Lower Breakpoint of Intracranial Amplitude-Pressure Relationship in Normal Pressure Hydrocephalus.

The relationship between intracranial pulse amplitude (AMP) and mean intracranial pressure (ICP) has been previously described. Generally, AMP increases proportionally to rises in ICP. However, at low ICP a lower breakpoint (LB) of amplitude-pressure relationship can be observed, below which pulse amplitude stays constant when ICP varies. Theoretically, below this breakpoint, the pressure-volume relationship is linear (good compensatory reserve, brain compliance stays constant); above the breakpoint, it is exponential (brain compliance decreases with rising ICP).Infusion tests performed in 169 patients diagnosed for idiopathic normal pressure hydrocephalus (iNPH) during the period 2004-2013 were available for analysis. A lower breakpoint was observed in 62 patients diagnosed for iNPH. Improvement after shunt surgery in patients in whom LB was recorded was 77% versus 90% in patients where LB was absent (p < 0.02). There was no correlation between improvement and slope of amplitude-pressure line above LB.The detection of a lower breakpoint is associated with less frequent improvement after shunting in NPH. It may be interpreted that cerebrospinal fluid dynamics of patients working on the flat part of the pressure-volume curve and having a 'luxurious' compensatory reserve, are more frequently caused by brain atrophy, which is obviously not responding to shunting.

Single Center Experience in Cerebrospinal Fluid Dynamics Testing.

Normal pressure hydrocephalus is more complex than a simple disturbance of the cerebrospinal fluid (CSF) circulation. Nevertheless, an assessment of CSF dynamics is key to making decisions about shunt insertion, shunt malfunction, and for further management if a patient fails to improve. We summarize our 25 years of single center experience in CSF dynamics assessment using pressure measurement and analysis. 4473 computerized infusion tests have been performed. We have shown that CSF infusion studies are safe, with incidence of infection at less than 1%. Raised resistance to CSF outflow positively correlates (p < 0.014) with improvement after shunting and is associated with disturbance of cerebral blood flow and its autoregulation (p < 0.02). CSF infusion studies are valuable in assessing possible shunt malfunction in vivo and for avoiding unnecessary revisions. Infusion tests are safe and provide useful information for clinical decision-making for the management of patients suffering from hydrocephalus.

Assessment of Pressure-Volume Index During Lumbar Infusion Study: What Is the Optimal Method?

INTRODUCTION: Assessment of the pressure-volume index (PVI) during lumbar infusion study (LIS) has been proposed to evaluate the overall compliance of the cranio-spinal system. It is calculated from the measurement of CSF pressure changes, ΔP from Pb to Pp, in response to repeated bolus injections of a volume (ΔV) within the lumbar subarachnoid space. MATERIAL AND METHODS: We retrospectively analyzed 18 patients who underwent LIS for suspicion of normal pressure hydrocephalus, including a series of three fast bolus injections of 3 mL of saline at different levels of CSF pressure. We compared two methods for PVI calculation: (a) PVIslope using the slope α of a linear fit ΔP = α(Pb - P 0), PVI = ΔV/log10(α + 1); (b) PVImean using the PVI calculated independently for each bolus injection assuming P 0 = 0, PVI = mean(ΔV/log10(Ppi/Pbi))i=1.3. RESULTS: We found a significant discrepancy between the two methods: the average difference (PVIslope - PVImean) was -3.93 mL (95% confidence interval [8.77; -16.64]). In the PVIslope, method, the mean P 0 was 2.12 mmHg (±3.41 mmHg). DISCUSSION: The clinical reliability of PVImean (assuming P 0 = 0) depends on the value of P 0. PVIslope provides results, independent of P 0. Future studies should focus on determining pathological PVI range rather than fixed cut-off values.

Midline shift in patients with closed traumatic brain injury may be driven by cerebral perfusion pressure not intracranial pressure.

BACKGROUND: In traumatic brain injury (TBI), swelling may disturb the potentially uniform pressure distribution in the brain, producing sustained intercompartmental pressure gradients which may associate with midline shift. The presence of pressure gradients is often neglected since bilateral invasive intracranial pressure (ICP) monitoring is not usually considered because of risks and high costs. We evaluated the presence of interhemispheric pressure gradients using bilateral transcranial Doppler (TCD) as means for noninvasive ICP (nICP) monitoring in TBI patients presenting midline shift. METHODS: From a retrospective cohort of 97 TBI patients with arterial blood pressure (ABP), ICP and bilateral TCD monitoring, 24 presented unilateral lesion and midline shift confirmed by computer tomography. nICP and noninvasive cerebral perfusion pressure (nCPP) on the left and right brain hemispheres were retrospectively calculated using a mathematical model associating TCD-derived cerebral blood flow velocity and ABP. RESULTS: The nCPP difference was correlated with midline shift (R=-0.34, P<0.01) showing a tendency to record higher CPP at the side of expansion. Accordingly, nICP at the side of expansion was significantly lower in comparison to the compressed side (18.86 [±5.71] mmHg [mean±standard deviation] versus 20.30 [±6.78] mmHg for expansion and compressed sides, respectively). Subsequently, nCPP was greater on the side of brain expansion (79.48±7.84, 78.03±8.93 mmHg [P<0.01], for expansion and compressed sides, respectively). CONCLUSIONS: TCD-based interhemispheric nCPP difference showed significant correlation with midline shift. Cerebral perfusion pressure was greater on the side of brain expansion, acting as the driving force to shift brain structures.

Planning, Development, and Implementation of a University-Led, Low-Cost Employee Wellness Program in a preK-12th-Grade Public School District.

BACKGROUND: A healthy preK-12th-grade school environment is critical to student well-being and success. As role models, school employees play a significant part in creating a healthy environment. Research suggests that employee wellness programs (EWPs) may help school employees adopt healthier lifestyles and, therefore, be healthier, more productive, and serve as healthy role models for students. This article describes the process by which a school district in central Texas partnered with a local university to plan, develop, and implement an affordable EWP. METHODS: A university-led leadership team sought input from employees, including administrators, and conducted a 4-week trial. These resulted in an EWP that provided health risk appraisals, fitness testing, group exercise classes, education seminars, online wellness resources, and blood draws/analysis. RESULTS: During the first 4 years, membership ranged from 107 to 384 (10-37%), and the annual cost of the program ranged from $49 to $116 per participating employee. CONCLUSIONS: University-led EWP programs can support, at a low cost, the health of school employees. Despite low employee engagement, need was demonstrated and feedback was positive. Challenges identified include time demands and lack of principals' support. Future considerations include targeting principals, utilizing the Human Resources Office, and strategically building a culture of health.

ICP and Antihypertensive Drugs.

OBJECTIVES: Arterial hypertension is among the leading risks for mortality. This burden requires in hypertensive patients the use of single, double or more antihypertensive drugs. The relationship between intracranial pressure (ICP) and arterial blood pressure is complex and still under debate. The impact of antihypertensive drugs on ICP is unknown. We wanted to understand whether the use of antihypertensive drugs has a significant influence on ICP and cerebrospinal fluid (CSF)/brain related parameters. MATERIALS AND METHODS: In a cohort of 95 patients with suspected normal pressure hydrocephalus, we prospectively collected drug details according to the Anatomical Therapeutic Chemical (ATC) classification. Lumbar infusion studies were performed. Using ICM+ software, we calculated at baseline and plateau ICP and pulse amplitude, resistance to CSF outflow, elastance, and pressure in the sagittal sinus and CSF production rate. We studied the influence of the administration of 1, 2, 3 or more antihypertensive drugs on ICP-derived parameters. We compared the data using Student's and Mann-Whitney tests or Chi-squared and Fisher's exact test. RESULTS: Elastance is significantly higher in patients with at least one antihypertensive drug compared with patients without medication. On the contrary, pressure volume index (PVI) is significantly decreased in patients with antihypertensive drugs compared with patients not on these medications. However, the number of antihypertensive drugs does not seem to influence other ICP parameters. CONCLUSIONS: Patients on antihypertensive drugs seem to have a stiffer brain than those not on them.

ICP: From Correlation to Causation.

Intracranial pressure (ICP) is a complex modality in the sense that it largely interconnects various systemic and intra-cranial variables such as cerebral blood flow and volume, cerebrospinal fluid flow and absoption, craniospinal container. In this context, although empirical correlation is an interesting tool for establishing relations between pairs of observed variables, it may be limited to establishing causation relations. For instance, if variables X and Y are mainly influenced by variable Z, their correlation is strong, but does not mean that X has a causation relation with Y or vice versa. In this work, we explore the use of the statistical concept of partial correlation to ICP and other derived measures to apprehend the interplay between correlation and causation.

Mathematical Modelling of CSF Pulsatile Flow in Aqueduct Cerebri.

OBJECTIVE: The phase-contrast MRI technique permits the non-invasive assessment of CSF movements in cerebrospinal fluid cavities of the central nervous system. Of particular interest is pulsatile cerebrospinal fluid (CSF) flow through the aqueduct cerebri. It is allegedly increased in hydrocephalus, having potential diagnostic value, although not all scientific reports contain unequivocally positive conclusions. METHODS: For the mathematical simulation of CSF flow, we used a computational model of cerebrospinal blood/fluid circulation designed by a former student as his PhD project. With this model, cerebral blood flow and CSF may be simulated in various vessels using a system of non-linear differential equations as time-varying signals. RESULTS: The amplitude of CSF flow seems to be positively related to the amplitude of pulse waveforms of intracranial pressure (ICP) in situations where mean ICP increases, such as during simulated infusion tests and following step increases of resistance to CSF outflow. An additional positive association between the pulse amplitude of ICP and CSF flow can be seen during simulated increases in the amplitude of arterial pulses (without changes in mean arterial pressure, MAP). The opposite effect can be observed during step increases in the resistance of the aqueduct cerebri and with decreasing elasticity of the system, where the CSF flow amplitude and the ICP pulse amplitude are related inversely. Vasodilatation caused by both gradual decreases in MAP and by increases in PaCO2 provokes an elevation in the observed amplitude of pulsatile CSF flow. CONCLUSIONS: Preliminary results indicate that the pulsations of CSF flow may carry information about both CSF-circulatory and cerebral vasogenic components. In most cases, the pulsations of CSF flow are positively related to the pulse amplitudes of both arterial pressure and ICP and to a degree of cerebrovascular dilatation.

Intracranial Pressure Is a Determinant of Sympathetic Activity.

Intracranial pressure (ICP) is the pressure within the cranium. ICP rise compresses brain vessels and reduces cerebral blood delivery. Massive ICP rise leads to cerebral ischemia, but it is also known to produce hypertension, bradycardia and respiratory irregularities due to a sympatho-adrenal mechanism termed Cushing response. One still unresolved question is whether the Cushing response is a non-synaptic acute brainstem ischemic mechanism or part of a larger physiological reflex for arterial blood pressure control and homeostasis regulation. We hypothesize that changes in ICP modulates sympathetic activity. Thus, modest ICP increase and decrease were achieved in mice and patients with respectively intra-ventricular and lumbar fluid infusion. Sympathetic activity was gauged directly by microneurography, recording renal sympathetic nerve activity in mice and muscle sympathetic nerve activity in patients, and gauged indirectly in both species by heart-rate variability analysis. In mice (n = 15), renal sympathetic activity increased from 29.9 ± 4.0 bursts.s-1 (baseline ICP 6.6 ± 0.7 mmHg) to 45.7 ± 6.4 bursts.s-1 (plateau ICP 38.6 ± 1.0 mmHg) and decreased to 34.8 ± 5.6 bursts.s-1 (post-infusion ICP 9.1 ± 0.8 mmHg). In patients (n = 10), muscle sympathetic activity increased from 51.2 ± 2.5 bursts.min-1 (baseline ICP 8.3 ± 1.0 mmHg) to 66.7 ± 2.9 bursts.min-1 (plateau ICP 25 ± 0.3 mmHg) and decreased to 58.8 ± 2.6 bursts.min-1 (post-infusion ICP 14.8 ± 0.9 mmHg). In patients 7 mmHg ICP rise significantly increases sympathetic activity by 17%. Heart-rate variability analysis demonstrated a significant vagal withdrawal during the ICP rise, in accordance with the microneurography findings. Mice and human results are alike. We demonstrate in animal and human that ICP is a reversible determinant of efferent sympathetic outflow, even at relatively low ICP levels. ICP is a biophysical stress related to the forces within the brain. But ICP has also to be considered as a physiological stressor, driving sympathetic activity. The results suggest a novel physiological ICP-mediated sympathetic modulation circuit and the existence of a possible intracranial (i.e., central) baroreflex. Modest ICP rise might participate to the pathophysiology of cardio-metabolic homeostasis imbalance with sympathetic over-activity, and to the pathogenesis of sympathetically-driven diseases.

Cerebral hemodynamic changes induced by a lumbar puncture in good-grade subarachnoid hemorrhage.

BACKGROUND: Patients with good-grade subarachnoid hemorrhage (SAH) are those without initial neurological deficit. However, they can die or present severe deficit due to secondary insult leading to brain ischemia. After SAH, in a known context of energy crisis, vasospasm, hydrocephalus and intracranial hypertension contribute to unfavorable outcome. Lumbar puncture (LP) is sometimes performed in an attempt to reduce intracranial pressure (ICP) and release headaches. We hypothesize that in good-grade SAH patients, a 20-ml LP releases headaches, reduces ICP and improves cerebral blood flow (CBF) as measured with O(15) PET scan. METHODS: Six good-grade (WFNS grade 1or 2) SAH patients (mean age 48 years, 2 women, 4 men) were prospectively included. All aneurysms (4 anterior communicating artery and 2 right middle cerebral artery) were coiled at day 1. Patients were managed according to our local protocol. LP was performed for severe headache (VAS >7) despite maximal painkiller treatment. Patients were included when the LP was clinically needed. The 20-ml LP was done in the PET scan (mean delay between SAH and LP: 3.5 days). LP allows hydrostatic measurement of ICP. Arterial blood pressure (ABP) was noninvasively gauged with photoplethysmography. Every signal was monitored and analyzed off-line. Regional CBF (rCBF) was measured semiquantitatively with O(15) PET before and after LP. Then we calculated the difference between baseline and post-LP condition for each area: positive value means augmentation of rCBF after the LP, negative value means reduction of rCBF. Individual descriptive analysis of CBF was first performed for each patient; then a statistical group analysis was done with SPM for all voxels using t statistics converted to Z scores (p < 0.01, Z score >3.2). RESULTS: A 20-ml LP yielded a reduction in pain (-4), a drop in ICP (24.3 ± 12.5 to 6.9 ± 4.7 mm Hg), but no change in ABP. Descriptive and statistical image analysis showed a heterogeneous and biphasic change in cerebral hemodynamics: rCBF was not kept constant and either augmented or decreased after the drop in ICP. Hence, cerebrovascular reactivity was spatially heterogeneous within the brain. rCBF seems to augment in the brain region roughly close to the bleed and to be reduced in the rest of the brain, with a rough plane of symmetry. CONCLUSIONS: In good-grade SAH, LP releases headaches and lowers ICP. LP and the drop in ICP have a heterogeneous and biphasic effect on rCBF, suggesting that cerebrovascular reactivity is not spatially homogeneous within the brain.

Effects of concurrent respiratory resistance training on health-related quality of life in wheelchair rugby athletes: a pilot study.

PURPOSE: To compare the effects of 9 weeks of training with a concurrent flow resistance (CFR) device versus a concurrent pressure threshold resistance (CPTR) device on health-related quality of life (HRQoL) in wheelchair rugby (WR) athletes. METHOD: Twenty-four male WR athletes (22 with tetraplegia, 1 with a spastic cerebral palsy, and 1 with congenital upper and lower limb deformities) were matched by lesion level, completeness of injury, and rugby classification prior to being randomly assigned to 1 of 3 groups: (1) CPTR (n=8), (2) CFR (n=8), or (3) controls (CON, n=8). Pre/post testing included assessment of HRQoL as measured by the Short-Form Health Survey Version 2.0 (SF-36v2). Manufacturer protocol guidelines for the CFR and CPTR groups were followed for breathing exercises. RESULTS: Sixteen participants completed the study (CPTR=4, CFR=5, CON=7). The Mann-Whitney U rank order revealed significantly greater reductions in bodily pain (P = .038) and improvements in vitality (P = .028) for CFR versus CON. CONCLUSION: Results from this study suggest that training with a CFR device improves some aspects of HRQoL (eg, vitality and bodily pain) in WR athletes. Further research with a larger sample size is needed to examine the impact of these devices on improving HRQoL for wheelchair athletes.

Nonlinear pressure-flow relationship is able to detect asymmetry of brain blood circulation associated with midline shift.

Reliable and noninvasive assessment of cerebral blood flow regulation is a major challenge in acute care monitoring. This study assessed dynamics of flow regulation and its relationship to asymmetry of initial computed tomography (CT) scan using multimodal pressure flow (MMPF) analysis. Data of 27 patients (38 +/- 15 years old) with traumatic brain injury (TBI) were analyzed. Patients were selected from bigger cohort according to criteria of having midline shift on initial CT scan and intact skull (no craniotomy or bone flap). The MMPF analysis was used to extract the oscillations in cerebral perfusion pressure (CPP) and blood flow velocity (BFV) signals at frequency of artificial ventilation, and to calculate the instantaneous phase difference between CPP and BFV oscillations. Mean CPP-BFV phase difference was used to quantify pressure and flow relationship. The TBI subjects had smaller mean BP-BFV phase shifts (left, 8.7 +/- 9.6; right 10.2 +/- 8.3 MCAs, mean +/- SD) than values previously obtained in healthy subjects (left, 37.3 +/- 7.6 degrees; right, 38.0 +/- 8.9 degrees; p < 0.0001), suggesting impaired blood flow regulation after TBI. The difference in phase shift between CPP and BFV in the left and right side was strongly correlated to the midline shift (R = 0.78; p < 0.0001). These findings indicate that the MMPF method allows reliable assessment of alterations in pressure and flow relationship after TBI. Moreover, mean pressure-flow phase shift is sensitive to the displacement of midline of the brain, and may potentially serve as a marker of asymmetry of cerebral autoregulation.

Effects of respiratory resistance training with a concurrent flow device on wheelchair athletes.

BACKGROUND/OBJECTIVE: To determine the effect of respiratory resistance training (RRT) with a concurrent flow respiratory (CFR) device on respiratory function and aerobic power in wheelchair athletes. METHODS: Ten male wheelchair athletes (8 with spinal cord injuries, 1 with a neurological disorder, and 1 with postpolio syndrome), were matched by lesion level and/or track rating before random assignment to either a RRT group (n = 5) or a control group (CON, n = 5). The RRT group performed 1 set of breathing exercises using Expand-a-Lung, a CFR device, 2 to 3 times daily for 10 weeks. Pre/posttesting included measurement of maximum voluntary ventilation (MVV), maximum inspiratory pressure (MIP), and peak oxygen consumption (V(O2peak)). RESULTS: Repeated measures ANOVA revealed a significant group difference in change for MIP from pre- to posttest (P < 0.05). The RRT group improved by 33.0 cm H2O, while the CON group improved by 0.6 cm H2O. Although not significant, the MW increased for the RRT group and decreased for the CON group. There was no significant group difference between V(O2peak) for pre/posttesting. Due to small sample sizes in both groups and violations of some parametric statistical assumptions, nonparametric tests were also conducted as a crosscheck of the findings. The results of the nonparametric tests concurred with the parametric results. CONCLUSIONS: These data demonstrate that 10 weeks of RRT training with a CFR device can effectively improve MIP in wheelchair athletes. Further research and a larger sample size are warranted to further characterize the impact of Expand-a-Lung on performance and other cardiorespiratory variables in wheelchair athletes.

Pulse pressure waveform in hydrocephalus: what it is and what it isn't.

OBJECT: Apart from its mean value, the pulse waveform of intracranial pressure (ICP) is an essential element of pressure recording. The authors reviewed their experience with the measurement and interpretation of ICP pulse amplitude by referring to a database of recordings in hydrocephalic patients. METHODS: The database contained computerized pressure recordings from 2100 infusion studies (either lumbar or intraventricular) or overnight ICP monitoring sessions in patients suffering from hydrocephalus of various types (both communicating and noncommunicating), origins, and stages of management (shunt or no shunt). Amplitude was calculated from ICP waveforms by using a spectral analysis methodology. RESULTS: The appearance of a pulse waveform amplitude is positive evidence of a technically correct recording of ICP and helps to distinguish between postural and vasogenic variations in ICP. Pulse amplitude is significantly correlated with the amplitude of cerebral blood flow velocity (R = 0.4, p = 0.012) as assessed using Doppler ultrasonography. Amplitude is positively correlated with a mean ICP (R = 0.21 in idiopathic normal-pressure hydrocephalus [NPH]; number of cases 131; p < 0.01) and resistance to cerebrospinal fluid outflow (R = 0.22) but does not seem to be correlated with cerebrospinal elasticity, dilation of ventricles, or severity of hydrocephalus (NPH score). Amplitude increases slightly with age (R = 0.39, p < 0.01; number of cases 46). A positive association between pulse amplitude and increased ICP during an infusion study is helpful in distinguishing between hydrocephalus and predominant brain atrophy. A large amplitude is associated with a good outcome after shunting (positive predictive power 0.9), whereas a low amplitude has no predictive power in outcome prognostication (0.5). Pulse amplitude is reduced by a properly functioning shunt. CONCLUSIONS: Proper recording, detection, and interpretation of ICP pulse waveforms provide clinically useful information about patients suffering from hydrocephalus.

Cerebrovascular effects of sodium nitroprusside in the anaesthetized baboon: a positron emission tomographic study.

The effects of sodium nitroprusside (SNP), a potent hypotensive agent, on cerebral blood flow (CBF) have been extensively studied in clinical and experimental situations but the results remain controversial. Whereas its properties would predict a dilatation of cerebral blood vessels, most studies report either no change or a decrease in CBF. The aim of this study was to investigate the effects of SNP on CBF, cerebral blood volume (CBV), and cerebral oxygen metabolism (CMRO2), by means of positron emission tomography in the anaesthetized baboon. Measurements were performed during normotension (mean arterial pressure (MABP): 97+/-16 mm Hg) and repeated following SNP-induced hypotension (MABP: 44+/-9 mm Hg). Sodium nitroprusside led to an increase in CBF and CBV (+30% and +37%, respectively, P<0.05), whereas no change in CMRO2 was noted. Linear regression analysis of CBF values as a function of MABP confirmed that CBF increases when MABP is reduced by SNP. The comparison between these cerebrovascular changes and those found during trimetaphan-induced hypotension in our previously published studies further argues for a direct dilatatory effect of SNP on cerebral blood vessels.

Symmetry of cerebral hemodynamic indices derived from bilateral transcranial Doppler.

OBJECTIVE: The authors evaluated with bilateral transcranial Doppler (TCD) ultrasonography the norm of interhemispheric difference for several cerebrovascular hemodynamic parameters. METHODS: Forty-four volunteers (33 male, 11 female; average age = 21 years; range, 20-23 years) were studied. The authors recorded bilateral systolic, diastolic, and mean flow velocity (FV) and noninvasive systolic, diastolic, and mean arterial blood pressure. Calculated indices included Gosling's pulsatility index (GPI), an index of autoregulation (Mx), critical closing pressure (CCP), and a noninvasive estimator of cerebral perfusion pressure (nCPP). All indices were averaged per side and patient. For each parameter, the left-right correlation coefficient (r2) and the 95% confidence limit of the left-right differences were calculated. RESULTS: All TCD-derived indices displayed significant correlations between the left and right sides: r2 = 0.49 for mean FV (FVm), r2 = 0.66 for GPI, r2 = 0.79 for Mx, r2 = 0.93 for CCP, and r2 = 0.94 for nCPP. The 95% confidence intervals for the left-right differences were 20 cm/s for FVm, 0.16 for GPI, 0.18 for Mx, 13 mm Hg for CCP, and 4.6 mm Hg for nCPP. CONCLUSIONS: This study gives the reference values for the assessment of left-right symmetry of cerebral hemodynamics using various TCD-derived indices. These reference values should be useful for clinical studies assessing the left-right asymmetry of cerebral hemodynamics on a daily basis.

Asymmetry of pressure autoregulation after traumatic brain injury.

OBJECT: The aim of this study was to assess the asymmetry of autoregulation between the left and right sides of the brain by using bilateral transcranial Doppler ultrasonography in a cohort of patients with head injuries. METHODS: Ninety-six patients with head injuries comprised the study population. All significant intracranial mass lesions were promptly removed. The patients were given medications to induce sedation and paralysis, and artificial ventilation. Arterial blood pressure (ABP) and intracranial pressure (ICP) were monitored in an invasive manner. A strategy based on the patient's cerebral perfusion pressure (CPP = ABP - ICP) was applied: CPP was maintained at a level higher than 70 mm Hg and ICP at a level lower than 25 mm Hg. The left and right middle cerebral arteries were insonated daily, and bilateral flow velocities (FVs) were recorded. The correlation coefficient between the CPP and FV, termed Mx, was calculated and time-averaged over each recording period on both sides. An Mx close to 1 signified that slow fluctuations in CPP produced synchronized slow changes in FV, indicating a defective autoregulation. An Mx close to 0 indicated preserved autoregulation. Computerized tomography scans in all patients were reviewed; the side on which the major brain lesion was located was noted and the extent of the midline shift was determined. Outcome was measured 6 months after discharge. The left-right difference in the Mx between the hemispheres was significantly higher in patients who died than in those who survived (0.16 +/- 0.04 compared with 0.08 +/- 0.01; p = 0.04). The left-right difference in the Mx was correlated with a midline shift (r = -0.42; p = 0.03). Autoregulation was worse on the side of the brain where the lesion was located (p < 0.035). CONCLUSIONS: The left-right difference in autoregulation is significantly associated with a fatal outcome. Autoregulation in the brain is worse on the side ipsilateral to the lesion and on the side of expansion in cases in which there is a midline shift.