Journal of Clinical Neurology最新文献

Background and purpose: We aimed to determine efficacy, safety, and predictors of response and side effects of lasmiditan in Korean patients with migraine.

Methods: We prospectively recruited patients who took lasmiditan at the Seoul National University Hospital between April 2023 and March 2024. We collected data on treatment, adverse events, and dosage adjustment profiles. Tolerability was defined as dosage maintenance or dosage increase. Logistic regression analyses were performed to identify predictors of a response to lasmiditan and adverse events.

Results: This study included 154 patients. At visit 1, 110 (71.4%) and 44 (28.6%) patients were prescribed 50 and 100 mg of lasmiditan daily, respectively, with a treatment response observed at visit 2 in 49 (44.5%) and 20 (45.5%) patients, respectively. Adverse events were reported in 75 (48.7%) patients. Multivariate logistic analyses showed that female sex (odds ratio [OR]= 4.51, 95% confidence interval [CI]=1.43-14.19, p=0.01) and higher daily dose (100 mg vs. 50 mg: OR=2.35, 95% CI=1.14-4.83, p=0.02) were independently associated with adverse events. Dosage increase, dosage reduction, and treatment discontinuation occurred in 56 (36.4%), 17 (11.0%), and 40 (26.0%) patients, respectively. Lasmiditan was well tolerated by 97 (63.0%) patients.

Conclusions: This was the first real-world study of lasmiditan in Korean patients with migraine. Although administered at a low dosage, lasmiditan was effective in approximately half of the patients. Dizziness was the most common adverse event, and it occurred at a higher rate than in clinical trials.

Traumatic brain injury (TBI) is one of the main mechanisms underlying health issues associated with functional and structural brain changes. While direct effects such as cognitive and physical impairments are well documented, recent research has linked TBI to neurodegenerative changes similar to dementia. TBI-related neurodegeneration includes progressive brain-tissue degeneration that leads to behavioral changes, cognitive decline, and dementia-like symptoms. The exact underlying mechanisms are complex, and include neuroinflammation, oxidative stress, excitotoxicity, and disruption to protein homeostasis. Neuroinflammation is controlled by the activation of astrocytes and microglia and causes neuronal damage and the prolonged release of proinflammatory cytokines. Oxidative stress damages cell and impairs mitochondrial function, while the accumulation of misfolded proteins such as tau and β-amyloid mimics the pathology of Alzheimer's disease. Excitotoxicity involves excessive neurotransmitter release that may lead to further injuries. Epidemiological studies show that the risk of dementia is increased after moderate-to-severe TBI and influenced by age and genetic factors. Current management strategies focus on symptom relief, and there is ongoing research aimed at improving the understanding of the underlying mechanisms and the development of effective treatments.

Background and purpose: Neuronal intranuclear inclusion disease (NIID) is a progressive neurodegenerative disease characterized by a wide range of clinical manifestations. GGC-repeat expansion in NOTCH2NLC was recently identified as the genetic cause of NIID. Here we report clinical, radiological, pathological, and genetic findings in NIID patients.

Methods: Twenty-five NIID patients from 22 unrelated families of Korean ancestry were reviewed from 9 referral centers in South Korea. We compared clinical features between sporadic and familial NIID patients. We classified NIID patients according to their prominent symptoms. The presence of GGC repeat expansion was analyzed in 19 patients.

Results: The 25 reviewed NIID patients comprised 12 (48.0%) sporadic and 13 (52.0%) familial cases, with the latter showing a significantly higher proportion of males (p=0.027). The patients were classified into three subtypes based on the prominent symptoms: NIID-Episodic (44.0%), NIID-EPS (extrapyramidal symptoms) (36.0%), and NIID-Dementia (20.0%). Most patients (92.0%) also exhibited other symptoms, including peripheral neuropathy (60.0%), bladder dysfunction (48.0%), or ophthalmic problems (56.0%). Hyperintensities along the corticomedullary junctions in diffusion-weighted imaging and extensive white-matter hyperintensities in fluid-attenuated inversion-recovery imaging were observed in 96.0% and 100% of the patients, respectively. GGC repeat expansion in NOTCH2NLC was identified in 6 sporadic and 10 familial cases. The number of GGC repeats was not correlated with the onset age or clinical symptoms.

Conclusions: This study has highlighted the diverse phenotypes and genetic profiles of Korean NIID patients, and provided valuable insights into this rare disorder.

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.