David K. Menon

Changing patterns in the epidemiology of traumatic brain injury

Traumatic brain injury (TBI) is a critical public health and socio-economic problem throughout the world. Reliable quantification of the burden caused by TBI is difficult owing to inadequate standardization and incomplete capture of data on the incidence and outcome of brain injury, with variability in the definition of TBI being partly to blame. Reports show changes in epidemiological patterns of TBI: the median age of individuals who experience TBI is increasing, and falls have now surpassed road traffic incidents as the leading cause of this injury. Despite claims to the contrary, no clear decrease in TBI-related mortality or improvement of overall outcome has been observed over the past two decades. In this Perspectives article, we discuss the strengths and limitations of epidemiological studies, address the variability in its definition, and highlight changing epidemiological patterns. Taken together, these analyses identify a great need for standardized epidemiological monitoring in TBI.

Critical Care Management of Patients Following Aneurysmal Subarachnoid Hemorrhage: Recommendations from the Neurocritical Care Society’s Multidisciplinary Consensus Conference

Subarachnoid hemorrhage (SAH) is an acute cerebrovascular event which can have devastating effects on the central nervous system as well as a profound impact on several other organs. SAH patients are routinely admitted to an intensive care unit and are cared for by a multidisciplinary team. A lack of high quality data has led to numerous approaches to management and limited guidance on choosing among them. Existing guidelines emphasize risk factors, prevention, natural history, and prevention of rebleeding, but provide limited discussion of the complex critical care issues involved in the care of SAH patients. The Neurocritical Care Society organized an international, multidisciplinary consensus conference on the critical care management of SAH to address this need. Experts from neurocritical care, neurosurgery, neurology, interventional neuroradiology, and neuroanesthesiology from Europe and North America were recruited based on their publications and expertise. A jury of four experienced neurointensivists was selected for their experience in clinical investigations and development of practice guidelines. Recommendations were developed based on literature review using the GRADE system, discussion integrating the literature with the collective experience of the participants and critical review by an impartial jury. Recommendations were developed using the GRADE system. Emphasis was placed on the principle that recommendations should be based not only on the quality of the data but also tradeoffs and translation into practice. Strong consideration was given to providing guidance and recommendations for all issues faced in the daily management of SAH patients, even in the absence of high quality data.

Position Statement: Definition of Traumatic Brain Injury

A clear, concise definition of traumatic brain injury (TBI) is fundamental for reporting, comparison, and interpretation of studies on TBI. Changing epidemiologic patterns, an increasing recognition of significance of mild TBI, and a better understanding of the subtler neurocognitive neuroaffective deficits that may result from these injuries make this need even more critical. The Demographics and Clinical Assessment Working Group of the International and Interagency Initiative toward Common Data Elements for Research on Traumatic Brain Injury and Psychological Health has therefore formed an expert group that proposes the following definition: In this article, we discuss criteria for considering or establishing a diagnosis of TBI, with a particular focus on the problems how a diagnosis of TBI can be made when patients present late after injury and how mild TBI may be differentiated from non-TBI causes with similar symptoms. Technologic advances in magnetic resonance imaging and the development of biomarkers offer potential for improving diagnostic accuracy in these situations.

Referral to an Extracorporeal Membrane Oxygenation Center and Mortality Among Patients With Severe 2009 Influenza A(H1N1)

CONTEXT Extracorporeal membrane oxygenation (ECMO) can support gas exchange in patients with severe acute respiratory distress syndrome (ARDS), but its role has remained controversial. ECMO was used to treat patients with ARDS during the 2009 influenza A(H1N1) pandemic. OBJECTIVE To compare the hospital mortality of patients with H1N1-related ARDS referred, accepted, and transferred for ECMO with matched patients who were not referred for ECMO. DESIGN, SETTING, AND PATIENTS A cohort study in which ECMO-referred patients were defined as all patients with H1N1-related ARDS who were referred, accepted, and transferred to 1 of the 4 adult ECMO centers in the United Kingdom during the H1N1 pandemic in winter 2009-2010. The ECMO-referred patients and the non-ECMO-referred patients were matched using data from a concurrent, longitudinal cohort study (Swine Flu Triage study) of critically ill patients with suspected or confirmed H1N1. Detailed demographic, physiological, and comorbidity data were used in 3 different matching techniques (individual matching, propensity score matching, and GenMatch matching). MAIN OUTCOME MEASURE Survival to hospital discharge analyzed according to the intention-to-treat principle. RESULTS Of 80 ECMO-referred patients, 69 received ECMO (86.3%) and 22 died (27.5%) prior to discharge from the hospital. From a pool of 1756 patients, there were 59 matched pairs of ECMO-referred patients and non-ECMO-referred patients identified using individual matching, 75 matched pairs identified using propensity score matching, and 75 matched pairs identified using GenMatch matching. The hospital mortality rate was 23.7% for ECMO-referred patients vs 52.5% for non-ECMO-referred patients (relative risk [RR], 0.45 [95% CI, 0.26-0.79]; P = .006) when individual matching was used; 24.0% vs 46.7%, respectively (RR, 0.51 [95% CI, 0.31-0.81]; P = .008) when propensity score matching was used; and 24.0% vs 50.7%, respectively (RR, 0.47 [95% CI, 0.31-0.72]; P = .001) when GenMatch matching was used. The results were robust to sensitivity analyses, including amending the inclusion criteria and restricting the location where the non-ECMO-referred patients were treated. CONCLUSION For patients with H1N1-related ARDS, referral and transfer to an ECMO center was associated with lower hospital mortality compared with matched non-ECMO-referred patients.

Continuous assessment of the cerebral vasomotor reactivity in head injury.

OBJECTIVE Cerebrovascular vasomotor reactivity reflects changes in smooth muscle tone in the arterial wall in response to changes in transmural pressure or the concentration of carbon dioxide in blood. We investigated whether slow waves in arterial blood pressure (ABP) and intracranial pressure (ICP) may be used to derive an index that reflects the reactivity of vessels to changes in ABP. METHODS A method for the continuous monitoring of the association between slow spontaneous waves in ICP and arterial pressure was adopted in a group of 82 patients with head injuries. ABP, ICP, and transcranial doppler blood flow velocity in the middle cerebral artery was recorded daily (20- to 120-min time periods). A Pressure-Reactivity Index (PRx) was calculated as a moving correlation coefficient between 40 consecutive samples of values for ICP and ABP averaged for a period of 5 seconds. A moving correlation coefficient (Mean Index) between spontaneous fluctuations of mean flow velocity and cerebral perfusion pressure, which was previously reported to describe cerebral blood flow autoregulation, was also calculated. RESULTS A positive PRx correlated with high ICP (r = 0.366; P < 0.001), low admission Glasgow Coma Scale score (r = 0.29; P < 0.01), and poor outcome at 6 months after injury (r = 0.48; P < 0.00001). During the first 2 days after injury, PRx was positive (P < 0.05), although only in patients with unfavorable outcomes. The correlation between PRx and Mean index (r = 0.63) was highly significant (P < 0.000001). CONCLUSION Computer analysis of slow waves in ABP and ICP is able to provide a continuous index of cerebrovascular reactivity to changes in arterial pressure, which is of prognostic significance.

Continuous monitoring of cerebrovascular pressure reactivity allows determination of optimal cerebral perfusion pressure in patients with traumatic brain injury.

Objectives To define optimal cerebral perfusion pressure (CPPOPT) in individual head-injured patients using continuous monitoring of cerebrovascular pressure reactivity. To test the hypothesis that patients with poor outcome were managed at a cerebral perfusion pressure (CPP) differing more from their CPPOPT than were patients with good outcome. Design Retrospective analysis of prospectively collected data. Setting Neurosciences critical care unit of a university hospital. Patients A total of 114 head-injured patients admitted between January 1997 and August 2000 with continuous monitoring of mean arterial blood pressure (MAP) and intracranial pressure (ICP). Measurements and Main Results MAP, ICP, and CPP were continuously recorded and a pressure reactivity index (PRx) was calculated online. PRx is the moving correlation coefficient recorded over 4-min periods between averaged values (6-sec periods) of MAP and ICP representing cerebrovascular pressure reactivity. When cerebrovascular reactivity is intact, PRx has negative or zero values, otherwise PRx is positive. Outcome was assessed at 6 months using the Glasgow Outcome Scale. A total of 13,633 hrs of data were recorded. CPPOPT was defined as the CPP where PRx reaches its minimum value when plotted against CPP. Identification of CPPOPT was possible in 68 patients (60%). In 22 patients (27%), CPPOPT was not found because it presumably lay outside the studied range of CPP. Patients’ outcome correlated with the difference between CPP and CPPOPT for patients who were managed on average below CPPOPT (r = .53, p < .001) and for patients whose mean CPP was above CPPOPT (r = −.40, p < .05). Conclusions CPPOPT could be identified in a majority of patients. Patients with a mean CPP close to CPPOPT were more likely to have a favorable outcome than those whose mean CPP was more different from CPPOPT. We propose use of the criterion of minimal achievable PRx to guide future trials of CPP oriented treatment in head injured patients.

Monitoring of Cerebral Autoregulation in Head-Injured Patients

BACKGROUND AND PURPOSE Disturbed cerebral autoregulation has been reported to correlate with an unfavorable outcome after head injury. Using transcranial Doppler ultrasonography, we investigated whether hemodynamic responses to spontaneous variations of cerebral perfusion pressure (CPP) provide reliable information on cerebral autoregulatory reserve. METHODS We studied 82 patients with head injury daily. Waveforms of intracranial pressure (ICP), arterial pressure, and transcranial Doppler flow velocity (FV) were captured during 2-hour periods. Time-averaged mean FV (FVm) and the FV during cardiac systole (FVs) were resolved. The correlation coefficient indices between FVm and CPP (Mx) and between FVs and CPP (Sx) during spontaneous fluctuations of CPP were calculated during 3-minute epochs and averaged for each investigation. RESULTS Mx and Sx correlated with CPP (r = -.34, P = < .002; r = -.2, P = NS. respectively), with ICP (r = .46, P < .0001; r = .34, P < .003, respectively), with admission Glasgow Coma Scale score (r = -.34, P < .0025; r = -.38, P < .0008, respectively), and with outcome after head injury (r = .41, P < .0002; r = .48, P < .00009, respectively). In patients who died, cerebral autoregulation was severely disturbed during the first 2 days after injury. CONCLUSIONS Indices derived from spontaneous fluctuations of FV waveform and CPP describe cerebral vascular pressure reactivity. They correlate with outcome after head injury and therefore may be used to guide autoregulation-oriented intensive therapy.

Proton MR spectroscopy of intracranial tumours: in vivo and in vitro studies.

Proton magnetic resonance spectroscopy (1H MRS) was used to investigate intracranial tumours in vitro and in vivo. Biopsy specimens were studied from 47 patients, 11 of whom were also examined in vivo. Analysis was based on the signals from N-acetylaspartate (NAA), phosphocreatine plus creatine (Cr), choline-containing compounds (Cho), alanine (Ala), and lactate. Biopsy data from 26 astrocytomas showed that the NAA/Cr ratio differs significantly in all grades from its value in normal white matter and that the Cho/Cr ratio differs significantly in grade IV tumours from its value in the other grades. Meningiomas have an unusually high Ala/Cr ratio. Spectra obtained in vivo are consistent with in vitro results from the same patients, and their lactate signal provides additional information about abnormal metabolism. We conclude that 1H MRS has a clear role in the diagnosis and biochemical assessment of intracranial tumours and in the evaluation and monitoring of therapy.

Redefining the functional organization of working memory processes within human lateral prefrontal cortex.

It is widely held that the frontal cortex plays a critical part in certain aspects of spatial and non‐spatial working memory. One unresolved issue is whether there are functionally distinct subdivisions of the lateral frontal cortex that subserve different aspects of working memory. The present study used positron emission tomography (PET) to demonstrate that working memory processes within the human mid‐dorsolateral and mid‐ventrolateral frontal regions are organized according to the type of processing required rather than according to the nature (i.e. spatial or non‐spatial), of the information being processed, as has been widely assumed. Two spatial working memory tasks were used which varied in the extent to which they required different executive processes. During a ‘spatial span’ task that required the subject to hold a sequence of five previously remembered locations in working memory a significant change in blood‐flow was observed in the right mid‐ventrolateral frontal cortex, but not in the anatomically and cytoarchitectonically distinct mid‐dorsolateral frontal‐lobe region. By contrast, during a ‘2‐back’ task that required the subject to continually update and manipulate an ongoing sequence of locations within working memory, significant blood flow increases were observed in both mid‐ventrolateral and mid‐dorsolateral frontal regions. When the two working memory tasks were compared directly, the one that emphasized manipulation of information within working memory yielded significantly greater activity in the right mid‐dorsolateral frontal cortex only. This dissociation provides unambiguous evidence that the mid‐dorsolateral and mid‐ventrolateral frontal cortical areas make distinct functional contributions to spatial working memory and corresponds with a fractionation of working memory processes in psychological terms.

Efficient Multi-Scale 3D CNN with Fully Connected CRF for Accurate Brain Lesion Segmentation

HIGHLIGHTSAn efficient 11‐layers deep, multi‐scale, 3D CNN architecture.A novel training strategy that significantly boosts performance.The first employment of a 3D fully connected CRF for post‐processing.State‐of‐the‐art performance on three challenging lesion segmentation tasks.New insights into the automatically learned intermediate representations. ABSTRACT We propose a dual pathway, 11‐layers deep, three‐dimensional Convolutional Neural Network for the challenging task of brain lesion segmentation. The devised architecture is the result of an in‐depth analysis of the limitations of current networks proposed for similar applications. To overcome the computational burden of processing 3D medical scans, we have devised an efficient and effective dense training scheme which joins the processing of adjacent image patches into one pass through the network while automatically adapting to the inherent class imbalance present in the data. Further, we analyze the development of deeper, thus more discriminative 3D CNNs. In order to incorporate both local and larger contextual information, we employ a dual pathway architecture that processes the input images at multiple scales simultaneously. For post‐processing of the networks soft segmentation, we use a 3D fully connected Conditional Random Field which effectively removes false positives. Our pipeline is extensively evaluated on three challenging tasks of lesion segmentation in multi‐channel MRI patient data with traumatic brain injuries, brain tumours, and ischemic stroke. We improve on the state‐of‐the‐art for all three applications, with top ranking performance on the public benchmarks BRATS 2015 and ISLES 2015. Our method is computationally efficient, which allows its adoption in a variety of research and clinical settings. The source code of our implementation is made publicly available.