Jung Seok Lee

Previous studies have reported mixed findings regarding sex differences in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), with some indicating earlier ischemic events in men, whereas others found no significant difference in stroke onset. However, evidence from Asian populations remains limited, where clinical manifestations and NOTCH3 variant distribution differ substantially from those in European cohorts. We investigated sex-specific variations in clinical phenotypes and brain MRI characteristics among Korean patients with CADASIL. In this nationwide retrospective study, 577 patients were screened for CADASIL across 26 centers in South Korea. After excluding those with benign or uncertain variants or insufficient clinical or MRI data, 368 individuals with pathogenic NOTCH3 variants were included in the final analysis. Clinical features, vascular risk factors, and NOTCH3 variant positions classified by epidermal growth factor–like repeat (EGFr) domains were compared between sexes. Brain MRI findings—including white matter hyperintensities (WMHs), lacunes, cerebral microbleeds, and atrophy—were evaluated. Sex differences in the onset of ischemic stroke and dementia were analyzed using Kaplan-Meier and Cox proportional hazards models. The mean age of the patients at data collection was 61.7 ± 11.9 years, and 48.6% were male. Thirty-six distinct pathogenic variants were identified. The most frequent variant was R544C (40.8%) located at the EGFr 13/14 interdomain boundary (corresponding to exon 11). Other recurrent variants were R75P (17.9%), C542R (5.4%), and R587C (4.6%). Men exhibited a higher prevalence of ischemic stroke (70.9% vs 44.4%, p < 0.001) and experienced their first event at an earlier age (median 53 vs 59 years, log-rank p < 0.001). On brain MRI, male sex was independently associated with a greater lacune burden (odds ratio 3.03, 95% CI 1.70–5.38, p < 0.001) while female sex tended to show higher WMH volume. This nationwide study highlights distinct sex differences in CADASIL presentation within a Korean population. Male patients exhibited a higher prevalence and earlier onset of ischemic stroke not fully explained by conventional vascular risk factors. These findings underscore the importance of integrating sex, hormonal, and genetic-epigenetic factors into future research to guide precision phenotyping and sex-informed clinical management in CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small vessel disease caused by variants in the NOTCH3 gene. The extracellular domain of NOTCH3 (N3ECD) has been proposed as a potential serum biomarker for CADASIL. However, its diagnostic utility remains uncertain. The aim of this study was to evaluate serum N3ECD levels in patients with CADASIL and assess their potential as a diagnostic or prognostic biomarker. Serum N3ECD levels were measured using ELISA in 2 independent CADASIL cohorts: a Korean cohort (n = 78) and a Japanese cohort (n = 64). Each group included patients with genetically confirmed CADASIL. In addition, the Korean cohort included age-matched and sex-matched healthy controls and patients with sporadic ischemic stroke. Statistical analyses assessed group differences and correlations with clinical and radiologic features. Serum N3ECD levels did not differ significantly among patients with CADASIL, healthy controls, and patients with ischemic stroke in the Korean cohort (p = 0.149). However, in the Korean cohort, N3ECD levels showed a positive correlation with age (r = 0.329, p = 0.001), particularly in individuals carrying the p.Arg544Cys variant. Similarly, in the Japanese cohort, age-related increases in N3ECD levels were observed in p.Arg75Pro variant carriers (r = 0.661, p = 0.014). No significant associations were found between N3ECD levels and MRI markers or clinical outcomes such as stroke occurrence or cognitive impairment. These findings suggest that serum N3ECD alone has limited value as a standalone diagnostic marker for CADASIL. However, the age-dependent increase in N3ECD levels observed in specific variant carriers may reflect underlying pathophysiologic changes and could serve as a clue to disease progression. Further studies are warranted to clarify the mechanistic role of N3ECD in CADASIL and to evaluate its potential as a marker for monitoring disease progression or therapeutic response. Continued biomarker discovery efforts are needed to improve diagnosis and management of CADASIL.

A 67-year-old woman with myeloperoxidase (MPO)-antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis presented with progressive cognitive decline and was diagnosed with amnestic mild cognitive impairment. Brain magnetic resonance imaging (MRI) revealed chronic infarcts consistent with cerebral small vessel disease. Although conventional vascular risk factors were present, they were insufficient to fully account for the imaging and clinical findings. This case suggests that MPO-ANCA-associated vasculitis should be considered in the differential diagnosis of patients presenting with vascular cognitive impairment, particularly in the presence of systemic inflammatory features.

Background: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small vessel disease caused by NOTCH3 mutations. While CADASIL affects both sexes, differences in clinical presentation and brain magnetic resonance imaging (MRI) findings remain unclear. This study aims to investigate sex-specific variations in vascular risk factors, clinical manifestations, and brain MRI features among Korean CADASIL patients. Methods: A nationwide retrospective study analyzed 368 CADASIL patients (179 men, 189 women). Clinical characteristics, vascular risk factors, and NOTCH3 variants were compared between sexes. Brain MRI findings, including white matter hyperintensity, lacunes, cerebral microbleeds, atrophy, and enlarged perivascular spaces, were evaluated. Kaplan-Meier analysis assessed sex differences in the onset of ischemic stroke, intracerebral hemorrhage (ICH), and dementia, and recurrent headaches. Results: Men exhibited a higher prevalence of ischemic stroke (70.9% vs. 44.4%, p<0.001), whereas women were more likely to report recurrent headaches (35.4% vs. 16.9%, p<0.001). Survival analysis showed that men had a significantly earlier onset of ischemic stroke (Hazard Ratio[HR]: 2.78, 95% CI: 1.92-4.03, p<0.001) while being male was associated with significantly later onset of recurrent headache (HR: 0.59, 95% CI: 0.38-0.90, p=0.016). No significant sex differences were observed for ICH (HR: 2.04, 95% CI: 0.80-5.18, p=0.136) or dementia (HR: 1.26, 95% CI: 0.56-2.84, p=0.579). On brain MRI, male sex was associated with significantly higher risk for lacune burden (Odds Ratio[OR] 3.03, 95% CI 1.70-5.38, p<0.001) along with age (OR 1.03, 95% CI 1.01-1.05, p=0.002) and hypertension (OR 1.86, 95% CI 1.15-3.03, p=0.002). Conclusion: This study highlights significant sex-based differences in CADASIL, with men experiencing earlier and higher risk of ischemic stroke, along with a greater burden of lacunes, while women showed an increased likelihood of recurrent headaches at an earlier age. These findings underscore the importance of integrating sex-specific considerations into CADASIL prognosis and treatment planning.

Intraoperative neurophysiologic monitoring during brain tumor surgery should acquire a baseline data as soon as possible. However, motor unit potentials (MEP) in our case showed baseline data could not be acquired in the early stage of surgery, but consecutive trials had abrupt appearance of MEP just after dura opening. This case shows the acquisition of baseline MEP during brain tumor surgery should not be given up until the dura is open especially in a state of raised intracranial pressure.

Complete surgical resection is a well-known therapeutic gold standard for spinal ependymoma, but it is associated with high postoperative morbidity. Intraoperative neuromonitoring (INM) is important for detecting and reducing the rate of surgical complications during this operative procedure. We report a case of postoperative paraplegia due to tumor bleeding during the operation. INM of the patient revealed abrupt loss of waveforms during the operation. This finding suggested that INM is helpful for detecting intraoperative hematomyelia and minimizing postoperative neurologic sequelae.

Maternally inherited diabetes and deafness (MIDD) is a disorder characterized by the occurrence of diabetes mellitus and hearing impairment at a young age, caused by point mutations in mitochondrial DNA. MIDD can be accompanied by various neurological symptoms. In this patient, memory impairment and ataxia were the predominant neurological symptoms. Herein, we report MIDD patients with the m.3243A>G mutation who present with cognitive decline and gait disturbance at the age of 59.

Journal of Intraoperative Neurophysiology는 수술중신경계감시 및 관련분야에 종사하는 의사, 보건의료인 및 기초 연구자들을 대상으로 하며, 수술중신경계감시와 관련분야의 모든 연구 결과 및 최신 소견 등을 게재한다. 타 학회지에 이미 게재된 내용의 원고는 게재하지 않으며, 본 학회지에 게재된 것을 임의로 다른 잡지에 게재할 수 없음을 원칙을 한다