The impact of blood pressure variability on the development of parenchymal hematoma in acute cerebral infarction with atrial fibrillation.

Although blood pressure variability (BPV) and reperfusion are associated with parenchymal hematoma (PH) after stroke, the relationship between BPV and PH in atrial fibrillation (AF) patients who are at risk of reperfusion injury with frequent spontaneous recanalization is unknown. This study aimed to investigate whether BPV within the first 48 h is associated with PH within 72 h in patients with AF and stroke in terms of major vessel occlusion status. A total of 131 patients with AF that were admitted within 24 h after stroke onset were enrolled. PH was defined as a confluent hemorrhage with mass effect. The maximum (max), minimum (min), and average blood pressure (BP) during the first 48 h after admission were calculated. BPV was analyzed by using range between maximum and minimum (max-min), successive variation (SV), standard deviation (SD), and coefficient of variation (CV). All parameters were applied for systemic (SBP), diastolic (DBP), and pulse pressure (PP). After adjusting for confounding variables, various BPV parameters were associated with PH, including SBPmax (p = 0.0426), SBPSV (p = 0.0006), DBPmax-min (p = 0.0437), DBPSV (p = 0.0358), DBPSD (p = 0.0393), PPmax-min (p = 0.0478), PPSV (p < 0.0001), PPSD (p = 0.0034), and PPCV (p = 0.0120). The relationship remained significant in patients with a patent major vessel responsible for infarction but not in patients with an occluded major vessel. In conclusion, this study revealed that high BPV was associated with PH in patients with AF and acute stroke, particularly for those with a patent major vessel. The control of BP and BPV after stroke may be considered in patients with AF.

Predicting Adverse Recanalization Therapy Outcomes in Acute Ischemic Stroke Patients Using Characteristic Gut Microbiota.

Recanalization therapy is the most effective treatment for eligible patients with acute ischemic stroke (AIS). Gut microbiota are involved in the pathological mechanisms and outcomes of AIS. However, the association of gut microbiota features with adverse recanalization therapy outcomes remains unclear. Herein, we investigated gut microbiota features associated with neurological deficits in patients with AIS after recanalization therapy and whether they predict the patients' functional outcomes. We collected fecal samples from 51 patients with AIS who received recanalization therapy and performed 16S rRNA gene sequencing (V3-V4). We compared the gut microbiota diversity and community composition between mild to moderate and severe disability groups. Next, the characteristic gut microbiota was compared between groups, and we noted that the characteristic gut microbiota in patients with mild to moderate disability included Bilophila, Butyricimonas, Oscillospiraceae_UCG-003, and Megamonas. Moreover, the relative abundance of Bacteroides fragilis, Fusobacterium sp., and Parabacteroides gordonii was high in patients with severe disability. The characteristic gut microbiota was correlated with neurological deficits, and areas under the receiver operating characteristic curves confirmed that the characteristic microbiota predicted adverse recanalization therapy outcomes. In conclusion, gut microbiota characteristics are correlated with recanalization therapy outcomes in patients with AIS. Gut microbiota may thus be a promising biomarker associated with early neurological deficits and predict recanalization therapy outcomes.

The Prognostic Biomarkers of Plasma Trimethylamine N-Oxide and Short-Chain Fatty Acids for Recanalization Therapy in Acute Ischemic Stroke.

Bidirectional communication of the microbiota-gut-brain axis is crucial in stroke. Recanalization therapy, namely intravenous thrombolysis (IVT) and endovascular thrombectomy (EVT), are recommended for eligible patients with acute ischemic stroke (AIS). It remains unclear whether gut microbiota metabolites, namely trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFAs), can predict the prognosis after recanalization therapy. This prospective study recruited patients with AIS receiving IVT, EVT, or both. The National Institutes of Health Stroke Scale (NIHSS) and modified Rankin scale (mRS) scores were used to assess the severity and functional outcomes of AIS, respectively. A functional outcome of mild-to-moderate disability was defined as a mRS score of 0-3 at discharge. Plasma TMAO and SCFA levels were measured through liquid chromatography with triple-quadrupole mass spectrometry. Fifty-six adults undergoing recanalization therapy for AIS were enrolled. Results showed that TMAO levels were not associated with stroke severity and functional outcomes, while isovalerate levels (one of the SCFAs) were negatively correlated with NIHSS scores at admission and discharge. In addition, high isovalerate levels were independently associated with a decreased likelihood of severe disability. The study concluded that an elevated plasma isovalerate level was correlated with mild stroke severity and disability after recanalization therapy for AIS.

Consistencies among miscellaneous scales for evaluation of post-stroke dysphagia.

PURPOSE: Post-stroke dysphagia (PSD) is the most common type of dysphagia. Stroke patients with sustained dysphagia have poorer outcomes. The severity of PSD is assessed using miscellaneous scales with unknown consistencies. We aim to investigate the consistencies among miscellaneous scales, which could aid in the assessment of PSD. METHODS: A total of 49 PSD patients were enrolled. Functional Oral Intake Scale (FOIS), Dysphagia Severity Scale (DSS), Ohkuma Questionnaire, Eating Assessment Tool-10, and Repetitive Saliva Swallowing Test were performed. FOIS was performed by physicians, and DSS was conducted by both the physicians and nurses; the physicians used either videofluoroscopy (VF) or videoendoscopy (VE) for evaluation; while, the nurses assessed PSD by observation and subjective judgment. RESULTS: When using VF (VF-DSS and VF-FOIS) as the gold standard for the evaluation, VE-FOIS (κ = 0.625, 95% CI 0.300-0.950, p < 0.001) has a substantial agreement with VF-FOIS, and VE-DSS (κ = 0.381, 95% CI 0.127-0.636, p = 0.007) has a fair agreement with VF-DSS. The weighted kappa of FOIS to DSS in VE (weighted κ = 0.577, 95% CI 0.414-0.740, p < 0.001) is not lower than that in VF (weighted kappa = 0.249, 95% CI 0.136-0.362, p < 0.001). CONCLUSION: For both DSS and FOIS, only VE has a statistically significant agreement with VF. Though VF has been viewed as the traditional gold standard of dysphagia screening, it has the limitations of being invasive and equipment dependent. For PSD, VE could be considered as a substitution when VF is not available or suitable.

Acidosis-related pain and its receptors as targets for chronic pain.

Sensing acidosis is an important somatosensory function in responses to ischemia, inflammation, and metabolic alteration. Accumulating evidence has shown that acidosis is an effective factor for pain induction and that many intractable chronic pain diseases are associated with acidosis signaling. Various receptors have been known to detect extracellular acidosis and all express in the somatosensory neurons, such as acid sensing ion channels (ASIC), transient receptor potential (TRP) channels and proton-sensing G-protein coupled receptors. In addition to sense noxious acidic stimulation, these proton-sensing receptors also play a vital role in pain processing. For example, ASICs and TRPs are involved in not only nociceptive activation but also anti-nociceptive effects as well as some other non-nociceptive pathways. Herein, we review recent progress in probing the roles of proton-sensing receptors in preclinical pain research and their clinical relevance. We also propose a new concept of sngception to address the specific somatosensory function of acid sensation. This review aims to connect these acid-sensing receptors with basic pain research and clinical pain diseases, thus helping with better understanding the acid-related pain pathogenesis and their potential therapeutic roles via the mechanism of acid-mediated antinociception.

Oxidative stress involves phenotype modulation of morbid soreness symptoms in fibromyalgia.

OBJECTIVES: Muscle soreness occurs after exercise and also in musculoskeletal diseases, such as fibromyalgia (FM). However, the nosography and pathoetiology of morbid soreness in FM remain unknown. This study aimed to investigate the morbid soreness of FM, evaluate its therapeutic responses and probe its pathophysiology with metabolomics profiling. METHODS: Patients with newly diagnosed FM were prospectively recruited and completed self-report questionnaires pertaining to musculoskeletal symptoms. The phenotypes and metabotypes were assessed with variance, classification and correlation analyses. RESULTS: Fifty-one patients and 41 healthy controls were included. Soreness symptoms were prevalent in FM individuals (92.2%). In terms of manifestations and metabolomic features, phenotypes diverged between patients with mixed pain and soreness symptoms (FM-PS) and those with pain dominant symptoms. Conventional treatment for FM did not ameliorate soreness severity despite its efficacy on pain. Moreover, despite the salient therapeutic efficacy on pain relief in FM-PS cases, conventional treatment did not improve their general disease severity. Metabolomics analyses suggested oxidative metabolism dysregulation in FM, and high malondialdehyde level indicated excessive oxidative stress in FM individuals as compared with controls (p=0.009). Contrary to exercise-induced soreness, lactate levels were significantly lower in FM individuals than controls, especially in FM-PS. Moreover, FM-PS cases exclusively featured increased malondialdehyde level (p=0.008) and a correlative trend between malondialdehyde expression and soreness intensity (r=0.337, p=0.086). CONCLUSIONS: Morbid soreness symptoms were prevalent in FM, with the presentation and therapeutic responses different from FM pain conditions. Oxidative stress rather than lactate accumulation involved phenotype modulation of the morbid soreness in FM. TRIAL REGISTRATION NUMBER: NCT04832100.

Effects of Perampanel on Seizure Control, Cognition, Behavior, and Psychological Status in Patients With Epilepsy: A Systematic Review.

BACKGROUND AND PURPOSE: Thoroughly acquainting physicians with the effects of antiseizure medications (ASMs) is essential for developing appropriate therapeutic regimens for seizure management. This review summarizes the available evidence regarding patients receiving the antiseizure agent perampanel (PER) and its effects on the cognition, behavior, and psychological status of patients. METHODS: The PubMed and Google Scholar databases were searched for all relevant articles published during 2015-2021 and without any other publication limitations, and also manually searched the reference lists in the identified articles. Outcomes of interest were changes in seizure frequency relative to baseline, 50% responder rate, seizure-free rate, and retention rate (proportion of participants continuing PER at study endpoints). Safety outcomes included adverse effects and the percentage of patients experiencing effects on cognitive, psychiatric, and behavioral symptoms. RESULTS: We identified 139 studies, of which 28 were included after screening. Most studies found reduced seizure frequencies and satisfactory responder and retention rates, demonstrating the effectiveness and tolerability of PER. No negative effects were found for cognitive function, but a nonnegligible impact on aggressive behavior was noted when compared with other ASMs. Patients with previous psychiatric comorbidities had a greater risk of psychiatric side effects under PER treatment. PER induces an overall improvement in quality of life. CONCLUSIONS: After synthesizing the study results, PER was a safe and effective choice as an additional therapy for patients with refractory epilepsy. A comprehensive evaluation of behavior and psychiatric risk is suggested before implementing PER.

Application of Micro-Western Array for Identifying Different Serum Protein Expression Profile among Healthy Control, Alzheimer's Disease Patients and Patients' Adult Children.

(1) Background: Alzheimer's disease (AD) is the most common form of dementia. Increased levels of inflammatory proteins have been observed in brain and plasma samples of AD patients; however, it is not clear if other serum proteins correlate to the development or disease progression of AD. (2) Methods: Micro-Western Array (MWA) is a high-throughput antibody-based proteomics system which allows detection of the expression levels of 24-96 different proteins within 6-30 samples simultaneously. We applied MWA to explore potential serum protein biomarkers correlated to the development and progression of AD by examining the difference in serum protein profile of 31 healthy control (HC), 30 patients with AD and 30 patients' adult children (ACS). (3) Results: Compared to HC, AD and ACS express similar pattern of serum proteins, including higher protein levels of ABCA1, ABCG1, SREBP1 and LXRß but lower protein levels of ApoD, ApoE, ApoH, c_Myc, COX2 and Hippo-YAP signaling proteins. AD patients had higher serum levels of ABCG1, ApoD, ApoH, COX2, LXRα and YAP, but lower levels of ABCA1, ApoE, c_Myc, LATS1, MST1, MST2, Nanog, NFκB_p50, PPARγ and SREBP2, as compared to ACS. Pearson's correlation analysis revealed that the protein expression level of ApoE, c_Myc, LATS1, MST2, NFκB p50, PPARγ and SREBP1 was negatively correlated to age, while that of ApoE, c_Myc, LATS1, MST1, MST2, Nanog, NFκB p50 and PPARγ was positively correlated to age. (4) Conclusions: We identified a group of serum proteins which may correlate to disease progression of AD and can be potential diagnostic serum protein biomarkers.

The impact of antiseizure medications on polysomnographic parameters: a systematic review and meta-analysis.

BACKGROUND: Oral antiseizure medications (ASMs) are first-line treatments for patients with epilepsy. However, ASMs may alter sleep architecture, adversely affecting patient outcomes. The meta-analysis aimed to elucidate the effect of ASMs on sleep architecture. METHODS: PubMed, Embase, and Cochrane Central database (up to Febrary 2021) were searched for randomized control trials (RCT) with effects of ASMs on polysomnography parameters. A meta-analysis using a random-effects model was performed. We did not set limitation to the participants with underlying diagnosis of epilepsy. RESULTS: Eighteen randomized-controlled trials fulfilled the eligibility criteria. The effects of five main groups of ASMs (sodium channel blockers, calcium channel blockers, GABA enhancers, synaptic vesicle glycoprotein 2A [SV2A] ligand, and broad-spetrum ASMs) on slow-wave sleep (SWS), rapid eye movement (REM) sleep, and sleep efficiency (SE) were analyzed. Compared with placebo, calcium channel blockers and GABA enhancers significantly increased SWS. GABA enhancers also decreased REM sleep percentage, whereas calcium channel blockers significantly increased SE. Sodium channel blockers, SV2A ligand and broad-spectrum ASMs did not affect SWS, REM sleep, or SE. The subgroup analysis revealed that gabapentin, pregabalin, and tiagabine increased the percentage of SWS. Tiagabine also decreased REM sleep, whereas pregabalin increased SE. Finally, levetiracetam did not affect SWS, REM sleep, and SE. CONCLUSIONS: This meta-analysis indicated that ASMs can have a statistically significant effect on sleep parameters; the effect differs between ASMs.