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Patients with chronic focal epilepsy commonly exhibit subcortical atrophy, particularly of the thalamus. The timing of these alterations remains uncertain, though preliminary evidence suggests that observable changes may already be present at diagnosis. It is also not yet known how these morphological changes are linked to the coherence of white matter pathways throughout the brain, or to neuropsychological function often compromised before antiseizure medication treatment. This study investigates localized atrophy in subcortical regions using surface shape analysis in individuals with newly diagnosed focal epilepsy (NDfE) and assesses their implications on brain connectivity and cognitive function. We collected structural (T1w) and diffusion‐weighted MRI and neuropsychological data from 104 patients with NDfE and 45 healthy controls (HCs) matched for age, sex, and education. A vertex‐based shape analysis was performed on subcortical structures to compare patients with NDfE and HC, adjusting for age, sex, and intracranial volume. The mean deformation of significance areas (pcor < 0.05) was used to identify white matter pathways associated with overall shape alterations in patients relative to controls using correlational tractography. Additionally, the relationship between significant subcortical shape values and neuropsychological outcomes was evaluated using a generalized canonical correlation approach. Shape analysis revealed bilateral focal inward deformation (a proxy for localized atrophy) in anterior areas of the right and left thalamus and right pallidum in patients with NDfE compared to HC (FWE corrected). No structures showed areas of outward deformation in patients. The connectometry analysis revealed that fractional anisotropy (FA) was positively correlated with thalamic and pallidal shape deformation, that is, reduced FA was associated with inward deformation in tracts proximal to and or connecting with the thalamus including the fornix, frontal, parahippocampal, and corticothalamic pathways. Thalamic and pallidal shape changes were also related to increased depression and anxiety and reduced memory and cognitive function. These findings suggest that atrophy of the thalamus, which has previously been associated with the generation and maintenance of focal seizures, may present at epilepsy diagnosis and relate to alterations in both white matter connectivity and cognitive performance. We suggest that at least some alterations in brain structure and consequent impact on cognitive and affective processes are the result of early epileptogenic processes rather than exclusively due to the chronicity of longstanding epilepsy, recurrent seizures, and treatment with antiseizure medication. [ABSTRACT FROM AUTHOR]

Objective: This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE). Methods: This is an ambispective, single-center, non-inferiority study comparing the effectiveness and safety of perampanel (PER) monotherapy and oxcarbazepine (OXC) monotherapy in children with newly diagnosed FE. The primary endpoint was a six-month seizure freedom rate. The secondary endpoints included retention, responder, and seizure freedom rates at 3, 6, and 12 months, respectively. Adverse events (AEs) were also recorded for both groups. Results: One hundred and thirty children and adolescents aged from 4 to 18years newly diagnosed with FE between May 2020 and November 2022 in Wuhan Children's Hospital were included. There were 71 patients in the PER group and 59 patients in the OXC group. In the per protocol set (PPS), 50 (78.1%) in the PER group and 43 (78.2%) in the OXC group completed six months of treatment without seizures. The lower 95% CI (66.0%--87.5%) limit of PER was higher than the non-inferiority margin of 62.4% (80% of the 6-month seizure freedom rate in the OXC group); PER was non-inferior to OXC. The 3-month and 12-month seizure freedom rates were 77.1% and 82.9% for the PER group, respectively, while they were 80.4% and 75.8% for the OXC group. There were no serious adverse events in both groups. Conclusion: PER showed comparable effectiveness and safety compared with OXC in children with newly diagnosed focal epilepsy, which might be an effective and safe treatment for children and adolescents with newly diagnosed FE. Clinical Trial Registration: Identifier ChiCTR2300074696 [ABSTRACT FROM AUTHOR]

Objective: This study aims to compare the effectiveness and safety of perampanel and oxcarbazepine as monotherapy in children with focal epilepsy (FE). Methods: This is an ambispective, single-center, non-inferiority study comparing the effectiveness and safety of perampanel (PER) monotherapy and oxcarbazepine (OXC) monotherapy in children with newly diagnosed FE. The primary endpoint was a six-month seizure freedom rate. The secondary endpoints included retention, responder, and seizure freedom rates at 3, 6, and 12 months, respectively. Adverse events (AEs) were also recorded for both groups. Results: One hundred and thirty children and adolescents aged from 4 to 18years newly diagnosed with FE between May 2020 and November 2022 in Wuhan Children's Hospital were included. There were 71 patients in the PER group and 59 patients in the OXC group. In the per protocol set (PPS), 50 (78.1%) in the PER group and 43 (78.2%) in the OXC group completed six months of treatment without seizures. The lower 95% CI (66.0%-87.5%) limit of PER was higher than the non-inferiority margin of 62.4% (80% of the 6-month seizure freedom rate in the OXC group); PER was non-inferior to OXC. The 3-month and 12-month seizure freedom rates were 77.1% and 82.9% for the PER group, respectively, while they were 80.4% and 75.8% for the OXC group. There were no serious adverse events in both groups. Conclusion: PER showed comparable effectiveness and safety compared with OXC in children with newly diagnosed focal epilepsy, which might be an effective and safe treatment for children and adolescents with newly diagnosed FE. Clinical Trial Registration: Identifier ChiCTR2300074696., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yi, Huang, Wu, Ma, Huang, Liang and Sun.)

• It is necessary to compare the long-term effectiveness and tolerability of the common AEDs for monotherapy. • LEV and LTG are significantly more effective than OXC for the treatment of newly diagnosed focal epilepsy. • LEV has milder adverse events than OXC and LTG in clinical practice. • LEV and LTG were significantly better than OXC in preventing first seizures. • LEV appeared to be the preferred treatment option due to the time to one-year remission. We performed observational cohort study to compare the long-term efficacy, tolerability, and safety of oxcarbazepine (OXC), lamotrigine (LTG), and levetiracetam (LEV) monotherapy for newly diagnosed focal epilepsy patients. Three hundred and eighty eight newly diagnosed focal epilepsy patients aged 1–70 years were enrolled in this study between June 2009 and March 2016. Among the patients, 191 were treated with OXC, 98 were treated with LTG, and 99 were treated with LEV monotherapy. The study was performed in a real-world setting and the primary outcomes were the one-year and three-year seizure-free rates. The secondary outcomes were the one-year and three-year withdrawal rates, the time to treatment withdrawal, the time to the first seizure, and the time to achieve one-year remission. The three-year seizure-free rates with LTG (39.8 %) and LEV (41.4 %) were significantly better than that with OXC (26.2 %) (both P < 0.05). However, no significant difference was observed among the three drugs for the one-year seizure-free rate. The three-year withdrawal rate was 50.8 %, 46.9 %, and 43.4 % for OXC, LTG, and LEV, respectively (all P > 0.05). The one-year withdrawal rate for OXC (31.7 %) was higher than those for LTG (30.6 %) and LEV (26.3 %) (all P > 0.05). LEV [Relative Risk (RR) = 0.69, 95 % CI: 0.49∼0.99] and LTG (RR = 0.63, 95 % CI: 0.44∼0.9) were significantly better than OXC in preventing first seizure. LEV appears to be the superior option with regard to the time to achieve one-year remission. The results of the study showed that LEV and LTG are significantly more effective than OXC for the treatment of newly diagnosed focal epilepsy. LEV has milder adverse events than OXC and LTG in clinical practice. [ABSTRACT FROM AUTHOR]