Physiological Mechanisms and Significance of Intracranial B Waves.

Objective: Recently published studies have described slow spontaneous cerebral blood flow (CBF) and cerebrospinal fluid (CSF) oscillations measured by magnetic resonance imaging (MRI) as potential drivers of brain glymphatic flow, with a similar frequency as intracranial B-waves. Aiming to establish the relationship between these waveforms, we performed additional analysis of frequency and waveform parameters, of our previously published transcranial Doppler (TCD) and intracranial pressure (ICP) recordings of intracranial B waves, to compare to published MRI frequency measurements of CBF and CSF slow oscillations. Patients and Methods: We analyzed digital recordings of B waves in 29 patients with head injury, including middle cerebral artery (MCA) flow velocity (FV), ICP, end tidal CO2, and arterial blood pressure (ABP). A subset of these recordings demonstrated high B wave activity and was further analyzed for parameters including frequency, interaction, and waveform distribution curve features. These measures were compared to published similar measurements of spontaneous CBF and CSF fluctuations evaluated using MRI. Results: In patients with at least 10% amplitude B wave activity, the MCA blood flow velocity oscillations comprising the B waves, had a maximum amplitude at 0.0245 Hz, and time derivative a maximum amplitude at 0.035 Hz. The frequency range of the B waves was between 0.6-2.3 cycles per min (0.011-0.038 Hz), which is in the same range as MRI measured CBF slow oscillations, reported in human volunteers. Waveform asymmetry in MCA velocity and ICP cycles during B waves, was also similar to published MRI measured CBF slow oscillations. Cross-correlation analysis showed equivalent time derivatives of FV vs. ICP in B waves, compared to MRI measured CBF slow oscillations vs. CSF flow fluctuations. Conclusions: The TCD and ICP recordings of intracranial B waves show a similar frequency range as CBF and CSF flow oscillations measured using MRI, and share other unique morphological wave features. These findings strongly suggest a common physiological mechanism underlying the two classes of phenomena. The slow blood flow and volume oscillations causing intracranial B waves appear to be part of a cascade that may provide a significant driving force for compartmentalized CSF movement and facilitate glymphatic flow.

Intraplaque hemorrhage, fibrous cap status, and microembolic signals in symptomatic patients with mild to moderate carotid artery stenosis: the Plaque at RISK study.

BACKGROUND AND PURPOSE: In patients with mild to moderate symptomatic carotid artery stenosis, intraplaque hemorrhage (IPH) and a thin/ruptured fibrous cap (FC) as evaluated with MRI, and the presence of microembolic signals (MESs) as detected with transcranial Doppler, are associated with an increased risk of a (recurrent) stroke. The objective of the present study is to determine whether the prevalence of MES differs in patients with and without IPH and thin/ruptured FC, and patients with only a thin/ruptured FC without IPH. METHODS: In this multicenter, diagnostic cohort study, patients with recent transient ischemic attack or minor stroke in the carotid territory and an ipsilateral mild to moderate carotid artery plaque were included. IPH and FC status were dichotomously scored. Analysis of transcranial Doppler data was done blinded for the MRI results. Differences between groups were analyzed with Fisher exact test. RESULTS: A total of 113 patients were included. Transcranial Doppler measurements were feasible in 105 patients (average recording time, 219 minutes). A total of 26 MESs were detected in 8 of 105 patients. In 44 of 105 plaques IPH was present. In 92 of 105 plaques FC status was assessable, 36 of these had a thin/ruptured FC. No significant difference in the prevalence of MES between patients with and without IPH (P=0.46) or with thick versus thin/ruptured FC (P=0.48) was found. CONCLUSIONS: In patients with a symptomatic mild to moderate carotid artery stenosis, IPH and FC status are not associated with MES. This suggests that MRI and transcranial Doppler provide different information on plaque vulnerability. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01709045.

Time course for autoregulation recovery following severe traumatic brain injury.

OBJECT: The aim of the present study was to evaluate the time course for cerebral autoregulation (AR) recovery following severe traumatic brain injury (TBI). METHODS: Thirty-six patients (27 males and 9 females, mean +/- SEM age 33 +/- 15.1 years) with severe TBI underwent serial dynamic AR studies with leg cuff deflation as a stimulus, until recovery of the AR responses was measured. RESULTS: The AR was impaired (AR index < 2.8) in 30 (83%) of 36 patients on Days 3-5 after injury, and in 19 individuals (53%) impairments were found on Days 9-11 after the injury. Nine (25%) of 36 patients exhibited a poor AR response (AR index < 1) on postinjury Days 12-14, which eventually recovered on Days 15-23. Fifty-eight percent of the patients with a Glasgow Coma Scale score of 3-5, 50% of those with diffuse brain injury, 54% of those with elevated intracranial pressure, and 40% of those with poor outcome had no AR recovery in the first 11 days after injury. CONCLUSIONS: Autoregulation recovery after severe TBI can be delayed, and failure to recover during the 2nd week after injury occurs mainly in patients with a lower Glasgow Coma Scale score, diffuse brain injury, elevated ICP, or unfavorable outcome. The finding suggests that perfusion pressure management should be considered in some of the patients for a period of at least 2 weeks.

Asymmetric dynamic cerebral autoregulatory response to cyclic stimuli.

BACKGROUND AND PURPOSE: Dynamic cerebral autoregulation has been shown to be fast and effective, but it is not well known if the mechanism is symmetric, that is to say, it acts with equal compensatory action to upward as compared with downward abrupt changes in arterial blood pressure (ABP). METHODS: Fourteen patients with head injuries and 10 normal subjects had bilateral transcranial Doppler and continuous ABP recording. Cyclic ABP stimuli were generated by large thigh cuffs, which were rapidly inflated above systolic pressure for 15 seconds alternating with 15 seconds of deflation. At least 8 such cycles were ensemble-averaged and the dynamic autoregulatory gain (AG(up) and AG(dn)) was estimated separately for upward and downward changes in ABP. The results were compared with the autoregulation index using conventional leg cuff releases. RESULTS: In normal subjects, AG(dn) was 0.74+/-0.18 and AG(up) was 0.77+/-0.17 (mean+/-SD); the difference was insignificant. The correlation between AG(dn) and AG(up), however, was weak (r=0.24). In the patients with head injury, AG(dn) was 0.30+/-0.21 and AG(up) was 1.27+/-0.76, the difference being highly significant (P<0.001). There was a negative relationship between AG(dn) and AG(up) (r=-0.33). Autoregulation index correlated well with AG(dn) (r=0.79) and weakly negatively with AG(up) (r=-0.47). CONCLUSIONS: A strongly asymmetric dynamic response of the cerebral autoregulation was seen the majority of patients with head injury. It might also have been present, albeit to a lesser degree, in the normal subjects. The findings suggest that nonlinear effects may be present in the operation of the cerebral autoregulation mechanism.

Cerebral autoregulation and vasomotor reactivity.

Various aspects of the cerebral blood-flow regulation can be assessed by transcranial Doppler (TCD). This chapter describes and discusses the approaches that have been reported in the literature. The steady-state characteristics of the cerebral autoregulation can be determined by changing the blood pressure level, and calculating the response of the vasomotors. Moreover, the lower limit of the autoregulatory 'plateau' can be investigated after lowering the blood pressure by pharmacological means. The excellent time-resolution of the TCD technique also facilitates the determination of the quasi-stationary and dynamic aspects of the autoregulatory response. The leg-cuff method shows that regulatory action is very fast, compensating for a sharp drop in blood pressure within seconds. Less intrusively, the autoregulatory characteristics can be assessed from recordings of spontaneous variations in blood pressure. Transfer function methods describe the faster aspects of the mechanism, while correlation techniques reveal the quasi-stationary characteristics. However, the repeatability and accuracy of methods based on spontaneous fluctuations are probably less than those of stimulus-response tests. In this chapter, the various CO2 and acetazolamide approaches that determine vasomotor reactivity are described and discussed.

Ambulatory transcranial Doppler cerebral embolic signal detection in symptomatic and asymptomatic carotid stenosis.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) ultrasound can detect asymptomatic emboli in carotid stenosis. Current systems are nonportable and can only record for short durations. A novel ambulatory TCD system allows prolonged recording. We applied this to patients with symptomatic and asymptomatic carotid stenosis to determine patterns of embolization in the 2 conditions and optimal recording protocols. METHODS: Ambulatory TCD recordings were performed in 12 symptomatic and 15 asymptomatic carotid stenosis (> or =50%) patients for 8 hours and then repeated on a second occasion. RESULTS: Nine (75%) of symptomatic subjects had embolic signals during the first recording. In this group, repeating the recording did not increase the proportion of positive patients. In asymptomatic patients, 4 (26.7%) had embolic signals on 1 recording, and this proportion increased to 46.7% after 2 recordings. There was significant clustering of embolic signals demonstrating that the process was nonrandom. CONCLUSIONS: Ambulatory TCD is possible in patients with carotid artery stenosis. By increasing the duration of recording, additional information is provided, particularly in asymptomatic patients. Our results also demonstrate clustering of embolic signals. Our study provides baseline data to allow studies in both asymptomatic and symptomatic carotid stenosis to be planned.

Long-term ambulatory monitoring for cerebral emboli using transcranial Doppler ultrasound.

BACKGROUND AND PURPOSE: Transcranial Doppler (TCD) monitoring for asymptomatic cerebral emboli is currently limited to short recordings by equipment size, restricting its clinical usefulness. We have developed a first ambulatory TCD system, evaluated it in at-risk patient groups, and used it to study the pattern of embolization in patients with symptomatic carotid stenosis. METHODS: The system comprises an 18x11.5x3.2 cm battery-powered Doppler unit (425 g) and a 13-mm servo-controlled 2 MHz transducer probe. The quadrature raw Doppler signal is stored on flash-disk. An autosearch algorithm restores vessel insonation should signal quality fall. Initial evaluation was in 20 ambulatory stroke patients. Subsequently, 12 recently symptomatic carotid patients had recordings for > or =5 hours. RESULTS: Recordings were well tolerated and a median of 96% of Doppler signal was suitable for analysis. Embolic signals were detected in 11 of the 12 symptomatic carotid patients. There was marked temporal variability in embolization and prolonging the recording increased the yield of embolic signal positive patients from 58% at 30 minutes to 92% at 150 minutes. In 3 subjects with frequent embolic signals, significant temporal clustering of embolic signals was observed. CONCLUSIONS: We have developed the first ambulatory TCD system. Good-quality recordings of > or =5 hours can be obtained. In view of the demonstrated temporal variability in embolization, this technique is likely to improve the predictive value of recording for asymptomatic embolic signals and may be particularly useful in patients in whom embolic signals are relatively infrequent, such as those with asymptomatic carotid stenosis and atrial fibrillation.

Dynamic pressure--flow velocity relationships in the human cerebral circulation.

BACKGROUND AND PURPOSE: The pressure-flow velocity relationship in the cerebral circulation is characterized by the critical closing pressure (CCP), which is the pressure at which flow ceases, and the linear slope of a plot between pressure and flow velocity. It has been suggested, but not validated, that CCP can be determined from arterial blood pressure (ABP) and transcranial Doppler (TCD) recordings during the cardiac cycle. We studied a group of patients in whom ventricular fibrillation (VF) was induced. The time interval before defibrillation enabled calculation of CCP from data in which flow approached zero. These estimates were compared with values calculated before and after fibrillation and during regular heartbeats. METHODS: TCD velocities and ABP in the radial artery were recorded before, during, and after 28 episodes of VF in 13 patients. CCPs were calculated by 3 different methods: (1) linear extrapolation from data during VF (gold standard); (2) linear extrapolation from normal heartbeat data; and (3) first harmonic Fourier filtering of normal heartbeat data. RESULTS: The CCP during VF calculated from long diastoles was 32.9+/-11 mm Hg (mean+/-SD). The regular heartbeat estimate was 6.0+/-4.3 mm Hg lower (P<0.05). The CCP estimate with the use of a Fourier filter was 1.4+/-3.9 mm Hg (P=NS) lower than during VF. During hyperemia after defibrillation, the CCP decreased by 13.3 mm Hg, while velocity increased by 63%. The decrease in CCP could explain half of the increase in flow velocity during hyperemia. CONCLUSIONS: CCP can be accurately estimated from regular heartbeat data and is an important factor in regulation of the cerebral circulation.

Cerebral blood flow and dynamic cerebral autoregulation during ethanol intoxication and hypercapnia.

More than one-third of patients diagnosed with head injury are intoxicated with ethanol. Most clinical and animal studies have shown alcohol to have a deleterious impact in the setting of cerebrovascular trauma; however, there are also data showing neuroprotective effects in low ethanol doses. Human studies using imaging modalities suggest that small doses of alcohol produce cerebral vasodilatation and higher doses cerebral vasoconstriction. The aim of this study was to investigate the effect of ethanol intake on dynamic cerebral autoregulation and velocities in the middle cerebral arteries, and compare these changes with the effects of hypercapnia. Dynamic cerebral autoregulation and cerebral blood flow velocities were analysed before and after alcohol intake (1.1 g/kg of body weight) in six adult volunteers. Cerebral blood flow velocities in both middle cerebral arteries were monitored continuously by transcranial Doppler. A value for dynamic cerebral autoregulation was calculated from the rate of increase in middle cerebral artery velocities after a rapid-step decrease in arterial blood pressure. A sudden decrease in blood pressure was achieved by the release of previously inflated large blood pressure cuffs around the subject's thighs. Three volunteers were also tested before alcohol intake with CO(2) challenge (breathing 6% CO(2)) during the autoregulation procedure. Blood alcohol level reached 90 mg/dl approximately 60 min after ethanol ingestion. Cerebral blood velocities increased by 8% from baseline for uncorrected end-tidal (et) CO(2) and by 24% for correction to et CO(2)=40. Dynamic cerebral autoregulation measured as an autoregulation index decreased from 4.3+/-1.3 to 2.9+/-1.1 (p=0.089), which did not reach statistical significance. During hypercapnic conditions, dynamic cerebral autoregulation dropped from 4+/-0.8 to 0.9+/-0.9. In conclusion, mild alcohol intoxication caused cerebral vasodilatation with a subsequent increase in cerebral blood flow of 8-24%. Dynamic cerebral autoregulation was not found to be significantly impaired by ethanol. Hypercapnia almost completely destroys the physiological autoregulatory mechanism. A mild hyper-ventilation to etCO(2)=34-36 may be a compensatory contra-measure for ethanol-induced vasodilatation in the setting of head trauma.

Autoregulatory response and CO2 reactivity of the basilar artery.

BACKGROUND AND PURPOSE: Transcranial Doppler has been extensively used to measure cerebrovascular control mechanisms, including autoregulation in humans and in patients with cerebrovascular diseases. There have been sufficient reports on the measurement of normal autoregulatory response (AR) and CO2 reactivity (CR) of the middle cerebral artery (MCA) but few reports of these indices for the basilar artery (BA). We measured AR and CR in the BA in healthy volunteers to determine normal values and compared them with simultaneous measurements made in the MCA. METHODS: Sixteen normal subjects were enrolled. Time-averaged mean velocities of maximum blood flow in the BA and MCA were continuously and simultaneously monitored by using transcranial Doppler along with continuous measurement of mean arterial blood pressure (MABP). Values were obtained during rest, alterations of end-tidal PaCO2 (ETCO2), and acute decrease and recovery of MABP. AR was evaluated by using the thigh cuff method and graded by the standard dynamic autoregulatory index (ARI), with values between 0 and 9. CR was measured as percentage change in time-averaged mean velocity per mm Hg ETCO2. RESULTS: The mean age of 16 subjects was 27.38+/-8.50 years. Average baseline values for MABP and ETCO2 were 82.29+/-7.10 and 42.75+/-3.77 mm Hg, respectively. Mean ARI was 4.62+/-1.26 for the BA and was 4.77+/-1.23 for the MCA (n=15) (P=0.598). Average CR was 2.54+/-0.39%/mm Hg ETCO2 for the BA and 2.51+/-0.29%/mm Hg ETCO2 for the MCA (n=16) (P=0.686). CONCLUSIONS: Our study demonstrates that ARI and CR values for the BA are similar to those for the MCA.

Transcranial Doppler assessment of cerebral vasospasm.

This review summarizes the use of transcranial Doppler (TCD) for assessment of cerebral vasospasm. The basic hemodynamic principles are presented, and used as a basis for discussing findings and interpretation methods. The need for additional information and measurements to correctly interpret TCD velocities is analyzed, and the use of a special extracranial Doppler technique is recommended. The advantages and limitations of the 'Lindegaard Index' (LI) are discussed. The recent advances in the use of TCD for cerebral autoregulation testing are opening up a new and promising avenue in diagnosis, monitoring and treatment of cerebral vasospasm.