The natural history of the cerebral blood flow regulation after acute ischaemic stroke

Acute stroke is known to lead to impairment of cerebral blood flow (CBF) regulation, but its natural history and techniques for its comprehensive assessment have not been previously reported. Noninvasive measurements of blood pressure (BP), end-tidal CO2 and CBF velocity (CBFv, using transcranial Doppler ultrasound) during active, passive and motor imagery paradigms were performed in healthy older controls (n=27) and in stroke patients (n=27). Two innovative analytical techniques were firstly used in stroke studies: subcomponent analysis and multivariate dynamic modeling. In controls, significant increase in CBFv during the paradigms with no significant difference in the response amplitude was found. A reproducibility study, not previously reported, was also performed. Following acute stroke, subcomponents analysis revealed a decrease of CBFv response to the passive paradigm and impairment of the myogenic pathways of CBF regulation. Multivariate dynamic modeling removed the influences of BP and PaCO[subscript 2] showing that the reduced CBFv response to neural activation was directly related and better expressed by the contribution of the stimulation component, instead of the CBFv raw change. The contribution of motor imagery in the CBFv increase was lower compared to the other two paradigms. Impairment of cerebrovascular reactivity to CO[subscript 2] was also detected by the model, without the need of performing specific tests for this purpose. The natural history of CBF regulation revealed a deterioration of control mechanisms in both the acute (< 72h) and subacute (2 weeks) phases, reaching the controls’ levels in the chronic phases (1 and 3 months). It has been demonstrated in this thesis that CBF regulation changes significantly over time after stroke (particularly in the first weeks after onset), having potential impact not only immediately post ictus but also during the subsequent rehabilitation phase

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 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 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

CAAos platform: an integrated platform for analysis of cerebral hemodynamics data

ObjectiveThe purpose of this article is to introduce the readers to the concept and structure of CAAos (Cerebral Autoregulation Assessment Open Source) platform, and provide evidence of its functionality.ApproachCAAos platform is a new open-source software research tool, developed in Python 3 language, that combines existing and novel methods for interactive visual inspection, batch processing and analysis of multichannel records. The platform is scalable, allowing for customization and inclusion of new tools.Main resultsCurrently CAAos platform is composed of two main modules, preprocessing (containing artefact removal, filtering and signal beat to beat extraction tools) and cerebral autoregulation (CA) analysis modules. Two methods for assessing CA have been implemented into CAAos platform: transfer function analysis (TFA) and autoregulation index (ARI). In order to provide validation of TFA and ARI estimates derived from CAAos platform, the results were compared with those derived from two other algorithms. Validation was performed using data from twenty-eight participants, corresponding to 13 acute ischemic stroke patients and 13 age- and sex-matched control subjects. Agreement between estimates was assessed by intraclass correlation coefficient and Bland-Altman analysis. No significant statistical difference between algorithms was found. Moreover, there was an excellent correspondence between the curves of all parameters analysed, with intraclass correlation coefficient ranging from 0.98 (95%CI 0.976-0.999) to 1.00 (95%CI 1 -1). The mean differences revealed a very small magnitude bias indicating an excellent agreement between the estimates.SignificanceAs open-source software, the source code for the software is freely available for non-commercial use, reducing barriers to performing CA analysis, allowing inspection of the inner-workings of the algorithms, and facilitating networked activities with common standards. CAAos platform is a tailored software solution for the scientific community in the cerebral hemodynamic field and contributes to increasing use and reproducibility of CA assessment

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

Abstract 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

The Effects of Induction and Treatment of Intracranial Hypertension on Cerebral Autoregulation: An Experimental Study

Background. This study aimed to analyse cerebral autoregulation (CA) during induction and treatment of intracranial hypertension (ICH) in an experimental model. Materials and Methods. Landrace and Duroc piglets were divided into mild and severe ICH groups. Four or seven millilitres of saline solution was infused into paediatric bladder catheter inserted in the parietal lobe (balloon inflation). After 1.5 h, a 3% saline solution was infused via venous catheter, and 30 min later, the bladder catheter balloon was deflated (surgery). The cerebral static autoregulation (sCA) index was evaluated using cerebral blood flow velocities (CBFV) obtained with Doppler ultrasound. Results. Balloon inflation increased ICP in both groups. The severe ICH group showed significantly lower sCA index values (p=0.001, ANOVA) after balloon inflation (ICH induction) and a higher sCA index after saline injection (p=0.02) and after surgery (p=0.04). ICP and the sCA index were inversely correlated (r=−0.68 and p<0.05). CPP and the sCA index were directly correlated (r=0.74 and p<0.05). Conclusion. ICH was associated with local balloon expansion, which triggered CA impairment, particularly in the severe ICH group. Moreover, ICP-reducing treatments were associated with improved CA in subjects with severe ICH