Long-Term Resveratrol Intake for Cognitive and Cerebral Blood Flow Impairment in Carotid Artery Stenosis/Occlusion.

BACKGROUND AND PURPOSE: Carotid artery stenosis or occlusion (CASO) is a causative disease of vascular cognitive impairment (VCI) attributed to cerebral hypoperfusion, even without the development of symptomatic ischemic stroke. Preclinically, resveratrol has been demonstrated to play an important role in improving cognitive function in rodent CASO models. This study investigated the association between long-term resveratrol intake and improvements in cognitive and cerebral hemodynamic impairments in patients with CASO. METHODS: A retrospective cohort study was conducted on patients with asymptomatic carotid artery stenosis of ≥50% or occlusion who underwent 15O-gas positron emission tomography (15O-gas PET) and neuropsychological tests such as Montreal Cognitive Assessment (MoCA) and Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 (ADAS-Cog) twice between July 2020 and March 2022 allowing >125-day interval. Patients were administered 30 mg/day resveratrol after the first 15O-gas PET and neuropsychological tests were compared with those who were not. RESULTS: A total of 79 patients were enrolled in this study; 36 received resveratrol and 43 did not. Over a mean follow-up of 221.2 and 244.8 days, long-term resveratrol treatment significantly improved visuospatial/executive function (P=0.020) in MoCA, and memory domain (P=0.007) and total score (P=0.019) in ADAS-Cog. Cerebral blood flow demonstrated improvement in the right frontal lobe (P=0.027), left lenticular nucleus (P=0.009), right thalamus (P=0.035), and left thalamus (P=0.010) on 15O-gas PET. No adverse events were reported. CONCLUSION: Long-term daily intake of oral resveratrol may prevent or treat VCI by improving the cerebral blood flow in asymptomatic patients with CASO.

Amplified Risk of Intracranial Artery Stenosis/Occlusion Associated With RNF213 p.R4810K in Familial Hypercholesterolemia.

Background: The RNF213 p.R4810K variant is associated with moyamoya disease in East Asian individuals and increases the risk of developing intracranial major artery stenosis/occlusion (ICASO) that affects anterior circulation. Meanwhile, 0.5% to 2.5% of asymptomatic East Asian individuals also carry this variant. As such, additional factors are likely required to develop ICASO in variant carriers. Familial hypercholesterolemia (FH) is a common genetic disorder in Japan that has a significant associated risk of developing premature coronary atherosclerosis; however, the relationship between ICASO and FH remains unknown. Objectives: This study aimed to determine if FH facilitates RNF213 p.R4810K carriers to develop ICASO. Methods: We enrolled patients with FH who had undergone brain magnetic resonance angiography at our hospital from May 2005 to March 2020. The RNF213 p.R4810K variant, and LDLR and PCSK9 mutations were genotyped. ICASO lesions in the brain magnetic resonance angiogram were analyzed. Results: Six RNF213 p.R4810K variant carriers were identified among 167 patients with FH (LDLR, n = 104; PCSK9, n = 22). Five of the carriers (83.3%) exhibited ICASO in the anterior circulation; a significant difference in ICASO frequency was observed between the variant carriers and noncarriers (P = 0.025). The median number of stenotic or occluded arteries in the anterior circulation was also significantly larger in the variant carriers (3 vs 1, P = 0.01); however, did not differ between patients with FH with LDLR and PCSK9 mutations. Conclusions: Patients with FH exhibit increased prevalence and severity of ICASO associated with RNF213 p.R4810K. Gene mutations for FH may confer an increased risk of ICASO in RNF213 p.R4810K carriers.

Extended Ensemble Molecular Dynamics Study of Ammonia-Cellulose I Complex Crystal Models: Free-Energy Landscape and Atomistic Pictures of Ammonia Diffusion in the Crystalline Phase.

Here, we report extended ensemble molecular dynamics simulations of ammonia-cellulose I complex crystal models to evaluate the diffusion behavior of the guest ammonia molecules and the potential of mean force (PMF), namely, the free energy change along the chosen reaction coordinate, for migration of an ammonia molecule in the crystal models. Accelerated molecular dynamics simulations confirmed that ammonia molecules almost exclusively diffused through the hydrophilic channel even when the crystal framework was retained. Adaptive steered molecular dynamics simulations detected distinct PMF peaks with heights of approximately 7 kcal/mol as the ammonia molecule passed through the cellulose-chain layers. Introducing hybrid quantum mechanical and molecular mechanics theory to the adaptive steered molecular dynamics simulation effectively lowered the heights of the PMF peaks to approximately 5 kcal/mol, accompanied by a slight decrease in the baseline. Removal of the ammonia molecules in the neighboring channels resulted in a continuous increase in the baseline for the migration of an ammonia molecule in the hydrophilic channel. When the halves of the crystal model were separated to widen the hydrophilic channel to 0.2 nm, the PMF profiles exhibited an unexpected increase. This resulted from water structuring in the expanded hydrophilic channel, which disappeared with further expansion of the hydrophilic channel to 0.3 nm.

Recognition of Strokes in the ICU: A Narrative Review.

Despite the remarkable progress in acute treatment for stroke, in-hospital stroke is still devastating. The mortality and neurological sequelae are worse in patients with in-hospital stroke than in those with community-onset stroke. The leading cause of this tragic situation is the delay in emergent treatment. To achieve better outcomes, early stroke recognition and immediate treatment are crucial. In general, in-hospital stroke is initially witnessed by non-neurologists, but it is sometimes challenging for non-neurologists to diagnose a patient's state as a stroke and respond quickly. Therefore, understanding the risk and characteristics of in-hospital stroke would be helpful for early recognition. First, we need to know "the epicenter of in-hospital stroke". Critically ill patients and patients who undergo surgery or procedures are admitted to the intensive care unit, and they are potentially at high risk for stroke. Moreover, since they are often sedated and intubated, evaluating their neurological status concisely is difficult. The limited evidence demonstrated that the intensive care unit is the most common place for in-hospital strokes. This paper presents a review of the literature and clarifies the causes and risks of stroke in the intensive care unit.

Sequential detection rates of intramural hematoma for diagnosing spontaneous intracranial artery dissection.

BACKGROUND AND PURPOSE: Spontaneous intracranial artery dissection (IAD) can be definitively diagnosed by detecting intramural hematoma (IMH) on arterial wall imaging. However, evidence of a time-dependent natural history for the development of radiological findings is lacking. Therefore, this study aimed to determine when imaging detects IAD. METHODS: We obtained data from our cohort databases between March 2011 and August 2018 on consecutive patients who had definite, probable, or possible IAD based on the multidisciplinary expert consensus criteria. We assessed IMH on initial and follow-up high-resolution three-dimensional T1-weighted imaging (HR-3D-T1WI). We retrospectively investigated the association between IMH detection and days from symptom onset to initial HR-3D-T1WI and compared the IMH detection rate with other definitive diagnostic arterial dissection findings. RESULTS: We analyzed 106 patients (mean age = 51 ± 13 years, 31 women) with at least initial HR-3D-T1WI data. The final diagnoses were definite, probable, and possible IAD in 83, 18, and 5 patients, respectively. IMHs were observed in 63 patients (59%, 95% confidence interval [CI] = 49%-69%). Overall IMH detection rate was 55% (95% CI = 45%-64%), 20% (95% CI = 3%-60%), 40% (95% CI = 21%-64%), and 50% (95% CI = 37%-63%) on the initial HR-3D-T1WI and Days 3, 7, and 13, respectively. Among 68 patients evaluated with digital subtraction angiography and HR-3D-T1WI, IMH was confirmed more frequently than other definitive diagnostic arterial dissection findings. CONCLUSIONS: The overall IMH detection rate on HR-3D-T1WI was >50% and peaked in 1-2 weeks. IMH was a frequently detectable finding for the diagnosis of IAD compared to other radiological findings.

A Case of Multiple Intracranial Major Artery Stenoses With Coexisting PCSK9 p.E32K and RNF213 p.R4810K Variants.

Objectives: Familial hypercholesterolemia (FH), caused by PCSK9 p.E32K, is characterized by early-onset coronary artery disease. However, the relationship between PCSK9 p.E32K and cerebrovascular disease is unclear. One of our patients with the PCSK9 p.E32K had several intracranial artery stenoses (ICAS). The objective of this case series was to identify factors that may be associated with ICAS in the variant carriers. Methods: A 75-year-old Japanese woman with FH carrying PCSK9 p.E32K was found to have 5 asymptomatic ICAS when brain magnetic resonance angiography (MRA) was performed. We retrospectively investigated additional patients with FH who underwent brain MRA at our institution to explore the unknown factors accelerating ICAS. Results: We investigated an additional 5 patients with FH who underwent brain MRA. Of them, only one had mild ICAS. The RNF213 p.R4810K that is an established genetic risk for ICAS, particularly in East Asians, was identified only in the patient with 5 ICAS. Discussion: PCSK9 and RNF213 play an important role in lipid metabolism and endothelial integrity. Therefore, together, these variants could be involved in the development of multiple ICAS. Our case series indicated that PCSK9 p.E32K carriers should undergo early brain screening to obtain appropriate stroke prevention measures in the asymptomatic stage.

We Should Pay Attention to "Referred Pain" - A Case of Acute Myocardial Infarction That Masked and Delayed the Diagnosis of Esophageal Perforation.

We herein report a 93-year-old woman diagnosed with acute myocardial infarction (AMI) based on typical laboratory findings of severe chest pain accompanied by throat pain. This condition was initially interpreted as referred pain of cardiac origin. However, the patient had persistent throat pain after successful percutaneous coronary intervention. Upper esophageal perforation with life-threatening acute mediastinitis was unexpectedly identified by a further examination. Clinicians should have a high index of suspicion in cases with persistent symptoms thought to be referred pain among AMI patients, as these symptoms may not be of cardiac origin but rather a sign of another concomitant critical disease.

A Nationwide Multi-Center Questionnaire Survey on the Real-World State and Clinical Management of Poststroke Dementia in Japan.

BACKGROUND: Poststroke dementia (PSD) is a serious problem for stroke survivors. However, there is still limited data on the real-world state and clinical management of PSD worldwide, and several countries already have a super-aged society. OBJECTIVE: We conducted a nationwide questionnaire survey to examine the real-world state and management of PSD in Japan. METHODS: A survey was conducted in the top 500 Japanese hospitals regarding the number of stroke patients treated between July 2018 and August 2019. Thirteen questions regarding PSD were mailed to doctors responsible for stroke management. RESULTS: Responses were obtained from 251 hospitals (50.2%). The chief doctors responsible for stroke management answered the questionnaires. The median numbers of patients admitted annually with stroke in the departments of neurology and neurosurgery in the hospitals were 281.0 (interquartile range [IQR], 231.8-385.3) and 253.5 (IQR, 210.0-335.3), respectively, and most hospitals were acute care hospitals. Executive dysfunction was the most common cognitive dysfunction (10.9%), followed by amnesia (9.5%) and apathy (4.1%). Surprisingly, many stroke survivors lived alone at home (23.7%). Montreal Cognitive Assessment was significantly uncommon compared to Mini-Mental State Examination (p < 0.01). Furthermore, objective evaluation tests for behavioral and psychological symptoms of dementia were not often performed. Cognitive rehabilitation treatments were performed more often and earlier than drug treatments. The first drug of choice for PSD was predominantly donepezil (79.1%), followed by galantamine (6.1%), cilostazol (4.9%), memantine (2.5%), and rivastigmine (1.8%). CONCLUSION: Our study provides real-world evidence for the state of clinical practice related to PSD in Japan.

Glucose Fluctuation and Severe Internal Carotid Artery Siphon Stenosis in Type 2 Diabetes Patients.

The impact of glucose fluctuation on intracranial artery stenosis remains to be elucidated. This study aimed to investigate the association between glucose fluctuation and intracranial artery stenosis. This was a cross-sectional study of type 2 diabetes mellitus (T2DM) patients equipped with the FreeStyle Libre Pro continuous glucose monitoring system (Abbott Laboratories) between February 2019 and June 2020. Glucose fluctuation was evaluated according to the standard deviation (SD) of blood glucose, coefficient of variation (%CV), and mean amplitude of glycemic excursions (MAGE). Magnetic resonance angiography was used to evaluate the degree of intracranial artery stenosis. Of the 103 patients, 8 patients developed severe internal carotid artery (ICA) siphon stenosis (≥70%). SD, %CV, and MAGE were significantly higher in the severe stenosis group than in the non-severe stenosis group (<70%), whereas there was no significant intergroup difference in the mean blood glucose and HbA1c. Multivariable logistic regression analysis adjusted for sex showed that SD, %CV, and MAGE were independent factors associated with severe ICA siphon stenosis. In conclusion, glucose fluctuation is significantly associated with severe ICA siphon stenosis in T2DM patients. Thus, glucose fluctuation can be a target of preventive therapies for intracranial artery stenosis and ischemic stroke.

Evaluation of the risk factors predicting thrombotic complications associated with intravenous immunoglobulin therapy in neuroimmunological diseases.

Intravenous immunoglobulin (IVIg) therapy is increasingly used for various conditions that include neuroimmunological disorders, such as chronic inflammatory demyelinating polyneuropathy, Guillain-Barré syndrome, myasthenia gravis, and myositis. Although IVIg therapy is considered a relatively safe treatment, previous studies have reported thrombotic complications associated with IVIg (TCI). The precise mechanisms and associated risk factors have not been fully elucidated to date. Three of our patients experienced TCI. Although immobility is one of the most common risk factors for venous thrombosis, all three patients could walk without assistance; their modified Rankin Scale (mRS) scores were 2. We assessed the clinical characteristics of these patients and compared their data with that of 65 patients who received IVIg from the years 2000 to 2019 without experiencing TCI to identify associated risk factors. The frequency of TCI among patients with neuroimmunological disorders at our hospital was 4.4% (3/68 patients). There were no significant differences between the patients with and without TCI regarding their mean age (69.7 vs 58.0 years, p = 0.244), percentage of females (66.7% vs 45.6%, p = 0.588), mean body mass index (22.67 vs 22.16, p = 0.878), mean mRS score (2.22 vs 2.00, p = 0.658), and use of oral prednisolone (66.7% vs 13.8%, p = 0.0658). Interestingly, the D-dimer levels of two of the patients with TCI were not elevated before treatment. Sixteen patients received anticoagulant therapy during IVIg treatment, and none suffered from TCI. As our analysis suggested, it might be important to monitor D-dimer levels before and after IVIg to help prevent and detect TCI.

A laceration of a wired silastic tracheostomy tube: A case report and review of the literature.

Fractured tracheostomy tube is a rare, late complication. It typically occurs at the junction of metallic tube. We report an atypical case with laceration of the main trunk of a silastic tube after short period of use (10 days).