Individual Patient Data Meta-Analysis of Dynamic Cerebral Autoregulation and Functional Outcome After Ischemic Stroke.

BACKGROUND: The relationship between dynamic cerebral autoregulation (dCA) and functional outcome after acute ischemic stroke (AIS) is unclear. Previous studies are limited by small sample sizes and heterogeneity. METHODS: We performed a 1-stage individual patient data meta-analysis to investigate associations between dCA and functional outcome after AIS. Participating centers were identified through a systematic search of the literature and direct invitation. We included centers with dCA data within 1 year of AIS in adults aged over 18 years, excluding intracerebral or subarachnoid hemorrhage. Data were obtained on phase, gain, coherence, and autoregulation index derived from transfer function analysis at low-frequency and very low-frequency bands. Cerebral blood velocity, arterial pressure, end-tidal carbon dioxide, heart rate, stroke severity and sub-type, and comorbidities were collected where available. Data were grouped into 4 time points after AIS: <24 hours, 24 to 72 hours, 4 to 7 days, and >3 months. The modified Rankin Scale assessed functional outcome at 3 months. Modified Rankin Scale was analyzed as both dichotomized (0 to 2 versus 3 to 6) and ordinal (modified Rankin Scale scores, 0-6) outcomes. Univariable and multivariable analyses were conducted to identify significant relationships between dCA parameters, comorbidities, and outcomes, for each time point using generalized linear (dichotomized outcome), or cumulative link (ordinal outcome) mixed models. The participating center was modeled as a random intercept to generate odds ratios with 95% CIs. RESULTS: The sample included 384 individuals (35% women) from 7 centers, aged 66.3±13.7 years, with predominantly nonlacunar stroke (n=348, 69%). In the affected hemisphere, higher phase at very low-frequency predicted better outcome (dichotomized modified Rankin Scale) at <24 (crude odds ratios, 2.17 [95% CI, 1.47-3.19]; P<0.001) hours, 24-72 (crude odds ratios, 1.95 [95% CI, 1.21-3.13]; P=0.006) hours, and phase at low-frequency predicted outcome at 3 (crude odds ratios, 3.03 [95% CI, 1.10-8.33]; P=0.032) months. These results remained after covariate adjustment. CONCLUSIONS: Greater transfer function analysis-derived phase was associated with improved functional outcome at 3 months after AIS. dCA parameters in the early phase of AIS may help to predict functional outcome.

Contribution of intracranial pressure to human dynamic cerebral autoregulation after acute brain injury.

Cerebral perfusion pressure (CPP) is normally expressed by the difference between mean arterial blood pressure (MAP) and intracranial pressure (ICP) but comparison of the separate contributions of MAP and ICP to human cerebral blood flow autoregulation has not been reported. In patients with acute brain injury (ABI), internal jugular vein compression (IJVC) was performed for 60 s. Dynamic cerebral autoregulation (dCA) was assessed in recordings of middle cerebral artery blood velocity (MCAv, transcranial Doppler), and invasive measurements of MAP and ICP. Patients were separated according to injury severity as having whole/undamaged skull, large fractures, or craniotomies, or following decompressive craniectomy. Glasgow coma score was not different for the three groups. IJVC induced changes in MCAv, MAP, ICP, and CPP in all three groups. The MCAv response to step changes in MAP and ICP expressed the dCA response to these two inputs and was quantified with the autoregulation index (ARI). In 85 patients, ARI was lower for the ICP input as compared with the MAP input (2.25 ± 2.46 vs. 3.39 ± 2.28; P < 0.0001), and particularly depressed in the decompressive craniectomy (DC) group (n = 24, 0.35 ± 0.62 vs. 2.21 ± 1.96; P < 0.0005). In patients with ABI, the dCA response to changes in ICP is less efficient than corresponding responses to MAP changes. These results should be taken into consideration in studies aimed to optimize dCA by manipulation of CPP in neurocritical patients.

Early tracheostomy in stroke patients: A meta-analysis and comparison with late tracheostomy.

Tracheostomy (TQT) timing and its benefits is a current discussion in medical society. We aimed to compare the outcomes of early (ET) versus late tracheostomy (LT) in stroke patients with systematic review and meta-analysis, according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Five hundred and nineteen studies were retrieved, whereas three were selected for the systematic review and meta-analysis. There were 5636 patients in the ET group (3151 male, 2470 female, 15 not reported - NR) and 7637 patients in the LT group (4098 male, 3542 female, and 33 NR). ET was significantly associated with fewer days in the hospital (weighted mean difference: -7.73 [95 % CI -8.59-6.86], p < 0.001) and reduced cases of ventilator-associated pneumonia (VAP) (risk difference: 0.71 [95 % CI 0.62-0.81], p < 0.001). There were no between-group statistical differences in intensive care unit stay duration, mechanical ventilation duration, or mortality. The findings from this meta-analysis cannot state that ET in severe stroke patients contributes to better outcomes when compared with LT. Scandalized assessments and randomized trials are encourage for better assessment.

The critical closing pressure contribution to dynamic cerebral autoregulation in humans: influence of arterial partial pressure of CO2.

KEY POINTS: Dynamic cerebral autoregulation (CA) is often expressed by the mean arterial blood pressure (MAP)-cerebral blood flow (CBF) relationship, with little attention given to the dynamic relationship between MAP and cerebrovascular resistance (CVR). In CBF velocity (CBFV) recordings with transcranial Doppler, evidence demonstrates that CVR should be replaced by a combination of a resistance-area product (RAP) with a critical closing pressure (CrCP) parameter, the blood pressure value where CBFV reaches zero due to vessels collapsing. Transfer function analysis of the MAP-CBFV relationship can be extended to the MAP-RAP and MAP-CrCP relationships, to assess their contribution to the dynamic CA response. During normocapnia, both RAP and CrCP make a significant contribution to explaining the MAP-CBFV relationship. Hypercapnia, a surrogate state of depressed CA, leads to marked changes in dynamic CA, that are entirely explained by the CrCP response, without further contribution from RAP in comparison with normocapnia. ABSTRACT: Dynamic cerebral autoregulation (CA) is manifested by changes in the diameter of intra-cerebral vessels, which control cerebrovascular resistance (CVR). We investigated the contribution of critical closing pressure (CrCP), an important determinant of CVR, to explain the cerebral blood flow (CBF) response to a sudden change in mean arterial blood pressure (MAP). In 76 healthy subjects (age range 21-70 years, 36 women), recordings of MAP (Finometer), CBF velocity (CBFV; transcranial Doppler ultrasound), end-tidal CO2 (capnography) and heart rate (ECG) were performed for 5 min at rest (normocapnia) and during hypercapnia induced by breathing 5% CO2 in air. CrCP and the resistance-area product (RAP) were obtained for each cardiac cycle and their dynamic response to a step change in MAP was calculated by means of transfer function analysis. The recovery of the CBFV response, following a step change in MAP, was mainly due to the contribution of RAP during both breathing conditions. However, CrCP made a highly significant contribution during normocapnia (P < 0.0001) and was the sole determinant of changes in the CBFV response, resulting from hypercapnia, which led to a reduction in the autoregulation index from 5.70 ± 1.58 (normocapnia) to 4.14 ± 2.05 (hypercapnia; P < 0.0001). In conclusion, CrCP makes a very significant contribution to the dynamic CBFV response to changes in MAP and plays a major role in explaining the deterioration of dynamic CA induced by hypercapnia. Further studies are needed to assess the relevance of CrCP contribution in physiological and clinical studies.

Cerebral autoregulation and response to intravenous thrombolysis for acute ischemic stroke.

We hypothesized that knowledge of cerebral autoregulation (CA) status during recanalization therapies could guide further studies aimed at neuroprotection targeting penumbral tissue, especially in patients that do not respond to therapy. Thus, we assessed CA status of patients with acute ischemic stroke (AIS) during intravenous r-tPA therapy and associated CA with response to therapy. AIS patients eligible for intravenous r-tPA therapy were recruited. Cerebral blood flow velocities (transcranial Doppler) from middle cerebral artery and blood pressure (Finometer) were recorded to calculate the autoregulation index (ARI, as surrogate for CA). National Institute of Health Stroke Score was assessed and used to define responders to therapy (improvement of ≥ 4 points on NIHSS measured 24-48 h after therapy). CA was considered impaired if ARI < 4. In 38 patients studied, compared to responders, non-responders had significantly lower ARI values (affected hemisphere: 5.0 vs. 3.6; unaffected hemisphere: 5.4 vs. 4.4, p = 0.03) and more likely to have impaired CA (32% vs. 62%, p = 0.02) during thrombolysis. In conclusion, CA during thrombolysis was impaired in patients who did not respond to therapy. This variable should be investigated as a predictor of the response to therapy and to subsequent neurological outcome.

COHmax: an algorithm to maximise coherence in estimates of dynamic cerebral autoregulation.

OBJECTIVE: The reliability of dynamic cerebral autoregulation (dCA) parameters, obtained with transfer function analysis (TFA) of spontaneous fluctuations in arterial blood pressure (BP), require statistically significant values of the coherence function. A new algorithm (COHmax) is proposed to increase values of coherence by means of the automated, selective removal of sub-segments of data. APPROACH: Healthy subjects were studied at baseline (normocapnia) and during 5% breathing of CO2 (hypercapnia). BP (Finapres), cerebral blood flow velocity (CBFV, transcranial Doppler), end-tidal CO2 (EtCO2, capnography) and heart rate (ECG) were recorded continuously during 5 min in each condition. TFA was performed with sub-segments of data of duration (SEGD) 100 s, 50 s or 25 s and the autoregulation index (ARI) was obtained from the CBFV response to a step change in BP. The area-under-the curve (AUC) was obtained from the receiver-operating characteristic (ROC) curve for the detection of changes in dCA resulting from hypercapnia. MAIN RESULTS: In 120 healthy subjects (69 male, age range 20-77 years), CO2 breathing was effective in changing mean EtCO2 and CBFV (p < 0.001). For SEGD = 100 s, ARI changed from 5.8 ± 1.4 (normocapnia) to 4.0 ± 1.7 (hypercapnia, p < 0.0001), with similar differences for SEGD = 50 s or 25 s. Depending on the value of SEGD, in normocapnia, 15.8% to 18.3% of ARI estimates were rejected due to poor coherence, with corresponding rates of 8.3% to 13.3% in hypercapnia. With increasing coherence, 36.4% to 63.2% of these could be recovered in normocapnia (p < 0.001) and 50.0% to 83.0% in hypercapnia (p < 0.005). For SEGD = 100 s, ROC AUC was not influenced by the algorithm, but it was superior to corresponding values for SEGD = 50 s or 25 s. SIGNIFICANCE: COHmax has the potential to improve the yield of TFA estimates of dCA parameters, without introducing a bias or deterioration of their ability to detect impairment of autoregulation. Further studies are needed to assess the behaviour of the algorithm in patients with different cerebrovascular conditions.

Chasing the evidence: the influence of data segmentation on estimates of dynamic cerebral autoregulation.

OBJECTIVE: Transfer function analysis (TFA) of dynamic cerebral autoregulation (dCA) requires smoothing of spectral estimates using segmentation of the data (SD). Systematic studies are required to elucidate the potential influence of SD on dCA parameters. APPROACH: Healthy subjects (HS, n = 237) and acute ischaemic stroke patients (AIS, n = 98) were included. Cerebral blood flow velocity (CBFV, transcranial Doppler ultrasound) was recorded supine at rest with continuous arterial blood pressure (BP, Finometer) for a minimum of 5 min. TFA was performed with durations SD = 100, 50 or 25 s and 50% superposition to derive estimates of coherence, gain and phase for the BP-CBFV relationship. The autoregulation index (ARI) was estimated from the CBFV step response. Intrasubject reproducibility was expressed by the intraclass correlation coefficient (ICC). MAIN RESULTS: In HS, the ARI, coherence, gain, and phase (low frequency) were influenced by SD, but in AIS, phase (very low frequency) and ARI were not affected. ICC was excellent (>0.75) for all parameters, for both HS and AIS. For SD = 100 s, ARI was different between HS and AIS (mean ± sdev: 5.70 ± 1.61 vs 5.1 ± 2.0; p < 0.01) and the significance of this difference was maintained for SD = 50 s and 25 s. Using SD = 100 s as reference, the rate of misclassification, based on a threshold of ARI ⩽ 4, was 6.3% for SD = 50 s and 8.1% for SD = 25 s in HS, with corresponding values of 11.7% and 8.2% in AIS patients, respectively. SIGNIFICANCE: Further studies are warranted with SD values lower than the recommended standard of SD = 100 s, to explore possibilities of improving the reproducibility, sensitivity and prognostic value of TFA parameters used as metrics of dCA.

Early Tracheostomy in Severe Traumatic Brain Injury Patients: A Meta-Analysis and Comparison With Late Tracheostomy.

OBJECTIVES: To elucidate the impact of early tracheostomy on hospitalization outcomes in patients with traumatic brain injury. DATA SOURCES: Lilacs, PubMed, and Cochrane databases were searched. The close-out date was August 8, 2018. STUDY SELECTION: Studies written in English, French, Spanish, or Portuguese with traumatic brain injury as the base trauma, clearly formulated question, patient's admission assessment, minimum follow-up during hospital stay, and minimum of two in-hospital outcomes were selected. Retrospective studies, prospective analyses, and case series were included. Studies without full reports or abstract, commentaries, editorials, and reviews were excluded. DATA EXTRACTION: The study design, year, patient's demographics, mean time between admission and tracheostomy, neurologic assessment at admission, confirmed ventilator-assisted pneumonia, median ICU stay, median hospital stay, mortality rates, and ICU and hospital costs were extracted. DATA SYNTHESIS: A total of 4,219 studies were retrieved and screened. Eight studies were selected for the systematic review; of these, seven were eligible for the meta-analysis. Comparative analyses were performed between the early tracheostomy and late tracheostomy groups. Mean time for early tracheostomy and late tracheostomy procedures was 5.59 days (SD, 0.34 d) and 11.8 days (SD, 0.81 d), respectively. Meta-analysis revealed that early tracheostomy was associated with shorter mechanical ventilation duration (-4.15 [95% CI, -6.30 to -1.99]) as well as ICU (-5.87 d [95% CI, -8.74 to -3.00 d]) and hospital (-6.68 d [95% CI, -8.03 to -5.32 d]) stay durations when compared with late tracheostomy. Early tracheostomy presented less risk difference for ventilator-associated pneumonia (risk difference, 0.78; 95% CI, 0.70-0.88). No statistical difference in mortality was found between the groups. CONCLUSIONS: The findings from this meta-analysis suggest that early tracheostomy in severe traumatic brain injury patients contributes to a lower exposure to secondary insults and nosocomial adverse events, increasing the opportunity of patient's early rehabilitation and discharge.

Can we assess dynamic cerebral autoregulation in stroke patients with high rates of cardiac ectopicity?

It is unclear whether physiological recordings containing high numbers of ectopic heartbeats can be used to measure the cerebral autoregulation (CA) of blood flow. This study evaluated the utility of such data for assessing dynamic CA capacity. Physiological recordings of cerebral blood flow velocity, heart rate, end-tidal CO2 and beat-to-beat blood pressure from acute ischaemic stroke (AIS) patients (n = 46) containing ectopic heartbeats of varying number (0.2 to 25 occurrences per minute) were analysed. Dynamic CA was determined using the autoregulation index (ARI) and the normalised mean square error (NMSE) was used to evaluate the fitting of the step response between BP and CBFV to Tiecks' model. We fitted linear mixed models on the CA variables incorporating ectopic burden, age, sex and hemisphere as predictor variables. Ectopic activity demonstrated an association with mean coherence (p = 0.006) but not with ARI (p = 0.162), impaired CA based on dichotomised ARI (p = 0.859) or NMSE (p = 0.671). Dynamic CA could be reliably assessed in AIS patients using physiological recordings with high rates of cardiac ectopic activity. This provides supportive data for future studies evaluating CA capability in AIS patients, with the potential to develop more individualised treatment strategies. Graphical Abstract.

Can we use short recordings for assessment of dynamic cerebral autoregulation? A sensitivity analysis study in acute ischaemic stroke and healthy subjects.

OBJECTIVE: It is unclear whether the duration of recordings influences estimates of dynamic cerebral autoregulation (dCA). Therefore, we performed a retrospective study of the effects of reducing recording durations on dCA estimates; with the potential to inform recording duration for reliable estimates in challenging clinical populations. APPROACH: Seventy-eight healthy control subjects and 79 acute ischaemic stroke (AIS) patients were included. Cerebral blood flow (CBF) velocity was recorded with transcranial Doppler (TCD) and continuous blood pressure (BP) with a Finapres device. The autoregulation index (ARI), derived with transfer function analysis (TFA), was calculated for recording durations at one-minute intervals between 1 and 5 min using the same starting point of each recording. MAIN RESULTS: Though recording duration did not affect the overall ARI value, when compared to control subjects, AIS patients had significantly lower ARI values for durations between 3 and 5 min (p  < 0.0001), but not 1 and 2 min. The intraclass correlation coefficient of all participants, for reproducibility of the five recording durations, was 0.69. AIS patients classified as having impaired cerebral autoregulation (CA; ARI ⩽ 4) at 5 min, had a 7.1% rate of false negatives for both 4 and 3 min recordings, reaching 42.9% for 1 min recording. The percentage of false-positives also increased with reduced recording durations (from 0% at 5 to 16.2% at 1 min). SIGNIFICANCE: Reducing recording durations from 5 to 3 min can still provide reliable estimates of ARI, and may facilitate CA studies in potentially medically unstable AIS patients, as well as in other patient groups.

Do acute stroke patients develop hypocapnia? A systematic review and meta-analysis.

PURPOSE: Carbon dioxide (CO2) is a potent cerebral vasomotor agent. Despite reduction in CO2 levels (hypocapnia) being described in several acute diseases, there is no clear data on baseline CO2 values in acute stroke. The aim of the study was to systematically assess CO2 levels in acute stroke. MATERIAL AND METHODS: Four online databases, Web of Science, MEDLINE, EMBASE and CENTRAL, were searched for articles that described either partial pressure of arterial CO2 (PaCO2) and end-tidal CO2 (EtCO2) in acute stroke. RESULTS: After screening, based on predefined inclusion and exclusion criteria, 20 studies were retained. There were 5 studies in intracerebral hemorrhage and 15 in ischemic stroke, totalling 660 stroke participants. Acute stroke was associated with a significant decrease in CO2 levels compared to controls. Cerebral haemodynamic studies using transcranial Doppler ultrasonography demonstrated a significant reduction in cerebral blood flow velocities and cerebral autoregulation in acute stroke patients. CONCLUSION: The evidence from this review suggests that acute stroke patients are significantly more likely than controls to be hypocapnic, supporting the value of routine CO2 assessment in the acute stroke setting. Further studies are required in order to evaluate the clinical impact of these findings.

Pooling data from different populations: should there be regional differences in cerebral haemodynamics?

BACKGROUND: Though genetic and environmental determinants of systemic haemodynamic have been reported, surprisingly little is known about their influences on cerebral haemodynamics. We assessed the potential geographical effect on cerebral haemodynamics by comparing the individual differences in cerebral blood flow velocity (CBFv), vasomotor tone (critical closing pressure- CrCP), vascular bed resistance (resistance-area product- RAP) and cerebral autoregulation (CA) mechanism on healthy subjects and acute ischaemic stroke (AIS) patients from two countries. METHODS: Participants were pooled from databases in Leicester, United Kingdom (LEI) and São Paulo, Brazil (SP) research centres. Stroke patients admitted within 48 h of ischaemic stroke onset, as well as age- and sex-matched controls were enrolled. Beat-to-beat blood pressure (BP) and bilateral mean CBFv were recorded during 5 min baseline. CrCP and RAP were calculated. CA was quantified using transfer function analysis (TFA) of spontaneous oscillations in arterial BP and mean CBFv, and the derived autoregulatory index (ARI). RESULTS: A total of 100 participants (50 LEI and 50 SP) were recruited. No geographical differences were found. Both LEI and SP AIS participants showed lower values of CA compared to controls. Moreover, the affected hemisphere presented lower resting CBFv and higher RAP compared to the unaffected hemisphere in both populations. CONCLUSIONS: Impairments of cerebral haemodynamics, demonstrated by several key parameters, was observed following AIS compared to controls irrespective of geographical region. These initial results should encourage further research on cerebral haemodynamic research with larger cohorts combining different populations.

Cerebral Haemodynamics following Acute Ischaemic Stroke: Effects of Stroke Severity and Stroke Subtype.

BACKGROUND: Acute ischaemic stroke (AIS) patients often show impaired cerebral autoregulation (CA). We tested the hypothesis that CA impairment and other alterations in cerebral haemodynamics are associated with stroke subtype and severity. METHODS: AIS patients (n = 143) were amalgamated from similar studies. Data from baseline (< 48 h stroke onset) physiological recordings (beat-to-beat blood pressure [BP], cerebral blood flow velocity (CBFV) from bilateral insonation of the middle cerebral arteries) were calculated for mean values and autoregulation index (ARI). Differences were assessed between stroke subtype (Oxfordshire Community Stroke Project [OCSP] classification) and severity (National Institutes of Health Stroke Scale [NIHSS] score < 5 and 5-25). Correlation coefficients assessed associations between NIHSS and physiological measurements. RESULTS: Thirty-two percent of AIS patients had impaired CA (ARI < 4) in affected hemisphere (AH) that was similar between stroke subtypes and severity. CBFV in AH was comparable between stroke subtype and severity. In unaffected hemisphere (UH), differences existed in mean CBFV between lacunar and total anterior circulation OCSP subtypes (42 vs. 56 cm•s-1, p < 0.01), and mild and moderate-to-severe stroke severity (45 vs. 51 cm•s-1, p = 0.04). NIHSS was associated with peripheral (diastolic and mean arterial BP) and cerebral haemodynamic parameters (CBFV and ARI) in the UH. CONCLUSIONS: AIS patients with different OCSP subtypes and severity have homogeneity in CA capability. Cerebral haemodynamic measurements in the UH were distinguishable between stroke subtype and severity, including the association between deteriorating ARI in UH with stroke severity. More studies are needed to determine their clinical significance and to understand the determinants of CA impairment in AIS patients.

Intracranial Hypertension and Cerebral Autoregulation: A Systematic Review and Meta-Analysis.

OBJECTIVE: To present a systematic review and meta-analysis to establish the relation between cerebral autoregulation (CA) and intracranial hypertension. METHODS: An electronic search using the term "Cerebral autoregulation and intracranial hypertension" was designed to identify studies that analyzed cerebral blood flow autoregulation in patients undergoing intracranial pressure (ICP) monitoring. The data were used in meta-analyses and sensitivity analyses. RESULTS: A static CA technique was applied in 10 studies (26.3%), a dynamic technique was applied in 25 studies (65.8%), and both techniques were used in 3 studies (7.9%). Static CA studies using the cerebral blood flow technique revealed impaired CA in patients with an ICP ≥20 (standardized mean difference [SMD] 5.44%, 95% confidence interval [CI] 0.25-10.65, P = 0.04); static CA studies with transcranial Doppler revealed a tendency toward impaired CA in patients with ICP ≥20 (SMD -7.83%, 95% CI -17.52 to 1.85, P = 0.11). Moving correlation studies reported impaired CA in patients with ICP ≥20 (SMD 0.06, 95% CI 0.07-0.14, P < 0.00001). A comparison of CA values and mean ICP revealed a correlation between greater ICP and impaired CA (SMD 5.47, 95% CI 1.39-10.1, P = 0.01). Patients with ICP ≥20 had an elevated risk of impaired CA (OR 2.27, 95% CI 1.20-4.31, P = 0.01). CONCLUSIONS: A clear tendency toward CA impairment was observed in patients with increased ICP.

Effects of cerebral ischemia on human neurovascular coupling, CO2 reactivity, and dynamic cerebral autoregulation.

Cerebral blood flow (CBF) regulation can be impaired in acute ischemic stroke but the combined effects of dynamic cerebral autoregulation (CA), CO2 cerebrovascular reactivity (CVR), and neurovascular coupling (NVC), obtained from simultaneous measurements, have not been described. CBF velocity in the middle cerebral artery (MCA) (CBFv, transcranial Doppler), blood pressure (BP, Finometer), and end-tidal Pco2 (PetCO2 , infrared capnography) were recorded during a 1-min passive movement of the arm in 27 healthy controls [mean age (SD) 61.4 (6.0) yr] and 27 acute stroke patients [age 63 (11.7) yr]. A multivariate autoregressive-moving average model was used to separate the contributions of BP, arterial Pco2 (PaCO2 ), and the neural activation to the CBFv responses. CBFv step responses for the BP, CO2, and stimulus inputs were also obtained. The contribution of the stimulus to the CBFv response was highly significant for the difference between the affected side [area under the curve (AUC) 104.5 (4.5)%] and controls [AUC 106.9 (4.3)%; P = 0.008]. CBFv step responses to CO2 [affected hemisphere 0.39 (0.7), unaffected 0.55 (0.8), controls 1.39 (0.9)%/mmHg; P = 0.01, affected vs. controls; P = 0.025, unaffected vs. controls] and motor stimulus inputs [affected hemisphere 0.20 (0.1), unaffected 0.22 (0.2), controls 0.37 (0.2) arbitrary units; P = 0.009, affected vs. controls; P = 0.02, unaffected vs. controls] were reduced in the stroke group compared with controls. The CBFv step responses to the BP input at baseline and during the paradigm were not different between groups (P = 0.07), but PetCO2 was lower in the stroke group (P < 0.05). These results provide new insights into the interaction of CA, CVR, and NVC in both health and disease states.

The longitudinal evolution of cerebral blood flow regulation after acute ischaemic stroke.

BACKGROUND: Acute stroke is known to impair cerebral blood flow (CBF) regulation, but the longitudinal changes of these effects have been poorly reported. The main CBF regulatory mechanisms [cerebral autoregulation (CA) and neurovascular coupling (NVC)] were assessed over 3 months after acute ischaemic stroke. METHODS: Recordings of CBF velocity (CBFv), blood pressure (BP), and end-tidal CO2 were performed during 5 min baseline and 1 min passive movement of the elbow. Stroke patients were assessed <72 h of stroke onset, and at 2 weeks, 1 and 3 months after stroke. RESULTS: Fifteen acute stroke subjects underwent all 4 sessions and were compared to 22 control subjects. Baseline recordings revealed a significantly lower CBFv in the affected hemisphere within 72 h after stroke compared to controls (p = 0.02) and a reduction in CA index most marked at 2 weeks (p = 0.009). CBFv rise in response to passive arm movement was decreased bilaterally after stroke, particularly in the affected hemisphere (p < 0.01). Both alterations in CA and NVC returned to control levels during recovery. CONCLUSION: The major novel finding of this study was that both CA and NVC regulatory mechanisms deteriorated initially following stroke onset, but returned to control levels during the recovery period. These findings are relevant to guide the timing of interventions to manipulate BP and potentially for the impact of intensive rehabilitation strategies that may precipitate acute physiological perturbations but require further exploration in a larger population that better reflects the heterogeneity of stroke. Further, they will also enable the potential influence of stroke subtype to be investigated.

Influence of CO2 on neurovascular coupling: interaction with dynamic cerebral autoregulation and cerebrovascular reactivity.

Abstract PaCO2 affects cerebral blood flow (CBF) and its regulatory mechanisms, but the interaction between neurovascular coupling (NVC), cerebral autoregulation (CA), and cerebrovascular reactivity to CO2 (CVR), in response to hypercapnia, is not known. Recordings of cerebral blood flow velocity (CBFv), blood pressure (BP), heart rate, and end-tidal CO2 (EtCO2) were performed in 18 subjects during normocapnia and 5% CO2 inhalation while performing a passive motor paradigm. Together with BP and EtCO2, a gate signal to represent the effect of stimulation was used as input to a multivariate autoregressive-moving average model to calculate their separate effects on CBFv. Hypercapnia led to a depression of dynamic CA at rest and during stimulation in both hemispheres (P < 0.02) as well as impairment of the NVC response, particularly in the ipsilateral hemisphere (P < 0.01). Neither hypercapnia nor the passive motor stimulation influenced CVR. Dynamic CA was not influenced by the motor paradigm during normocapnia. The CBFv step responses to each individual input (BP, EtCO2, stimulation) allowed identification of the influences of hypercapnia and neuromotor stimulation on CA, CVR, and NVC, which have not been previously described, and also confirmed the depressing effects of hypercapnia on CA and NVC. The stability of CVR during these maneuvers and the lack of influence of stimulation on dynamic CA are novel findings which deserve further investigation. Dynamic multivariate modeling can identify the complex interplay between different CBF regulatory mechanisms and should be recommended for studies involving similar interactions, such as the effects of exercise or posture on cerebral hemodynamics.