Regulation of the cerebral circulation: bedside assessment and clinical implications

The regulation of the cerebral circulation relies on the complex interplay between cardiovascular, respiratory, and neural physiology. In health, these physiologic systems act to maintain an adequate cerebral blood flow (CBF) through modulation of hydrodynamic parameters; the resistance of cerebral vessels, and the arterial, intracranial, and venous pressures. In critical illness, however, one or more of these parameters can be compromised raising the possibility of disturbed CBF regulation and its pathophysiologic sequelae. The rigorous assessment of the cerebral circulation requires not only measuring CBF and its hydrodynamic determinants but also assessing the stability of CBF in response to changes in arterial pressure (cerebral autoregulation), the reactivity of CBF to a vasodilator (CO₂ reactivity for example), and the dynamic regulation of arterial pressure (baroreceptor sensitivity). Ideally, cerebral circulation monitors in critical care should be continuous, physically robust, allow for both regional and global CBF assessment, and be conducive to application at the bedside. The regulation of the cerebral circulation is impaired not only in primary neurologic conditions that affect the vasculature such as subarachnoid haemorrhage and stroke, but also in conditions that affect the regulation of intracranial pressure (such as traumatic brain injury and hydrocephalus) or arterial blood pressure (sepsis, or cardiac dysfunction). Importantly, this impairment is often associated with poor patient outcome. At present, the assessment of the cerebral circulation is primarily used as a research tool to elucidate pathophysiology or prognosis. However, when combined with other physiologic signals and online analytical techniques, cerebral circulation monitoring has the appealing potential to not only prognosticate patients, but also direct critical care management.JD is supported by a Woolf Fisher scholarship (NZ). MC is partially supported by the NIHR

Can interhemispheric desynchronization of cerebral blood flow anticipate upcoming vasospasm in aneurysmal subarachnoid haemorrhage patients?

BACKGROUND: Asymmetry of cerebral autoregulation (CA) was demonstrated in patients after aneurysmal subarachnoid haemorrhage (aSAH). A classical method for CA assessment requires simultaneous measurement of both arterial blood pressure (ABP) and cerebral blood flow velocity (CBFV). In this study, we have proposed a cerebral blood flow asymmetry index based only on CBFV and analysed its association with the occurrence of vasospasm after aSAH. NEW METHOD: The phase shifts (PS) between slow oscillations in left and right CBFV (side-to-side PS) and between ABP and CBFV (CBFV-ABP PS) were estimated using multichannel matching pursuit (MMP) and cross-spectral analysis. RESULTS: We retrospectively analysed data collected from 45 aSAH patients (26 with vasospasm). Data were analysed up to 7th day after aSAH unless the vasospasm was detected earlier. A progressive asymmetry, manifested by a gradual increase in side-to-side PS on consecutive days after aSAH, was observed in patients who developed vasospasm (Radj2 = 0.14, p = 0.009). In these patients, early side-to-side PS was more positive than in patients without vasospasm (2.8° ± 5.6° vs -1.7° ± 5.7°, p = 0.011). No such a difference was found in CBFV-ABP PS. Patients with positive side-to-side PS were more likely to develop vasospasm than patients with negative side-to-side PS (21/7 vs 5/12, p = 0.0047). COMPARISON WITH EXISTING METHOD: MMP, in contrast to the spectral approach, accounts for non-stationarity of analysed signals. MMP applied to the PS estimation reflects the cerebral blood flow asymmetry in aSAH better than the spectral analysis. CONCLUSIONS: Changes in side-to-side PS might be helpful to identify patients who are at risk of vasospasm

Association of transcranial Doppler blood flow velocity slow waves with delayed cerebral ischemia in patients suffering from subarachnoid hemorrhage: a retrospective study.

BACKGROUND: Cerebral vasospasm (VS) and delayed cerebral ischemia (DCI) constitute major complications following subarachnoid hemorrhage (SAH). A few studies have examined the relationship between different indices of cerebrovascular dynamics with the occurrence of VS. However, their potential association with the development of DCI remains elusive. In this study, we investigated the pattern of changes of different transcranial Doppler (TCD)-derived indices of cerebrovascular dynamics during vasospasm in patients suffering from subarachnoid hemorrhage, dichotomized by the presence of delayed cerebral ischemia. METHODS: A retrospective analysis was performed using recordings from 32 SAH patients, diagnosed with VS. Patients were divided in two groups, depending on development of DCI. Magnitude of slow waves (SWs) of cerebral blood flow velocity (CBFV) was measured. Cerebral autoregulation was estimated using the moving correlation coefficient Mxa. Cerebral arterial time constant (tau) was expressed as the product of resistance and compliance. Complexity of CBFV was estimated through measurement of sample entropy (SampEn). RESULTS: In the whole population (N = 32), magnitude of SWs of ipsilateral to VS side CBFV was higher during vasospasm (4.15 ± 1.55 vs before: 2.86 ± 1.21 cm/s, p < 0.001). Ipsilateral SWs of CBFV before VS had higher magnitude in DCI group (N = 19, p < 0.001) and were strongly predictive of DCI, with area under the curve (AUC) = 0.745 (p = 0.02). Vasospasm caused a non-significant shortening of ipsilateral values of tau and increase in SampEn in all patients related to pre-VS measurements, as well as an insignificant increase of Mxa in DCI related to non-DCI group (N = 13). CONCLUSIONS: In patients suffering from subarachnoid hemorrhage, TCD-detected VS was associated with higher ipsilateral CBFV SWs, related to pre-VS measurements. Higher CBFV SWs before VS were significantly predictive of delayed cerebral ischemia

Robotic Semi-Automated Transcranial Doppler Assessment of Cerebrovascular Autoregulation in Post Concussional Syndrome: Methodological Considerations

Abstract Introduction Post-concussive syndrome (PCS) refers to a constellation of physical, cognitive, and emotional symptoms after traumatic brain injury (TBI). Despite its incidence, the underlying mechanisms are unclear. We hypothesised that impaired cerebral autoregulation (CA) is a contributor. Method A prospective, observational study was integrated into outpatient clinics at a tertiary neurosurgical centre. Data points included: demographics, symptoms (Post-Concussion Symptom Scale [PCSS]), neuropsychological assessment (Cambridge Neuropsychological Test Automated-Battery [CANTAB]) and cerebrovascular metrics (Mxa co-efficient and the transient hyperaemic-response ratio [THRR]) - via transcranial Doppler (TCD), plethysmography and bespoke software (ICM+). Results 12 participants were recruited with 2 excluded after unsuccessful cerebrovascular TCD insonation. 10 participants (5 TBI patients, 5 healthy controls) were included in the analysis (median age 26.5, male:female 7:3). Median PCSS scores were 6/126 (TBI subgroup). Median CANTAB percentiles were 78 (healthy controls) and 25 (TBI). Mxa was calculated for 90% and THRR for 50% of participants. Median study time was 127.5 minutes and feedback (n = 6) highlighted the perceived acceptability of the study. Conclusions This pilot study has demonstrated a feasible and reproducible assessment of PCS and CA metrics (non-invasively) in a real-world setting. By scaling this methodology, we hope to test whether CA changes are correlated with symptomatic PCS in patients post-TBI. </jats:sec

Baroreflex sensitivity and heart rate variability are predictors of mortality in patients with aneurysmal subarachnoid haemorrhage.

OBJECT: We aimed to investigate the link between the autonomic nervous system (ANS) impairment, assessed using baroreflex sensitivity (BRS) and heart rate variability (HRV) indices, and mortality after aneurysmal subarachnoid haemorrhage (aSAH). METHODS: A total of 57 patients (56 ± 18 years) diagnosed with aSAH were retrospectively enrolled in the study, where 25% of patients died in the hospital. BRS was calculated using a modified cross-correlation method. Time- and frequency-domain HRV indices were calculated from a time-series of systolic peak intervals of arterial blood pressure signals. Additionally, cerebral autoregulation (CA) was assessed using the mean velocity index (Mxa), where Mxa > 0 indicates impaired CA. RESULTS: Both BRS and HRV indices were lower in non-survivors than in survivors. The patients with disturbed BRS and HRV had more extensive haemorrhage in the H-H scale (p = .040) and were more likely to die (p = .013) when compared to patients with the intact ANS. The logistic regression model for mortality included: the APACHE II score (p = .002; OR 0.794) and the normalised high frequency power of the HRV (p < <.001; OR 0.636). A positive relationship was found between the Mxa and BRS (R = 0.48, p = .003), which suggests that increasing BRS is moderately strongly associated with worsening CA. CONCLUSION: Our results indicated that lower values of HRV indices and BRS correlate with mortality and that there is a link between cerebral dysautoregulation and the analysed estimates of the ANS in aSAH patients

Exactly solvable Richardson–Gaudin models and their applications

3 pages, 1 table, 1 figure.--PACS nrs.: 21.60.Cs, 21.60.Fw, 02.30.Ik.--Arxiv pre-print available at: http://arxiv.org/abs/math-ph/0609022v1We first show that the quantum pairing problem can be mapped exactly on to a classical electrostatic problem in two dimensions and then use this analogy to obtain a pictorial representation of how superconductivity arises in a finite fermionic system. Specific application to the nuclei 114−116Sn suggests some new insight into the evolution of pairing correlations in a quantum system with few active particles. We also summarize other recent work on exactly solvable pairing models, including their applications in a wide variety of strongly correlated quantum systems.The work reported herein was supported in part by the US National Science Foundation under grant no PHY-0140036 and in part by the Spanish DGI under grant no BFM2003-05316-C02-02.Peer reviewe

Robotic Semi-Automated Transcranial Doppler Assessment of Cerebrovascular Autoregulation in Post-Concussion Syndrome: Methodological Considerations.

Post-concussion syndrome (PCS) refers to a constellation of physical, cognitive, and emotional symptoms after traumatic brain injury (TBI). Despite its incidence and impact, the underlying mechanisms of PCS are unclear. We hypothesized that impaired cerebral autoregulation (CA) is a contributor. In this article, we present our protocol for non-invasively assessing CA in patients with TBI and PCS in a real-world clinical setting. A prospective, observational study was integrated into outpatient clinics at a tertiary neurosurgical center. Data points included: demographics, symptom profile (Post-Concussion Symptom Scale [PCSS]) and neuropsychological assessment (Cambridge Neuropsychological Test Automated-Battery [CANTAB]). Cerebrovascular metrics (nMxa co-efficient and the transient hyperaemic-response ratio [THRR]) were collected using transcranial Doppler (TCD), finger plethysmography, and bespoke software (ICM+). Twelve participants were initially recruited but 2 were excluded after unsuccessful insonation of the middle cerebral artery (MCA); 10 participants (5 patients with TBI, 5 healthy controls) were included in the analysis (median age 26.5 years, male to female ratio: 7:3). Median PCSS scores were 6/126 for the TBI patient sub-groups. Median CANTAB percentiles were 78 (healthy controls) and 25 (TBI). nMxa was calculated for 90% of included patients, whereas THRR was calculated for 50%. Median study time was 127.5 min and feedback (n = 6) highlighted the perceived acceptability of the study. This pilot study has demonstrated a reproducible assessment of PCS and CA metrics (non-invasively) in a real-world setting. This protocol is feasible and is acceptable to participants. By scaling this methodology, we hope to test whether CA changes are correlated with symptomatic PCS in patients post-TBI

Comparison of frequency and time domain methods of assessment of cerebral autoregulation in traumatic brain injury.

The impulse response (IR)-based autoregulation index (ARI) allows for continuous monitoring of cerebral autoregulation using spontaneous fluctuations of arterial blood pressure (ABP) and cerebral flow velocity (FV). We compared three methods of autoregulation assessment in 288 traumatic brain injury (TBI) patients managed in the Neurocritical Care Unit: (1) IR-based ARI; (2) transfer function (TF) phase, gain, and coherence; and (3) mean flow index (Mx). Autoregulation index was calculated using the TF estimation (Welch method) and classified according to the original Tiecks' model. Mx was calculated as a correlation coefficient between 10-second averages of ABP and FV using a moving 300-second data window. Transfer function phase, gain, and coherence were extracted in the very low frequency (VLF, 0 to 0.05 Hz) and low frequency (LF, 0.05 to 0.15 Hz) bandwidths. We studied the relationship between these parameters and also compared them with patients' Glasgow outcome score. The calculations were performed using both cerebral perfusion pressure (CPP; suffix 'c') as input and ABP (suffix 'a'). The result showed a significant relationship between ARI and Mx when using either ABP (r=-0.38, P<0.001) or CPP (r=-0.404, P<0.001) as input. Transfer function phase and coherence_a were significantly correlated with ARI_a and ARI_c (P<0.05). Only ARI_a, ARI_c, Mx_a, Mx_c, and phase_c were significantly correlated with patients' outcome, with Mx_c showing the strongest association.This is the accepted manuscript. The final version's available from Nature Publishing at http://dx.doi/10.1038/jcbfm.2014.192

What comes first? The dynamics of cerebral oxygenation and blood flow in response to changes in arterial pressure and intracranial pressure after head injury

Background Brain tissue partial oxygen pressure (PbtO2) and near-infrared spectroscopy (NIRS) are novel methods to evaluate cerebral oxygenation. We studied the response patterns of PbtO2, NIRS, and cerebral blood flow velocity (CBFV) to changes in arterial pressure (AP) and intracranial pressure (ICP). Methods Digital recordings of multimodal brain monitoring from 42 head-injured patients were retrospectively analysed. Response latencies and patterns of PbtO2, NIRS-derived parameters [tissue oxygenation index (TOI) and total haemoglobin index (THI)], and CBFV reactions to fluctuations of AP and ICP were studied. Results One hundred and twenty-one events were identified. In reaction to alterations of AP, ICP reacted first [4.3 s; inter-quartile range (IQR) −4.9 to 22.0 s, followed by NIRS-derived parameters and CBFV (10.9 s; IQR: −5.9 to 39.6 s, 12.1 s; IQR: −3.0 to 49.1 s, 14.7 s; IQR: −8.8 to 52.3 s for THI, CBFV, and TOI, respectively), with PbtO2 reacting last (39.6 s; IQR: 16.4 to 66.0 s). The differences in reaction time between NIRS parameters and PbtO2 were significant (P<0.001). Similarly when reactions to ICP changes were analysed, NIRS parameters preceded PbtO2 (7.1 s; IQR: −8.8 to 195.0 s, 18.1 s; IQR: −20.6 to 80.7 s, 22.9 s; IQR: 11.0 to 53.0 s for THI, TOI, and PbtO2, respectively). Two main patterns of responses to AP changes were identified. With preserved cerebrovascular reactivity, TOI and PbtO2 followed the direction of AP. With impaired cerebrovascular reactivity, TOI and PbtO2 decreased while AP and ICP increased. In 77% of events, the direction of TOI changes was concordant with PbtO2. Conclusions NIRS and transcranial Doppler signals reacted first to AP and ICP changes. The reaction of PbtO2 is delayed. The results imply that the analysed modalities monitor different stages of cerebral oxygenatio