Arterial transit artifact as a short-term prognostic indicator in acute ischemic stroke.

BACKGROUND: Arterial transit artifact (ATA) observed on arterial spin labeling (ASL) was recently suggested to be associated with improved functional outcomes following acute ischemic stroke (AIS). AIS is a heterogeneous disease with diverse pathogenic mechanisms depending on the stroke subtype. This study aimed to investigate the association between ATA and 3-month functional outcomes in AIS patients according to etiology subtypes. METHODS: Consecutive patients with AIS were included. All patients underwent ASL MRI with postlabeling delay (PLD) of 1.5 and 2.5 s. ATA was assessed from the ASL images of both PLDs. Stroke etiologic subtypes were determined according to the modified TOAST (Trial of ORG 10172 in Acute Stroke Treatment) classification. Short-term functional outcomes were evaluated using the 3-month modified Rankin scale (mRS). Log-binomial regression was applied to analyze the association between ATA and functional outcomes at 3 months after stroke. RESULTS: Ninety-eight AIS patients (62.73 ± 13.05 years; 68 men) were finally included. ATA was detected in forty-six patients and most frequently seen in the large-artery atherosclerosis (LAA) subtype (35/46). The ATA group exhibited a lower percentage of patients with mRS > 2 compared to the group without ATA (36.5% vs. 19.6%; P < 0.001). ATA was independently associated with better 3-month clinical outcomes (adjusted risk ratio, 0.35[95% CI, 0.16-0.74]) in the multivariate log-binomial regression model. After stratification by TOAST subtypes, a significant association was found between ATA and better outcomes in the LAA subtype (adjusted risk ratio, 0.20[ 95% CI, 0.05-0.72]) but not in cardioembolism and small artery occlusion (SVO) subtype. CONCLUSION: ATA is associated with better outcomes at 3 months in patients with AIS, especially in the LAA subtype, but this association attenuated in the cardioembolism and SVO subtypes.

Association of tirofiban with improvement of functional outcomes of direct thrombectomy for acute anterior circulation occlusion: a retrospective, nonrandomized, multicenter, real-world study.

OBJECTIVE: Although tirofiban and endovascular thrombectomy have been widely used in the treatment of acute ischemic stroke (AIS) patients, the effectiveness of their combined application remains a subject of debate. This study aimed to assess the efficacy and safety of tirofiban in direct thrombectomy for AIS with anterior circulation vessel occlusion. METHODS: A total of 204 patients undergoing direct thrombectomy between January 2020 and December 2021 for AIS with anterior circulation vessel occlusion from four hospitals were included in this study. Patients at high risk of reocclusion with severe atherosclerosis, those who achieved successful recanalization for ≥ 3 stent retriever passes, or those who underwent emergency stenting or balloon angioplasty for severe residual stenosis were treated with tirofiban. Following a low-dose intra-arterial bolus (0.25-1 mg) immediately after endovascular treatment, tirofiban was administered continuously through intravenous infusion (0.1 µg/kg/min) for 12-24 hours. The primary efficacy outcome was evaluated using the 90-day modified Rankin Scale score. The safety outcome was assessed using symptomatic intracerebral hemorrhage (sICH) and mortality rates. RESULTS: The tirofiban group and nontirofiban group each included 102 patients. The favorable outcome rate in the tirofiban group was significantly higher than that in the nontirofiban group (53.9% vs 35.3%, p = 0.007). However, the sICH and 90-day mortality rates were lower in the tirofiban group, despite a lack of statistical significance (sICH: 15.7% vs 16.7%, p = 0.849; 90-day mortality: 16.67% vs 24.51%, p = 0.166). Finally, it was found that older patients (> 72 years), male patients, patients with admission National Institutes of Health Stroke Scale scores > 14, patients with a time from onset to reperfusion > 327 minutes, and patients with a medical history of diabetes tend to benefit from tirofiban treatment. CONCLUSIONS: This study suggests that tirofiban combined with direct thrombectomy improves functional outcomes of AIS and reduces the 90-day mortality rate. Therefore, it could be considered as a suitable treatment option for AIS patients with anterior circulation vessel occlusion.

Homocysteine is related to enlarged perivascular spaces in the brainstem in patients with isolated pontine infarction.

BACKGROUND: Homocysteine is correlated with several imaging features of cerebral small vessel disease including white matter hyperintensities, lacunes, and enlarged perivascular spaces (EPVS) in the basal ganglia. However, little is known about EPVS in the brainstem. This study aimed to investigate the correlation between serum total homocysteine (tHcy) and EPVS in the brainstem in patients with acute isolated pontine infarction. METHODS: Consecutive patients with isolated pontine infarction were retrospectively enrolled. Clinical characteristics and laboratory tests including tHcy were recorded. Imaging markers of cerebral small vessel disease including EPVS in the basal ganglia (BG-EPVS), EPVS in the centrum semiovale, and EPVS in the midbrain or pons (brainstem-EPVS) were assessed using conventional magnetic resonance imaging. The relation between tHcy and EPVS of different parts in the brain was analyzed using univariate and multivariate regression model. RESULTS: A total of 227 patients were included (mean age 67.10 ± 9.38 years, male sex 58.6%). The frequencies of brainstem-EPVS and moderate to severe BG-EPVS accounted for 40.1% (91/227) and 40.5% (92/227) respectively. After controlling for confounding factors, multivariate logistic regression analyses showed that tHcy was an independent risk factor for both moderate to severe BG-EPVS (P = 0.003, P for trend < 0.001) and the presence of brainstem-EPVS (P < 0.001, P for trend < 0.001) in a dose-dependent manner. Furthermore, multivariate linear regression model indicated that the presence of brainstem-EPVS (ß = 0.264, 95% confidence interval = 0.143-0.402, P < 0.001) and the severity of BG-EPVS (ß = 0.162, 95% confidence interval = 0.024-0.197, P = 0.013) were positively associated with serum tHcy. CONCLUSIONS: Serum tHcy is correlated with brainstem-EPVS and BG-EPVS dose-dependently. This study may support a contributing role for homocysteine in the pathophysiology of EPVS in the brainstem and the basal ganglia.

The association between retinal vessel abnormalities and H-type hypertension.

BACKGROUND: This study aimed to investigate the relationship between H-type hypertension and retinal vessel abnormalities. METHODS: Hypertensive patients were retrospectively enrolled in this study. According to plasma homocysteine (HCY), patients were divided into isolated hypertension and H-type hypertension groups. The diameter of retinal vessels and retinopathy were evaluated by retinal fundus photography. The differences of retinal vessel abnormalities between H-type hypertension and isolated hypertension were investigated by univariate and multivariate regression. RESULTS: A total of 191 hypertensive patients were included, of which 86 were with isolated hypertension and 105 with H-type hypertension. The H-type hypertension group had a higher ratio of retinopathy(P = 0.004) and higher degree of retinal arteriosclerosis (P = 0.005) than the isolated hypertension group. CRAE (107.47 ± 13.99µ m vs. 113.49 ± 11.72µ m, P = 0.002) and AVR (0.55 ± 0.06 vs. 0.58 ± 0.06, P = 0.001) were smaller in H-type hypertension group than those in isolated hypertension group. Multivariate analysis showed that after adjusting for age, sex, course of hypertension and diabetes, H-type hypertension was an independent risk factor of retinopathy (OR, 2.259; 95%CI, 1.165-4.378; P = 0.016), CRAE (ß=-5.669; 95%CI, -9.452--1.886; P = 0.004), and AVR (ß=-0.023; 95%CI, -0.039--0.007; P = 0.005). CONCLUSIONS: H-type hypertension is closely related to more retinal vessel abnormalities than isolated hypertension. Controlling H-type hypertension may reduce the risk of small vascular damage.

Early Neurological Deterioration and Hypoperfusion Volume Ratio on Arterial Spin Labeling in Patients with Acute Ischemic Stroke.

BACKGROUND: Arterial spin labeling (ASL) is a magnetic resonance imaging (MRI) technique used to quantify cerebral blood perfusion by labeling blood water as it flows throughout the brain. Hypoperfusion volume ratio (HVR) can be calculated using proportional hypoperfusion volume on ASL-based cerebral blood flow (CBF). This study aimed to explore the relation between HVR and early neurological deterioration (END) in AIS patients. SUBJECTS AND METHODS: Patients with AIS were recruited consecutively, and ASL and regular MRI scans were performed. HVR was calculated from 1.5 and 2.5s post labeling delay (PLD) ASL-CBF maps. END was defined as ≥2 points increment of NIHSS within 72 hours of stroke onset. Univariate and multivariate analysis were used to evaluate the relation between HVR and END. Receiver operating characteristic (ROC) curves were used to determine the ability of HVR in predicting END. RESULTS: Of the 52 enrolled patients, 18 (34.5%) were determined with END. In patients with END, the median hypoperfusion volume was 20 mL [Inter Quartile Range)IQR, 6-72.5 mL] at 1.5s PLD, and 11.2 mL (IQR, 5.3-26 mL) at 2.5s PLD; Sixteen (88.9%) patients had HVR ≥50%, and 13 (72.2%) patients hypoperfusion volume at 2.5s PLD ASL were greater than diffusion-weighted imaging (DWI) infarct volume. In patients without END, median hypoperfusion volume was 7 mL (IQR, 4-30 mL) at 1.5s PLD, and 4 mL (IQR, 1.5-8.5 mL) at 2.5s; Eleven (32.4%) patients had HVR ≥50%, and 10 (29.4%) patients hypoperfusion volume at 2.5s PLD ASL were greater than DWI infarct volume. The proportion of HVR ≥50% and hypoperfusion volume >DWI infarct volume were more frequent in patients with END than patients without (all P<0.001). After adjusted for age, admission NIHSS, proportion of hypoperfusion volume > DWI infarct and arterial transit artifact (ATA) by logistic regression analysis, HVR ≥50% (OR=13.1, P=0.003) was an independent risk factor for END. ROC analysis demonstrated that the HVR could predict END with an area under the curve of 0.794 (P=0.001). CONCLUSIONS: HVR obtained from the 1.5 and 2.5s PLD ASL may be a useful predictor of END in AIS. The value of HVR may be a marker for hemodynamic impairments.

The role of S-nitrosylation of kainate-type of ionotropic glutamate receptor 2 in epilepsy induced by kainic acid.

Epilepsy is a chronic brain disease affecting millions of individuals. Kainate receptors, especially kainate-type of ionotropic glutamate receptor 2 (GluK2), play an important role in epileptogenesis. Recent data showed that GluK2 could undergo post-translational modifications in terms of S-nitrosylation (SNO), and affect the signaling pathway of cell death in cerebral ischemia-reperfusion. However, it is unclear whether S-nitrosylation of GluK2 (SNO-GluK2) contributes to cell death induced by epilepsy. Here, we report that kainic acid-induced SNO-GluK2 is mediated by GluK2 itself, regulated by neuronal nitric oxide synthase (nNOS) and the level of cytoplasmic calcium in vivo and in vitro hippocampus neurons. The whole-cell patch clamp recordings showed the influence of SNO-GluK2 on ion channel characterization of GluK2-Kainate receptors. Moreover, immunohistochemistry staining results showed that inhibition of SNO-GluK2 by blocking nNOS or GluK2 or by reducing the level of cytoplasmic calcium-protected hippocampal neurons from kainic acid-induced injury. Finally, immunoprecipitation and western blotting data revealed the involvement of assembly of a GluK2-PSD95-nNOS signaling complex in epilepsy. Taken together, our results showed that the SNO-GluK2 plays an important role in neuronal injury of epileptic rats by forming GluK2-PSD95-nNOS signaling module in a cytoplasmic calcium-dependent way, suggesting a potential therapeutic target site for epilepsy.

Mobilization of Circulating Endothelial Progenitor Cells by dl-3-n-Butylphthalide in Acute Ischemic Stroke Patients.

OBJECTIVE: The research aim was to investigate the effects of dl-3-n-butylphthalide (NBP) on the level of circulating endothelial progenitor cells (EPCs) and clinical outcome in patients with acute ischemic stroke (AIS). MATERIALS AND METHODS: A total of 170 patients were included and randomly assigned to NBP group and control group. All patients were administrated a basic antiplatelet and lipid-lowering therapy. Among the patients, 86 received additional NBP administration for 30 days, whereas 84 received only basic therapy (the control). The level of circulating EPCs (marked with CD34(+)/CD133(+)/KDR(+)) was determined by flow cytometry at baseline and days 7, 14, and 30 after therapy. Impairment of neurological function was evaluated by the National Institutes of Health Stroke Scale (NIHSS) on days 7, 14, 30, and 90 after therapy. The association between the increased level of circulating EPCs and improvement of NIHSS score was evaluated by Pearson analysis. The clinical outcome was evaluated by modified Rankin Scale (mRS) on day 90. During the observation period, any adverse events related to drugs were reported. RESULTS: The levels of circulating EPCs on days 14 and 30 were significantly higher in the NBP group than in the control group. In contrast, NIHSS score was notably lower in NBP group on day 14, 30 and day 90. Pearson correlation analysis revealed a significant association between the increased level of EPCs and improvement of NIHSS score. Also, the mRS score in the NBP group was lower on day 90. Importantly, the reported adverse events in the 2 groups were comparable. CONCLUSION: NBP significantly increases the circulating level and improves clinical outcome in patients with AIS.

NMDA receptor activity determines neuronal fate: location or number?

Abstract It is widely believed that the proper activation of N-methyl-D-aspartate (NMDA) receptors (NMDARs) promotes neuronal survival, whereas an excessive activation of NMDARs leads to neuronal damage. NMDARs are found at both synaptic and extrasynaptic sites. One current prevailing theory proposes the dichotomy of NMDAR activity. The role of the two population receptors is mutual antagonism. The activation of synaptic NMDARs, such as synaptic activity at physiological levels, promotes neuronal survival. However, the activation of extrasynaptic NMDARs occurring during stroke, brain injury, and chronic neurological diseases contributes to neuronal death. Thus, the location of NMDARs determines the neuronal fate. However, the theory is greatly challenged. Several studies suggested that synaptic NMDARs are involved in neuronal death. Recently, our work further showed that the coactivation of synaptic and extrasynaptic NMDARs contributes to neuronal death under neuronal insults. Therefore, we propose that the magnitude and duration of NMDAR activation determines the neuronal fate. More interestingly, there appears to be some subtle differences in the affinity between synaptic and extrasynaptic NMDARs, shedding light on the development of selective drugs to block extrasynaptic NMDARs.

Correlation of atherosclerotic renal artery stenosis with extracranial carotid and intracranial cerebral artery atherosclerosis in patients with ischemic stroke.

OBJECTIVE: This study was to evaluate the relationship of atherosclerotic renal artery stenosis (ARAS) with extracranial carotid arteries atherosclerosis (ECAS) and intracranial cerebral atherosclerosis (ICAS) in ischemic stroke (IS) patients. METHODS: This study was a prospective cohort analysis of consecutive patients with IS who had not a history of renal artery stenosis (RAS). Abdominal aortography was performed to screen for RAS after the cerebrovascular diagnostic procedure. Multivariate logistic regression analysis was performed to investigate the association of the clinical variables with significant ARAS (≥ 50%). RESULTS: ARAS was identified in 61 (23.1%) of all patients and 34 patients (12.9%) had significant ARAS (≥ 50%). ECAS (≥ 70%) and ICAS (≥ 50%) was found in 66 (25%) and 48 (18.2%) respectively. Patients with ECAS (≥ 70%) were more likely to have significant ARAS than patients without ECAS (28.8% vs 6.2%, p < 0.001). In multivariate analysis, only advanced age (≥ 60 years) (OR = 2.84, 95% CI 1.01-7.91) and ECAS (≥ 70%) (OR = 5.27, 95% CI 2.396-11.60) were independent risk factors for significant ARAS. CONCLUSION: Incidental ARAS is a relatively common finding among patients with IS, and there is a close relationship between ARAS and ECAS. Abdominal aortography should be performed to identify ARAS in elderly patients with IS, especially combined with severe ECAS.

Correlation between enlarged perivascular space and brain white matter hyperintensities in patients with recent small subcortical infarct.

BACKGROUND: This study aimed to investigate the correlation between enlarged perivascular space (EPVS) and white matter hyperintensities (WMH) at different locations in patients with recent small subcortical infarct (RSSI). METHODS: Data were collected from patients with RSSI who were hospitalized at Changzhou Second People's Hospital between October 2020 and December 2021. All patients underwent cranial magnetic resonance imaging, and the grades of EPVS and WMH were assessed, including basal ganglia EPVS (BG-EPVS), centrum semiovale EPVS (CSO-EPVS), deep WMH (DWMH), and periventricular WMH (PWMH). The volumes of EPVS and WMH at different locations were quantified using 3D Slicer software. Patients were grouped according to the severity of BG-EPVS and CSO-EPVS. Univariate and multivariate analyses were used to analyze the relationship between EPVS and WMH. RESULTS: A total of 215 patients with RSSI were included in the analysis. Patients with moderate-to-severe BG-EPVS had higher DWMH and PWMH severity than those with mild BG-EPVS, both in terms of volume and grade. There was no significant difference in WMH severity between patients with mild CSO-EPVS and those with moderate-to-severe CSO-EPVS. Multivariate analysis indicated that after adjustments were made for confounding factors, DWMH volume (ß = 0.311; 95% CI, 0.089-0.400; p = .002) and PWMH volume (ß = 0.296; 95% CI, 0.083-0.424; p = .004) were independently associated with BG-EPVS. Pearson correlation showed that PWMH volume (r = .589; p < .001) and DWMH volume (r = .596; p < .001) were positively related to BG-EPVS volume. CONCLUSION: DWMH and PWMH are closely related to BG-EPVS in patients with RSSI.

Remnant cholesterol and mild cognitive impairment: A cross-sectional study.

Objective: Emerging evidence suggests that elevated remnant cholesterol (RC) correlates with several health conditions. To explore the association of plasma RC with MCI incidence and the relationship between plasma RC and different domains of cognition in MCI patients. Methods: Thirty-six MCI patients and 38 cognitively healthy controls (HC) were enrolled in the present cross-sectional study. Using total cholesterol (TC) minus high-density lipoprotein cholesterol (HDL-C) minus low-density lipoprotein cholesterol (LDL-C) as the formula for calculating fasting RC. Cognition was assessed using the Chinese version of the Montreal cognitive assessment (MoCA), Auditory Verbal Learning Test (AVLT), Digit Symbol Substitution Test (DSST), Trail Making Test (TMT), and Rey-Osterrieth Complex Figure Test (ROCF). Results: Compared to healthy controls, MCI patients had a higher level of RC, the median difference in RC levels between these two groups was 8.13 mg/dl (95.0%CI: 0.97-16.1). Concurrently, plasma RC level was positively associated with MCI risk (OR = 1.05, 95%CI: 1.01-1.10). Notably, elevated RC level was correlated with impaired cognition in MCI patients, such as DSST (pr = -0.45, p = 0.008), ROCF- Long Delayed Recall (pr = -0.45, p = 0.008), AVLT-Immediate Recall (pr = -0.38, p = 0.028), and TMT-A (pr = 0.44, p = 0.009). Conversely, no significant correlation was found between RC and the AVLT-Long Delayed Recall test. Conclusion: This study found that plasma remnant cholesterol was associated with MCI. Further large longitudinal studies are needed in the future to confirm the results and clarify the cause-and-effect relationship.

Correlation between Carotid Blood Flow Velocity and Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease in Patients with Recent Small Subcortical Infarcts.

BACKGROUND: The common and internal carotid arteries are the upstream vessels of the small cerebral vessels. The relationship between hemodynamic changes in the significant cervical vessels and cerebral small vessel disease (CSVD) remains uncertain. This research sought to analyze the correlation between carotid blood flow velocity and the total magnetic resonance imaging (MRI) burden of CSVD in patients with recent small subcortical infarcts (RSSIs). METHODS: Data were gathered from individuals diagnosed with RSSIs admitted to Changzhou Second People's Hospital between January 2022 and June 2023. Brain MRI was performed on every patient to determine the overall MRI burden of CSVD, along with carotid duplex ultrasound to evaluate carotid blood flow velocity and pulsatility index (PI) of the common carotid (CCA) and internal carotid (ICA) arteries. The association between carotid blood flow velocity and the total MRI load of CSVD was examined using univariate and multivariate analyses. RESULTS: For our investigation, 272 individuals with RSSIs were screened. 82 individuals had a moderate to severe load of CSVD, while 190 participants showed a mild burden. Patients with moderate to severe burden of CSVD had lower end-diastolic velocity (EDV) and higher PI in CCA and ICA than those with mild load (P < 0.001). After adjusting for variables like age, hypertension, systolic blood pressure, and blood homocysteine levels, multivariate logistic regression analysis showed that EDV in CCA (OR, 0.894; P = 0.011), PI in CCA (OR, 5.869; P = 0.017), EDV in ICA (OR, 0.909; P = 0.008), and PI in ICA (OR, 5.324; P = 0.041) were independently related to moderate to severe CSVD burden. Spearman correlation analysis showed that EDV in CCA and ICA was negatively related to the total MRI load of CSVD in patients with RSSIs (P < 0.001). PI in CCA and ICA was positively associated with the whole MRI load of CSVD (P < 0.001). CONCLUSION: Low carotid blood flow velocity and high carotid pulsatility index are independently associated with moderate to severe burden of CSVD.

The role of asymmetrical prominent veins sign in early neurological deterioration of acute ischemic stroke patients.

Background and purpose: Asymmetrical prominent veins sign (APVS) often appears on susceptibility-weighted angiography (SWAN) images in patients with acute stroke. Early neurological deterioration (END) is highly correlated with survival prognosis in patients with ischemic stroke. This study sought to explore the relationship between APVS and END in patients with acute stroke. Methods: The subjects retrospectively enrolled in this study were patients with acute ischemic stroke in the middle cerebral artery supply area. All patients underwent head MRI, including the SWAN sequence, within 7 days of stroke symptom onset. END was defined as clinical deterioration or recurrence within 72 h after ischemic stroke. The volume of infarction on diffusion-weighted imaging was measured. Univariate and multivariate analyses were used to analyze the relationship between APVS and END. Spearman correlation between APVS grades and infarct volume, white matter hyperintensity (WMH) volume, and offending vessel were also analyzed. Results: A total of 157 patients with middle cerebral artery infarct between September 2018 and April 2020 were included in the study. APVS appeared on MRI in 84 of 157 patients, and 34 of 157 patients were diagnosed with END. In patients with END, the proportion of severe APVS was higher than in patients without END (P = 0.001, x 2 = 14.659). Patients with END were older and had a larger volume of infarct and WMH than patients without END (all P < 0.05). After adjustments were made for related risk factors of END, the severity of APVS was still related to END (OR = 2.56, 95% CI, 1.38-4.75; P for trend = 0.003). Spearman correlation showed that APVS grades were positively related to infarct volume (r = 0.289, P < 0.001) and 3-month modified Rankin Scale score (r = 0.203, P = 0.011) and negatively related to offending vessels (r = -0.170, P = 0.034). Conclusion: APVS may be an important predictor of END in patients with acute ischemic stroke.

A Presurgical Unfavorable Prediction Scale of Endovascular Treatment for Acute Ischemic Stroke.

Objective: To develop a prognostic prediction model of endovascular treatment (EVT) for acute ischemic stroke (AIS) induced by large-vessel occlusion (LVO), this study applied machine learning classification model light gradient boosting machine (LightGBM) to construct a unique prediction model. Methods: A total of 973 patients were enrolled, primary outcome was assessed with modified Rankin scale (mRS) at 90 days, and favorable outcome was defined using mRS 0-2 scores. Besides, LightGBM algorithm and logistic regression (LR) were used to construct a prediction model. Then, a prediction scale was further established and verified by both internal data and other external data. Results: A total of 20 presurgical variables were analyzed using LR and LightGBM. The results of LightGBM algorithm indicated that the accuracy and precision of the prediction model were 73.77 and 73.16%, respectively. The area under the curve (AUC) was 0.824. Furthermore, the top 5 variables suggesting unfavorable outcomes were namely admitting blood glucose levels, age, onset to EVT time, onset to hospital time, and National Institutes of Health Stroke Scale (NIHSS) scores (importance = 130.9, 102.6, 96.5, 89.5 and 84.4, respectively). According to AUC, we established the key cutoff points and constructed prediction scale based on their respective weightings. Then, the established prediction scale was verified in raw and external data and the sensitivity was 80.4 and 83.5%, respectively. Finally, scores >3 demonstrated better accuracy in predicting unfavorable outcomes. Conclusion: Presurgical prediction scale is feasible and accurate in identifying unfavorable outcomes of AIS after EVT.

Correlation Between Retinal Microvascular Abnormalities and Total Magnetic Resonance Imaging Burden of Cerebral Small Vessel Disease in Patients With Type 2 Diabetes.

Background and Purpose: Diabetic retinopathy (DR) is one of the common microvascular complications in diabetes. The total magnetic resonance imaging (MRI) burden of cerebral small vessel disease (CSVD) tends to be increased in diabetic patients and is a marker of microvascular disease; however, the relationship between DR and CSVD is unclear. This study aimed to explore the relationship between retinal microvascular abnormalities and the total MRI burden of CSVD in patients with type 2 diabetes. Methods: Data were collected from patients with type 2 diabetes who were hospitalized between December 2019 and November 2020 in Changzhou Second People's Hospital affiliated to Nanjing Medical University. All patients underwent retinal photography and cerebral MRI. The central retinal artery equivalent (CRAE), the central retinal venous equivalent (CRVE), and arteriole-to-venule ratio (AVR) were calculated using Image J software to determine the retinal vascular calibers for each patient. The total MRI burden score for CSVD was determined, and the relationship between retinal microvascular abnormalities and the total MRI burden of CSVD was analyzed. Results: Of the 151 diabetic patients included in the study, 84 (55.6%) had no diabetic retinopathy (NDR), 27 (17.9%) had mild DR, and 40 (26.5%) had moderate, or severe non-proliferative DR (grouped together for this study as "more than mild DR"). In patients with more than mild DR, the proportion of moderate to severe burden of CSVD was 75%, which was higher than in patients with mild DR (48.1%) or NDR (26.2%). Patients with moderate to severe burden of CSVD were more likely than those with mild burden of CSVD to have narrowed retinal arterioles (105.24 ± 8.42 µm vs. 109.45 ± 7.93 µm), widened retinal venules (201.67 ± 16.25 µm vs. 193.95 ± 13.54 µm), and lower arteriole-to-venule ratio (0.52 ± 0.05 vs. 0.57 ± 0.04) (P < 0.05 for all). The degree of DR (r = 0.465, P < 0.001) and CRVE (r = 0.366, P < 0.001) were positively correlated with the total MRI burden of CSVD. Multivariate logistic regression analysis indicated that, after adjustments were made for age, smoking, alcohol consumption, hypertension, and other factors, more than mild DR (OR, 4.383; P = 0.028), CRAE (OR, 0.490; P = 0.031), and CRVE (OR, 1.475; P = 0.041) were independently associated with moderate to severe burden of CSVD. Conclusion: Retinal microvascular abnormalities in patients with type 2 diabetes are associated with the presence of cerebral small vessel lesions. The degree of DR and retinal vessel changes can be used as predictors of intracranial microcirculation lesions.

Peripheral BDNF/TrkB protein expression is decreased in Parkinson's disease but not in Essential tremor.

BDNF-to-TrkB signaling pathways plays an important role in the long-term maintenance of the nigrostriatal system and that its deficiency may contribute to the onset and progression of Parkinson's disease (PD). To our knowledge this is the first study to investigate the expression of the brain-derived neurotrophic factor (BDNF) and phosphorylation status of TrkB in peripheral blood lymphocytes of 28 PD and 28 Essential tremor (ET) patients and 28 healthy controls using western blot analysis. Compared with controls, no significant difference of BDNF and total and phosphorylated TrkB levels were observed in ET, whereas BDNF and phosphorylated TrkB levels were significantly decreased in the PD groups (p < 0.001). Interestingly, BDNF and phosphorylated TrkB levels were positively correlated with disease duration, UPDRS score, Hoehn-Yahr staging, as well as L-DOPA medication in PD patients. These results suggest that the decreased peripheral alteration of BDNF/TrkB levels found in patients with PD is directly related to the dopaminergic neurons neurodegeneration and that decreased expression of BDNF/TrkB may lead to the development of innovative biomarkers of PD, whereas the increased level of BDNF and phosphorylated TrkB at advanced stages may due to L-DOPA medication.

Restraint devices for repetitive transcranial magnetic stimulation in mice and rats.

INTRODUCTION: Repetitive transcranial magnetic stimulation has been widely used for the treatment of neurological and psychiatric diseases. Rodent animals including mice and rats are often used to investigate the potential cellular and molecular mechanisms for the therapeutic effects of repetitive transcranial magnetic stimulation. So far there is no report about an easy-to-use device to restrain rodent animals for repetitive transcranial magnetic stimulation. METHODS AND RESULTS: We introduced the design and use of the restraint device for mice or rats. In the mouse device, western blot and real-time PCR analysis showed that，in stimulated mouse frontal cortex, 10 Hz high frequency stimulation for 10 sessions resulted in enhanced expression of NR2B-containing N-methyl-D-aspartic acid receptors and reduced α1 subunit of inhibitory GABAA receptors, whereas 0.5 Hz low frequency stimulation for 10 sessions caused decreased expression of NR2B subunit and increased α1 subunit of GABAA receptors. In the rat device, measures of motor evoke potentials indicated that 10 Hz stimulation for 10 sessions increased the excitability of stimulated cortex, whereas 0.5 Hz for 10 sessions reduced it. CONCLUSIONS: These results suggested the effectiveness of the devices. Thus, the two devices are practical and easy-to-use to investigate the mechanisms of repetitive transcranial magnetic stimulation.

Repetitive transcranial magnetic stimulation in combination with neuromuscular electrical stimulation for treatment of post-stroke dysphagia.

OBJECTIVE: This study was performed to determine whether repetitive transcranial magnetic stimulation (rTMS) combined with neuromuscular electrical stimulation (NMES) effectively ameliorates dysphagia and how rTMS protocols (bilateral vs. unilateral) combined with NMES can be optimized. METHODS: Sixty-four patients were randomly divided into four groups using a random distribution table: the sham rTMS plus NMES (Sham-rTMS/NMES), ipsilesional 10-Hz rTMS plus NMES (Ipsi-rTMS/NMES), contralesional 1-Hz rTMS plus NMES (Contra-rTMS/NMES), and bilateral rTMS plus NMES (Bi-rTMS/NMES) groups. Cortical excitability as measured by the amplitude of the motor evoked potential at the mylohyoid muscle cortical representative area, swallowing function as measured by the Standardized Swallowing Assessment, and the degree of dysphagia were evaluated at baseline, after the stimulation course, and at the 1-month follow-up. RESULTS: Bi-rTMS/NMES produced higher cortical excitability and better swallowing function recovery. Compared with NMES alone, unilateral rTMS plus NMES had additional effects on cortical excitability and rehabilitation of dysphagia, but there were no differences between the Contra-rTMS/NMES and Ipsi-rTMS/NMES groups. No adverse events occurred. CONCLUSION: The combination of rTMS with NMES was superior to NMES alone in improving the recovery of post-stroke dysphagia, and the combination of bilateral rTMS with NMES was more effective than unilateral rTMS combined with NMES.

Serum concentration and clinical significance of brain-derived neurotrophic factor in patients with Parkinson's disease or essential tremor.

Objectives The serum concentration of brain-derived neurotrophic factor (BDNF) was compared among patients with Parkinson's disease (PD), patients with essential tremor (ET), and healthy participants, and its association with clinical features of PD and ET was assessed. Methods Demographic and clinical data were collected from 60 patients with PD at different clinical stages, 60 patients with ET, and 60 controls. All participants' serum BDNF concentrations were measured. Their motor abilities and activity were assessed by the Unified PD Rating Scale and the Hoehn and Yahr (H-Y) staging scale. Results Serum BDNF was significantly lower in patients with PD than in patients with ET and controls. BDNF decreased only in the early disease stages (H-Y stages I and II), but increased markedly in the advanced stages (H-Y stages III-V). There was no significant difference between patients with ET and controls. The BDNF concentration was negatively correlated with age at PD onset and positively associated with disease duration, severity of PD symptoms, and treatment with L-DOPA. Conclusions A low serum BDNF concentration may serve as a biomarker in the early stages of PD, whereas a high concentration with PD progression may be due to treatment with L-DOPA in the advanced stages.

The degree of leukoaraiosis predicts clinical outcomes and prognosis in patients with middle cerebral artery occlusion after intravenous thrombolysis.

Leukoaraiosis (LA) is common in elderly patients with ischemic stroke on magnetic resonance imaging. In this study, we investigate whether the degree of LA is associated with clinical outcomes and prognosis of patients with middle cerebral artery occlusion following intravenous thrombolytic. Ninety-seven patients were recruited and divided into three groups based on the degree of LA (no, mild and moderate to severe LA) by the Fazekas scale. Clinical outcomes, recurrent stroke, Fugl-Meyer rating scale (FMS) and complications of intravenous thrombolysis were assessed. The association between the degree of LA and functional outcomes was analyzed by multivariable logistic regression model. Patients enrolled were divided into three groups: 26 patients with no LA, 43 patients with mild LA and 28 patients with moderate to severe LA. Impressively, the patients with mild LA were better in early neurological recovery and 90-day FMS score than patients in the other two groups. Multivariate logistic analysis revealed that moderate to severe LA was an independent predictor of poor functional outcome (OR: 10.482; 95% CI: 1.442-76.181; P = .020). Moreover, the patients with moderate to severe LA have a higher rate of hemorrhagic transformation and recurrent stroke as compared with two other groups during 90-day follow-up. Different degrees of LA differentially affect clinical outcome and prognosis in patients with middle cerebral artery occlusion following intravenous thrombolytic. Moderate to severe LA is a risk factor of poor prognosis. Mild LA is associated with early neurological recovery and good motor functional outcome.