca indica oil-in-water nanoemulsion-entrapped carboxymethyl xanthan gum microspheres appeared to be useful for monitoring oxcarbazepine release and managing epileptic seizures.
Topics: Microspheres; Animals; Rats; Mannans; Hydrogels; Particle Size; Epilepsy; Male; Drug Carriers; Emulsions; Seizures; Drug Liberation; Plant Oils; Anticonvulsants; Galactose
PubMed: 38825290
DOI: 10.1016/j.ijbiomac.2024.132739 -
Frontiers in Pediatrics 2024Levetiracetam (LEV) and oxcarbazepine (OXC) are new antiseizure medications (ASMs). In recent years, OXC monotherapy is widely used in children with epilepsy; however,...
BACKGROUND
Levetiracetam (LEV) and oxcarbazepine (OXC) are new antiseizure medications (ASMs). In recent years, OXC monotherapy is widely used in children with epilepsy; however, no consensus exists on applying LEV monotherapy among children with epilepsy.
OBJECTIVE
The present work focused on comparing the efficacy and safety of LEV and OXC monotherapy in treating children with epilepsy.
METHODS
We conducted a comprehensive search across multiple databases including PubMed, Cochrane Library, Embase, Web of Science, CNKI, Wanfang Database, VIP, and China Biology Medicine disc, covering studies from inception to August 26, 2023. We included randomized controlled trials (RCTs) and cohort studies evaluating the efficacy and safety of LEV and OXC monotherapy for treating epilepsy in children. We utilized Cochrane Risk of Bias Tool in RevMan 5.3 software for assessing included RCTs quality. In addition, included cohort studies quality was determined using Newcastle-Ottawa Scale (NOS). A random-effects model was utilized to summarize the results.
RESULTS
This meta-analysis included altogether 14 studies, including 893 children with epilepsy. LEV and OXC monotherapy was not statistical different among children with epilepsy in seizure-free rate (relative risk [RR] = 1.010, 95% confidence interval [CI] [0.822, 1.242], > 0.05) and seizure frequency decrease of ≥50% compared with baseline [RR = 0.938, 95% CI (0.676, 1.301), > 0.05]. Differences in total adverse reaction rate [RR = 1.113, 95% CI (0.710, 1.744), > 0.05] and failure rate because of serious adverse reaction [RR = 1.001, 95% CI (0.349, 2.871), > 0.05] were not statistical different between LEV and OXC treatments among children with epilepsy. However, the effects of OXC monotherapy on thyroid among children with epilepsy was statistically correlated than that of LEV (thyroid stimulating hormone: standardized mean difference [SMD] = -0.144, 95% CI [-0.613, 0.325], > 0.05; free thyroxine: SMD = 1.663, 95% CI [0.179, 3.147], < 0.05).
CONCLUSION
The efficacy of LEV and OXC monotherapy in treating children with epilepsy is similar. However, OXC having a more significant effect on the thyroid than that of LEV. Therefore, LEV may be safer for children with epilepsy who are predisposed to thyroid disease than OXC.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/, PROSPERO (CRD42024514016).
PubMed: 38711491
DOI: 10.3389/fped.2024.1336744