Predictive Value of Nutritional Risk for All-Cause Death and Functional Outcomes in Chinese Elderly Patients with Acute Stroke: A 3-Year Follow-Up Study.

Purpose: To explore the predictive value of nutritional risk for all-cause death and functional outcomes among elderly acute stroke patients. Patients and Methods: A total of 479 elderly acute stroke patients were enrolled in this study. The nutritional risk of patients was screened by the GNRI and NRS-2002. The primary outcome was all-cause death, and the secondary outcome was poor prognosis defined as a modified Rankin Scale (mRS) score ≥3. Results: Based on the NRS-2002, patients with nutritional risk had a higher risk of all-cause death at 3 months (adjusted OR: 3.642, 95% CI 1.046~12.689) and at 3 years (adjusted OR: 2.266, 95% CI 1.259~4.076) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.748, 95% CI 1.518~4.972. Based on the GNRI, compared to those without nutritional risk, patients with mild malnutrition also had a higher risk of all-cause death at 3 months (adjusted OR: 7.186, 95% CI 1.550~33.315) and at 3 years (adjusted OR: 2.255, 95% CI 1.211~4.199) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 1.947, 95% CI 1.030~3.680), so patients with moderate and severe malnutrition had a higher risk of all-cause death at 3 months (adjusted OR: 6.535, 95% CI 1.380~30.945) and at 3 years (adjusted OR: 2.498, 95% CI 1.301~4.799) and a higher risk of adverse functional outcomes at 3 months (adjusted OR: 2.213, 95% CI 1.144~4.279). Conclusion: Nutritional risk increases the risk of poor short-term and long-term outcomes in elderly patients with acute stroke. For elderly stroke patients, we should pay attention to early nutritional risk screening, and effective intervention should be provided to improve the prognosis of such patients.

Photobiomodulation for Alzheimer's disease: photoelectric coupling effect on attenuating Aß neurotoxicity.

Alzheimer's disease (AD) and dementia are the most worrying health problems faced by people globally today. Although the pathological features of AD consisting of amyloid-beta (Aß) plaques in the extracellular space (ECS) and intracellular tau tangles are well established, the developed medicines targeting these two proteins have not obtained the expected clinical effects. Photobiomodulation (PBM) describes the therapeutic use of red light (RL) or near-infrared light (NIR) to serve as a noninvasive neuroprotective strategy for brain diseases. The present review discusses the mechanisms of the photoelectric coupling effect (light energy-induced special electronic transition-related alterations in protein structure) of PBM on reducing Aß toxicity. On the one hand, RL or NIR can directly disassemble Aß in vitro and in vivo. On the other hand, formaldehyde (FA)-inhibited catalase (CAT) and H2O2-inactived formaldehyde dehydrogenase (FDH) are formed a vicious circle in AD; however, light energy not only activates FDH to degrade excessive FA (which crosslinks Aß monomer to form Aß oligomers and senile plaques) but also sensitizes CAT to reduce hydrogen peroxide levels (H2O2, which can facilitate Aß aggregation and enhance FA generation). In addition, it also activates mitochondrial cytochrome-c to produce ATP in the neurons. Clinical trials of phototherapeutics or oral coenzyme Q10 have shown positive effects in AD patients. Hence, a promising strategy combined PBM with nanopacked Q10 has been proposed to apply for treating AD.

Reduced serum vitamin D levels are associated with poor sleep quality in early stroke patients.

Background: Poor sleep quality and vitamin D deficiency are common in stroke patients. Our aim was to evaluate the possible association between vitamin D and sleep quality in acute ischemic stroke (AIS) patients. Methods: A total of 301 AIS patients were screened and completed 1-month follow-up. Serum 25-hydroxyvitamin D [25(OH)D] was used to assess the vitamin D status by a competitive protein-binding assay at baseline. All patients were divided into equal quartile according to the distribution of 25(OH)D. One month after stroke, sleep quality was evaluated by using Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) questionnaire; depression status was confirmed by 17-item Hamilton Depression Scale (HAMD). Results: There were 89 (29.6%) AIS patients with poor sleep quality 1-month post-event. Within 24 h after admission, serum 25(OH)D levels were significantly lower in patients with poor sleep quality after stroke (P < 0.001). In the results of multivariate-adjusted logistic regression analysis, the odds ratio (OR) of poor sleep quality was 6.199 (95% CI, 2.066-18.600) for the lowest quartile of 25(OH)D compared with the highest quartile. In patients without depression, reduced 25(OH)D were still significantly associated with poor sleep quality (OR = 8.174, 95% CI = 2.432-27.473). Furthermore, 25(OH)D and HAMD score were combined to enhance the diagnostic accuracy of poor sleep quality, with the area under the receiver operating characteristic curve of 0.775. Conclusion: Reduced serum levels of vitamin D at admission were independently and significantly associated with poor sleep quality at 1 month after stroke. Our findings suggested the combination of vitamin D and depression status could provide important predictive information for post-stroke sleep quality.

Fasting blood glucose-to-glycated hemoglobin ratio and all-cause mortality among Chinese in-hospital patients with acute stroke: a 12-month follow-up study.

BACKGROUND: Stroke is a leading cause of death and functional impairment in older people. To assess the prospective association between fasting blood glucose-to-glycated hemoglobin ratio and all-cause mortality and poor prognosis in stroke patients. METHODS: A total of 971 Chinese inpatients with acute stroke (mean age of 65.7) were consecutively enrolled in the prospective clinical study and followed up for 12 months after discharge. Stress hyperglycemia was measured using the ratio of fasting blood glucose (FBG, mmol/L)/glycated hemoglobin (HbA1c, %). The primary outcome was all-cause mortality, and secondary outcomes were poor prognosis defined as infectious complications, a National Institutes of Health Stroke Scale (NIHSS) score ≥ 6, a Barthel Index score ≤ 60, or a modified Rankin Scale (mRS) score of 3-6, presented as multivariate-adjusted odds ratios (ORs) with 95% confidence intervals (CIs) across the quartiles of the FBG/HbA1c ratio. RESULTS: There were 35 (4.1%) all-cause deaths at 3 months and 85 (11.4%) at 12 months. The inpatients with the highest quartile of the FBG/HbA1c ratio had a higher risk of all-cause death at 3 months (adjusted OR: 5.16, 95% CI: 1.03-25.74) and at 12 months (adjusted OR: 2.59, 95% CI: 1.14-5.89)) and a higher risk of infectious complications (adjusted OR 2.37, 95% CI 1.27-4.43) and dysfunction (adjusted OR 1.79, 95% CI 1.06-3.01) during hospitalization than inpatients with the lowest quartile. CONCLUSIONS: Stress hyperglycemia, measured by the FBG/HbA1c ratio, was associated with an increased risk of adverse outcomes, including all-cause death, infectious complications, and dysfunction after stroke.

Ruscogenin Attenuates Lipopolysaccharide-Induced Septic Vascular Endothelial Dysfunction by Modulating the miR-146a-5p/NRP2/SSH1 Axis.

Introduction: Endothelial dysfunction (ED) is associated with the progression of sepsis. Ruscogenin (RUS) has shown considerable efficacy in treating ED and sepsis. In the current study, the effects of RUS on sepsis-induced ED were assessed, and the mechanism was explored by focusing on the interactions of RUS with miRs. Methods: Sepsis was induced in mice and in human umbilical vein endothelial cells (HUVECs) using LPS method. Expression profile of miRs responding to sepsis was determined. Symptoms associated with sepsis and ED were examined after treatment with RUS. Changes in mouse survival, arterial structure, systemic inflammation, cell viability, apoptosis, and the miR-146a-5p/NRP2/SSH1 axis were analyzed. Results: Based on the microarray results, miR-146a-5p was selected as the therapeutic target. RUS improved survival rates and arterial structure, suppressed proinflammatory cytokines, down-regulated miR-146a-5p, and up-regulated NPR2 and SSH1 in septic mice. In HUVECs, RUS increased cell viability, suppressed apoptosis, inhibited inflammation, downregulated miR-146a-5p, and increased NRP2 and SSH1 levels. The re-induction of miR-146a-5p-5p impaired the protective effects of RUS on HUVECs. Discussion: Effects of RUS on sepsis-induced impairments in endothelium relied on the suppression of miR-146a-5p.

Association Between Obesity and Post-stroke Anxiety in Patients With Acute Ischemic Stroke.

Post-stroke anxiety (PSA) is serious psychosomatic comorbidity among patients with stroke, but whether obesity could be positively associated with PSA is currently unknown. The purpose of this study was to investigate the potential association between obesity and subsequent anxiety risk in patients with stroke. A total of 441 patients with acute ischemic stroke (AIS) onset were consecutively recruited within 7 days, and PSA and post-stroke depression (PSD) were evaluated by using a 14-item Hamilton anxiety scale (HAMA) and 17-item Hamilton depression scale (HAMD) at the end of 1-month follow-up. The odds ratio (OR) with 95% CI was estimated for the incidental PSA by using logistic regression analysis. The incidence of PSA was 25.85% at the end of 1-month follow-up, with a significant difference between patients with and without abdominal obesity. Relative fat mass (RFM) and abdominal obesity were significantly associated with an elevated risk of PSA, and the crude ORs were 1.04 (95% CI: 1.01-1.08) and 1.93 (95% CI: 1.11-3.34), respectively. Even after adjustment for obesity-related risk factors and PSA-related clinical measurements, the association remained to be pronounced with abdominal obesity. However, RFM (OR = 1.03, 95% CI: 0.99-1.06, P = 0.053) and abdominal obesity (OR = 1.31, 95% CI: 0.80-2.15, P = 0.280) were not significantly associated with an elevated risk of PSD. Abdominal obesity was independently associated with the PSA instead of PSD, which may help predict PSA risk in clinical practice. Further prospective clinical studies with a long follow-up duration are warranted to verify this finding.

Comparing the prognostic significance of nutritional screening tools and ESPEN-DCM on 3-month and 12-month outcomes in stroke patients.

BACKGROUND AND AIMS: Malnutrition is prevalent among individuals with acute ischaemic stroke (AIS) and may worsen clinical outcomes. There is no consensus on the best tool for nutritional screening in this population. The present study compared four screening tools and one diagnostic tool in terms of their prognostic significance in predicting short-term and long-term outcomes in AIS patients. METHODS: We included patients admitted to five major hospitals in Wenzhou and diagnosed with a primary diagnosis of AIS from October 1 to December 31, 2018. The Controlling Nutritional Status (CONUT) score, the Geriatric Nutritional Risk Index (GNRI), the Malnutrition Universal Screening Tool (MUST), the Nutritional Risk Screening Tool 2002 (NRS-2002) and the European Society for Clinical Nutrition and Metabolism diagnostic criteria for malnutrition (ESPEN-DCM) were assessed at admission. The clinical outcomes were evaluated by the modified Rankin Scale (mRS) and mortality at 3 months and 12 months after discharge. RESULTS: Five hundred and ninety-three patients were included in our prospective study. The mean age was 67.3 ± 12.0 years. Based on the mRS score, 125 patients exhibited poor functional recovery (an mRS ≥3) at 3 months after discharge. Seventeen patients died during the 3-month follow-up period, and the other 25 did not survive 12 months. Multivariate binary logistic regression revealed that inadequate nutritional status at admission, as determined by the CONUT, GNRI, MUST, NRS-2002 and ESPEN-DCM, were independently associated with poor outcomes in AIS patients 3 months after discharge. Both MUST ≥2 and NRS-2002 ≥ 3 showed significant associations with poor outcomes at 12-month post-discharge. Further analysis with the receiver operator characteristic (ROC) curve showed similar results, where all the tools predicted the poor outcomes at 3 months while only the NRS-2002 and MUST scores were significantly associated with the mRS at 12 months post-discharge. Moreover, the area under the curve (AUC) of MUST and NRS-2002 were significantly larger than those for the other tools. The optimal cut-off values of the MUST and NRS-2002 to predict poor outcomes were scores of ≥2 and ≥ 3 points, respectively. CONCLUSIONS: Our data supported a deleterious effect of inadequate nutrition, as evidenced by the nutrition screening tools or ESPEN-DCM, on clinical outcomes during and beyond the acute phase of AIS. We recommended the use of the MUST and NRS-2002 in guiding nutritional support in AIS patients, as they have higher predictive power and can predict both short-term and long-term outcomes.

Being at risk of malnutrition predicts poor outcomes at 3 months in acute ischemic stroke patients.

BACKGROUND: Malnutrition is confirmed to be associated with poor outcomes in stroke patients. The present study aimed to confirm that being at risk of malnutrition assessed by Nutritional Risk Screening Tool 2002 (NRS-2002) and the Controlling Nutritional Status (CONUT) score predicts poor outcomes at 3 months in acute ischemic stroke (AIS) patients. METHODS: In total, 682 patients with AIS were recruited within 7 days of stroke onset consecutively and 110 were dropped out. They were screened for risk of malnutrition using NRS-2002 and the CONUT score. The primary outcome is the follow-up modified Rankin Scale (mRS) score. Poor outcomes were defined as an (mRS) score ≥ 3 at 3 months post discharge. RESULTS: There was a significant difference in the mRS score at 3 months between patients at risk of malnutrition compared to those not at risk assessed by NRS-2002(P < 0.001) and CONUT (P = 0.011). The logistic regression model showed that the risk of malnourishment (according to NRS-2002), low risk of malnourishment (according to CONUT), and the moderate-to-severe risk of malnourishment (according to CONUT) were associated with higher risk of poor outcomes at 3 months (P < 0.001, P = 0.033, and P = 0.007). The multivariate logistic regression model (adjusted for confounding factors) demonstrated that the risk of malnourishment, according to the NRS-2002, was associated with the increasing risk of poor outcomes at 3 months (odds ratio = 2.31; 95% CI: 1.24-4.30; P = 0.008). CONCLUSIONS: The risk of malnutrition assessed by NRS-2002 and CONUT can predict poor outcomes at 3 months in AIS patients. NRS-2002 is superior to CONUT in predicting poor outcomes at 3 months.

Primary central nervous system lymphoma with no enhancement initially and no significant progression over a long term: a case report and review of the literature.

Primary central nervous system lymphoma, a rare primary intracranial tumor, is highly malignant and usually associated with poor prognosis. Recent years, owing to the remarkable progress in intervention techniques, survival time reported has been significantly prolonged. Strategies targeting alleviation and remission are primarily depended on the early diagnosis. However, due to the heterogeneity of the clinical symptoms and imaging features, the disease is frequently misdiagnosed especially in the early phase, rendering a delay of optimal treatment. Herein, we reported the case of a 61-year-old man who was initially misdiagnosed as demyelinating encephalopathy. MRI images showed multifocal lesions across the cerebral cortex and deep white matter, which are not strengthened on contrast enhancements. In respect of clinical symptoms, no significant progress was observed over about 11 months. Finally, the diagnosis was revealed by brain biopsy. After reviewing all the images of the patient, we found that the corpus callosum was involved early in the course of the disease. Therefore, for multifocal intracranial lesions involving the corpus callosum, we should always be vigilant about the possibility of primary central nervous system lymphoma. Histopathological examination of brain biopsy is helpful for early definitive diagnosis.

Inhibiting of GRASP65 Phosphorylation by DL-3-N-Butylphthalide Protects against Cerebral Ischemia-Reperfusion Injury via ERK Signaling.

BACKGROUND AND PURPOSE: The aim of this study was to explore the role of DL-3-n-butylphthalide (NBP) in cerebral ischemia-reperfusion injury (CIRI) mice model. The involvement of extracellular signal-regulated kinase (ERK) signaling pathway was also investigated. METHODS: All mice were divided into five groups: sham-operated group, CIRI group, NBP pretreatment group, NBP treatment group, and NBP pretreatment + treatment group. The CIRI mice model was established by the use of the Pulsinelli four-vessel occlusion method. Pretreatment mice received NBP (90 mg/kg/d) three times a day within four days before reperfusion by gavage. Treatment mice received NBP (90 mg/kg/d) three times a day within five days after reperfusion by gavage. We detected the infarction area, the neurological severity, and the superoxide dismutase and malondialdehyde levels. Furthermore, we observed the expressions of GRASP65, phosphorylation of GRASP65 (pGRASP65), ERK, and phosphorylation of ERK (pERK) by the use of Western blotting. RESULTS: The result showed that the ERK pathway was activated in response to CIRI. NBP decreases the expressions of pERK and pGRASP65 following CIRI. Additionally, NBP could decrease MDA and increase SOD level in brain tissues. Decreased infarct volume was also observed in the NBP group. Thereby, NBP inhibited the activation of the ERK pathway induced by CIRI and reduced the GRASP65 phosphorylation. CONCLUSIONS: The current finding suggested that NBP protected the cerebrum from CIRI mediated by inhibiting the ERK signaling pathway and subsequently reducing GRASP65 phosphorylation.

Leukoaraiosis is Associated with Worse Short-Term Functional and Cognitive Recovery after Minor Stroke.

Whether leukoaraiosis burden retards short-term recovery after minor stroke is unclear. We investigated the association between leukoaraiosis and early recovery of neurological function after a first minor ischemic stroke in 217 acute stroke patients (National Institutes of Health Stroke Scale (NIHSS) score ≤5). Leukoaraiosis severity was graded according to the Fazekas scale and categorized into none to mild (0-2; n = 143) or severe (3-6; n = 74) groups. NIHSS and Minimum Mental State Examination (MMSE) were assessed at baseline and at 30 days. Univariate analysis revealed that the severe leukoaraiosis group was older in age (P < 0.001) and had fewer low MMSE patients than non-mild group at baseline (39.1% vs 55.9%, P = 0.003). However, the MMSE improved in none to mild group but not in the severe group at 30-day (15.4% vs 36.5%, P < 0.001). At 30-day, the severe leukoaraiosis group had higher NIHSS scores than the none-mild group (P = 0.04). Multiple linear regression analyses demonstrated that leukoaraiosis severity and admission NIHSS were independently associated with the NIHSS score on day 30 (P = 0.034, 95% CI 0.004-0.091 and P = 0.001, 95% CI 0.011-0.04). Binary regression analyses showed that leukoaraiosis severity and admission MMSE were significantly associated with MMSE (dichotomized) at 30-day (OR 2.1, P < 0.01, 95% CI 1.7-2.6 and OR 5.1, P < 0.01, 95% CI 2.1-12.8). Leukoaraiosis burden is an independent predictor of worse short-term functional and cognitive recovery after a minor ischemic stroke.

Association Between Serum Levels of Vitamin D and the Risk of Post-Stroke Anxiety.

Low levels of serum vitamin D are common in patients with mood disorders and stroke. It has been shown that low levels of serum vitamin D indicate a risk of depression in post-stroke subjects. Our aim was to determine the relationship between vitamin D and post-stroke anxiety (PSA).A consecutive series of 226 first acute ischemic stroke patients were recruited and followed up for 1 month. Serum levels of vitamin D were measured within 24 hours of admission. Patients with significant clinical symptoms of anxiety and a Hamilton anxiety scale score >7 were diagnosed as having PSA. In addition, 100 healthy subjects were recruited as controls and underwent measurements of serum vitamin D.A total of 60 patients (26.55%) showed anxiety at 1 month. Both PSA patients and non-PSA patients had lower serum levels of vitamin D than healthy subjects. A significant relationship was found between PSA and serum levels of vitamin D. Low serum levels of vitamin D (≤38.48 nmol/L) were independently associated with the development of PSA (OR: 2.49, 95% CI: 1.21-5.13, P = 0.01).Serum vitamin D status is related to the occurrence of anxiety in post-stroke patients and may be an independent risk factor of PSA after 1 month.

Association between Serum Magnesium Levels and Depression in Stroke Patients.

Post-stroke depression (PSD) is a common psychiatric complication of stroke that is associated with a poor outcome in stroke patients. Our aim was to assess the association between the serum magnesium levels and the presence of PSD in Chinese patients. Two hundred nine stroke patients were included in the study. Depressive symptoms were measured by the 17-Hamilton Rating Scale for Depression at 3 months after stroke. Based on the depressive symptoms, diagnoses of depression were made in line with the DSM-IV criteria for PSD. Serum magnesium levels were evaluated using the dimethyl aniline blue colorimetric method at admission. Multivariate analyses were conducted using logistic regression models. Further, 120 normal subjects were recruited, and their serum magnesium levels were also measured as control. At 3 months, fifty-nine patients (28.2%) were diagnosed as PSD. The serum magnesium levels were significantly lower in both PSD patients and non-PSD patients than in normal subjects (p < 0.001). Indeed, patients with PSD showed lower serum magnesium levels (p < 0.001) than did non-PSD patients at admission. In the multivariate analyses, after adjusting for potential variables, we found that an increased risk of PSD was associated with serum magnesium levels ≤ 0.84mmol/L (OR 2.614, 95% CI 1.178-5.798, p=0.018). Low serum magnesium levels at admission were found to be associated with the presence of PSD at 3 months after stroke.

Bulbocavernosus reflex and pudendal nerve somatosensory-evoked potentials responses in female patients with nerve system diseases.

To assess the value of bulbocavernosus reflex (BCR) and pudendal nerve somatosensory-evoked potential (SSEP) in the topical diagnosis of central and peripheral nervous system diseases in female patients. Neuroelectrophysiologic technique was adopted to determine both BCR and SSEP of 41 healthy adult females (control group), 30 female patients with spinal cord lesions (central group), and 50 female patients with peripheral nerve lesions (peripheral group), including nine female patients with acute cauda equina syndrome. The abnormality rates of BCR were 8.33% and 70.00% in the central group and the peripheral group, respectively, and there were statistical differences between the two groups. The abnormality rates of BCR were 72.22% in the patients with acute cauda equina syndrome abnormal, who have at least one side of the abnormal BCR. The abnormality rates of SSEP P41 were 86.67% and 82.00% in the control and peripheral groups, respectively, and there were no statistical differences between the two groups. The abnormality rates of SSEP P41 were 88.89% in the patients with acute cauda equina syndrome abnormal. Also, there were no statistical differences between the peripheral group and the patients with acute cauda equina syndrome in the abnormality rates of SSEP or BCR. Both BCR and SSEP changed in the peripheral group, especially in the patients with acute cauda equina syndrome, but only SSEP changed in the central group. BCR and SSEP are valuable in the topical diagnosis of nervous system diseases in females.