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1.  Brain Monitoring: Do We Need a Hole? An Update on Invasive and Noninvasive Brain Monitoring Modalities 
The Scientific World Journal  2014;2014:795762.
The ability to measure reliably the changes in the physical and biochemical environment after a brain injury is of great value in the prevention, treatment, and understanding of the secondary injuries. Three categories of multimodal brain monitoring exist: direct signals which are monitored invasively; variables which may be monitored noninvasively; and variables describing brain pathophysiology which are not monitored directly but are calculated at the bedside by dedicated computer software. Intracranial pressure (ICP) monitoring, either as stand-alone value or study of a dynamic trend, has become an important diagnostic tool in the diagnosis and management of multiple neurological conditions. Attempts have been made to measure ICP non-invasively, but this is not a clinical reality yet. There is contrasting evidence that monitoring of ICP is associated with better outcome, and further RCTs based on management protocol are warranted. Computer bedside calculation of “secondary parameters” has shown to be potentially helpful, particularly in helping to optimize “CPP-guided therapy.” In this paper we describe the most popular invasive and non invasive monitoring modalities, with great attention to their clinical interpretation based on the current published evidence.
doi:10.1155/2014/795762
PMCID: PMC3930194  PMID: 24672373
2.  What comes first? The dynamics of cerebral oxygenation and blood flow in response to changes in arterial pressure and intracranial pressure after head injury 
Background
Brain tissue partial oxygen pressure (PbtO2) and near-infrared spectroscopy (NIRS) are novel methods to evaluate cerebral oxygenation. We studied the response patterns of PbtO2, NIRS, and cerebral blood flow velocity (CBFV) to changes in arterial pressure (AP) and intracranial pressure (ICP).
Methods
Digital recordings of multimodal brain monitoring from 42 head-injured patients were retrospectively analysed. Response latencies and patterns of PbtO2, NIRS-derived parameters [tissue oxygenation index (TOI) and total haemoglobin index (THI)], and CBFV reactions to fluctuations of AP and ICP were studied.
Results
One hundred and twenty-one events were identified. In reaction to alterations of AP, ICP reacted first [4.3 s; inter-quartile range (IQR) −4.9 to 22.0 s, followed by NIRS-derived parameters and CBFV (10.9 s; IQR: −5.9 to 39.6 s, 12.1 s; IQR: −3.0 to 49.1 s, 14.7 s; IQR: −8.8 to 52.3 s for THI, CBFV, and TOI, respectively), with PbtO2 reacting last (39.6 s; IQR: 16.4 to 66.0 s). The differences in reaction time between NIRS parameters and PbtO2 were significant (P<0.001). Similarly when reactions to ICP changes were analysed, NIRS parameters preceded PbtO2 (7.1 s; IQR: −8.8 to 195.0 s, 18.1 s; IQR: −20.6 to 80.7 s, 22.9 s; IQR: 11.0 to 53.0 s for THI, TOI, and PbtO2, respectively). Two main patterns of responses to AP changes were identified. With preserved cerebrovascular reactivity, TOI and PbtO2 followed the direction of AP. With impaired cerebrovascular reactivity, TOI and PbtO2 decreased while AP and ICP increased. In 77% of events, the direction of TOI changes was concordant with PbtO2.
Conclusions
NIRS and transcranial Doppler signals reacted first to AP and ICP changes. The reaction of PbtO2 is delayed. The results imply that the analysed modalities monitor different stages of cerebral oxygenation.
doi:10.1093/bja/aer324
PMCID: PMC3236021  PMID: 22037222
brain tissue partial oxygen pressure; cerebral haemodynamics; cerebral oxygenation; cerebrovascular reactivity; near-infrared spectroscopy; tissue haemoglobin index; tissue oxygenation index
3.  Effect of age on intraoperative cerebrovascular autoregulation and near-infrared spectroscopy-derived cerebral oxygenation 
BJA: British Journal of Anaesthesia  2011;107(5):742-748.
Background
Age is an important risk factor for perioperative cerebral complications such as stroke, postoperative cognitive dysfunction, and delirium. We explored the hypothesis that intraoperative cerebrovascular autoregulation is less efficient and brain tissue oxygenation lower in elderly patients, thus, increasing the vulnerability of elderly brains to systemic insults such as hypotension.
Methods
We monitored intraoperative cerebral perfusion in 50 patients aged 18–40 and 77 patients >65 yr at two Swiss university hospitals. Mean arterial pressure (MAP) was measured continuously using a plethysmographic method. An index of cerebrovascular autoregulation (Mx) was calculated based on changes in transcranial Doppler flow velocity due to changes in MAP. Cerebral oxygenation was assessed by the tissue oxygenation index (TOI) using near-infrared spectroscopy. End-tidal CO2, O2, and sevoflurane concentrations and peripheral oxygen saturation were recorded continuously. Standardized anaesthesia was administered in all patients (thiopental, sevoflurane, fentanyl, atracurium).
Results
Autoregulation was less efficient in patients aged >65 yr [by 0.10 (se 0.04; P=0.020)] in a multivariable linear regression analysis. This difference was not attributable to differences in MAP, end-tidal CO2, or higher doses of sevoflurane. TOI was not significantly associated with age, sevoflurane dose, or Mx but increased with increasing flow velocity [by 0.09 (se 0.04; P=0.028)] and increasing MAP [by 0.11 (se 0.05; P=0.043)].
Conclusions
Our results do not support the hypothesis that older patients' brains are more vulnerable to systemic insults. The difference of autoregulation between the two groups was small and most likely clinically insignificant.
doi:10.1093/bja/aer252
PMCID: PMC3192482  PMID: 21835838
age groups; anaesthesia; cerebrovascular circulation
6.  Asymmetry of critical closing pressure following head injury 
Objective: Critical closing pressure (CCP) is the arterial pressure below which the vessels collapse. Hypothetically it is the sum of intracranial pressure (ICP) and vessel wall tension in the cerebral circulation. This study investigated transhemispherical asymmetry of CCP by studying its correlation with radiological findings on computed tomography (CT) scans in head injury patients.
Method: ICP, arterial blood pressure, and middle cerebral artery blood flow velocity were recorded daily in 119 ventilated patients. Waveforms were processed to calculate CCP. CT scans were analysed according to a system based on the Marshall classification.
Results: Left–right differences in CCP correlated with midline shift on the CT scan (r = 0.48; p<0.02). Asymmetry of CCP also corresponded with the side of the head lesion (p<0.007) and the side of the craniotomy where it was performed (p<0.006). Absolute CCP weakly correlated with brain swelling (r = –0.23; p<0.03) and arterial pressure (r = 0.21; p<0.02) but did not correlate with ICP. Cerebral perfusion pressure calculated as the difference between mean arterial pressure and CCP did not correlate with outcome, but "traditional" cerebral perfusion pressure (mean arterial pressure minus intracranial pressure) did.
Conclusions: Critical closing pressure is disturbed by localised brain lesions. Its asymmetry corresponds to asymmetrical findings on CT scans. CCP seems to describe vascular resistance better than ICP.
doi:10.1136/jnnp.2004.059493
PMCID: PMC1739415  PMID: 16227554
7.  Brain tissue oxygenation: more than a number 
Critical Care  2008;12(Suppl 2):P109.
doi:10.1186/cc6330
PMCID: PMC4088480
8.  Plateau waves: changes of cerebrovascular pressure transmission 
Summary
Objective
To test the validity of the hypothesis that active vasodilatation and vasoconstriction underlie the occurrence of intracranial pressure (ICP) plateau waves by evaluating corresponding changes of cerebrovascular pressure transmission of arterial blood pressure (ABP) to ICP.
Methods
Digitized recordings of ICP and ABP sampled at 30 Hz were obtained from nine patients with traumatic brain injury. For each 16.5 s recording interval mean values of ICP, ABP, cerebral perfusion pressure (CPP), and the corresponding highest modal frequency (HMF) of cerebrovascular pressure transmission were calculated.
Results
Mean ICP and HMF significantly increased (P < 0.003) and mean CPP decreased significantly (P < 0.00036) at onset of the wave. Conversely at termination, mean ICP and HMF significantly decreased (P < 0.026) and mean CPP significantly increased (P < 0.028). In addition, the strong negative correlations between mean ICP and mean CPP (r = −0.87) and mean HMF and CPP (r = −0.87) were demonstrated.
Conclusion
The findings that HMF increased at onset and decreased at the termination of plateau wave support the validity of the vasodilatatory/constriction cascade model that postulates active vasodilation at the onset and active vasoconstriction of the cerebrovascular bed at the termination of a plateau wave.
PMCID: PMC1444891  PMID: 16463875
Plateau waves; vasodilation; vasoconstriction; cerebrovascular pressure transmission; highest modal frequency
9.  Monitoring and interpretation of intracranial pressure 
Although there is no "Class I" evidence, ICP monitoring is useful, if not essential, in head injury, poor grade subarachnoid haemorrhage, stroke, intracerebral haematoma, meningitis, acute liver failure, hydrocephalus, benign intracranial hypertension, craniosynostosis etc. Information which can be derived from ICP and its waveforms includes cerebral perfusion pressure (CPP), regulation of cerebral blood flow and volume, CSF absorption capacity, brain compensatory reserve, and content of vasogenic events. Some of these parameters allow prediction of prognosis of survival following head injury and optimisation of "CPP-guided therapy". In hydrocephalus CSF dynamic tests aid diagnosis and subsequent monitoring of shunt function.
doi:10.1136/jnnp.2003.033126
PMCID: PMC1739058  PMID: 15145991
10.  Predictive value of Glasgow coma scale after brain trauma: change in trend over the past ten years 
Methods: Data from 358 subjects with head injury, collected between 1992 and 2001, were analysed retrospectively. Patients were grouped according to year of admission. Glasgow Outcome Scores (GOS) were determined at six months. Spearman's correlation coefficients between GCS and GOS scores were calculated for each year.
Results: On average 34 (SD: 7) patients were monitored every year. We found a significant correlation between the GCS and GOS for the first five years (overall 1992–1996: r = 0.41; p<0.00001; n = 183) and consistent lack of correlations from 1997 onwards (overall 1997–2001: r = 0.091; p = 0.226; n = 175). In contrast, correlations between age and GOS were in both time periods significant and similar (r = -0.24 v r = -0.24; p<0.002).
Conclusions: The admission GCS lost its predictive value for outcome in this group of patients from 1997 onwards. The predictive value of the GCS should be carefully reconsidered when building prognostic models incorporating multimodality monitoring after head injury.
PMCID: PMC1757441  PMID: 14707332
12.  Calculation of the resistance to CSF outflow 
doi:10.1136/jnnp.74.9.1354
PMCID: PMC1738661  PMID: 12933962
13.  Cerebrovascular pressure reactivity is related to global cerebral oxygen metabolism after head injury 
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.
doi:10.1136/jnnp.74.6.765
PMCID: PMC1738479  PMID: 12754348
14.  Continuous monitoring of cerebrovascular autoregulation: a validation study 
Background: Continuous monitoring of dynamic cerebral autoregulation, using a moving correlation index of cerebral perfusion pressure and mean middle cerebral artery flow velocity, may be useful in patients with severe traumatic brain injury to guide treatment, and has been shown to be of prognostic value.
Objective: To compare an index of dynamic cerebral autoregulation (Mx) with an index of static cerebral autoregulation (sRoR).
Methods: Mx was validated in a prospective comparative study against sRoR, using 83 testing sessions in 17 patients with traumatic brain injury. sRoR and Mx were calculated simultaneously during pharmacologically induced blood pressure variations.
Results: Mx was significantly correlated with sRoR (R = -0.78, p < 0.05). Nine patients were found to have failure of cerebral autoregulation, with an sRoR value < 50%. If an Mx value of 0.3 was used as the cut off point for failure of cerebral autoregulation, this index had 100% sensitivity and 90% specificity for demonstrating failure of autoregulation compared with the sRoR. An increase in cerebral blood flow velocity correlated significantly with Mx (R = 0.73, p < 0.05) but not with cerebral perfusion pressure (R = 0.41).
Conclusions: Dynamic and static cerebral autoregulation are significantly correlated in traumatic brain injury. Cerebral autoregulation can be monitored continuously, graded, and reliably assessed using a moving correlation analysis of cerebral perfusion pressure and cerebral blood flow velocity (Mx). The Mx index can be used to monitor cerebral blood flow regulation. It is useful in traumatic brain injury because it does not require any external stimulus.
doi:10.1136/jnnp.72.5.583
PMCID: PMC1737892  PMID: 11971041
15.  Preliminary experience of the estimation of cerebral perfusion pressure using transcranial Doppler ultrasonography 
OBJECTIVE—The direct calculation of cerebral perfusion pressure (CPP) as the difference between mean arterial pressure and intracranial pressure (ICP) produces a number which does not always adequately describe conditions for brain perfusion. A non-invasive method of CPP measurement has previously been reported based on waveform analysis of blood flow velocity measured in the middle cerebral artery (MCA) by transcranial Doppler. This study describes the results of clinical tests of the prototype bilateral transcranial Doppler based apparatus for non-invasive CPP measurement (nCPP).
METHODS—Twenty five consecutive, paralysed, sedated, and ventilated patients with head injury were studied. Intracranial pressure (ICP) and arterial blood pressure (ABP) were monitored continuously. The left and right MCAs were insonated daily (108 measurements) using a purpose built transcranial Doppler monitor (Neuro QTM, Deltex Ltd, Chichester, UK) with software capable of the non-invasive estimation of CPP. Time averaged values of mean and diastolic flow velocities (FVm, FVd) and ABP were calculated. nCPP was then computed as: ABP×FVd/FVm+14.
RESULTS—The absolute difference between real CPP and nCPP (daily averages) was less than 10 mm Hg in 89% of measurements and less than 13 mm Hg in 92% of measurements. The 95% confidence range for predictors was no wider than ±12 mm Hg (n=25) for the CPP, varying from 70 to 95 mm Hg. The absolute value of side to side differences in nCPP was significantly greater (p<0.05) when CT based evidence of brain swelling was present and was also positively correlated (p<0.05) with mean ICP.
CONCLUSION—The device is of potential benefit for intermittent or continuous monitoring of brain perfusion pressure in situations where the direct measurement is not available or its reliability is in question.


doi:10.1136/jnnp.70.2.198
PMCID: PMC1737197  PMID: 11160468
18.  Critical closing pressure: a valid concept? 
doi:10.1136/jnnp.68.1.121
PMCID: PMC1760607  PMID: 10671135
19.  Specific patterns of cognitive impairment in patients with idiopathic normal pressure hydrocephalus and Alzheimer's disease: a pilot study 
OBJECTIVES—Eleven patients with idiopathic normal pressure hydrocephalus (NPH) were selected from an initial cohort of 43 patients. The patients with NPH fell into two distinctive subgroups: preshunt, group 1 (n=5) scored less than 24 on the mini mental state examination (MMSE) and were classified as demented and group 2 (n=6) scored 24 or above on the MMSE and were classified as non-demented.
METHODS—All patients were neuropsychologically assessed on two occasions: preshunt and then again 6 months postshunt. Group 1 completed the mini mental state examination (MMSE) and the Kendrick object learning test (KOLT). In addition to the MMSE and KOLT, group 2 completed further tasks including verbal fluency and memory and attentional tasks from the CANTAB battery. Nine of the 11patients also underwent postshunt MRI.
RESULTS—Group 1, who, preshunt, performed in the dementing range on both the MMSE and KOLT, showed a significant postoperative recovery, with all patients now scoring within the normal non-demented range. Group 2, although showing no signs of dementia according to the MMSE and KOLT either preshunt or postshunt, did show a specific pattern of impairment on tests sensitive to frontostriatal dysfunction compared with healthy volunteers, and this pattern remained postoperatively. Importantly, this pattern is distinct from that exhibited by patients with mild Alzheimer's disease. Eight of the nine patterns of structural damage corresponded well to cognitive performance.
CONCLUSIONS—These findings are useful for three main reasons: (1) they detail the structural and functional profile of impairment seen in NPH, (2) they demonstrate the heterogeneity found in this population and show how severity of initial cognitive impairment can affect outcome postshunt, and (3) they may inform and provide a means of monitoring the cognitive outcome of new procedures in shunt surgery.


PMCID: PMC1736677  PMID: 10567486
22.  Jugular venous and arterial concentrations of serum S-100B protein in patients with severe head injury: a pilot study 
The objective of this study was to analyse the temporal course of the jugular venous-arterial gradient of S-100B protein after severe head injury and the correlation between the absolute concentrations of serum S-100B protein and outcome, CT findings, and clinical variables.
 Fifteen patients were included in this pilot study. All patients were treated according to a standard therapy protocol targeted to maintain cerebral perfusion pressure. The serum concentration of S-100 protein was measured daily for five consecutive days after injury by a monoclonal two site immunoluminometric assay. Nine patients showed favourable and six unfavourable outcome after 6 months with a mortality rate of 33% (five patients). The mean gradient between jugular venous and arterial blood was 8.2% (p<0.05). Patients showing an unfavourable outcome had significantly higher jugular venous or arterial S-100 values compared with those with a favourable outcome (jugular venous S-100B 2.78 µg/l v 1.22 µg/l, p<0.05; arterial S-100B 2.48 µg/l v 1.19 µg/l, p<0.05). All patients with an initial or secondary increase in S-100B value of >2 µg/l were found to have an unfavourable outcome. S-100B was found to be an independent predictor of outcome after severe head injury. The persisting increase of S-100B for three to five days even in patients with favourable outcome and no signs of secondary insults might reflect continuing damage to the blood-brain barrier or ongoing glial cell death.


PMCID: PMC2170409  PMID: 9854976
24.  Laboratory testing of the Spiegelberg brain pressure monitor: a technical report 
OBJECTIVES—The Spiegelberg brain pressure monitor is a low cost intracranial pressure monitoring system that has been used clinically for some time, mainly in Germany. To provide a rigorous bench comparison of the Spiegelberg monitor with the Camino pressure monitor an evaluation programme has been carried out in the UK Shunt Evaluation Laboratory.
DESIGN—Drift over 72 hours and with temperature, a frequency response, and the accuracy of measurement of both static and pulsatile pressures have been tested simultanously in Camino and Spiegelberg transducers using a computerised rig.
RESULTS—Long term zero drift was less than 0.7 mm Hg in both transducers. The Spiegelberg monitor showed no temperature drift whereas the Camino monitor had a drift of around 0.3 mm Hg/°C. The Spiegelberg monitor underread mean pressures <40 mm Hg by <1 mm Hg, but the error increased to 4.7 mm Hg at 100 mm Hg. The frequency bandwidth of the Spiegelberg monitor was 4 Hz at a low pressure. Underreading of the amplitude increased with the mean pressure, with a delay of about 0.1 s in the detection of the peaks of pulse waveform.
CONCLUSION—The Spiegelberg transducer had excellent accuracy for static intracranial pressure measurement, but complex waveform analysis may be biased by its limited dynamic response.


PMCID: PMC2169866  PMID: 9416806
25.  Contribution of mathematical modelling to the interpretation of bedside tests of cerebrovascular autoregulation 
OBJECTIVES—Cerebral haemodynamic responses to short and longlasting episodes of decreased cerebral perfusion pressure contain information about the state of autoregulation of cerebral blood flow. Mathematical simulation may help to elucidate which of the indices, that can be derived using transcranial Doppler ultrasonography and trends of intracranial pressure and blood pressure, are useful in clinical tests of autoregulatory reserve.
METHODS—Time dependent interactions between pressure, flow, and volume of cerebral blood and CSF were modelled using a set of non-linear differential equations. The model simulates changes in arterial blood inflow and storage, arteriolar and capillary blood flow controlled by cerebral autoregulation, venous blood storage and venous outflow modulated by changes in ICP, and CSF storage and reabsorption. The model was used to simulate patterns of blood flow during either short or longlasting decreases in cerebral perfusion pressure. These simulations can be considered as clinically equivalent to a short compression of the common carotid artery, systemic hypotension, and intracranial hypertension. Simulations were performed in autoregulating and non-autoregulating systems and compared with recordings obtained in patients.
RESULTS—After brief compression of the common carotid artery, a subsequent transient hyperaemia can be interpreted as evidence of intact autoregulation. During longlasting sustained hypoperfusion, a gradual increase in the systolic value of the blood flow velocity waveform along with a decrease in the diastolic value is specific for an autoregulating cerebrovascular system.
CONCLUSION—Modelling studies help to interpret both clinical and experimental cerebral haemodynamic phenomena and their dependence on the state of autoregulation.


PMCID: PMC2169860  PMID: 9416805

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