Nathalie Nasr

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.

Autonomic Impairment in Severe Traumatic Brain Injury: A Multimodal Neuromonitoring Study.

Objectives:Autonomic impairment after acute traumatic brain injury has been associated independently with both increased morbidity and mortality. Links between autonomic impairment and increased intracranial pressure or impaired cerebral autoregulation have been described as well. However, relationships between autonomic impairment, intracranial pressure, impaired cerebral autoregulation, and outcome remain poorly explored. Using continuous measurements of heart rate variability and baroreflex sensitivity we aimed to test whether autonomic markers are associated with functional outcome and mortality independently of intracranial variables. Further, we aimed to evaluate the relationships between autonomic functions, intracranial pressure, and cerebral autoregulation. Design:Retrospective analysis of a prospective database. Setting:Neurocritical care unit in a university hospital. Subjects:Sedated patients with severe traumatic brain injury. Measurements and Main Results:Waveforms of intracranial pressure and arterial blood pressure, baseline Glasgow Coma Scale and 6 months Glasgow Outcome Scale were recorded. Baroreflex sensitivity was assessed every 10 seconds using a modified cross-correlational method. Frequency domain analyses of heart rate variability were performed automatically every 10 seconds from a moving 300 seconds of the monitoring time window. Mean values of baroreflex sensitivity, heart rate variability, intracranial pressure, arterial blood pressure, cerebral perfusion pressure, and impaired cerebral autoregulation over the entire monitoring period were calculated for each patient. Two hundred and sixty-two patients with a median age of 36 years entered the analysis. The median admission Glasgow Coma Scale was 6, the median Glasgow Outcome Scale was 3, and the mortality at 6 months was 23%. Baroreflex sensitivity (adjusted odds ratio, 0.9; p = 0.02) and relative power of a high frequency band of heart rate variability (adjusted odds ratio, 1.05; p < 0.001) were individually associated with mortality, independently of age, admission Glasgow Coma Scale, intracranial pressure, pressure reactivity index, or cerebral perfusion pressure. Baroreflex sensitivity showed no correlation with intracranial pressure or cerebral perfusion pressure; the correlation with pressure reactivity index was strong in older patients (age, > 60 yr). The relative power of high frequency correlated significantly with intracranial pressure and cerebral perfusion pressure, but not with pressure reactivity index. The relative power of low frequency correlated significantly with pressure reactivity index. Conclusions:Autonomic impairment, as measured by heart rate variability and baroreflex sensitivity, is significantly associated with increased mortality after traumatic brain injury. These effects, though partially interlinked, seem to be independent of age, trauma severity, intracranial pressure, or autoregulatory status, and thus represent a discrete phenomenon in the pathophysiology of traumatic brain injury. Continuous measurements of heart rate variability and baroreflex sensitivity in the neuromonitoring setting of severe traumatic brain injury may carry novel pathophysiological and predictive information.

Derangement of Cerebral Blood Flow Autoregulation During Intracranial Pressure Plateau Waves as Detected by Time and Frequency-Based Methods

Plateau waves are sudden elevations of intracranial pressure (ICP) above 40 mmHg, lasting at least 5 min, and are associated with cerebral vasodilatation. We studied the performance of several parameters for cerebral autoregulation assessment during 30 plateau waves of 24 patients with traumatic brain injury. Continuous signals were collected for ICP, arterial blood pressure (ABP) and transcranial Doppler flow velocity (FV). Parameters both in the time domain (autoregulation index, ARI and mean flow index, Mx) and the frequency domain (transfer function gain, phase and coherence) were analysed. The role of different inputs, using either ABP or cerebral perfusion pressure (CPP) as input, was also tested.Autoregulation deteriorated from baseline to plateau, which could be demonstrated by a significant decrease in both ARI between ABP and FV (p = 0.013) and ARI between CPP and FV (p = 0.014). There was also a significant increase in Mx between CPP and FV (p = 0.004), but not in Mx between ABP and FV (p = 0.472). From the baseline to plateau, there was a significant increase in coherence between the ABP and FV at the very low frequency (p = 0.004). The transfer function phase and gain, on the other hand, revealed inconsistent performance.

Cerebral vasospasm affects arterial critical closing pressure.

The effect of cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (SAH) on critical closing pressure (CrCP) has not been fully delineated. Using cerebral impedance methodology, we sought to assess the behavior of CrCP during CVS. As CrCP expresses the sum of intracranial pressure (ICP) and vascular wall tension, we also explored its role in reflecting changes in vascular tone occurring in small vessels distal to spasm. This retrospective analysis was performed using recordings from 52 patients, diagnosed with CVS through transcranial Doppler measurements. Critical closing pressure was calculated noninvasively using arterial blood pressure and blood flow velocity. Outcome was assessed at both discharge and 3 months after ictus with the Glasgow Outcome Scale. The onset of CVS caused significant decreases in CrCP (P=0.025), without any observed significant changes in ICP (P=0.134). Vasospasm induced asymmetry, with CrCP ipsilateral to CVS becoming significantly lower than contralateral (P=0.025). Unfavorable outcomes were associated with a significantly lower CrCP after the onset of CVS (discharge: P=0.014; 3 months after SAH: P=0.020). Critical closing pressure is reduced in the presence of CVS in both temporal and spatial assessments. As ICP remained unchanged during CVS, reduced CrCP most probably reflects a lower wall tension in dilated small vessels distal to spasm.

Baroreflex Impairment After Subarachnoid Hemorrhage Is Associated With Unfavorable Outcome

Background and Purpose— Aneurysmal subarachnoid hemorrhage (SAH) is characterized by important changes in the autonomic nervous system with potentially adverse consequences. The baroreflex has a key role in regulating the autonomic nervous system. Its role in SAH outcome is not known. The purpose of this study was to evaluate the association between the baroreflex and the functional 3-month outcome in SAH. Methods— The study used a prospective database of 101 patients hospitalized for SAH. We excluded patients receiving &bgr;-blockers or noradrenaline. Baroreflex sensitivity (BRS) was measured using the cross-correlation method. A good outcome was defined by a Glasgow Outcome Scale score at 4 or 5 at 3 months. Results— Forty-eight patients were included. Median age was 58 years old (36–76 years); women/men: 34/14. The World Federation of Neurosurgery clinical severity score on admission was 1 or 2 for 73% of patients. In the univariate analysis, BRS (P=0.007), sedation (P=0.001), World Federation of Neurosurgery score (P=0.001), Glasgow score (P=0.002), Fisher score (P=0.022), and heart rate (P=0.037) were associated with outcome. The area under the receiver operating characteristic curve for the model with BRS as a single predictor was estimated at 0.835. For each unit increase in BRS, the odds for a good outcome were predicted to increase by 31%. Area under the receiver operating characteristic curve for heart rate alone was 0.670. In the multivariate analysis, BRS (odds ratio, 1.312; 95% confidence interval, 1.048–1.818; P=0.018) and World Federation of Neurosurgery (odds ratio, 0.382; 95% confidence interval, 0.171–0.706; P=0.001) were significantly associated with outcome. Area under the receiver operating characteristic curve was estimated at 0.900. Conclusions— In SAH, early BRS was associated with 3-month outcome. This conclusion requires confirmation on a larger number of patients in a multicentre study.

Cerebral autoregulation in migraine with aura: A case control study

Background Migraine with aura is independently associated with increased risk of ischemic stroke, especially in younger subjects. This association might be related to an impairment of cerebral autoregulation, which normally maintains cerebral blood flow independent of arterial blood pressure variations. Methods Patients aged 30–55, fulfilling ICHD-3 beta criteria for migraine with aura, were prospectively enrolled and compared with gender- and age-matched healthy controls without a history of migraine. Patients and controls with a history of stroke or any disease potentially impairing cerebral autoregulation were excluded. We assessed cerebral autoregulation with two different methods: Transfer function analysis, and the correlation coefficient index Mx. The transfer function phase and gain reflect responses of cerebral blood flow velocities to relatively fast fluctuations of arterial blood pressure, whereas Mx also reflects responses to slower arterial blood pressure fluctuations. Results A total of 22 migraine with aura patients (median age [IQR]: 39.5 [12.5] years) and 22 controls (39 [9.75] years) were included. Transfer function parameters and Mx were not different between patients and controls. However, Mx was inversely correlated with age in patients (ρ = −0.567, p = 0.006) and not in controls (ρ = −0.084, p = 0.509). Mx was also inversely correlated with migraine with aura duration (ρ = −0.617, p = 0.002), suggesting improvement of cerebral autoregulation efficiency with disease duration. Conclusions Cerebral autoregulation did not differ between patients and controls aged 30–55. However, cerebral autoregulation efficiency was strongly correlated with migraine with aura duration. Further studies in younger patients are needed to determine whether cerebral autoregulation is impaired early in the course of disease. Trial Registration NCT02708797.