The effect of posture on the age dependence of neurovascular coupling.

Previous studies report contradicting age-related neurovascular coupling (NVC). Few studies assess postural effects, but less investigate relationships between age and NVC within different postures. Therefore, this study investigated the effect of age on NVC in different postures with varying cognitive stimuli. Beat-to-beat blood pressure, heart rate and end-tidal carbon dioxide were assessed alongside middle and posterior cerebral artery velocities (MCAv and PCAv, respectively) using transcranial Doppler ultrasonography in 78 participants (31 young-, 23 middle- and 24 older-aged) with visuospatial (VST) and attention tasks (AT) in various postures at two timepoints (T2 and T3). Between-group significance testing utilized one-way analysis-of-variance (ANOVA) (Tukey post-hoc). Mixed three-way/one-way ANOVAs explored task, posture, and age interactions. Significant effects of posture on NVC were driven by a 3.8% increase from seated to supine. For AT, mean supine %MCAv increase was greatest in younger (5.44%) versus middle (0.12%) and older-age (0.09%) at T3 (p = 0.005). For VST, mean supine %PCAv increase was greatest at T2 and T3 in middle (10.99%/10.12%) and older-age (17.36%/17.26%) versus younger (9.44%/8.89%) (p = 0.004/p = 0.002). We identified significant age-related NVC effects with VST-induced hyperactivation. This may reflect age-related compensatory processes in supine. Further work is required, using complex stimuli while standing/walking, examining NVC, aging and falls.

Neurovascular coupling methods in healthy individuals using transcranial doppler ultrasonography: A systematic review and consensus agreement.

Neurovascular coupling (NVC) is the perturbation of cerebral blood flow (CBF) to meet varying metabolic demands induced by various levels of neural activity. NVC may be assessed by Transcranial Doppler ultrasonography (TCD), using task activation protocols, but with significant methodological heterogeneity between studies, hindering cross-study comparisons. Therefore, this review aimed to summarise and compare available methods for TCD-based healthy NVC assessments. Medline (Ovid), Scopus, Web of Science, EMBASE (Ovid) and CINAHL were searched using a predefined search strategy (PROSPERO: CRD42019153228), generating 6006 articles. Included studies contained TCD-based assessments of NVC in healthy adults. Study quality was assessed using a checklist, and findings were synthesised narratively. 76 studies (2697 participants) met the review criteria. There was significant heterogeneity in the participant position used (e.g., seated vs supine), in TCD equipment, and vessel insonated (e.g. middle, posterior, and anterior cerebral arteries). Larger, more significant, TCD-based NVC responses typically included a seated position, baseline durations >one-minute, extraneous light control, and implementation of previously validated protocols. In addition, complementary, combined position, vessel insonated and stimulation type protocols were associated with more significant NVC results. Recommendations are detailed here, but further investigation is required in patient populations, for further optimisation of TCD-based NVC assessments.

The complexity of cerebral blood flow regulation: the interaction of posture and vasomotor reactivity.

Arterial carbon dioxide (PaCO2) and posture influence the middle (MCAv) and posterior (PCAv) cerebral artery blood velocitiesbut there is paucity of data about their interaction and need for an integrated model of their effects, including dynamic cerebral autoregulation (dCA). In 22 participants (11 male, age 30.2 ± 14.3 years), blood pressure (BP, Finometer), dominant MCAv and non-dominant PCAv (transcranial Doppler ultrasound), end-tidal CO2 (EtCO2, capnography) and heart rate (HR, ECG) were recorded continuously. Two recordings (R) were taken when the participant was supine (R1, R2), two taken when the participant was sitting (R3, R4), and two taken when the participant was standing (R5, R6). R1, R3 and R5 consisted of 3 minutes of 5% CO2 through a mask and R2, R4 and R6 consisted of 3 minutes of paced hyperventilation. The effects of PaCO2 were expressed with a logistic curve model (LCM) for each parameter. dCA was expressed by the autoregulation index (ARI), dervived by transfer function analysis. Standing shifted LCM to the left for MCAv (p<0.001), PCAv (p<0.001), BP (p=0.03) and ARI (p=0.001); downwards for MCAv and PCAv (both p<0.001), and upwards for HR (p<0.001). For BP, LCM was shifted downwards by sitting and standing (p=0.024). For ARI, the hypercapnic range of LCM was shifted upwards during standing (p<0.001). A more complete mapping of the combined effects of posture and arterial CO2 on the cerebral circulation and peripheral variables can be obtained with the LCM over a broad physiological range of EtCO2 values.

Early neurological deterioration in acute lacunar ischemic stroke: Systematic review of incidence, mechanisms, and prospects for treatment.

BACKGROUND: Cerebral small vessel disease (CSVD) causes between 25% and 30% of all ischemic strokes. In acute lacunar ischemic stroke, despite often mild initial symptoms, early neurological deterioration (END) occurs in approximately 15-20% of patients and is associated with poor functional outcome, yet its mechanisms are not well understood. AIMS: In this review, we systematically evaluated data on: (1) definitions and incidence of END, (2) mechanisms of small vessel occlusion, (3) predictors and mechanisms of END, and (4) prospects for the prevention or treatment of patients with END. SUMMARY OF REVIEW: We identified 67 reports (including 13,407 participants) describing the incidence of END in acute lacunar ischemic stroke. The specified timescale for END varied from <24 h to 3 weeks. The rate of END ranged between 2.3% and 47.5% with a pooled incidence of 23.54% (95% confidence interval (CI) = 21.02-26.05) but heterogeneity was high (I2 = 90.29%). The rates of END defined by National Institutes of Health Stroke Scale (NIHSS) decreases of ⩾1, ⩾2, ⩾3, and 4 points were as follows: 24.17 (21.19-27.16)%, 22.98 (20.48-25.30)%, 23.33 (16.23-30.42)%, and 10.79 (2.09-23.13)%, respectively, with lowest heterogeneity and greatest precision for a cutoff of ⩾2 points. Of the 20/67 studies (30%) reporting associations of END with clinical outcome, 19/20 (95%) reported worse outcomes (usually measured using the modified Rankin score at 90 days or at hospital discharge) in patients with END. In a meta-regression analysis, female sex, hypertension, diabetes, and smoking were associated with END. CONCLUSIONS: END occurs in more than 20% of patients with acute lacunar ischemic stroke and might provide a novel target for clinical trials. A definition of an NIHSS ⩾2 decrease is most used and provides the best between-study homogeneity. END is consistently associated with poor functional outcome. Further research is needed to better identify patients at risk of END, to understand the underlying mechanisms, and to carry out new trials to test potential interventions.

Arterial blood pressure monitoring in stroke cohorts: the impact of reduced sampling rates to optimise remote patient monitoring.

OBJECTIVE: Remote patient monitoring (RPM) beat-to-beat blood pressure (BP) provides an opportunity to measure poststroke BP variability (BPV), which is associated with clinical stroke outcomes. BP sampling interval (SI) influences ambulatory BPV, but RPM BP SI optimisation research is limited. SI and RPM device capabilities require compromises, meaning SI impact requires investigation. Therefore, this study assessed healthy and stroke subtype BPV via optimised BP sampling, aiding sudden BP change identification and potentially assisting cardiovascular event (recurrent stroke) prediction. METHODS: Leicester Cerebral Haemodynamic Database ischaemic [acute ischaemic stroke (AIS), n = 68] and haemorrhagic stroke (intracerebral haemorrhage, n = 12) patient and healthy control (HC, n = 40) baseline BP data were analysed. Intrasubject and interpatient SD (SDi/SDp) represented individual/population variability with synthetically altered SIs. Matched-filter approaches using cross-correlation function detected sudden BP changes. RESULTS: At SIs between 1 and 180 s, SBP and DBP SDi staticised while SDp increased at SI < 30 s. Mean BP and HR SDi and SDp increased at SI < 60s. AIS BPV, normalised to SI1s, increased at SI30s (26%-131%) and SI120s (1%-274%). BPV increased concomitantly with SI. Cross-correlation analysis showed HC and AIS BP sudden change detection accuracy reductions with increasing SI. Positive BP deviation detection fell 48.48% (SI10s) to 78.79% (SI75s) in HC and 67.5% (SI10s) to 100% (SI75s) in AIS. Negative BP deviation detection fell 50% (SI10s) to 82.35% (SI75s) in HC and 52.27% (SI10s) to 95.45% (SI75s) in AIS. CONCLUSION: Sudden BP change detection and BPV are relatively robust to SI increases within certain limits, but accuracy reductions generate unacceptable estimates, considerable within RPM device design. This research warrants further SI optimisation.

The effect of CO2 on the age dependence of neurovascular coupling.

Prior studies have identified variable effects of aging on neurovascular coupling (NVC). Carbon dioxide (CO2) affects both cerebral blood velocity (CBv) and NVC, but the effects of age on NVC under different CO2 conditions are unknown. Therefore, we investigated the effects of aging on NVC in different CO2 states during cognitive paradigms. Seventy-eight participants (18-78 yr), with well-controlled comorbidities, underwent continuous recordings of CBv by bilateral insonation of middle (MCA) and posterior (PCA) cerebral arteries (transcranial Doppler), blood pressure, end-tidal CO2, and heart rate during poikilocapnia, hypercapnia (5% CO2 inhalation), and hypocapnia (paced hyperventilation). Neuroactivation via visuospatial (VS) and attention tasks (AT) was used to stimulate NVC. Peak percentage and absolute change in MCAv/PCAv, were compared between CO2 conditions and age groups (≤30, 31-60, and >60 yr). For the VS task, in poikilocapnia, younger adults had a lower NVC response compared with older adults [mean difference (MD): -7.92% (standard deviation (SD): 2.37), P = 0.004], but comparable between younger and middle-aged groups. In hypercapnia, both younger [MD: -4.75% (SD: 1.56), P = 0.009] and middle [MD: -4.58% (SD: 1.69), P = 0.023] age groups had lower NVC responses compared with older adults. Finally, in hypocapnia, both older [MD: 5.92% (SD: 2.21), P = 0.025] and middle [MD: 5.44% (SD: 2.27), P = 0.049] age groups had greater NVC responses, compared with younger adults. In conclusion, the magnitude of NVC response suppression from baseline during hyper- and hypocapnia, did not differ significantly between age groups. However, the middle age group demonstrated a different NVC response while under hypercapnic conditions, compared with hypocapnia.NEW & NOTEWORTHY This study describes the effects of age on neurovascular coupling under altered CO2 conditions. We demonstrated that both hypercapnia and hypocapnia suppress neurovascular coupling (NVC) responses. Furthermore, that middle age exhibits an NVC response comparable with younger adults under hypercapnia, and older adults under hypocapnia.

Dynamics of Critical Closing Pressure Explain Cerebral Autoregulation Impairment in Acute Cerebrovascular Disease.

INTRODUCTION: Cerebral autoregulation (CA) is impaired in acute ischemic stroke (AIS) and is associated with worse patient outcomes, but the underlying physiological cause is unclear. This study tests whether depressed CA in AIS can be linked to the dynamic responses of critical closing pressure (CrCP) and resistance area product (RAP). METHODS: Continuous recordings of middle cerebral blood velocity (MCAv, transcranial Doppler), arterial blood pressure (BP), end-tidal CO2 and electrocardiography allowed dynamic analysis of the instantaneous MCAv-BP relationship to obtain estimates of CrCP and RAP. The dynamic response of CrCP and RAP to a sudden change in mean BP was obtained by transfer function analysis. Comparisons were made between younger controls (≤50 years), older controls (>50 years), and AIS patients. RESULTS: Data from 24 younger controls (36.4 ± 10.9 years, 9 male), 38 older controls (64.7 ± 8.2 years, 20 male), and 20 AIS patients (63.4 ± 13.8 years, 9 male) were included. Dynamic CA was impaired in AIS, with lower autoregulation index (affected hemisphere: 4.0 ± 2.3, unaffected: 4.5 ± 1.8) compared to younger (right: 5.8 ± 1.4, left: 5.8 ± 1.4) and older (right: 4.9 ± 1.6, left: 5.1 ± 1.5) controls. AIS patients also demonstrated an early (0-3 s) peak in CrCP dynamic response that was not influenced by age. CONCLUSION: These early transient differences in the CrCP dynamic response are a novel finding in stroke and occur too early to reflect underlying regulatory mechanisms. Instead, these may be caused by structural changes to cerebral vasculature.

Blood pressure variability at rest and during pressor challenges in patients with acute ischemic stroke.

INTRODUCTION: Patients with acute ischemic stroke (AIS) have elevated blood pressure (BP) variability (BPV) and reduced baroreflex sensitivity (BRS) at rest for several days after initial stroke symptoms. We aimed to assess BPV and BRS in AIS patients during pressor challenge maneuvers in the acute and subacute phases of stroke. Pressor challenge maneuvers simulate day-to-day activities and can predict the quality of life. METHODS: Continuous beat-to-beat BP and ECG in 15 AIS patients (mean age 69 ±â€…7.5 years) and 15 healthy controls (57 ±â€…16 years) were recorded at rest and during a 5-min rapid head positioning (RHP) paradigm. Patients were assessed within 24 h (acute phase) and 7 days (subacute phase) of stroke onset. Low frequency (LF) SBP power (measure of BPV), LF-α, and combined α-index (measure of BRS) were calculated from the recordings. RESULTS: In the acute phase, at rest, LF-SBP power was higher ( P  = 0.024) and α-index was lower ( P  = 0.006) in AIS patients than in healthy controls. There was no change in LF-SBP during RHP in the patients but in healthy controls, it increased significantly ( P  = 0.018). In the subacute phase, at rest, the alpha-index increased ( P  = 0.037) and LF-SBP decreased ( P  = 0.029) significantly in the AIS patients, however, there was still no rise in the LF-SBP power during RHP ( P  = 0.240). CONCLUSION: AIS patients have a high resting BPV. High resting BPV may be responsible for blunted BPV responses during pressor challenge maneuvers such as RHP, suggesting ongoing autonomic dysfunction and compromised quality of life.

Determinants of the dynamic cerebral critical closing pressure response to changes in mean arterial pressure.

Objective. Cerebral critical closing pressure (CrCP) represents the value of arterial blood pressure (BP) where cerebral blood flow (CBF) becomes zero. Its dynamic response to a step change in mean BP (MAP) has been shown to reflect CBF autoregulation, but robust methods for its estimation are lacking. We aim to improve the quality of estimates of the CrCP dynamic response.Approach. Retrospective analysis of 437 healthy subjects (aged 18-87 years, 218 males) baseline recordings with measurements of cerebral blood velocity in the middle cerebral artery (MCAv, transcranial Doppler), non-invasive arterial BP (Finometer) and end-tidal CO2(EtCO2, capnography). For each cardiac cycle CrCP was estimated from the instantaneous MCAv-BP relationship. Transfer function analysis of the MAP and MCAv (MAP-MCAv) and CrCP (MAP-CrCP) allowed estimation of the corresponding step responses (SR) to changes in MAP, with the output in MCAv (SRVMCAv) representing the autoregulation index (ARI), ranging from 0 to 9. Four main parameters were considered as potential determinants of the SRVCrCPtemporal pattern, including the coherence function, MAP spectral power and the reconstruction error for SRVMAP, from the other three separate SRs.Main results. The reconstruction error for SRVMAPwas the main determinant of SRVCrCPsignal quality, by removing the largest number of outliers (Grubbs test) compared to the other three parameters. SRVCrCPshowed highly significant (p< 0.001) changes with time, but its amplitude or temporal pattern was not influenced by sex or age. The main physiological determinants of SRVCrCPwere the ARI and the mean CrCP for the entire 5 min baseline period. The early phase (2-3 s) of SRVCrCPresponse was influenced by heart rate whereas the late phase (10-14 s) was influenced by diastolic BP.Significance. These results should allow better planning and quality of future research and clinical trials of novel metrics of CBF regulation.

A Multi-Parametric Approach for Characterising Cerebral Haemodynamics in Acute Ischaemic and Haemorrhagic Stroke.

BACKGROUND AND PURPOSE: Early differentiation between acute ischaemic (AIS) and haemorrhagic stroke (ICH), based on cerebral and peripheral hemodynamic parameters, would be advantageous to allow for pre-hospital interventions. In this preliminary study, we explored the potential of multiple parameters, including dynamic cerebral autoregulation, for phenotyping and differentiating each stroke sub-type. METHODS: Eighty patients were included with clinical stroke syndromes confirmed by computed tomography within 48 h of symptom onset. Continuous recordings of bilateral cerebral blood velocity (transcranial Doppler ultrasound), end-tidal CO2 (capnography), electrocardiogram (ECG), and arterial blood pressure (ABP, Finometer) were used to derive 67 cerebral and peripheral parameters. RESULTS: A total of 68 patients with AIS (mean age 66.8 ± SD 12.4 years) and 12 patients with ICH (67.8 ± 16.2 years) were included. The median ± SD NIHSS of the cohort was 5 ± 4.6. Statistically significant differences between AIS and ICH were observed for (i) an autoregulation index (ARI) that was higher in the unaffected hemisphere (UH) for ICH compared to AIS (5.9 ± 1.7 vs. 4.9 ± 1.8 p = 0.07); (ii) coherence function for both hemispheres in different frequency bands (AH, p < 0.01; UH p < 0.02); (iii) a baroreceptor sensitivity (BRS) for the low-frequency (LF) bands that was higher for AIS (6.7 ± 4.2 vs. 4.10 ± 2.13 ms/mmHg, p = 0.04) compared to ICH, and that the mean gain of the BRS in the LF range was higher in the AIS than in the ICH (5.8 ± 5.3 vs. 2.7 ± 1.8 ms/mmHg, p = 0.0005); (iv) Systolic and diastolic velocities of the affected hemisphere (AH) that were significantly higher in ICH than in AIS (82.5 ± 28.09 vs. 61.9 ± 18.9 cm/s), systolic velocity (p = 0.002), and diastolic velocity (p = 0.05). CONCLUSION: Further multivariate modelling might improve the ability of multiple parameters to discriminate between AIS and ICH and warrants future prospective studies of ultra-early classification (<4 h post symptom onset) of stroke sub-types.

Physiological Variability during Prehospital Stroke Care: Which Monitoring and Interventions Are Used?

Prehospital care is a fundamental component of stroke care that predominantly focuses on shortening the time between diagnosis and reaching definitive stroke management. With growing evidence of the physiological parameters affecting long-term patient outcomes, prehospital clinicians need to consider the balance between rapid transfer and increased physiological-parameter monitoring and intervention. This systematic review explores the existing literature on prehospital physiological monitoring and intervention to modify these parameters in stroke patients. The systematic review was registered on PROSPERO (CRD42022308991) and conducted across four databases with citation cascading. Based on the identified inclusion and exclusion criteria, 19 studies were retained for this review. The studies were classified into two themes: physiological-monitoring intervention and pharmacological-therapy intervention. A total of 14 included studies explored prehospital physiological monitoring. Elevated blood pressure was associated with increased hematoma volume in intracerebral hemorrhage and, in some reports, with increased rates of early neurological deterioration and prehospital neurological deterioration. A reduction in prehospital heart rate variability was associated with unfavorable clinical outcomes. Further, five of the included records investigated the delivery of pharmacological therapy in the prehospital environment for patients presenting with acute stroke. BP-lowering interventions were successfully demonstrated through three trials; however, evidence of their benefit to clinical outcomes is limited. Two studies investigating the use of oxygen and magnesium sulfate as neuroprotective agents did not demonstrate an improvement in patient's outcomes. This systematic review highlights the absence of continuous physiological parameter monitoring, investigates fundamental physiological parameters, and provides recommendations for future work, with the aim of improving stroke patient outcomes.

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.

Tratamiento antiagregante plaquetario oral para el ictus isquémico agudo: una revisión Cochrane / Oral antiplatelet therapy for acute ischaemic stroke: a Cochrane review

Pregunta de la revisión. Queríamos comparar la seguridad y la eficacia del tratamiento antiplaquetario oral frente a placebo o ningún tratamiento en personas con ictus isquémico agudo para ver si los antiplaquetarios orales reducían el número de muertes y mejoraban los resultados a largo plazo en los supervivientes. Fundamento. La mayoría de los ictus están causados por una obstrucción repentina de una arteria del cerebro que suele deberse a un coágulo de sangre (lo que se denomina ictus isquémico). El tratamiento inmediato con antiagregantes plaquetarios, como la aspirina, puede evitar la formación de nuevos coágulos y mejorar así la recuperación tras el ictus. Sin embargo, los antiagregantes plaquetarios también pueden provocar hemorragias cerebrales, lo que podría anular sus efectos beneficiosos. Características del estudio. Se identificaron 11 estudios, hasta agosto de 2020, para su inclusión en la revisión. Estos estudios incluyeron 42.226 participantes. Tres eran nuevos ensayos desde la última actualización. Como en la versión anterior de esta revisión, dos estudios aportaron el 96% de los datos. La mayoría de los participantes en la revisión eran ancianos, con una proporción significativa de más de 70 años. Los hombres y las mujeres estaban representados casi por igual en los ensayos. Parecía haber alguna variación en la gravedad del accidente cerebrovascular entre los ensayos incluidos. La duración programada del tratamiento varió de 5 días a 3 meses y el periodo de seguimiento programado varió de 10 días a 6 meses. Resultados clave. La aspirina, en dosis de 160 mg a 300 mg diarios, iniciada en las 48 horas siguientes a la aparición de los síntomas del ictus, salvó vidas y redujo el riesgo de que se produjera un nuevo ictus en las dos primeras semanas... (AU)

Tratamiento antiagregante plaquetario oral para el ictus isquémico agudo: una revisión Cochrane / Oral antiplatelet therapy for acute ischaemic stroke: a Cochrane review

Pregunta de la revisión. Queríamos comparar la seguridad y la eficacia del tratamiento antiplaquetario oral frente a placebo o ningún tratamiento en personas con ictus isquémico agudo para ver si los antiplaquetarios orales reducían el número de muertes y mejoraban los resultados a largo plazo en los supervivientes. Fundamento. La mayoría de los ictus están causados por una obstrucción repentina de una arteria del cerebro que suele deberse a un coágulo de sangre (lo que se denomina ictus isquémico). El tratamiento inmediato con antiagregantes plaquetarios, como la aspirina, puede evitar la formación de nuevos coágulos y mejorar así la recuperación tras el ictus. Sin embargo, los antiagregantes plaquetarios también pueden provocar hemorragias cerebrales, lo que podría anular sus efectos beneficiosos. Características del estudio. Se identificaron 11 estudios, hasta agosto de 2020, para su inclusión en la revisión. Estos estudios incluyeron 42.226 participantes. Tres eran nuevos ensayos desde la última actualización. Como en la versión anterior de esta revisión, dos estudios aportaron el 96% de los datos. La mayoría de los participantes en la revisión eran ancianos, con una proporción significativa de más de 70 años. Los hombres y las mujeres estaban representados casi por igual en los ensayos. Parecía haber alguna variación en la gravedad del accidente cerebrovascular entre los ensayos incluidos. La duración programada del tratamiento varió de 5 días a 3 meses y el periodo de seguimiento programado varió de 10 días a 6 meses. Resultados clave. La aspirina, en dosis de 160 mg a 300 mg diarios, iniciada en las 48 horas siguientes a la aparición de los síntomas del ictus, salvó vidas y redujo el riesgo de que se produjera un nuevo ictus en las dos primeras semanas... (AU)

The effect of hypercapnia on the directional sensitivity of dynamic cerebral autoregulation and the influence of age and sex.

The cerebral circulation responds differently to increases in mean arterial pressure (MAP), compared to reductions in MAP. We tested the hypothesis that this directional sensitivity is reduced by hypercapnia. Retrospective analysis of 104 healthy subjects (46 male (44%), age range 19-74 years), with five minute recordings of middle cerebral blood velocity (MCAv, transcranial Doppler), non-invasive MAP (Finometer) and end-tidal CO2 (capnography) at rest, during both poikilocapnia and hypercapnia (5% CO2 breathing in air) produced MCAv step responses allowing estimation of the classical Autoregulation Index (ARIORIG), and corresponding values for both positive (ARI+D) and negative (ARI-D) changes in MAP. Hypercapnia led to marked reductions in ARIORIG, ARI+D and ARI-D (p < 0.0001, all cases). Females had a lower value of ARIORIG compared to males (p = 0.030) at poikilocapnia (4.44 ± 1.74 vs 4.74 ± 1.48) and hypercapnia (2.44 ± 1.93 vs 3.33 ± 1.61). The strength of directional sensitivity (ARI+D-ARI-D) was not influenced by hypercapnia (p = 0.46), sex (p = 0.76) or age (p = 0.61). During poikilocapnia, ARI+D decreased with age in females (p = 0.027), but not in males. Directional sensitivity was not affected by hypercapnia, suggesting that its origins are more likely to be inherent to the mechanics of vascular smooth muscle than to myogenic pathways.

Point/counterpoint: Cerebrovascular resistance is a flawed concept.

The relationship between cerebral blood flow and blood pressure is a critical part of investigation of cerebral autoregulation. Conventionally, cerebrovascular resistance (CVR) has been used to describe this relationship, but the underlying principles used for this method is flawed in real-world application for several reasons. Despite this, the use of CVR remains entrenched within current literature. This 'Point/Counterpoint' review provides a summary of the flaws in using CVR and explains the benefits of calculating the more accurate critical closing pressure (CrCP) and resistance-area product (RAP) parameters, with support of real-world data.

The role of the autonomic nervous system in cerebral blood flow regulation in stroke: A review.

Stroke is a pathophysiological condition which results in alterations in cerebral blood flow (CBF). The mechanism by which the brain maintains adequate CBF in presence of fluctuating cerebral perfusion pressure (CPP) is known as cerebral autoregulation (CA). Disturbances in CA may be influenced by a number of physiological pathways including the autonomic nervous system (ANS). The cerebrovascular system is innervated by adrenergic and cholinergic nerve fibers. The role of the ANS in regulating CBF is widely disputed owing to several factors including the complexity of the ANS and cerebrovascular interactions, limitations to measurements, variation in methods to assess the ANS in relation to CBF as well as experimental approaches that can or cannot provide insight into the sympathetic control of CBF. CA is known to be impaired in stroke however the number of studies investigating the mechanisms by which this occurs are limited. This literature review will focus on highlighting the assessment of the ANS and CBF via indices derived from the analyses of heart rate variability (HRV), and baroreflex sensitivity (BRS), and providing a summary of both clinical and animal model studies investigating the role of the ANS in influencing CA in stroke. Understanding the mechanisms by which the ANS influences CBF in stroke patients may provide the foundation for novel therapeutic approaches to improve functional outcomes in stroke patients.

Mortality in a Multiethnic Population Attending a One-Stop TIA Clinic.

INTRODUCTION: Studies indicate a 13-27% mortality rate following a transient ischaemic attack (TIA). However, outcomes following TIA/minor stroke since the introduction of rapid-access TIA clinics and prompt vascular risk factor intervention are not known. Specifically, there is paucity of data comparing outcomes between people who are diagnosed with an "acute cerebrovascular" (CV) event or an alternative non-cardiovascular diagnosis (non-CV) in a rapid-access TIA clinic. We aimed to assess the mortality in such a setting. METHODS: A retrospective observational study was undertaken at the Leicester rapid-access secondary care TIA clinic. Data included information collected at the first clinic visit (including comorbidities, and primary diagnosis, categorized as CV and non-CV) and the date of death for people dying during follow-up. RESULTS: 11,524 subjects were included with 33,164 years of follow-up data; 4,746 (41.2%) received a CV diagnosis. The median follow-up time was 2.75 years (interquartile range 1.36-4.32). The crude mortality rate was 37.3 (95% CI: 35.3-39.5) per 1,000 person-years (PTPY). The mortality rate was higher following a CV diagnosis (50.8 [47.2-54.7] PTPY) compared to a non-CV diagnosis (27.9 [25.7-30.4] PTPY), and for males, older people, those of white ethnicity, and people with orthostatic hypotension (OH). DISCUSSION: This study identified possible risk factors associated with a higher mortality in TIA clinic attendees, who may benefit from specific intervention. Future research should explore the underlying causes and the effect of specific targeted management strategies.

Transfer function analysis of dynamic cerebral autoregulation: A CARNet white paper 2022 update.

Cerebral autoregulation (CA) refers to the control of cerebral tissue blood flow (CBF) in response to changes in perfusion pressure. Due to the challenges of measuring intracranial pressure, CA is often described as the relationship between mean arterial pressure (MAP) and CBF. Dynamic CA (dCA) can be assessed using multiple techniques, with transfer function analysis (TFA) being the most common. A 2016 white paper by members of an international Cerebrovascular Research Network (CARNet) that is focused on CA strove to improve TFA standardization by way of introducing data acquisition, analysis, and reporting guidelines. Since then, additional evidence has allowed for the improvement and refinement of the original recommendations, as well as for the inclusion of new guidelines to reflect recent advances in the field. This second edition of the white paper contains more robust, evidence-based recommendations, which have been expanded to address current streams of inquiry, including optimizing MAP variability, acquiring CBF estimates from alternative methods, estimating alternative dCA metrics, and incorporating dCA quantification into clinical trials. Implementation of these new and revised recommendations is important to improve the reliability and reproducibility of dCA studies, and to facilitate inter-institutional collaboration and the comparison of results between studies.