Robot-Assisted Transcranial Doppler Versus Transthoracic Echocardiography for Right to Left Shunt Detection.

BACKGROUND: Right to left shunt (RLS), including patent foramen ovale, is a recognized risk factor for stroke. RLS/patent foramen ovale diagnosis is made by transthoracic echocardiography (TTE), which is insensitive, transesophageal echocardiography, which is invasive, and transcranial Doppler (TCD), which is noninvasive and accurate but scarce. METHODS: We conducted a prospective, single-arm device clinical trial of robot-assisted TCD (raTCD) versus TTE for RLS diagnosis at 6 clinical sites in patients who presented with an event suspicious for embolic cerebrovascular ischemia from October 6, 2020 to October 20, 2021. raTCD was performed with standard TCD bubble study technique. TTE bubble study was performed per local standards. The primary outcome was rate of RLS detection by raTCD versus TTE. RESULTS: A total of 154 patients were enrolled, 129 evaluable (intent to scan) and 121 subjects had complete data per protocol. In the intent to scan cohort, mean age was 60±15 years, 47% were women, and all qualifying events were diagnosed as ischemic stroke or transient ischemic attack. raTCD was positive for RLS in 82 subjects (64%) and TTE was positive in 26 (20%; absolute difference 43.4% [95% CI, 35.2%-52.0%]; P<0.001). On prespecified secondary analysis, large RLS was detected by raTCD in 35 subjects (27%) versus 13 (10%) by TTE (absolute difference 17.0% [95% CI, 11.5%-24.5%]; P<0.001). There were no serious adverse events. CONCLUSIONS: raTCD was safe and ≈3 times more likely to diagnose RLS than TTE. TTE completely missed or underdiagnosed two thirds of large shunts diagnosed by raTCD. The raTCD device, used by health professionals with no prior TCD training, may allow providers to achieve the known sensitivity of TCD for RLS and patent foramen ovale detection without the need for an experienced operator to perform the test. Pending confirmatory studies, TCD appears to be the superior screen for RLS compared with TTE (funded by NeuraSignal). REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04604015.

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.

The effect of caffeine on dilated cerebral circulation and on diagnostic CO2 reactivity testing.

Reduction of cerebral blood flow by caffeine has been shown in multiple studies. However, the effect of this substance on pathologically dilated cerebral vessels is not clearly defined. The aim of this study was to investigate the effect of caffeine on an already dilated cerebral circulation and specify if these vessels are still able to constrict as a consequence of caffeine stimulation. A second aim of this study was to compare results of cerebral vasomotor CO(2) reactivity testing with and without caffeine ingestion. Seventeen healthy adult volunteers had vasomotor reactivity tested before and thirty minutes after ingestion of 300 mg of caffeine. Each vasomotor reactivity test consisted of velocity measurements from both middle cerebral arteries using transcranial Doppler ultrasound during normocapnia, hypercapnia, and hypocapnia. Hemodynamic data and end-tidal CO(2) (etCO(2)) concentration were also recorded. The vasomotor reactivity (VMR) and CO(2) reactivity were calculated from a measured data pool. At a level of etCO(2)=40 mmHg the resting velocity in the middle cerebral artery (V(MCA)) dropped from 70.7+/-22.8 cm/sec to 60.7 +/- 15.4 cm/sec 30 minutes after caffeine stimulation (14.1% decrease, p<0.001). During hypercapnia of etCO(2)=50 mmHg there was also a significant decline of V(MCA) from 103.1+/-25.4 to 91.4+/-21.8 cm/sec (11.3%, p<0.001). There was not a statistically significant reduction of V(MCA) during hypocapnia. Calculated VMR and CO(2) reactivity before and after caffeine intake were not statistically significant. The presented data demonstrate a significant decrease in cerebral blood flow velocities after caffeine ingestion both in a normal cerebrovascular bed and under conditions of peripheral cerebrovascular vasodilatation. These findings support the important role of caffeine in regulation of CBF under different pathological conditions. Despite significant reactive vasodilatation in the brain microcirculation, caffeine is still able to act as a competitive antagonist of CO(2) on cerebral microvessels. The fact that caffeine may decrease CBF despite significant pathological vasodilatation offers the possibility of therapeutic manipulation in patients with traumatic vasoparalysis. For routine clinical testing of CO(2) reactivity it is not necessary to insist on pre-test dietary restrictions.

Transcranial Doppler grading criteria for basilar artery vasospasm.

OBJECTIVE: Transcranial Doppler (TCD) criteria for basilar artery (BA) vasospasm are poorly defined, and grading criteria for vertebrobasilar vasospasm are unavailable. The purpose of the present study was to define TCD grading criteria for BA vasospasm on the basis of the absolute flow velocities and the intracranial to extracranial flow velocity ratios for the posterior circulation, and to improve the sensitivity and specificity of TCD for diagnosis of BA vasospasm. METHODS: One hundred twenty-three patients with aneurysmal subarachnoid hemorrhage underwent 144 cerebral arteriograms with views of the BA during the acute phase of vasospasm (Days 3-14 after hemorrhage). BA diameters were measured and compared with diameters obtained from baseline arteriograms. Both BA and extracranial vertebral artery flow velocities were measured by TCD within 4 hours before the arteriogram. RESULTS: The velocity ratio between the BA and the extracranial vertebral arteries (VA) strongly correlated with the degree of BA narrowing (r2 = 0.648; P < 0.0001). A ratio higher than 2.0 was associated with 73% sensitivity and 80% specificity for BA vasospasm. A ratio higher than 2.5 with BA velocity greater than 85 cm/s was associated with 86% sensitivity and 97% specificity for BA narrowing of more than 25%. A BA/VA ratio higher than 3.0 with BA velocities higher than 85 cm/s was associated with 92% sensitivity and 97% specificity for BA narrowing of more than 50%. CONCLUSION: The BA/VA ratio improves the sensitivity and specificity of TCD detection of BA vasospasm. On the basis of the BA/VA ratio and BA mean velocities, we suggest new TCD grading criteria for BA vasospasm.

Basilar artery vasospasm and delayed posterior circulation ischemia after aneurysmal subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: The clinical and hemodynamic impacts of basilar artery (BA) vasospasm (VS) after aneurysmal subarachnoid hemorrhage (SAH) are ill-defined. The purpose of the present study was to evaluate the relationship between BA-VS and regional cerebral blood flow (rCBF) with posterior circulation after aneurysmal SAH. METHODS: Daily transcranial Doppler (TCD) measurements of posterior and anterior circulation arteries were conducted in 162 patients with aneurysmal SAH. rCBF to the brain stem (BS) and other brain territories was assessed by multiple single-photon emission computed tomography with (99m)Tc ethyl cysteinate dimer single-photon emission computed tomography (ECD-SPECT) imaging during the course of VS. RESULTS: SPECT imaging showed delayed BS hypoperfusion in 29 patients (17.9%). Of them, 23 patients (79.3%) were found to have BA-VS. Patients with very high BA flow velocities (FVs; >115 cm/s) had a 50% chance of developing delayed BS ischemia. BA-VS was found at a higher rate in patients who experienced reduced rCBF in the cerebellum (56.3%), thalamic nuclei (68.4%), and occipital lobe (81.8%). Although patients with delayed BS hypoperfusion did not present with a higher clinical grade, their clinical outcome was significantly worse (Glasgow Outcome Score after 30 days 2.48+/-1.16 versus 3.3+/-1.27; P=0.001). CONCLUSIONS: These findings suggest for the first time that BA-VS after aneurysmal SAH is associated with hypoperfusion to BS and other posterior circulation territories. The risk for delayed BS ischemia increased significantly when TCD BA-FVs were >115 cm/s.

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.