Heart Rate Variability in Patients with Spontaneous Intracerebral Hemorrhage and its Relationship with Clinical Outcomes.

BACKGROUND: Although abnormal heart rate variability (HRV) is frequently observed in patients with spontaneous intracerebral hemorrhage (ICH), its time course and presentation of different indices remain unclear, and few studies have focused on its association with clinical outcomes. METHODS: We prospectively recruited consecutive patients with spontaneous ICH between June 2014 and June 2021. HRV was evaluated twice during hospitalization (within 7 days and 10-14 days after stroke). Time and frequency domain indices were calculated. A modified Rankin Scale score ≥ 3 at 3 months was defined as a poor outcome. RESULTS: Finally, 122 patients with ICH and 122 age- and sex-matched volunteers were included. Compared with controls, time domain and absolute frequency domain HRV parameters (total power, low frequency [LF], and high frequency [HF]) in the ICH group were significantly decreased within 7 days and 10-14 days. For relative values, normalized LF (LF%) and LF/HF were significantly higher, whereas normalized HF (HF%) was significantly lower, in the patient group than in the control group. Furthermore, LF% and HF% measured at 10-14 days were independently associated with 3-month outcomes. CONCLUSIONS: HRV values were impaired significantly within 14 days after ICH. Furthermore, HRV indices measured 10-14 days after ICH were independently associated with 3-month outcomes.

Role of lipocalin 2 in stroke.

Stroke is the second leading cause of death worldwide; however, the treatment choices available to neurologists are limited in clinical practice. Lipocalin 2 (LCN2) is a secreted protein, belonging to the lipocalin superfamily, with multiple biological functions in mediating innate immune response, inflammatory response, iron-homeostasis, cell migration and differentiation, energy metabolism, and other processes in the body. LCN2 is expressed at low levels in the brain under normal physiological conditions, but its expression is significantly up-regulated in multiple acute stimulations and chronic pathologies. An up-regulation of LCN2 has been found in the blood/cerebrospinal fluid of patients with ischemic/hemorrhagic stroke, and could serve as a potential biomarker for the prediction of the severity of acute stroke. LCN2 activates reactive astrocytes and microglia, promotes neutrophil infiltration, amplifies post-stroke inflammation, promotes blood-brain barrier disruption, white matter injury, and neuronal death. Moreover, LCN2 is involved in brain injury induced by thrombin and erythrocyte lysates, as well as microvascular thrombosis after hemorrhage. In this paper, we review the role of LCN2 in the pathological processes of ischemic stroke; intracerebral hemorrhage; subarachnoid hemorrhage; and stroke-related brain diseases, such as vascular dementia and post-stroke depression, and their underlying mechanisms. We hope that this review will help elucidate the value of LCN2 as a therapeutic target in stroke.

Remote ischemic conditioning attenuates blood-brain barrier disruption after recombinant tissue plasminogen activator treatment via reducing PDGF-CC.

Treatment of acute ischemic stroke with the recombinant tissue plasminogen activator (rtPA) is associated with increased blood-brain barrier (BBB) disruption and hemorrhagic transformation. Remote ischemic conditioning (RIC) has demonstrated neuroprotective effects against acute ischemic stroke. However, whether and how RIC regulates rtPA-associated BBB disruption remains unclear. Here, a rodent model of thromboembolic stroke followed by rtPA thrombolysis at different time points was performed with or without RIC. Brain infarction, neurological outcomes, BBB permeability, and intracerebral hemorrhage were assessed. The platelet-derived growth factor CC (PDGF-CC)/PDGFRα pathway in the brain tissue, PDGF-CC levels in the skeletal muscle and peripheral blood were also measured. Furthermore, impact of RIC on serum PDGF-CC levels were measured in healthy subjects and AIS patients. Our results showed that RIC substantially reduced BBB injury, intracerebral hemorrhage, cerebral infarction, and neurological deficits after stroke, even when rtPA was administrated in a delayed therapeutic time window. Mechanistically, RIC significantly decreased PDGFRα activation in ischemic brain tissue and reduced blood PDGF-CC levels, which partially resulted from PDGF-CC reduction in the skeletal muscle of RIC-applied hindlimbs and platelets. Intravenous or intraventricular recombinant PDGF-CC supplementation abolished RIC protective effects on BBB integrity. Moreover, similar changes of PDGF-CC in serum by RIC were also observed in healthy humans and acute ischemic stroke patients. Together, our study demonstrates that RIC can attenuate rtPA-aggravated BBB disruption after ischemic stroke via reducing the PDGF-CC/PDGFRα pathway and thus supports RIC as a potential approach for BBB disruption prevention or treatment following thrombolysis.

Dynamic Cerebral Autoregulation After Carotid Endarterectomy.

OBJECTIVE: Studies have shown that dynamic cerebral autoregulation (dCA) is impaired in patients with severe internal carotid artery (ICA) stenosis and that carotid endarterectomy (CEA) may improve dCA in these patients. However, the time course of dCA changes in patients after CEA remains unclear. Therefore, this study aimed to investigate the effects of CEA on the dCA in patients with carotid artery stenosis at different time points. METHODS: This prospective study enrolled 44 patients (19 symptomatic stenosis patients and 25 asymptomatic stenosis patients) who underwent CEA and 44 age- and sex-matched controls. In the CEA group, the patients underwent dCA measurements at baseline, within 3 days, and 1 month after CEA. Transfer function parameters, phase difference (PD), and gain were used to quantify dCA. Changes in dCA before and after CEA were analyzed in detail. RESULTS: The bilateral PD of the patients before CEA was significantly lower than that of the control group. This damage did not improve within 3 days after surgery. One month after surgery, the PD on the affected side of the patients significantly improved compared with before surgery and reached the level of the control group. The PD of affected side across time points in symptomatic and asymptomatic stenosis patients is consistent with that in all patients. CONCLUSIONS: The dCA level did not improve immediately after CEA but significantly improved 1 month after surgery. This suggests that the occurrence of stroke should be considered in the acute period after CEA surgery, and its preventive effect on stroke may be effective after 1 month. CLINICAL IMPACT: We found the dCA level did not improve immediately after CEA but significantly improved 1 month after surgury. This suggests that the occuttencce of stroke and surgical complications (such as cerebral hyperperfusion syndrome) associated with impaired dCA in the acute phase after CEA surgery should be of particular concern.

Spatiotemporal lipidomics reveals key features of brain lipid dynamic changes after cerebral ischemia and reperfusion therapy.

Reperfusion therapy with recombinant tissue plasminogen activator (rtPA) or mechanical thrombectomy is the most effective treatment for ischemic stroke. However, a large proportion of stroke patients remain severely disabled even after receiving timely reperfusion therapy. It remains unclear how reperfusion therapy results in secondary injury to the brain tissue and whether different reperfusion therapies induce differential effects. Here, we comprehensively determined the spatiotemporal dynamic changes in brain lipids during the acute phase after reperfusion in a mouse model of transient middle cerebral artery occlusion, with or without rtPA administration, using desorption electrospray ionization (DESI)-mass spectrometry imaging (MSI). Several phospholipids, sphingolipids, and neutral lipids were significantly altered both spatially and temporally at multiple timepoints after reperfusion, many of which were closely associated with expansion of the brain infarction territory and neurological function impairment. Furthermore, rtPA treatment significantly increased brain infarction, cerebral edema, and neurological deficits. Consistently, rtPA treatment caused extensive brain lipid alterations by facilitating brain-wide changes in lipid metabolism and inducing ischemic region-specific lipid changes. Overall, these results provide novel insights into how reperfusion therapy affects brain tissue and the outcome of stroke patients, and thus may facilitate the optimization of the treatment of ischemic stroke.

Validity of high resolution magnetic resonance imaging in detecting giant cell arteritis: a meta-analysis.

OBJECTIVES: This study was designed to evaluate the performance of high-resolution magnetic resonance imaging (HR-MRI) in detecting giant cell arteritis (GCA), evaluate superficial extracranial artery and other MRI abnormalities, and compare three-dimensional (3D) and two-dimensional (2D) techniques. METHODS: PubMed, Web of Science, and Cochrane Library were screened up to March 7, 2021, and further selection was performed according to the eligibility criteria. Quality Assessment of Diagnostic Accuracy Studies-2 was used for quality assessment, and heterogeneity assessment and statistical calculations were also performed. RESULTS: In total, 1851 records were retrieved from online databases, and 15 studies were finally included. Regarding the performance of HR-MRI, the superficial extracranial artery had 75% sensitivity and 89% specificity, respectively, with an area under the receiver operating characteristic curve (AUC) of 0.91. Positive and negative post-test possibilities were 86% and 20%, respectively, with clinical diagnosis as reference. When referenced with temporal artery biopsy, the sensitivity was 91%, specificity was 78%, AUC was 0.92, and positive and negative post-test possibilities were 78% and 10%, respectively. 3D HR-MRI and 2D HR-MRI had 70% and 72% sensitivity, respectively, and 91% and 84% specificity, respectively. CONCLUSIONS: HR-MRI is a valuable imaging modality for GCA diagnosis. It provided high accuracy in the diagnosis of GCA and played a potential role in identifying GCA-related ischemic optic neuropathy. 3D HR-MRI had better specificity than 2D HR-MRI. KEY POINTS: HR-MRI helps clinicians to diagnose GCA. Superficial extracranial arteries and other MRI abnormalities can be assessed with HR-MRI. HR-MRI can help in assessing GCA-related optic neuropathy.

Association between abnormal body weight and stroke outcome: A meta-analysis and systematic review.

BACKGROUND AND PURPOSE: To test the hypothesis that "obesity paradox" exists in stroke patients, we conducted a meta-analysis and systematic review on the association between abnormal body weight (obesity, overweight, or underweight) and the outcome of different types of stroke. METHODS: This meta-analysis and systematic review was performed in conformity to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines in Appendix S2. Studies investigating the association between abnormal body weight and the outcome of different types of stroke were searched for in the PubMed and Embase databases from their inception to 20 March 2021. RESULTS: Thirty-three articles including 84,660 patients were included in this study. Obesity and overweight were associated with longer survival in mixed-stroke patients (acute ischemic stroke [AIS] combined with one or more other stroke subtypes) than was normal weight, whereas underweight was related to shorter survival; the pooled hazard ratios (HRs) of mortality were 0.77 (95% confidence interval [CI] = 0.71-0.83) for obesity, 0.76 (95% CI = 0.72-0.80) for overweight, and 1.71 (95% CI = 1.56-1.87) for underweight. However, only obesity was associated with longer survival in AIS patients compared with normal weight, and underweight was related to shorter survival; the pooled HR of mortality was 0.75 (95% CI = 0.64-0.88) for obesity and 1.53 (95% CI = 1.27-1.85) for underweight. After merging mixed-stroke and AIS patients, we obtained similar results as in mixed-stroke patients. CONCLUSIONS: Our results suggested that in patients with mixed stroke or AIS, obesity was associated with a longer survival time than normal weight, whereas underweight was associated with a shorter survival time.

Safety and efficacy of tirofiban combined with endovascular therapy compared with endovascular therapy alone in acute ischemic stroke: a meta-analysis.

Endovascular treatment (EVT) has been widely used for treating acute ischemic stroke (AIS). However, the safety and efficacy of treating AIS with tirofiban combined with EVT remain controversial. Therefore, we conducted a meta-analysis to evaluate this treatment. Randomized controlled trials and cohort studies that compared treatment with tirofiban combined with EVT and EVT alone were included in our meta-analysis. Those published from inception to March 31, 2020, were searched using the PubMed, Web of Science, Embase, and Cochrane Library databases. Safety was assessed based on symptomatic intracranial hemorrhage (sICH) incidence and 3-month mortality. Efficacy was assessed based on modified Rankin Scale (mRS) scores at 3 months post-EVT and recanalization rates. Data were analyzed using either the random-effects or fixed-effects model based on the heterogeneity of studies. In total, one RCT, six prospective studies, and four retrospective studies (2387 AIS cases) were assessed. Our meta-analysis showed that tirofiban combined with EVT did not increase sICH risk (RR, 1.06; 95%CI, 0.79 to 1.42; P = 0.72) and 3-month mortality (RR, 0.87; 95%CI, 0.74 to 1.04; P = 0.12). Recanalization rates were not significantly different between patients treated with tirofiban combined with EVT and those treated with EVT alone (RR, 1.04; 95%CI, 1.00 to 1.08; P = 0.07), but tirofiban combined with EVT was significantly associated with favorable functional outcomes (mRS score, 0-2) in AIS patients (RR, 1.13; 95%CI, 1.02 to 1.25; P = 0.02). Tirofiban combined with EVT appears to be safe and potentially effective in treating AIS.

The Impact of Remote Ischaemic Conditioning on Beat-to-Beat Heart Rate Variability Circadian Rhythm in Healthy Adults.

BACKGROUND: Remote ischaemic conditioning (RIC) is an intervention that may exert a protective effect over multiple tissues or organs by regulating neuronal signal transduction. Heart rate variability (HRV) can assess the state of the autonomic nervous system. However, whether RIC can also regulate HRV in humans remains unknown. METHOD: This was a self-controlled interventional study in which serial beat-to-beat monitoring was performed at the same seven time points (7, 9, and 11 AM; 2, 5, and 8 PM; and 8 AM on the next day) with or without RIC in 50 healthy adults. The seven time points on the RIC day were defined as baseline, 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, and 24 hours after RIC. The RIC protocol consisted of 4×5-minute inflation/deflation in one arm and one thigh cuff at 200 mmHg pressure from 7:20 to 8 AM. This study is registered on ClinicalTrials.gov (NCT02965547). RESULTS: We included 50 healthy adult volunteers (aged 34.54±12.01 years, 22 men [44%], all Asian). The variables analysed in frequency-domain measures performed as power of low-frequency in normalised units (0.04-0.15 Hz), high-frequency in normalised units (0.15-0.40 Hz), and ratio of low frequency to high frequency. The time-domain parameters standard deviation (SD) of all normal to normal (NN) intervals (SDNN), mean of the 5-minute SD of the NN intervals, SD of the consecutive 5-minute averages of NN intervals, and the root mean square of successive differences of NN intervals, and time-domain parameters calculated from Poincaré plots, SD of the short diagonal axis in Poincaré plot (SD1), SD of the long diagonal axis in Poincaré plot (SD2), and SD1/SD2 were also obtained. The SDNN and SD2 significantly increased 1 hour after RIC (p=0.029 and p=0.045, respectively). Additionally, the SD2 increased a second time 12 hours after RIC (p=0.041), which represented inhibited sympathetic activity. CONCLUSIONS: Heart rate variability increase and sympathetic inhibition induced by RIC appeared both on the early and delayed protective window of RIC, which may indicate some of the underlying mechanisms by which RIC may offer protection.

Venous sinus stenting improves cerebral autoregulation in a patient with venous sinus stenosis: a case report.

BACKGROUND: Venous sinus stenosis (VSS) is a type of cerebral venous vascular disease. Cerebral autoregulation is an indicator of cerebral arterial function. The cerebral circulatory system is composed of the venous system and arterial system. Impaired venous function may affect arterial function. Thus, cerebral venous stenosis may influence cerebral autoregulation. CASE PRESENTATION: In this case, a 50-year-old woman with transient blindness and headache was admitted to the hospital. The patient was diagnosed with VSS. A stent was placed at the stenosis. The stent released the intravenous pressure and remitted the patient's symptoms. Measurements of dynamic cerebral autoregulation (dCA) were performed at 3 time points: before stenting, after stenting, and 3 months later. The dCA gradually improved after stenting. CONCLUSION: VSS may have an influence on cerebral autoregulation, and effective treatment improves cerebral autoregulation in patients with VSS.

Meta-analysis of the Smoker's Paradox in Acute Ischemic Stroke Patients Receiving Intravenous Thrombolysis or Endovascular Treatment.

INTRODUCTION: The existence of the smoker's paradox is controversial and potential mechanisms have not been explained. We aimed to explore the association between cigarette smoking and functional outcome at 3 months in patients with acute ischemic stroke who were treated with intravenous thrombolysis (IVT) or endovascular treatment (EVT). METHODS: This meta-analysis was conducted in accordance with the PRISMA guidelines. Studies exploring the association between smoking and good functional outcome (modified Rankin Scale score ≤ 2) following IVT or EVT were searched via the databases of PubMed, Embase, and the Cochrane Library from inception to August 8, 2018. Information on the characteristics of included studies was independently extracted by two investigators. Data were pooled using a random-effects or fixed-effects meta-analysis according to the heterogeneity of included studies. RESULTS: Among 20 identified studies, 15 reported functional outcomes following IVT, and five reported functional outcomes following EVT. Unadjusted analyses showed that smoking increased the odds of good functional outcomes with a pooled odds ratio (OR) of 1.48 (95% confidence interval [CI]: 1.36-1.60) after IVT and 2.10 (95% CI: 1.47-3.20) after EVT. Of IVT studies, only eight reported outcomes adjusted for covariates and none of the EVT studies reported adjusted outcomes. After adjustment, the relation between smoking and good functional outcome following IVT lost statistical significance (OR 1.14 [95% CI: 0.81-1.59]). CONCLUSION: Our meta-analysis suggested that smoking was not associated with good functional outcome (mRS ≤ 2) at 3 months in patients with acute ischemic stroke who were treated with intravenous thrombolysis. IMPLICATIONS: The existence of the smoker's paradox is controversial. A previous letter by Plas et al. published in 2013 reported a positive result for the association between smoking and good functional outcome at 3 months in acute ischemic stroke patients who received intravenous thrombolysis (IVT). However, a major limitation of their meta-analysis was that the process of data synthesis was based on unadjusted data. Therefore, we conducted this meta-analysis to investigate the association based on adjusted data and a larger sample size. Our meta-analysis suggested that smoking was not associated with good functional outcome after adjusting for covariates.

Eagle Syndrome as a Cause of Cerebral Venous Sinus Thrombosis.

A 15-year-old teenager presented with a 2-month history of headache. Neurological examination was normal except for papilledema. Further lumbar puncture indicated intracranial hypertension (330 mm H2O). Brain magnetic resonance imaging (MRI) was normal but phase contrast-magnetic resonance venography (PC-MRV) (Figure 1(A)) suggested possible left transverse-sigmoid sinus thrombosis; subsequent contrast-enhanced 3D fat-saturated T1 volumetric isotropic turbo spin echo acquisition (VISTA) MRI (Figure 1(B)) confirmed the pathology. Hyper-coagulable panel results (including six steroid sex hormones, antithrombin III, protein C, protein S, lupus anticoagulant, and anticardiolipin antibodies) were all within normal range. In further examination, computed tomography (CT) venography images (Figure 1(C) and (D)) showed that the left jugular vein was compressed by the styloid process, consistent with Eagle syndrome.1 The patient who refused the recommended surgical treatment, however, chose anticoagulant therapy consisting of low-molecular weight heparin subcutaneous injection in addition to new oral anticoagulant. At 18-month follow-up, the patient reported no symptoms remained.

Study on the Clinical, Imaging, and Pathological Characteristics of 18 Cases with Primary Central Nervous System Vasculitis.

BACKGROUND: To summarize the characteristics of primary central nervous system vasculitis from clinical, imaging, and pathological aspects by retrospective study. METHODS: From March 2015 to December 2017, the data of the inpatients of primary central nervous system vasculitis in first Hospital of Jilin University were collected, and their clinical manifestation, imaging, and pathological characteristics were analyzed by using a descriptive method. RESULTS: There were 18 patients, 10 males (55.56%) and 8 females (44.44%) separately. The age ranges from 16 years old to 49 years old, with the median age of 32 years old. There were 8 cases (44.44%) of epileptic seizure, 6 cases (33.33%) of abnormal behavior and cognition, 10 cases (55.56%) with sensorimotor abnormalities, 4 cases (22.22%) with dizziness, 4 cases (22.22%) with headache, 2 cases (11.11%) with facial pain, 2 cases (11.11%) with blurred vision, and 2 cases (11.11%) with unstable walking. Eight patients (44.44%) were identified with cerebral spinal fluid abnormalities. There were 12 cases (66.67%) with bilateral lesions and 6 cases (33.33%) with unilateral lesions, including the frontal lobe (18 cases, 100%), the parietal lobe (10 cases, 55.56%), the temporal and occipital lobe (8 cases, 44.44%). There were 12 cases (66.67%) combined with subcortical white matter involvement, 6 cases (33.33%) combined with meningeal involvement, 2 cases (11.11%) complicated with basal ganglia involvement and 2 cases (11.11%) complicated with spinal cord involvement. Most of the lesions were with unclear border (16 cases, 88.89%), 2 cases (11.11%) were with clear border. Cortical atrophy was identified in 6 cases (33.33%). There were 12 cases (66.67%) with the enhancement of the lesions and meningeal. The 3D Vessel Wall magnetic resonance imaging (VW-MRI) showed uniform thickness in all patients (18/18) with contrast enhancement of the vessel wall of the vasculitis artery. CONCLUSIONS: The clinical manifestation and imaging in primary central nervous system vasculitis are diverse. The 3D VW-MRI could achieve quantification assessment of vasculitis and provide more utility for primary angiitis of the central nervous system.

Compromised dynamic cerebral autoregulation in patients with generalized anxiety disorder: a study using transfer function analysis.

BACKGROUND: Patients with generalized anxiety disorder (GAD) usually present with various neurological symptoms, but the mechanisms remain unclear. We aimed to analyze the characteristics of dynamic cerebral autoregulation (dCA) in patients with GAD. METHODS: Patients (aged ≥18 years) who were diagnosed with GAD were enrolled in this study. Medically and psychiatrically healthy volunteers were recruited as controls. Subjects received the Hamilton Rating Scale for Anxiety (HAMA) and 17-item Hamilton Depression Rating Scale (HAMD) evaluation. Noninvasive continuous arterial blood pressure and bilateral middle cerebral artery blood flow velocity were recorded simultaneously from each subject. Transfer function analysis was used to derive the autoregulatory parameters, including phase difference, gain, and coherence function. RESULTS: A total of 57 patients with GAD and 40 healthy volunteers were enrolled. We found that the phase difference values were significantly compromised in patients with GAD. In the Spearman correlation analysis, the phase difference values were negatively correlated with the HAMA scores and the HAMD scores. In the multiple linear regression analysis, GAD is negatively correlated with the phase difference values, whereas age is positively correlated with the phase difference values. CONCLUSIONS: Our results suggested that the dCA was compromised in patients with GAD and negatively correlated with the score of anxiety. Improving the dCA may be a potential therapeutic method for treating the neurological symptoms of GAD patients.

Hyperbaric Oxygen Reduces Infarction Volume and Hemorrhagic Transformation Through ATP/NAD+/Sirt1 Pathway in Hyperglycemic Middle Cerebral Artery Occlusion Rats.

BACKGROUND AND PURPOSE: Energy depletion is a critical factor leading to cell death and brain dysfunction after ischemic stroke. In this study, we investigated whether energy depletion is involved in hyperglycemia-induced hemorrhagic transformation after ischemic stroke and determined the pathway underlying the beneficial effects of hyperbaric oxygen (HBO). METHODS: After 2-hour middle cerebral artery occlusion, hyperglycemia was induced by injecting 50% dextrose (6 mL/kg) intraperitoneally at the onset of reperfusion. Immediately after it, rats were exposed to HBO at 2 atmospheres absolutes for 1 hour. ATP synthase inhibitor oligomycin A, nicotinamide phosphoribosyl transferase inhibitor FK866, or silent mating type information regulation 2 homolog 1 siRNA was administrated for interventions. Infarct volume, hemorrhagic volume, and neurobehavioral deficits were recorded; the level of blood glucose, ATP, and nicotinamide adenine dinucleotide and the activity of nicotinamide phosphoribosyl transferase were monitored; the expression of silent mating type information regulation 2 homolog 1, acetylated p53, acetylated nuclear factor-κB, and cleaved caspase 3 were detected by Western blots; and the activity of matrix metalloproteinase-9 was assayed by zymography. RESULTS: Hyperglycemia deteriorated energy metabolism and reduced the level of ATP and nicotinamide adenine dinucleotide and exaggerated hemorrhagic transformation, blood-brain barrier disruption, and neurological deficits after middle cerebral artery occlusion. HBO treatment increased the levels of the ATP and nicotinamide adenine dinucleotide and consequently increased silent mating type information regulation 2 homolog 1, resulting in attenuation of hemorrhagic transformation, brain infarction, as well as improvement of neurological function in hyperglycemic middle cerebral artery occlusion rats. CONCLUSIONS: HBO induced activation of ATP/nicotinamide adenine dinucleotide/silent mating type information regulation 2 homolog 1 pathway and protected blood-brain barrier in hyperglycemic middle cerebral artery occlusion rats. HBO might be promising approach for treatment of acute ischemic stroke patients, especially patients with diabetes mellitus or treated with r-tPA (recombinant tissue-type plasminogen activator).

Impaired cerebral autoregulation: measurement and application to stroke.

Cerebral autoregulation (CA) is a protective mechanism that maintains cerebral blood flow at a relatively constant level despite fluctuations of cerebral perfusion pressure or arterial blood pressure. It is a universal physiological mechanism that may involve myogenic, neural control as well as metabolic regulations of cerebral vasculature in response to changes in pressure or cerebral blood flow. Traditionally, CA has been represented by a sigmoid curve with a wide plateau between about 50 mm Hg and 170 mm Hg of steady-state changes in mean arterial pressure, defined as static CA. With the advent of transcranial Doppler, measurement of cerebral blood flow in response to transient changes in arterial pressure has been used to assess dynamic CA. However, a gold standard for measuring CA is not currently available. Stroke has been the leading cause of long-term adult disability throughout the world. A better understanding of CA and its response to pathological derangements can help assess the severity of stroke, guide management decisions, assess response to interventions and provide prognostic information. The objective of this review is to provide a comprehensive insight about physiology of autoregulation, measurement methodologies and clinical applications in stroke to help build a consensus for what should be included in an internationally agreed protocol for CA testing and monitoring, and to promote its translation into clinical bedside practice for stroke management.

Characteristics of cardio-Cerebrovascular modulation in patients with generalized anxiety disorder: an observational study.

BACKGROUND: Generalized anxiety disorder (GAD) has been shown in previous studies to display abnormal cerebral blood flow velocity (CBFV); however, the characteristics of cardio-cerebrovascular modulation are unknown. We aimed to analyze cardio-cerebrovascular modulation using parameters from a supine-to-standing test. METHODS: There are 2 parts to this study; in Part 1, 125 participants with Hamilton Anxiety scale scores ≥14 were enrolled, and 33 age- and sex-matched medically and psychiatrically healthy volunteers were recruited as control participants. Patients were divided by score into mild, moderate, and severe anxiety groups. The cardio-cerebrovascular modulation using the parameters of dynamic changes of CBFV and heart rate in response to an orthostatic challenge were investigated. In Part 2, we followed up the severe GAD patients for 6 months and repeated the supine-to-standing test, and severe GAD patients were divided into recovery and non-recovery groups. RESULTS: In part 1, the GAD group displayed more marked CBFV and heart rate changes than the healthy group, but there was no difference in the CBFV and heart rate changes from the supine to upright position in mild, moderate, and severe anxiety groups. In part 2, The recovery group demonstrated significant improvement in changes in the CBFV and heart rate values from the supine to the upright position after treatment compared with before treatment. In the non-recovery group, the CBFV and heart rate changes were significantly higher than the healthy group regardless of treatment. CONCLUSIONS: Cardio-cerebrovascular modulation is compromised in patients with GAD, however, this impairment can be restored to normal after the disappearance of anxiety.

The prevalence, awareness, treatment, and control of dyslipidemia in northeast China: a population-based cross-sectional survey.

BACKGROUND: Dyslipidemia is an important independent modifiable risk factor for cardiovascular disease. The aim of this study was to explore the current prevalence, awareness, treatment and control of dyslipidemia and its associated influence factors in northeast China. METHODS: In this population-based cross-sectional study, we adopted a multi-stage, stratified sampling method to obtain a representative sample of 4052 permanent residents aged 40 years and over from different urban and rural regions in Dehui City of Jilin Province. All subjects completed a questionnaire and were examined for risk factors. Continuous data were presented as means ± standard deviations (SD) and compared using the Student's t-test. Categorical variables were presented as proportions and compared using the Rao-Scott-χ 2 test in different subgroups. The associated influence factors for the prevalence, awareness, treatment and control of dyslipidemia were evaluated through multivariate logistic regression. RESULTS: The prevalence of dyslipidemia was 62.1% overall, with 33.5, 43.9, 0.6, and 8.8% for high total cholesterol, triglyceride, low-density lipoprotein cholesterol, and low high-density lipoprotein cholesterol, respectively. Among those with dyslipidemia, the proportion of subjects who were aware, treated, and controlled was 14.4, 33.9, and 19.9%, respectively. Overweight or obesity (OR = 2.156; 95% CI: 1.863, 2.533), hypertension (OR = 1.643; 95% CI: 1.425, 1.893), or diabetes mellitus (OR = 2.173; 95% CI: 1.661, 2.844) increased the prevalence of dyslipidemia, also these participants were more likely to be aware of their condition, however, this did not increase the likelihood of treatment and control. Living in urban areas and higher education level also increased the awareness of dyslipidemia. Personal history of coronary heart disease was the strongest influence factors associated with better awareness, treatment and control of dyslipidemia. Overweight or obesity (OR = 0.404; 95% CI: 0.235, 0.695) and lack of exercise (OR = 0.423; 95% CI: 0.215, 0.830) were associated with poor control of dyslipidemia. CONCLUSION: The prevalence of dyslipidemia among adults aged 40 years and over in northeast China was high, however, the awareness, treatment, and control of dyslipidemia was measured at far from desirable levels. Renewed efforts taking influence factors into account are needed to improve the current unsatisfactory condition.

Temporal Course of Dynamic Cerebral Autoregulation in Patients With Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Cerebral autoregulation is crucial in patients with intracerebral hemorrhage. Dynamic cerebral autoregulation is probably altered in acute intracerebral hemorrhage; however, the temporal course of dynamic cerebral autoregulation and its correlation with clinical factors and outcomes are poorly understood. METHODS: Forty-three acute supratentorial intracerebral hemorrhage patients (53.7±10.0 years old, 30 men) were enrolled for serial measurements performed on days 1 to 2, 4 to 6, 10 to 12, and 30 days after ictus. Noninvasive continuous cerebral blood flow velocity and arterial blood pressure were recorded simultaneously using transcranial Doppler and a servo-controlled plethysmograph, respectively. Transfer function analysis was used to derive the autoregulatory parameters, including phase difference (PD), gain, and the rate of recovery of cerebral blood flow velocity. Results were compared with healthy controls and correlated with clinical factors and the 90-day outcome. RESULTS: PD did not differ between affected and unaffected hemispheres over time. A significant lower PD (indicating dynamic cerebral autoregulation impaired) was found in bilateral hemispheres on days 1 to 2, 4 to 6, and 10 to 12, followed by later recovery on day 30. Lower bilateral PD on days 1 to 2 was associated with poorer Glasgow Coma Scale score at that time. Lower affected-side PD on days 4 to 6 was an independent predictive value for a poorer modified Rankin Scale at 90 days. CONCLUSIONS: In patients with supratentorial intracerebral hemorrhage, dynamic cerebral autoregulation is bilaterally impaired lasting at least 10 to 12 days and recovers within a month. Individual PD value is associated with clinical status at acute stage and affected-side PD on days 4 to 6 can be an independent predictor for clinical outcome.

Lipoxin A4 Reduces Inflammation Through Formyl Peptide Receptor 2/p38 MAPK Signaling Pathway in Subarachnoid Hemorrhage Rats.

BACKGROUND AND PURPOSE: Lipoxin A4 (LXA4) has been reported to reduce inflammation in several neurological injury models. We studied the effects of LXA4 on neuroinflammation after subarachnoid hemorrhage (SAH) in a rat model. METHODS: Two hundred and thirty-eight Sprague-Dawley male rats, weight 280-320 g, were used. Exogenous LXA4 (0.3 and 1.0 nmol) were injected intracerebroventricularly at 1.5 hours after SAH. Neurological scores, brain water content, and blood-brain barrier were evaluated at 24 hours after SAH; Morris water maze and T-maze tests were examined at 21 days after SAH. The expression of endogenous LXA4 and its receptor formyl peptide receptor 2 (FPR2), as well as p38, interleukin-1ß, and interleukin-6 were studied either by ELISA or by Western blots. Neutrophil infiltration was observed by myeloperoxidase staining. FPR2 siRNA was used to knock down LXA4 receptor. RESULTS: The expression of endogenous LXA4 decreased, and the expression of FPR2 increased after SAH. Exogenous LXA4 decreased brain water content, reduced Evans blue extravasation, and improved neurological functions and improved the learning and memory ability after SAH. LXA4 reduced neutrophil infiltration and phosphorylation of p38, interleukin-1ß, and interleukin-6. These effects of LXA4 were abolished by FPR2 siRNA. CONCLUSIONS: Exogenous LXA4 inhibited inflammation by activating FPR2 and inhibiting p38 after SAH. LXA4 may serve as an alternative treatment to relieve early brain injury after SAH.