Background and Objectives Late-onset unexplained epilepsy (LOUE) represents a substantial proportion of epilepsies with onset after 50 years and often manifests as temporal lobe epilepsy (LO-TLE). Although a link with Alzheimer disease (AD) has been suggested, only a subset of LO-TLE shows AD-related biomarkers, indicating biological heterogeneity. This study aims to characterize the cognitive and CSF phenotype of LO-TLE and compare it with healthy controls (HCs) and patients with mild cognitive impairment due to AD (MCI-AD). Methods This Italian cross-sectional cohort study included LO-TLE patients with normal CSF β-amyloid (Aβ) biomarkers, MCI-AD, and age-matched and sex-matched HC. Participants underwent structural MRI, neuropsychological assessment, and CSF biomarkers assay, including neurofilament light chain (NfL) and the phosphorylated-to-total tau ratio (p/t-tau). Cortical thickness and subcortical volumes were quantified from structural MRI. Cognitive performance was summarized using principal component analyses. Group differences in imaging, cognition, and CSF biomarkers were assessed, and associations between CSF markers and cognition were examined within groups. Results The study included 18 LO-TLE, 24 MCI-AD, and 17 HC. LO-TLE showed preserved cortical thickness and subcortical volumes comparable with HC, whereas MCI-AD exhibited widespread cortical thinning and medial temporal atrophy. Despite normal imaging, LO-TLE showed lower performance compared with HC in episodic memory (t(53) = −7.79, pFDR < 0.001), short-term memory (t(53) = −2.94, pFDR = 0.007), language (t(53) = 4.12, pFDR < 0.001), and executive functions (t(53) = −3.76, pFDR < 0.001), while attention was preserved. Global cognitive performance further distinguished LO-TLE from MCI-AD, with the former group performing better (t(53) = 4.21, pFDR < 0.001). LO-TLE CSF profiles were characterized by low NfL levels and a p/t-tau ratio below the proposed cutoff of 0.17, whereas MCI-AD showed pathologic Aβ and tau alterations, elevated NfL, and p/t-tau ratio above 0.17. In LO-TLE, a higher p/t-tau ratio was associated with better performance on global cognition (rs = 0.585, pFDR = 0.032) and short-term memory (rs = 0.588, pFDR = 0.032), whereas no associations emerged in MCI-AD. Discussion LO-TLE with normal CSF AD biomarkers is characterized by distinct cognitive and biological features compared with MCI-AD, suggesting a disease process independent of AD. The low p/t-tau ratio may reflect alternative pathophysiologic mechanisms and warrants further investigation in larger longitudinal studies to clarify the underlying pathology and clinical trajectories.
Alessia Casarini, Alice Ballerini, Riccardo Maramotti et al.· Neurology· 0 citations
Background and Objectives Reliable prediction of short-term mortality in status epilepticus (SE) can contribute to guide clinical decisions. Current prognostic systems achieve only acceptable predictive power and show lack of generalizability or poor calibration. We aimed to identify clinical predictors of short-term mortality in patients with nonhypoxic SE and develop a predictive score. Methods This was a multicenter, multinational cohort study based on registry data. Participants were consecutive episodes of SE in participants aged 14 years or older from Modena (Italy) (derivation cohort) and in participants aged 18 years or older from Salzburg (Austria) (validation cohort). The predefined outcome was 30-day mortality after the onset of SE. Age, sex, level of consciousness before treatment, semiology of SE, level of disability at baseline before SE, etiology, and treatment refractoriness were assessed. Adjusted regression coefficients of each independent predictor were transformed to produce a points-based risk scoring system. Results The Italian cohort included 689 episodes, and the Austrian cohort comprised 569 episodes of SE. In the derivation cohort, the 30-day mortality rate was 27.3%. The independent risk factors were aged 75 years or older (odds ratio [OR] 5.52, 95% CI 3.45–8.83; p < 0.001), consciousness impairment (stuporous or comatose) before SE treatment (OR 1.76, 95% CI 1.09–2.82; p = 0.020), acute etiology due to primary CNS pathology (OR 2.60, 95% CI 1.60–4.23; p < 0.001), refractoriness to treatment (OR 6.40, 95% CI 3.91–10.46; p < 0.001), and disability before SE onset (OR 3.53, 95% CI 2.22–5.61; p < 0.001); remote etiology was independently associated with a lower likelihood of 30-day mortality (OR 0.28, 95% 0.13–0.61; p = 0.001). An integer-based scoring system termed Age, Consciousness, Aetiology, Refractoriness, Disability (ACARD) was developed by combining these independent predictors. In the validation cohort, the 30-day mortality rate was 11.6%. The area under the curve of the ACARD score was 0.864 (95% CI 0.836–0.891) in the derivation cohort and 0.845 (95% CI 0.801–0.888) in the validation cohort. Calibration plot indicated good fit of predicted and observed data in both cohorts. Discussion The ACARD score is a user-friendly tool developed to predict 30-day mortality after nonhypoxic SE. It has the potential to identify participants at high risk of short-term mortality and outperform the performance of other available scoring systems.
Simona Lattanzi, E. Trinka, P. Bosque-Varela et al.· Neurology· 0 citations
