Background: and Purpose Temporal dissociation between electrographic and clinical seizure onset in mesial temporal lobe epilepsy (MTLE) implies network heterogeneity. We hypothesized that MTLE consists of distinct electroclinical phenotypes defined by divergent seizure propagation dynamics. Methods: We retrospectively analyzed 167 seizures from 13 patients with drug-resistant MTLE who achieved Engel Class I surgical outcomes. Based on the predominant relationship between scalp electroencephalography (EEG) and clinical onset, patients were classified as EEG-first (n=7) or Clinical-first (n=6). Seizure onset patterns, propagation pathways, and temporal dynamics were assessed using scalp and stereoelectroencephalography (SEEG). Results: The cohort included 83 scalp and 84 SEEG seizures. By definition, onset order differed: in EEG-first seizures, scalp changes preceded clinical signs in 70.5%, whereas the reverse occurred in 65.8% of Clinical-first seizures (p<0.001). EEG-first seizures demonstrated longer SEEG-to-clinical latency (28.8±7.7 s vs. 13.0±7.7 s; p=0.004) and rhythmic theta onset on scalp EEG with focal SEEG low-voltage fast activity or preictal spikes. In contrast, Clinical-first seizures showed heterogeneous scalp patterns (theta, delta–theta, or delta slowing). Propagation tended to differ, with anterior pathways more common in EEG-first (69.6%) and posterior pathways in Clinical-first (26.3%), though with partial overlap (p=0.138). Conclusions MTLE comprises two pathophysiologically distinct phenotypes: EEG-first, reflecting a slowly propagating anterior mesial network, and Clinical-first, involving a rapidly spreading posterior network. This classification offers a mechanistic framework for understanding electroclinical dissociation and may refine presurgical evaluation.

Background: and Purpose Live cell-based assays (LCBA) are increasingly used for serological antibody detection due to their ability to preserve antigen conformation, offering moderately higher sensitivity than fixed cell-based assays. However, the clinical necessity of prioritizing LCBA for the detection of aquaporin-4 immunoglobulin G (AQP4-IgG) in neuromyelitis optica spectrum disorder (NMOSD) remains unclear, especially when compared to its established role in diagnosing myelin oligodendrocyte glycoprotein antibody-associated disease. Methods: We compared the performance of live cell-based assays using immunofluorescence (LCBA-IF) and fixed cell-based assays using immunofluorescence (FCBA-IF) in detecting AQP4-IgG in 90 cases of NMOSD meeting 2015 International Panel for Neuromyelitis Optica Diagnosis criteria, alongside 40 controls. Additionally, we further investigated the relationship between AQP4-IgG titers as measured by LCBA-IF and FCBA-IF and clinical parameters in NMOSD patients. Results: Results showed 96.9% agreement between LCBA-IF and FCBA-IF (Cohen’s κ=0.935), with a strong Spearman correlation (0.977, p<0.001). Both methods demonstrated 100% specificity, with LCBA-IF showing slightly higher sensitivity compared to FCBA-IF. Within LCBAIF-tested groups, statistically significant differences in annualized relapse rates were observed across all pairwise comparisons (low-titer vs. moderate-titer, low-titer vs. high-titer, and moderate-titer vs. high-titer; all p<0.050). However, this association reached statistical significance in some FCBA-IF-tested groups. Conclusions Overall, there is a strong concordance between LCBA-IF and FCBA-IF in detecting AQP4-IgG, where LCBA-IF shows slightly higher sensitivity. Furthermore, there is a potential link between elevated AQP4-IgG titers and an increased risk of relapse, and this correlation may appear more pronounced when using LCBA-IF.

Background: and Purpose To compare the epidemiological and clinical features of the rare patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) with age- and sex-matched controls in a nationwide cohort from South Korea. Methods: This observational cohort study analyzed newly diagnosed CADASIL patients aged at least 20 years and matched controls using data from the National Health Information Database for 2004–2022. The cumulative incidence of CADASIL was assessed by age and sex, and compared between regions. Neurologic and systemic diseases were compared between the CADASIL and control groups. Results: The study analyzed 816 CADASIL patients and 816 age- and sex-matched controls aged 56.8±15.2 years (mean±standard deviation), among whom 48.3% were male. The cumulative incidence of CADASIL was 1.86 per 100,000 people (95% confidence interval [CI]=1.85– 1.87 per 100,000), and peaked at 60–69 years of age. In terms of regional distribution, the incidence was highest for Jeju, at 39.67 per 100,000 (95% CI 37.84–41.49 per 100,000). Neurologic diseases were more frequent in CADASIL patients, including Alzheimer’s disease (33.1% vs.20.0%), vascular dementia (84.9% vs. 5.0%), epilepsy (34.6% vs. 15.9%), stroke (70.7% vs. 27.6%), parkinsonism (18.9% vs. 11.0%), and depression (60.8% vs. 44.9%). Systemic diseases such as diabetes mellitus (78.9% vs. 68.9%) were also more common in CADASIL patients, while cancer (27.9% vs. 38.7%) and myocardial infarction (10.0% vs. 13.6%) were less common than in controls. The onset ages of all diseases were lower in CADASIL patients. Conclusions This study has provided a precise nationwide estimate of the CADASIL incidence and its regional distribution in South Korea. CADASIL patients showed higher incidence rates and earlier onsets of diverse clinical manifestations.

Background: and Purpose Criteria for amyloid-related imaging abnormalities in anti-amyloid therapy are based on T2* gradient-recalled echo (GRE), but susceptibility-weighted imaging (SWI) is widely used, creating uncertainty. This study quantitatively compared the detectability of SWI and GRE for cerebral microbleeds and established evidence supporting distinct microbleed criteria for each. Methods: A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed and Embase were searched for studies directly comparing SWI and GRE up to August 8, 2024. Study quality was assessed with QUADAS-2. The pooled proportion of microbleed detection and detection ratio were calculated. Subgroup analyses were performed based on magnetic field strength (1.5 T vs. 3 T) and SWI slice thickness (<2 mm vs. ≥2 mm), equipment vendor, and study quality. Results: Thirteen studies were included. SWI detected cerebral microbleeds approximately 1.6times more effectively than GRE. At 3.0 T and 1.5 T, SWI exhibited 1.7-fold and 1.5-fold greater detectability, respectively. SWI with thinner slices (<2 mm) showed a 1.9-fold improvement, while thicker slices (≥2 mm) showed a 1.3-fold improvement. Subgroup analyses revealed no significant differences between vendors (0.61 vs. 0.60, p=0.89), or by study quality (0.61 vs. 0.59,p=0.89). Conclusions SWI detects cerebral microbleeds about 1.6 times more effectively than GRE, highlighting important differences between the two techniques. Cautious exploration of adjusted thresholds may be needed, and prospective validation in therapy-specific cohorts will be essential before clinical application.

Background: and Purpose Neuropsychiatric symptoms (NPS) are frequent in dementia and mild cognitive impairment (MCI), yet their reported associations with white matter hyperintensities (WMHs) remain inconsistent. We examined item-level associations between WMHs and NPS across Alzheimer’s disease dementia (ADD), dementia with Lewy bodies (DLB), and amnestic MCI (aMCI). Methods: This multicenter retrospective study involved 523 patients: 276 with ADD, 67 with DLB, and 180 with aMCI. Three-dimensional T1-weighted and T2–fluid-attenuated inversion recovery magnetic resonance images were processed with BAAD (Brain Anatomical Analysis using Diffeomorphic Deformation) software to quantify WMH volume (WMHV) and gray matter volume (GMV), normalized to total intracranial volume (TIV). NPS were assessed using the Neuropsychiatric Inventory. Multiple regression analyses were performed within each group, adjusting for GMV/TIV, age, sex, years of education, Clinical Dementia Rating–Sum of Boxes score, and institution. Results: In the aMCI group, higher WMHV/TIV was positively associated with depression, apathy, and disinhibition, and negatively with delusions. Subregional analyses revealed NPSspecific topographic patterns. No significant associations were detected in the ADD or DLB group. GMV/TIV was positively associated with delusions in the ADD group, but negatively associated with hallucinations in the DLB group. Conclusions Associations between WMHs and NPS were evident in the aMCI group but absent in the ADD and DLB groups, suggesting a stage-dependent effect. WMHs may contribute to NPS primarily in prodromal stages, whereas their influence may be overshadowed by neurodegenerative pathology in dementia. Clarifying the mechanisms underlying WMHs is critical for evaluating their potential as intervention targets.

Background: and Purpose Induced hypertension therapy (IHT) is effective for treating early neurological deterioration (END) in patients with single subcortical infarction (SSI). However, the underlying pathophysiology of SSI is diverse and may affect the efficacy of IHT. Methods: We reviewed patients with SSI who experienced END and received IHT were enrolled. END was defined as ≥2-point increase in the National Institutes of Health Stroke Scale (NIHSS) score, ≥1 motor point increase. IHT was performed by using phenylephrine infusion to raise systolic blood pressure by 10%–20% over baseline. SSI was classified into three subtypes: distal (dSSI), proximal (pSSI), and SSI with parental artery disease (SSIPAD; with stenosis at parental artery disease <50%). Responders were defined as patients who showed neurological improvement (decrease of ≥2 points in NIHSS, ≥1 motor point decrease) within one day after IHT initiation. Multivariable analysis identified factors associated with responders. Results: Characteristics were compared between responders and non-responders, and factors associated with response to IHT were investigated. Among 96 patients (mean age, 64.7± 12.9 years; 61.5% male), 49 (51.0%) patients were categorized as responders. Multivariable analysis showed that pSSI (adjusted odds ratio [aOR]=18.10, 95% confidence interval [CI] 5.04–80.60, p<0.001) and SSIPAD (aOR=4.56, 95% CI 1.31–19.00, p=0.024) were associated with a positive response to IHT compared to dSSI. Additionally, less white matter changes (Fazekas scale 0–1) were associated with a better response to IHT (aOR=0.15, 95% CI 0.03–0.67,p=0.019). Conclusions Response to IHT varied according to SSI subtypes and the severity of small vessel changes.