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Purpose: To delineate the characteristics of probable antibody-negative pediatric autoimmune encephalitis (probable Ab-negative AE), we compared the clinical features of probable Ab-negative AE to those of major antibody-positive AE. Methods: We retrospectively reviewed the clinical features of 18 patients with probable Ab-negative AE, 13 with anti-N-methyl-D-aspartate receptor encephalitis (NMDARE), and 13 with myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Clinical characteristics, neuroimaging findings, treatments, and outcomes were analyzed. Results: The age of onset and length of hospital stay were significantly higher in the NMDARE group than in the other groups (p = 0.02 and p < 0.01). Regarding initial neurological symptoms, acute symptomatic seizures in the probable Ab-negative AE group (67%) were significantly more frequent than in the NMDARE (15%) and MOGAD (23%) groups (p < 0.01). Paraclinical evidence of neuroinflammation within 1 month of disease onset revealed that single-photon emission computed tomography (SPECT) detected abnormal alterations in 14/14 (100%), cerebrospinal fluid (CSF) analysis in 15/18 (83%), and magnetic resonance imaging (MRI) in 11/18 (61%) in patients with probable Ab-negative AE. In the probable Ab-negative AE group, seven patients (39%) developed autoimmune-associated epilepsy, whereas one patient (8%) had both NMDARE and MOGAD (not statistically significant, p = 0.07). Conclusion: Patients with probable Ab-negative AE exhibited acute symptomatic seizures as initial neurological symptoms significantly more frequently. They developed autoimmune-associated epilepsy more frequently than those with NMDARE and MOGAD, which was not statistically significant. SPECT within 1 month of disease onset might be a valuable surrogate marker of ongoing neuroinflammation and neuronal dysfunction, even in patients with negative MRI findings.
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BACKGROUND: Febrile seizures are the most common type of convulsions affecting children aged six months to five years. However, febrile seizures can be difficult to identify due to the vague nature of the symptoms, which can lead to incorrect diagnosis and treatment. Thus, this study explores febrile seizure-related uncertainty, knowledge, and anxiety among mothers. DESIGN AND METHODS: A cross-sectional design included 190 Jordanian mothers, about half with children having febrile seizure history. Instruments included the State-Trait Anxiety Inventory (STAI), Parental Perception of Uncertainty Scale (PPUS), and Parental Knowledge, Attitudes, Concerns, and Practices (KACP). RESULTS: Mothers exhibited poor febrile seizure knowledge, with affected mothers significantly scoring higher than unaffected. Affected mothers had higher state and trait anxiety and uncertainty. Correlations showed uncertainty positively correlated with anxiety. Regression analysis showed that trait anxiety and knowledge predicted uncertainty in affected mothers, while only trait anxiety predicted uncertainty in unaffected mothers. CONCLUSION: Mothers, especially those with affected children, demonstrated low febrile seizure knowledge, high anxiety, and uncertainty. Lack of knowledge may contribute to ineffective febrile seizure management. The study identifies trait anxiety and knowledge as predictors of uncertainty, emphasizing the need for tailored interventions. PRACTICE IMPLICATIONS: Healthcare professionals can design interventions targeting febrile seizure education and anxiety reduction. Policymakers should focus on raising awareness and allocating resources for effective interventions, potentially improving children with febrile seizure outcomes. This study underscores the importance of addressing maternal knowledge gaps, anxiety, and uncertainty related to febrile seizures, suggesting the need for comprehensive educational programs and support strategies for mothers.
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Asynchronous distributed multielectrode stimulation (ADMES) is a novel approach to deep brain stimulation for medication resistant temporal lobe epilepsy that has shown promise in rodent and in vitro seizure models. To further evaluate its effects on a pre-clinical model, we characterized the effect of unilateral ADMES in an NHP model of temporal lobe seizures induced by intra-hippocampal injection of penicillin (PCN). Four non-human primates were used for this study in two contemporaneous cohorts. One cohort (n = 3 hemispheres) was implanted with the Medtronic RC + S stimulation (GIN cohort) and recording system connected to two 4-contact ring electrodes to evaluate three unilateral stimulation patterns: 7 Hz Ring ADMES, 20 Hz Dual Ring, and 125 Hz Dual Ring (analog of clinical stimulation). In an additional cohort (EPC cohort, n = 2), two 12-contact segmented electrodes were implanted in the right hippocampus and connected to an externalized recording and stimulation system to allow more flexibility in the stimulation pattern. In this second cohort, 4 variations of stimulation were evaluated (7 Hz Full ADMES, 7 Hz Ring ADMES, 31 Hz Wide Ring, and 31 Hz Dual Ring). In the GIN cohort, we found an increase in seizure frequency and time spent in seizure during the 7 Hz Ring ADMES stimulation compared to the respective post-stimulation. A similar post-stimulation effect was found in the EPC cohort. We also found an increase in seizure frequency during the 7Hz full ADMES compared to the respective post-stimulation. However, we did not find a difference between pre-stimulation and stimulation conditions suggesting a possible post stimulation effect of the 7Hz hippocampal stimulation. In conclusion, in the NHP PCN model of temporal lobe seizures, acute asynchronous hippocampal stimulation was not therapeutic, however, our findings related to the post-stimulation effect can support future studies using hippocampal stimulation for the treatment of temporal lobe epilepsy.
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BACKGROUND: Status epilepticus is a common and potentially life-threatening neurological emergency with a high risk for cognitive and neurobiological impairment. Our aim was to evaluate the neuroprotective effects of centrally administered irisin and acute exhausting exercise against oxidative brain injury and memory dysfunction due to a pentylenetetrazole (PTZ)-induced single seizure. Male Sprague Dawley rats with intracerebroventricular (icv) cannulas were randomly divided into intraperitoneally (ip) saline-injected control and PTZ-injected (45 mg/kg) seizure groups. Both the control and PTZ groups were then treated with irisin (7.5 µg/kg, 2 µl, icv), saline (2 µl, icv) or were forced to an acute bout of strenuous exercise before the ip injection of saline (control) or PTZ. Seizures were evaluated using the Racine score. To evaluate memory performance, a passive avoidance test was performed before and after PTZ injection. Following euthanasia at the 24th hour of seizure induction, brain tissues were removed for histopathological examination and for evaluating oxidative damage, antioxidant capacity, and neurotransmitter levels. RESULTS: Glutamate/GABA imbalance observed in PTZ rats was corrected by irisin administration (p < 0.001/p < 0.01), while irisin prevented the generation of reactive oxygen species and lipid peroxidation (p < 0.05 - 0.001) and replenished the antioxidant catalase and glutathione levels (p < 0.01-0.01) in the cerebral tissue, and reduced the histologically evident neuronal injury due to a single seizure (p < 0.05 - 0.01). Irisin also delayed the onset of seizures (p < 0.05) and improved memory dysfunction (p < 0.05), but did not affect the severity of seizures. The acute exhaustive swimming exercise completed before PTZ-seizure depressed glutamate level (p < 0.001), maintained the oxidant/antioxidant balance, alleviated neuronal injury (p < 0.05 - 0.01) and upregulated cerebral BDNF expression (p < 0.05). CONCLUSION: In conclusion, acute high-intensity exercise or exogenously administered irisin provides neuroprotection by maintaining the balance of excitatory/inhibitory neurotransmitters and oxidant/antioxidant systems.
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Fibronectinas , Trastornos de la Memoria , Pentilenotetrazol , Condicionamiento Físico Animal , Ratas Sprague-Dawley , Convulsiones , Animales , Masculino , Trastornos de la Memoria/etiología , Condicionamiento Físico Animal/fisiología , Condicionamiento Físico Animal/métodos , Fibronectinas/metabolismo , Fibronectinas/administración & dosificación , Ratas , Enfermedades Neuroinflamatorias , Epilepsia , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/administración & dosificación , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiologíaRESUMEN
Background: Gliomas, the most common primary brain tumors, pose surgical challenges in eloquent cortex regions due to potential deficits affecting patients' quality of life (QOL) and increased mortality risk. This study investigates motor and sensory recovery postresection of Rolandic cortex gliomas in 40 patients, alongside seizure outcomes and the efficacy of intraoperative techniques such as awake craniotomy. Methods: This was a 10-year monocentric retrospective study based on the experience of a neurosurgeon in the resection of Rolandic gliomas and its impact on 40 patients' QOL in a period from 2011 to 2020. The primary outcomes were tumor recurrence and the efficacy of the surgery defined as survival status, seizure status, and sensory and motor neurological deficits. Data collection included demographic, tumor, and surgical outcome variables. The extent of resection (EOR) was classified as gross total resection (GTR) (EOR ≥95%) or subtotal resection (EOR <95%). Statistical analysis involved descriptive statistics and inferential tests for outcome comparisons. Results: Patients were aged an average of 42.3 ± 14 years and distributed between 72.5% of males and 27.5% of females. The most common presentation was seizures (65%). The tumor was located in the frontal lobe at 65%, the motor at 75%, and the top tumor pathology was oligodendroglioma (42.5%). The recurrence rate in the study was 20% (8 of 40), and the 1-year survival rate was 92.5%. After the resection, significant improvement was shown in Karnofsky's performance status (P = 0.007), in normal daily activities (P = 0.001), in fine motor skills (P = 0.020), and work hobbies (P = 0.046). No statistically significant improvement was shown in seizures and deficit rates. Recurrence was not associated with the demographic characteristics, clinical presentation, tumor-related characteristics (location, area, side, and mutation), tumor resection, and adjuvant treatment (P > 0.05). Conclusion: GTR of Rolandic gliomas can be achieved with the use of meticulous stimulation mapping, and complete functional recovery is attainable despite common belief.
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The mesial temporal lobe epilepsy (MTLE) seizures are believed to originate from medial temporal structures, including the amygdala, hippocampus, and temporal cortex. Thus, the seizures onset zones (SOZs) of MTLE locate in these regions. However, whether the neural features of SOZs are specific to different medial temporal structures are still unclear and need more investigation. To address this question, the present study tracked the features of two different high frequency oscillations (HFOs) in the SOZs of these regions during MTLE seizures from 10 drug-resistant MTLE patients, who received the stereo electroencephalography (SEEG) electrodes implantation surgery in the medial temporal structures. Remarkable difference of HFOs features, including the proportions of HFOs contacts, percentages of HFOs contacts with significant coupling and firing rates of HFOs, could be observed in the SOZs among three medial temporal structures during seizures. Specifically, we found that the amygdala might contribute to the generation of MTLE seizures, while the hippocampus plays a critical role for the propagation of MTLE seizures. In addition, the HFOs firing rates in SOZ regions were significantly larger than those in NonSOZ regions, suggesting the potential biomarkers of HFOs for MTLE seizure. Moreover, there existed higher percentages of SOZs contacts in the HFOs contacts than in all SEEG contacts, especially those with significant coupling to slow oscillations, implying that specific HFOs features would help identify the SOZ regions. Taken together, our results displayed the features of HFOs in different medial temporal structures during MTLE seizures, and could deepen our understanding concerning the neural mechanism of MTLE.
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OBJECTIVE: To evaluate the long-term outcomes of subtotal hemispherotomy (SH) in treating drug-resistant epilepsy caused by unilateral hemispheric lesions and try to give the prognostic factors for these outcomes. METHODS: We retrospectively reviewed the clinical data of 19 patients who underwent SH in Sanbo Brain Hospital, Capital Medical University, Beijing, China, from May 2008 to April 2021. All clinical data and factors related to surgical and functional outcomes, including motor, neuropsychiatric, and language function, were collected and analyzed. RESULTS: The surgical outcomes showed 13 (68â¯%) patients were seizure-free at the last follow-up (2-14 years, mean: 5.6±2.9). No changes were found in motor outcomes in 12 (63â¯%) patients; seven (37â¯%) patients had new permanent motor deficits (NPMD). Improvement in the full-scale intelligence quotient (FIQ) (p = 0.009) was observed. Univariate analysis found that patients who did not achieve seizure freedom had a significantly older age at surgery (p = 0.017) and acute post-operative seizures (APOS) (p = 0.046). Kaplan-Meier analysis also identified significant differences in seizure outcomes between the children and adult subgroups (p = 0.0017). Multivariate Cox analysis showed that older age at surgery (HR=1.055, p = 0.034) was associated with shorter time-to-seizure-recurrence. Resection of the central operculum and insula (OR= 80.433, p =0.031) and higher monthly seizure frequency (OR= 1.073, p = 0.040) were also poor prognostic factors for motor function outcomes. CONCLUSION: SH is an effective treatment procedure in treating patients with drug-resistant epilepsy caused by hemispheric lesions with satisfied seizure outcomes, limited impairment of motor function, and preserving neuropsychiatric outcomes.
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The uncommon, benign dysembryoplastic neuroepithelial tumor (DNET, WHO grade 1) is frequently linked to epilepsy. It is a glioneuronal neoplasm in the cerebral cortex of children or young adults defined by the presence of a pathognomonic glioneuronal element that may be linked to glial nodules and activating mutations of fibroblast growth factor receptor 1 (FGFR1) (CNS WHO grade 1 according to WHO classification of CNS and pituitary tumors, 2021 ). The cerebral cortex is primarily affected. The most frequent areas are the temporal lobe, particularly the medial lobe, frontal lobe, and other cortex. This study reports the instance of a 31-year-old male who had a history of seizures for the past 20 years and complained of a sudden headache and vomiting at the hospital. MRI revealed a cortical-based lesion in the left posterior temporo-occipital region. A biopsy sample was sent for histopathological examination. DNETs are usually benign, non-recurring lesions and rarely can be a malignant transformation. Although they are frequently stable tumors, surgical excision seldom results in recurrence.
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This case report presents a 23-year-old male diagnosed with Charcot-Marie-Tooth (CMT) disease, who exhibited additional neurological symptoms suggestive of leukodystrophy. The patient experienced recurrent episodes of slurred speech, imbalance, and a recent tonic-clonic seizure, prompting admission. Neurological examination and imaging revealed bilateral white matter changes, raising suspicion of leukoencephalopathy. Further investigations confirmed a nonsense mutation c.64C>T (p.Arg22*) in the gap junction beta 1 (GJB1) gene. This case underscores the complexity of Charcot-Marie-Tooth disease type 1 (CMTX1) with atypical central nervous system (CNS) manifestations, highlighting the importance of comprehensive diagnostic evaluations and a multidisciplinary approach to management.
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Objective: This study aimed to examine differences in factors influencing quality of life (QOL) in people with extratemporal lobe epilepsy (ETLE) and mesial temporal lobe epilepsy (MTLE). Methods: We obtained data from the medical records of 84 (47 ETLE and 37 MTLE) people with epilepsy. The data included age, sex, employment, seizure frequency, number of antiseizure medication (ASM), Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) score, and Quality of Life in Epilepsy Inventory-31 (QOLIE-31) score. Multiple regression analyses were performed using QOLIE-31 as the dependent variable and age, sex, employment, seizure frequency, number of ASM, and NDDI-E score as the independent variables in ETLE or MTLE. Results: From the results of the multiple regression analyses, QOLIE-31 in ETLE was associated with NDDI-E (ß = -0.757, p < 0.001) and employment (ß = 0.388, p = 0.008). Meanwhile, QOLIE-31 in MTLE was associated with NDDI-E (ß = -0.625, p < 0.001), employment (ß = 0.396, p = 0.041), and number of ASMs (ß = -0.399, p = 0.018). Conclusion: Overall, our findings indicate that the number of ASMs is potentially an influence on QOL of MTLE but similar effect is not observed in ETLE.
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BACKGROUND: Deep brain stimulation of central thalamus (CT-DBS) has potential for modulating states of consciousness, but it can also trigger electrographic seizures, including poly-spike-wave trains (PSWT). OBJECTIVES: To report the probability of inducing PSWTs during CT-DBS in awake, freely-moving mice. METHODS: Mice were implanted with electrodes to deliver unilateral and bilateral CT-DBS at different frequencies while recording EEG. We titrated stimulation current by gradually increasing it at each frequency until a PSWT appeared. Subsequent stimulations to test arousal modulation were performed at the current one step below the current that caused a PSWT during titration. RESULTS: In 2.21% of the test stimulations (10 out of 12 mice), CT-DBS caused PSWTs at currents lower than the titrated current, at currents as low as 20 µA. CONCLUSION: Our study found a small but significant probability of inducing PSWTs even after titration and at relatively low currents. EEG should be closely monitored for electrographic seizures when performing CT-DBS in both research and clinical settings.
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Automatic seizure detection from Electroencephalography (EEG) is of great importance in aiding the diagnosis and treatment of epilepsy due to the advantages of convenience and economy. Existing seizure detection methods are usually patient-specific, the training and testing are carried out on the same patient, limiting their scalability to other patients. To address this issue, we propose a cross-subject seizure detection method via unsupervised domain adaptation. The proposed method aims to obtain seizure specific information through shallow and deep feature alignments. For shallow feature alignment, we use convolutional neural network (CNN) to extract seizure-related features. The distribution gap of the shallow features between different patients is minimized by multi-kernel maximum mean discrepancies (MK-MMD). For deep feature alignment, adversarial learning is utilized. The feature extractor tries to learn feature representations that try to confuse the domain classifier, making the extracted deep features more generalizable to new patients. The performance of our method is evaluated on the CHB-MIT and Siena databases in epoch-based experiments. Additionally, event-based experiments are also conducted on the CHB-MIT dataset. The results validate the feasibility of our method in diminishing the domain disparities among different patients.
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Electroencefalografía , Redes Neurales de la Computación , Convulsiones , Aprendizaje Automático no Supervisado , Humanos , Electroencefalografía/métodos , Convulsiones/diagnóstico , Convulsiones/fisiopatología , Aprendizaje Profundo , Procesamiento de Señales Asistido por ComputadorRESUMEN
BACKGROUND: Automatic prediction of seizures is a major goal in the field of epilepsy. However, the high variability of Electroencephalogram (EEG) signals in different patients limits the use of prediction models in clinical applications. METHODS: This paper proposes a patient-independent seizure prediction model, named MFCC-CNN, to improve the generalization ability. MFCC-CNN model introduces Mel-Frequency Cepstrum Coefficients (MFCC) features and Linear Predictive Cepstral Coefficients (LPCC) features concentrated in the low frequency region, which contains more detailed information. Convolutional neural network (CNN) is used to construct a seizure prediction model. RESULTS: Experimental results showed that the proposed model obtained accuracy of 96 % , sensitivity of 92 % , specificity of 84 % and F1-score of 85 % for 24 cases in CNHB-MIT dataset. The overall performance of MFCC-CNN model is better than the other models. CONCLUSION: MFCC-CNN model does not need to be specifically customized for different patients. As a patient-independent seizure prediction model, it has good generalization ability.
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BACKGROUND: This retrospective clinical study performed at a single clinical center aimed to identify the prevalence of seizures in individuals with urea cycle disorders (UCDs) with and without hyperammonemic (HA) crises. In addition, we sought to correlate the utility of biochemical markers and electroencephalography (EEG) in detecting subclinical seizures during HA. METHODS: Medical records of individuals with UCDs enrolled in Urea Cycle Disorders Consortium Longitudinal Study (UCDC-LS) (NCT00237315) at Children's National Hospital between 2006 and 2022 were reviewed for evidence of clinical and subclinical seizuress during HA crises, and initial biochemical levels concurrently. RESULTS: Eighty-five individuals with UCD were included in the analyses. Fifty-six of the 85 patients (66%) experienced HA crises, with a total of 163 HA events. Seizures are observed in 13% of HA events. Among all HA events with concomitant EEG, subclinical seizures were identified in 27% of crises of encephalopathy without clinical seizures and 53% of crises with clinical seizures. The odds of seizures increases 2.65 (95% confidence interval [CI], 1.51 to 4.66) times for every 100 µmol/L increase in ammonia and 1.14 (95% CI, 1.04 to 1.25) times for every 100 µmol/L increase in glutamine. CONCLUSIONS: This study highlights the utility of EEG monitoring during crises for patients presenting with clinical seizures or encephalopathy with HA. During HA events, measurement of initial ammonia and glutamine can help determine risk for seizures and guide EEG monitoring decisions.
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PURPOSE: Inconsistent access to healthcare for people with epilepsy results in reduced adherence to antiseizure medications, increased seizure frequency, and fewer appropriate referrals for epilepsy surgery. Identifying and addressing factors that impede access to care should consequently improve patient outcomes. We hypothesized that health insurance and transportation affect access to outpatient neurology care for adults living with epilepsy in the United States (US). METHODS: We conducted a retrospective cross-sectional study of US adults with active epilepsy surveyed via the National Health Interview Survey (NHIS) in 2015 and 2017. We established whether patients reported seeing a neurologist in the past year and used multiple logistic regression to determine whether health insurance status and transportation access were associated with this outcome. RESULTS: We identified 735 respondents from 2015 and 2017, representing an estimated 2.98 million US adults with active epilepsy. After adjusting for socioeconomic and seizure-related co-variates, we found that a lack of health insurance coverage was associated with no epilepsy care in the past year (adjusted odds ratio [aOR] 0.22; 95â¯% confidence interval [CI]: 0.09 - 0.54). Delayed care due to inadequate transportation (aOR 0.42; 95â¯% CI: 0.19 - 0.93) also resulted in reduced patient access to a neurologist. CONCLUSION: Due to the inherent nature of their condition, people with epilepsy are less likely to have employer-sponsored health insurance or consistent driving privileges. Yet, these factors also impact patient access to neurological care. We must address transportation and insurance barriers through long-term investment and partnership between community, healthcare, and government stakeholders.
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PURPOSE: There is limited research on the proportion of individuals with epilepsy who maintain response to ketogenic diet therapy (KDT) after discontinuing treatment. We aimed to determine the proportion of individuals who did / did not maintain response post KDT and explore factors that may influence the likelihood of maintaining response. METHODS: Retrospective data were collected from 97 individuals from 9 KDT centres. Individuals had achieved ≥50 % seizure reduction on KDT for at least 12 months, with seizure frequency data available at 3 months+ post diet. Outcome 1 was: recurrence of seizures or increase in seizure frequency post diet; outcome 2: recurrence of seizures, increase in seizure frequency or an additional anti-seizure treatment started post diet. RESULTS: 61/97 (62.9 %) individuals maintained response at latest follow-up (mean 2.5[2.0] years since stopping KDT). Approximately one third maintained response without further anti-seizure treatments. One quarter of individuals had an increase in frequency or recurrence of seizures within 6 months (95 %CI 4, 12) for outcome 1 and within 3 months (3, 6) for outcome 2. Individuals who did not achieve seizure freedom on diet were significantly more likely to have an increase in seizures or to require additional anti-seizure treatments post diet compared to those who were seizure-free on diet (hazard ratio 4.02, 95 %CI (1.46, 11.16) p < 0.01). CONCLUSION: Our findings should help guide clinical teams with the information they provide patients and their families regarding likelihood of long-term seizure response to KDT. Realistic costings for KDT services may need to be considered.
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INTRODUCTION: Magnetic resonance-guided laser interstitial thermal therapy (MRg-LITT) is a promising new technique to ablate epileptic foci in patients with hypothalamic hamartoma (HH). We aim to systematically synthesize all available evidence and determine the effectiveness of MRg-LITT in reducing seizures in patients with HH. METHODS: We systematically searched MEDLINE (PubMed), Embase (Ovid), Scopus, and Google Scholar for all relevant articles. We used Open[Meta]Analyst to pool the number of seizure free patients after MRg-LITT treatment in a Random Effects model. Risk ratios (RRs) were calculated, and subgroups were analyzed. Comprehensive Meta Analysis was used to assess publication bias via funnel plots, Egger's regression test and Begg's correlation test. This review complies with the PRISMA guidelines. RESULTS: After screening the titles, abstracts, and full texts, we included seventeen articles in our meta-analysis, which revealed a 77.1% rate of seizure freedom (95% CI 0.696 to 0.837, p < 0.001), with moderate heterogeneity (I2 = 49.46%). Subgroup analysis by study design and sensitivity analyses excluding one study at a time did not impact the results substantially, and we found no evidence of publication bias. Adverse effects included electrolyte imbalances, weight gain, and transient neurologic disturbances. CONCLUSION: Magnetic resonance-guided laser interstitial thermal therapy might be a feasible and effective technique for ablation of epileptic foci, leading to seizure freedom in a large proportion of patients with hypothalamic hamartoma. However, there is a paucity of literature on the topic, and prospective clinical trials with larger number of participants, comparing MRg-LITT to open surgery, are needed.
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OBJECTIVE: Women of childbearing age with juvenile absence epilepsy (JAE) face treatment challenges due to limited access to safe and effective anti-seizure medications (ASMs). In a previous study we compared the effectiveness of levetiracetam (LEV) and lamotrigine (LTG) in women with idiopathic generalized epilepsy (IGE), highlighting a superiority of LEV in juvenile myoclonic epilepsy. In this study, we specifically reanalyzed, through a Bayesian approach and by expanding the previously published cohort, the comparative effectiveness of these ASMs as initial monotherapy in JAE. METHODS: We conducted a multicenter, retrospective, comparative effectiveness study on women of childbearing age diagnosed with JAE and prescribed LEV or LTG as the initial ASM. Inverse probability treatment weighting (IPTW) Bayesian Cox proportional hazard models were employed to evaluate treatment failure (TF) due to ineffectiveness and ASM retention. The patients' center of provenance and year of prescription were considered as random effect factors. Posterior probabilities and relative log-risk distribution were computed, and the distribution of posterior draws was analyzed to assess the evidence supporting LTG superiority over LEV. RESULTS: Of 123 patients, those treated with LTG (n = 67) demonstrated lower TF and higher ASM retention than those treated with LEV (n = 56), with the IPTW-weighted Bayesian Cox proportional hazards model showing a 99.2% posterior probability of LTG being superior on TF and a 99.5% probability on ASM retention. Additional analyses on ≥50% and ≥75% seizure reduction through IPTW-weighted Bayesian logistic regression largely confirmed these findings, whereas the two ASMs did not show evident differences in terms of seizure freedom. The two ASMs showed comparable safety profiles, with only a minority of patients discontinuing treatment due to side effects. SIGNIFICANCE: Bayesian reanalysis supports LTG as first-line monotherapy for JAE in women of childbearing age, emphasizing the importance of individualized treatment strategies in women with IGE. This study underscores the value of Bayesian methods in refining clinical research and treatment decisions.
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Introduction: Epilepsy is a widespread disease requiring long-term drug treatment. The aim of this study was to collect information on reported suspected adverse drug reactions (sADRs) of antiseizure medications (ASMs) and study their seriousness and outcomes in various system organ classifications (SOCs). We intended to compare old and new ASMs' ADRs. Methods: Using EudraVigilance (EV) database, we extracted line listings of reported sADRs with different ASMs over the period from January 2012 to December 2021. The list of ASMs was compiled according to the Anatomical therapeutic chemical classification system. The Medical Dictionary for Regulatory Activities version 24.0 was used for determining the SOCs of individual reported preferred terms (PTs) sADRs. In addition, we calculated the Reporting Odds Ratio (ROR), 95% confidence interval (95% CI), p-value (statistically significant if p< 0.05) and chi-square statistics. Results: A total of 276,694 reports were contained in the exported line listings which included 1,051,142 individual sADRs reported as PTs such as seizure (3.49%), drug ineffective (2.46%), somnolence (1.32%), dizziness (1.29%) and represented four SOCs: nervous system disorders (19.26%), general disorders and administration site conditions (14.39%), psychiatric disorders (11.29%) and injury, poisoning and procedural complications (9.79). Among patients, the age group between 18 and 64 years had the highest percentage (52.40%), followed by those aged over 64 years (18.75%). Of all the reported PTs, 882,706 (83.98%) had reported seriousness. Old ASMs had a significant positive association with "caused/prolonged hospitalisation", "congenital anomaly", "disabling", "life threatening" and "results in death", while new ASMS with 'other medically important condition'. There were 386 (0.04%) PTs related to Sudden Unexpected Death in Epilepsy (SUDEP). Conclusion: In our study, we examined 10 years' reported sADRs of ASMs in the EV international database. The majority of PTs were serious. Old ASMs were generally more commonly associated with undesired outcomes and seriousness. Considering their expected seriousness and outcomes, the safety profile of the different ASMs, can play a cardinal role in the selection of ASMs.
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Epilepsy associated with high-titer glutamic acid decarboxylase 65 (GAD65) IgG is often refractory to immunotherapies and antiseizure medication. This study sought to determine the efficacy of vagus nerve stimulation (VNS) and surgical resection in patients with drug-resistant epilepsy associated with GAD65-IgG. We retrospectively identified 15 patients with drug-resistant epilepsy and high serum GAD65 antibody titers (>20 nmol·L-1) who underwent VNS implantation (n = 6), surgical resection (n = 7), or both (n = 2). A responder to VNS was defined as someone with a ≥50% reduction in seizure frequency, and a favorable surgical outcome was defined as Engel I-II. Of the eight patients who underwent VNS implantation, three (37.5%) were initially responders, but this was not sustained in two. Of the nine patients who underwent surgical resection, three (33.3%) had a favorable outcome; however, only one patient was seizure-free at last follow-up. Pathology was available in six patients, and only one had evidence of inflammation; this patient had seizure onset 1 year prior to surgery. Favorable seizure outcome correlated with older age at time of resective surgery, with a trend favoring later age of seizure onset. Taken together, surgical resection and VNS implantation may have limited efficacy in this patient population but can be considered in carefully selected cases.