Relationship Between Baroreflex and Cerebral Autoregulation in Patients With Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Introduction: Common consequences following aneurysmal subarachnoid hemorrhage (aSAH) are cerebral vasospasm (CV), impaired cerebral autoregulation (CA), and disturbance in the autonomic nervous system, as indicated by lower baroreflex sensitivity (BRS). The compensatory interaction between BRS and CA has been shown in healthy volunteers and stable pathological conditions such as carotid atherosclerosis. The aim of this study was to investigate whether the inverse correlation between BRS and CA would be lost in patients after aSAH during vasospasm. A secondary objective was to analyze the time-trend of BRS after aSAH.Materials and Methods: Retrospective analysis of prospectively collected data was performed at the Neuro-Critical Care Unit of Addenbrooke's Hospital (Cambridge, UK) between June 2010 and January 2012. The cerebral blood flow velocity (CBFV) was measured in the middle cerebral artery using transcranial Doppler ultrasonography (TCD). The arterial blood pressure (ABP) was monitored invasively through an arterial line. CA was quantified by the correlation coefficient (Mxa) between slow oscillations in ABP and CBFV. BRS was calculated using the sequential cross-correlation method using the ABP signal.Results: A total of 73 patients with aSAH were included. The age [median (lower-upper quartile)] was 58 (50–67). WFNS scale was 2 (1–4) and the modified Fisher scale was 3 (1–3). In the total group, 31 patients (42%) had a CV and 42 (58%) had no CV. ABP and CBFV were higher in patients with CV during vasospasm compared to patients without CV (p = 0.001 and p < 0.001). There was no significant correlation between Mxa and BRS in patients with CV, neither during nor before vasospasm. In patients without CV, a significant, although moderate correlation was found between BRS and Mxa (rS = 0.31; p = 0.040), with higher BRS being associated with worse CA. Multiple linear regression analysis showed a significant worsening of BRS after aSAH in patients with CV (Rp = −0.42; p < 0.001).Conclusions: Inverse compensatory correlation between BRS and CA was lost in patients who developed CV after aSAH, both before and during vasospasm. The impact of these findings on the prognosis of aSAH should be investigated in larger studies.

Effects of LI11 Acupuncture on CO2 reactivity in the anterior and middle cerebral arteries during hyperventilation-induced hypocapnia in normal subjects: A before and after study

Objectives: The LI11 (Quchi) acupuncture point has always been included in the Seven acupoints for stroke; however, additional LI11 acupuncture research is needed. In this study, the effect of LI11 acupuncture on cerebral blood flow of the anterior cerebral arteries (ACA) and middle cerebral arteries (MCA) was investigated.Method: This study included 10 healthy young male subjects. Cerebral blood flow velocity and cerebrovascular reactivity were measured using transcranial Doppler sonography. Changes in hyperventilation-induced carbon dioxide (CO2) reactivity and modified ACA and MCA blood flow velocity at 40 mmHg (CV40), blood pressure, and heart rate were observed before and after LI11 acupuncture treatment.Results: A statistically significant increase in contralateral anterior cerebral artery CO2 reactivity (p=0.036) and decrease in contralateral middle cerebral artery CV40 (p=0.047) were observed. No significant difference in mean blood pressure was shown. A statistically significant increase in heart rate occurred after LI11 acupuncture; however, it was not clinically significant as there were negligible changes in the heart rhythm.Conclusions: LI11 acupuncture treatment could improve cerebral blood flow velocity. These results might be explained by regulating endothelium-dependent vessel dilation in the anterior cerebral artery region.Trial registration: This trial has been registered with Clinical Research Information Service, a service of the Korea Centers for Disease Control and Prevention: KCT0004494 (retrospectively registered). https://cris.nih.go.kr/cris/search/search_result_st01.jsp?seq=15359

Analysis of relative changes in pulse shapes of intracranial pressure and cerebral blood flow velocity during infusion test

Objective: Analysis of relative changes in the shapes of pulse waveform of intracranial pressure (ICP) and transcranial Doppler cerebral blood flow velocity (CBFV) may provide information on intracranial compliance. We tested this hypothesis, introducing an index named the Ratio of Pulse Slopes (RPS) that is based on inclinations of the ascending parts of ICP and CBFV pulse waveforms. It has hypothetically a simple interpretation: 1 – good compliance, the less than 1, reduced compliance. Here, we investigated the usefulness of RPS for intracranial compliance assessment. Approach: ICP and CBFV signals recorded simultaneously in 30 normal pressure hydrocephalus patients during infusion test were retrospectively analysed. CBFV was measured in the middle cerebral artery. Changes in RPS during the test were compared to changes in the height ratio of the first and second peak of ICP pulse (P1/P2) and the shape of ICP pulse classified from normal (1) to pathological (4). Values are medians (lower, upper quartiles). Main results: There was a significant correlation between baseline RPS and brain elasticity (R = -0.55, p=0.0018). During infusion test, both RPS and P1/P2 decreased with rising ICP (RPS: 0.80 (0.56, 0.92) vs. 0.63 (0.44, 0.80), p = 0.00015; P1/P2: 0.58 (0.50, 0.91) vs. 0.52 (0.36, 071), p=0.00009) while the ICP pulses became more pathological in shape (class: 3 (2, 3) vs. 3 (3, 4), p=0.04). The magnitude of decrease in RPS during infusion was inversely correlated with baseline P1/P2 (R= -0.40, p<0.03). Significance: During infusion, the slopes of ascending parts of ICP and CBFV pulses become increasingly divergent with a shift in opposite directions. RPS seems a promising methodological tool to monitor brain compliance with no additional volumetric manipulation required.

P.199 Variability descriptors of cerebral blood flow velocity as predictors of vasospasm in Subarachnoid Hemorrhage: A feasibility study

Background: Transcranial Doppler (TCD) measurements poorly predict vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH). Variability descriptors of mean cerebral blood flow velocity (mean-CBFV) may improve this prediction. We assessed the feasibility of generating reliable mean-CBFV variability metrics using extended TCD recordings in aSAH patients and healthy controls. We also explored whether these parameters are capable to discriminate aSAH patients from healthy controls, and between patients with and without vasospasm. Methods: Bilateral mean-CBFV, systemic blood pressure and heart rate were recorded for 40 minutes in 3 groups: aSAH patients (n=8) within the first 5 days post-ictus, age-matched healthy controls (n=8) and young healthy controls (n=8). We obtained linear [standard deviations, coefficient of variations, very-low, low and high-frequency power-spectra] and non-linear [Fractality, deterministic Chaos analyses] variability metrics. Results: All TCD recordings provided consistent variability metrics. aSAH patients showed higher correlation dimensions, increased high-frequency spectral power, and decreased very-low frequency power than healthy controls. aSAH patients who developed vasospasm (n=3) showed higher mean-CBFV and lower coefficient of variations than those without vasospasm (n=5). Conclusions: Descriptors of mean-CBFV variability may distinguish between aSAH patients with and without vasospasm. Future studies are required to evaluate the role of these variability parameters for risk stratification in aSAH.

Is Lumbar Puncture Needed? – Noninvasive Assessment of ICP Facilitates Decision Making in Patients with Suspected Idiopathic Intracranial Hypertension

Purpose Idiopathic intracranial hypertension (IIH) usually occurs in obese women of childbearing age. Typical symptoms are headache and sight impairment. Lumbar puncture (LP) is routinely used for both diagnosis and therapy (via cerebrospinal fluid drainage) of IIH. In this study, noninvasively assessed intracranial pressure (nICP) was compared to LP pressure (LPP) in order to clarify its feasibility for the diagnosis of IIH. Materials and Methods nICP was calculated using continuous signals of arterial blood pressure and cerebral blood flow velocity in the middle cerebral artery, a method which has been introduced recently. In 26 patients (f = 24, m = 2; age: 33 ± 11 years), nICP was assessed one hour prior to LPP. If LPP was > 20 cmH2O, lumbar drainage was performed, LPP was measured again, and also nICP was reassessed. Results In total, LPP and nICP correlated with R = 0.85 (p < 0.001; N = 38). The mean difference of nICP-LPP was 0.45 ± 4.93 cmH2O. The capability of nICP to diagnose increased LPP (LPP > 20 cmH2O) was assessed by ROC analysis. The optimal cutoff for nICP was close to 20 cmH2O with both a sensitivity and specificity of 0.92. Presuming 20 cmH2O as a critical threshold for the indication of lumbar drainage, the clinical implications would coincide in both methods in 35 of 38 cases. Conclusion The TCD-based nICP assessment seems to be suitable for a pre-diagnosis of increased LPP and might eliminated the need for painful lumbar puncture if low nICP is detected.

Transcranial Doppler ultrasonography (uses, limitations, and potentials): a review article

Background The additional information that transcranial Doppler can provide as part of a multimodal imaging protocol in many clinical settings has not been evaluated. Main body Transcranial Doppler is a bedside procedure used to assess cerebral blood flow velocity via cerebral circulation and pulsatility index (PI). Many diseases can lead to cerebral vessels vasospasm as in subarachnoid hemorrhage and trauma. Cerebral vessels vasospasm represented by abnormal elevation of cerebral blood flow velocity. Intracranial pressure can be monitored by pulsatility index which reflects blood flow resistance in cerebral vessels. Transcranial Doppler ultrasonography is also the unique modality for detection of micro emboli in high-risk patients. Also, it can be used for evaluation of circulatory arrest with subsequent confirmation of brain death Conclusion Transcranial Doppler ultrasonography is the only diagnostic modality that provides a reliable assessment of cerebral blood flow patterns in real time. The physiological information obtained from TCD is complementary to the anatomical details obtained from other neuroimaging modalities. TCD is relatively cheap, can be performed bedside, and allows monitoring in acute emergency settings.

Simulation study on the effects of cancellous bone structure in the skull on ultrasonic wave propagation

The transcranial Doppler method (TCD) enables the measurement of cerebral blood flow velocity and detection of emboli by applying an ultrasound probe to the temporal bone window, or the orbital or greater occipital foramina. TCD is widely used for evaluation of cerebral vasospasm after subarachnoid hemorrhage, early detection of patients with arterial stenosis, and the assessment of brain death. However, measurements often become difficult in older women. Among various factors contributing to this problem, we focused on the effect of the diploe in the skull bone on the penetration of ultrasound into the brain. In particular, the effect of the cancellous bone structure in the diploe was investigated. Using a 2D digital bone model, wave propagation through the skull bone was investigated using the finite-difference time-domain (FDTD) method. We fabricated digital bone models with similar structure but different BV/TV (bone volume/total volume) values in the diploe. At a BV/TV of approximately 50–60% (similar to that of older women), the minimum ultrasound amplitude was observed as a result of scattering and multiple reflections in the cancellous diploe. These results suggest that structural changes such as osteoporosis may be one factor hampering TCD measurements.

Cuff-Method Thigh Arterial Occlusion Counteracts Cerebral Hypoperfusion Against the Push–Pull Effect in Humans

Exposure to acute transition from negative (−Gz) to positive (+ Gz) gravity significantly impairs cerebral perfusion in pilots of high-performance aircraft during push—pull maneuver. This push—pull effect may raise the risk for loss of vision or consciousness. The aim of the present study was to explore effective countermeasures against cerebral hypoperfusion induced by the push—pull effect. Twenty healthy young volunteers (male, 21 ± 1 year old) were tested during the simulated push–pull maneuver by tilting. A thigh cuff (TC) pressure of 200 mmHg was applied before and during simulated push—pull maneuver (−0.87 to + 1.00 Gz). Beat-to-beat cerebral and systemic hemodynamics were measured continuously. During rapid −Gz to + Gz transition, mean cerebral blood flow velocity (CBFV) was decreased, but to a lesser extent, in the TC bout compared with the control bout (−3.1 ± 4.9 vs. −7.8 ± 4.4 cm/s, P &lt; 0.001). Similarly, brain-level mean blood pressure showed smaller reduction in the TC bout than in the control bout (−46 ± 12 vs. −61 ± 13 mmHg, P &lt; 0.001). The systolic CBFV was lower but diastolic CBFV was higher in the TC bout. The systemic blood pressure response was blunted in the TC bout, along with similar heart rate increase, smaller decrease, and earlier recovery of total peripheral resistance index than control during the gravitational transition. These data demonstrated that restricting thigh blood flow can effectively mitigate the transient cerebral hypoperfusion induced by rapid shift from −Gz to + Gz, characterized by remarkable improvement of cerebral diastolic flow.

Investigating the association between depressive disorders and cerebral haemodynamics

AimsAlterations in cerebral blood flow (CBF) may contribute to the development of depression, and serve as a novel biomarker. The aim of this review is to summarise and synthesise the available evidence on alterations in cerebral haemodynamics in depressive disorders relative to healthy control populations.MethodMEDLINE (1946- present), EMBASE (1947– present), Web of Science (1970–present), PsycINFO (1984–present), CINAHL (1976–present) and CENTRAL were searched using a predefined search strategy. Studies which compared the cerebral haemodynamics of adult patients (>18 years old) with depressive disorders against healthy controls (HC), by any imagining modality, were included. Studies with varying severity and chronicity of depressive disorder were included. A meta-analysis was conducted in four groups: 1) CBF (ml/min/100g) 2) Cerebral blood flow velocity (CBFv) (cm/s) 3) Combined CBF and CBFv 4) Ratio of uptake of radiotracer. A random effects model was used and heterogeneity and publication bias were assessed. Data are presented as mean difference (MD) or standardised mean difference (SMD) and 95% confidence interval (95% CI). A narrative synthesis of the remaining studies was performed.Result87 studies met the inclusion criteria. CBF (ml/min/100g) was significantly reduced in patients with depression compared to HC (15 studies, 538 patients, 416 HC, MD: −2.24 (95% CI −4.12, −0.36), p = 0.02, I2 = 64%). There were no statistically significant differences between patients and controls in the other three outcomes. CBFv (cm/s): 6 studies, 305 patients, 198 HC, MD: −1.23 (95% CI −6.10, 3.64, p = 0.62, I2 = 65%. Combined CBF and CBFv: 20 studies, 804 patients, 573 HC, SMD: −0.16 (95% CI −0.32, 0.01), p = 0.06 I2 = 51%. Ratio of uptake of radiotracer: 3 studies, 60 patients, 53 HC, MD: −0.11 (95% CI −0.11, 0.11), p = 1.00, I2 = 0%). The narrative synthesis revealed varying results, with many studies identifying a decrease in CBF in depressed patients compared to controls, but other studies identifying an increase, or mixed results. Multiple regions of impairment were identified, including the anterior cingulate cortex and prefrontal cortex.ConclusionThere was a statistically significant reduction in CBF in depressed patients compared to controls. The narrative synthesis revealed varying results, however specific regions of interest have been identified. Further research is needed to explore the effect of antidepressant medication, utilising different imaging modalities, and at different levels of disease severity.

Neutrophil-to-lymphocyte ratio is associated with increased cerebral blood flow velocity in acute bacterial meningitis

In community-acquired bacterial meningitis (CABM) intracranial vascular alterations are devastating complications which are triggered by neuroinflammation and result in worse clinical outcome. The Neutrophil-to-Lymphocyte ratio (NLR) represents a reliable parameter of the inflammatory response. In this study we analyzed the association between NLR and elevated cerebral blood flow velocity (CBFv) in CABM-patients. This study included all (CABM)-patients admitted to a German tertiary center between 2006 and 2016. Patients’ demographics, in-hospital measures, neuroradiological data and clinical outcome were retrieved from institutional databases. CBFv was assessed by transcranial doppler (TCD). Patients’, radiological and laboratory characteristics were compared between patients with/without elevated CBFv. Multivariate-analysis investigated parameters independently associated with elevated CBFv. Receiver operating characteristic(ROC-)curve analysis was undertaken to identify the best cut-off for NLR to discriminate between increased CBFv. 108 patients with CABM were identified. 27.8% (30/108) showed elevated CBFv. Patients with elevated CBFv and normal CBFv, respectively had a worse clinical status on admission (Glasgow Coma Scale: 12 [9–14] vs. 14 [11–15]; p = 0.005) and required more often intensive care (30/30 [100.0%] vs. 63/78 [80.8%]; p = 0.01).The causative pathogen was S. pneumoniae in 70%. Patients with elevated CBFv developed more often cerebrovascular complications with delayed cerebral ischemia (DCI) within hospital stay (p = 0.031). A significantly higher admission-NLR was observed in patients with elevated CBFv (median [IQR]: elevated CBFv:24.0 [20.4–30.2] vs. normal CBFv:13.5 [8.4–19.5]; p < 0.001). Multivariate analysis, revealed NLR to be significantly associated with increased CBFv (Odds ratio [95%CI] 1.042 [1.003–1.084]; p = 0.036). ROC-analysis identified a NLR of 20.9 as best cut-off value to discriminate between elevated CBFv (AUC = 0.713, p < 0.0001, Youden's Index = 0.441;elevated CBFv: NLR ≥ 20.9 19/30[63.5%] vs. normal CBFv: NLR > 20.9 15/78[19.2%]; p < 0.001). Intracranial vascular complications are common among CABM-patients and are a risk factor for unfavorable outcome at discharge. Elevated NLR is independently associated with high CBFv and may be useful in predicting patients’ prognosis.