Journal of Clinical Neurology最新文献

Background and purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a major hereditary small-vessel disease caused by mutations in NOTCH3. We hypothesized that the gut microbiota may serve as an environmental factor influencing disease progression or phenotype diversity among patients. Our previous study identified taxonomic differences between CADASIL patients and controls. In this study, we aimed to replicate our initial findings and further analyze gut microbial metabolites.

Methods: We performed 16S rRNA sequencing of gut microbiota in the 24 patients and 17 controls. Of these, 15 patients and 13 controls underwent analyses of fecal metabolites.

Results: Among the 24 CADASIL patients and 17 controls recruited, 16S rRNA sequencing of fecal samples revealed a significant difference in b-diversity (p=0.015), while no significant difference was observed in a-diversity. Taxonomic analysis identified significant differences in specific bacterial genera, particularly Bacteroides dorei. These findings confirm our previous results, demonstrating that gut microbiota composition differs between CADASIL patients and controls. Additionally, metabolite analysis of fecal samples from 15 CADASIL patients and 13 controls showed a significant elevation of the indole concentration in the patients. Moreover, indole levels were positively correlated with the abundance of Streptococcus mutans and Streptococcus parasanguinis.

Conclusions: Both indole and Streptococcus species have been reported to be associated with atherosclerosis. Our results suggest that alterations in gut microbiota and their metabolites may be associated with the pathophysiology of CADASIL by promoting atherosclerosis.

Background and purpose: Given the widespread use of digital media, this study aimed to investigate the relationship between bedtime digital media use and sleep disturbances, with a focus on age-related variations.

Methods: We conducted a nationwide cross-sectional study of 4,000 participants aged 20-69 years using an online survey between January 2022 and February 2022. The questionnaire assessed the frequency and duration of bedtime digital media use and resulting sleep procrastination, Insomnia Severity Index (ISI), and awareness of digital media's impact on sleep.

Results: Daily bedtime digital media use and sleep procrastination were reported by 64.1% and 23.5% of the participants, respectively. Bedtime digital media usage was correlated with insomnia symptoms, with the highest risk in older males (adjusted odds ratio [aOR], 4.627; 95% confidence interval [CI], 1.868 to 11.463 for ISI≥15 in daily users). Video content (aOR, 1.208; 95% CI, 1.006 to 1.450) and social networking service use (aOR, 1.215; 95% CI, 1.001 to 1.474) were linked to ISI≥10, though these associations became insignificant after adjusting for the frequency and duration of use. Older age was associated with lower awareness of the potential sleep-disrupting effects of bedtime digital media use (aOR, 0.977; 95% CI, 0.971 to 0.982 per year).

Conclusions: Bedtime digital media use and resulting sleep procrastination are highly prevalent. Older adults are particularly susceptible to insomnia linked to bedtime digital media use and have a lower awareness of its negative effects. These results indicate a need for public health initiatives to increase awareness and mitigate the negative impacts of digital media on sleep.

Background and purpose: Research suggests that CYP2C19 loss-of-function (LoF) alleles impede the metabolism of clopidogrel. However, there is limited research on the relationship between these alleles and the risk of stroke or transient ischemic attack (TIA) recurrence in patients taking clopidogrel. This updated meta-analysis aims to evaluate the relationship between CYP2C19 LoF alleles and the risk of stroke or TIA recurrence among patients receiving clopidogrel.

Methods: Relevant literature was obtained from searches of PubMed, Scopus, Cochrane Central Register Controlled Trials (CENTRAL), and Embase. The outcome measures of included studies were stroke or TIA, composite vascular events as an efficacy, and bleeding as a safety outcome. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines (PROSPERO ID: CRD42024564771).

Results: An analysis of 28 studies encompassing 11,401 patients treated with clopidogrel following stroke or TIA revealed that carriers of CYP2C19 LoF alleles had significantly higher risk of stroke recurrence compared to non-carriers (risk ratio [RR], 1.89; 95% confidence interval [CI]: 1.55-2.32). Composite vascular events were also significantly more frequent in carriers of the CYP2C19 LoF allele than in non-carriers (RR, 1.54; 95% CI: 1.16-2.04). Both observational studies (RR, 2.20; 95% CI: 1.74-2.79) and post-hoc analyses of randomized controlled trials (RR, 1.44; 95% CI: 1.04-1.99) demonstrated significantly increased recurrence risk among carriers of these alleles. This risk was especially pronounced in Asian populations (RR, 1.97; 95% CI: 1.60-2.43). There was insufficient data specific to other ethnic groups for definite conclusions. The incidence of bleeding events was similar between groups.

Conclusions: Carriers of CYP2C19 LoF alleles treated with clopidogrel had a higher risk of stroke or TIA recurrence than non-carriers. This risk was higher in Asian populations.

Background and purpose: Diagnosing spontaneous intracranial hypotension (SIH) remains a clinical challenge. The Bern score offered a structured scoring system for estimating the probability of spinal extradural cerebrospinal fluid leaks. We aimed to validate the Bern score in an East Asian cohort from a headache clinic.

Methods: Patients with SIH were recruited from 2022 to 2023, and age- and sex-matched controls with primary headache and normal brain MRI were included. All SIH patients underwent brain MRI and spine MR myelography before epidural blood patch. The Bern score was assessed and validated by two neurologists and one neuroradiologist. We evaluated its diagnostic performance with a receiver operating characteristic (ROC) curve and visualized the temporal profile of Bern scores using a LOESS (locally weighted scatterplot smoothing) graph.

Results: A total of 45 patients with SIH and 45 age-sex-matched controls were included. The ROC curve showed moderate diagnostic accuracy (area under the curve 0.775, 95% confidence interval 0.675-0.874; sensitivity 42.2%, specificity 95.6%) using the original cutoff of 3. Using a revised cutoff was ≥2, the Youden index was highest (sensitivity 66.7%, specificity 84.4%, accuracy 75.6%). Still, its performance remains suboptimal. The Bern score declined after 50 days from symptom onset.

Conclusions: The Bern score showed high specificity but limited sensitivity in our cohort, indicating it should not be used alone as a screening tool. A lower cutoff may improve its diagnostic performance, and timing from symptom onset should be considered when interpreting the score.

Background and purpose: Paroxysmal atrial fibrillation (PAF) can cause embolic stroke but is often asymptomatic and may resolve before it can be detected. We developed a simple, practical scoring system to improve the detection of PAF in stroke patients.

Methods: Patients with acute ischemic stroke hospitalized in three stroke centers between 2014 and 2021 were retrospectively examined. Multivariate logistic regression analysis was used to identify independent risk factors for PAF in a derivation cohort. Using these factors, a scoring system was developed and validated in a separate cohort.

Results: The derivation and validation cohorts included 649 and 583 patients, respectively. Median follow-up was 606 and 101 days, respectively. The independent risk factors for PAF were brain natriuretic peptide (BNP) ≥55 pg/mL, atrial premature contractions (APCs), National Institutes of Health Stroke Scale (NIHSS) score ≥11, corrected QT interval (QTc) ≥0.46 seconds, and multiple acute cerebral infarcts (MACIs). The BANQMR score assigns points based on these factors (BNP=3, APC=3, NIHSS score=2, QTc=1, and MACIs=1) and classifies patients into three risk grades based on points: low (0-2), moderate (3-5), and high (6-10). PAF was actually detected in 53.4% of high-risk patients, 15.0% of moderate-risk patients, and 4.6% of low-risk patients. The BANQMR score outperformed other existing scoring systems in terms of PAF prediction.

Conclusions: The BANQMR score is a simple, accurate tool for predicting PAF in ischemic stroke patients shortly after hospitalization, providing a clinically applicable method for early detection.

Background and purpose: This study aimed to characterize the clinical heterogeneity of Alzheimer's disease (AD) by implementing an integrated biological and clinical staging scheme for AD.

Methods: Clinical staging was performed in 193 participants from the Alzheimer's Disease Neuroimaging Initiative based on cognitive scores, while biological staging was performed based on global tau deposition in tau positron-emission tomography (PET). The discrepancy between clinical and biological stages was quantified as standardized residuals (W-scores), and classified into the following groups: concordant clinical and biological stages (W₀), worse clinical stage (W_-), and better clinical stage (W₊). Longitudinal changes in cognition, clinical progression, copathology burden, and brain metabolism on [18F]-fluorodeoxyglucose PET scans were compared between these groups.

Results: Relative to the W₀ group, the W_- group showed a faster cognitive decline and higher progression risk (hazard ratio [HR]=2.40, 95% confidence interval [CI]=1.20-4.83), while the W₊ group had a lower progression risk (HR=0.43, 95% CI=0.19-0.96). The copathology burden at autopsy (n=7) was correlated with the W-score (partial r=-0.87, p=0.023); however, this finding should be interpreted with caution due to the small sample. The ratio of cerebrospinal fluid α-synuclein positivity differed significantly between the groups, reaching 56.3% in the W_- group. Brain metabolism in the occipital, orbitofrontal, dorsolateral frontal, inferior and medial temporal cortex, and precuneus was lower in the W_- group than in the W₀ group, whereas it was higher in the W₊ group in the prefrontal, parietal, and temporal cortex.

Conclusions: The integration of clinical and biological staging has significant potential in clinical practice by providing information about copathologies, underlying neurodegeneration, and the progression of AD.