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Medical Journal, Armed Forces India 2023Classic Toxic Epidermal Necrolysis (TEN) in Lupus Erythematosus (LE) is rare and that caused by oxcarbazepine is even rarer. It can be triggered/induced by various...
Classic Toxic Epidermal Necrolysis (TEN) in Lupus Erythematosus (LE) is rare and that caused by oxcarbazepine is even rarer. It can be triggered/induced by various insults, the most prominent being drugs. Herein, we describe a young female, a diagnosed case of LE with lupus nephritis, with recent-onset central nervous system vasculitis (incidentally detected on neuroimaging while she was being evaluated for a recent-onset behavioural change), who within a month of exposure to the drug developed an extensive exfoliating skin rash with mucosal lesions, which on histopathological evaluation showed TEN in LE, triggered by Oxcarbazepine, which was commenced for seizure prophylaxis. She was managed with pulse methylprednisolone, followed by intravenous immunoglobulin (IVIg), after which she made a satisfactory recovery. It is highlighted that TEN in LE patterns must be recognized in an emergency and Acute Syndrome of Apoptotic Panepidermolysis (ASAP) concept applied promptly without awaiting diagnoses. Further, many common drugs possibly trigger this pathology making the rara-avis not rare anymore!
PubMed: 37193523
DOI: 10.1016/j.mjafi.2021.04.018 -
Seizure Jul 2023Levetiracetam (LEV) is widely used in the clinical monotherapy or multi-drug combination treatment of seizures due to its good tolerability and efficacy. Due to a lack...
BACKGROUND
Levetiracetam (LEV) is widely used in the clinical monotherapy or multi-drug combination treatment of seizures due to its good tolerability and efficacy. Due to a lack of large-scale clinical studies, the relationship between levetiracetam concentrations, disease activity and adverse is unclear, limiting the usefulness of therapeutic drug monitoring (TDM) based LEV plasma levels. This study was intended to investigate factors influencing the pharmacokinetics of and the appropriate reference range of LEV concentration using available LEV TDM data.
METHODS
A rapid, accurate and sensitive high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS) method was established to determine LEV plasma concentrations. In this study, the levetiracetam plasma concentration monitoring data from 352 samples (taken from 248 patients) were used to explore the relationship between levetiracetam dose, age, combined administration with other antiseizure medications in patients with epilepsy.
RESULTS
Age and combined administration emerged as important affecting factors for the correlation of LEV concentration and dose. The correlation between concentration and dose was better in monotherapy. Combined administration may affect LEV concentration, especially when LEV is combined with oxcarbazepine, which might decrease the LEV concentration.
CONCLUSION
These findings emphasize the need to monitor LEV routinely LEV, especially among children and older adults when other antiseizure comedications are prescribed in the treatment regimen. LEV TDM is a well-established tool for the management of patients with epilepsy.
Topics: Humans; Anticonvulsants; Drug Monitoring; East Asian People; Epilepsy; Levetiracetam; Reference Values
PubMed: 37192596
DOI: 10.1016/j.seizure.2023.05.010 -
Cells Apr 2023Patients diagnosed with isocitrate dehydrogenase mutant (IDH) gliomas suffer frequently from seizures. Although the clinical course is less aggressive than that of its...
Patients diagnosed with isocitrate dehydrogenase mutant (IDH) gliomas suffer frequently from seizures. Although the clinical course is less aggressive than that of its IDH wildtype counterpart, recent discoveries have shown that epileptic activity can promote tumor proliferation. However, it is not known if antiepileptic drugs confer additional value by inhibiting tumor growth. In this study, the antineoplastic properties of 20 FDA-approved antiepileptic drugs (AEDs) were tested in six patient-derived IDH glioma stem-like cells (GSCs). Cell proliferation was assessed using the CellTiterGlo-3D assay. Two of the screened drugs (oxcarbazepine and perampanel) demonstrated an antiproliferative effect. A subsequent eight-point dose-response curve proved the dose-dependent growth inhibition for both drugs, but only oxcarbazepine reached an IC value below 100 µM in 5/6 GSCs (mean 44.7 µM; range 17.4-98.0 µM), approximating the possible c for oxcarbazepine in patient serums. Furthermore, the treated GSC spheroids were 82% smaller (mean volume 1.6 nL vs. 8.7 nL; = 0.01 (live/dead fluorescence staining)), and the apoptotic events increased by more than 50% (caspase-3/7 activity; = 0.006). Taken together, this drug screen of a large series of antiepileptic drugs identified oxcarbazepine as a potent proapoptotic drug in IDH GSCs, which combines antiepileptic and antineoplastic properties to treat this seizure-prone patient population.
Topics: Humans; Anticonvulsants; Oxcarbazepine; Isocitrate Dehydrogenase; Brain Neoplasms; Glioma
PubMed: 37190109
DOI: 10.3390/cells12081200 -
Ear and HearingTypewriter tinnitus refers to a special kind of staccato tinnitus, which is mostly described by patients as Morse code, popcorn, or machine-gun. It has been accepted...
INTRODUCTION
Typewriter tinnitus refers to a special kind of staccato tinnitus, which is mostly described by patients as Morse code, popcorn, or machine-gun. It has been accepted that the mechanism of typewriter tinnitus is caused by the neurovascular compression of the cochleovestibular nerve. Patients who suffered from typewriter tinnitus have exhibited a good response to carbamazepine or oxcarbazepine, but there is a risk of recurrence after treatment cessation. The present study aims to determine the value of auditory brainstem response (ABR) in diagnosing typewriter tinnitus and predicting relapse after drug withdrawal.
METHODS
Patients who presented with typewriter tinnitus from March 2019 to March 2022 were included for the present retrospective study. The auditory and vestibular test results and drug treatment effects were collected and analyzed. Patients with idiopathic unilateral subjective tinnitus, who were matched by age to patients with typewriter tinnitus at a ratio of 2:1, were consecutively recruited for the control group.
RESULTS
Eighteen patients with typewriter tinnitus and 38 controls were included. Ears with typewriter tinnitus had longer interpeak latency (IPL) I-III, and wave III and V latencies, and a higher ratio of IPL I-III ≥2.3 ms based on ABR, when compared to the unaffected side and controls ( p <0.05). Seventeen patients with typewriter tinnitus responded positively to medication. Among these patients, seven patients had a relapse after drug cessation, while 10 patients did not have a relapse. The relapse group had significantly longer IPL I-III and wave V latency, older age, and poorer hearing, when compared to the nonrelapse group ( p < 0.05). Furthermore, IPL I-III had the largest area under the receiver operating characteristic curve, and the optimal cutoff was 2.4 ms (sensitivity, 100.0%; specificity, 66.7%). There were no significant differences in other demography or other clinical test results between the relapse and nonrelapse groups ( p > 0.05). Ramsay Hunt syndrome and neuromyelitis optica spectrum disorders were identified in two cases.
CONCLUSION
Prolonged IPL I-III based on ABR can help in the diagnosis of typewriter tinnitus and its prognosis after treatment cessation. Patients with IPL I-III greater than 2.4 ms, older age and poorer hearing are more likely to relapse. In addition to the neurovascular conflict of the cochleovestibular nerve, the etiologies of neuroinflammation and demyelinating diseases are also possible for typewriter tinnitus.
Topics: Humans; Tinnitus; Retrospective Studies; Prognosis; Evoked Potentials, Auditory, Brain Stem; Recurrence
PubMed: 37171375
DOI: 10.1097/AUD.0000000000001382 -
Frontiers in Molecular Neuroscience 2023We admitted a female patient with infantile onset epilepsy (<3-month-old). The use of oxcarbazepine exacerbated epileptic seizures in the patient. In the present study,...
OBJECTIVE
We admitted a female patient with infantile onset epilepsy (<3-month-old). The use of oxcarbazepine exacerbated epileptic seizures in the patient. In the present study, we aimed to identify the genetic basis of the infantile onset epilepsy in the patient, and determine the correlations among genotype, phenotype, and clinical drug response.
METHODS
We described the clinical characteristics of an infant with refractory epilepsy. Whole exome sequencing (WES) was used to screen for the pathogenic variant. Whole-cell patch-clamp was performed to determine functional outcomes of the variant.
RESULTS
WES identified a novel variant (c.468 G > C, p.K156N) in the patient. In comparison with wildtype, electrophysiology revealed that -K156N variant in transfected cells demonstrated reduced sodium current density, delayed activation and accelerated inactivation process of Na channel, all of which suggested a loss-of-function (LOF) of Na1.2 channel.
CONCLUSION
We showed the importance of functional analysis for a variant with unknown significance to determine pathogenicity, drug reactions, and genotype-phenotype correlations. For patients suffering from early infantile epilepsies, the use of oxcarbazepine in some -related epilepsies requires vigilance to assess the possibility of epilepsy worsening.
PubMed: 37152433
DOI: 10.3389/fnmol.2023.1159649 -
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 -
JAMA Neurology Jun 2023Prenatal antiseizure medication (ASM) exposure has been associated with adverse early neurodevelopment, but associations with a wider range of psychiatric end points...
IMPORTANCE
Prenatal antiseizure medication (ASM) exposure has been associated with adverse early neurodevelopment, but associations with a wider range of psychiatric end points have not been studied.
OBJECTIVE
To examine the association between prenatal exposure to ASM with a spectrum of psychiatric disorders in childhood and adolescence in children of mothers with epilepsy.
DESIGN, SETTING, AND PARTICIPANTS
This prospective, population-based register study assessed 4 546 605 singleton children born alive in Denmark, Finland, Iceland, Norway, and Sweden from January 1, 1996, to December 31, 2017. Of the 4 546 605 children, 54 953 with chromosomal disorders or uncertain birth characteristics were excluded, and 38 661 children of mothers with epilepsy were identified. Data analysis was performed from August 2021 to January 2023.
EXPOSURES
Prenatal exposure to ASM was defined as maternal prescription fills from 30 days before the first day of the last menstrual period until birth.
MAIN OUTCOMES AND MEASURES
The main outcome measure was diagnosis of psychiatric disorders (a combined end point and 13 individual disorders). Estimated adjusted hazard ratios (aHRs) using Cox proportional hazards regression and cumulative incidences with 95% CIs are reported.
RESULTS
Among the 38 661 children of mothers with epilepsy (16 458 [42.6%] exposed to ASM; 19 582 [51.3%] male; mean [SD] age at the end of study, 7.5 [4.6] years), prenatal valproate exposure was associated with an increased risk of the combined psychiatric end point (aHR, 1.80 [95% CI, 1.60-2.03]; cumulative risk at 18 years in ASM-exposed children, 42.1% [95% CI, 38.2%-45.8%]; cumulative risk at 18 years in unexposed children, 31.3% [95% CI, 28.9%-33.6%]), which was driven mainly by disorders within the neurodevelopmental spectrum. Prenatal exposure to lamotrigine, carbamazepine, and oxcarbazepine was not associated with an increased risk of psychiatric disorders, whereas associations were found for prenatal exposure to topiramate with attention-deficit/hyperactivity disorder (aHR, 2.38; 95% CI, 1.40-4.06) and exposure to levetiracetam with anxiety (aHR, 2.17; 95% CI, 1.26-3.72) and attention-deficit/hyperactivity disorder (aHR, 1.78; 95% CI, 1.03-3.07).
CONCLUSIONS AND RELEVANCE
Findings from this explorative study strengthen the evidence for the warning against the use of valproate in pregnancy and raise concern of risks of specific psychiatric disorders associated with topiramate and levetiracetam. This study provides reassuring evidence that lamotrigine, carbamazepine, and oxcarbazepine are not associated with long-term behavioral or developmental disorders but cannot rule out risks with higher doses.
Topics: Pregnancy; Child; Female; Male; Adolescent; Humans; Child, Preschool; Valproic Acid; Lamotrigine; Incidence; Levetiracetam; Topiramate; Prenatal Exposure Delayed Effects; Prospective Studies; Anticonvulsants; Epilepsy; Oxcarbazepine; Carbamazepine; Attention Deficit Disorder with Hyperactivity
PubMed: 37067807
DOI: 10.1001/jamaneurol.2023.0674 -
Headache Apr 2023First-line treatment for trigeminal neuralgia (TN) is limited to carbamazepine and oxcarbazepine, and in refractory cases, alternatives are scarce. Lacosamide has been...
BACKGROUND AND OBJECTIVES
First-line treatment for trigeminal neuralgia (TN) is limited to carbamazepine and oxcarbazepine, and in refractory cases, alternatives are scarce. Lacosamide has been suggested as a valid option. In this study, we describe a series of patients who received oral lacosamide as treatment for TN after first-line drug failure.
METHODS
In this retrospective descriptive cohort study, we included patients with refractory TN who attended a tertiary center between 2015 and 2021 and were prescribed oral lacosamide after first-line treatment failure. The primary endpoints were pain relief and adverse effects. We secondarily analyzed clinical outcomes and compared responders versus nonresponders in the search for potential predictors of response.
RESULTS
Eighty-six patients were included (mean age: 62 [SD 15.6] years; 54/86 [63%] female). The TN etiology was secondary in 16/86 (19%) patients. Concomitant continuous pain was present in 29/86 (34%) patients. The mean number of previous treatments was 2.7 [SD 1.5]. Pain relief was achieved in 57/86 (66%) cases, with 28/86 (33%) patients presenting adverse effects, all of which were mild. No statistically significant differences were observed between responders and nonresponders, but subtle clinical differences suggested potential predictors of response.
CONCLUSION
Lacosamide may be an effective and relatively safe treatment for refractory pain in TN patients after first-line treatment failure.
Topics: Humans; Female; Middle Aged; Male; Trigeminal Neuralgia; Retrospective Studies; Lacosamide; Cohort Studies; Treatment Outcome; Pain
PubMed: 37036126
DOI: 10.1111/head.14505 -
Cephalalgia : An International Journal... May 2023Acute trigeminal neuralgia exacerbation is a common reason for frequent emergency department visits, that often occurs while waiting for surgery, but evidence on...
INTRODUCTION
Acute trigeminal neuralgia exacerbation is a common reason for frequent emergency department visits, that often occurs while waiting for surgery, but evidence on effective drugs for acute trigeminal neuralgia is scant. Whether lidocaine aerosol could be a rescue option for the treatment of acute trigeminal neuralgia exacerbations is worth exploring. Positive predictors of the analgesic effects of lidocaine aerosol also warrant further investigation.
METHODS
This is a retrospective study with a total of 152 patients. We analyzed the efficacy of lidocaine aerosol for the treatment of acute trigeminal neuralgia exacerbations. A positive response was considered a decrease in the VAS score of at least 50% at 30 min of treatment. Multivariable logistic analyses were performed to identify predictive factors for lidocaine aerosol response.
RESULTS
In the group of 109 responders, the VAS score decreased from 8.3 ± 1.1 cm to 0.8 ± 1.0 cm at 15 min, and 1.7 ± 1.0 cm at 30 min. The effective rate at 15 min and 30 min were 77.6% and 70.4%, respectively. Multivariate logistic analyses showed the treatment may provide better clinical outcomes in V2 trigeminal neuralgia (OR 0.01, 95%Cl 0.001-0.15, p < 0.001), V3 trigeminal neuralgia (OR 0.02, 95%Cl 0.001-0.16, p = 0.001), and V2 + V3 trigeminal neuralgia (OR 0.01, 95%Cl 0.001-0.13, p < 0.001), patients who were taking carbamazepine or oxcarbazepine with a maximum dose (OR 6.15, 95%Cl 2.11-17.93, p = 0.001) were less likely to experience immediate pain relief.
CONCLUSION
Lidocaine aerosol sprayed on oral and/or nasal mucosa is beneficial for immediate pain relief in patients with acute trigeminal neuralgia exacerbations. It is expected to become a promising treatment option for patients with V2 and/or V3 trigeminal neuralgia.
Topics: Humans; Trigeminal Neuralgia; Lidocaine; Retrospective Studies; Aerosols; Nasal Mucosa; Pain; Treatment Outcome
PubMed: 37032614
DOI: 10.1177/03331024231168086 -
Epilepsia Open Sep 2023To investigate the antiseizure medication (ASM) doses required to achieve seizure freedom and their correlation with the World Health Organization's defined daily doses...
OBJECTIVES
To investigate the antiseizure medication (ASM) doses required to achieve seizure freedom and their correlation with the World Health Organization's defined daily doses (DDDs) in patients aged 16 years or older with newly diagnosed epilepsy.
METHODS
The study included 459 patients with a validated diagnosis of new-onset epilepsy. Patient records were retrospectively analyzed to determine the ASM doses in patients with or without seizure freedom during follow-up. The DDD of the relevant ASM was then retrieved.
RESULTS
The seizure-freedom rate with first and subsequent ASMs was 88% (404/459 patients) during the follow-up. The mean prescribed doses (PDDs) and PDD/DDD ratio of the most commonly used ASMs, ie, oxcarbazepine (OXC), carbamazepine (CBZ), and valproic acid (VPA), differed significantly between seizure-free and non-seizure-free status (992 mg and 0.99 vs 1132 mg and 1.13; 547 mg and 0.55 vs 659 mg and 0.66; and 953 mg and 0.64 vs 1260 mg and 0.84, respectively). The effect of the OXC dose as the first failed ASM on the possibility of achieving seizure freedom was significant (Fisher's exact test, p = 0.002). Thirty-four of 43 patients (79%) in which an OXC dose of ≤900 mg failed became seizure-free, as compared with 24 of 54 patients (44%) with a failed OXC dose >900 mg.
SIGNIFICANCE
The present study provides new insights into the doses of the commonly used ASMs such as OXC, CBZ, and VPA that can lead to seizure freedom as monotherapy or as combination therapy. The higher PDD/DDD ratio of OXC (0.99) than that of CBZ or VPA renders a generalized PDD/DDD comparison highly problematic.
Topics: Humans; Anticonvulsants; Retrospective Studies; Epilepsy; Oxcarbazepine; Carbamazepine; Valproic Acid; Benzodiazepines; Freedom
PubMed: 37010264
DOI: 10.1002/epi4.12737