Assessment of dynamic cerebral autoregulation in near-infrared spectroscopy using short channels: A feasibility study in acute ischemic stroke patients

So you assessed that there is a problem, offered NO solution. What the hell are you doing in stroke anyway? Isn't it to solve stroke problems?

Assessment of dynamic cerebral autoregulation in near-infrared spectroscopy using short channels: A feasibility study in acute ischemic stroke patients

Sabeth Becker^1*, Franziska Klein², Katja König^1,3, Christian Mathys^4,5, Thomas Liman^1,3 and Karsten Witt^1,3,4

• ¹Department of Neurology, School of Medicine and Health Sciences, Carl von Ossietzky University of Oldenburg, Oldenburg, Germany
• ²Neurocognition and Functional Neurorehabilitation Group, Neuropsychology Lab, Department of Psychology, Faculty of Medicine and Health Sciences, University of Oldenburg, Oldenburg, Germany
• ³University Clinic for Neurology, Evangelical Hospital, Oldenburg, Germany
• ⁴Institute of Radiology and Neuroradiology, Evangelical Hospital, Oldenburg, Germany
• ⁵Research Centre Neurosensory Science, Department of Human Medicine, Faculty of Medicine and Health Sciences, University of Oldenburg, Oldenburg, Germany

Introduction: In acute ischemic stroke, progressive impairment of cerebral autoregulation (CA) is frequent and associated with unfavorable outcomes. Easy assessment of cerebral blood flow and CA in stroke units bedside tools like near-infrared spectroscopy (NIRS) might improve early detection of CA deterioration. This study aimed to assess dynamic CA with multichannel CW-NIRS in acute ischemic stroke (AIS) patients compared to agematched healthy controls.

Methods: CA reaction was amplified by changes in head of bed position. Long- and short channels were used to monitor systemic artery pressure- and intracranial oscillations simultaneously. Gain and phase shift in spontaneous low- and very low-frequency oscillations (LFO, VLFO) of blood pressure were assessed.

Results: A total of 54 participants, 27 with AIS and 27 age-matched controls were included. Gain was significantly lower in the AIS group in the LFO range (i) when the upper body was steadily elevated to 30. and (ii) after its abrupt elevation to 30°. No other differences were found between groups.

Discussion: This study demonstrates the feasibility of NIRS short channels to measure CA in AIS patients in one single instrument. A lower gain in AIS might indicate decreased CA activity in this pilot study, but further studies investigating the role of NIRS short channels in AIS are needed.

Introduction

Cerebral blood flow is substantially regulated by the mechanism of cerebral autoregulation (CA). CA continuously adjusts vascular resistance and diameter to intercept systemic blood pressure (BP) changes. For that, it uses myogenic mechanisms (1–4), the autonomic nervous system (2–7), and CO2 partial pressure changes (8). CA protects brain tissue from reduced perfusion and hence brain ischemia and remains unaltered with aging and hypertension (9, 10). However, major impairment of CA is frequent in AIS (11–13). The effect of postural changes on cerebral blood flow (14–16), e.g., seen in controlled changes in an orthostatic maneuver [changes in upper body position, head of bed (HOB)] serves as an indicator for severity of CA impairment. This orthostatic maneuver could be analyzed with spontaneous blood pressure oscillations that provide comprehensive information on CA (17).

Near-infrared spectroscopy (NIRS) measures hemodynamic changes. By using optodes (i.e., light sources and light detectors) near-infrared light is transmitted through the head surface into the tissue. Hence, hemoglobin absorption can be quantified as concentration changes in oxygenated and deoxygenated hemoglobin in vivo (18). NIRS provides information on both scalp perfusion, which represents regulation of the extracerebral vessels, and cerebral perfusion, which is constantly modified by CA. Hence, NIRS is an excellent tool to assess the differences between extra- and intracerebral vascular autoregulation. It is a useful, non-invasive and investigator-independent bedside measurement for CA (19). Global blood flow regulation processes are the main source of physiological signals measured superficially by NIRS in the scalp (20, 21), and is often considered as disturbing factor. In the past years, extracerebral NIRS signals have been eliminated using short distance correction as a filter to obtain only the adjusted intracerebral signals (22–24).

NIRS records cerebral changes in the local oxygenated and deoxygenated hemoglobin concentrations on the cerebral cortex. In this signal, systemic arterial BP oscillations can indirectly be displayed (25–27), and subdivided into frequency ranges. Each range provides information about different aspects of CA: Low-frequency oscillations (LFO or Mayer waves, ~0.1 Hz) reflect the local myogenic activity in the terminal arterioles and are further influenced by sympathetic tone and control mechanisms (28, 29). Very low-frequency oscillations (VLFO or B-Waves) range in the minute range (30). Upper VLFO (~0.05 Hz) stem from large arterioles under neurogenic innervation (31–33) and are modulated by arterial CO2 partial pressure (34, 35). Lower VLFO (~0.01 Hz) are endothelial dependent and thus connected to metabolic changes in the microvessels (36). Intact CA constantly modifies spontaneous dynamic oscillations resulting in higher desynchronization of intra- and extracranial BP oscillations. However, an impaired CA (as in AIS) is unable to modulate BP, and therefore intracranial oscillations passively and synchronously follow those of systemic BP (37).

So far, in NIRS studies on (dynamic) CA, the use of an external tool that measures systematic blood pressure variations were necessary: While intracranial BP changes have been assessed by NIRS or transcranial doppler, systemic BP changes were recorded using a finger plethysmograph (26, 38–41) or an arterial or aortic catheter (32, 42, 43). Afterwards, these independent datasets needed to be synchronized to detect modulation by CA. However, this synchronization, accurate to milliseconds, is complex and error-prone. Therefore, one main aim of the present study was to address this using the short channel signal instead.

To assess the synchronicity of extra- and intracerebral oscillations and, therefore, the extent of modification by CA, fourier analyses such as discrete fourier transform (DFT) are commonly used (17). By DFT, measuring points are periodically continued into sinus curves. Input-sinusoids (=systemic BP-signal) are transformed into sinusoids of the same frequency at the output (=intracranial BP-signal) but with a different amplitude (gain) and shifted in time (the phase shift of the response). In this study, the synchronicity of two signals will be assessed: The oscillation in the short channels (input signal), which detect the systemic oscillations of the ABP via the scalp, and the oscillation modified by CA, which is measured via long channels (output signal).

The feasibility of NIRS has rarely been tested in AIS patients. The aims of this study are (i) to detect CA changes in AIS patients in comparison to matched-healthy controls and (ii) to test if these changes can be assessed using a single NIRS system, including short- and long channels, in an acute stroke unit setting.

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Cerebral Augmentation Effect Induced by External Counterpulsation Is Not Related to Impaired Dynamic Cerebral Autoregulation in Ischemic Stroke

 Someone with medical training needs to put this together with leg compressions and leg wraps and create a protocol.  Has your hospital implemented remote ischemic conditioning yet? I think that is another name for external counterpulsation. WHAT THE FUCK ARE THEY WAITING FOR?

• leg compressions (16 posts to September 2015)

• leg wraps (7 posts to May 2013) 

 

Cerebral Augmentation Effect Induced by External Counterpulsation Is Not Related to Impaired Dynamic Cerebral Autoregulation in Ischemic Stroke

Li Xiong^1,2*, Xiangyan Chen^3*, Jia Liu⁴, Lawrence Ka Sing Wong² and Thomas W. Leung²

• ¹Clinical Trials Centre, The Eighth Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
• ²Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
• ³Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Shatin, Hong Kong SAR, China
• ⁴Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

Background and Purpose: Dynamic cerebral autoregulation is impaired after ischemic stroke. External counterpulsation (ECP) augments the cerebral blood flow of patients with ischemic stroke by elevation of blood pressure (BP). We aimed to investigate if cerebral augmentation effects during ECP were associated with impaired dynamic cerebral autoregulation in patients after acute ischemic stroke.

Methods: Forty patients with unilateral ischemic stroke and large artery atherosclerosis in the anterior circulation territory within 7 days from symptom onset and eighteen healthy controls were recruited. We monitored changes in mean flow velocity over both middle cerebral arteries (MCA) by transcranial Doppler (TCD) before, during, and immediately after ECP. Cerebral augmentation index was MCA mean flow velocity increase in percentage during ECP compared with baseline to evaluate the augmentation effects of ECP. Spontaneous arterial BP and cerebral blood flow velocity in both bilateral MCAs were recorded using a servo-controlled plethysmograph and TCD, respectively. Transfer function analysis was used to derive the autoregulatory parameters, including phase difference (PD), and gain.

Results: The cerebral augmentation index in patients with stroke was significantly higher on both the ipsilateral and contralateral sides than that in controls, while the PD in patients with stroke was significantly lower on both sides than those in controls (all P < 0.05). The cerebral augmentation index did not correlate with PD and gain on either the ipsilateral or contralateral side of patients with stroke or in controls (all P > 0.05). The cerebral augmentation index of patients with stroke was significantly related to mean BP change on the ipsilateral side (R² = 0.108, P = 0.038).

Conclusion: The degree of ECP-induced cerebral augmentation effects as measured by the cerebral augmentation index did not correlate with the magnitude of impaired dynamic cerebral autoregulation.

Introduction

In the traditional view, cerebral autoregulation ensures the constancy of cerebral blood flow to the brain as the systemic blood pressure (BP), and hence, cerebral perfusion pressure changes over a wide range. However, considering the compelling evidence currently available, cerebral blood flow regulation is far more pressure-passive in nature than traditionally believed. Indeed, cerebral blood flow will not necessarily remain stable in some physiological/clinical conditions (1). Cerebral autoregulation is impaired after ischemic stroke (2, 3). The brain becomes more vulnerable to ischemic damage caused by changes in systemic BP or intracranial pressure. Although the management of BP following acute ischemic stroke remains controversial, the available clinical data suggest that the use of BP augmentation may improve perfusion to ischemic tissue, which can result in at least short-term neurological improvement (4, 5).

External counterpulsation (ECP) is a noninvasive and well-established method for ischemic heart disease (6–8). ECP operates by applying electrocardiography-triggered diastolic pressure to the lower extremities through air-filled cuffs. The diastolic augmentation of the blood flow and the simultaneously decreasing systolic afterload increases the blood flow of vital organs such as the heart, brain, and kidneys (9, 10). Our pilot study showed that ECP is feasible for patients with ischemic stroke with large artery disease by improving neurological deficits (11). ECP may improve cerebral perfusion and collateral blood supply in ischemic stroke by augmenting BP and cerebral blood flow velocity (CBFV) (12). Without cerebral autoregulation, CBFV would passively follow BP. The cerebral augmentation effects induced by ECP possibly worked via impaired cerebral autoregulation. Furthermore, we first proposed the cerebral augmentation index to evaluate the degree of cerebral augmentation effects induced by ECP. Recently, we found that the higher cerebral augmentation index on the side ipsilateral to the infarct was independently correlated with an unfavorable functional outcome after acute ischemic stroke (13).

Without too much cooperation from patients, transfer function analysis (TFA) is a frequently used method to assess dynamic cerebral autoregulation using spontaneous oscillations in BP and CBFV despite the controversies and variations in its interpretation from different research groups (14, 15). TFA quantifies cerebral autoregulation in the parameters phase difference (PD), gain, and coherence with the assumption that cerebral autoregulation is a linear control system. It is based on the concept that cerebral autoregulation minimizes the effect of dynamic BP fluctuations on CBFV, which is reflected by reduced low-frequency gain and phase-lead of CBFV over BP (16, 17). Without cerebral autoregulation, CBFV would passively follow BP, and TFA would show constant gain and zero phases across the low-frequency band. In acute ischemic stroke, recent meta-analyses of TFA parameters, obtained from spontaneous fluctuations of BP at rest, have demonstrated that PD and the autoregulation index can show highly significant differences in comparison with healthy controls, while less clear-cut results were obtained for gain (18).

Therefore, in this study, we aimed to investigate whether the degree of cerebral blood flow augmentation effects induced by ECP was related to the magnitude of impaired dynamic cerebral autoregulation in patients with ischemic stroke, assessed by cerebral augmentation index and PD and gain, respectively.

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Cerebral Autoregulation and Neurovascular Coupling in Acute and Chronic Stroke

So we still have no protocols for blood pressure management. You'd better hope your doctor guesses right about what to do. A wrong guess can be disastrous for you but won't affect your doctor at all. There are no consequences for your doctor not getting you 100% recovered.

 

,Cerebral Autoregulation and Neurovascular Coupling in Acute and Chronic Stroke

Lucy C. Beishon^1* and Jatinder S. Minhas^1,2

• ¹Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom
• ²National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, British Heart Foundation Cardiovascular Research Centre, Glenfield Hospital, Leicester, United Kingdom

Introduction

Stroke is currently the second leading cause of death worldwide, and results in significant morbidity, and poorer quality of life for those affected (1). Stroke can be classified under two major sub-types: ischaemic and haemorrhagic. Ischaemic stroke accounts for ~70% of all stroke, and results from arterial occlusion, usually through embolism or small vessel thrombosis (2). Haemorrhagic stroke is a result of arterial rupture in the brain (2). However, the two sub-types frequently co-exist, with similar risk factors (e.g., hypertension), and overlap in pathological mechanisms (3).

Although stroke incidence has declined in high-income countries, it remains a prevalent issue amongst low and middle-income countries, disproportionately affecting a younger, working age population in these areas (1). The treatment of acute ischaemic stroke (AIS) has advanced over recent decades. Notably, the advent of both thrombolysis and mechanical thrombectomy has revolutionised the management of AIS, associated with reduced mortality, and improved functional outcome (2, 4, 5). Despite these advances, the management of haemorrhagic stroke has lagged behind, and treatment options are largely confined to reversal of anticoagulants and intensive blood pressure (BP) lowering (2). Conversely, in AIS, the target for BP management remains uncertain, and trials have largely shown equivalence (6, 7), or harm (8), associated with aggressive BP management strategies. To understand the mechanistic implications of BP lowering in AIS, studies have investigated the temporal changes in cerebral autoregulation (CA) following stroke (9). In healthy states, CA maintains a constant cerebral perfusion, despite fluctuations in systemic BP (10). However, the ability of the brain maintain CA may be compromised in the acute phase of stroke, increasing the vulnerability of the brain to hypoperfusion with intensive BP management strategies (11, 12). Conversely, surges in BP during this vulnerable phase may risk haemorrhagic transformation of the infarct, resulting in poorer outcomes (11, 12). Thus, understanding the temporal nature of CA in the acute phase of stroke could provide important mechanistic insights to guide BP management strategies in the clinical setting.

A related concept to CA is the physiological mechanism of neurovascular coupling (NVC). Under healthy conditions, neuronal activity is tightly coupled to cerebral blood flow (CBF), such that increases in neuronal activity will result in increases in CBF to ensure the metabolic demands of the brain are met. Intact NVC is integral to maintain optimal cognitive function, and thus may be an important physiological mechanism in the chronic or rehabilitation phase of stroke. The following sections consider the evidence to support a role for CA and NVC as important mechanistic factors in the acute and chronic phases of stroke, and the key clinical and research implications going forward.

CA

Dynamic cerebral autoregulation (dCA) has now been carefully characterised at rest in AIS (13), acute intracerebral haemorrhage (ICH) (14) and chronic stroke (15) states. Furthermore, several studies have modelled the relationship between arterial CO₂ (PaCO₂), cerebral blood flow and dynamic cerebral autoregulation (16, 17). Hypercapnia causes vasodilation and deteriorates CA, with hypocapnia conversely causing vasoconstriction and an improvement in CA status (16, 17). Meta-analyses, albeit with significant heterogeneity, have demonstrated transfer function analysis parameter [phase and autoregulation index (ARI)] impairment in large and small artery AIS, lower phase in ICH and “rebounding phase” in chronic stroke (13). Unfortunately, limitations of existing transcranial Doppler based haemodynamic studies include low assessment frequency post stroke [particularly lacking data in ultra-acute (hours) and medium to longer term (weeks to months)] and clarification of dCA “cut-points” for impairment. Until very recently, there was a lack of dCA data peri- mechanical thrombectomy (MT), however, recent studies have shown worse dCA in the first 24 h associated with higher rates of haemorrhagic transformation and lower rates of recanalization (18). Specific learnings from this data suggest incomplete recanalisation of large-vessel occlusion, with impaired autoregulation status confer complication—raising the importance of adequate blood pressure control in this context (18). Whilst there are confounders to consider when assessing dCA pre-, during or post- MT including blood pressure (19, 20), end-tidal carbon dioxide level (21) and mode of anaesthesia (22)—their behaviour and interactions are yet to be determined. Higher end-tidal CO₂ levels in those with incomplete recanalisation, especially beyond 72 h post large-vessel occlusion (LVO) is of significant interest (18). In ICH, the storey differs, with severe hypocapnia (low arterial CO₂ levels) associated with poor prognosis (23). Furthermore, lowering BP during acute hypertensive states during ICH, in the setting of low arterial CO₂ levels, leads to a greater risk of ischaemic lesions on MRI imaging (23). These differences in acute haemodynamics between stroke sub-types could be explained by nature of structural lesion (infarct vs. haematoma), existence of pre-existing chronic hypertension or differing responses to blood pressure lowering. Given personalised autoregulation-based BP targets are now possible in both a ward based stroke setting (24) and neurocritical care (25). Unfortunately, there still remains an inability to quantify the potential modulation of dCA by chronic hypertension before, during and immediately after acute stroke. The perceived “rightward shift” in the dCA curve is yet to be proven in acute (within 96 h) and sub-acute (7 to 14 days) contexts with ongoing hypertension or antihypertensive treatment being administered (26).

Recent advancements have further highlighted the need to recognise inter-subject variability (27) and responders vs. non-responders (28). There is evidence to suggest dCA impairment is greatest in regions with critically reduced perfusion (greatest volume of viable tissue), though dCA impairment can be present across the entire hemisphere to varying degrees (27). In ICH, through routinely obtained MRI scans in the first 7 days post-event, initial BP, nadir BP, and arterial CO₂ were independent predictors of diffusion-restricted lesion incidence (23). Pooled individual patient data meta-analyses from the ATACH-2 and MISTIE III trials demonstrated in a heterogeneous cohort of patients with ICH, diffusion-weighted imaging (DWI) lesions were associated with 2.5-fold heightened risk of stroke among ICH survivors—with elevated risk persisting for AIS but not for recurrent ICH (29). In order to determine whether ischaemic lesions noted on DWI are preventable, or indeed governed by therapeutic variation in BP approaches (30)—mechanistic dCA studies at time of BP lowering, with continuous end-tidal CO₂ measurement are needed, with MRI DWI assessment at 7 days. White matter ischaemic change may be attributed to by high blood pressure variability in addition to adverse adaptations of CA. In hypertensives without acute stroke disease, dCA (assessed using ARI) and CO₂ reactivity were not related to white matter lesions—however, relationships with duration of hypertension and nocturnal BP dipping were shown (31). Ultimately, there exists a complex interdependent relationship between acute and chronic hypertensive states, dCA, and chronic cerebrovascular ischaemic injury. Crucially, we have evidence to support the hypothesis that carbon dioxide change in the acute setting post-stroke may modify risk, through interaction with BP lowering and dCA status, increasing the ischaemic stroke risk post ICH (23).

In both AIS and ICH, there exist adverse pathophysiologically driven complications including vasogenic oedema and haematoma expansion, respectively. The behaviour of cerebrovascular tone (critical closing pressure, CrCP) and resistance (resistance area product, RAP) is less well-understood. There is debate as to the sensitivity of CrCP to variation in intracranial pressure (ICP) (32). However, the presence of a haematoma in ICH as compared to controls, during normocapnic and hypocapnic conditions, showed significant differences in CrCP and RAP (33). Beyond common indices of dCA, there is limited knowledge of tone and resistance parameters in acute cerebrovascular states as compared to the traumatic brain injury literature.

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