Evaluating Therapeutic Equivalence of Generic and Original Levetiracetam in Patients with Epilepsy: A Retrospective Study.

The brand interchangeability of antiepileptic drugs (AEDs) is a topic of debate, especially regarding their therapeutic equivalence. This study evaluates the efficacy and tolerability of generic levetiracetam compared to the brand-name equivalent in a routine clinical setting. We conducted a retrospective study, examining patients with stable seizure frequency who received generic levetiracetam after the brand-name drug. During the six-month substitution period, changes in seizure frequency, hospitalization due to seizure exacerbation, adverse events, composite outcomes related to adjusting the AED dosage, and switching back to original levetiracetam were analyzed. Seventy-five patients were enrolled; the majority (85.3%) had focal onset seizures, and almost half (49.3%) had refractory epilepsy. Six months after the substitution, the mean seizure frequency per month was not significantly different (3.15 ± 14.47 vs. 2.77 ± 11.41; p = 0.970). In patients with controlled seizures before the change, the seizure frequency increased significantly (0.56 ± 1.83 vs. 0.03 ± 0.16; p = 0.012). Adverse events occurred in six patients. We have observed recurrent seizures or adverse events from 14 days after the transition. The original drug return rates due to recurrent seizures and adverse events were 5.3% and 1.3%, respectively. Generic levetiracetam might not show therapeutic equivalence to the original molecule, especially in patients adequately controlled by the brand-name drug.

BOLD mapping of human epileptic spikes recorded during simultaneous intracranial EEG-fMRI: The impact of automated spike classification.

OBJECTIVES: Simultaneous intracranial EEG and functional MRI (icEEG-fMRI) can be used to map the haemodynamic (BOLD) changes associated with the generation of IEDs. Unlike scalp EEG-fMRI, in most patients who undergo icEEG-fMRI, IEDs recorded intracranially are numerous and show variability in terms of field amplitude and morphology. Therefore, visual marking can be highly subjective and time consuming. In this study, we applied an automated spike classification algorithm, Wave_clus (WC), to IEDs marked visually on icEEG data acquired during simultaneous fMRI acquisition. The motivation of this work is to determine whether using a potentially more consistent and unbiased automated approach can produce more biologically meaningful BOLD patterns compared to the BOLD patterns obtained based on the conventional, visual classification. METHODS: We analysed simultaneous icEEG-fMRI data from eight patients with severe drug resistant epilepsy, and who subsequently underwent resective surgery that resulted in a good outcome: confirmed epileptogenic zone (EZ). For each patient two fMRI analyses were performed: one based on the conventional visual IED classification and the other based on the automated classification. We used the concordance of the IED-related BOLD maps with the confirmed EZ as an indication of their biological meaning, which we compared for the automated and visual classifications for all IED originating in the EZ. RESULTS: Across the group, the visual and automated classifications resulted in 32 and 24 EZ IED classes respectively, for which 75% vs 83% of the corresponding BOLD maps were concordant. At the single-subject level, the BOLD maps for the automated approach had greater concordance in four patients, and less concordance in one patient, compared to those obtained using the conventional visual classification, and equal concordance for three remaining patients. These differences did not reach statistical significance. CONCLUSION: We found automated IED classification on icEEG data recorded during fMRI to be feasible and to result in IED-related BOLD maps that may contain similar or greater biological meaning compared to the conventional approach in the majority of the cases studied. We anticipate that this approach will help to gain significant new insights into the brain networks associated with IEDs and in relation to postsurgical outcome.

The impact of mapping interictal discharges using EEG-fMRI on the epilepsy presurgical clinical decision making process: A prospective study.

PURPOSE: We set out to establish the clinical utility of EEG-correlated fMRI as part of the presurgical evaluation, by measuring prospectively its effects on the clinical decision. METHODS: Patients with refractory extra-temporal focal epilepsy, referred for presurgical evaluation were recruited in a period of 18 months. The EEG-fMRI based localization was presented during a multi-disciplinary meeting after the team had defined the presumed RESULTS: Sixteen patients (six women), with a median age of 28 years, were recruited. Interpretable EEG-fMRI results were available in 13: interictal epileptic discharges (IEDs) were recorded in eleven patients and seizures were recorded in two patients. In three patients, no epileptic activity was captured during EEG-fMRI acquisition and in two of those an IED topographic map correlation was performed (between EEG recorded inside the scanner and long-term video EEG monitoring). EEG-fMRI results presentation had no impact on the initial clinical decision in three patients (23%) of the thirteen and resulted in a modification of the initial surgical plan in ten patients (77%) of the thirteen finally presented in MDT; in eight patients the impact was on the planned placement of invasive electrodes and in two patients the EEG-fMRI led to additional non-invasive tests before proceeding further with surgery. CONCLUSION: The study is a prospective observational cohort study specifically designed to assess the impact of EEG-fMRI on the clinical decision making process, suggesting a significant influence of EEG-fMRI on epilepsy surgery planning.

A novel scheme for the validation of an automated classification method for epileptic spikes by comparison with multiple observers.

OBJECTIVE: To validate the application of an automated neuronal spike classification algorithm, Wave_clus (WC), on interictal epileptiform discharges (IED) obtained from human intracranial EEG (icEEG) data. METHOD: Five 10-min segments of icEEG recorded in 5 patients were used. WC and three expert EEG reviewers independently classified one hundred IED events into IED classes or non-IEDs. First, we determined whether WC-human agreement variability falls within inter-reviewer agreement variability by calculating the variation of information for each classifier pair and quantifying the overlap between all WC-reviewer and all reviewer-reviewer pairs. Second, we compared WC and EEG reviewers' spike identification and individual spike class labels visually and quantitatively. RESULTS: The overlap between all WC-human pairs and all human pairs was >80% for 3/5 patients and >58% for the other 2 patients demonstrating WC falling within inter-human variation. The average sensitivity of spike marking for WC was 91% and >87% for all three EEG reviewers. Finally, there was a strong visual and quantitative similarity between WC and EEG reviewers. CONCLUSIONS: WC performance is indistinguishable to that of EEG reviewers' suggesting it could be a valid clinical tool for the assessment of IEDs. SIGNIFICANCE: WC can be used to provide quantitative analysis of epileptic spikes.

Cost-Utility of Video-Electroencephalography Monitoring Followed by Surgery in Adults with Drug-Resistant Focal Epilepsy in Thailand.

OBJECTIVES: This study assessed whether video-electroencephalography (VEEG) monitoring followed by surgery was cost-effective in adult patients with drug-resistant focal epilepsy under Thai health care context, as compared with continued medical treatment without VEEG. METHODS: The total cost (in Thai Baht, THB) and effectiveness (in quality-adjusted life years, QALYs) were estimated over a lifetime horizon, using a decision tree and a Markov model. Data on short-term surgical outcomes, direct health care costs, and utilities were collected from Thai patients in a specialized hospital. Long-term outcomes and relative effectiveness of the surgery over medical treatment were derived, using systematic reviews of published literature. RESULTS: Seizure-free rates at years 1 and 2 after surgery were 79.4% and 77.8%, respectively. Costs of VEEG and surgery plus 1-year follow-up care were 216,782 THB, of which the VEEG and other necessary investigations were the main cost drivers (42.8%). On the basis of societal perspective, the total cost over a 40-year horizon accrued to 1,168,679 THB for the VEEG option, 64,939 THB higher than that for no VEEG. The VEEG option contributed to an additional 1.50 QALYs over no VEEG, resulting in an incremental cost-effectiveness ratio of 43,251 THB (USD 1236) per 1 QALY gained. Changes in key parameters had a minimal impact on the incremental cost-effectiveness ratio. Accounting for uncertainty, there was an 84% probability that the VEEG option was cost-effective on the basis of Thailand's cost-effective threshold of 160,000 THB/QALY. CONCLUSIONS: For patients with drug-resistant epilepsy, VEEG monitoring followed by epilepsy surgery was cost-effective in Thailand. Therefore it should be recommended for health insurance coverage.