Journal of Clinical Neurology最新文献

Background and purpose: Acute necrotizing encephalopathy (ANE) is a rare and severe type of parainfectious encephalopathy. The pathogenesis and genetic features of ANE remain underinvestigated. In this study we aimed to characterize the genetic profiles of ANE, including novel variants and pathways.

Methods: We conducted a retrospective cohort study of 16 ANE patients and 7 controls, collecting clinical data, cerebrospinal fluid (CSF) findings, neuroimaging findings, and treatment information. Whole-exome sequencing (WES) was performed to investigate potential function-impacting genetic mutations in RANBP2, CPT II, and RNH1. Enrichment analyses were conducted to explore the associated pathways.

Results: The median age of the ANE patients was 21 years, and viral infections such as SARS-CoV-2 and influenza were common triggers. The CSF interleukin-6 level was elevated in four patients (median=598 pg/mL, interquartile range=101-4,000 pg/mL). WES identified 278 low-frequency variants. Four pathogenic/likely pathogenic mutations (p.T585M and p.I656V) and one novel mutation of uncertain significance (p.P2733S) were identified in RANBP2, while the susceptibility alleles of p.F352C and p.V368I in CPT II were detected in three patients. Functional enrichment analyses revealed that, relative to the control group, pathways including nucleocytoplasmic transport, defense response to virus, positive regulation of tumor necrosis factor production, and JAK-STAT signaling pathways were significantly enriched in ANE patients.

Conclusions: This study integrated genetic profiles with the clinical characteristics of ANE patients, and revealed the role of RANBP2 as well as the potential involvement of cytokine pathways in ANE pathogenesis.

Background and purpose: We developed and validated an automated hyperdense artery sign (HAS) segmentation algorithm for the distal internal carotid artery and middle cerebral artery on noncontrast brain computed tomography (NCCT) using a multicenter dataset with independent annotation performed by two experts.

Methods: For training and external validation, we included patients with ischemic stroke who underwent concurrent NCCT and CT angiography between May 2011 and December 2022 at six hospitals and one hospital, respectively. For clinical validation, nonoverlapping patients admitted within 24 hours of onset were consecutively included between December 2020 and April 2023 from six hospitals. The model was trained using the 2D U-Net deep-learning architecture with manual annotation by two experts. We constructed models trained on datasets annotated individually by each expert, and an ensemble model using shuffled annotations by both experts. The performance of the models was compared using the area under the receiver operating characteristic curve (AUROC), sensitivity, and specificity.

Results: This study included 673, 365, and 774 patients in the training/internal validation, external validation, and clinical validation datasets, respectively, who were aged 68.8±13.2, 67.8±13.4, and 68.8±13.6 years (mean±standard deviation) and comprised 55.0%, 59.5%, and 57.6% males. The ensemble model achieved higher AUROC and sensitivity than the models trained on annotations by a single expert in the external validation. For the clinical validation dataset, the ensemble model exhibited an AUROC of 0.846 (95% confidence interval [CI], 0.819-0.871), sensitivity of 76.8% (95% CI, 65.1%-86.1%), and specificity of 88.5% (95% CI, 85.9%-90.8%). The predicted volume of the clot was correlated with the infarct volume in follow-up diffusion-weighted imaging (r=0.42, p<0.001).

Conclusions: Our new algorithm can rapidly and accurately identify the HAS, and so can facilitate the screening of potential patients requiring intervention.

This corrects the article on p. 190 in vol. 21, PMID: 40308014.

Background and purpose: To determine whether the RNF213 p.R4810K mutation modifies the number of moyamoya disease manifestations and recurrent strokes in isolated intracranial arterial steno-occlusive disease (ICAD).

Methods: This retrospective case-control study analyzed patients who visited the Asan Medical Center with steno-occlusive lesions in the M1 segment of the middle cerebral artery and terminal internal carotid artery, and underwent RNF213 genetic testing for screening moyamoya disease between January 2010 and November 2022. Patients with supportive findings of moyamoya disease or moderate-to-severe stenosis in the extracranial arteries were excluded. After matching antiplatelet drugs, the presentation of moyamoya disease and stroke recurrence were analyzed using chi-squared analysis and Kaplan-Meier survival curve analysis.

Results: The 1,567 patients who underwent evaluations of RNF213 polymorphisms included 753 with ICAD, among whom females predominated (n=452, 60.0%) and 289 (38.4%) had an RNF213 mutation. The follow-up period was 2.47±3.51 years (mean±standard deviation; median=1.00 year, interquartile range=0-4 years). The risk of progression to moyamoya disease was higher in the RNF213-related-vasculopathy group than the RNF213-negative stenosis group (n=27 [9.3%] versus n=6 [1.3%], p<0.01), as were the risks of ischemic stroke (n=13 [4.5%] versus n=7 [1.5%], p=0.01) and hemorrhagic stroke (n=5 [1.7%] versus n=1 [0.2%], p=0.02, respectively). Furthermore, the presence of an RNF213 mutation was significantly associated with the risk of stroke recurrence (odds ratio=2.34, 95% confidence interval=1.44-3.80, p<0.01).

Conclusions: Evaluations of RNF213 polymorphisms may help to identify patients with isolated ICAD at a high risk of progression to moyamoya disease and stroke.

Background and purpose: We aimed to determine the proportion of Korean patients with early Alzheimer's disease (AD) who are eligible to receive lecanemab based on the United States Appropriate Use Recommendations (US AUR), and also identify the barriers to this treatment.

Methods: We retrospectively enrolled 6,132 patients with amnestic mild cognitive impairment or mild amnestic dementia at 13 hospitals from June 2023 to May 2024. Among them, 2,058 patients underwent amyloid positron emission tomography (PET) and 1,199 (58.3%) of these patients were amyloid-positive on PET. We excluded 732 patients who did not undergo brain magnetic resonance imaging between June 2023 and May 2024. Finally, 467 patients were included in the present study.

Results: When applying the criteria of the US AUR, approximately 50% of patients with early AD were eligible to receive lecanemab treatment. Among the 467 included patients, 36.8% did not meet the inclusion criterion of a Mini-Mental State Examination (MMSE) score of ≥22.

Conclusions: Eligibility for lecanemab treatment was not restricted to Korean patients with early AD except for those with an MMSE score of ≥22. The MMSE criteria should therefore be reconsidered in areas with a higher proportion of older people, who tend to have lower levels of education.