Pre-Stroke Antihypertensive Therapy Affects Stroke Severity and 3-Month Outcome of Ischemic MCA-Territory Stroke.

OBJECTIVES: Whether different antihypertensive drug classes in high blood pressure (HBP) pre-stroke treatment affect dynamic cerebral autoregulation (dCA), stroke severity, and outcome. METHODS: Among 337 consecutive ischemic stroke patients (female 102; median age 71 years [interquartile range, [IQR 60; 78]; NIHSS median 3 [IQR 1; 6]) with assessment of dCA, 183 exhibited the diagnosis of HBP. dCA parameters' gain and phase were determined by transfer function analysis of spontaneous oscillations of blood pressure and cerebral blood flow velocity. RESULTS: Patients used beta-blockers (n = 76), calcium channel blockers (60), diuretics (77), angiotensin-converting enzyme inhibitors (59), or angiotensin-1 receptor blockers (79), mostly in various combinations of two or three drug classes. dCA parameters did not differ between the non-HBP and the different HBP medication groups. Multinomial ordinal logistic regression models revealed that the use of diuretics decreased the likelihood of a less severe stroke (odds ratio 0.691, 95% CI 0.493; 0.972; p = 0.01) and that beta-blockers decreased the likelihood of a better modified Rankin score at 3 months (odds ratio 0.981, 95% CI 0.970; 0.992; p = 0.009). Other independent factors associated with stroke outcome were penumbra and infarct volume, treatment with mechanical thrombectomy, and the initial National Institute of Health Stroke Scale score. INTERPRETATION: In this cohort of ischemic minor to moderate stroke patients, pre-stroke antihypertensive treatment with diuretics was associated with a more severe neurological deficit on admission and pre-stroke treatment with beta-blockers with a poorer 3-month outcome. The antihypertensive drug class used pre-stroke did not impact dCA.

Impaired dynamic cerebral autoregulation measured in the middle cerebral artery in patients with vertebrobasilar ischemia is associated with autonomic failure.

OBJECTIVES: To assess whether vertebrobasilar artery ischemia (VBI) affects cortical cerebral blood flow (CBF) regulation. MATERIAL AND METHODS: 107 consecutive patients (mean age 65 ± 15 years; women 21) with VBI underwent structured stroke care with assessment of dynamic cerebral autoregulation (dCA) in both middle cerebral arteries (MCAs) by transfer function analysis using spontaneous oscillations of blood pressure (BP) and CBF velocity that yields by extraction of phase and gain information in the very low (0.02-0.07 Hz), low (0.07-0.15 Hz) and high frequency (0.15-0.5 Hz) ranges. Additionally, power spectrum analysis of BP and heart rate variability (HRV) was performed. The control group consists of 29 age- and sex-matched healthy persons. RESULTS: Compared to controls, phase in the VBI patients was significantly reduced and gain increased in the very low frequencies (VLF), in the low (LF), phase was significantly reduced only ipsilaterally. In the high frequencies (HF), phase reduction was only marginally significant. BP power spectral density (PSD) was much higher in the patients than in the controls across all frequencies. In the PSD of heart rate variability the controls but not the patients exhibited a strong peak around 0.11Hz, while the patients, but not the controls, exhibit a strong peak around 0.36 Hz. In regression analysis, patient's phase and gain results were not related to age, sex, arterial hypertension, diabetes mellitus, renal dysfunction, heart failure as indicated by left ventricular ejection fraction, stroke subtype, presence or absence of cerebral small vessel disease. CONCLUSION: Patients with VBI exhibit bilateral cortical autoregulation impairment in association with an autonomic nervous system disbalance. GOV IDENTIFIER: NCT04611672.

Middle cerebral artery dynamic cerebral autoregulation is impaired by infarctions in the anterior but not the posterior cerebral artery territory in patients with mild strokes.

Objective: The aim of this study was to ascertain whether dynamic cerebral autoregulation (CA) in the middle cerebral artery (MCA) is disturbed by cerebral infarctions outside the MCA territory. Methods: We estimated transfer function parameters gain and phase from simultaneous recordings of spontaneous oscillation in blood pressure and MCA cerebral blood flow velocity in 10 consecutive patients with isolated anterior cerebral artery (ACA) infarctions and in 22 consecutive patients with isolated posterior cerebral artery (PCA) infarctions. All ACA infarctions were in the motor, premotor, or supplementary motor cortex areas and presented with pronounced leg hemiparesis. Twenty-eight age- and sex-matched healthy subjects served as controls. Results: Compared to controls, phase was significantly reduced in the MCA ipsilateral to the lesion site and in the contralateral MCA (unaffected hemisphere) in the very low (0.02-0.07 Hz) and low (0.07-0.15 Hz) frequency ranges in the ACA infarctions but not in the PCA infarctions. Gain was reduced only in the very low frequency range in the MCA contralateral to the ACA lesion site. Systemic factors were unrelated to phase and gain results. Conclusion: Bilateral impairment of MCA dynamic CA in patients with a unilateral ACA infarction is frequent.

Automated Supra- and Infratentorial Brain Infarct Volume Estimation on Diffusion Weighted Imaging Using the RAPID Software.

Purpose: The present computerized techniques have limits to estimate the ischemic lesion volume especially in vertebrobasilar ischemia (VBI) automatically. We investigated the ability of the RAPID AI (RAPID) software on diffusion-weighted imaging (DWI) to estimate the infarct size in VBI in comparison to supratentorial ischemia (STI). Methods: Among 123 stroke patients (39 women, 84 men, mean age 66 ± 11 years) having undergone DWI, 41 had had a VBI and 82 a STI. The infarct volume calculation by RAPID was compared to volume calculations by 2 neurologists using the ABC/2 method. For inter-reader and between-method analysis intraclass correlation coefficient (ICC), area under the curve (AUC) estimations, and Bland-Altman plots were used. Results: ICC between the two neurologists and each neurologist and RAPID were >0.946 (largest 95% CI boundaries 0.917-0.988) in the STI group, and > 0.757 (95% CI boundaries between 0.544 and 0.982) in the VBI group. In the STI group, AUC values ranged between 0.982 and 0.999 (95% CI 0.971-1) between the 2 neurologists and between 0.875 and 1 (95% CI 0.787-1) between the neurologists and RAPID; in the VBI group, they ranged between 0.925 and 0.965 (95% CI 0.801-1) between the neurologists, and between 0.788 and 0.931 (95% CI 0.663-1) between RAPID and the neurologists. Compared to the visual DWI interpretation by the neurologists, RAPID did not recognize a substantial number of infarct volumes of ≤ 2 ml. Conclusion: The ability of the RAPID software to depict strokes in the vertebrobasilar artery system seems close to its ability in the supratentorial brain tissue. However, small lesion volumes ≤ 2 ml remain still undetected in both brain areas.

Cerebral macro- and microcirculatory blood flow dynamics in successfully treated chronic hypertensive patients with and without white mater lesions.

The mechanisms of high blood pressure (HBP) -related brain pathology progression remain relatively unclear. We investigated whether lowering BP in chronic HBP patients normalizes cerebral perfusion dynamics at resistance vessel and capillary levels. Sixty-seven patients with HBP and 49 age- and sex-matched healthy controls underwent simultaneous recordings of middle cerebral artery blood flow velocity (CBFV), BP, and end-tidal CO2 concentration. Thirty-four controls and 28 patients underwent additional near-infrared spectroscopy recordings (oxygenated [O2Hb] and deoxygenated [HHb] hemoglobin). Degree of microcirculatory white matter lesions was graded by Fazekas scale. Dynamic cerebral autoregulation (dCA) was assessed by transfer function analysis. BP was successfully lowered (patients = 89 ± 15 mm Hg, controls = 87 ± 17), but cerebrovascular resistance was higher in BP patients (p < 0.05). BP-CBFV phase was lower in very low frequency (VLF) (left/right: 48 ± 20°/44 ± 17; controls: 61 ± 20/60 ± 21; p < 0.001) and low frequency (LF) (34 ± 14/35 ± 14; controls: 48 ± 20/44 ± 17; p < 0.05) ranges. Gain was higher in VLF range (in %/ mm Hg 0.56 ± 0.44/0.59 ± 0.49; controls: 0.32 ± 0.29/0.34 ± 0.32; p ≤ 0.005). BP-CBFV phase and gain did not differ across Fazekas groups. Across all patients, the capillary phases and gains (CBFV-[O2Hb], CBFV-[HHb]) were comparable to controls. Successfully treated chronic HBP results in normal brain capillary hemodynamics while the resistance vessel state is disturbed (phase decrease, gain increase).

Cerebral Microcirculatory Blood Flow Dynamics During Rest and a Continuous Motor Task.

Objectives: To examine the brain's microcirculatory response over the course of a continuous 5-min elbow movement task in order to estimate its potential role in grading vaso-neural coupling compared to the macrocirculatory response. Methods: We simultaneously recorded cerebral blood flow velocity (CBFV), changes in oxygenated/deoxygenated hemoglobin concentrations ([oxHb], [deoxHb]), blood pressure (BP), and end-tidal CO2 over 5-min periods of rest and left elbow movements in 24 healthy persons (13 women and 11 men of mean age ± SD, 38 ± 11 years). A low frequency range (0.07-0.15 Hz) was used for analysis by transfer function estimates of phase and gain. Results: Elbow movement led to a small BP increase (mean BP at rest 83 mm Hg, at movement 87; p < 0.01) and a small ETCO2 decrease (at rest 44.6 mm Hg, at movement 41.7 mm Hg; p < 0.01). Further, it increased BP-[oxHb] phase from 55° (both sides) to 74° (right; p < 0.05)/69° (left; p < 0.05), and BP-[deoxHb] phase from 264° (right)/270° (left) to 288° (right; p < 0.05)/297° (left; p = 0.09). The cerebral mean transit time at 0.1 Hz of 5.6 s of rest remained unchanged by movement. Elbow movement significantly decreased BP-CBFV gain on both sides, and BP-CBFV phase only on the right side (p = 0.05). Conclusion: Elbow movement leads to an increased time delay between BP and [oxHb]/[deoxHb] while leaving the cerebral mean transit time unchanged. Phase shifting is usually the more robust parameter when using a transfer function to estimate dynamic cerebral autoregulation; phase shifting at the microcirculatory level seems to be a better marker of VNC-induced changes than phase shifting between BP and CBFV.

Incomplete recovery of cerebral blood flow dynamics in sufficiently treated high blood pressure.

OBJECTIVE: Whether cerebrovascular regulation is different in patients with controlled high blood pressure (HBP) with and without small vessel disease (SVD). METHODS: Sixty-seven healthy controls (mean age ±â€ŠSD, 45 ±â€Š16 years; 30 women, 37 men) and 40 patients (mean age, 64 ±â€Š13 years; 14 women, 26 men) with HBP and different stages of SVD, underwent simultaneous recordings of the spontaneous fluctuations of BP, blood flow velocity (CBFV) in both middle cerebral arteries (MCA), and of end-tidal CO2 (ETCO2). Coherence and transfer function gain and phase between BP and CBFV were assessed in the frequency ranges of VLF (0.02-0.07 Hz), low frequency (0.07-0.15), and high frequency (>0.15). BP SD indicated BP variability (BPV). RESULTS: In controls (BP, 86 ±â€Š13 mmHg; ETCO2, 39 ±â€Š4 mmHg; BPV, 15 ±â€Š6 mmHg), gain, phase and coherence were not age-dependent in simple or a multiple regression models. BPV correlated significantly in both MCAs with gain in low frequency and high frequency, and with phase in VLF and high frequency. In patients (BP, 91 ±â€Š16 mmHg, ETCO2, 39 ±â€Š4 mmHg, BPV 18 ±â€Š5 mmHg), only gain showed some differences between different SVD groups. Comparing all patients with 25 controls of similar age and sex, patients exhibited significantly (P < 0.05-P < 0.005): increased coherence and gain in VLF, decreased phase in VLF and low frequency, correlations between BPV with phase in low frequency (left) and with gain in VLF (left) and in high frequency (left and right). CONCLUSION: Phase seems an age independent autoregulatory index. In controlled HBP, CBF regulation is degraded at longlasting CBF changes; BPV effects lose their physiological bilateral distribution.

Assessment of the Brain's Macro- and Micro-Circulatory Blood Flow Responses to CO2 via Transfer Function Analysis.

OBJECTIVES: At present, there is no standard bedside method for assessing cerebral autoregulation (CA) with high temporal resolution. We combined the two methods most commonly used for this purpose, transcranial Doppler sonography (TCD, macro-circulation level), and near-infrared spectroscopy (NIRS, micro-circulation level), in an attempt to identify the most promising approach. METHODS: In eight healthy subjects (5 women; mean age, 38 ± 10 years), CA disturbance was achieved by adding carbon dioxide (CO2) to the breathing air. We simultaneously recorded end-tidal CO2 (ETCO2), blood pressure (BP; non-invasively at the fingertip), and cerebral blood flow velocity (CBFV) in both middle cerebral arteries using TCD and determined oxygenated and deoxygenated hemoglobin levels using NIRS. For the analysis, we used transfer function calculations in the low-frequency band (0.07-0.15 Hz) to compare BP-CBFV, BP-oxygenated hemoglobin (OxHb), BP-tissue oxygenation index (TOI), CBFV-OxHb, and CBFV-TOI. RESULTS: ETCO2 increased from 37 ± 2 to 44 ± 3 mmHg. The CO2-induced CBFV increase significantly correlated with the OxHb increase (R (2) = 0.526, p < 0.001). Compared with baseline, the mean CO2 administration phase shift (in radians) significantly increased (p < 0.005) from -0.67 ± 0.20 to -0.51 ± 0.25 in the BP-CBFV system, and decreased from 1.21 ± 0.81 to -0.05 ± 0.91 in the CBFV-OxHb system, and from 0.94 ± 1.22 to -0.24 ± 1.0 in the CBFV-TOI system; no change was observed for BP-OxHb (0.38 ± 1.17 to 0.41 ± 1.42). Gain changed significantly only in the BP-CBFV system. The correlation between the ETCO2 change and phase change was higher in the CBFV-OxHb system [r = -0.60; 95% confidence interval (CI): -0.16, -0.84; p < 0.01] than in the BP-CBFV system (r = 0.52; 95% CI: 0.03, 0.08; p < 0.05). CONCLUSION: The transfer function characterizes the blood flow transition from macro- to micro-circulation by time delay only. The CBFV-OxHb system response with a broader phase shift distribution offers the prospect of a more detailed grading of CA responses. Whether this is of clinical relevance needs further studies in different patient populations.

Assessing internal carotid artery stenosis with a semiautomated computed tomography angiography tool and duplex ultrasound.

OBJECTIVE: Duplex ultrasound (DUS) and computed tomography angiography (CTA) are both used as first-line noninvasive methods to investigate patients for internal carotid artery (ICA) disease. Although manual assessment of CTA is well established, semiautomated vessel analysis programs have yet to prove their clinical benefit. We compared one such vessel analysis program (TeraRecon, Foster City, Calif) with DUS. METHODS: A total of 85 arteries in 50 patients (35 men, 15 women; mean age, 73 ± 10 years) were eligible for comparison with the North American Symptomatic Carotid Endarterectomy Trial method. Duplex scanning comprised stenosis estimation based on (1) the intrastenotic and distal ICA diameter measurements on color-coded imaging (CCI), (2) the application of German Society for Ultrasound in Medicine (DEGUM) criteria (intrastenotic peak systolic velocity [PSV] ≥ 2 00 cm/s indicates 50% stenosis; intrastenotic PSV ≥ 300 cm/s together with a PSV of ≥ 50 cm/s in the distal ICA indicates 70% stenosis), and (3) the application of the University of Washington stenosis criteria (≥ 50% stenosis is indicated by PSV >125 cm/s and end-diastolic velocity <140 cm/s; ≥ 80% stenosis is indicated by PSV >125 cm/s and end-diastolic velocity ≥ 140 cm/s). The minimum and maximum diameters at the stenosis site and at the distal reference ICA were automatically measured with the CTA vessel analysis tool. In addition, automated tracking generated corresponding cross-sectional areas at these two sites. Angiographic stenosis was then calculated using the minimum diameter (CTAmin), the average of the minimum and maximum diameters (CTAavg), and the areas (CTAarea) at both sites. RESULTS: Compared with duplex CCI, the three CTA modalities exhibited only a moderate agreement in terms of regression analysis (R(2) = 0.41-0.54) and Bland-Altman analysis (the standard deviation of the stenosis differences was >20%). In terms of sensitivity, specificity, positive predictive value, negative predictive value, and accuracy, DEGUM stenosis graduation was best balanced by duplex CCI (50% stenosis: 100%, 93%, 85%, 100%, 95%; 70% stenosis: 71%, 100%, 100%, 97%, 98%) followed by CTAarea (50% stenosis: 80%, 73%, 54%, 90%, 75%; 70% stenosis: 66%, 94%, 55%, 96%, 96%). University of Washington stenosis was best balanced by duplex CCI followed by CTAarea. CONCLUSIONS: CTA analysis with a semiautomated vessel analysis tool provides variable results. Large discrepancies between methods in the degree of reported stenosis must be taken into consideration when CTA and DUS are used for clinical purposes. The semiautomated software tools need further improvements.

A comparison of dynamic cerebral autoregulation across changes in cerebral blood flow velocity for 200 s.

OBJECTIVES: The dynamic interaction between blood pressure (BP) and cerebral blood flow velocity (CBFV) is not fully understood, especially for CBFV changes lasting longer than 50 s. The interaction between BP and CBFV is relatively well characterized for periods <50 s using transfer function (TF) estimations of phase, gain, and coherence. We used TF estimations to compare the phase and gain for periods >50 s with those for periods <50 s. MATERIALS AND METHODS: BP and CBFV (of the middle cerebral artery) were simultaneously recorded in 23 healthy subjects (10 men, 13 women, mean age 35 ± 10 years) under normo- and hypocapnia (induced by hyperventilation). TF and coherence estimations were based on Welch's periodogram method with a windowing of 200 s (frequency resolution, 0.005 Hz, corresponding to a period of 200 s). Means of the phase, gain, and coherence were calculated over frequency periods of 0.005-0.02 Hz (sVLF), 0.02-0.07 Hz (VLF), 0.07-0.15 Hz (LF), and 0.15-0.40 Hz (HF) and analyzed using the t-test and Pearson correlation. RESULTS: Compared with the VLF range, normo- and hypocapnia phases were slightly but significantly lower in sVLF, while gain and coherence were not different. Hypocapnia induced significant (mostly p < 0.01) phase increases and gain decreases as well as coherence decreases in all frequency ranges. The phase and gain correlated significantly (-0.87 < r > -0.99) (p < 0.001) and inversely in all frequency ranges <0.15 Hz under both respiratory conditions. In some instances, the phase indicated disturbed autoregulation. CONCLUSION: In the frequency range <0.15 Hz, the phase and gain correlate highly and linearly with high consistency. The phase, gain, and coherence were similar in sVLF and VLF ranges. The phase was slightly lower in the sVLF range than in the VLF range. Notably, the data suggest that autoregulatory failure may occur in healthy persons.