Cerebrovascular Autoregulation Monitoring in the Management of Adult Severe Traumatic Brain Injury: A Delphi Consensus of Clinicians.

BACKGROUND: Several methods have been proposed to measure cerebrovascular autoregulation (CA) in traumatic brain injury (TBI), but the lack of a gold standard and the absence of prospective clinical data on risks, impact on care and outcomes of implementation of CA-guided management lead to uncertainty. AIM: To formulate statements using a Delphi consensus approach employing a group of expert clinicians, that reflect current knowledge of CA, aspects that can be implemented in TBI management and CA research priorities. METHODS: A group of 25 international academic experts with clinical expertise in the management of adult severe TBI patients participated in this consensus process. Seventy-seven statements and multiple-choice questions were submitted to the group in two online surveys, followed by a face-to-face meeting and a third online survey. Participants received feedback on average scores and the rationale for resubmission or rephrasing of statements. Consensus on a statement was defined as agreement of more than 75% of participants. RESULTS: Consensus amongst participants was achieved on the importance of CA status in adult severe TBI pathophysiology, the dynamic non-binary nature of CA impairment, its association with outcome and the inadvisability of employing universal and absolute cerebral perfusion pressure targets. Consensus could not be reached on the accuracy, reliability and validation of any current CA assessment method. There was also no consensus on how to implement CA information in clinical management protocols, reflecting insufficient clinical evidence. CONCLUSION: The Delphi process resulted in 25 consensus statements addressing the pathophysiology of impaired CA, and its impact on cerebral perfusion pressure targets and outcome. A research agenda was proposed emphasizing the need for better validated CA assessment methods as well as the focused investigation of the application of CA-guided management in clinical care using prospective safety, feasibility and efficacy studies.

Pressure Reactivity-Based Optimal Cerebral Perfusion Pressure in a Traumatic Brain Injury Cohort.

OBJECTIVES: Retrospective data from patients with severe traumatic brain injury (TBI) indicate that deviation from the continuously calculated pressure reactivity-based "optimal" cerebral perfusion pressure (CPPopt) is associated with worse patient outcome. The objective of this study was to assess the relationship between prospectively collected CPPopt data and patient outcome after TBI. METHODS: We prospectively collected intracranial pressure (ICP) monitoring data from 231 patients with severe TBI at Addenbrooke's Hospital, UK. Uncleaned arterial blood pressure and ICP signals were recording using ICM+® software on dedicated bedside computers. CPPopt was determined using an automatic curve fitting procedure of the relationship between pressure reactivity index (PRx) and CPP using a 4-h window, as previously described. The difference between an instantaneous CPP value and its corresponding CPPopt value was denoted every minute as ΔCPPopt. A negative ΔCPPopt that was associated with impaired PRx (>+0.15) was denoted as being below the lower limit of reactivity (LLR). Glasgow Outcome Scale (GOS) score was assessed at 6 months post-ictus. RESULTS: When ΔCPPopt was plotted against PRx and stratified by GOS groupings, data belonging to patients with a more unfavourable outcome had a U-shaped curve that shifted upwards. More time spent with a ΔCPPopt value below the LLR was positively associated with mortality (area under the receiver operating characteristic curve = 0.76 [0.68-0.84]). CONCLUSIONS: In a recent cohort of patients with severe TBI, the time spent with a CPP below the CPPopt-derived LLR is related to mortality. Despite aggressive CPP- and ICP-oriented therapies, TBI patients with a fatal outcome spend a significant amount of time with a CPP below their individualised CPPopt, indicating a possible therapeutic target.

Intraoperative non invasive intracranial pressure monitoring during pneumoperitoneum: a case report and a review of the published cases and case report series.

Non-invasive measurement of ICP (nICP) can be warranted in patients at risk for developing increased ICP during pneumoperitoneum (PP). Our aim was to assess available data on the application of nICP monitoring during these procedures and to present a patient assessed with an innovative combination of noninvasive tools. Literature review of nICP assessment during PP did not find any studies comparing different methods intraprocedurally and only few studies of any nICP monitoring were available: transcranial Doppler (TCD) studies used the pulsatility index (PI) as an estimator of ICP and failed to detect a significant ICP increase during PP, whereas two out of three optic nerve sheath diameter (ONSD) studies detected a statistically significant ICP increase. In the case study, we describe a 52 year old man with a high grade thalamic glioma who underwent urgent laparoscopic cholecystectomy. Considering the high intraoperative risk of developing intracranial hypertension, he was monitored through parallel ONSD ultrasound measurement and TCD derived formulae (flow velocity diastolic formula, FVdnICP, and PI). ONSD and FVdnICP methods indicated a significant ICP increase during PP, whereas PI was not significantly increased. Our experience, combined with the literature review, seems to suggest that PI might not detect ICP changes in this context, however we indicate a possible interest of nICP monitoring during PP by means of ONSD and of TCD derived FVdNICP, especially for patients at risk for increased ICP.

Variability of the autoregulation index decreases after removing the effect of the very low frequency band.

Dynamic cerebral autoregulation (dCA) estimates show large between and within subject variability. Sources of variability include low coherence and influence of CO2 in the very low frequency (VLF) band, where dCA is active. This may lead to unreliable transfer function and autoregulation index (ARI) estimates. We tested whether variability of the ARI could be decreased by suppressing the effect of the VLF band through filtering. We also evaluated whether filtering had any effect on mean group differences between healthy subjects and acute stroke patients. Data from a recent mobilization stroke study were re-analyzed. Middle cerebral artery cerebral blood flow velocity (MCA-CBFV), mean arterial blood pressure (MABP) and end tidal PCO2 (PetCO2) were obtained in 16 healthy subjects and 27 acute ischemic stroke patients in the supine position. The ARI index was calculated from the transfer function (TF) by using spontaneous BP fluctuations. Three different filtering strategies were compared; no filtering (NF), a high pass filter at 0.04 Hz (Time Domain Filtering: TDF) and a high pass Transfer Function Filter (TFF) at 0.04 Hz. In addition, a simulation study was done to obtain further insight into the effects of the applied filters. The variability of the ARI index decreased significantly only with TFF in healthy subjects (standard deviation (left vs. right) after NF 2.28 vs. 2.36, after TDF 2.13 vs. 2.31 after TFF 1.09 vs. 1.19, p<0.001). Variability was not significantly reduced in stroke patients. The mean ARI was significantly lower in stroke patients compared to healthy subjects after TFF (affected hemisphere 5.85±1.96 vs. 7.13±1.09, non-affected hemisphere 5.96±1.64 vs. 7.31±1.19, p<0.01 for both hemispheres), but not after NF or TDF. The simulation study showed that TFF results in an overestimation of the ARI index at low ARI levels (0-3), but in correct estimates at higher ARI levels. Removing the effect of the VLF band with TFF results in less ARI variability in healthy subjects, and in more pronounced group differences between stroke patients and healthy subjects. This will improve diagnostic properties when using TFA for ARI calculation.

Reproducibility and variability of dynamic cerebral autoregulation during passive cyclic leg raising.

Dynamic cerebral autoregulation (dCA) estimates require mean arterial blood pressure (MABP) fluctuations of sufficient amplitude. Current methods to induce fluctuations are not easily implemented or require patient cooperation. In search of an alternative method, we evaluated if MABP fluctuations could be increased by passive cyclic leg raising (LR) and tested if reproducibility and variability of dCA parameters could be improved. Middle cerebral artery cerebral blood flow velocity (CBFV), MABP and end tidal CO2 (PetCO2) were obtained at rest and during LR at 0.1 Hz in 16 healthy subjects. The MABP-CBFV phase difference and gain were determined at 0.1 Hz and in the low frequency (LF) range (0.06-0.14 Hz). In addition the autoregulation index (ARI) was calculated. The LR maneuver increased the power of MABP fluctuations at 0.1 Hz and across the LF range. Despite a clear correlation between both phase and gain reproducibility and MABP variability in the rest condition, only the reproducibility of gain increased significantly with the maneuver. During the maneuver patients were breathing faster and more irregularly, accompanied by increased PetCO2 fluctuations and increased coherence between PetCO2 and CBFV. Multiple regression analysis showed that these concomitant changes were negatively correlated with the MABP-CBFV phase difference at 0.1 Hz Variability was not reduced by LR for any of the dCA parameters. The clinical utility of cyclic passive leg raising is limited because of the concomitant changes in PetCO2. This limits reproducibility of the most important dCA parameters. Future research on reproducibility and variability of dCA parameters should incorporate PetCO2 variability or find methods to keep PetCO2 levels constant.

The sNIHSS-4 predicts outcome in right and left anterior circulation strokes.

BACKGROUND AND PURPOSE: Stroke severity measured by the National Institutes of Health Stroke Scale (NIHSS) is a strong predictor of functional outcome. A short version, the sNIHSS-5, scoring only strength in right and left leg, gaze, visual fields and language, was developed for use in the prehospital setting. Because scoring both legs in anterior circulation strokes is not contributive, we assessed the value of a 4-item score (the sNIHSS-4), omitting the item 'strength in the unaffected leg', in predicting stroke outcome. METHODS: The study population consisted of anterior circulation ischemic stroke patients who participated in the LUB-INT-9 trial. We included all patients in whom the following data were available: NIHSS within 6h after stroke onset and daily between days 2 and 5, and the 12-week modified Rankin Scale (mRS) score. Poor outcome was defined as a mRS score>3. RESULTS: There was an excellent correlation between the NIHSS and sNIHSS-4 at all time points for both left and right-sided strokes. Scores at day 2 were a good predictor of poor outcome. Cutoff scores for NIHSS and sNIHSS-4 at day 2 were 15 and 5 in left hemispheric strokes, and 12 and 4 in right hemispheric strokes. CONCLUSION: The sNIHSS-4 is as good as the NIHSS at predicting stroke outcome in both right and left anterior circulation strokes.

Pulsatile intracranial pressure and cerebral autoregulation after traumatic brain injury.

BACKGROUND: Strong correlation between mean intracranial pressure (ICP) and its pulse wave amplitude (AMP) has been demonstrated in different clinical scenarios. We investigated the relationship between invasive mean arterial blood pressure (ABP) and AMP to explore its potential role as a descriptor of cerebrovascular pressure reactivity after traumatic brain injury (TBI). METHODS: We retrospectively analyzed data of patients suffering from TBI with brain monitoring. Transcranial Doppler blood flow velocity, ABP, ICP were recorded digitally. Cerebral perfusion pressure (CPP) and AMP were derived. A new index-pressure-amplitude index (PAx)-was calculated as the Pearson correlation between (averaged over 10 s intervals) ABP and AMP with a 5 min long moving average window. The previously introduced transcranial Doppler-based autoregulation index Mx was evaluated in a similar way, as the moving correlation between blood flow velocity and CPP. The clinical outcome was assessed after 6 months using the Glasgow outcome score. RESULTS: 293 patients were studied. The mean PAx was -0.09 (standard deviation 0.21). This negative value indicates that, on average, an increase in ABP causes a decrease in AMP and vice versa. PAx correlated strong with Mx (R (2) = 0.46, P < 0.0002). PAx also correlated with age (R (2) = 0.18, P < 0.05). PAx was found to have as good predictive outcome value (area under curve 0.71, P < 0.001) as Mx (area under curve 0.69, P < 0.001). CONCLUSIONS: We demonstrated significant correlation between the known cerebral autoregulation index Mx and PAx. This new index of cerebrovascular pressure reactivity using ICP pulse wave information showed to have a strong association with outcome in TBI patients.

Traumatic cervical artery dissection in head injury: the value of follow-up brain imaging.

INTRODUCTION: Traumatic cervical artery dissection (TCAD) is a relative infrequent complication of traumatic brain injury (TBI). Since TCAD is associated with morbidity in a considerable percentage of patients, it is important to obtain clues for recognising TCAD in this category of patients. METHODS: Retrospective case-cohort study in severe TBI patients. RESULTS: Five patients with traumatic cervical artery dissection after severe TBI, leading to ischemic strokes, are described. Secondary deterioration to coma was present in four out of five patients during admission. The diagnosis of TCAD was delayed in most cases because the secondary deterioration was often attributed to multisystem problems related to trauma patients, i.e. shock or hypoxia or medication effects. Local clinical symptoms and signs suggestive of TCAD are difficult to detect in this patient group. In all patients, the CT-scan on admission demonstrated no abnormalities. A follow-up scan at day 2 revealed that in all patients abnormalities in the vascular territories had evolved. CONCLUSION: With this case-cohort study we underline the importance of considering TCAD in severe TBI patients and emphasise the role for standard follow-up brain imaging. Also possible treatment consequences are discussed.

An aid to the diagnosis of genetic disorders underlying adult-onset renal failure: a literature review.

Several genetic disorders can present in adult patients with renal insufficiency. Genetic renal disease other than ADPKD accounts for ESRD in 3% of the adult Dutch population. Because of this low prevalence and their clinical heterogeneity most adult nephrologists are less familiar with these disorders. As a guideline to differential diagnosis, we provide an overview of the clinical manifestations and the pathogenesis of the main genetic disorders with chronic renal insufficiency surfacing in adulthood and add an algorithm plus 4 tables. We also indicate where molecular genetics nowadays can be of aid in the diagnostic process. The following disorders are discussed by mode of inheritance: 1) Autosomal dominant: autosomal dominant polycystic kidney disease, nephropathies associated with uromodulin (medullary cystic disease and familial juvenile hyperuricemic nephropathy), renal cysts and diabetes syndrome, nail-patella syndrome, glomerulopathy with fibronectin deposits. 2) Not autosomal dominant: Nephronophthisis, Fabry disease, primary oxalosis, Adenine Phosphoribosyl Transferase deficiency, Alport syndrome, Lecithin-cholesterol acyltransferase deficiency, adult-onset cystinosis.

tPA treatment for acute ischaemic stroke in patients with leukoaraiosis.

BACKGROUND AND PURPOSE: Whether leukoaraiosis on baseline CT is associated with an increased risk of symptomatic intracerebral haemorrhage (sICH) or poor outcome following tissue plasminogen activator (tPA) treatment for acute ischaemic stroke is still a matter of debate. OBJECTIVE: To investigate the relationship between the presence and severity of leukoaraiosis on baseline CT and the risk of sICH and functional outcome after tPA treatment for acute ischaemic stroke. METHODS: A single-center observational cohort study with a retrospective analysis on consecutive patients with ischaemic stroke treated with tPA in the period 2002-2008. Outcome measures were the occurrence of sICH and functional outcome at 3 months. RESULTS: Of the 400 patients, 24% had leukoaraiosis on their baseline CT. Eleven patients (11%) with leukoaraiosis versus thirteen (4%) patients without leukoaraiosis had a sICH [odds ratio (OR) 2.85 95%-CI 1.23-6.60, P = 0.02]. Multivariate analysis showed a non-significant trend towards an association of leukoaraiosis and sICH (OR 1.9, 95%-CI 0.78-4.68, P = 0.16). Leukoaraiosis was independently associated with poor functional outcome (OR 2.39, 95%-CI 1.21-4.72, P = 0.01). No difference was observed in the outcome measures amongst patients with moderate or severe leukoaraiosis. CONCLUSION: Our study demonstrates that patients treated with tPA and leukoaraiosis on their baseline CT are at greater risk of sICH and have a worse functional outcome compared to patients without leukoaraiosis. It is important to note that these results should not lead to exclusion of patients with leukoaraiosis for tPA treatment.

Hyperdense middle cerebral artery sign and outcome after intravenous thrombolysis for acute ischemic stroke.

BACKGROUND: The presence of a hyperdense middle cerebral artery sign (HMCAS) on baseline brain CT is associated with poor clinical outcome in stroke patients treated with intravenous recombinant tissue plasminogen activator (tPA). It remains uncertain whether the presence of HMCAS is associated with acute neurological deterioration after tPA treatment. OBJECTIVE: To evaluate the effect of HMCAS in routinely intravenous tPA-treated patients with anterior circulation stroke on acute neurological deterioration, the 3-month functional outcome and the occurrence of symptomatic ICH. METHODS: We analyzed data from a single stroke unit registry of 384 consecutive patients with anterior circulation infarction, treated with intravenous tPA. Logistic regression models were used to assess if HMCAS was independently associated with predefined outcome definitions. RESULTS: We found a HMCAS in 104 patients (27%). The HMCAS was related to the risk of early neurological deterioration (p=0.04) and poor functional outcome (p<0.001) on univariate analysis. The incidence of symptomatic ICH was not significantly different between patients with and without HMCAS (7% versus 6%, p=0.81). In the multivariable analysis, the presence of HMCAS was significantly associated with a poor outcome (p=0.004). CONCLUSIONS: The HMCAS is associated with early neurological deterioration and poor functional outcome, but not with symptomatic ICH.

Does smoking influence outcome after intravenous thrombolysis for acute ischaemic stroke?

BACKGROUND AND PURPOSE: It remains uncertain whether current smoking influences outcome in patients with acute ischaemic stroke. OBJECTIVES: To evaluate the effect of current smoking in routinely tissue plasminogen activator (tPA)-treated stroke patients on the 3-month functional outcome and the occurrence of symptomatic intracerebral hemorrhage (ICH). METHODS: We analyzed data from a single stroke care unit registry of 345 consecutive patients with ischaemic stroke, treated with tPA. Logistic regression models were used to assess if smoking was independently associated with 3-months good outcome defined as a modified Rankin Scale score of < or =2, and the occurrence of symptomatic ICH. RESULTS: In the multivariable models, smoking was not associated with a good outcome or a decreased risk of symptomatic ICH. CONCLUSION: Current smoking did not affect functional outcome at 3 months or the risk of symptomatic ICH in patients routinely treated with tPA for ischaemic stroke.