Frailty as a comprehensive health measure beyond seizure control in patients with epilepsy: A cross-sectional study.

OBJECTIVE: Due to the high clinical heterogeneity of epilepsy, there is a critical need for novel metrics aimed at capturing its biological and phenotypic complexity. Frailty is increasingly recognized in various medical disciplines as a useful construct to understand differences in susceptibility to adverse outcomes. Here, we develop a frailty index (FI) for patients with epilepsy (PwE) and explore its association with demographic and clinical features. METHODS: In this cross-sectional study, we consecutively enrolled 153 PwE from an outpatient epilepsy clinic. Participants were assessed for various health deficits to calculate the FI. Associations between FI and demographic/clinical features, antiseizure medications (ASMs), and patient-reported outcomes were analyzed using general linear models and Spearman correlation. RESULTS: The median age at the time of study visit was 47 years (interquartile range = 33-60), and 89 (58.2%) patients were females. Multiple linear regression revealed that the developed 33-item FI showed an independent association with age, female sex, higher body mass index, family history of epilepsy, intellectual disability, and the number of ASMs used. A robust analysis of covariance showed higher FI levels in patients using cytochrome P450 3A4-inducer ASMs. We found a moderate positive correlation between FI and psychological distress, lower quality of life, and physical frailty, measured by the Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy Inventory-10, and handgrip strength, respectively. Finally, a weak association was observed between higher FI scores and an increased number of epileptic falls. SIGNIFICANCE: This study highlights the significance of frailty as a comprehensive health measure in epilepsy. It suggests that frailty in this specific population is not only a manifestation of aging but is inherently linked to epilepsy and treatment-related factors. Future research is warranted to validate and refine the FI in diverse epilepsy populations and investigate its impact on specific adverse outcomes in longitudinal studies.

Alzheimer's Disease with Epileptiform EEG Activity: Abnormal Cortical Sources of Resting State Delta Rhythms in Patients with Amnesic Mild Cognitive Impairment.

BACKGROUND: Patients with amnesic mild cognitive impairment due to Alzheimer's disease (ADMCI) typically show a "slowing" of cortical resting-state eyes-closed electroencephalographic (rsEEG) rhythms. Some of them also show subclinical, non-convulsive, and epileptiform EEG activity (EEA) with an unclear relationship with that "slowing." OBJECTIVE: Here we tested the hypothesis that the "slowing" of rsEEG rhythms is related to EEA in ADMCI patients. METHODS: Clinical and instrumental datasets in 62 ADMCI patients and 38 normal elderly (Nold) subjects were available in a national archive. No participant had received a clinical diagnosis of epilepsy. The eLORETA freeware estimated rsEEG cortical sources. The area under the receiver operating characteristic curve (AUROCC) indexed the accuracy of eLORETA solutions in the classification between ADMCI-EEA and ADMCI-noEEA individuals. RESULTS: EEA was observed in 15% (N = 8) of the ADMCI patients. The ADMCI-EEA group showed: 1) more abnormal Aß42 levels in the cerebrospinal fluid as compared to the ADMCI-noEEA group and 2) higher temporal and occipital delta (<4 Hz) rsEEG source activities as compared to the ADMCI-noEEA and Nold groups. Those source activities showed moderate accuracy (AUROCC = 0.70-0.75) in the discrimination between ADMCI-noEEA versus ADMCI-EEA individuals. CONCLUSION: It can be speculated that in ADMCI-EEA patients, AD-related amyloid neuropathology may be related to an over-excitation in neurophysiological low-frequency (delta) oscillatory mechanisms underpinning cortical arousal and quiet vigilance.

Seizure outcome trajectories in a well-defined cohort of newly diagnosed juvenile myoclonic epilepsy patients.

OBJECTIVE: To investigate the temporal course of medication response and associated prognostic factors in a cohort of juvenile myoclonic epilepsy (JME) patients over a long-term follow-up. MATERIALS AND METHODS: Data from 113 JME patients diagnosed according to recently proposed class II criteria were retrospectively reviewed. Early sustained remission was defined as 4-year seizure remission starting within 2 years from the first antiseizure medication (ASM) intake, as opposed to delayed sustained remission. Spontaneous relapse rate (ie, not related to ASM withdrawal) was also investigated, along with factors associated with seizure relapse. RESULTS: Four-year seizure remission was obtained by 76/113 (67.3%) subjects. Early sustained remission was achieved by 45/76 (59.2%) patients. Absence seizures were significantly associated with no-remission at multivariable multinomial logistic regression analysis. Catamenial seizures and earlier age at epilepsy onset significantly predicted delayed sustained remission. Spontaneous seizure relapse after 4-year remission occurred in 15.7% of patients with early sustained remission and in 35.5% of those with delayed sustained remission (p = 0.045). The most common concomitant factors for a spontaneous relapse were irregular lifestyle habits and pregnancy-related switch from valproate to another ASM. Patients with a history of catamenial seizures were more likely to experience a spontaneous generalized tonic-clonic seizure relapse after 4-year remission at univariable analysis. SIGNIFICANCE: Our data support the prognostic relevance of early medication response in JME patients. Furthermore, the prognostic significance of catamenial seizures and the impact of valproate switch on seizure relapse after a prolonged remission account for the challenging therapeutic management of women with childbearing potential.

High rates of early remission pattern in adult-onset compared with earlier-onset idiopathic generalized epilepsy: A long-term follow-up study.

OBJECTIVE: To investigate electroclinical characteristics and prognostic patterns of adult-onset vs. younger-onset idiopathic generalized epilepsy (IGE) patients during long-term follow-up. METHODS: In this single-center retrospective cohort comparative study, adult-onset IGE was defined as onset after 20 years of age. Patients with a follow-up duration between 10 and 30 years from epilepsy diagnosis were enrolled. Maximum follow-up duration was limited to 30 years to ensure a better comparison of prognostic data between adult-onset and younger-onset patients. The Benjamini-Hochberg false discovery rate (FDR) method was applied to obtain FDR-adjusted p-values. RESULTS: A total of 177 IGE patients were recruited and 27 adult-onset IGE patients were identified (15.3%). Follow-up duration was similar between younger- and adult-onset IGE patients and 74% of subjects performed at least one 24-hour EEG recording. Of adult-onset IGE patients, 8/27 were diagnosed with juvenile myoclonic epilepsy, while 19/27 were diagnosed with generalized tonic-clonic seizures (GTCS) only. EEG photosensitivity and absence seizures were significantly less frequent among adult-onset IGE patients as compared with younger subjects. When considering prognostic patterns, an early remission pattern was significantly higher among adult-onset IGE patients as compared with younger-onset IGE patients (55.6% vs. 24%, adjusted p value = 0.007). Antiseizure medication withdrawal was attempted in 3/27 adult-onset patients, and all had GTCS relapses. CONCLUSION: Our study contributes to better defining the electroclinical characteristics and long-term follow-up of adult-onset IGE patients. A favorable long-term seizure outcome was found in adult-onset IGE patients, as evidenced by the high rates of early remission pattern when compared with younger onset patients.

Reconsidering the role of selective sodium channel blockers in genetic generalized epilepsy.

OBJECTIVE: Selective sodium channel blockers (SSCBs) have a limited use in genetic generalized epilepsy (GGE), due to their well-known risk of seizure worsening. Although their therapeutic potential in GGE has been suggested by recent evidence, electro-clinical data supporting their prescription are lacking. We aimed to investigate SSCB safety and effectiveness in a GGE cohort. METHODS: Subjects who received SSCBs and had ≥5-year follow-up were enrolled. Lamotrigine was excluded from analysis due to its broader pharmacodynamic spectrum and its better-documented efficacy in GGE. RESULTS: Fifty-six patients (median follow-up 28.5 years) were included. The most used SSCB was carbamazepine in 40 subjects. At the last medical observation, only 9 subjects were still receiving SSCBs. The occurrence of generalized polyspike-wave discharges (GPSWDs) predicted reduced SSCB retention in Cox multivariate analysis. A seizure reduction ≥50% occurred in 53.5% (30/56) of subjects when considering all seizure types; however, the proportion of responders increased to 67.9% when considering only generalized tonic-clonic seizures (GTCS). GPSWDs were significantly associated with a reduced response rate, whereas GGE with GTCS only syndrome with a better outcome. The switch from SSCBs to antiseizure medications licensed for GGE improved seizure control in 65% of patients. Seizure worsening was reported in 5/56 patients; juvenile myoclonic epilepsy and a family history of epilepsy were significantly associated with seizure aggravation. CONCLUSION: SSCBs appeared effective on GTCS, but epilepsy aggravation and unsatisfactory control of other seizure types were not uncommon. Our study contributes to identifying new clinical and EEG variables associated with SSCB effectiveness and safety which may help neurologists in patients' management.

Acute-onset binocular diplopia in neurological unit: Aetiological factors and diagnostic assessment.

OBJECTIVES: To investigate the aetiology of acute-onset binocular diplopia (AOBD) in neurological units and identify the key diagnostic procedures in this setting. MATERIALS AND METHODS: Clinico-demographic data from patients hospitalized for AOBD from 2008 to 2019 were retrospectively reviewed. AOBD due to an underlying neurological disorder known to cause diplopia was addressed as secondary diplopia. Ophthalmoparesis plus was defined when subtle neurological signs/symptoms other than ophthalmoparesis were detected during neurological examination. RESULTS: A total of 171 patients (mean age 57.6 years) were included in the study. A total of 89 subjects (52%) had an oculomotor disturbance consistent with sixth nerve palsy, and 42 (24.6%) showed multiple oculomotor nerve involvement. The most common cause of AOBD was presumed to be microvascular in 56 patients (32.7%), while a secondary aetiology was identified in 102 (59.6%). Ophthalmoparesis plus and multiple oculomotor nerve involvement significantly predicted a secondary aetiology in multivariable logistic regression analysis. Brain CT was never diagnostic in isolated ophthalmoparesis. A combination of neuroimaging examinations established AOBD diagnosis in 54.9% of subjects, whereas rachicentesis and neurophysiological examinations were found to be performant in the remaining cases. CONCLUSIONS: AOBD may herald insidious neurological disease, and an extensive diagnostic workup is often needed to establish a diagnosis. Neurological examination was pivotal in identifying patients at higher risk of secondary aetiology. Even in cases of apparently benign presentation, a serious underlying disease cannot be excluded. Brain MRI was found to perform well in all clinical scenarios, and it should be always considered when managing AOBD.