Efficacy of Cerebral Autoregulation in Early Ischemic Stroke Predicts Smaller Infarcts and Better Outcome

© 2017 Castro, Serrador, Rocha, Sorond and Azevedo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Background and purpose: Effective cerebral autoregulation (CA) may protect the vulnerable ischemic penumbra from blood pressure fluctuations and minimize neurological injury. We aimed to measure dynamic CA within 6 h of ischemic stroke (IS) symptoms onset and to evaluate the relationship between CA, stroke volume, and neurological outcome. Methods: We enrolled 30 patients with acute middle cerebral artery IS. Within 6 h of IS, we measured for 10 min arterial blood pressure (Finometer), cerebral blood flow velocity (transcranial Doppler), and end-tidal-CO2. Transfer function analysis (coherence, phase, and gain) assessed dynamic CA, and receiver-operating curves calculated relevant cut-off values. National Institute of Health Stroke Scale was measured at baseline. Computed tomography at 24 h evaluated infarct volume. Modified Rankin Scale (MRS) at 3 months evaluated the outcome. Results: The odds of being independent at 3 months (MRS 0–2) was 14-fold higher when 6 h CA was intact (Phase > 37°) (adjusted OR = 14.0 (IC 95% 1.7–74.0), p = 0.013). Similarly, infarct volume was significantly smaller with intact CA [median (range) 1.1 (0.2–7.0) vs 13.1 (1.3–110.5) ml, p = 0.002]. Conclusion: In this pilot study, early effective CA was associated with better neurological outcome in patients with IS. Dynamic CA may carry significant prognostic implications.This study was part of Ph.D. thesis of PC and received publiC national grant from Fundação para a Ciência e a Tecnologia (FCT), Portugal, PTDC/SAU-ORG/113329/2009. FS is supported by R01 NS085002 (NINDS).info:eu-repo/semantics/publishedVersio

Vestibular Effects on Cerebral Blood Flow

Background: Humans demonstrate a number of unique adaptations that allow for the maintenance of blood pressure and brain blood flow when upright. While several physiological systems, including cerebral autoregulation, are involved in this adaptation the unique role the vestibular system plays in helping to maintain brain blood flow is just beginning to be elucidated. In this study, we tested the hypothesis that stimulation of the vestibular system, specifically the otoliths organs, would result in changes in cerebral blood flow. Results: To test our hypothesis, we stimulated the vestibular organs of 25 healthy subjects by pitch tilt (stimulates both canals and otoliths) and by translation on a centrifuge (stimulates otoliths and not the canals) at five frequencies: 0.5, 0.25, 0.125 and 0.0625 Hz for 80 sec and 0.03125 Hz for 160 sec. Changes in cerebral flow velocity (by transcranial Doppler) and blood pressure (by Finapres) were similar during both stimuli and dependent on frequency of stimulation (P < 0.01). However, changes in cerebral blood flow were in opposition to changes in blood pressure and not fully dependent on changes in end tidal CO2. Conclusion: The experimental results support our hypothesis and provide evidence that activation of the vestibular apparatus, specifically the otolith organs, directly affects cerebral blood flow regulation, independent of blood pressure and end tidal CO2 changes

Impact of galvanic vestibular stimulation-induced stochastic resonance on the output of the vestibular system : a systematic review

With an ageing population, techniques to improve balance function are necessary and likely to reduce the risk of falling due to age-related vestibular dysfunction. Previous work has shown that Galvanic Vestibular Stimulation (GVS) improves balance function in regards to vestibular output measures including Centre of Pressure (CoP) sway and Ocular Vestibular Evoked Myogenic Potentials (oVEMPs). Presumably these improvements are due to the modulation of primary vestibular afferents and vestibular hair cells, possibly via the phenomenon of Stochastic Resonance (SR). Specifically, SR is defined by the application of low-level noise which increases the detectability of subthreshold signals in non-linear systems, including the vestibular system. Major limitations to determining the most effective therapeutic approach to improve balance function using GVS-induced SR are the limited number of studies assessing the direct impact of GVS on vestibular function, and the heterogeneity of reported GVS stimulus parameters used. Indeed, there is a near complete paucity of comparative investigations between the major types of GVS including stochastic and white noise stimuli. Thus, the question arises - whether an optimal set of stimulus parameters to improve vestibular output can be ascertained from the currently available data? We conducted a systematic appraisal of the literature regarding the impact of GVS on vestibular function in healthy individuals as a means for answering this question

Cerebral Hypoperfusion Precedes Nausea During Centrifugation

Nausea and motion sickness are important operational concerns for aviators and astronauts. Understanding underlying mechanisms associated with motion sickness may lead to new treatments. The goal of this work was to determine if cerebral blood flow changes precede the development of nausea in motion sick susceptible subjects. Cerebral flow velocity in the middle cerebral artery (transcranial Doppler), blood pressure (Finapres) and end-tidal CO2 were measured while subjects were rotated on a centrifuge (250 degrees/sec). Following 5 min of rotation, subjects were translated 0.504 m off-center, creating a +lGx centripetal acceleration in the nasal-occipital plane. Ten subjects completed the protocol without symptoms while 5 developed nausea (4 while 6ff-center and 1 while rotating on-center). Prior to nausea, subjects had significant increases in blood pressure (+13plus or minus 3 mmHg, P less than 0.05) and cerebrovascular resistance (+46 plus or minus 17%, P less than 0.05) and decreases in cerebral flow velocity both in the second (-13 plus or minus 4%) and last minute (-22 plus or minus 5%) before symptoms (P less than 0.05). In comparison, controls demonstrated no change in blood pressure or cerebrovascular resistance in the last minute of off-center rotation and only a 7 plus or minus 2% decrease in cerebral flow velocity. All subjects had significant hypocapnia (-3.8 plus or minus 0.4 mmHg, P less than 0.05), however this hypocapnia could not fully explain the cerebral hypoperfusion associated with the development of nausea. These data indicate that reductions in cerebral blood flow precede the development of nausea. Further work is necessary to determine what role cerebral hypoperfusion plays in motion sickness and whether cerebral hypoperfusion can be used to predict the development of nausea in susceptible individuals

Blood pressure wave propagation : a multisensor setup for cerebral autoregulation studies

Objective. Cerebral autoregulation is critically important to maintain proper brain perfusion and supply the brain with oxygenated blood. Non-invasive measures of blood pressure (BP) are critical in assessing cerebral autoregulation. Wave propagation velocity may be a useful technique to estimate BP but the effect of the location of the sensors on the readings has not been thoroughly examined. In this paper, we were interested in studying whether the propagation velocity of a pressure wave in the direction from the heart to the brain may differ compared with propagation from the heart to the periphery, as well as across different physiological tasks and/or health conditions. Using non-invasive sensors simultaneously placed at different locations of the human body allows for the study of how the propagation velocity of the pressure wave, based on pulse transit time (PTT), varies across different directions. Approach. We present a multi-sensor BP wave propagation measurement setup intended for cerebral autoregulation studies. The presented sensor setup consists of three sensors, one placed on each of the neck, chest and finger, allowing simultaneous measurement of changes in BP propagation velocity towards the brain and to the periphery. We show how commonly tested physiological tasks affect the relative changes of PTT and correlations with BP. Main results. We observed that during maximal blow, valsalva and breath hold breathing tasks, the relative changes of PTT were higher when PTT was measured in the direction from the heart to the brain than from the heart to the peripherals. In contrast, during a deep breathing task, the relative change in PTT from the heart to the brain was lower. In addition, we present a short literature review of the PTT methods used in brain research. Significance. These preliminary data suggest that the physiological task and direction of PTT measurement may affect relative PTT changes. The presented three-sensor setup provides an easy and neuroimaging compatible method for cerebral autoregulation studies by allowing measurement of BP wave propagation velocity towards the brain versus towards the periphery

Effects of Vestibular Loss on Orthostatic Responses to Tilts in the Pitch Plane

The purpose of this study was to determine the extent to which vestibular loss might impair orthostatic responses to passive tilts in the pitch plane in human subjects. Data were obtained from six subjects having chronic bilateral vestibular loss and six healthy individuals matched for age, gender, and body mass index. Vestibular loss was assessed with a comprehensive battery including dynamic posturography, vestibulo-ocular and optokinetic reflexes, vestibular evoked myogenic potentials, and ocular counterrolling. Head up tilt tests were conducted using a motorized two-axis table that allowed subjects to be tilted in the pitch plane from either a supine or prone body orientation at a slow rate (8 deg/s). The sessions consisted of three tilts, each consisting of20 min rest in a horizontal position, tilt to 80 deg upright for 10 min, and then return to the horizontal position for 5 min. The tilts were performed in darkness (supine and prone) or in light (supine only). Background music was used to mask auditory orientation cues. Autonomic measurements included beat-to-beat recordings of blood pressure (Finapres), heart rate (ECG), cerebral blood flow velocity in the middle cerebral artery (transcranial Doppler), end tidal CO2, respiratory rate and volume (Respritrace), and stroke volume (impedance cardiography). For both patients and control subjects, cerebral blood flow appeared to exhibit the most rapid adjustment following transient changes in posture. Outside of a greater cerebral hypoperfusion in patients during the later stages of tilt, responses did not differ dramatically between the vestibular loss and control subjects, or between tilts performed in light and dark room conditions. Thus, with the 'exception of cerebrovascular regulation, we conclude that orthostatic responses during slow postural tilts are not substantially impaired in humans following chronic loss of vestibular function, a result that might reflect compensation by nonvisual graviceptor inputs (e.g., somatosensory) or other circulatory reflex mechanisms

Vestibular effects on cerebral blood flow

Humans demonstrate a number of unique adaptations that allow the maintenance of blood pressure and brain blood flow after transition to the upright position. While these adaptations maintain heart-level mean arterial pressure similar to supine values, the brain remains ~30 cm above the heart, resulting in a ~25% decrease in perfusion pressure. To maintain brain blood flow, the cerebral vessels must dilate in response to this change in position. While several physiological systems are involved in adaptation to the upright posture, including cerebral autoregulation, the unique role that the vestibular system plays in helping to maintain brain blood flow is just beginning to be elucidated. Since the vestibular system not only assists in balance control and locomotion but provides direct information about the body&#x27;s position relative to gravity, it can, within milliseconds, detect a change in posture. Thus it is possible that a vestibular signal indicating upright could assist in this necessary cerebral vasodilation. In this work we demonstrate a direct effect of vestibular activation on cerebral blood flow regulation. By stimulating the otoliths, the organs that sense gravity, using sinusoidal translation or tilt in the dark at five frequencies, we found that cerebral blood flow was modulated according to the frequency of stimulation. In addition, changes in cerebral blood flow were in opposition to blood pressure changes, likely indicating a direct effect of otolith activation on cerebral blood flow regulation. We anticipate these findings may lead to new treatment modalities for cerebral hypoperfusion under a variety of circumstances. For example, with aging there is well documented vestibular loss that might contribute to a general age-associated reduction in global cerebral blood flow. Similarly, patients with orthostatic intolerance could have vestibular impairment that exacerbates cerebral hypoperfusion when upright

The consideration of post-exercise impact on SCAT3 scores in athletes immediately following a head injury

Examine effects of high-intensity exercise and physical impacts during rugby match on self-report symptoms in The Sport Concussion Assessment Tool (SCAT3), and its ability to differentiate head-injured players from controls. Methods: Symptoms were assessed immediately following completion of a rugby match (median 60 minutes). Players removed from the match for assessment due to a head hit were classified as head injured. Controls completed match without head hit. Results: 209 players (67 female; 33 ± 13 years) participated with 80 experiencing a head injury. Symptom severity was significantly greater in head injured (26.2 ± 17.6) compared with controls (8.9 ± 11.5, P 16 symptom severity, misclassifying them as suspected concussion. There were no significant sex differences. Factor analysis produced four symptom clusters of which Headache was most discriminatory between the head injured (median = 1.7) and controls (median = 0.0). Conclusion: These findings demonstrate that exercise and contact during a game affect symptom assessment, increasing the likelihood of misclassifying players with suspected concussion. Factor characterization of symptoms associated with head injury using an exercised comparison group provides more useful discrimination. These results highlight the necessity for objective measures to diagnose concussions outside of symptom self-report

A Retrospective Cohort Study of U.S. Service Members Returning from Afghanistan and Iraq: Is Physical Health Worsening Over time?

Background: High rates of mental health disorders have been reported in veterans returning from deployment to Afghanistan (Operation Enduring Freedom: OEF) and Iraq (Operation Iraqi Freedom: OIF); however, less is known about physical health functioning and its temporal course post-deployment. Therefore, our goal is to study physical health functioning in OEF/OIF veterans after deployment. Methods: We analyzed self-reported physical health functioning as physical component summary (PCS) scores on the Veterans version of the Short Form 36 health survey in 679 OEF/OIF veterans clinically evaluated at a post-deployment health clinic. Veterans were stratified into four groups based on time post-deployment: (1Yr) 0 – 365 days; (2Yr) 366 – 730 days; (3Yr) 731 – 1095 days; and (4Yr+) > 1095 days. To assess the possibility that our effect was specific to a treatment-seeking sample, we also analyzed PCS scores from a separate military community sample of 768 OEF/OIF veterans evaluated pre-deployment and up to one-year post-deployment. Results: In veterans evaluated at our clinic, we observed significantly lower PCS scores as time post-deployment increased (p = 0.018) after adjusting for probable post-traumatic stress disorder (PTSD). We similarly observed in our community sample that PCS scores were lower both immediately after and one year after return from deployment (p < 0.001) relative to pre-deployment PCS. Further, PCS scores obtained 1-year post-deployment were significantly lower than scores obtained immediately post-deployment (p = 0.02). Conclusion: In our clinical sample, the longer the duration between return from deployment and their visit to our clinic, the worse the Veteran’s physical health even after adjusting for PTSD. Additionally, a decline is also present in a military community sample of OEF/OIF veterans. These data suggest that, as time since deployment length increases, physical health may deteriorate for some veterans

Improving Balance Function Using Low Levels of Electrical Stimulation of the Balance Organs

Crewmembers returning from long-duration space flight face significant challenges due to the microgravity-induced inappropriate adaptations in balance/sensorimotor function. The Neuroscience Laboratory at JSC is developing a method based on stochastic resonance to enhance the brain's ability to detect signals from the balance organs of the inner ear and use them for rapid improvement in balance skill, especially when combined with balance training exercises. This method involves a stimulus delivery system that is wearable/portable and provides imperceptible electrical stimulation to the balance organs of the human body. Stochastic resonance (SR) is a phenomenon whereby the response of a nonlinear system to a weak periodic input signal is optimized by the presence of a particular non-zero level of noise. This phenomenon of SR is based on the concept of maximizing the flow of information through a system by a non-zero level of noise. Application of imperceptible SR noise coupled with sensory input in humans has been shown to improve motor, cardiovascular, visual, hearing, and balance functions. SR increases contrast sensitivity and luminance detection; lowers the absolute threshold for tone detection in normal hearing individuals; improves homeostatic function in the human blood pressure regulatory system; improves noise-enhanced muscle spindle function; and improves detection of weak tactile stimuli using mechanical or electrical stimulation. SR noise has been shown to improve postural control when applied as mechanical noise to the soles of the feet, or when applied as electrical noise at the knee and to the back muscles. SR using imperceptible stochastic electrical stimulation of the vestibular system (stochastic vestibular stimulation, SVS) applied to normal subjects has shown to improve the degree of association between the weak input periodic signals introduced via venous blood pressure receptors and the heart-rate responses. Also, application of SVS over 24 hours improves the long-term heart-rate dynamics and motor responsiveness as indicated by daytime trunk activity measurements in patients with multi-system atrophy, Parkinson s disease, or both, including patients who were unresponsive to standard therapy for Parkinson s disease. Recent studies conducted at the NASA JSC Neurosciences Laboratories showed that imperceptible SVS, when applied to normal young healthy subjects, leads to significantly improved balance performance during postural disturbances on unstable compliant surfaces. These studies have shown the benefit of SR noise characteristic optimization with imperceptible SVS in the frequency range of 0-30 Hz, and amplitudes of stimulation have ranged from 100 to 400 microamperes