Gionata Strigaro

Objective: Cenobamate is approved for treatment of focal seizures in adults, but evidence on non‐seizure outcomes remains limited. This interim statistical analysis of the cenoBamate in aduLts with focal‐onsEt SeizureS (BLESS) study evaluated patient‐ and clinician‐reported outcomes for up to 52 weeks of cenobamate treatment. Methods: BLESS is an observational, retrospective and prospective cohort study designed to assess the real‐world effectiveness and safety of adjunctive cenobamate in adults with uncontrolled focal epilepsy. Outcomes included patient‐reported health‐related quality of life, sleepiness, anxiety, mood, and global functioning assessed by the 31‐item Quality of Life in Epilepsy Inventory (QOLIE‐31), the Epworth Sleepiness Scale (ESS), the Hospital Anxiety and Depression Scale (HADS), and the Clinical Global Impression (CGI) scales. Results: A total of 377 participants were included. Among subjects with an available score at 12 ( n = 197), 24 ( n = 363), and 52 ( n = 197) weeks, the QOLIE‐31 overall score remained stable. Subjects with sustained seizure freedom at 24 weeks showed a significantly higher QOLIE‐31 overall score ( p = 0.041) and cognitive functioning scores ( p = 0.019) compared with those who did not reach sustained seizure freedom. More than 68% of participants had normal daytime sleepiness (total ESS score 0–10) and did not report anxiety or depression according to the HADS‐A and HADS‐D subscales at each assessment up to 52 weeks. Clinicians rated 91.3% ( n / N = 179/196), 85.7% ( n / N = 300/350), and 87.4% ( n / N = 167/191) of subjects as improved for their overall condition from the initiation of treatment according to the CGI—Improvement or change (CGI‐I) scale, at 12, 24, and 52 weeks. Significance: This interim analysis provides preliminary descriptive evidence on non‐seizure outcomes in subjects treated with adjunctive cenobamate. Patient‐reported outcome scores remained stable from 12 weeks and up to 52 weeks, consistent with preserved overall well‐being. Better quality of life and cognitive functioning emerged in sustained vs non‐sustained seizure‐free participants. Based on clinicians' judgment, there was signal of improvement in overall condition compared to baseline in most treated subjects throughout the observation period. Study Registration: NCT05859854.

Objective.The pathophysiology of amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD) is still a matter of debate. Visual system might be precociously altered, especially for its cholinergic connections. We thus studied patients with aMCI compared to AD with paired-pulse flash-visual evoked potentials (paired-F-VEPs), a putative marker of cholinergic function. Methods. We enrolled 12 adult patients with aMCI and 12 with AD. 14 normal age- and sex-matched subjects acted as controls (HS). Stimuli were single flashes, with interspersed random flash pairs at critical interstimulus intervals (ISIs, 16.5 to 125 ms) with closed eyes. The “single” (unconditioned) F-VEP was split into a “main complex” (50 to 200 ms after the flash) and a “late response” (200 to 400 ms). As for paired stimulation, the “test” F-VEP emerged from electronic subtraction of the “single” F-VEP from the “paired”-F-VEP. Results. In the single F-VEP, P2 latency was prolonged in patients (aMCI and AD) compared to HS ( p < .05). As to the paired F-VEPs, in aMCI the “late response” normal inhibition was abolished at ISIs 50–62.5 ms ( p ≤ .016), compared to AD and controls. No changes were detected for the “main complex”. Conclusions. Paired-F-VEPs demonstrate a defective neural inhibition in the visual system of patients with aMCI at critical intervals. It may represent a compensatory mechanism against neuronal loss, the failure of which may be involved in AD development. Paired-F-VEPs may warrant inclusion in future preclinical/clinical studies, to evaluate its potential role in the pathophysiology and management of aMCI.

Cognition was assessed in hepatitis C virus (HCV) patients, who did not meet the criteria for a minimal hepatic encephalopathy. Their liver function was compensated. We then disentangled potential cognitive changes associated with a sustained virologic response at 12 weeks (SVR-12), following treatment with direct antiviral agents (DAAs). We studied 23 selected HCV patients with a battery of standard neuropsychological tests, and with recordings of the P300 wave, a cerebral potential of “cognitive” significance. There was a baseline evaluation (T0) and a second one 6 months later (T1). We had 2 control groups of comparable age and sex, i.e., 15 patients suffering from non-alcoholic fatty liver disease (NAFLD) and 15 healthy subjects. At T0, we detected a significant (p < 0.05) cognitive impairment in the HCV group, which involved episodic and working memory, attention, visuospatial and verbal abilities, executive functions, and logic reasoning. The P300 latency was significantly (p < 0.05) delayed in the group. At T1, we observed some significant (p < 0.05) HCV recovery in given test domains, e.g., memory, executive functions, and reasoning. Accordingly, the P300 latency shortened significantly (p < 0.05). HCV patients exhibited subtle cognitive defects, somehow independent of their liver condition, possibly linked to direct or indirect brain involvement by the virus. These defects partly recovered following the SVR-12, as achieved through DAAs. The P300 wave was a valid neurophysiologic counterpart of these changes. DAAs can have a role in the early preservation of cognition in HCVs.