Measurement of Intraspinal Pressure After Spinal Cord Injury: Technical Note from the Injured Spinal Cord Pressure Evaluation Study.

Intracranial pressure (ICP) is routinely measured in patients with severe traumatic brain injury (TBI). We describe a novel technique that allowed us to monitor intraspinal pressure (ISP) at the injury site in 14 patients who had severe acute traumatic spinal cord injury (TSCI), analogous to monitoring ICP after brain injury. A Codman probe was inserted subdurally to measure the pressure of the injured spinal cord compressed against the surrounding dura. Our key finding is that it is feasible and safe to monitor ISP for up to a week in patients after TSCI, starting within 72 h of the injury. With practice, probe insertion and calibration take less than 10 min. The ISP signal characteristics after TSCI were similar to the ICP signal characteristics recorded after TBI. Importantly, there were no associated complications. Future studies are required to determine whether reducing ISP improves neurological outcome after severe TSCI

Porohyperelastic anatomical models for hydrocephalus and idiopathic intracranial hypertension

This is the accepted manuscript of a paper published in the Journal of Neurosurgery, Published online February 6, 2015; DOI: 10.3171/2014.12.JNS14516.OBJECT Brain deformation can be seen in hydrocephalus and idiopathic intracranial hypertension (IIH) via medical images. The phenomenology of local effects, brain shift, and raised intracranial pressure and herniation are textbook concepts. However, there are still uncertainties regarding the specific processes that occur when brain tissue is subject to the mechanical stress of different temporal and spatial profiles of the 2 neurological disorders. Moreover, recent studies suggest that IIH and hydrocephalus may be diseases with opposite pathogenesis. Nevertheless, the similarities and differences between the 2 subjects have not been thoroughly investigated. METHODS An anatomical porohyperelastic finite element model was used to assess the brain tissue responses associated with hydrocephalus and IIH. The same set of boundary conditions, with the exception of brain loading for development of the transmantle pressure gradient, was applied for the 2 models. The distribution of stress and strain during tissue distortion is described by the mechanical parameters. RESULTS The results of both the hydrocephalus and IIH models correlated with pathological characteristics. For the hydrocephalus model, periventricular edema was associated with the presence of positive volumetric strain and void ratio in the lateral ventricle horns. By contrast, the IIH model revealed edema across the cerebral mantle, including the centrum semiovale, with a positive void ratio and volumetric strain. CONCLUSIONS The model simulates all the clinical features in correlation with the MR images obtained in patients with hydrocephalus and IIH, thus providing support for the role of the transmantle pressure gradient and capillary CSF absorption in CSF-related brain deformation. The finite element methods can be used for a better understanding of the pathophysiological mechanisms of neurological disorders associated with parenchymal volumetric fluctuation.Dr. M. Czosnyka is a consultant for J&J (Codman), and has received payment for lectures from Integra Lifescience. This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRFK) funded by the Ministry of Science, ICT, & Future Planning (2013R1A1A1004827); and the International Research & Development Program of the NRFK funded by the Ministry of Education, Science, and Technology of Korea (Grant No. 2014K1A3A1A21001366)

Assessment of non-invasive ICP during CSF infusion test: an approach with transcranial Doppler.

BACKGROUND: This study aimed to compare four non-invasive intracranial pressure (nICP) methods in a prospective cohort of hydrocephalus patients whose cerebrospinal fluid dynamics was investigated using infusion tests involving controllable test-rise of ICP. METHOD: Cerebral blood flow velocity (FV), ICP and non-invasive arterial blood pressure (ABP) were recorded in 53 patients diagnosed for hydrocephalus. Non-invasive ICP methods were based on: (1) interaction between FV and ABP using black-box model (nICP_BB); (2) diastolic FV (nICP_FVd); (3) critical closing pressure (nICP_CrCP); (4) transcranial Doppler-derived pulsatility index (nICP_PI). Correlation between rise in ICP (∆ICP) and ∆nICP and averaged correlations for changes in time between ICP and nICP during infusion test were investigated. RESULTS: From baseline to plateau, all nICP estimators increased significantly. Correlations between ∆ICP and ∆nICP were better represented by nICP_PI and nICP_BB: 0.45 and 0.30 (p < 0.05). nICP_FVd and nICP_CrCP presented non-significant correlations: -0.17 (p = 0.21), 0.21 (p = 0.13). For changes in ICP during individual infusion test nICP_PI, nICP_BB and nICP_FVd presented similar correlations with ICP: 0.39 ± 0.40, 0.39 ± 0.43 and 0.35 ± 0.41 respectively. However, nICP_CrCP presented a weaker correlation (R = 0.29 ± 0.24). CONCLUSIONS: Out of the four methods, nICP_PI was the one with best performance for predicting changes in ∆ICP during infusion test, followed by nICP_BB. Unreliable correlations were shown by nICP_FVd and nICP_CrCP. Changes of ICP observed during the test were expressed by nICP values with only moderate correlations.DC is supported by a Cambridge Commonwealth, European & International Trust Scholarship, University of Cambridge. JD is supported by a Woolf Fisher Trust Scholarship. XL is supported by a Gates Cambridge Trust Scholarship. BCTC is supported by CNPQ (Research Project 203792/2014-9). DC and MC are partially supported by NIHR Brain Injury Healthcare Technology Co-operative, Cambridge, UK.This is the final version of the article. It was first available from Springer via http://dx.doi.org/10.1007/s00701-015-2661-

Diffusion tensor imaging profiles reveal specific neural tract distortion in normal pressure hydrocephalus

BACKGROUND: The pathogenesis of normal pressure hydrocephalus (NPH) remains unclear which limits both early diagnosis and prognostication. The responsiveness to intervention of differing, complex and concurrent injury patterns on imaging have not been well-characterized. We used diffusion tensor imaging (DTI) to explore the topography and reversibility of white matter injury in NPH pre- and early after shunting. METHODS: Twenty-five participants (sixteen NPH patients and nine healthy controls) underwent DTI, pre-operatively and at two weeks post-intervention in patients. We interrogated 40 datasets to generate a full panel of DTI measures and corroborated findings with plots of isotropy (p) vs. anisotropy (q). RESULTS: Concurrent examination of DTI measures revealed distinct profiles for NPH patients vs. controls. PQ plots demonstrated that patterns of injury occupied discrete white matter districts. DTI profiles for different white matter tracts showed changes consistent with i) predominant transependymal diffusion with stretch/ compression, ii) oedema with or without stretch/ compression and iii) predominant stretch/ compression. Findings were specific to individual tracts and dependent upon their proximity to the ventricles. At two weeks post-intervention, there was a 6·7% drop in axial diffusivity (p = 0·022) in the posterior limb of the internal capsule, compatible with improvement in stretch/ compression, that preceded any discernible changes in clinical outcome. On PQ plots, the trajectories of the posterior limb of the internal capsule and inferior longitudinal fasciculus suggested attempted 'round trips'. i.e. return to normality. CONCLUSION: DTI profiling with p:q correlation may offer a non-invasive biomarker of the characteristics of potentially reversible white matter injury.Nicole C Keong was supported by a Joint Royal College of Surgeons of England and Dunhill Medical Trust Fellowship and a Tunku Abdul Rahman Centenary Grant and other from National Medical Research Council Transition Award Grant, Singapore (supporting ongoing work). A Medical Research Council Programme Grant [Wolfson Brain Imaging Centre Cooperative] supported the study imaging work. Marek Czosnyka was supported by grants from Johnson and Johnson – Codman, Integra, Sophysa and Aesculap. Zofia Czosnyka was supported by grants from Johnson and Johnson – Codman, Integra, Sophysa and Aesculap. Elise DeVito was funded by the Pinsent-Darwin Studentship in Mental Pathology. Charlotte Housden took up employment with Cambridge Cognition Ltd following her PhD. Barbara J Sahakian was supported by a Medical Research Council Grant and reports personal fees from Cambridge Cognition, Lundbeck, Servier, grants from Janssen/J&J, other from Otsuka and personal fees from Peak (Brainbow). JDP was supported by an NIHR Senior Investigator Award, a Medical Research Council Programme grant and an NIHR Cambridge Biomedical Research Centre grant [brain injury theme] and also wishes to declare the following - Past advisor to Codman and Medtronic international advisory board, Director (unpaid) of Medicam, Scientific Collaboration with GSK (unpaid), Trustee of Brain Research Trust, Patron of Headway Cambridgeshire, Honorary Director of National Institute for Health Research Brain Injury Healthcare Technology Cooperative

Comparison of ventricular drain location and infusion test in hydrocephalus

OBJECTIVES: Suspected cerebrospinal fluid shunt (CSF) dysfunction in hydrocephalic patients poses a diagnostic uncertainty. The clinical picture can be non-specific and CT imaging alone is not always pathognomonic. Infusion tests are an increasingly used investigation for real-time hydrodynamic assessment of shunt patency. We report the correlation between infusion test results with the quality of ventricular drain placement on CT scans in a large retrospective group of hydrocephalic patients. MATERIALS & METHODS: Three hundred and six infusion test results performed in 200 patients were correlated with 306 corresponding CT head scans. Nominal logistic regression was used to correlate shunt catheter position on CT imaging to patency of ventricular drain as determined by infusion tests. RESULTS: Infusion test results of shunt patency are statistically congruent with the analysis of shunt catheter position on CT head scans. Catheter tips completely surrounded by either parenchyma or CSF on CT imaging are strongly associated with evidence of occlusion or patency from infusion tests, respectively (χ² = 51.68, P < 0.0001, n = 306 and χ² = 31.04, P < 0.0001, n = 306). CONCLUSIONS: The most important anatomical factor for shunt patency is the catheter tip being completely surrounded by CSF. Infusion tests provide functional and reliable assessment of shunt patency in vivo and are strongly correlated with the position of the ventricular catheter on CT imaging.No funding source

Robotic Semi-Automated Transcranial Doppler Assessment of Cerebrovascular Autoregulation in Post-Concussion Syndrome: Methodological Considerations.

Post-concussion syndrome (PCS) refers to a constellation of physical, cognitive, and emotional symptoms after traumatic brain injury (TBI). Despite its incidence and impact, the underlying mechanisms of PCS are unclear. We hypothesized that impaired cerebral autoregulation (CA) is a contributor. In this article, we present our protocol for non-invasively assessing CA in patients with TBI and PCS in a real-world clinical setting. A prospective, observational study was integrated into outpatient clinics at a tertiary neurosurgical center. Data points included: demographics, symptom profile (Post-Concussion Symptom Scale [PCSS]) and neuropsychological assessment (Cambridge Neuropsychological Test Automated-Battery [CANTAB]). Cerebrovascular metrics (nMxa co-efficient and the transient hyperaemic-response ratio [THRR]) were collected using transcranial Doppler (TCD), finger plethysmography, and bespoke software (ICM+). Twelve participants were initially recruited but 2 were excluded after unsuccessful insonation of the middle cerebral artery (MCA); 10 participants (5 patients with TBI, 5 healthy controls) were included in the analysis (median age 26.5 years, male to female ratio: 7:3). Median PCSS scores were 6/126 for the TBI patient sub-groups. Median CANTAB percentiles were 78 (healthy controls) and 25 (TBI). nMxa was calculated for 90% of included patients, whereas THRR was calculated for 50%. Median study time was 127.5 min and feedback (n = 6) highlighted the perceived acceptability of the study. This pilot study has demonstrated a reproducible assessment of PCS and CA metrics (non-invasively) in a real-world setting. This protocol is feasible and is acceptable to participants. By scaling this methodology, we hope to test whether CA changes are correlated with symptomatic PCS in patients post-TBI

Multiplicity of cerebrospinal fluid functions: New challenges in health and disease

This review integrates eight aspects of cerebrospinal fluid (CSF) circulatory dynamics: formation rate, pressure, flow, volume, turnover rate, composition, recycling and reabsorption. Novel ways to modulate CSF formation emanate from recent analyses of choroid plexus transcription factors (E2F5), ion transporters (NaHCO3 cotransport), transport enzymes (isoforms of carbonic anhydrase), aquaporin 1 regulation, and plasticity of receptors for fluid-regulating neuropeptides. A greater appreciation of CSF pressure (CSFP) is being generated by fresh insights on peptidergic regulatory servomechanisms, the role of dysfunctional ependyma and circumventricular organs in causing congenital hydrocephalus, and the clinical use of algorithms to delineate CSFP waveforms for diagnostic and prognostic utility. Increasing attention focuses on CSF flow: how it impacts cerebral metabolism and hemodynamics, neural stem cell progression in the subventricular zone, and catabolite/peptide clearance from the CNS. The pathophysiological significance of changes in CSF volume is assessed from the respective viewpoints of hemodynamics (choroid plexus blood flow and pulsatility), hydrodynamics (choroidal hypo- and hypersecretion) and neuroendocrine factors (i.e., coordinated regulation by atrial natriuretic peptide, arginine vasopressin and basic fibroblast growth factor). In aging, normal pressure hydrocephalus and Alzheimer's disease, the expanding CSF space reduces the CSF turnover rate, thus compromising the CSF sink action to clear harmful metabolites (e.g., amyloid) from the CNS. Dwindling CSF dynamics greatly harms the interstitial environment of neurons. Accordingly the altered CSF composition in neurodegenerative diseases and senescence, because of adverse effects on neural processes and cognition, needs more effective clinical management. CSF recycling between subarachnoid space, brain and ventricles promotes interstitial fluid (ISF) convection with both trophic and excretory benefits. Finally, CSF reabsorption via multiple pathways (olfactory and spinal arachnoidal bulk flow) is likely complemented by fluid clearance across capillary walls (aquaporin 4) and arachnoid villi when CSFP and fluid retention are markedly elevated. A model is presented that links CSF and ISF homeostasis to coordinated fluxes of water and solutes at both the blood-CSF and blood-brain transport interfaces

Predictors of Access to Rehabilitation in the Year Following Traumatic Brain Injury : A European Prospective and Multicenter Study

Background Although rehabilitation is beneficial for individuals with traumatic brain injury (TBI), a significant proportion of them do not receive adequate rehabilitation after acute care. Objective Therefore, the goal of this prospective and multicenter study was to investigate predictors of access to rehabilitation in the year following injury in patients with TBI. Methods Data from a large European study (CENTER-TBI), including TBIs of all severities between December 2014 and December 2017 were used (N = 4498 patients). Participants were dichotomized into those who had and those who did not have access to rehabilitation in the year following TBI. Potential predictors included sociodemographic factors, psychoactive substance use, preinjury medical history, injury-related factors, and factors related to medical care, complications, and discharge. Results In the year following traumatic injury, 31.4% of patients received rehabilitation services. Access to rehabilitation was positively and significantly predicted by female sex (odds ratio [OR] = 1.50), increased number of years of education completed (OR = 1.05), living in Northern (OR = 1.62; reference: Western Europe) or Southern Europe (OR = 1.74), lower prehospital Glasgow Coma Scale score (OR = 1.03), higher Injury Severity Score (OR = 1.01), intracranial (OR = 1.33) and extracranial (OR = 1.99) surgery, and extracranial complication (OR = 1.75). On contrast, significant negative predictors were lack of preinjury employment (OR = 0.80), living in Central and Eastern Europe (OR = 0.42), and admission to hospital ward (OR = 0.47; reference: admission to intensive care unit) or direct discharge from emergency room (OR = 0.24). Conclusions Based on these findings, there is an urgent need to implement national and international guidelines and strategies for access to rehabilitation after TBI.Peer reviewe

Tracheal intubation in traumatic brain injury: a multicentre prospective observational study

Background We aimed to study the associations between pre- and in-hospital tracheal intubation and outcomes in traumatic brain injury (TBI), and whether the association varied according to injury severity. Methods Data from the international prospective pan-European cohort study, Collaborative European NeuroTrauma Effectiveness Research for TBI (CENTER-TBI), were used (n=4509). For prehospital intubation, we excluded self-presenters. For in-hospital intubation, patients whose tracheas were intubated on-scene were excluded. The association between intubation and outcome was analysed with ordinal regression with adjustment for the International Mission for Prognosis and Analysis of Clinical Trials in TBI variables and extracranial injury. We assessed whether the effect of intubation varied by injury severity by testing the added value of an interaction term with likelihood ratio tests. Results In the prehospital analysis, 890/3736 (24%) patients had their tracheas intubated at scene. In the in-hospital analysis, 460/2930 (16%) patients had their tracheas intubated in the emergency department. There was no adjusted overall effect on functional outcome of prehospital intubation (odds ratio=1.01; 95% confidence interval, 0.79–1.28; P=0.96), and the adjusted overall effect of in-hospital intubation was not significant (odds ratio=0.86; 95% confidence interval, 0.65–1.13; P=0.28). However, prehospital intubation was associated with better functional outcome in patients with higher thorax and abdominal Abbreviated Injury Scale scores (P=0.009 and P=0.02, respectively), whereas in-hospital intubation was associated with better outcome in patients with lower Glasgow Coma Scale scores (P=0.01): in-hospital intubation was associated with better functional outcome in patients with Glasgow Coma Scale scores of 10 or lower. Conclusion The benefits and harms of tracheal intubation should be carefully evaluated in patients with TBI to optimise benefit. This study suggests that extracranial injury should influence the decision in the prehospital setting, and level of consciousness in the in-hospital setting. Clinical trial registration NCT02210221