Levetiracetam (LEV) is often a first-line epilepsy treatment due to its broad efficacy and favorable side effect profile. While LEV-induced seizure aggravation (LISA) has been reported in up to 18 % of LEV users in certain patient populations, the risk factors for LISA have not been well delineated. This study aims to provide a comprehensive assessment of seizure aggravation associated with LEV. We conducted a comprehensive literature review of LISA case reports and case series. Additionally, we report a case series of seven patients treated at Hadassah Medical Center from 2015 to 2025 who experienced LISA. Our literature review identified 26 papers comprising 143 patient descriptions of LISA. Patients were 9 months to 80 years old, and seizure aggravation manifested as increased seizure frequency, status epilepticus, and the appearance of non-habitual seizures. Patients had both focal and generalized epilepsy, secondary to a variety of underlying lesion, and genetic mutation. LEV dosing ranged from 500 to 4500 mg per day. All patients in our case series experienced increased seizure frequency during LEV treatment, with two patients developing epilepsia partialis continua. Reducing or stopping LEV decreased seizures, sometimes leading to seizure freedom. We found that LISA can occur across different age groups, epilepsy types and underlying etiologies. Clinicians should consider LISA in the differential diagnosis of seizure exacerbation following LEV treatment and evaluate the potential benefits of LEV discontinuation. Further studies are needed to determine the occurrence and risk factors of LISA to optimize ASM treatment.

Psychogenic non-epileptic seizures (PNES) resemble epileptic seizures (ES) but lack the associated brain electrical disruptions. Their underlying mechanism remains elusive, even though cognitive deficits are commonly reported in both ES and PNES patients. This preliminary cross-sectional study compared attention and executive functions in 20 patients with ES (ES group) and 18 with PNES or comorbid PNES and ES (PNES group) using the Stroop task and attentional network task (ANT). Both groups exhibited a significant Stroop effect, with no significant differences between them. In the ANT assessment, the ES group had significantly slower reaction times (RTs) in non-tone conditions compared to in-tone conditions (P < 0.05). Meanwhile, the PNES group displayed no significant difference in RTs between these conditions, indicating a more pronounced alerting effect in the ES compared to PNES group. No significant disparities emerged in executive control and orientation between the groups. The findings underscore differences in attentional processing between these groups, emphasizing the clinical significance of understanding these cognitive deficits for accurate diagnosis and tailored neuropsychological rehabilitation.

Functional near-infrared spectroscopy (fNIRS) is a non-invasive method for monitoring brain activity by detecting hemodynamic changes. Studies have shown that it can identify ictal and pre-ictal hemodynamic variations, supporting its potential use as a complement to electroencephalography (EEG) in epilepsy monitoring. This study explores an expanded illumination and detection approach utilizing wide-based optodes and increased emitter–detector separation (EDS) to enhance fNIRS sensitivity to cortical hemodynamic changes while minimizing scalp contamination. A Monte Carlo simulation was designed to assess signal amplitude and sensitivity of fNIRS with varying emitter and detector diameters (1–15 mm) and EDS (30–50 mm). Signal strength, grey matter to scalp path ratio (GSPR), and percentage signal change per absorption coefficients (AC) variation were analyzed. Sensitivity to changes in AC of superficial and deep grey matter (SGM, DGM) and scalp was assessed. Increasing emitter and detector diameters substantially increased total detected photon packet weights, enabling practical use at larger EDS. Sensitivity to SGM AC changes tripled at 50 mm EDS, while GSPR increased by 80%, indicating reduced signal contamination from the scalp. Sensitivity to deep cortical hemodynamic changes also improved. Therefore, wide-based fNIRS optodes with increased EDS can enhance seizure-related hemodynamic detection, potentially improving epilepsy diagnostics.