Publications by authors named "Piotr Smielewski"

35 Publications

Single Center Experience in Cerebrospinal Fluid Dynamics Testing.

Acta Neurochir Suppl 2021 ;131:311-313

Division of Neurosurgery, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

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.
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http://dx.doi.org/10.1007/978-3-030-59436-7_58DOI Listing
June 2021

Analysis of Intracranial Pressure Pulse-Pressure Relationship: Experimental Validation.

Acta Neurochir Suppl 2021 ;131:279-282

Faculty of Electronics and Information Technology, Institute of Electronic Systems, Warsaw University of Technology, Warsaw, Poland.

The slope of linear relationship between the amplitude of pulsations in intracranial pressure (ICP) versus mean ICP has recently been suggested as a useful guide for selecting patients for shunt surgery in normal pressure hydrocephalus (NPH). To better understand how the pathophysiology of cerebral circulation influences this parameter, we aimed to study the relationship between mean pressure and pulsation amplitude in a wide range of conditions affecting cerebrovascular tone and ICP in experimental conditions.We retrospectively analysed experimental material collected previously. Three physiological manoeuvres were studied in 29 New Zealand white rabbits: lumbar infusion with an infusion rate ≤0.2 mL/min to induce mild intracranial hypertension (n = 43), sympathetic blockade to induce arterial hypotension (n = 19), and modulation of the ventilator tidal volume, simultaneously influencing arterial carbon dioxide partial pressure (PaCO) to induce hypocapnia or hypercapnia (n = 17). We investigated whether the slope of the pulse amplitude (AMP)-ICP line depended on PaCO and arterial blood pressure (ABP) changes.We found a linear correlation between AMP-ICP and ICP with positive slope. Regression of slope against mean ABP showed a negative dependence (p = 0.03). In contrast, the relationship between slope and PaCO was positive, although not reaching statistical significance (p = 0.18).The slope of amplitude-pressure line is strongly modulated by systemic vascular variables and therefore should be taken as a descriptor of cerebrospinal fluid dynamics with great care.
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http://dx.doi.org/10.1007/978-3-030-59436-7_52DOI Listing
June 2021

Waveform Analysis of Intraspinal Pressure After Traumatic Spinal Cord Injury: An Observational Study (O-64).

Acta Neurochir Suppl 2016 ;122:335-8

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Following a traumatic brain injury (TBI), intracranial pressure (ICP) increases, often resulting in secondary brain insults. After a spinal cord injury, here the cord may be swollen, leading to a local increase in intraspinal pressure (ISP). We hypothesised that waveform analysis methodology similar to that used for ICP after TBI may be applicable for the monitoring of patients with spinal cord injury.An initial cohort of 10 patients with spinal cord injury, as presented by the first author at a meeting in Cambridge in May 2012, were included in this observational study. The whole group (18 patients) was recently presented in the context of clinically oriented findings (Werndle et al., Crit Care Med, 42(3):646-655, 2014, PMID: 24231762). Mean pressure, pulse and respiratory waveform were analysed along slow vasogenic waves.Slow, respiratory and pulse components of ISP were characterised in the time and frequency domains. Mean ISP was 22.5 ± 5.1, mean pulse amplitude 1.57 ± 0.97, mean respiratory amplitude 0.65 ± 0.45 and mean magnitude of slow waves (a 20-s to 3-min period) was 3.97 ± 3.1 (all in millimetres of mercury). With increasing mean ISP, the pulse amplitude increased in all cases. This suggests that the ISP signal is of a similar character to ICP recorded after TBI. Therefore, the methods of ICP analysis can be helpful in ISP analysis.
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http://dx.doi.org/10.1007/978-3-319-22533-3_66DOI Listing
July 2017

Increasing Intracranial Pressure After Head Injury: Impact on Respiratory Oscillations in Cerebral Blood Flow Velocity.

Acta Neurochir Suppl 2016 ;122:171-5

Division of Neurosurgery, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.

Experiments have shown that closed-box conditions alter the transmission of respiratory oscillations (R waves) to organ blood flow already at a marginal pressure increase. How does the increasing intracranial pressure (ICP) interact with R waves in cerebral blood flow after head injury (HI)?Twenty-two head-injured patients requiring sedation and mechanical ventilation were monitored for ICP, Doppler flow velocity (FV) in the middle cerebral arteries, and arterial blood pressure (ABP). The analysis included transfer function gains of R waves (9-20 cpm) from ABP to FV, and indices of pressure-volume reserve (RAP) and autoregulation (Mx). Increasing ICP has dampened R-wave gains from day 1 to day 4 after HI in all patients. A large impact (ΔGain /ΔICP right: 0.14 ± 0.06; left: 0.18 ± 0.08) was associated with exhausted reserves (RAP ≥0.85). When RAP was <0.85, rising ICP had a lower impact on R-wave gains (ΔGain /ΔICP right: 0.05 ± 0.02; left: 0.06 ± 0.04; p < 0.05), but increased the pulsatility indices (right: 1.35 ± 0.55; left: 1.25 ± 0.52) and Mx indices (right: 0.30 ± 0.12; left: 0.28 ± 0.08, p < 0.05). Monitoring of R waves in blood pressure and cerebral blood flow velocity has suggested that rising ICP after HI might have an impact on cerebral blood flow directly, even before autoregulation is impaired.
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http://dx.doi.org/10.1007/978-3-319-22533-3_35DOI Listing
July 2017

Phase-shift between arterial flow and ICP pulse during infusion test.

Acta Neurochir (Wien) 2015 Apr 3;157(4):633-8. Epub 2015 Feb 3.

Departments of Brain and Cognitive Engineering, Korea University, Anam-dong, Seongbu-gu, 136-713, Seoul, South Korea,

Background: The dynamic relationship between pulse waveform of intracranial pressure (ICP) and transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) may contain information about cerebrospinal compliance. This study investigated the possibility by focusing on the phase shift between fundamental harmonics of CBFV and ICP.

Methods: Thirty-seven normal pressure hydrocephalus patients (20 men, mean age 58) underwent the cerebrospinal fluid (CSF) infusion tests. The infusion was performed via pre-implanted Ommaya reservoir. The TCD FV was recorded in the middle cerebral artery. Resulting continuous ICP and pressure-volume (PV) signals were analyzed by ICM+ software.

Results: In initial stage of the CSF infusion, the phase shift was negative (median value = -11°, range = +60 to -117). There was significant inverse association of phase shift with brain elasticity (R = -0.51; p = 0.0009). In all tests, phase shift consistently decreased during gradual elevation of ICP (p = 0.00001). Magnitude of decrease in phase shift was inversely related to the peak-to-peak amplitude of ICP pulse waveform at a baseline (R = -0.51; p = 0.001).

Conclusions: Phase shift between fundamental harmonics of ICP and TCD waveforms decreases during elevation of ICP. This is caused by an increase of time delay between systolic peak of flow velocity wave and ICP pulse.
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http://dx.doi.org/10.1007/s00701-015-2353-4DOI Listing
April 2015

Traumatic brain injury: increasing ICP attenuates respiratory modulations of cerebral blood flow velocity.

Med Eng Phys 2015 Feb 29;37(2):175-9. Epub 2014 Dec 29.

Department of Academic Neurosurgery, Addenbrooke's Hospital, Cambridge, UK.

In vitro experiments have suggested that respiratory oscillations (R waves) in cerebral blood flow velocity are reduced as soon as the intracranial pressure-volume reserve is exhausted. Could R waves hence, provide indication for increasing ICP after traumatic brain injury (TBI)? On days 1 to 4 after TBI, 22 sedated and ventilated patients were monitored for intracranial pressure (ICP) in brain parenchyma, Doppler flow velocity (FV) in the middle cerebral arteries (MCA), and arterial blood pressure (ABP). The analysis included the transfer function gains of R waves (respiratory rate of 9-20 cpm) between ABP and FV (GainFv) as well as between ABP and ICP (GainICP). Also, the index of the intracranial pressure-volume reserve (RAP) was calculated. The rise of ICP (day 1: 14.10 ± 6.22 mmHg; to day 4: 29.69 ± 12.35 mmHg) and increase of RAP (day 1: 0.72 ± 0.22; to day 4: 0.85 ± 0.18) were accompanied by a decrease of GainFv (right MCA; day 1: 1.78 ± 1.0; day 4: 0.84 ± 0.47; left MCA day 1: 1.74 ± 1.10; day 4: 0.86 ± 0.46; p < 0.01) but no significant change in GainICP day 1: 1.50 ± 0.77; day 4: 1.15 ± 0.47; p = 0.07). The transfer of ventilatory oscillations to the intracerebral arteries after TBI appears to be dampened by increasing ICP and exhausted intracranial pressure-volume reserves. Results warrant prospective studies of whether respiratory waves in cerebral blood flow velocity may anticipate intracranial hypertension non-invasively.
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http://dx.doi.org/10.1016/j.medengphy.2014.11.009DOI Listing
February 2015

Cerebrovascular time constant in patients suffering from hydrocephalus.

Neurol Res 2014 Mar;36(3):255-61

Objectives: We studied possible link between cerebrospinal fluid (CSF) compensation and indices describing pulsatile inflow of cerebral arterial blood.

Methods: A total of 50 infusion tests performed in patients with symptoms of normal pressure hydrocephalus (NPH) were examined retrospectively. Waveforms of CSF pressure, noninvasive arterial blood pressure (ABP), and transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) were used to estimate relative changes in cerebral arterial compliance (Ca) and cerebrovascular resistance (CVR). Product of Ca and CVR, called cerebral arterial time constant (τ, unit: seconds), was calculated at the baseline and plateau phase of the test and compared with CSF compensatory parameters such as resistance to CSF outflow, elasticity, slope of amplitude-pressure line, and pulse amplitude of CSF pressure.

Results: Neither of CSF compensatory parameters correlated with hemodynamic indices. However, the change in cerebral perfusion pressure (CPP) provoked change in τ (R  =  0.33; P  =  0.017) secondary to a change in CVR (R  =  0.81; P < 0.0001). Changes in CVR and Ca had a reciprocal character (R  =  -0.64; P < 0.0001) with magnitude of variation in CVR (68%) prevailing over magnitude of changes in Ca (49%).

Discussion: Hemodynamics of pulsatile inflow of cerebral arterial blood assessed by cerebral arterial time constant is not directly linked to dynamics of CSF circulation and pressure-volume compensation but is sensitive to changes in CPP during infusion test.
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http://dx.doi.org/10.1179/1743132813Y.0000000282DOI Listing
March 2014

Doppler flow velocity and intra-cranial pressure: responses to short-term mild hypocapnia help to assess the pressure-volume relationship after head injury.

Ultrasound Med Biol 2013 Sep 3;39(9):1521-6. Epub 2013 Jul 3.

Department of Academic Neurosurgery, Addenbrooke's Hospital, Cambridge, UK.

To anticipate an increase in intra-cranial pressure (ICP), information about pressure-volume (p/v) compliance is required. ICP monitoring often fails at this task after head injury. Could a test that transiently shifts intra-cranial blood volume produce consistent information about the p/v relationship? Doppler flow velocities in the middle cerebral arteries (left: 80.8 ± 34.7 cm/s; right: 65.9 ± 28.0 cm/s) and ICP (16.4 ± 6.7 mm Hg) were measured in 29 patients with head injury, before and during moderate hypocapnia (4.4 ± 3.0 kPa). The ratio of vasomotor response to change in ICP differed between those with high (left: 14.8 ± 6.9, right: 14.4 ± 6.6 cm/s/kPa/mm Hg) and low (left: 1.8 ± 0.6, right: 2.2 ± 0.9 cm/s/kPa/mm g) intra-cranial compliance. Additionally, the ratio identified 12 patients deviating from the classic non-linear p/v curve (left: 5.7 ± 1.3, right: 5.8 ± 1.0 cm/s/kPa/mm Hg). They exhibited an almost proportional relationship between vasomotor and ICP responses (R = 0.69, p < 0.01). Results suggest that a test that combines the responses of two intra-cranial compartments may provide consistent information about intra-cranial p/v compliance, even if the parameters derived from ICP monitoring are inconclusive.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2013.03.020DOI Listing
September 2013

Optimal cerebral perfusion pressure: are we ready for it?

Neurol Res 2013 Mar;35(2):138-48

Academic Neurosurgical Unit, University of Cambridge Clinical School, Cambridge, UK.

Objectives: Cerebral perfusion pressure (CPP)-oriented therapy and the Lund concept lie on opposite ends of the CPP scale, in the management of head injury. Optimization of CPP by monitoring cerebral vascular pressure reactivity is an alternative approach that may reconcile these two divergent approaches, preventing both injurious hypotension and hypertension with an individualized CPP target.

Methods: Indices describing cerebral vascular reactivity or cerebral blood flow autoregulation, derived from intracranial pressure, near-infrared spectroscopy, or transcranial Doppler are reviewed in this manuscript.

Results: Indices of cerebrovascular reactivity and autoregulation typically converge to a U-shape curve when viewed as a function of CPP, with the best reactivity metrics indicating optimal CPP. In a retrospective study of prospectively collected data from head-injured patients, Steiner et al. demonstrated that a greater distance between averaged over total monitoring time-CPP and optimal CPP, correlated with unfavourable outcome. A recent study of 300 head-injured patients (2003-2009) showed that hypotension below optimal CPP was associated with greater mortality rate, while hypertension above optimal CPP was associated with an increase in severe disability.

Discussion: Pilot studies indicating feasibility of autoregulation-oriented CPP optimization have been performed in adult and paediatric traumatic brain injury, aneurysmal subarachnoid haemorrhage, and in patients undergoing cardiothoracic surgery. It remains to be prospectively demonstrated whether optimal CPP management is able to improve outcome.
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http://dx.doi.org/10.1179/1743132812Y.0000000150DOI Listing
March 2013

How does moderate hypocapnia affect cerebral autoregulation in response to changes in perfusion pressure in TBI patients?

Acta Neurochir Suppl 2012 ;114:153-6

Department of Academic Neurosurgery, Addenbrooke's Hospital, Cambridge, UK.

In traumatic brain injury, the hypocapnic effects on blood pressure autoregulation may vary from beneficial to detrimental. The consequences of moderate hypocapnia (HC) on the autoregulation of cerebral perfusion pressure (CPP) have not been monitored so far.Thirty head injured patients requiring sedation and mechanical ventilation were studied during normocapnia (5.1 ± 0.4 kPa) and moderate HC (4.4 ± 3.0 kPa). Transcranial Doppler flow velocity (Fv) of the middle cerebral arteries (MCA), invasive arterial blood pressure, and intracranial pressure were monitored. CPP was calculated. The responsiveness of Fv to slow oscillations in CPP was assessed by means of the moving correlation coefficient, the Mx autoregulatory index. Hypocapnic effects on Mx were increasing with its deviation from normal baseline (left MCA: R (2) = 0.67; right MCA: R (2) = 0.51; p < 0.05). Mx indicating normal autoregulation (left: -0.23 ± 0.23; right: -0.21 ± 0.24) was not significantly changed by moderate HC. Impaired Mx autoregulation, however, (left: 0.37 ± 0.13; right: 0.33 ± 0.26) was improved (left: 0.12 ± 0.25; right: -0.0003 ± 0.19; p < 0.01) during moderate HC. Mx was adjusted to normal despite no significant change in CPP levels. Our study showed that short-term moderate HC may optimize the autoregulatory response to spontaneous CPP fluctuations with only a small CPP increase. Patients with impaired autoregulation seemed to benefit the most.
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http://dx.doi.org/10.1007/978-3-7091-0956-4_28DOI Listing
May 2012

Cerebrovascular time constant: dependence on cerebral perfusion pressure and end-tidal carbon dioxide concentration.

Neurol Res 2012 Jan;34(1):17-24

Academic Neurosurgical Unit, Addenbrooke's Hospital, Cambridge, UK.

Objective: The cerebrovascular time constant (τ) describes the time to establish a change in cerebral blood volume after a step transient in arterial blood pressure (ABP). We studied the relationship between τ, ABP, intracranial pressure (ICP), and end-tidal carbon dioxide concentration (EtCO2).

Method: Recordings from 46 anaesthetized, paralysed and ventilated New Zealand rabbits were analysed retrospectively. ABP was directly monitored in the femoral artery, transcranial Doppler (TCD) cerebral blood flow velocity (CBFV) from the basilar artery, and ICP using an intraparenchymal sensor. In nine animals end-tidal CO2 (EtCO2) was monitored continuously. ABP was decreased with injection of trimetophan (n = 11) or haemorrhage (n = 6) and increased by boluses of dopamine (n = 11). ICP was increased by infusion of normal saline into the lumbar cerebrospinal fluid space (n = 9). Changes in cerebral compliance (C(a)) were estimated as a ratio of the pulse amplitude of the cerebral arterial blood volume (CBV) and the pulse amplitude of ABP. Changes in cerebrovascular resistance (CVR) were expressed as mean ABP or cerebral perfusion pressure (CPP) divided by mean CBFV. Time constant τ was calculated as the product of CVR and C(a).

Results: The time constant changed inversely to the direction of the change in ABP (during arterial hypo- and hypertension) and CPP (during intracranial hypertension). C(a) increased with decreasing CPP, while CVR decreased. During a decrease in CPP, changes in C(a) exceeded changes in CVR. In contrast, during hypercapnia, the decrease in CVR was more pronounced than the increase in C(a), resulting in a decrease in τ.

Conclusion: Cerebrovascular time constant τ is modulated by ABP, ICP, and EtCO2.
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http://dx.doi.org/10.1179/1743132811Y.0000000040DOI Listing
January 2012

Short-term moderate hypocapnia augments detection of optimal cerebral perfusion pressure.

J Neurotrauma 2011 Jul 15;28(7):1133-7. Epub 2011 Apr 15.

Department of Academic Neurosurgery, Addenbrooke's Hospital, Cambridge, England.

An autoregulation-oriented strategy has been proposed to guide neurocritical therapy toward the optimal cerebral perfusion pressure (CPPOPT). The influence of ventilation changes is, however, unclear. We sought to find out whether short-term moderate hypocapnia (HC) shifts the CPPOPT or affects its detection. Thirty patients with traumatic brain injury (TBI), who required sedation and mechanical ventilation, were studied during 20 min of normocapnia (5.1±0.4 kPa) and 30 min of moderate HC (4.4±3.0 kPa). Monitoring included bilateral transcranial Doppler of the middle cerebral arteries (MCA), invasive arterial blood pressure (ABP), and intracranial pressure (ICP). Mx -autoregulatory index provided a measure for the CPP responsiveness of MCA flow velocity. CPPOPT was assessed as the CPP at which autoregulation (Mx) was working with the maximal efficiency. During normocapnia, CPPOPT (left: 80.65±6.18; right: 79.11±5.84 mm Hg) was detectable in 12 of 30 patients. Moderate HC did not shift this CPPOPT but enabled its detection in another 17 patients (CPPOPT left: 83.94±14.82; right: 85.28±14.73 mm Hg). The detection of CPPOPT was achieved via significantly improved Mx-autoregulatory index and an increase of CPP mean. It appeared that short-term moderate HC augmented the detection of an optimum CPP, and may therefore usefully support CPP-guided therapy in patients with TBI.
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http://dx.doi.org/10.1089/neu.2010.1577DOI Listing
July 2011

Slow vasogenic fluctuations of intracranial pressure and cerebral near infrared spectroscopy--an observational study.

Acta Neurochir (Wien) 2010 Oct 11;152(10):1763-9. Epub 2010 Aug 11.

University of Cambridge, Addenbrooke's Hospital, UK.

Background/purpose: Increased slow-wave activity in intracranial pressure (ICP) signifies an exhausted cerebrospinal compensatory reserve across a range of conditions. In this study, we attempted to describe synchronisation between slow waves of ICP and of near-infrared spectroscopy (NIRS) variables during controlled elevation of ICP.

Method: Nineteen patients presenting with symptomatic hydrocephalus underwent a Computerised Infusion Test. NIRS-derived indices, ICP and arterial blood pressure (ABP) were recorded simultaneously.

Findings: ICP increased from 9.3 (6.0) mmHg to a 17.1 (8.9) mmHg during infusion. Slow waves in ICP were accompanied by concurrent waves in each NIRS variable (including deoxygenated haemoglobin (Hb) and oxygenated haemoglobin (HbO2)) with a mean coherence of >0.7 and no significant phase shift. In the same bandwidth (0.3-1.8 min(-1)), ABP fluctuations occurred with a coherence of 0.77 and phase lead of 40° with respect to ICP. The power of ICP slow waves increased significantly during infusion plateau with a corresponding increase in power of Hb waves.

Conclusions: Slow fluctuations in cerebral oximetry as detected by NIRS coincide with and are implicated in the origin of ICP slow waves and increases during periods of exhausted cerebrospinal compensatory reserve. NIRS may be used as a non-invasive marker of increased ICP slow waves (and therefore reduced CSF compensatory reserve).
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http://dx.doi.org/10.1007/s00701-010-0748-9DOI Listing
October 2010

Plateau waves in head injured patients requiring neurocritical care.

Neurocrit Care 2009 30;11(2):143-50. Epub 2009 Jun 30.

Academic Neurosurgical Unit, Addenbrooke's Hospital, University of Cambridge, Cambridge, UK.

Object: Plateau waves often develop in neurointensive care patients. They are sudden increases in intracranial pressure (ICP) that lead to dramatic decreases of cerebral perfusion pressure (CPP) and can therefore contribute to ischemic secondary brain insult. The aim of this study was to analyze the occurrence of plateau waves in head injured patients requiring neurocritical care, their relation with cerebral autoregulation and impact on outcome.

Methods: Data were analyzed retrospectively in 444 head injured patients admitted to Neuroscience Critical Care Unit of Addenbrooke's Hospital in Cambridge, UK. Arterial blood pressure (ABP), intracranial pressure (ICP), heart rate (HR) were digitally recorded and derived indices calculated. Primary monitoring data, autoregulation indices, outcome of patients, initial CT findings (in a subgroup of patients), brain tissue monitoring data (in a subgroup) were compared between patients who developed plateau waves and those who did not.

Results: Plateau waves were observed in 109/444 patients (24.5%). They were significantly more frequent in younger patients. Impaired cerebrovascular pressure reactivity and depleted compensatory reserve were associated with vasodilatation on the top of the wave. Plateau waves were not associated with poorer outcome unless the episodes lasted for a long time (longer than 30-40 min). Plateau waves were more frequently seen in patients with lesser midline shift, lower volume of contusion on CT scan, absence of skull fractures, and lower brain tissue concentration of carbon dioxide.

Conclusions: Plateau waves are frequent phenomenon. They are not associated with worse outcome unless they lead to sustained intracranial hypertension.
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http://dx.doi.org/10.1007/s12028-009-9235-7DOI Listing
April 2010

Monitoring of cerebrovascular autoregulation: facts, myths, and missing links.

Neurocrit Care 2009 6;10(3):373-86. Epub 2009 Jan 6.

Department of Clinical Neurosciences, Neurosurgical Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

Unlabelled: The methods for continuous assessment of cerebral autoregulation using correlation, phase shift, or transmission (either in time- or frequency-domain) were introduced a decade ago. They express dynamic relationships between slow waves of transcranial Doppler (TCD), blood flow velocity (FV) and cerebral perfusion pressure (CPP), or arterial pressure (ABP). We review a methodology and clinical application of indices useful for monitoring cerebral autoregulation and pressure-reactivity in various scenarios of neuro-critical care.

Facts: Poor autoregulation and loss of pressure-reactivity are independent predictors of fatal outcome following head injury. Autoregulation is impaired by too low or too high CPP when compared to autoregulation with normal CPP (usually between 60 and 85 mmHg; and these limits are highly individual). Hemispheric asymmetry of the bi-laterally assessed autoregulation has been associated with asymmetry of CT scan findings: autoregulation was found to be worse ipsilateral to contusion or lateralized edema causing midline shift. The pressure-reactivity (PRx index) correlated with a state of low CBF and CMRO2 revealed using PET studies. The PRx is easier to monitor over prolonged periods of time than the TCD-based indices as it does not require fixation of external probes. Continuous monitoring with the PRx can be used to direct CPP-oriented therapy by determining the optimal CPP for pressure-reactivity. Autoregulation indices are able to reflect transient changes of autoregulation, as seen during plateau waves of ICP. However, minute-to-minute assessment of autoregulation has a poor signal-to-noise ratio. Averaging across time (30 min) or by combining with other relevant parameters improves the accuracy. MYTHS: It is debatable whether the TCD-based indices in head injured patients can be calculated using ABP instead of CPP. Thresholds for functional and disturbed autoregulation dramatically depends on arterial tension of CO2--therefore, comparison between patients cannot be performed without comparing their PaCO2. The TCD pulsatility index cannot accurately detect the lower limit of autoregulation. MISSING LINKS: We still do not know whether autoregulation-oriented therapy can be understood as a consensus between CPP-directed protocols and the Lund-concept. What are the links between endothelial function and autoregulation indices? Can autoregulation after head injury be improved with statins or EPO, as in subarachnoid hemorrhage? In conclusion, monitoring cerebral autoregulation can be used in a variety of clinical scenarios and may be helpful in delineating optimal therapeutic strategies.
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http://dx.doi.org/10.1007/s12028-008-9175-7DOI Listing
September 2009

Early derangements in oxygen and glucose metabolism following head injury: the ischemic penumbra and pathophysiological heterogeneity.

Neurocrit Care 2008 ;9(3):319-25

The Division of Anaesthesia, Addenbrooke's Hospital, University of Cambridge, Box 93, Cambridge, CB2 2QQ, UK.

Introduction: Conclusive evidence of cerebral ischemia following head injury has been elusive. We aimed to use (15)O and (18)Fluorodeoxyglucose positron emission tomography (PET) to investigate pathophysiological derangements following head injury.

Results: Eight patients underwent PET within 24 h of injury to map cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), oxygen extraction fraction (OEF), and cerebral glucose metabolism (CMRglc). Physiological regions of interest (ROI) were generated for each subject using a range of OEF values from very low (<10), low (10-30), normal range (30-50), high (50-70), and critically high (> or =70%). We applied these ROIs to each subject to generate data that would examine the balance between blood flow and metabolism across the injured brain independent of structural injury.

Discussion: Compared to the normal range, brain regions with higher OEF demonstrate a progressive CBF reduction (P < 0.01), CMRO2 increase (P < 0.05), and no change in CMRglc, while regions with lower OEF are associated with reductions in CBF, CMRO2, and CMRglc (P < 0.01). Although all subjects demonstrate a decrease in CBF with increases in OEF > 70%, CMRO2 and CMRglc were generally unchanged. One subject demonstrated a reduction in CBF and small fall in CMRO2 within the high OEF region (>70%), combined with a progressive increase in CMRglc.

Conclusions: The low CBF and maintained CMRO2 in the high OEF ROIs is consistent with classical cerebral ischemia and the presence of an 'ischemic penumbra' following early head injury, while the metabolic heterogeneity that we observed suggests significant pathophysiological complexity. Other mechanisms of energy failure are clearly important and further study is required to delineate the processes involved.
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http://dx.doi.org/10.1007/s12028-008-9119-2DOI Listing
January 2009

An assessment of dynamic autoregulation from spontaneous fluctuations of cerebral blood flow velocity: a comparison of two models, index of autoregulation and mean flow index.

Anesth Analg 2008 Jan;106(1):234-9, table of contents

Academic Neurosurgical Unit, Addenbrooke's Hospital, Cambridge, UK.

Background: Various methods of assessment of cerebral autoregulation, using spontaneous slow fluctuations of blood flow velocity (FV), arterial blood pressure, and cerebral perfusion pressure, have been used in clinical practice. We studied the association between the dynamic index of autoregulation (ARI) and time correlation index (mean flow index, Mx) in a group of patients after head injury.

Methods: Fifty head-injured patients of an average age of 31 yr, sedated, paralyzed, and ventilated (mild hypocapnia) with continuous monitoring of arterial blood pressure and intracranial pressure were studied. Cerebral blood FV was monitored daily for 3 days after injury during periods that were free from interventions (e.g., suctioning). Digitally recorded data were analyzed retrospectively. ARI was calculated as a coefficient graded from 0 (absence of autoregulation) to 9 (strongest autoregulation), describing a dynamic model of autoregulation. Mx was calculated as the correlation coefficient between 40 consecutive 6-s averages of FV and cerebral perfusion pressure and then averaged over the whole recording period. ARI and Mx values, assessed during the first 3 days after injury, were averaged for each patient.

Results: ARI and Mx showed moderately strong mutual linear relationship with correlation r = -0.62; P = 0.0001. Both indices correlated with outcome, indicating worse autoregulation in patients achieving unfavorable outcome.

Conclusion: ARI and Mx agree relatively well in head-injured patients. Autoregulation affects outcome after head injury.
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http://dx.doi.org/10.1213/01.ane.0000295802.89962.13DOI Listing
January 2008

Cerebrovascular reactivity and autonomic drive following traumatic brain injury.

Acta Neurochir Suppl 2008 ;102:3-7

Institute of Anaesthesiology and Intensive Care Medicine, Ospedale Civile, Pzz.le Spedali Civili, 1, 25100 Brescia, Italy.

Introduction: The autonomic nervous system exerts tonic control on cerebral vessels, which in turn determine the autoregulation of cerebral blood flow. We hypothesize that the impairment of cerebral autoregulation following traumatic brain injury might be related to the acute failure of the autonomic system.

Methods: This prospective, observational study included patients with severe traumatic brain injury requiring mechanical ventilation and invasive monitoring of intracranial pressure (ICP) and arterial blood pressure (ABP). Pressure reactivity index (PRx), a validated index of cerebrovascular reactivity, was continuously monitored using bedside computers. Autonomic drive was assessed by means of heart rate variability (HRV) using frequency domain analysis.

Findings: Eighteen TBI patients were included in the study. Cerebrovascular reactivity impairment (PRx above 0.2) and autonomic failure (low spectral power of HRV) are significantly and independently associated with fatal outcome (P = 0.032 and P < 0.001, respectively). We observed a significant correlation between PRx and HRV spectral power (P < 0.001). The high frequency component of HRV (HF, 0.15-0.4Hz) can be used to predict impaired autoregulation (PRx > 0.2), although sensitivity and specificity are low (ROC AUC = 0.67; P = 0.001).

Conclusion: Following traumatic brain injury, autonomic failure and cerebrovascular autoregulation impairment are both associated with fatal outcome. Impairment of cerebrovascular autoregulation and autonomic drive are interdependent phenomena. With some refinements, HRV might become a tool for screening patients at risk for cerebral autoregulation derangement following TBI.
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http://dx.doi.org/10.1007/978-3-211-85578-2_1DOI Listing
June 2009

Continuous time-domain analysis of cerebrovascular autoregulation using near-infrared spectroscopy.

Stroke 2007 Oct 30;38(10):2818-25. Epub 2007 Aug 30.

Johns Hopkins University School of Medicine, Department of Anesthesiology, Division of Pediatric Anesthesiology and Critical Care Medicine, 600 North Wolfe Street, Blalock 904, Baltimore, MD 21287, USA.

Background And Purpose: Assessment of autoregulation in the time domain is a promising monitoring method for actively optimizating cerebral perfusion pressure (CPP) in critically ill patients. The ability to detect loss of autoregulatory vasoreactivity to spontaneous fluctuations in CPP was tested with a new time-domain method that used near-infrared spectroscopic measurements of tissue oxyhemoglobin saturation in an infant animal model.

Methods: Piglets were made progressively hypotensive over 4 to 5 hours by inflation of a balloon catheter in the inferior vena cava, and the breakpoint of autoregulation was determined using laser-Doppler flowmetry. The cerebral oximetry index (COx) was determined as a moving linear correlation coefficient between CPP and INVOS cerebral oximeter waveforms during 300-second periods. A laser-Doppler derived time-domain analysis of spontaneous autoregulation with the same parameters (LDx) was also determined.

Results: An increase in the correlation coefficient between cerebral oximetry values and dynamic CPP fluctuations, indicative of a pressure-passive relationship, occurred when CPP was below the steady state autoregulatory breakpoint. This COx had 92% sensitivity (73% to 99%) and 63% specificity (48% to 76%) for detecting loss of autoregulation attributable to hypotension when COx was above a threshold of 0.36. The area under the receiver-operator characteristics curve for the COx was 0.89. COx correlated with LDx when values were sorted and averaged according to the CPP at which they were obtained (r=0.67).

Conclusions: The COx is sensitive for loss of autoregulation attributable to hypotension and is a promising monitoring tool for determining optimal CPP for patients with acute brain injury.
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http://dx.doi.org/10.1161/STROKEAHA.107.485706DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2377358PMC
October 2007

Is there a direct link between cerebrovascular activity and cerebrospinal fluid pressure-volume compensation?

Stroke 2007 Oct 16;38(10):2677-80. Epub 2007 Aug 16.

Department of Academic Neurosurgery, Box 167 Addenbrooke's Hospital, Cambridge, UK.

Background And Purpose: Cerebral blood flow is coupled to brain metabolism by means of active modulation of cerebrovascular resistance. This homeostatic vasogenic activity is reflected in slow waves of cerebral blood flow velocities (FV) which can also be detected in intracranial pressure (ICP). However, effects of increased ICP on the modulation of cerebral blood flow are still poorly understood. This study focused on the question whether ICP has an independent impact on slow waves of FV within the normal cerebral perfusion pressures range.

Methods: Twenty patients presenting with communicating hydrocephalus underwent a diagnostic intraventricular constant-flow infusion test. Blood flow velocities in the middle cerebral artery and posterior cerebral arteries were measured using Transcranial Doppler. Pulsatility index, FV variability of slow vasogenic waves (3 to 9 bpm), ICP, and arterial blood pressure were simultaneously monitored.

Results: During the test, ICP increased from a baseline of 11 (6) mm Hg to a plateau value of 21 (6) mm Hg (P=0.00005). Although the infusion did not induce significant changes in cerebral perfusion pressures, FV, pulsatility index, or index of autoregulation, the magnitude of FV vasogenic waves at plateau became inversely correlated to ICP (middle cerebral artery: r=-0.58, P<0.01; posterior cerebral arteries: r=-0.54, P<0.01).

Conclusions: This study shows that even moderately increased ICP can limit the modulation of cerebral blood flow in both vascular territories within the autoregulatory range of cerebral perfusion pressures. The exhaustion of cerebrospinal fluid volume buffering reserve during infusion studies elicits a direct interaction between the cerebrospinal fluid space and the cerebrovascular compartment.
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http://dx.doi.org/10.1161/STROKEAHA.107.485847DOI Listing
October 2007

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

Neurosurg Focus 2007 Apr 15;22(4):E2. Epub 2007 Apr 15.

Academic Neurosurgical Unit, Addenbrooke's Hospital, Cambridge, United Kingdom.

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.
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http://dx.doi.org/10.3171/foc.2007.22.4.3DOI Listing
April 2007

Slow oscillations in middle cerebral artery cerebral blood flow velocity and aging.

Neurol Res 2007 Apr;29(3):260-3

Department of Neurosurgery, Alfred Hospital, Prahran, Victoria, Australia.

Objective: A recent study using near infrared spectroscopy (NIRS) showed that low frequency oscillations of regional cerebral blood flow (CBF) decline with age. Using transcranial Doppler ultrasound (TCD), it is possible to monitor similar fluctuations in cerebral blood velocity (CBV) in basal cerebral vessels. Such oscillations have been used widely in the assessment of cerebral autoregulation. We postulated that it should be possible to observe similar age related reductions in the amplitude of slow waves recorded using TCD.

Methods: We studied 187 patients with head injury, who were admitted to Addenbrooke's Neuro Critical Care unit between 1992 and 1998. Intermittent recordings of CBV were undertaken using TCD, which were subsequently analysed using software developed in-house. Power spectra were computed in the very low frequency (VLF: 0.01-0.05 Hz) and low frequency (LF: 0.07-0.11 Hz) ranges for all signals and a regression analysis was performed to assess the correlation between power in each frequency band and age.

Results: No significant correlation was found between VLF or LF power and age (VLF: r=0.037; p=0.63; LF: r=-0.05, p=0.517).

Discussion: While remaining cogniscent of the complex nature of our patient group, we find that age dependent reductions in CBF oscillations seen using NIRS do not translate to recordings of CBV in the middle cerebral artery in patients with head injury.
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http://dx.doi.org/10.1179/174313206X153987DOI Listing
April 2007

Noninvasive evaluation of dynamic cerebrovascular autoregulation using Finapres plethysmograph and transcranial Doppler.

Stroke 2007 Feb 11;38(2):402-4. Epub 2007 Jan 11.

Department of Academic Neurosurgery, Box 167, Addenbrooke's Hospital, Cambridge, UK.

Background And Purpose: Mx is an index of cerebrovascular autoregulation. It is calculated as the correlation coefficient between slow spontaneous fluctuations of cerebral perfusion pressure (cerebral perfusion pressure=arterial blood pressure-intracranial pressure) and cerebral blood flow velocity. Mx can be estimated noninvasively (nMxa) with the use of a finger plethysmograph arterial blood pressure measurement instead of an invasive cerebral perfusion pressure measurement. We investigated the agreement between nMxa and the previously validated index Mx.

Methods: The study included 10 head-injured adults. Intracranial pressure was monitored with a parenchymal probe. Arterial blood pressure was monitored simultaneously with an arterial catheter and with the Finapres plethysmograph. Flow velocity in the middle cerebral artery was measured bilaterally with transcranial Doppler. Mx and nMxa were computed in both hemispheres, and asymmetry of autoregulation was calculated.

Results: Ninety-six measures of Mx and nMxa were obtained (48 for each side) in 10 patients. Mx correlated with nMxa (R=0.755, P<0.001; 95% agreement=+/-0.36; bias=0.01). Asymmetry in autoregulation assessed with Mx correlated significantly with asymmetry estimated with nMxa (R=0.857, P<0.0001; 95% agreement=+/-0.26; bias=-0.03).

Conclusions: The noninvasive index of autoregulation nMxa correlates with Mx and is sensitive enough to detect autoregulation asymmetry. nMxa is proposed as a practical tool to assess cerebral autoregulation in patients who do not require invasive monitoring.
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http://dx.doi.org/10.1161/01.STR.0000254551.92209.5cDOI Listing
February 2007

Impact of intracranial pressure and cerebral perfusion pressure on severe disability and mortality after head injury.

Neurocrit Care 2006 ;4(1):8-13

Academic Neurosurgical Unit Addenbrooke's Hospital, Cambridge, UK.

Objective: To investigate the relationships between intracranial pressure (ICP), cerebral perfusion pressure (CPP), and outcome after traumatic brain injury.

Material And Methods: A retrospective analysis of prospectively recorded data from 429 patients after head injury requiring intensive treatment on the Neuroscience Intensive Annex and the Neuro Critical Care Unit, Cambridge, UK. ICP, CPP, and arterial blood pressure (ABP) were continuously recorded. Mean values of pressures were compared to outcome assessed at 6 months after injury (using the Glasgow Outcome Scale).

Results: The mortality rate was greater in those having mean ICP greater than 20 mmHg (17% below versus 47% above; p < 0.0001). The mortality rate was dramatically increased for CPP below 55 mmHg (81% below versus 23% above; p < 0.0001). For values of CPP greater than 95 mmHg, favorable outcome was less frequent (50% below versus 28% above; p < 0.033). The rate of severe disability showed the tendency to increase with CPP ( r = 0.87; p = 0.02), suggesting that a higher CPP does not help in achieving favorable outcomes. ICP was greater in those who died in comparison to those who survived (27 +/- 19 mmHg versus 16 +/- 6 mmHg; p < 0.10 - 7), and CPP was lower (68 +/- 21 versus 76 +/- 10 mmHg; p < 0.0002). There was no difference between mean ICP and CPP in good/moderate and severe disability outcome groups.

Conclusion: High ICP is strongly associated with fatal outcome. Excessive CPP seems to reduce the probability of achieving a favorable outcome following head trauma.
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http://dx.doi.org/10.1385/NCC:4:1:008DOI Listing
May 2006

Age, intracranial pressure, autoregulation, and outcome after brain trauma.

J Neurosurg 2005 Mar;102(3):450-4

Academic Neurosurgical Unit, Addenbrooke's Hospital, Cambridge, United Kingdom.

Object: The object of this study was to investigate whether a failure of cerebrovascular autoregulation contributes to the relationship between age and outcome in patients following head injury.

Methods: Data obtained from continuous bedside monitoring of intracranial pressure (ICP), arterial blood pressure (ABP), and cerebral perfusion pressure (CPP = ABP - ICP) in 358 patients with head injuries and intermittent monitoring of transcranial Doppler blood flow velocity (FV) in the middle cerebral artery in 237 patients were analyzed retrospectively. Indices used to describe cerebral autoregulation and pressure reactivity were calculated as correlation coefficients between slow waves of systolic FV and CPP (autoregulation index [ARI]) and between ABP and ICP (pressure reactivity index [PRI]). Older patients had worse outcomes after brain trauma than younger patients (p = 0.00001), despite the fact that the older patients had higher initial Glasgow Coma Scale scores (p = 0.006). When age was considered as an independent variable, it appeared that ICP decreased with age (p = 0.005), resulting in an increasing mean CPP (p = 0.0005). Blood FV was not dependent on age (p = 0.58). Indices of autoregulation and pressure reactivity demonstrated a deterioration in cerebrovascular control with advancing age (PRI: p = 0.003; ARI: p = 0.007).

Conclusions: An age-related decline in cerebrovascular autoregulation was associated with a relative deterioration in outcome in elderly patients following head trauma.
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http://dx.doi.org/10.3171/jns.2005.102.3.0450DOI Listing
March 2005

Does the acute diffusion-weighted imaging lesion represent penumbra as well as core? A combined quantitative PET/MRI voxel-based study.

J Cereb Blood Flow Metab 2004 Nov;24(11):1249-54

Department of Clinical Neurosciences, University of Cambridge, Cambridge CB2 2QQ, UK.

In acute ischemic stroke, the diffusion-weighted imaging (DWI) lesion is widely held to represent the core of irreversible damage and is therefore crucial in selecting patients for thrombolysis. However, recent research suggests it may also represent penumbra. An illustrative patient was imaged 7 hours after stroke onset with back-to-back 3T diffusion tensor imaging and quantitative positron emission tomography, which showed a DWI lesion and misery perfusion, respectively. Using previously validated voxel-based probabilistic CBF, CMRO2, and Oxygen Extraction Fraction (OEF) thresholds, the authors show that the DWI lesion contained not only core but also substantial proportions of penumbra. Also, severe apparent diffusion coefficient reductions were present within the potentially salvageable penumbra as well as in the core. These findings have potential implications regarding treatment decisions.
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http://dx.doi.org/10.1097/01.WCB.0000141557.32867.6BDOI Listing
November 2004

Relationship between flow-metabolism uncoupling and evolving axonal injury after experimental traumatic brain injury.

J Cereb Blood Flow Metab 2004 Sep;24(9):1025-36

Academic Neurosurgery, Center for Brain Repair, University of Cambridge, Robinson Way, UK.

Blood flow-metabolism uncoupling is a well-documented phenomenon after traumatic brain injury, but little is known about the direct consequences for white matter. The aim of this study was to quantitatively assess the topographic interrelationship between local cerebral blood flow (LCBF) and glucose metabolism (LCMRglc) after controlled cortical impact injury and to determine the degree of correspondence with the evolving axonal injury. LCMRglc and LCBF measurements were obtained at 3 hours in the same rat from 18F-fluorodeoxyglucose and 14C-iodoantipyrine coregistered autoradiographic images, and compared to the density of damaged axonal profiles in adjacent sections and in an additional group at 24 hours using beta-amyloid precursor protein (beta-APP) immunohistochemistry. LCBF was significantly reduced over the ipsilateral hemisphere by 48 +/- 15% compared with sham-controls, whereas LCMRglc was unaffected, apart from foci of elevated LCMRglc in the contusion margin. Flow-metabolism was uncoupled, indicated by a significant 2-fold elevation in the LCMRglc/LCBF ratio within most ipsilateral structures. There was a significant increase in beta-APP-stained axons from 3 to 24 hours, which was negatively correlated with LCBF and positively correlated with the LCMRglc/LCBF ratio at 3 hours in the cingulum and corpus callosum. Our study indicates a possible dependence of axonal outcome on flow-metabolism in the acute injury stage.
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http://dx.doi.org/10.1097/01.WCB.0000129415.34520.47DOI Listing
September 2004

Pressure autoregulation and positron emission tomography-derived cerebral blood flow acetazolamide reactivity in patients with carotid artery stenosis.

Neurosurgery 2004 Jul;55(1):63-7; discussion 67-8

Wolfson Brain Imaging Centre and Academic Department of Neurosurgery, Addenbrooke's Hospital, Cambridge, England.

Objective: Testing autoregulation is of importance in predicting risk of stroke and managing patients with occlusive carotid arterial disease. The use of small spontaneous changes in arterial blood pressure and transcranial Doppler (TCD) flow velocity can be used to assess autoregulation noninvasively without the need for a cerebrovascular challenge. We have previously described an index (called "Mx") that achieves this. Negative or low positive values (<0.4) indicate intact pressure autoregulation, whereas an Mx greater than 0.4 indicates diminished autoregulation. The objective of this study was to compare acetazolamide reactivity of positron emission tomography (PET)-derived cerebral blood flow (CBF) with Mx in patients with carotid arterial disease.

Methods: In 40 patients with carotid arterial disease, we used bilateral TCD recordings of the middle cerebral artery to derive Mx and compared this with PET-derived CBF measurements of acetazolamide reactivity.

Results: Mx correlated inversely with baseline PET CBF (P = 0.042, R = -0.349) but not with postacetazolamide CBF or cerebrovascular reactivity to acetazolamide. This may reflect discordance between pressure autoregulation and acetazolamide reactivity. Mx correlated significantly with degree of internal carotid artery stenosis (P = 0.022, R = 0.38), whereas CBF reactivity to acetazolamide did not correlate with Mx (P = 0.22). After the administration of acetazolamide, slow-wave activity in blood pressure and TCD flow velocity recordings was seen to diminish, rendering the calculation of Mx unreliable after acetazolamide.

Conclusion: The measurement of Mx offers a noninvasive, safe technique for assessing abnormalities of pressure autoregulation in patients with carotid arterial disease.
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http://dx.doi.org/10.1227/01.neu.0000126876.10254.05DOI Listing
July 2004

Changes in cerebral blood flow during cerebrospinal fluid pressure manipulation in patients with normal pressure hydrocephalus: a methodological study.

J Cereb Blood Flow Metab 2004 May;24(5):579-87

Academic Neurosurgery Unit, Addenbrooke's Hospital, University of Cambridge, Cambridge, United Kingdom.

The combination of cerebral blood flow measurement using (15)O-water positron emission tomography with magnetic resonance coregistration and CSF infusion studies was used to study the global and regional changes in CBF with changes in CSF pressure in 15 patients with normal pressure hydrocephalus. With increases in CSF pressure, there was a variable increase in arterial blood pressure between individuals and global CBF was reduced, including in the cerebellum. Regionally, mean CBF decreased in the thalamus and basal ganglia, as well as in white matter regions. These reductions in CBF were significantly correlated with changes in the CSF pressure and with proximity to the ventricles. A three-dimensional finite-element analysis was used to analyze the effects on ventricular size and the distribution of stress during infusion. To study regional cerebral autoregulation in patients with possible normal pressure hydrocephalus, a sensitive CBF technique is required that provides absolute, not relative normalized, values for regional CBF and an adequate change in cerebral perfusion pressure must be provoked.
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http://dx.doi.org/10.1097/00004647-200405000-00012DOI Listing
May 2004

Incidence and mechanisms of cerebral ischemia in early clinical head injury.

J Cereb Blood Flow Metab 2004 Feb;24(2):202-11

The Division of Anaesthesia, and The Wolfson Brain Imaging Centre, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

Antemortem demonstration of ischemia has proved elusive in head injury because regional CBF reductions may represent hypoperfusion appropriately coupled to hypometabolism. Fifteen patients underwent positron emission tomography within 24 hours of head injury to map cerebral blood flow (CBF), cerebral oxygen metabolism (CMRO2), and oxygen extraction fraction (OEF). We estimated the volume of ischemic brain (IBV) and used the standard deviation of the OEF distribution to estimate the efficiency of coupling between CBF and CMRO2. The IBV in patients was significantly higher than controls (67 +/- 69 vs. 2 +/- 3 mL; P < 0.01). The coexistence of relative ischemia and hyperemia in some patients implies mismatching of perfusion to oxygen use. Whereas the saturation of jugular bulb blood (SjO2) correlated with the IBV (r = 0.8, P < 0.01), SjO2 values of 50% were only achieved at an IBV of 170 +/- 63 mL (mean +/- 95% CI), which equates to 13 +/- 5% of the brain. Increases in IBV correlated with a poor Glasgow Outcome Score 6 months after injury (rho = -0.6, P < 0.05). These results suggest significant ischemia within the first day after head injury. The ischemic burden represented by this "traumatic penumbra" is poorly detected by bedside clinical monitors and has significant associations with outcome.
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http://dx.doi.org/10.1097/01.WCB.0000103022.98348.24DOI Listing
February 2004