Effects of sufficient anticoagulation on ischemic stroke outcomes in patients with nonvalvular atrial fibrillation

Background Optimal anticoagulation therapy reduces the risk of ischemic stroke in patients with nonvalvular atrial fibrillation (AF). Therefore, we aimed to evaluate the effects of prior anticoagulation therapy with vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs) on ischemic stroke outcomes in patients with nonvalvular AF. Methods We enrolled 487 patients with ischemic stroke and nonvalvular AF between January 2013 and August 2020. The infarct volume was semi-automatically evaluated using diffusion-weighted magnetic resonance imaging. Patients were categorized into no anticoagulation, undertreated anticoagulation, and sufficient anticoagulation (with VKA or DOAC) groups based on their pre-admission anticoagulant use, and the clinical characteristics were compared between the groups. Results Among the included patients, 374 (76.8%), 50 (10.3%), 10 (2.1%), and 53 (10.9%) patients received no anticoagulants, were undertreated with a VKA, were sufficiently treated with a VKA, and received DOACs, respectively, before stroke. Multivariate analysis revealed that optimal anticoagulation was independently associated with a low risk of severe stroke (odds ratio, 0.553; 95% confidence interval, 0.308–0.992; P=0.047). Additionally, the DOAC group had a significantly smaller mean infarct volume than the other groups (45.8±73.2, 45.0±69.1, 30.9±24.7, and 12.6±24.9 mL in the no anticoagulation, insufficient VKA, sufficient VKA, and DOAC groups, respectively; P=0.011). Conclusion Sufficient pre-stroke anticoagulation is associated with mild stroke severity and good outcomes at 3 months post-stroke. Additionally, pre-stroke DOAC treatment is associated with smaller infarct volume in patients with ischemic stroke and nonvalvular AF

Diurnal variation in quantitative pupillary reactivity in large hemispheric stroke

Background Pupillary light reflex (PLR) assessment is an important neurological examination reflecting neurological deterioration in severe stroke cases. This study investigated the impact of diurnal variation in the PLR using quantitative pupillometry in stable patients with large hemispheric stroke. Methods We included 35 patients with large hemispheric stroke without neurological worsening, who were admitted to the neurological intensive care unit between April 2017 and November 2021. Quantitative pupillometry was performed every 4 hours. Pupillometer parameters of maximum pupil size, percentage of constriction (%CH), latency (LAT), constriction velocity (CV), dilation velocity (DV), maximum constriction velocity (MCV), and neurological pupil index (NPi) score were recorded. We evaluated changes in the pupillometer parameters over time using linear mixed model analysis. Results The diurnal variations revealed that the following parameters were significantly higher at 04:00 than at 20:00: maximum pupil size (right [Rt]: 3.59 vs. 3.21 mm, P<0.001; left [Lt]: 3.51 vs. 3.18 mm, P<0.001), %CH (Rt: 31.48 vs. 25.72, P<0.001; Lt: 31.42 vs. 24.98, P<0.001), CV (Rt: 1.97 vs. 1.68 mm/sec, P<0.001; Lt: 1.98 vs. 1.65 mm/sec, P<0.001), and DV (Rt: 0.97 vs. 0.84 mm/sec, P<0.001; Lt: 0.94 vs. 0.82 mm/sec, P=0.001). However, no significant diurnal variations were observed in the NPi values. Conclusion Pupillary dynamics based on quantitative pupillometer parameters, including the NPi, demonstrated diurnal variations over 24 hours in large hemispheric stroke patients without neurological worsening. However, all changes in the pupillometer parameters were within normal ranges

Gene Expression Profile of the Hypothalamus in DNP-KLH Immunized Mice Following Electroacupuncture Stimulation

Clinical evidence indicates that electroacupuncture (EA) is effective for allergic disorder. Recent animal studies have shown that EA treatment reduces levels of IgE and Th2 cytokines in BALB/c mice immunized with 2,4-dinitrophenylated keyhole limpet protein (DNP-KLH). The hypothalamus, a brain center of the neural-immune system, is known to be activated by EA stimulation. This study was performed to identify and characterize the differentially expressed genes in the hypothalamus of DNP-KLH immunized mice that were stimulated with EA or only restrained. To this aim, we conducted a microarray analysis to evaluate the global gene expression profiles, using the hypothalamic RNA samples taken from three groups of mice: (i) normal control group (no treatments); (ii) IMH group (DNP-KLH immunization + restraint); and (iii) IMEA group (immunization + EA stimulation). The microarray analysis revealed that total 39 genes were altered in their expression levels by EA treatment. Ten genes, including T-cell receptor alpha variable region family 13 subfamily 1 (Tcra-V13.1), heat shock protein 1B (Hspa1b) and 2′–5′ oligoadenylate synthetase 1F (Oas1f), were up-regulated in the IMEA group when compared with the IMH group. In contrast, 29 genes, including decay accelerating factor 2 (Daf2), NAD(P)H dehydrogenase, quinone 1 (Nqo1) and programmed cell death 1 ligand 2 (Pdcd1lg2) were down-regulated in the IMEA group as compared with the IMH group. These results suggest that EA treatment can modulate immune response in DNP-KLH immunized mice by regulating expression levels of genes that are associated with innate immune, cellular defense and/or other kinds of immune system in the hypothalamus

Nutritional support and brain tissue glucose metabolism in poor-grade SAH: a retrospective observational study

INTRODUCTION: We sought to determine the effect of nutritional support and insulin infusion therapy on serum and brain glucose levels and cerebral metabolic crisis after aneurysmal subarachnoid hemorrhage (SAH). METHODS: We used a retrospective observational cohort study of 50 mechanically ventilated poor-grade (Hunt-Hess 4 or 5) aneurysmal SAH patients who underwent brain microdialysis monitoring for an average of 109 hours. Enteral nutrition was started within 72 hours of admission whenever feasible. Intensive insulin therapy was used to maintain serum glucose levels between 5.5 and 7.8 mmol/l. Serum glucose, insulin and caloric intake from enteral tube feeds, dextrose and propofol were recorded hourly. Cerebral metabolic distress was defined as a lactate to pyruvate ratio (LPR) > 40. Time-series data were analyzed using a general linear model extended by generalized estimation equations (GEE). RESULTS: Daily mean caloric intake received was 13.8 ± 6.9 cal/kg and mean serum glucose was 7.9 ± 1 mmol/l. A total of 32% of hourly recordings indicated a state of metabolic distress and < 1% indicated a state of critical brain hypoglycemia (< 0.2 mmol/l). Calories received from enteral tube feeds were associated with higher serum glucose concentrations (Wald = 6.07, P = 0.048), more insulin administered (Wald = 108, P < 0.001), higher body mass index (Wald = 213.47, P < 0.001), and lower body temperature (Wald = 4.1, P = 0.043). Enteral feeding (Wald = 1.743, P = 0.418) was not related to brain glucose concentrations after accounting for serum glucose concentrations (Wald = 67.41, P < 0.001). In the presence of metabolic distress, increased insulin administration was associated with a relative reduction of interstitial brain glucose concentrations (Wald = 8.26, P = 0.017), independent of serum glucose levels. CONCLUSIONS: In the presence of metabolic distress, insulin administration is associated with reductions in brain glucose concentration that are independent of serum glucose levels. Further study is needed to understand how nutritional support and insulin administration can be optimized to minimize secondary injury after subarachnoid hemorrhage

Infantile Marfan syndrome in a Korean tertiary referral center

PurposeInfantile Marfan syndrome (MFS) is a rare congenital inheritable connective tissue disorder with poor prognosis. This study aimed to evaluate the cardiovascular manifestations and overall prognosis of infantile MFS diagnosed in a tertiary referral center in Korea.MethodsEight patients diagnosed with infantile MFS between 2004 and 2014 were retrospectively evaluated.ResultsTheir median age at the time of diagnosis was 2.5 months (range, 0–20 months). The median follow-up period was 25.5 months (range, 0–94 months). The median length at birth was 50.0 cm (range, 48–53 cm); however, height became more prominent over time, and the patients were taller than the 97th percentile at the time of the study. None of the patients had any relevant family history. Four of the 5 patients who underwent DNA sequencing had a fibrillin 1 gene mutation. All the patients with echocardiographic data of the aortic root had a z score of >2. All had mitral and tricuspid valve prolapse, and various degrees of mitral and tricuspid regurgitation. Five patients underwent open-heart surgery, including mitral valve replacement, of whom two required multiple operations. The median age at mitral valve replacement was 28.5 months (range, 5–69 months). Seven patients showed congestive heart failure before surgery or during follow-up, and required multiple anti-heart failure medications. Four patients died of heart failure at a median age of 12 months.ConclusionThe prognosis of infantile MFS is poor; thus, early diagnosis and timely cautious treatment are essential to prevent further morbidity and mortality

Mesenchymal stem cell-derived magnetic extracellular nanovesicles for targeting and treatment of ischemic stroke

Exosomes and extracellular nanovesicles (NV) derived from mesenchymal stem cells (MSC) may be used for the treatment of ischemic stroke owing to their multifaceted therapeutic benefits that include the induction of angiogenesis, anti-apoptosis, and anti-inflammation. However, the most serious drawback of using exosomes and NV for ischemic stroke is the poor targeting on the ischemic lesion of brain after systemic administration, thereby yielding a poor therapeutic outcome. In this study, we show that magnetic NV (MNV) derived from iron oxide nanoparticles (IONP)-harboring MSC can drastically improve the ischemic-lesion targeting and the therapeutic outcome. Because IONP stimulated expressions of therapeutic growth factors in the MSC, MNV contained greater amounts of those therapeutic molecules compared to NV derived from naive MSC. Following the systemic injection of MNV into transient middle-cerebral-artery-occlusion (MCAO)-induced rats, the magnetic navigation increased the MNV localization to the ischemic lesion by 5.1 times. The MNV injection and subsequent magnetic navigation promoted the anti-inflammatory response, angiogenesis, and anti-apoptosis in the ischemic brain lesion, thereby yielding a considerably decreased infarction volume and improved motor function. Overall, the proposed MNV approach may overcome the major drawback of the conventional MSC-exosome therapy or NV therapy for the treatment of ischemic stroke.

Early Detection of Cerebral Infarction With Middle Cerebral Artery Occlusion With Functional Near-Infrared Spectroscopy: A Pilot Study

Background: NIRSIT, a functional near-infrared spectroscopy (fNIRS) device with 204 channels, can measure oxyhemoglobin (HbO2) and deoxyhemoglobin (HbR) in non-pulsatile blood flow non-invasively using the absorption difference between HbO2 and HbR at a wavelength of 700–1,000 nm and can display the perfusion status in real time.Objective: We applied NIRSIT to patients with stroke to evaluate the usefulness of NIRSIT as an fNIRS device for the early detection of stroke.Methods: We performed a prospective pilot study in an emergency department (ED). Adult patients who had suspected symptoms and signs of stroke within 12 h of the first abnormal time and who underwent intravenous thrombolysis (IVT) or intra-arterial thrombectomy with acute middle cerebral artery (MCA) or internal carotid artery (ICA) infarction were enrolled. NIRSIT was applied to the patients before the imaging study, and the perfusion status of the brain was displayed in real time at the bedside. We compared the NIRSIT results with the mean transit time (MTT) map from perfusion computed tomography (PCT) and the time-to-peak (TTP) map from perfusion-weighted magnetic resonance imaging (PWI).Results: Six male and three female patients were enrolled, and the median age was 74 years. The most common symptom was unilateral extremity weakness (77.8%), followed by dysarthria (33.3%) and aphasia (11.1%). The median National Institutes of Health Stroke Scale (NIHSS) score was 17. All cases of MCA infarction showed different cerebral oxygen saturation values between bilateral lobes of the brain in fNIRS imaging, and these values matched the PCT and PWI results.Conclusions: The brain hemisphere with low oxygen saturation on fNIRS showed hypoperfusion on PCT or PWI. The fNIRS device could be useful in assessing the perfusion status of the brain and detecting MCA or ICA infarction in real time at the bedside

Targeted delivery of iron oxide nanoparticle-loaded human embryonic stem cell-derived spherical neural masses for treating intracerebral hemorrhage

This study evaluated the potential of iron oxide nanoparticle-loaded human embryonic stem cell (ESC)-derived spherical neural masses (SNMs) to improve the transportation of stem cells to the brain, ameliorate brain damage from intracerebral hemorrhage (ICH), and recover the functional status after ICH under an external magnetic field of a magnet attached to a helmet. At 24 h after induction of ICH, rats were randomly separated into three experimental groups: ICH with injection of phosphate-buffered saline (PBS group), ICH with intravenous injection of magnetosome-like ferrimagnetic iron oxide nanocubes (FION)-labeled SNMs (SNMs* group), and ICH with intravenous injection of FION-labeled SNMs followed by three days of external magnetic field exposure for targeted delivery by a magnet-embedded helmet (SNMs*+Helmet group). On day 3 after ICH induction, an increased Prussian blue-stained area and decreased swelling volume were observed in the SNMs*+Helmet group compared with that of the other groups. A significantly decreased recruitment of macrophages and neutrophils and a downregulation of pro-inflammatory cytokines followed by improved neurological function three days after ICH were observed in the SNMs*+Helmet group. Hemispheric atrophy at six weeks after ICH was significantly decreased in the SNMs*+Helmet group compared with that of the PBS group. In conclusion, we have developed a targeted delivery system using FION tagged to stem cells and a magnet-embedded helmet. The targeted delivery of SNMs might have the potential for developing novel therapeutic strategies for ICH.