Clinical applications of intracranial pressure monitoring in traumatic brain injury

Intracranial pressure (ICP) monitoring has been for decades a cornerstone of traumatic brain injury (TBI) management. Nevertheless, in recent years, its usefulness has been questioned in several reports. A group of neurosurgeons and neurointensivists met to openly discuss, and provide consensus on, practical applications of ICP in severe adult TBI. A consensus conference was held in Milan on October 5, 2013, putting together neurosurgeons and intensivists with recognized expertise in treatment of TBI. Four topics have been selected and addressed in pro-con presentations: 1) ICP indications in diffuse brain injury, 2) cerebral contusions, 3) secondary decompressive craniectomy (DC), and 4) after evacuation of intracranial traumatic hematomas. The participants were asked to elaborate on the existing published evidence (without a systematic review) and their personal clinical experience. Based on the presentations and discussions of the conference, some drafts were circulated among the attendants. After remarks and further contributions were collected, a final document was approved by the participants. The group made the following recommendations: 1) in comatose TBI patients, in case of normal computed tomography (CT) scan, there is no indication for ICP monitoring; 2) ICP monitoring is indicated in comatose TBI patients with cerebral contusions in whom the interruption of sedation to check neurological status is dangerous and when the clinical examination is not completely reliable. The probe should be positioned on the side of the larger contusion; 3) ICP monitoring is generally recommended following a secondary DC in order to assess the effectiveness of DC in terms of ICP control and guide further therapy; 4) ICP monitoring after evacuation of an acute supratentorial intracranial hematoma should be considered for salvageable patients at increased risk of intracranial hypertension with particular perioperative features

Development of Circadian Oscillators in Neurosphere Cultures during Adult Neurogenesis

Circadian rhythms are common in many cell types but are reported to be lacking in embryonic stem cells. Recent studies have described possible interactions between the molecular mechanism of circadian clocks and the signaling pathways that regulate stem cell differentiation. Circadian rhythms have not been examined well in neural stem cells and progenitor cells that produce new neurons and glial cells during adult neurogenesis. To evaluate circadian timing abilities of cells undergoing neural differentiation, neurospheres were prepared from the mouse subventricular zone (SVZ), a rich source of adult neural stem cells. Circadian rhythms in mPer1 gene expression were recorded in individual spheres, and cell types were characterized by confocal immunofluorescence microscopy at early and late developmental stages in vitro. Circadian rhythms were observed in neurospheres induced to differentiate into neurons or glia, and rhythms emerged within 3-4 days as differentiation proceeded, suggesting that the neural stem cell state suppresses the functioning of the circadian clock. Evidence was also provided that neural stem progenitor cells derived from the SVZ of adult mice are self-sufficient clock cells capable of producing a circadian rhythm without input from known circadian pacemakers of the organism. Expression of mPer1 occurred in high frequency oscillations before circadian rhythms were detected, which may represent a role for this circadian clock gene in the fast cycling of gene expression responsible for early cell differentiation

Intracranial Pressure Monitoring: Fundamental Considerations and Rationale for Monitoring

Traumatic brain injury (TBI) is a major cause of death and disability worldwide. In large part critical care for TBI is focused on the identification and management of secondary brain injury. This requires effective neuromonitoring that traditionally has centered on intracranial pressure (ICP). The purpose of this paper is to review the fundamental literature relative to the clinical application of ICP monitoring in TBI critical care and to provide recommendations on how the technique maybe applied to help patient management and enhance outcome. A PubMed search between 1980 and September 2013 identified 2,253 articles; 244 of which were reviewed in detail to prepare this report and the evidentiary tables. Several important concepts emerge from this review. ICP monitoring is safe and is best performed using a parenchymal monitor or ventricular catheter. While the indications for ICP monitoring are well established, there remains great variability in its use. Increased ICP, particularly the pattern of the increase and ICP refractory to treatment is associated with increased mortality. Class I evidence is lacking on how monitoring and management of ICP influences outcome. However, a large body of observational data suggests that ICP management has the potential to influence outcome, particularly when care is targeted and individualized and supplemented with data from other monitors including the clinical examination and imaging

Genetic drivers of cerebral blood flow dysfunction in TBI: a speculative synthesis

Cerebral autoregulatory dysfunction after traumatic brain injury (TBI) is strongly linked to poor global outcome in patients at 6 months after injury. However, our understanding of what drives this dysfunction is limited. Genetic variation among individuals within a population gives rise to single nucleotide polymorphisms (SNPs) that have the potential to influence a given patient’s cerebrovascular response to an injury. Associations have been reported between a variety of genetic polymorphisms and global outcome in patients with TBI, but few studies have explored the association between genetics and cerebrovascular function after injury. In this Review, we explore polymorphisms that might play an important part in cerebral autoregulatory capacity after TBI. We outline a variety of SNPs, their biological substrates and their potential role in mediating cerebrovascular reactivity. A number of candidate polymorphisms exist in genes that are involved in myogenic, endothelial, metabolic and neurogenic vascular responses to injury. Furthermore, polymorphisms in genes involved in inflammation, the central autonomic response and spreading cortical depression might drive cerebrovascular reactivity. Identification of candidate genes involved in cerebral autoregulation after TBI provides a platform and rationale for further prospective investigation of the link between genetic polymorphisms and autoregulatory function