Takao Urabe

The gut microbiota has been implicated in cardiovascular disease, but its association with subclinical carotid atherosclerosis (AS) and potential sex differences remain incompletely understood. Associations between gut microbiota composition and subclinical carotid AS were investigated in 82 asymptomatic Japanese adults (39 men, 43 women) undergoing brain health screening. Carotid AS was defined as maximum intima–media thickness (IMT) ≥ 1.1 mm, and gut microbiota composition was assessed by 16S rRNA gene sequencing. Multivariable differential abundance analysis was performed using MaAsLin 3, adjusting for age, body mass index as appropriate, hypertension, diabetes mellitus, and dyslipidemia in sex-stratified analyses. Phascolarctobacterium and Turicibacter in men, and Megasphaera, Streptococcus, Allisonella, Bacillus, and Ruthenibacterium in women were identified as candidate taxa associated with carotid AS status. Integrated models combining clinical factors with these microbial signatures showed areas under the receiver operating characteristic curve of 0.79 in men and 0.95 in women. These findings suggest that gut microbial signatures associated with subclinical carotid AS differ by sex and may provide complementary information for characterizing early vascular changes. Larger prospective studies with independent validation are required to confirm these exploratory findings.

Sudden unexpected death in epilepsy (SUDEP) refers to unpredictable demise of a person following a seizure. Electroencephalograms can directly measure electrical activity in the brain; however, it cannot predict when seizures will occur. The use of electrocardiograms (ECGs) to monitor changes in brain electrical activity has gained attention, recently. In this case report, we retrospectively reviewed ECGs taken before and after seizure activity in a 75‐year‐old male who had a remote subarachnoid hemorrhage. Interestingly, U‐waves appeared prior to his seizures and disappeared afterward, which suggests ECGs can be used to predict epilepsy in a certain population.

Introduction: Atrial septal aneurysms increase the risk of stroke recurrence in cryptogenic stroke patients with a patent foramen ovale. Factors related to stroke recurrence according to the patent foramen ovale risk stratification have not been fully evaluated. Methods: Data from a multicenter observational registry of ischemic stroke patients undergoing transesophageal echocardiography, with a comprehensive database including clinical characteristics and long-term prognosis, were used for this study. Patients were classified into three groups: high-risk patent foramen ovale group, large shunt patent foramen ovale (≥20 microbubbles) or patent foramen ovale with atrial septal aneurysm; right-to-left shunt group, right-to-left shunt including patent foramen ovale with Results: In total, 586 patients (185 females; 65.5 ± 13.2 years) were analyzed. In cryptogenic stroke (329 patients) with median follow-up of 4.2 (interquartile range, 1.0– 6.1) years, 55 patients had stroke recurrence. The negative right-to-left shunt, right-to-left shunt, and high-risk patent foramen ovale groups included 179, 90, and 60 patients, in which stroke recurrence occurred in 5.3%, 2.5%, and 4.6% per person-year, respectively. In patients with high-risk patent foramen ovale, the NIH stroke scale score (hazard ratio 1.257, 95% CI 1.034-1.530, P =0.022) and periventricular hyperintensity (hazard ratio 3.369, 95% CI 1.103-10.294, P =0.035) were predictive markers for stroke recurrence on multivariate Cox Hazards analysis, but no factors were related to stroke recurrence in the right-to-left shunt and negative right-to-left shunt groups. Conclusion: High-risk patent foramen ovale is an important embolic source in cryptogenic stroke. Periventricular hyperintensity was shown to predict recurrent stroke in patients with a high-risk patent foramen ovale. In such cases, percutaneous patent foramen ovale closure might be effective at <60 years of age.

Background: Cerebrovascular diseases are common comorbidities in patients with cancer. Although active cancer causes ischemic stroke by multiple pathological conditions, including thromboembolism attributable to Trousseau syndrome, the relationship between stroke and inactive cancer is poorly known. The aim of this study was to elucidate the different underlying pathogeneses of cryptogenic stroke in active and inactive patients with cancer, with detailed investigation by transesophageal echocardiography. Methods and Results: CHALLENGE ESUS/CS (Mechanisms of Embolic Stroke Clarified by Transesophageal Echocardiography for Embolic Stroke of Undetermined Source/Cryptogenic Stroke) registry is a multicenter registry including data of patients initially diagnosed as having cryptogenic stroke and undergoing transesophageal echocardiography. Patients were divided into active cancer, inactive cancer, and noncancer groups, and their clinical features were compared. Of the total 667 enrolled patients (age, 68.7±12.8 years; 455 men), 41 (6.1%) had active cancer, and 51 (7.5%) had a history of inactive cancer. On multinomial logistic regression analysis, infarctions in multiple vascular territories (odds ratio [OR], 2.73; 95% CI, 1.39–5.40) and CRP (C‐reactive protein) (OR, 1.10; 95% CI, 1.01–1.19) were independently associated with active cancer, whereas age (OR, 1.05; 95% CI, 1.01–1.08), contralateral carotid stenosis from the index stroke lesion (OR, 4.05; 95% CI, 1.60–10.27), calcification of the aortic valve (OR, 2.10; 95% CI, 1.09–4.05), and complicated lesion of the aortic arch (OR, 2.13; 95% CI, 1.11–4.10) were significantly associated with inactive cancer. Conclusions: Patients with cancer were not rare in cryptogenic stroke. Although patients with active cancer had more multiple infarctions, patients with inactive cancer had more atherosclerotic embolic sources potentially causing arteriogenic strokes. Registration: URL: https://www.umin.ac.jp/ctr/ ; Unique identifier: UMIN000032957.

Although l-carnitine alleviated white-matter lesions in an experimental study, the treatment effects of l-carnitine on white-matter microstructural damage and cognitive decline in hemodialysis patients are unknown. Using novel diffusion magnetic resonance imaging (dMRI) techniques, white-matter microstructural changes together with cognitive decline in hemodialysis patients and the effects of l-carnitine on such disorders were investigated. Fourteen hemodialysis patients underwent dMRI and laboratory and neuropsychological tests, which were compared across seven patients each in two groups according to duration of l-carnitine treatment: (1) no or short-term l-carnitine treatment (NSTLC), and (2) long-term l-carnitine treatment (LTLC). Ten age- and sex-matched controls were enrolled. Compared to controls, microstructural disorders of white matter were widely detected on dMRI of patients. An autopsy study of one patient in the NSTLC group showed rarefaction of myelinated fibers in white matter. With LTLC, microstructural damage on dMRI was alleviated along with lower levels of high-sensitivity C-reactive protein and substantial increases in carnitine levels. The LTLC group showed better achievement on trail making test A, which was correlated with amelioration of disorders in some white-matter tracts. Novel dMRI tractography detected abnormalities of white-matter tracts after hemodialysis. Long-term treatment with l-carnitine might alleviate white-matter microstructural damage and cognitive impairment in hemodialysis patients.

Enlarged perivascular spaces (PVS) are common magnetic resonance imaging (MRI) findings, whereas widespread enlarged PVS are extremely rare. Although most patients with widespread enlarged PVS remain asymptomatic, some develop neurological dysfunctions; however, it remains unclear whether these are the consequence of widespread enlarged PVS. A 64-year-old female patient developed consciousness disturbance, cognitive dysfunctions, fluent aphasia, agraphia, acalculia, and left-right disorientation after suffering from bronchopneumonia. Brain MRI revealed unusually widespread enlarged PVS predominantly in the left cerebral hemisphere. Following bronchopneumonia treatment, her cognitive dysfunction, fluent aphasia, agraphia, acalculia, and left-right disorientation persisted despite improvement of her general condition. Furthermore, the hypoperfusion area on single photon emission computed tomography and slow wave sites on electroencephalography were consistent with the location of enlarged PVS, indicating that severe enlarged PVS impaired focal brain functions. This case suggested that widespread enlarged PVS could be a potential cause of neurological deficits. We propose that impaired perivascular circulation due to enlarged PVS might lead to focal brain dysfunction.