Cerebrovascular Autoregulation in Preterm Infants Using Heart Rate or Blood Pressure: A Pilot Study.

BACKGROUND: Cerebrovascular autoregulation (CAR) is often impaired in preterm infants but requires invasive mean arterial blood pressure (MABP) measurements for continuous assessment. We aimed to assess whether using heart rate (HR) results in different CAR assessment compared with using MABP. METHODS: We compared CAR (moving window correlation-coefficient with cerebral oxygenation saturation (rcSO2)), and percentage of time with impaired CAR (%timeCARi) calculated by either HR (TOHRx, tissue oxygenation heart rate reactivity index) or MABP (COx, cerebral oximetry index) during the first 72 h after birth, and its association with short-term cerebral injury. RESULTS: We included 32 infants, median gestational age of 25 + 5/7 weeks (interquartile range 24 + 6/7-27 + 5/7). COx and TOHRx correlation coefficients (cc) were significantly different in the first two days after birth (individual means ranging from 0.02 to 0.07 and -0.05 to 0.01). %TimeCARi using MABP (cc cut-off 0.3), was higher on day 1 (26.1% vs. 17.7%) and day 3 (23.4% vs. 16.9%) compared with HR (cc cutoff -0.3). During 65.7-69.6% of the time, both methods indicated impaired CAR simultaneously. The aforementioned calculations were not associated with early cerebral injury. CONCLUSIONS: In conclusion, HR and MABP do not seem interchangeable when assessing CAR in preterm infants.

Nimodipine Protects Vascular and Cognitive Function in an Animal Model of Cerebral Small Vessel Disease.

BACKGROUND: Cerebral small vessel disease is a common cause of vascular cognitive impairment and dementia. There is an urgent need for preventative treatments for vascular cognitive impairment and dementia, and reducing vascular dysfunction may provide a therapeutic route. Here, we investigate whether the chronic administration of nimodipine, a central nervous system-selective dihydropyridine calcium channel blocking agent, protects vascular, metabolic, and cognitive function in an animal model of cerebral small vessel disease, the spontaneously hypertensive stroke-prone rat. METHODS: Male spontaneously hypertensive stroke-prone rats were randomly allocated to receive either a placebo (n=24) or nimodipine (n=24) diet between 3 and 6 months of age. Animals were examined daily for any neurological deficits, and vascular function was assessed in terms of neurovascular and neurometabolic coupling at 3 and 6 months of age, and cerebrovascular reactivity at 6 months of age. Cognitive function was evaluated using the novel object recognition test at 6 months of age. RESULTS: Six untreated control animals were terminated prematurely due to strokes, including one due to seizure, but no treated animals experienced strokes and so had a higher survival (P=0.0088). Vascular function was significantly impaired with disease progression, but nimodipine treatment partially preserved neurovascular coupling and neurometabolic coupling, indicated by larger (P<0.001) and more prompt responses (P<0.01), and less habituation upon repeated stimulation (P<0.01). Also, animals treated with nimodipine showed greater cerebrovascular reactivity, indicated by larger dilation of arterioles (P=0.015) and an increase in blood flow velocity (P=0.001). This protection of vascular and metabolic function achieved by nimodipine treatment was associated with better cognitive function (P<0.001) in the treated animals. CONCLUSIONS: Chronic treatment with nimodipine protects from strokes, and vascular and cognitive deficits in spontaneously hypertensive stroke-prone rat. Nimodipine may provide an effective preventive treatment for stroke and cognitive decline in cerebral small vessel disease.

Exploring the relationship between embolic acute stroke distribution and supra-aortic vessel patency: key findings from an in vitro model study.

BACKGROUND: We investigated differences in intracranial embolus distribution through communicating arteries in relation to supra-aortic vessel (SAV) patency. METHODS: For this experimental analysis, we created a silicone model of the extracranial and intracranial circulations using a blood-mimicking fluid under physiological pulsatile flow. We examined the sequence of embolus lodgment on injecting 104 frangible clot analogues (406 emboli) through the right internal carotid artery (CA) as SAV patency changed: (a) all SAV patent (baseline), (b) emboli from a CA occlusion, (c) emboli contralateral to a CA occlusion and (d) occlusion of the posterior circulation. The statistical analysis included a descriptive analysis of thrombi location after occlusion (absolute and relative frequencies). Sequences of occlusions were displayed in Sankey flow charts for the four SAV conditions. Associations between SAV conditions and occlusion location were tested by Fisher's exact test. Two-sided p values were compared with a significance level of 0.05. RESULTS: The total number of emboli was 406 (median fragments/clot: 4 (IQR: 3-5)). Embolus lodgment was dependent on SAV patency (p<0.0001). In all scenarios, embolism lodging in the anterior cerebral artery (ACA) occurred after a previous middle cerebral artery (MCA) embolism (MCA first lodge: 96%, 100/104). The rate of ipsilateral ACA embolism was 28.9% (28/97) at baseline, decreasing significantly when emboli originated from an occluded CA (16%, 14/88). There were more bihemispheric embolisations in cases of contralateral CA occlusion (37%, 45/122), with bilateral ACA embolisms preceding contralateral MCA embolism in 56% of cases (14/25 opposite MCA and ACA embolism). CONCLUSIONS: All emboli in the ACA occurred after a previous ipsilateral MCA embolism. Bihemispheric embolisms were rare, except when there was a coexisting occlusion in either CA, particularly in cases of a contralateral CA occlusion.

Effects of induced arterial hypertension for vasospasm on unruptured and unsecured cerebral aneurysms (growth and rupture). A retrospective case-control study.

OBJECTIVES: Unruptured cerebral aneurysms (UCAs) often coexist with the ruptured one but are typically left unsecured during the weeks following aneurysmal subarachnoid hemorrhage (aSAH). We compared the rate of UCAs rupture or volume growth (≥5 mm3) between patients exposed to induced arterial hypertension (iHTN) for vasospasm and those not exposed (control group). MATERIALS AND METHODS: From 2013 to 2021, we retrospectively included consecutive adult patients with aSAH who had ≥1 UCA. Custom software for digital subtraction angiography (DSA) image analysis characterized UCAs volume, going beyond merely considering UCAs long axis. RESULTS: We analyzed 118 patients (180 UCAs): 45 in the iHTN group (64 UCAs) and 73 in the control group (116 UCAs). Systolic blood pressure in the iHTN group was significantly higher than in the control group for several days after aSAH. During the 107 day-monitoring period [interquartile range(IQR):92;128], no UCA rupture occurred in either group. UCA volume analysis was performed in 44 patients (60 UCAs): none of the UCAs in the iHTN group and 3 out of 42 (7%) in the control group had a >5 mm3 volume growth (p=0.55). Other morphologic parameters did not exhibit any variations that might indicate an increased risk of rupture in the iHTN group compared to the control group. CONCLUSION: iHTN did not increase the risk of rupture or volume growth of UCAs within several weeks following aSAH. These reassuring results encourage not to refrain, because of the existence of UCAs, from iHTN as an option to prevent cerebral infarction during cerebral vasospasm.

Revascularisation patterns and characteristics after erythropoietin pretreatment and multiple burr holes in patients who had acute stroke with perfusion impairment.

BACKGROUND: Transdural collaterals, originating mainly from the extracalvarial superficial temporal artery and intracalvarial middle meningeal artery via the external carotid artery (ECA), have been observed after revascularisation surgery. However, the origin of these collaterals in patients with stroke with perfusion insufficiency is not yet known. Therefore, we studied the revascularisation patterns and characteristics based on the origin of these collaterals. METHODS: We employed erythropoietin pretreatment and performed multiple burr holes under local anaesthesia to achieve transdural revascularisation in patients with acute stroke with perfusion insufficiency. After 6 months, we reassessed the transfemoral cerebral angiography to evaluate the revascularisation patterns. The collaterals were categorised into intracalvarial ECA-dominant (originating from the middle meningeal artery), extracalvarial ECA-dominant (originating from the superficial temporal or occipital artery) and balanced groups. We compared various imaging parameters among these groups. RESULTS: Overall, 87 patients with 103 treated hemispheres were involved. Among them, 57.3% were classified as intracalvarial ECA-dominant, 20.4% as extracalvarial ECA-dominant and 22.3% as balanced. Most of the hemispheres with intracalvarial or extracalvarial collaterals (vs balanced collaterals) showed successful revascularisation (78/80 (97.5%) vs 12/23 (52.1%)), p<0.001). In ultrasonographic haemodynamic changes according to revascularisation pattern, only the intracalvarial ECA-dominant revascularisation was significantly associated with specific changes in ECA blood flow, leading to the conversion to a low-resistance ECA Doppler sonography waveform. CONCLUSIONS: Our findings suggest that intracalvarial ECA-dominant revascularisation plays a crucial role in the formation of transdural collaterals following combined therapy. These distinct changes in ECA haemodynamics can be non-invasively identified through bedside ultrasound studies.

Cerebral Autoregulation: A Target for Improving Neurological Outcomes in Extracorporeal Life Support.

Despite improvements in survival after illnesses requiring extracorporeal life support, cerebral injury continues to hinder successful outcomes. Cerebral autoregulation (CA) is an innate protective mechanism that maintains constant cerebral blood flow in the face of varying systemic blood pressure. However, it is impaired in certain disease states and, potentially, following initiation of extracorporeal circulatory support. In this review, we first discuss patient-related factors pertaining to venovenous and venoarterial extracorporeal membrane oxygenation (ECMO) and their potential role in CA impairment. Next, we examine factors intrinsic to ECMO that may affect CA, such as cannulation, changes in pulsatility, the inflammatory and adaptive immune response, intracranial hemorrhage, and ischemic stroke, in addition to ECMO management factors, such as oxygenation, ventilation, flow rates, and blood pressure management. We highlight potential mechanisms that lead to disruption of CA in both pediatric and adult populations, the challenges of measuring CA in these patients, and potential associations with neurological outcome. Altogether, we discuss individualized CA monitoring as a potential target for improving neurological outcomes in extracorporeal life support.

Near-Infrared II Photobiomodulation Preconditioning Ameliorates Stroke Injury via Phosphorylation of eNOS.

BACKGROUND: The current management of patients with stroke with intravenous thrombolysis and endovascular thrombectomy is effective only when it is timely performed on an appropriately selected but minor fraction of patients. The development of novel adjunctive therapy is highly desired to reduce morbidity and mortality with stroke. Since endothelial dysfunction is implicated in the pathogenesis of stroke and is featured with suppressed endothelial nitric oxide synthase (eNOS) with concomitant nitric oxide deficiency, restoring endothelial nitric oxide represents a promising approach to treating stroke injury. METHODS: This is a preclinical proof-of-concept study to determine the therapeutic effect of transcranial treatment with a low-power near-infrared laser in a mouse model of ischemic stroke. The laser treatment was performed before the middle cerebral artery occlusion with a filament. To determine the involvement of eNOS phosphorylation, unphosphorylatable eNOS S1176A knock-in mice were used. Each measurement was analyzed by a 2-way ANOVA to assess the effect of the treatment on cerebral blood flow with laser Doppler flowmetry, eNOS phosphorylation by immunoblot analysis, and stroke outcomes by infarct volumes and neurological deficits. RESULTS: Pretreatment with a 1064-nm laser at an irradiance of 50 mW/cm2 improved cerebral blood flow, eNOS phosphorylation, and stroke outcomes. CONCLUSIONS: Near-infrared II photobiomodulation could offer a noninvasive and low-risk adjunctive therapy for stroke injury. This new modality using a physical parameter merits further consideration to develop innovative therapies to prevent and treat a wide array of cardiovascular diseases.

Lipoprotein Particles in Cerebrospinal Fluid.

The brain is the most lipid-rich organ in the body, and the intricate interplay between lipid metabolism and pathologies associated with neurodegenerative disorders is being increasingly recognized. The brain is bathed in cerebrospinal fluid (CSF), which, like plasma, contains lipid-protein complexes called lipoproteins that are responsible for extracellular lipid transport. Multiple CSF lipoprotein populations exist, some of which are produced de novo in the central nervous system and others that appear to be generated from protein constituents that are produced in the periphery. These CSF lipoproteins are thought to play key roles in maintaining lipid homeostasis in the central nervous system, while little else is known due to their limited accessibility and their low abundance in CSF. Recent work has provided new insights into the compositional complexity of CSF lipoprotein families and their metabolism in cerebral circulation. The purpose of this review is to summarize our current state of knowledge on the composition, origin, and metabolism of CSF lipoproteins.

Circadian and Diurnal Regulation of Cerebral Blood Flow.

Circadian and diurnal variation in cerebral blood flow directly contributes to the diurnal variation in the risk of stroke, either through factors that trigger stroke or due to impaired compensatory mechanisms. Cerebral blood flow results from the integration of systemic hemodynamics, including heart rate, cardiac output, and blood pressure, with cerebrovascular regulatory mechanisms, including cerebrovascular reactivity, autoregulation, and neurovascular coupling. We review the evidence for the circadian and diurnal variation in each of these mechanisms and their integration, from the detailed evidence for mechanisms underlying the nocturnal nadir and morning surge in blood pressure to identifying limited available evidence for circadian and diurnal variation in cerebrovascular compensatory mechanisms. We, thus, identify key systemic hemodynamic factors related to the diurnal variation in the risk of stroke but particularly identify the need for further research focused on cerebrovascular regulatory mechanisms.

Hypertension: Causes and Consequences of Circadian Rhythms in Blood Pressure.

Hypertension is extremely common, affecting approximately 1 in every 2 adults globally. Chronic hypertension is the leading modifiable risk factor for cardiovascular disease and premature mortality worldwide. Despite considerable efforts to define mechanisms that underlie hypertension, a potentially major component of the disease, the role of circadian biology has been relatively overlooked in both preclinical models and humans. Although the presence of daily and circadian patterns has been observed from the level of the genome to the whole organism, the functional and structural impact of biological rhythms, including mechanisms such as circadian misalignment, remains relatively poorly defined. Here, we review the impact of daily rhythms and circadian systems in regulating blood pressure and the onset, progression, and consequences of hypertension. There is an emphasis on the impact of circadian biology in relation to vascular disease and end-organ effects that, individually or in combination, contribute to complex phenotypes such as cognitive decline and the loss of cardiac and brain health. Despite effective treatment options for some individuals, control of blood pressure remains inadequate in a substantial portion of the hypertensive population. Greater insight into circadian biology may form a foundation for novel and more widely effective molecular therapies or interventions to help in the prevention, treatment, and management of hypertension and its related pathophysiology.

Association between occlusion location, net water uptake and ischemic lesion growth in large vessel anterior circulation strokes.

Ischemic lesion net water uptake (NWU) represents a quantitative imaging biomarker for cerebral edema in acute ischemic stroke. Data on NWU for distinct occlusion locations remain scarce, but might help to improve the prognostic value of NWU. In this retrospective multicenter cohort study, we compared NWU between patients with proximal large vessel occlusion (pLVO; ICA or proximal M1) and distal large vessel occlusion (dLVO; distal M1 or M2). NWU was quantified by densitometric measurements of the early ischemic region. Arterial collateral status was assessed using the Maas scale. Regression analysis was used to investigate the relationship between occlusion location, NWU and ischemic lesion growth. A total of 685 patients met inclusion criteria. Early ischemic lesion NWU was higher in patients with pLVO compared with dLVO (7.7% vs 3.9%, P < .001). The relationship between occlusion location and NWU was partially mediated by arterial collateral status. NWU was associated with absolute ischemic lesion growth between admission and follow-up imaging (ß estimate, 5.50, 95% CI, 3.81-7.19, P < .001). This study establishes a framework for the relationship between occlusion location, arterial collateral status, early ischemic lesion NWU and ischemic lesion growth. Future prognostic thresholds for NWU might be optimized by adjusting for the occlusion location.

Cerebral circulation time on DSA after thrombectomy associated with hemorrhagic transformation in acute ischemic stroke.

BACKGROUND: To investigate the association between cerebral circulation time (CCT) on digital subtraction angiography immediately after thrombectomy and hemorrhagic transformation (HT) in acute ischemic stroke (AIS). METHODS: Retrospectively enrolled consecutive AIS patients presented with large vessel occlusion who received thrombectomy and achieved successful recanalization between January 2019 and June 2021. The time interval from the beginning of the siphon segment of internal carotid artery visualization until the end of the arterial phase during cerebral angiography was calculated as CCT. The independent association of CCT with HT was evaluated using logistic regression analyses. The receiver operating characteristic curve was analyzed to evaluate the association between CCT and HT. RESULTS: Two hundred and twenty-four patients were included, of whom 86 (38.4%) suffered HT. Compared with patients without HT, patients with HT were of advanced age, less commonly male, had more diabetes mellitus, had higher baseline National Institutes of Health Stroke Scale score, lower Alberta Stroke Program Early Computed Tomographic Score, and shorter CCT (P < 0.05). Multivariable logistic regression suggested that CCT was independently associated with HT (adjusted odds ratio, 0.170; 95% confidence interval, 0.004-0.450; P < 0.001). According to the receiver operating characteristic curve, the optimal cut-off value for the strong correlation between CCT and HT was 1.72 s, which had 76.6% sensitivity, 81.6% specificity, and the area under the curve was 0.846. CONCLUSION: Shorter post-thrombectomy CCT was independently associated with HT.

A novel 5-stage visual rating scale for global arterial spin labeling perfusion assessment in the brain: Simplifying evaluation for clinical implementation.

Objectives: The aim of this study was to develop and validate a visual rating scale for evaluating global arterial spin labeling (ASL) perfusion changes in the brain, with potential applications in a variety of conditions that impact general brain blood supply and perfusion. Methods: We employed a five-stage scale (0 being normal and 4 indicating the most severe perfusion decline) to assess 156 patients using a 3D pulsed ASL technique. Three radiologists independently reviewed the images, and inter-rater reliability of the visual rating scale was evaluated. Results: The ASL stages showed a consistent distribution among the patients. The inter-rater reliability among the three radiologists, as measured by the Intraclass Correlation Coefficient (ICC), was 0.982. Conclusion: Our findings suggest that this visual rating scale can be effectively implemented in everyday practice to evaluate global perfusion changes in the context of cardiovascular diseases, cerebrovascular diseases, cerebral small vessel disease, and other conditions that alter brain vascularization and perfusion. Further research is needed to explore the full range of clinical applications and to refine the scale for optimal utility.

Synchronous Superficial Middle Cerebral Vein Outflow Correlates Favorable Tissue Fate After Mechanical Thrombectomy for Acute Ischemic Stroke.

RATIONALE AND OBJECTIVES: The purpose of this study was to determine the association between hemispheric synchrony in venous outflow at baseline and tissue fate after mechanical thrombectomy (MT) for acute ischemic stroke (AIS). MATERIALS AND METHODS: A two-center retrospective analysis involving AIS patients who underwent MT was performed. The four cortical veins of interest include the superficial middle cerebral vein (SMCV), sphenoparietal sinus (SS), vein of Labbé (VOL), and vein of Trolard (VOT). Baseline computed tomography perfusion data were used to compare the following outflow parameters between the hemispheres: first filling time (△FFT), time to peak (△TTP) and total filling time (△TFT). Synchronous venous outflow was defined as △FFT = 0. Multivariable regression analyses were performed to evaluate the association of venous outflow synchrony with penumbral salvage, infarct growth, and intracranial hemorrhage (ICH) after MT. RESULTS: A total of 151 patients (71.4 ± 13.2 years, 65.6% women) were evaluated. Patients with synchronous SMCV outflow demonstrated significantly greater penumbral salvage (41.3 mL vs. 33.1 mL, P = 0.005) and lower infarct growth (9.0 mL vs. 14.4 mL, P = 0.015) compared to those with delayed SMCV outflow. Higher △FFTSMCV (ß = -1.44, P = 0.013) and △TTPSMCV (ß = -0.996, P = 0.003) significantly associated with lower penumbral salvage, while higher △FFTSMCV significantly associated with larger infarct growth (ß = 1.09, P = 0.005) and increased risk of ICH (odds ratio [OR] = 1.519, P = 0.047). CONCLUSION: Synchronous SMCV outflow is an independent predictor of favorable tissue outcome and low ICH risk, and thereby carries the potential as an auxiliary radiological marker aiding the treatment planning of AIS patients.

Assessing the Adequacy of Superficial Temporal Artery Blood Flow in Korean Patients Undergoing STA-MCA Anastomosis.

OBJECTIVE: Superficial temporal artery (STA)-middle cerebral artery (MCA) anastomosis is conducted for flow augmentation. In this study, we measured the STA cut flow of a Korean population and evaluated the relationship between STA cut flow and long-term patency of the bypass. METHODS: A retrospective study was conducted. Intraoperative measurement of STA flow was conducted using a microvascular flow meter on patients who underwent STA-MCA. After cutting the distal end, the STA flow rate was measured with no resistance and recorded. After finishing anastomosis, STA flow was measured and recorded. The cut flow index was calculated by dividing post anastomosis flow by cut flow in intracranial atherosclerotic stenosis patients. RESULTS: The median STA cut flow was 35.0 mL/min and the post anastomosis flow was 24.0 mL/min. The cut flow of STA decreased with aging (p=0.027) and increased with diameter (p=0.004). The cut flow showed no correlation with history of hypertension or diabetes mellitus (p=0.713 and p=0.786), but did correlate a positively with history of hyperlipidemia (p=0.004). There were no statistical differences in cut flow, STA diameter, and post anastomosis flow between the frontal and parietal branches (p=0.081, p=0.853, and p=0.990, respectively). CONCLUSION: The median STA cut flow of a Korean population was 35 mL/min. Upon reviewing previous articles, it appears that there are differences in the STA cut flow between Western and Asian patients.

Ten-year follow-up investigation of stroke risk in systemic lupus erythematosus.

BACKGROUND AND PURPOSE: To analyse the long-term risk of ischaemic stroke and the clinical effects of antithrombotics on the risk of haemorrhagic stroke in patients with systemic lupus erythematosus (SLE). METHODS: A retrospective cohort study was conducted using a population-based database taken from Taiwan National Health Insurance Research Database. Patients with SLE between 2000 and 2008 were registered and matched with two controls by the index date, age, gender and Charlson Comorbidity Index (CCI). These subjects were followed until either stroke event or 31 December 2013. Adjusted HRs (aHRs) for strokes were estimated with Cox regression models, and the cumulative incidence of ischaemic stroke was analysed by log-rank test and Kaplan-Meier survival analysis. RESULTS: In total, 8310 patients with SLE and 16 620 patients without SLE were included. In general, patients with SLE had higher rates of ischaemic stroke (5.4% vs 3.3%) and haemorrhagic stroke (1.5% vs 0.6%) than in controls. In multivariate analysis adjusted to age, gender, CCI, urbanisation level and antithrombotics uses, aHRs of all strokes, ischaemic stroke and haemorrhagic stroke were 1.73 (95% CI: 1.54 to 1.94), 1.65 (95% CI: 1.45 to 1.87) and 2.24 (95% CI: 1.71 to 2.95), respectively, in patients with SLE. Patients with SLE were significantly more likely to suffer ischaemic stroke than patients without SLE, even 10 years after SLE diagnosis (6.12% vs 3.50%, p<0.001). Antiplatelet use increased the risk of haemorrhagic stroke in SLE group (aHR=1.74, 95% CI: 1.18 to 2.57). CONCLUSIONS: Patients with SLE are at greater risk of developing ischaemic stroke that lasts for 10 years. Antiplatelets should be carefully administered to prevent cardiovascular events in patients with SLE due to the risk of haemorrhagic stroke.