Early Detection of Increased Intracranial Pressure Episodes in Traumatic Brain Injury: External Validation in an Adult and in a Pediatric Cohort.

OBJECTIVE: A model for early detection of episodes of increased intracranial pressure in traumatic brain injury patients has been previously developed and validated based on retrospective adult patient data from the multicenter Brain-IT database. The purpose of the present study is to validate this early detection model in different cohorts of recently treated adult and pediatric traumatic brain injury patients. DESIGN: Prognostic modeling. Noninterventional, observational, retrospective study. SETTING AND PATIENTS: The adult validation cohort comprised recent traumatic brain injury patients from San Gerardo Hospital in Monza (n = 50), Leuven University Hospital (n = 26), Antwerp University Hospital (n = 19), Tübingen University Hospital (n = 18), and Southern General Hospital in Glasgow (n = 8). The pediatric validation cohort comprised patients from neurosurgical and intensive care centers in Edinburgh and Newcastle (n = 79). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The model's performance was evaluated with respect to discrimination, calibration, overall performance, and clinical usefulness. In the recent adult validation cohort, the model retained excellent performance as in the original study. In the pediatric validation cohort, the model retained good discrimination and a positive net benefit, albeit with a performance drop in the remaining criteria. CONCLUSIONS: The obtained external validation results confirm the robustness of the model to predict future increased intracranial pressure events 30 minutes in advance, in adult and pediatric traumatic brain injury patients. These results are a large step toward an early warning system for increased intracranial pressure that can be generally applied. Furthermore, the sparseness of this model that uses only two routinely monitored signals as inputs (intracranial pressure and mean arterial blood pressure) is an additional asset.

Can Optimal Cerebral Perfusion Pressure in Patients with Severe Traumatic Brain Injury Be Calculated Based on Minute-by-Minute Data Monitoring?

BACKGROUND: The concept of CPPopt, a variable cerebral perfusion pressure (CPP) target based on cerebrovascular autoregulatory capacity in severe traumatic brain injury (TBI), is promising. CPPopt calculation is based on the continuous plotting of the pressure reactivity Index (PRx) against CPP and requires processing of waveform quality data. The aim of this study is to investigate whether CPPopt can also be calculated based on minute-by-minute data. METHODS: A low-resolution autoregulation index (LAx) was defined as the minute-by-minute intracranial pressure-mean arterial pressure correlation over varying time intervals. A matrix of LAx-CPP plots was built using different LAx values and varying time windows. CPPopt was calculated as the weighted average of the CPPopt values resulting from each plot. The method was assessed in a database of 21 patients with TBI with 60-Hz data. RESULTS: No significant difference was observed between PRx-based and LAx-based CPPopt values. The new method was able to issue a CPPopt recommendation throughout almost the entire monitoring time. The absolute difference between CPP and CPPopt was inversely associated with survival. CONCLUSION: CPPopt calculation based on standard resolution data compared well with PRx-based CPPopt and may represent a promising alternative method, avoiding the need for waveform quality data capture. Further validation of this new method is required.

The value of dynamic radiographic myelography in addition to magnetic resonance imaging in detection lumbar spinal canal stenosis: A prospective study.

OBJECTIVE: MRI is regarded as the study of choice in the diagnosis of lumbar spinal stenosis. In some cases, the supine MRI leads to a misdiagnosis in the extent of lumbar spinal stenosis. Dynamic myelography can detect lumbar spinal stenosis in these cases of where the MRI may not be as sensitive. To compare the sensitivities of dynamic radiographic myelography and supine MRI in lumbar canal stenosis (LCS) patients and to determine whether dynamic radiographic myelography is a valuable diagnostic exam in the work-up of lumbar canal stenosis. PATIENTS & METHODS: Over two years, the imaging data of 100 consecutive patients who were suspected of having LCS were prospectively analyzed. All lumbar intervertebral segments were evaluated in each patient on sagittal MR T2-weighted images and lateral plane images by myelography using a semi-quantitative scoring system. The differences in scores for 5 motion segments under 3 conditions (supine MRI, upright sitting myelography and standing myelography with extension) were analyzed statistically. RESULTS: Of 100 patients with 500 analyzed intervertebral segments, 23 patients with inconclusive supine MRI results had LCS in standing myelography with extension. Compared with upright sitting myelography and supine MRI, standing myelography with extension yielded the highest score for every segment from L1/2 to L5/S1. Compared with the upright sitting myelography position, 61 more patients received a diagnosis of lumbar stenosis in the standing myelography with extension position, and 121 more stenotic segments were diagnosed. Compared with the supine MRI position, standing myelography with extension detected 64 more stenotic patients and 137 more stenotic segments. CONCLUSIO: n Based on a large patient sample, dynamic myelography is a valuable diagnostic tool in detecting lumbar spinal stenosis. Patients with lumbar spinal stenosis may have inconclusive supine MRI in 23% of cases being misdiagnosed as normal. This missed rate of LCS patients with unclear supine MRI results can be avoided with dynamic myelography. The combination of supine MRI and dynamic myelography is critical in the evaluation of LCS, especially if multisegmental findings are detected.

Pressure autoregulation monitoring and cerebral perfusion pressure target recommendation in patients with severe traumatic brain injury based on minute-by-minute monitoring data.

OBJECT: In severe traumatic brain injury, a universal target for cerebral perfusion pressure (CPP) has been abandoned. Attempts to identify a dynamic CPP target based on the patient's cerebrovascular autoregulatory capacity have been promising so far. Bedside monitoring of pressure autoregulatory capacity has become possible by a number of methods, Czosnyka's pressure reactivity index (PRx) being the most frequently used. The PRx is calculated as the moving correlation coefficient between 40 consecutive 5-second averages of intracranial pressure (ICP) and mean arterial blood pressure (MABP) values. Plotting PRx against CPP produces a U-shaped curve in roughly two-thirds of monitoring time, with the bottom of this curve representing a CPP range corresponding with optimal autoregulatory capacity (CPPopt). In retrospective series, keeping CPP close to CPPopt corresponded with better outcomes. Monitoring of PRx requires high-frequency signal processing. The aim of the present study is to investigate how the processing of the information on cerebrovascular pressure reactivity that can be obtained from routine minute-by-minute ICP and MABP data can be enhanced to enable CPPopt recommendations that do not differ from those obtained by the PRx method, show the same associations with outcome, and can be generated in more than two-thirds of monitoring time. METHODS: The low-frequency autoregulation index (LAx) was defined as the moving minute-by-minute ICP/MABP correlation coefficient calculated over time intervals varying from 3 to 120 minutes. The CPPopt calculation was based on LAx-CPP plots and done for time windows between 1 and 24 hours and for each LAx type. The resulting matrix of CPPopts were then averaged in a weighted manner, with the weight based on the goodness of fit of a U-shape and the lower value of the LAx corresponding to the U-bottom, to result in a final CPPopt recommendation. The association between actual CPP/CPPopt and outcome was assessed in the multicenter Brain Monitoring with Information Technology Research Group (BrainIT) database (n = 180). In the Leuven-Tübingen database (60-Hz waveform data, n = 21), LAx- and PRx-based CPPopts were compared. RESULTS: In the BrainIT database, CPPopt recommendations were generated in 95% of monitoring time. Actual CPP being close to LAx-based CPPopt was associated with increased survival. In a multivariate model using the Corticosteroid Randomization After Significant Head Injury (CRASH) model as covariates, the average absolute difference between actual CPP and CPPopt was independently associated with increased mortality. In the high-frequency data set no significant difference was observed between PRx-based and LAx-based CPPopts. The new method issued a CPPopt recommendation in 97% of monitoring time, as opposed to 44% for PRx-based CPPopt. CONCLUSIONS: Minute-by-minute ICP/MABP data contain relevant information for autoregulation monitoring. In this study, the authors' new method based on minute-by-minute data resolution allowed for CPPopt calculation in nearly the entire monitoring time. This will facilitate the use of pressure reactivity monitoring in all ICUs.

Spinal robotics: current applications and future perspectives.

Even though robotic technology holds great potential for performing spinal surgery and advancing neurosurgical techniques, it is of utmost importance to establish its practicality and to demonstrate better clinical outcomes compared with traditional techniques, especially in the current cost-effective era. Several systems have proved to be safe and reliable in the execution of tasks on a routine basis, are commercially available, and are used for specific indications in spine surgery. However, workflow, usability, interdisciplinary setups, efficacy, and cost-effectiveness have to be proven prospectively. This article includes a short description of robotic structures and workflow, followed by preliminary results of a randomized prospective study comparing conventional free-hand techniques with routine spine navigation and robotic-assisted procedures. Additionally, we present cases performed with a spinal robotic device, assessing not only the accuracy of the robotic-assisted procedure but also other factors (eg, minimal invasiveness, radiation dosage, and learning curves). Currently, the use of robotics in spinal surgery greatly enhances the application of minimally invasive procedures by increasing accuracy and reducing radiation exposure for patients and surgeons compared with standard procedures. Second-generation hardware and software upgrades of existing devices will enhance workflow and intraoperative setup. As more studies are published in this field, robot-assisted therapies will gain wider acceptance in the near future.

Fractional anisotropy levels derived from diffusion tensor imaging in cervical syringomyelia.

BACKGROUND: Syringomyelia can result in major functional disability. Conventional imaging techniques frequently fail to detect the underlying cause of syringomyelia. The prediction as to whether syringomyelia might lead to neurological deficits is still challenging. OBJECTIVE: We hypothesized that fractional anisotropy (FA) derived from diffusion tensor imaging (DTI) is a parameter to detect dynamic forms of syringomyelia. METHODS: Six patients with cervical syringomyelia, all comparable in size, shape, and location, were examined, along with 2 volunteers. Patients underwent electrophysiological recordings (somatosensory evoked potentials, motor evoked potentials, silent periods). Magnetic resonance imaging (1.5 T) was performed with a 6-element spine coil. Anatomic images were acquired with a 3-dimensional, constructive interference in steady-state sequence, and DTI with an echo-planar imaging sequence (5-mm thickness, b value 800 s/mm) using the generalized autocalibrating partially parallel acquisitions technique. The positions were centered on the syrinx in the volunteers between the C2 and Th1. DTI data were interpolated to a spatial resolution of 0.5 mm. After calculation of a diffusion tensor in each pixel, an FA map was calculated and profiles of the FA values across the spinal cord were calculated in all slices. RESULTS: FA values were lower at the level of all examined syrinxes and reached normal values beyond them. Electrophysiological results correlated with the decrease in FA value. There were no presyrinx changes in the white matter tracts in terms of signs of FA changes beneath the syrinx. CONCLUSION: DTI of syringomyelia can demonstrate white matter fiber tracts around and beyond the syrinx consistent with electrophysiological values. DTI of the cervical spine can provide quantitative information about the pathological characteristics beyond the abnormalities visible on magnetic resonance imaging.

Upregulation of HERG channels by the serum and glucocorticoid inducible kinase isoform SGK3.

Human ether-a-go-go (HERG) channels participate in the repolarization of the cardiac action potential. Loss of function mutations of HERG lead to delayed cardiac repolarization reflected by prolonged QT interval. HERG channels are regulated through a signaling cascade involving phosphatidylinositol 3 (PI3) kinase. Downstream targets of PI3 kinase include the serum and glucocorticoid inducible kinase (SGK) and protein kinase B (PKB) isoforms. The present study has been performed to explore whether SGK1 and SGK3 participate in the regulation of HERG channel activity. HERG was expressed in Xenopus oocytes with or without additional expression of SGK1 or SGK3. Chemiluminescence was employed to determine HERG plasma membrane protein abundance. Coexpression of SGK3 but not of SGK1 in Xenopus oocytes resulted in an increase of steady state current (I(HERG)) and enhanced cell membrane protein abundance without affecting gating kinetics of the channel. Replacement of serine by alanine at the two SGK consensus sites decreased I(HERG) but neither mutation abolished the stimulating effect of SGK3. In conclusion, SGK3 participates in the regulation of HERG by increasing HERG protein abundance in the plasma membrane and may thus modify the duration of the cardiac action potential.

Association of the serum and glucocorticoid regulated kinase (sgk1) gene with QT interval.

The serum and glucocorticoid inducible kinase (SGK1) is well known to up-regulate the renal epithelial Na(+) channel ENaC. Excessive SGK1 activity would be expected to cause renal Na(+) retention and blood pressure increase. Certain polymorphisms of the SGK1 gene (E8CC/CT;I6CC) are indeed associated with moderately enhanced blood pressure. We have recently disclosed another function of SGK1, i.e. the stimulation of the slowly activating K(+) channel KCNE1/KCNQ1. Among the functions of this channel is the repolarisation of cardiac myocytes. Accordingly, defective KCNE1 and/or KCNQ1 lead to long QT syndrome, a disorder causing fainting and sudden cardiac death. In the present study we demonstrate that coexpression of SGK1 in Xenopus oocytes increases KCNQ1/KCNE1 induced current without significantly altering voltage dependence, activation and deactivation kinetics. To test for the relevance of SGK1 in human cardiac repolarization, we analysed the ECG of monozygotic (MZ) (126 pairs) and dizygotic (DZ) (70 pairs) twin subjects and parents of DZ twins. The E8CC/CT;I6CC polymorphism was indeed significantly (p<0.025) associated with shortened age and gender corrected QT interval. No significant differences were observed in any other ECG parameter, including heart rate, P, PQ and QRS. We conclude that the regulation of KCNE1/KCNQ1 by SGK1 is similarly relevant for the repolarization of cardiac myocytes as for regulation of renal ENaC activity and blood pressure control.