The results support our hypothesis and may lead to a technique for assessing the competence of cerebral autoregulation.

Although the assessment of dynamic cerebral autoregulation (CA) based on measurements of spontaneous fluctuations in arterial blood pressure (ABP) and cerebral blood flow (CBF) is a convenient and much used method, there remains uncertainty about its reliability. We tested the effects of increasing ABP variability, provoked by a modification of the thigh cuff method, on the ability of the autoregulation index to discriminate between normal and impaired CA, using hypercapnia as a surrogate for dynamic CA impairment. In 30 healthy volunteers, ABP (Finapres) and CBF velocity (CBFV, transcranial Doppler) were recorded at rest and during 5% CO 2 breathing, with and without pseudo-random sequence inflation and deflation of bilateral thigh cuffs. The application of thigh cuffs increased ABP and CBFV variabilities and was not associated with a distortion of the CBFV step response estimates for both normocapnic and hypercapnic conditions (P ¼ 0.59 and P ¼ 0.96, respectively). Sensitivity and specificity of CA impairment detection were improved with the thigh cuff method, with the area under the receiver-operator curve increasing from 0.746 to 0.859 (P ¼ 0.031). We conclude that the new method is a safe, efficient, and appealing alternative to currently existing assessment methods for the investigation of the status of CA.

SummaryTranscranial Doppler ultrasonography measures cerebral blood flow velocity (CBFv) of basal intracranial vessels and is used clinically to detect stroke risk in children with sickle cell anaemia (SCA). Co‐inheritance in SCA of alpha‐thalassaemia and glucose‐6‐phosphate dehydrogenase (G6PD) polymorphisms is reported to associate with high CBFv and/or risk of stroke. The effect of a common functional polymorphism of haptoglobin (HP) is unknown. We investigated the effect of co‐inheritance of these polymorphisms on CBFv in 601 stroke‐free Tanzanian SCA patients aged <24 years. Homozygosity for alpha‐thalassaemia 3·7 deletion was significantly associated with reduced mean CBFv compared to wild‐type (β‐coefficient −16·1 cm/s, P = 0·002) adjusted for age and survey year. Inheritance of 1 or 2 alpha‐thalassaemia deletions was associated with decreased risk of abnormally high CBFv, compared to published data from Kenyan healthy control children (Relative risk ratio [RRR] = 0·53 [95% confidence interval (CI):0·35–0·8] & RRR = 0·43 [95% CI:0·23–0·78]), and reduced risk of abnormally low CBFv for 1 deletion only (RRR = 0·38 [95% CI:0·17–0·83]). No effects were observed for G6PD or HP polymorphisms. This is the first report of the effects of co‐inheritance of common polymorphisms, including the HP polymorphism, on CBFv in SCA patients resident in Africa and confirms the importance of alpha‐thalassaemia in reducing risk of abnormal CBFv.

PurposeRaised intracranial pressure (ICP) is a potentially treatable cause of morbidity and mortality but tools for monitoring are invasive. We sought to investigate the utility of the tympanic membrane displacement (TMD) analyser for non-invasive measurement of ICP in children.MethodsWe made TMD observations on normal and acutely comatose children presenting to Kilifi District Hospital (KDH) at the rural coast of Kenya and on children on follow-up for idiopathic intracranial hypertension at Evelina Children’s Hospital (ECH), in London, UK.ResultsWe recruited 63 patients (median age 3.3 (inter-quartile range (IQR) 2.0–4.3) years) at KDH and 14 children (median age 10 (IQR 5–11) years) at ECH. We observed significantly higher (more negative) TMD measurements in KDH children presenting with coma compared to normal children seen at the hospital’s outpatient department, in both semi-recumbent [mean −61.3 (95 % confidence interval (95 % CI) −93.5 to 29.1) nl versus mean −7.1 (95 % CI −54.0 to 68.3) nl, respectively; P = 0.03] and recumbent postures [mean −61.4 (95 % CI −93.4 to −29.3) nl, n = 59) versus mean −25.9 (95 % CI −71.4 to 123.2) nl, respectively; P = 0.03]. We also observed higher TMD measurements in ECH children with raised ICP measurements, as indicated by lumbar puncture manometry, compared to those with normal ICP, in both semi-recumbent [mean −259.3 (95 % CI −363.8 to −154.8) nl versus mean 26.7 (95 % CI −52.3 to 105.7) nl, respectively; P < 0.01] and recumbent postures [mean −137.5 (95 % CI −260.6 to −14.4) nl versus mean 96.6 (95 % CI 6.5 to 186.6) nl, respectively; P < 0.01].ConclusionThe TMD analyser has a potential utility in monitoring ICP in a variety of clinical circumstances.

Changes in cerebral blood flow (CBF) can be assessed directly with xenon clearance (XeC) or indirectly by measuring changes in middle cerebral artery blood velocity (Vmca) with transcranial Doppler (TCD). The aim of this study was to compare the changes in CBF and Vmca following caffeine ingestion.Nineteen patients (age 48-86, recovering from an acute stroke) and ten controls (age 52-85) were each studied twice. Bilateral measurements of CBF and Vmca were made before and after ingestion of 250 mg caffeine or matched placebo. The percentage change in CBF and Vmca after caffeine was calculated. Full results (CBF and Vmca) were obtained from 14 patients and 9 controls. There was no significant difference between patients and controls, so results were combined.Caffeine reduced CBF by 22% (95% confidence interval (CI) = 17% to 28%) and reduced Vmca by 13% (95% CI = 10% to 17%). The fall in Vmca was significantly less than that in CBF (p = 0.0016), showing that caffeine reduces mca diameter. Analysis based on Poiseuille flow in the arterioles suggests that caffeine reduced arteriole diameter by 5.9% (95% CI = 4.6% to 7.3%) and mca diameter by 4.3% (95% CI = 2.0% to 6.6%).TCD is being used as an alternative to XeC for assessing the effect of vasoconstrictors and vasodilators on CBF. This study has demonstrated that mca diameter can be changed by the vasoactive agents, and that changes in Vmca do not necessarily reflect changes in CBF.

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A forced periodic variation in blood pressure produces a similar variation in cerebral blood velocity. The amplitudes and phases of the pressure and velocity waveforms are indicative of the dynamic response of the cerebral autoregulation. The phase of the velocity leads the pressure; the greater the phase difference the faster the autoregulation response. Various techniques have been employed to oscillate arterial blood pressure but measurement reproducibility has been poor. The purpose of this study was to assess the reproducibility of phase measurements when sinusoidal lower body negative pressure is used to vary blood pressure. Five healthy volunteers were assessed at two vacuum levels on each of eight visits. For each measurement a 12 s sinusoidal cycle was maintained for 5 min. The Fourier components of blood pressure and the middle cerebral artery velocity were determined at the oscillation frequency. The phase of velocity consistently led the pressure. The mean phase difference was 42+/-13 degrees for the stronger vacuum and 36+/-42 degrees for the weaker vacuum. The variation given is the within-subjects standard deviation estimated from a one-way analysis of variance. Sinusoidal lower body negative pressure is a useful stimulus for investigating autoregulation; it has advantages over other methods. High vacuums show good reproducibility but are too uncomfortable for patient use.

Dynamic cerebral autoregulation, that is the transient response of cerebral blood flow to changes in arterial blood pressure, is currently assessed using a variety of different time series methods and data collection protocols. In the continuing absence of a gold standard for the study of cerebral autoregulation it is unclear to what extent does the assessment depend on the choice of a computational method and protocol. We use continuous measurements of blood pressure and cerebral blood flow velocity in the middle cerebral artery from the cohorts of 18 normotensive subjects performing sit-to-stand manoeuvre. We estimate cerebral autoregulation using a wide variety of black-box approaches (including the following six autoregulation indices ARI, Mx, Sx, Dx, FIR and ARX) and compare them in the context of reproducibility and variability. For all autoregulation indices, considered here, the intra-class correlation was greater during the standing protocol, however, it was significantly greater (Fisher's Z-test) for Mx (p < 0.03), Sx (p < 0.003) and Dx (p < 0.03). In the specific case of the sit-to-stand manoeuvre, measurements taken immediately after standing up greatly improve the reproducibility of the autoregulation coefficients. This is generally coupled with an increase of the within-group spread of the estimates.