Search

Significance: Intracranial pressure (ICP), variability in perfusion, and resulting ischemia are leading causes of secondary brain injury in patients treated in the neurointensive care unit. Continuous, accurate monitoring of cerebral blood flow (CBF) and ICP guide intervention and ultimately reduce morbidity and mortality. Currently, only invasive tools are used to monitor patients at high risk for intracranial hypertension. Aim: Diffuse correlation spectroscopy (DCS), a noninvasive near-infrared optical technique, is emerging as a possible method for continuous monitoring of CBF and critical closing pressure (CrCP or zero-flow pressure), a parameter directly related to ICP. Approach: We optimized DCS hardware and algorithms for the quantification of CrCP. Toward its clinical translation, we validated the DCS estimates of cerebral blood flow index (CBFi) and CrCP in ischemic stroke patients with respect to simultaneously acquired transcranial Doppler ultrasound (TCD) cerebral blood flow velocity (CBFV) and CrCP. Results: We found CrCP derived from DCS and TCD were highly linearly correlated (ipsilateral R2 = 0.77, p = 9 × 10 − 7; contralateral R2 = 0.83, p = 7 × 10 − 8). We found weaker correlations between CBFi and CBFV (ipsilateral R2 = 0.25, p = 0.03; contralateral R2 = 0.48, p = 1 × 10 − 3) probably due to the different vasculature measured. Conclusion: Our results suggest DCS is a valid alternative to TCD for continuous monitoring of CrCP.

Objective: The time constant of the cerebral arterial bed (τ), which is an index of brain haemodynamics, can be estimated in patients using continuous monitoring of arterial blood pressure (ABP), transcranial Doppler cerebral blood flow velocity (CBFV) and intracranial pressure (ICP) if these measures are available. But, in some clinical scenarios invasive measurement of ABP is not feasible. Therefore, in this study we aimed to investigate whether invasive ABP can be replaced with non-invasive ABP, monitored using the Finapres photoplethysmograph (fABP). Approach: Forty-six recordings of ICP, ABP, fABP, and CBFV in the right and left middle cerebral arteries were performed daily for approximately 30 min in 10 head injury patients. Two modelling approaches (constant flow forward [CFF, pulsatile blood inflow and steady blood outflow] and pulsatile flow forward [PFF, where both blood inflow and outflow are pulsatile]) were applied to estimate τ using either invasive ABP (τCFF, τPFF) or non-invasive ABP (fτCFF, fτPFF). Main results: Bland–Altman analysis showed quite poor agreement between the fτ and τ methods of estimation. The fτ method produced significantly higher values than the τ method when calculated using both the CFF and PFF models (p < .001 for both). The correlation between fτCFF and τCFF was moderately high (r s = 0.63; p < .001), whereas that between fτPFF and τPFF was weaker (r s = 0.40; p = .009). Significance: Our results suggest that using non-invasive ABP for estimation of τ is inaccurate in head injury patients.

Postischaemic pyrexia exacerbates neuronal damage. Hyperthermia related cerebral changes have still not been well investigated in humans.To study how pyrexia affects neurochemistry and cerebral oxygenation after acute brain injury.18 acutely brain injured patients were studied at the onset and resolution of febrile episodes (brain temperatureor = 38.7 degrees C). Intracranial pressure (ICP), brain tissue oxygen tension (PbrO2), and brain tissue temperature (Tbr) were recorded continuously; jugular venous blood was sampled intermittently. Microdialysis probes were inserted in the cerebral cortex and in subcutaneous tissue. Glucose, lactate, pyruvate, and glutamate were measured hourly. The lactate to pyruvate ratio was calculated.Mean (SD) Tbr rose from 38 (0.5) to 39.3 (0.3) degrees C. Arteriojugular oxygen content difference (AJD(O2)) fell from 4.2 (0.7) to 3.8 (0.5) vol% (p0.05) and PbrO2 rose from 32 (21) to 37 (22) mm Hg (p0.05). ICP increased slightly and no significant neurochemical alterations occurred. Opposite changes were recorded when brain temperature returned towards baseline.As long as substrate and oxygen delivery remain adequate, hyperthermia on its own does not seem to induce any further significant neurochemical alterations. Changes in cerebral blood volume may, however, affect intracranial pressure.

Background: It has been suggested that a moving correlation index between mean arterial blood pressure and intracranial pressure, called PRx, can be used to monitor and quantify cerebral vasomotor reactivity in patients with head injury. Objectives: To validate this index and study its relation with cerebral blood flow velocity and cerebral autoregulation; and to identify variables associated with impairment or preservation of cerebral vasomotor reactivity. Methods: The PRx was validated in a prospective study of 40 head injured patients. A PRx value of less than 0.3 indicates intact cerebral vasomotor reactivity, and a value of more than 0.3, impaired reactivity. Arterial blood pressure, intracranial pressure, mean cerebral perfusion pressure, and cerebral blood flow velocity, measured bilaterally with transcranial Doppler ultrasound, were recorded. Dynamic cerebrovascular autoregulation was measured using a moving correlation coefficient between arterial blood pressure and cerebral blood flow velocity, the Mx, for each cerebral hemisphere. All variables were compared in patients with intact and impaired cerebral vasomotor reactivity. Results: No correlation between arterial blood pressure or cerebral perfusion pressure and cerebral blood flow velocity was seen in 19 patients with intact cerebral vasomotor reactivity. In contrast, the correlation between these variables was significant in 21 patients with impaired cerebral vasomotor reactivity, whose cerebral autoregulation was reduced. There was no correlation with intracranial pressure, arterial blood pressure, cerebral perfusion pressure, or interhemispheric cerebral autoregulation differences, but the values for these indices were largely within normal limits. Conclusions: The PRx is valid for monitoring and quantifying cerebral vasomotor reactivity in patients with head injury. This intracranial pressure based index reflects changes in cerebral blood flow and cerebral autoregulatory capacity, suggesting a close link between blood flow and intracranial pressure in head injured patients. This explains why increases in arterial blood pressure and cerebral perfusion pressure may be useful for reducing intracranial pressure in selected head injured patients (those with intact cerebral vasomotor reactivity).

Objective: To evaluate the effects of a brain tissue oxygen (P ti o 2 ) guided treatment in patients with traumatic brain injury. Methods: P ti o 2 was monitored in 93 patients with severe traumatic brain injury. Forty patients admitted from 1993 to 1996 were treated with intracranial pressure/cerebral perfusion pressure (ICP/CPP) management alone (ICP 70 mm Hg). Fifty three patients admitted from 1997 to 2000 were treated using ICP/CPP management, but in this second group CPP was also increased as individually required to raise the P ti o 2 above 1.33 kPa (10 mm Hg) (P ti o 2 guided group). Results: Cerebral hypoxic phases with P ti o 2 values below 1.33 kPa occurred significantly less often in the P ti o 2 guided group. P ti o 2 values were higher over the whole monitoring period. No statistical differences could be observed in outcome at six months, despite a positive trend in the P ti o 2 guided group. Conclusions: Cerebral hypoxic events can be reduced significantly by increasing cerebral perfusion pressure as required. To show a clear beneficial effect of P ti o 2 guided cerebral perfusion pressure management on outcome, a multicentre randomised trial needs to be undertaken.

Background: After head injury, impaired cerebrovascular autoregulation has been associated with abnormally high or low cerebral blood flow. The physiological relevance of cerebral blood flow levels is difficult to assess in these patients, whose cerebral metabolic rate for oxygen (CMRO2) is known to be abnormal. Investigation of these relations requires quantitative measures of cerebral blood flow and CMRO2, to allow assessment of oxygen supply and demand relations. Objectives: To investigate the relation between dysautoregulation and global cerebral oxygen metabolism following head injury. Methods: Using positron emission tomography, global cerebral blood flow, CMRO2, and oxygen extraction fraction were determined in 22 patients who were investigated in 26 examinations on days 1 to 11 (mean (SD), 3.5 (2.3)) after head injury. Cerebrovascular pressure reactivity was assessed using a pressure reactivity index, calculated as the moving linear correlation coefficient between mean arterial blood pressure and intracranial pressure. Outcome was assessed six months after injury using the Glasgow outcome scale. Results: Low CMRO2 was associated with disturbed pressure reactivity (inverse function, R2 = 0.21, p = 0.018) and there was a correlation between disturbed pressure reactivity and oxygen extraction fraction (quadratic function, R2 = 0.55, p = 0.0001). There was no significant relation between pressure reactivity and cerebral blood flow. An unfavourable outcome was associated with disturbed pressure reactivity. There was no significant relation between outcome and CMRO2 or oxygen extraction fraction. Conclusions: There is a close relation between dysautoregulation and abnormal cerebral metabolism but not blood flow. Further studies are needed to determine whether metabolic dysfunction is a result of or a cause of disturbed pressure reactivity, and to establish if there is a relation between cerebral oxygen metabolism and outcome.

Objectives: There is little reliable quantitative information on preoperative quality of life of patients with brain tumours. The aim of this study was to clarify the effect of the volume, location, and histological grade of brain tumours on the preoperative quality of life of patients. Methods: The study population consisted of 101 successive patients with brain tumour at Oulu Clinic for Neurosurgery studied with CT or MRI for preoperative determination of tumour location and size. The Nottingham health profile (NHP) and Sintonen's 15D scale were used at that time to measure quality of life. Results: Tumour size did not correlate linearly with impairment of quality of life. Large tumours (>25 ml) were associated with poorer quality of life than small tumours (≤25 ml). The patients with a tumour located on the right side or in the anterior region reported a poorer quality of life than those with a tumour on the left side or posteriorly. Quality of life assessments made by doctors using the Karnofsky performance scale showed no differences between the two hemispheres. Patients with the most malignant gliomas (grades III-IV) displayed the poorest quality of life. Conclusions: Large tumours apparently damage several parts of the brain and/or raise intracranial pressure to a level that exceeds the brain's compensatory capacity. Contrary to earlier understanding, tumours in the right hemisphere seemed to be related to poorer quality of life. This effect was especially clear in the patients' subjective evaluation of their quality of life. As the location of the brain tumour thus affects perceived quality of life, any measurements of the quality of life of patients with brain tumours should take into account the location and laterality of the tumour.

Background: Arachnoid cysts (AC) can cause a wide spectrum of clinical symptoms. Only a limited number of studies have investigated intracranial pressure in patients with AC. We wished to investigate the relationship between intracystic pressure, preoperative complaints and postoperative symptom relief in adult patients operated on for a unilateral temporal AC. Material and methods: This was a prospective, population based study involving 38 adult (>18 years) patients (mean age 43 years; range 18–69) with a previously untreated unilateral temporal AC. Results: For all cyst types, mean pressure was 131 mm H 2 O. The main preoperative complaints were headache and dizziness/nausea. By median split, patients were divided into a low pressure ( 2 O) and a high pressure (>130 mm H 2 O) group. Patients with high intracystic pressure had a significantly higher preoperative visual analogue scale (VAS) score (54.7) than that found in patients with low intracystic pressure (39.4). Both pressure groups had a significant fall in VAS score after surgical decompression of the cyst. Intracystic pressure correlated significantly with arterial pCO 2 and mean arterial pressure. Conclusion: There was a significant correlation between intracystic pressure and the preoperative level of complaints. Mean intracystic pressure in adult patients with unilateral temporal AC seems to lie within the limits of normal intracranial pressure. We therefore hypothesise that factors other than absolute pressure, such as altered compliance and impedance of the brain, may be involved in the pathophysiology of intracranial AC.

Objective: To determine the statistical characteristics of blood pressure (BP) readings from a large number of head-injured patients. Methods: The BrainIT group has collected high time-resolution physiological and clinical data from head-injured patients who require intracranial pressure (ICP) monitoring. The statistical features of this dataset of BP measurements with time resolution of 1 min from 200 patients is examined. The distributions of BP measurements and their relationship with simultaneous ICP measurements are described. Results: The distributions of mean, systolic and diastolic readings are close to normal with modest skewing towards higher values. There is a trend towards an increase in blood pressure with advancing age, but this is not significant. Simultaneous blood pressure and ICP values suggest a triphasic relationship with a BP rising at 0.28 mm Hg/mm Hg of ICP, for ICP up to 32 mm Hg, and 0.9 mm Hg/mm Hg of ICP for ICP from 33 to 55 mm Hg, and falling sharply with rising ICP for ICP >55 mm Hg. Conclusions: Patients with head injury appear to have a near normal distribution of blood pressure readings that are skewed towards higher values. The relationship between BP and ICP may be triphasic.

Objective: To investigate the temporal relationship between cerebrovascular pressure reactivity and brain tissue oxygenation in patients with severe head injury. Methods: In 40 patients, brain tissue oxygenation and intracranial pressure were monitored. Time-averaged values for intracranial pressure (ICP), mean arterial pressure (MAP), cerebral perfusion pressure (CPP) and brain tissue oxygenation (PtiO 2 ) were computed. The pressure reactivity index (PRx) was calculated. The mean values of the variables were obtained at the 6-h and 72-h post-injury time points, and the difference between the two time points for each of the variables was denoted as delta (δ). Results: Of the 40 patients, 32 were survivors and 8 were non-survivors. Statistically significant differences were present between these two groups with regard to δMAP (p = 0.013), ICP at 6 h (p = 0.027), CPP at 72 h (p = 0.018), δCPP (p = 0.033), PRx at 6 h (p = 0.029), PRx at 72 h (p = 0.002), PtiO 2 at 72 h (p 2 (p = 0.023) values, reflecting an improvement with time in survivors and a deterioration with time in non-survivors. In non-survivors, the magnitude of change in PtiO 2 and CPP with time correlated in a negative linear fashion (p = 0.042 and 0.029, respectively) with the change in PRx with time, whereas no such relationship was seen in survivors. Conclusion: The severity of brain tissue oxygenation derangement correlates with increasing cerebrovascular dysautoregulation in patients succumbing to severe head injury, supporting the utility of PRx as a monitoring variable and the rationale for a target-driven approach to head injury management.

Background: The principal strategy for managing head injury is to reduce the frequency and severity of secondary brain insults from intracranial pressure (ICP) and cerebral perfusion pressure (CPP), and hence improve outcome. Precise critical threshold levels have not been determined in head injured children. Objective: To create a novel pressure–time index (PTI) measuring both duration and amplitude of insult, and then employ it to determine critical insult thresholds of ICP and CPP in children. Methods: Prospective, observational, physiologically based study from Edinburgh and Newcastle, using patient monitored blood pressure, ICP, and CPP time series data. The PTI for ICP and CPP for 81 children, using theoretical values derived from physiological norms, was varied systematically to derive critical insult thresholds which delineate Glasgow outcome scale categories. Results: The PTI for CPP had a very high predictive value for outcome (receiver operating characteristic analyses: area under curve = 0.957 and 0.890 for mortality and favourable outcome, respectively) and was more predictive than for ICP. Initial physiological values most accurately predicted favourable outcome. The CPP critical threshold values determined for children aged 2–6, 7–10, and 11–15 years were 48, 54, and 58 mm Hg. respectively. Conclusions: The PTI is the first substantive paediatric index of total ICP and CPP following head injury. The insult thresholds generated are identical to age related physiological values. Management guidelines for paediatric head injuries should take account of these CPP thresholds to titrate appropriate pressor therapy.

The symptoms in idiopathic adult hydrocephalus syndrome (IAHS) are consistent with pathology involving the periventricular white matter, presumably reflecting ischaemia and CSF hydrodynamic disturbance.To investigate whether a change in intracranial pressure (ICP) can affect energy metabolism in deep white matter.A microdialysis catheter, a brain tissue oxygen tension probe, and an ICP transducer were inserted into the periventricular white matter 0-7 mm from the right frontal horn in 10 patients with IAHS. ICP and intracerebral Ptio2 were recorded continuously during lumbar CSF constant pressure infusion test. ICP was raised to pressure levels of 35 and 45 mm Hg for 10 minutes each, after which CSF drainage was undertaken. Microdialysis samples were collected every three minutes and analysed for glucose, lactate, pyruvate, and glutamate.When raising the ICP, a reversible drop in the extracellular concentrations of glucose, lactate, and pyruvate was found. Comparing the values during baseline to values at the highest pressure level, the fall in glucose, lactate, and pyruvate was significant (p0.05, Wilcoxon sign rank). There was no change in glutamate or the lactate to pyruvate ratio during ICP elevation. Ptio2 did not decrease during ICP elevation, but was significantly increased following CSF drainage.Raising intracranial pressure induces an immediate and reversible change in energy metabolism in periventricular white matter, without any sign of ischaemia. Theoretically, frequent ICP peaks (B waves) over a long period could eventually cause persisting axonal disturbance and subsequently the symptoms noted in IAHS.

B waves, slow and rhythmic oscillations in intracranial pressure (ICP), are claimed to be one of the best predictors of outcome after surgery for normal pressure hydrocephalus (NPH).To determine the relation between the percentage of B waves and outcome in patients with hydrocephalus, and also the diurnal variation of B waves.ICP and patient behaviour were recorded overnight (17 to 26 hours) in 29 patients with non-communicating hydrocephalus and 26 with NPH. The B wave activity, measured with an amplitude threshold of 0.5, 0.75, 1.0, 1.5, 2.0, 3.0, and 5.0 mm Hg, was estimated as the percentage of total monitoring time (% B waves) using a computer algorithm, and correlated with postoperative outcome, defined as changes in 12 standardised symptoms and signs.There was no linear correlation between improvement after surgery in the 55 patients and total % B waves, but a correlation was found between improvement and % B waves during sleep (r = 0.39, p = 0.04). The percentage of B waves was the same during sleep and wakefulness, and patients with NPH had the same proportion of B waves as the non-communicating patients.B waves are commonly observed in patients with both communicating and non-communicating hydrocephalus, but are only weakly related to the degree of postsurgical improvement.

Objectives: To explore the outcome of management of possible shunt related symptoms using intracranial pressure (ICP) monitoring, and to identify potential methodological limitations with the current strategies of ICP assessment. Methods: The distribution of persistent symptoms related to extracranial shunt treatment was compared before and after management of shunt failure in 69 consecutive hydrocephalic cases. Management was heavily based on ICP monitoring (calculation of mean ICP and visual determination of plateau waves). After the end of patient management, all ICP curves were re-evaluated using a quantitative method and software (SensometricsTM pressure analyser). The ICP curves were presented as a matrix of numbers of ICP elevations (20 to 35 mm Hg) or depressions (-10 to -5 mm Hg) of different durations (0.5, 1, or 5 minutes). The numbers of ICP elevations/depressions standardised to 10 hours recording time were calculated to allow comparisons of ICP between individuals. Results: After ICP monitoring and management of the putative shunt related symptoms, the symptoms remained unchanged in as many as 58% of the cases, with the highest percentages in those patients with ICP considered normal or too low at the time of ICP monitoring. The quantitative analysis revealed a high frequency of ICP elevations (20 to 35 mm Hg lasting 0.5 to 1 minute) and ICP depressions (-10 to -5 mm Hg lasting 0.5, 1, or 5 minutes), particularly in patients with ICP considered normal. Conclusions: The value of continuous ICP monitoring with ICP analysis using current criteria appears doubtful in the management of possible shunt related symptoms. This may reflect limitations in the strategies of ICP analysis. Calculation of the exact numbers of ICP elevations and depressions may provide a more accurate description of the ICP profile.

Objectives: Increases in the extracellular concentration of the excitatory amino acids glutamate and aspartate during cerebral ischaemia in patients are well recognised. Less emphasis has been placed on the concentrations of the inhibitory amino acid neurotransmitters, notably γ-amino-butyric acid (GABA), despite evidence from animal studies that GABA may act as a neuroprotectant in models of ischaemia. The objective of this study was to investigate the concentrations of various excitatory, inhibitory and non-transmitter amino acids under basal conditions and during periods of cerebral ischaemia in patients with head injury or a subarachnoid haemorrhage. Methods: Cerebral microdialysis was established in 12 patients with head injury (n=7) or subarachnoid haemorrhage (n=5). Analysis was performed using high performance liquid chromatography for a total of 19 (excitatory, inhibitory and non-transmitter) amino acids. Patients were monitored in neurointensive care or during aneurysm clipping. Results: During stable periods of monitoring the concentrations of amino acids were relatively constant enabling basal values to be established. In six patients, cerebral ischaemia was associated with increases (up to 1350 fold) in the concentration of GABA, in addition to the glutamate and aspartate. Parallel increases in the concentration of glutamate and GABA were found ( r =0.71, p Conclusions: The results suggest that, in the human brain, acute cerebral ischaemia is not accompanied by an imbalance between excitatory and inhibitory amino acids, but by an increase in all neurotransmitter amino acids. These findings concur with the animal models of ischaemia and raise the possibility of an endogenous GABA mediated neuroprotective mechanism in humans.