Antiepileptic Drug Withdrawal Research Articles

Factors influencing withdrawal of anti-epileptic drugs and management of recurrent seizure: A systematic review

Factors influencing withdrawal of anti-epileptic drugs and management of recurrent seizure: A systematic review

Predictors of Seizure Recurrence after Antiepileptic Drugs Withdrawal: A prospective study in Zagazig University Hospitals

Predictors of Seizure Recurrence after Antiepileptic Drugs Withdrawal: A prospective study in Zagazig University Hospitals

Predictors for seizure relapse in children with epilepsy after antiepileptic drug withdrawal: case-control study

Background Epilepsy is defined as a neurologic condition caused by a pathological brain condition. Epilepsy patients who have stopped treatment and are seizure-free for two years are considered to have achieved complete remission. Relapse occurs when seizures return after anti-epileptic drug (AED) withdrawal. Several studies reported that frequent seizures, prolonged duration to control seizures, number of AEDs consumed, and abnormal electroencephalography (EEG) found during AEDs tapered, were reported as predictors of relapse. Methods This retrospective, case-control study was carried out from 2012 – 2016 using multisite medical record evaluation, followed by interviews and EEG examinations. The case group included children with epilepsy who had seizure relapse, while the control group included children with complete remission of epilepsy. Bivariate and multivariate analyses were performed to identify predictors of relapse. Results Relapse predictors in bivariate analysis were symptomatic etiology epilepsy (OR 5.000; 95%CI 2.345 to 10.660; P<0.001), time to seizure control ?1 year (OR 3.689; 95%CI 1.493 to 9.116; P=0.003), and worsened EEG evolution at pre-withdrawal compared to EEG at the time of diagnosis (OR 2.310; 95%CI 1.132 to 4.717; P=0.021). Statistically significant relapse predictors in multivariate analysis were symptomatic etiology epilepsy (OR 4.384; 95%CI 1.985 to 9.681; P<0.001) and slow (?1 year) time to seizure control (OR 4.355; 95%CI 1.753 to 10.817; P 0.002). Conclusion Symptomatic etiology epilepsy and time to seizure control ?1 year are independent predictive factors for seizure relapse in children with epilepsy. Therefore, children with these conditions require a longer period and careful, gradual dose reduction before antiepileptic drugs withdrawal.

Postoperative interictal epileptiform discharges predict seizure recurrence after antiepileptic drug withdrawal regardless of concordance with surgical site

ObjectiveThe study aimed to explore the association between the site of interictal epileptic discharges (IEDs) on postoperative electroencephalogram (EEG) and seizure recurrence after antiepileptic drug (AED) withdrawal. The study hypothesizes...

Spontaneous fast-ultradian dynamics of polymorphic interictal events in drug-resistant focal epilepsy.

We studied the rate dynamics of interictal events occurring over fast-ultradian time scales, as commonly examined in clinics to guide surgical planning in epilepsy. Stereo-electroencephalography (SEEG) traces of 35 patients with good surgical outcome (Engel I) were analyzed. For this we developed a general data mining method aimed at clustering the plethora of transient waveform shapes including interictal epileptiform discharges (IEDs) and assessed the temporal fluctuations in the capability of mapping the epileptogenic zone (EZ) of each type of event. We found that the fast-ultradian dynamics of the IED rate may effectively impair the precision of EZ identification, and appear to occur spontaneously, that is, not triggered by or exclusively associated with a particular cognitive task, wakefulness, sleep, seizure occurrence, post-ictal state, or antiepileptic drug withdrawal. Propagation of IEDs from the EZ to the propagation zone (PZ) could explain the observed fast-ultradian fluctuations in a reduced fraction of the analyzed patients, suggesting that other factors like the excitability of the epileptogenic tissue could play a more relevant role. A novel link was found between the fast-ultradian dynamics of the overall rate of polymorphic events and the rate of specific IEDs subtypes. We exploited this feature to estimate in each patient the 5 min interictal epoch for near-optimal EZ and resected-zone (RZ) localization. This approach produces at the population level a better EZ/RZ classification when compared to both (1) the whole time series available in each patient (p = .084 for EZ, p < .001 for RZ, Wilcoxon signed-rank test) and (2) 5 min epochs sampled randomly from the interictal recordings of each patient (p < .05 for EZ, p < .001 for RZ, 105 random samplings). Our results highlight the relevance of the fast-ultradian IED dynamics in mapping the EZ, and show how this dynamics can be estimated prospectively to inform surgical planning in epilepsy.

Stroke-like presentation of acute toxic leukoencephalopathy due to capecitabine treatment with extensive intramyelinic edema.

Stroke-like presentation of acute toxic leukoencephalopathy due to capecitabine treatment with extensive intramyelinic edema.

Amino acid metabolism characteristics of Banxia Baizhu Tianma Decoction in realizing drug withdrawal based on transcriptomic analysis

This study aimed to demonstrate the effect of Banxia Baizhu Tianma Decoction(BBTD) on realizing withdrawal of anti-epileptic drugs and explore the relationship between BBTD and the amino acid metabolism by transcriptomic analysis in the rat model of epilepsy induced by lithium chloride-pilocarpine. The rats with epilepsy were divided into a control group(Ctrl), an epilepsy group(Ep), a BBTD &amp; antiepileptic drug integrative group(BADIG), and an antiepileptic drug withdrawal group(ADWG). The Ctrl and Ep were given ultrapure water by gavage for 12 weeks. The BADIG was given BBTD extract and carbamazepine solution by gavage for 12 weeks. The ADWG was given carbamazepine solution and BBTD extract by gavage for the former 6 weeks, and then only given BBTD extract for the latter 6 weeks. The therapeutic effect was evaluated by behavioral observation, electroencephalogram(EEG), and hippocampal neuronal morphological changes. High-throughput sequencing was used to obtain amino acid metabolism-related differen-tial genes in the hippocampus, and the mRNA expression in the hippocampus of each group was verified by real-time quantitative polymerase chain reaction(RT-qPCR). The hub genes were screened out through protein-protein interaction(PPI) network, and Gene Ontology(GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis were performed. Two ceRNA networks, namely circRNA-miRNA-mRNA and lncRNA-miRNA-mRNA, were constructed for ADWG vs BADIG. The experimental results showed that compared with those in Ep, rats in ADWG were significantly improved in the behavioral observation, EEG, and hippocampal neuronal impairment. Thirty-four amino acid metabolism-related differential genes were obtained by transcriptomic analysis, and the sequencing results were confirmed by RT-qPCR. Eight hub genes were obtained through PPI network, involving several biological processes, molecular functions, and signal pathways related to amino acid metabolism. Finally, the circRNA-miRNA-mRNA ternary transcription network of 17 circRNA, 5 miRNA, and 2 mRNA, and a lncRNA-miRNA-mRNA ternary network of 10 lncRNA, 5 miRNA, and 2 mRNA were constructed in ADWG vs BADIG. In conclusion, BBTD can effectively achieve the withdrawal of antiepileptic drugs, which may be related to the transcriptomic regulation of amino acid metabolism.

Evaluation of Nonconvulsive Status Epilepticus and Nonconvulsive Seizures in a Pediatric Intensive Care Unit.

We aimed to identify nonconvulsive seizures (NCS) and nonconvulsive status epilepticus (NCSE) in a pediatric intensive care unit (PICU). A prospective cohort study on 35 patients who underwent continuous electroencephalographic monitoring in the PICU was done. The patients were evaluated to collect data of their demographics, clinical diagnoses, clinical seizures by electroencephalography, and neuroimaging findings. One case with NCSE and 4 cases with NCS were diagnosed among the 35 patients. The etiology of the patient with NCSE showed antiepileptic drug (AED) withdrawal. The etiology of the patients with NCS included electrical injury, head trauma, subarachnoid hemorrhage, and pneumonia. The findings suggest that younger age, epilepsy, acute structural brain abnormalities, abrupt cessation of AED, and clinically overt seizures before NCSE/NCS are associated with significant risk for NCS/NCSE. In addition, the electrical injury may also be considered as a risk factor for electrographic seizure though such a case has not yet been reported.

Relapse After Drug Withdrawal in Patients with Epilepsy After Two Years of Seizure-Free: A Cohort Study.

Antiepileptic drugs are the first choice of treatment for patients with epilepsy. However, the withdrawal of antiepileptic drugs after seizure-free remains a significant focus for the majority of patients with epilepsy and their families. In this study, we evaluated the risk factors associated with relapse after drug withdrawal in patients with seizure free for 2 years. We aimed to guide patients in seizure-free to assess the risk of drug withdrawal. Through screening, 452 patients with epilepsy were included in the study.Patients were followed up for at least 2 years or more. Analyzed their clinical data by applying the χ2-test, Kaplan-Meier survival analysis and multivariate Cox regression analysis. 423 patients completed follow-up, of which 304 cases recurred (71.9%).Related recurrence factors include age of onset, type of seizure, number of AEDs, seizure-free time before withdrawal, and electroencephalogram (EEG) results before drug withdrawal (P<0.05). The results of correlation analysis showed that age of onset, seizure frequency, seizure type, number of AEDs, the period from AEDs treatment to a seizure-free status, EEG results before drug withdrawal, and pre-medication course, were all significantly related to the recurrence of seizures after drug reduction and withdrawal (P<0.05). We identified a range of independent risk factors, including onset age, seizure frequency, Multiple AEDs and the period from AEDs treatment to a seizure-free status. The overall recurrence rate of epilepsy in our patient cohort was high, and the peak recurrence period was within one-year of drug withdrawal. Patients with partial seizures, a short seizure-free time before withdrawal, severe EEG abnormalities before drug reduction, and a long course of the disease, are prone to relapse. Patients with an older age at onset and a high frequency of attack, those taking multi-drug combination therapy, and those that take a long time to gain control, should be managed carefully to AEDs withdrawal.

Лекарственно-индуцированная красная волчанка

This article presents a clinical case in which a patient observed by neurologists with a diagnosis of neuropathy and treated with anticonvulsants and antidepressants developed new clinical manifestations and laboratory changes characteristic of systemic lupus erythematosus. A clinical version emerged that the neurological changes were the disease onset, followed by the development of the remaining clinical and laboratory symptoms (the diagnosis fully met the 2019 EULAR criteria — a score of 16 points, 10 points are sufficient to make a diagnosis). However, after a very short and low-dose therapy with methylprednisolone and hydroxychloroquine and withdrawal of anticonvulsants, there was a rapid recovery of specific antibodies and improvement of clinical symptoms, which allowed assuming drug-induced lupus erythematosus in this patient. Currently, the list of drugs that can cause this problem includes more than 100 drugs.

Ketogenic diet therapy in children with epilepsy caused by SLC2A1 mutations: a single-center single-arm retrospective study.

This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency syndrome. Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome sequencing. We analyzed the patients' convulsions and treatment with antiepileptic drugs. The patients were followed up at different time periods after ketogenic diet therapies. Six patients with SLC2A1 mutations were included in this study. The patients had seizures of different types and frequencies, and they took antiepileptic drugs to relieve their symptoms. They were then treated with a ketogenic diet for at least four months. We analyzed epilepsy control rates at 1, 2, 3, 6, and 12months after ketogenic diet treatment. All patients were seizure-free within a month of receiving the diet therapy. All patients were followed up for six months, three were followed up for 12months after the treatment, and there was no recurrence of epilepsy during this period. After antiepileptic drug withdrawal, none of the patients experienced seizure relapse when receiving ketogenic diet treatment alone. No severe adverse events occurred during the therapy. Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 mutations. Therefore, patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.

CYTOTOXIC LESIONS OF THE CORPUS CALLOSUM: MAGNETIC RESONANCE IMAGING FINDINGS AND ETIOLOGIC FACTORS

Objective: Cytotoxic lesions of the corpus callosum (CLOCCs) are usually detected as a diffusion restriction in the splenium of the corpus callosum. They are rare secondary radiological findings associated with various clinical entities. The aim of this study is to evaluate the magnetic resonance imaging (MRI) findings and underlying clinical factors of cases with CLOCCs. Materials and Methods: The MRI images of 850 patients who were admitted to the emergency services between January 2017 and March 2021 with encephalopathy and epilepsy-like neurological complaints were scanned retrospectively. Twenty nine patients (20 men, 9 women) with CLOCCs were included in the study. Their radiological and clinical findings were evaluated. Results: The mean age was calculated as 26.4 years (5-72 years). The patients had neurological symptoms such as dysarthria, confusion, ataxia, syncope, epileptic seizure, and headache. Lesions were developed secondary to various infections in 20 (68.9%) patients. Diabetic decompensation was found in three patients and uremic decompensation in one patient. In the remaining patients, subarachnoid hemorrhage, asthma attack, trauma, high-dose lithium-levetiracetam intake and anti-epileptic drug withdrawal were responsible. Twenty patients had MRI control. In 16 (80%) patients, MRI findings returned to normal between 6 days and 8 months (median 30, Mean 53.8 days). One of the other 4 patients had partial regression, and 3 patients recovered with sequelae gliosis. Conclusion: CLOCCs are nonspecific MRI findings associated with a broad underlying clinical spectrum. They are usually reversible. Determination of the underlying clinical etiology, avoidance of an ischemic stroke and tumor-like misdiagnoses are important for appropriate patient management.

Establishing the worth of deprescribing inappropriate medications: are we there yet?

Establishing the worth of deprescribing inappropriate medications: are we there yet?

A review on interventions for psychogenic nonepileptic seizures: which treatments improve outcome?

Introduction Psychogenic nonepileptic seizures (PNES), the most common conversion disorder, are episodic alterations in behaviour that resemble epileptic seizures without its characteristic EEG changes. PNES presumably reflect a physical manifestation of underlying psychological distress and can be as disabling as epilepsy. Standardized treatment approaches for PNES care are lacking.ObjectivesOur aim is to review the literature for therapeutic interventions in PNES.MethodsA literature search was conducted in PubMed/MEDLINE database for randomized controlled trials (RCTs) examining the effect(s) of specific intervention(s) in patients with PNES. Search terms were “psychogenic-nonepileptic-seizures” and selection was based on the abstracts of all the studies retrieved. Priority outcome was frequency of PNES.ResultsWe identified 8 eligible RCTs. Samples ranged from 19 to 82 patients. Follow-up periods varied from 6 weeks to 18 months. Regarding reduction of PNES frequency, several interventions were effective: motivational interviewing combined with psychotherapy; cognitive behavioural therapy informed psychotherapy (CBT-ip); combination of CBT-ip and sertraline; immediate withdrawal of antiepileptic drugs after PNES diagnosis; a standardized diagnostic approach associated with psychiatric inpatient consultation. Treatment with sertraline alone and brief educational interventions didn’t reduce PNES frequency significantly. Beside PNES rate reduction, most interventions conveyed some type of benefit such as improvement in quality of life, mood or functionality.ConclusionsThe majority of the beneficial interventions included a structured communicational approach and/or psychotherapeutic treatment. Our analysis highlights the importance of a multidisciplinary strategy that includes psychotherapy. Further studies with larger samples and longer follow-up periods are needed to robustly inform evidence-based treatment for PNES.DisclosureNo significant relationships.

Abnormal electroencephalogram (EEG) after drug withdrawal is a risk factor for epilepsy recurrence in children: a systematic review and meta-analysis.

BackgroundThe relationship between abnormal electroencephalogram (EEG) and epilepsy recurrence after antiepileptic drug (AED) withdrawal has been controversial. We aimed to explore the relationship between abnormal EEG after AED withdrawal and the risk of epilepsy recurrence in children.MethodsLiterature retrieval was performed using the PubMed, EMBASE, Medline, CENTRAL, and China National Knowledge Infrastructure (CNKI) databases. Included literatures were subjects of pediatric epilepsy patients who discontinued medication. The recurrence rate of epilepsy in patients with normal and abnormal EEG after AED withdrawal was observed. The Newcastle-Ottawa scale (NOS) was used to evaluate the quality of literatures. The Chi-square test was used to test heterogeneity. If heterogeneity between the articles existed, a random-effects model was used; otherwise, fixed-effects models were used. Subgroup analysis was used to explore the causes of heterogeneity. The odds ratio (OR) and 95% confidence interval (CI) were calculated using the Mantel-Haenszel statistical method. OR was not adjusted for other factors.ResultsA total of 843 articles were retrieved. Nine studies were included, with a total of 1,663 patients, including 1,299 patients with normal EEG and 364 patients with abnormal EEG. Compared with the normal EEG patients, the OR of recurrence rate after AEDs withdrawal was 3.02 (P=0.0003), with heterogeneity (P<0.0001). The funnel plot indicated that there was no publication bias among the studies. The not partial seizure group analysis showed OR =1.70 (P=0.003) and no heterogeneity (P=0.70) in patients with abnormal EEG compared to those with normal EEG. In the partial seizures subgroup, the OR of the recurrence rate after AED withdrawal was 8.08 (P<0.00001) compared with the normal EEG patients, and there was no heterogeneity (P=0.29). The funnel chart shows that the partial seizures type subgroup analysis revealed positive results, while the not partial seizure group analysis reported negative results, indicating publication bias.ConclusionsThe risk of epilepsy recurrence is higher in children with abnormal EEG after AED withdrawal, regardless of seizure type. For pediatric epilepsy patients with abnormal EEG after AED withdrawal, a more cautious discontinuation regimen, closer follow-up and monitoring are required.

Reappraisal of the Medical Research Council Antiepileptic Drug Withdrawal Study: Contamination-adjusted and dose-response re-analysis.

ObjectiveThe 1991 Medical Research Council (MRC) Study compared seizure relapse for seizure‐free patients randomized to withdraw vs continue of antiseizure medications (ASMs). We re‐analyzed this trial to account for crossover between arms using contamination‐adjusted intention to treat (CA ITT) methods, to explore dose‐response curves, and to validate predictions against external data. ITT assesses the effect of being randomized to withdraw, as‐treated analysis assesses the confounded effect of withdrawing, but CA ITT assesses the unconfounded effect of actually withdrawing.MethodsCA ITT involves two stages. First, we used randomized arm to predict whether patients withdrew their ASM (logistic) or total daily ASM dose (linear). Second, we used those values to predict seizure occurrence (logistic).ResultsThe trial randomized 503 patients to withdraw and 501 patients to continue ASMs. We found that 316 of 376 patients (88%) who were randomized to withdraw decreased their dose at every pre‐seizure visit, compared with 35 of 424 (8%) who were randomized to continue (p < .01). Adjusted odds ratios of a 2‐year seizure for those who withdrew vs those who did not was 1.3 (95% confidence interval [CI] 0.9–1.9) in the as‐treated analysis, 2.5 (95% CI 1.9–3.4) comparing those randomized to withdraw vs continue for ITT, and 3.1 (95% CI 2.1–4.5) for CA ITT. Probabilities (withdrawal vs continue) were 28% vs 24% (as‐treated), 40% vs 22% (ITT), and 43% vs 21% (CA ITT). Differences between ITT and CA ITT were greater when varying the predictor (reaching zero ASMs) or outcome (1‐year seizures). As‐treated dose‐response curves demonstrated little to no effects, but larger effects in CA ITT analysis. MRC data overpredicted risk in Lossius data, with moderate discrimination (areas under the curve ~0.70).SignificanceCA ITT results (the effect of actually withdrawing ASMs on seizures) were slightly greater than ITT effects (the effect of recommend withdrawing ASMs on seizures). How these findings affect clinical practice must be individualized.

Withdrawal of Antiepileptic Drugs After MRI–Guided Laser Interstitial Thermal Therapy in Extra-Temporal Lobe Epilepsy (P8-8.005)

Withdrawal of Antiepileptic Drugs After MRI–Guided Laser Interstitial Thermal Therapy in Extra-Temporal Lobe Epilepsy (P8-8.005)

Prediction of seizure recurrence using electroencephalogram analysis with multiscale deep neural networks before withdrawal of antiepileptic drugs.

The decision to continue or discontinue antiepileptic drug (AED) treatment in patients who are seizure free for a prolonged time is critical. Studies have used certain risk factors or electroencephalogram (EEG) findings to predict seizure recurrence after the withdrawal of AEDs. However, applicable biomarkers to guide the withdrawal of AEDs are lacking. In this study, we used EEG analysis based on multiscale deep neural networks (MSDNN) to establish a method for predicting seizure recurrence after the withdrawal of AEDs. A total of 60 patients with epilepsy were divided into two groups (30 in the recurrence group and 30 in the non-recurrence group). All patients were seizure free for at least 2 years. Before AED withdrawal, an EEG was performed for each patient, which showed no epileptiform discharges. These EEG recordings were classified using MSDNN. We found that the performance indices of classification between recurrence and non-recurrence groups had a mean sensitivity, mean specificity, mean accuracy, and mean area under the receiver operating characteristic curve of 74.23%, 75.83%, 74.66%, and 82.66%, respectively. Our proposed method is a promising tool to help physicians to predict seizure recurrence after AED withdrawal among seizure-free patients.

Preoperative antiepileptic drug prophylaxis for early postoperative seizures in supratentorial meningioma: a single-center experience.

Perioperative antiepileptic drug (AED) prophylaxis for early postoperative seizures (EPSs) in patients with supratentorial meningiomas without preoperative seizures is controversial. This paper discusses the incidence, risk factors, control rate and AED withdrawal indications of EPS in patients undergoing supratentorial convexity and parasagittal/falx meningioma resection without preoperative seizures. Patients treated for a histologically confirmed supratentorial convexity and parasagittal/falx meningioma at the authors' institution between 2015 and 2021 were retrospectively examined. Clinical and imaging data were assessed. Variates were analyzed using univariate and multivariate regression analyses. A PubMed review of the literature published between 2011 and 2021 was performed. In total, 517 patients met the selection criteria. EPS (within the first postoperative week) was observed in 30/517 cases (5.8%). Multivariate analysis revealed that surgical/medical complications (OR 16.33, 95% CI 7.07-37.7, P < 0.001) were the only independent predictors of EPS. The dose of valproic was increased and levetiracetam was added based on the frequency of seizures (≤ 2, > 2 times and status epilepticus). EPS control rates were 94.1% (16/17) and 92.3% (12/13), respectively. AEDs were discontinued at 2weeks and 4-6weeks, respectively. The authors identified 10 relevant studies in the literature. Based on their review of the literature, the incidence of EPS was 3.7% (47/1282) with AED use and 6.2% (95/1525) without AED use patients in supratentorial meningiomas without preoperative seizures. The incidence of EPS was 9.0% (19/209) in patients without AED use with convexity and parasagittal/falx meningiomas without preoperative seizures. AED prophylaxis can reduce the incidence of EPS in patients with convexity and parasagittal/falx meningiomas without preoperative seizures. Avoiding postoperative complications is an important means to prevent EPS. Combined medication has a significant effect on controlling repeated EPS. The timing of AED withdrawal was evaluated according to the clinical symptoms and imaging findings.

The Outcome of Status Epilepticus Among Adults in Aseer Region of Saudi Arabia

IntroductionEpileptic seizure episodes can vary from brief and nearly undetectable to long periods of vigorous shaking. These episodes can result in physical injuries, occasionally including broken bones. With epilepsy, seizures tend to recur and, as a rule, have no immediate underlying cause. Status epilepticus (SE) is an attack of a seizure lasting for more than five minutes or two or more seizures without the person returning to normal between the attacks. Previous definitions used a 30-minute time limit. This study aimed to assess the clinical outcome of SE among adult patients in the Aseer region.Materials and methodsA retrospective record-based cohort study design was conducted, targeting all accessible medical files of adult patients with SE who were admitted to the Aseer central hospital and military hospital from 2010 to 2017. Data were extracted from all complete and accessible files. Records with missing data were excluded. Clinical outcomes for the cases included were assessed and categorized into cases of complete recovery (without sequelae), cases with incomplete recovery, and death.ResultsThe study included 19 adult patients with SE whose ages ranged from seven to 87 years with a mean age of 33.4 ± 22.5 years. Men made up 63.2% of the cases. Infection was the most recorded risk factor among the cases, followed by anti-epileptic drug withdrawal. Only two cases recovered with sequelae, while the remaining 17 cases recovered completely. There were no deaths.ConclusionsThe study revealed that nearly all cases recovered completely with no complications, particularly men who immediately received IV treatment. Early diagnosis and receiving treatment under careful observation via follow-up are recommended.