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Fluids and Barriers of the CNS Apr 2019The fine balance between the secretion, composition, volume and turnover of cerebrospinal fluid (CSF) is strictly regulated. However, during certain neurological... (Review)
Review
The fine balance between the secretion, composition, volume and turnover of cerebrospinal fluid (CSF) is strictly regulated. However, during certain neurological diseases, this balance can be disrupted. A significant disruption to the normal CSF circulation can be life threatening, leading to increased intracranial pressure (ICP), and is implicated in hydrocephalus, idiopathic intracranial hypertension, brain trauma, brain tumours and stroke. Yet, the exact cellular, molecular and physiological mechanisms that contribute to altered hydrodynamic pathways in these diseases are poorly defined or hotly debated. The traditional views and concepts of CSF secretion, flow and drainage have been challenged, also due to recent findings suggesting more complex mechanisms of brain fluid dynamics than previously proposed. This review evaluates and summarises current hypotheses of CSF dynamics and presents evidence for the role of impaired CSF dynamics in elevated ICP, alongside discussion of the proteins that are potentially involved in altered CSF physiology during neurological disease. Undoubtedly CSF secretion, absorption and drainage are important aspects of brain fluid homeostasis in maintaining a stable ICP. Traditionally, pharmacological interventions or CSF drainage have been used to reduce ICP elevation due to over production of CSF. However, these drugs are used only as a temporary solution due to their undesirable side effects. Emerging evidence suggests that pharmacological targeting of aquaporins, transient receptor potential vanilloid type 4 (TRPV4), and the Na-K-2Cl cotransporter (NKCC1) merit further investigation as potential targets in neurological diseases involving impaired brain fluid dynamics and elevated ICP.
Topics: Animals; Cerebrospinal Fluid; Humans; Hydrodynamics; Intracranial Pressure; Nervous System Diseases
PubMed: 30967147
DOI: 10.1186/s12987-019-0129-6 -
Fluids and Barriers of the CNS Jun 2020Measurement of intracranial pressure (ICP) is crucial in the management of many neurological conditions. However, due to the invasiveness, high cost, and required... (Review)
Review
Measurement of intracranial pressure (ICP) is crucial in the management of many neurological conditions. However, due to the invasiveness, high cost, and required expertise of available ICP monitoring techniques, many patients who could benefit from ICP monitoring do not receive it. As a result, there has been a substantial effort to explore and develop novel noninvasive ICP monitoring techniques to improve the overall clinical care of patients who may be suffering from ICP disorders. This review attempts to summarize the general pathophysiology of ICP, discuss the importance and current state of ICP monitoring, and describe the many methods that have been proposed for noninvasive ICP monitoring. These noninvasive methods can be broken down into four major categories: fluid dynamic, otic, ophthalmic, and electrophysiologic. Each category is discussed in detail along with its associated techniques and their advantages, disadvantages, and reported accuracy. A particular emphasis in this review will be dedicated to methods based on the use of transcranial Doppler ultrasound. At present, it appears that the available noninvasive methods are either not sufficiently accurate, reliable, or robust enough for widespread clinical adoption or require additional independent validation. However, several methods appear promising and through additional study and clinical validation, could eventually make their way into clinical practice.
Topics: Humans; Intracranial Hypertension; Intracranial Pressure; Neurophysiological Monitoring; Ultrasonography, Doppler, Transcranial
PubMed: 32576216
DOI: 10.1186/s12987-020-00201-8 -
Der Nervenarzt Oct 2023Traumatic brain injury (TBI) describes parenchymal brain damage caused by external forces to the head. It has a massive personal and socioeconomic impact, as it is...
Traumatic brain injury (TBI) describes parenchymal brain damage caused by external forces to the head. It has a massive personal and socioeconomic impact, as it is a disease with high morbidity and mortality. Both young and old people are affected, as a result of traffic or sports accidents as well as due to falls at home. The term TBI encompasses various clinical pictures, differing considerably in cause, prognosis and therapy. What they all have in common is the pathophysiological cascade that develops immediately after the initial trauma and which can persist for several days and weeks. In this phase, medical treatment, whether surgical or pharmacological, attempts to reduce the consequences of the primary damage. The aim is to maintain adequate cerebral perfusion pressure and to reduce intracranial pressure.
Topics: Humans; Brain Injuries, Traumatic; Prognosis; Accidents; Intracranial Pressure; Cerebrovascular Circulation
PubMed: 37676293
DOI: 10.1007/s00115-023-01546-9 -
Neurosurgery Feb 2020Hypertonic saline (HTS) and mannitol are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their simultaneous effect... (Comparative Study)
Comparative Study
Hypertonic Saline is Superior to Mannitol for the Combined Effect on Intracranial Pressure and Cerebral Perfusion Pressure Burdens in Patients With Severe Traumatic Brain Injury.
BACKGROUND
Hypertonic saline (HTS) and mannitol are effective in reducing intracranial pressure (ICP) after severe traumatic brain injury (TBI). However, their simultaneous effect on the cerebral perfusion pressure (CPP) and ICP has not been studied rigorously.
OBJECTIVE
To determine the difference in effects of HTS and mannitol on the combined burden of high ICP and low CPP in patients with severe TBI.
METHODS
We performed a case-control study using prospectively collected data from the New York State TBI-trac® database (Brain Trauma Foundation, New York, New York). Patients who received only 1 hyperosmotic agent, either mannitol or HTS for raised ICP, were included. Patients in the 2 groups were matched (1:1 and 1:2) for factors associated with 2-wk mortality: age, Glasgow Coma Scale score, pupillary reactivity, hypotension, abnormal computed tomography scans, and craniotomy. Primary endpoint was the combined burden of ICPhigh (> 25 mm Hg) and CPPlow (< 60 mm Hg).
RESULTS
There were 25 matched pairs for 1:1 comparison and 24 HTS patients matched to 48 mannitol patients in 1:2 comparisons. Cumulative median osmolar doses in the 2 groups were similar. In patients treated with HTS compared to mannitol, total number of days (0.6 ± 0.8 vs 2.4 ± 2.3 d, P < .01), percentage of days with (8.8 ± 10.6 vs 28.1 ± 26.9%, P < .01), and the total duration of ICPhigh + CPPlow (11.12 ± 14.11 vs 30.56 ± 31.89 h, P = .01) were significantly lower. These results were replicated in the 1:2 match comparisons.
CONCLUSION
HTS bolus therapy appears to be superior to mannitol in reduction of the combined burden of intracranial hypertension and associated hypoperfusion in severe TBI patients.
Topics: Adolescent; Adult; Brain Injuries, Traumatic; Case-Control Studies; Cerebrovascular Circulation; Diuretics, Osmotic; Female; Glasgow Coma Scale; Humans; Intracranial Hypertension; Intracranial Pressure; Male; Mannitol; Middle Aged; Prospective Studies; Saline Solution, Hypertonic; Treatment Outcome; Young Adult
PubMed: 30877299
DOI: 10.1093/neuros/nyz046 -
AJNR. American Journal of Neuroradiology Jan 2023The Monro-Kellie doctrine is a well-accepted principle of intracranial hemodynamics. It has undergone few consequential revisions since it was established. Its principle... (Review)
Review
The Monro-Kellie doctrine is a well-accepted principle of intracranial hemodynamics. It has undergone few consequential revisions since it was established. Its principle is straightforward: The combined volume of neuronal tissue, blood, and CSF is constant. To maintain homeostatic intracranial pressure, any increase or decrease in one of these elements leads to a reciprocal and opposite change in the others. The Monro-Kellie doctrine assumes a rigid, unadaptable calvaria. Recent studies have disproven this assumption. The skull expands and grows in response to pathologic changes in intracranial pressure. In this review, we outline what is known about calvarial changes in the setting of pressure dysregulation and suggest a revision to the Monro-Kellie doctrine that includes an adaptable skull as a fourth component.
Topics: Humans; Intracranial Pressure; Skull
PubMed: 36456084
DOI: 10.3174/ajnr.A7721 -
The Cochrane Database of Systematic... Jan 2020Increased intracranial pressure has been shown to be strongly associated with poor neurological outcomes and mortality for patients with acute traumatic brain injury.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Increased intracranial pressure has been shown to be strongly associated with poor neurological outcomes and mortality for patients with acute traumatic brain injury. Currently, most efforts to treat these injuries focus on controlling the intracranial pressure. Hypertonic saline is a hyperosmolar therapy that is used in traumatic brain injury to reduce intracranial pressure. The effectiveness of hypertonic saline compared with other intracranial pressure-lowering agents in the management of acute traumatic brain injury is still debated, both in the short and the long term.
OBJECTIVES
To assess the comparative efficacy and safety of hypertonic saline versus other intracranial pressure-lowering agents in the management of acute traumatic brain injury.
SEARCH METHODS
We searched Cochrane Injuries' Specialised Register, CENTRAL, PubMed, Embase Classic+Embase, ISI Web of Science: Science Citation Index and Conference Proceedings Citation Index-Science, as well as trials registers, on 11 December 2019. We supplemented these searches with searches of four major Chinese databases on 19 September 2018. We also checked bibliographies, and contacted trial authors to identify additional trials.
SELECTION CRITERIA
We sought to identify all randomised controlled trials (RCTs) of hypertonic saline versus other intracranial pressure-lowering agents for people with acute traumatic brain injury of any severity. We excluded cross-over trials as incompatible with assessing long-term outcomes.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened search results to identify potentially eligible trials and extracted data using a standard data extraction form. Outcome measures included: mortality at end of follow-up (all-cause); death or disability (as measured by the Glasgow Outcome Scale (GOS)); uncontrolled intracranial pressure (defined as failure to decrease the intracranial pressure to target and/or requiring additional intervention); and adverse events e.g. rebound phenomena; pulmonary oedema; acute renal failure during treatment).
MAIN RESULTS
Six trials, involving data from 287 people, met the inclusion criteria. The majority of participants (91%) had a diagnosis of severe traumatic brain injury. We had concerns about particular domains of risk of bias in each trial, as physicians were not reliably blinded to allocation, two trials contained participants with conditions other than traumatic brain injury and in one trial, we had concerns about missing data for important outcomes. The original protocol was available for only one trial and other trials (where registered) were registered retrospectively. Meta-analysis for both the primary outcome (mortality at final follow-up) and for 'poor outcome' as per conventionally dichotomised GOS criteria, was only possible for two trials. Synthesis of long-term outcomes was inhibited by the fact that two trials ceased data collection within two hours of a single bolus dose of an intracranial pressure-lowering agent and one at discharge from the intensive care unit (ICU). Only three trials collected data after participants were released from hospital, one of which did not report mortality and reported a 'poor outcome' by GOS criteria in an unconventional way. Substantial missing data in a key trial meant that in meta-analysis we report 'best-case' and 'worst-case' estimates alongside available case analysis. In no scenario did we discern a clear difference between treatments for either mortality or poor neurological outcome. Due to variation in modes of drug administration (including whether it followed or did not follow cerebrospinal fluid (CSF) drainage, as well as different follow-up times and ways of reporting changes in intracranial pressure, as well as no uniform definition of 'uncontrolled intracranial pressure', we did not perform meta-analysis for this outcome and report results narratively, by individual trial. Trials tended to report both treatments to be effective in reducing elevated intracranial pressure but that hypertonic saline had increased benefits, usually adding that pretreatment factors need to be considered (e.g. serum sodium and both system and brain haemodynamics). No trial provided data for our other outcomes of interest. We consider evidence quality for all outcomes to be very low, as assessed by GRADE; we downgraded all conclusions due to imprecision (small sample size), indirectness (due to choice of measurement and/or selection of participants without traumatic brain injury), and in some cases, risk of bias and inconsistency. Only one of the included trials reported data on adverse effects; a rebound phenomenon, which was present only in the comparator group (mannitol). None of the trials reported data on pulmonary oedema or acute renal failure during treatment. On the whole, trial authors do not seem to have rigorously sought to collect data on adverse events.
AUTHORS' CONCLUSIONS
This review set out to find trials comparing hypertonic saline to a potential range of other intracranial pressure-lowering agents, but only identified trials comparing it with mannitol or mannitol in combination with glycerol. Based on limited data, there is weak evidence to suggest that hypertonic saline is no better than mannitol in efficacy and safety in the long-term management of acute traumatic brain injury. Future research should be comprised of large, multi-site trials, prospectively registered, reported in accordance with current best practice. Trials should investigate issues such as the type of traumatic brain injury suffered by participants and concentration of infusion and length of time over which the infusion is given.
Topics: Brain Injuries; Brain Injuries, Traumatic; Glasgow Outcome Scale; Humans; Intracranial Hypertension; Intracranial Pressure; Randomized Controlled Trials as Topic; Saline Solution, Hypertonic
PubMed: 31978260
DOI: 10.1002/14651858.CD010904.pub3 -
Critical Care Medicine Nov 2017A relationship between reduced brain tissue oxygenation and poor outcome following severe traumatic brain injury has been reported in observational studies. We designed... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
A relationship between reduced brain tissue oxygenation and poor outcome following severe traumatic brain injury has been reported in observational studies. We designed a Phase II trial to assess whether a neurocritical care management protocol could improve brain tissue oxygenation levels in patients with severe traumatic brain injury and the feasibility of a Phase III efficacy study.
DESIGN
Randomized prospective clinical trial.
SETTING
Ten ICUs in the United States.
PATIENTS
One hundred nineteen severe traumatic brain injury patients.
INTERVENTIONS
Patients were randomized to treatment protocol based on intracranial pressure plus brain tissue oxygenation monitoring versus intracranial pressure monitoring alone. Brain tissue oxygenation data were recorded in the intracranial pressure -only group in blinded fashion. Tiered interventions in each arm were specified and impact on intracranial pressure and brain tissue oxygenation measured. Monitors were removed if values were normal for 48 hours consecutively, or after 5 days. Outcome was measured at 6 months using the Glasgow Outcome Scale-Extended.
MEASUREMENTS AND MAIN RESULTS
A management protocol based on brain tissue oxygenation and intracranial pressure monitoring reduced the proportion of time with brain tissue hypoxia after severe traumatic brain injury (0.45 in intracranial pressure-only group and 0.16 in intracranial pressure plus brain tissue oxygenation group; p < 0.0001). Intracranial pressure control was similar in both groups. Safety and feasibility of the tiered treatment protocol were confirmed. There were no procedure-related complications. Treatment of secondary injury after severe traumatic brain injury based on brain tissue oxygenation and intracranial pressure values was consistent with reduced mortality and increased proportions of patients with good recovery compared with intracranial pressure-only management; however, the study was not powered for clinical efficacy.
CONCLUSIONS
Management of severe traumatic brain injury informed by multimodal intracranial pressure and brain tissue oxygenation monitoring reduced brain tissue hypoxia with a trend toward lower mortality and more favorable outcomes than intracranial pressure-only treatment. A Phase III randomized trial to assess impact on neurologic outcome of intracranial pressure plus brain tissue oxygenation-directed treatment of severe traumatic brain injury is warranted.
Topics: Adult; Brain; Brain Injuries, Traumatic; Female; Glasgow Coma Scale; Humans; Intensive Care Units; Intracranial Pressure; Male; Middle Aged; Monitoring, Physiologic; Oxygen; Prospective Studies; Single-Blind Method
PubMed: 29028696
DOI: 10.1097/CCM.0000000000002619 -
Current Opinion in Critical Care Dec 2023To provide an overview of recent studies discussing novel strategies, controversies, and challenges in the management of severe traumatic brain injury (sTBI) in the... (Review)
Review
PURPOSE OF REVIEW
To provide an overview of recent studies discussing novel strategies, controversies, and challenges in the management of severe traumatic brain injury (sTBI) in the initial postinjury hours.
RECENT FINDINGS
Prehospital management of sTBI should adhere to Advanced Trauma Life Support (ATLS) principles. Maintaining oxygen saturation and blood pressure within target ranges on-scene by anesthetist, emergency physician or trained paramedics has resulted in improved outcomes. Emergency department (ED) management prioritizes airway control, stable blood pressure, spinal immobilization, and correction of impaired coagulation. Noninvasive techniques such as optic nerve sheath diameter measurement, pupillometry, and transcranial Doppler may aid in detecting intracranial hypertension. Osmotherapy and hyperventilation are effective as temporary measures to reduce intracranial pressure (ICP). Emergent computed tomography (CT) findings guide surgical interventions such as decompressive craniectomy, or evacuation of mass lesions. There are no neuroprotective drugs with proven clinical benefit, and steroids and hypothermia cannot be recommended due to adverse effects in randomized controlled trials.
SUMMARY
Advancement of the prehospital and ED care that include stabilization of physiological parameters, rapid correction of impaired coagulation, noninvasive techniques to identify raised ICP, emergent surgical evacuation of mass lesions and/or decompressive craniectomy, and temporary measures to counteract increased ICP play pivotal roles in the initial management of sTBI. Individualized approaches considering the underlying pathology are crucial for accurate outcome prediction.
Topics: Humans; Decompressive Craniectomy; Brain Injuries, Traumatic; Brain Injuries; Tomography, X-Ray Computed; Intracranial Hypertension; Intracranial Pressure
PubMed: 37851061
DOI: 10.1097/MCC.0000000000001094 -
Eye (London, England) Jan 2020Despite glaucoma being the second leading cause of blindness globally, its pathogenesis remains incompletely understood. Although intraocular pressure (IOP) contributes... (Review)
Review
Despite glaucoma being the second leading cause of blindness globally, its pathogenesis remains incompletely understood. Although intraocular pressure (IOP) contributes to glaucoma, and reducing IOP slows progress of the disease, some patients progress despite normal IOP (NTG). Glaucomatous damage causes characteristic cupping of the optic nerve where it passes through the lamina cribrosa. There is evidence that cerebrospinal fluid (CSF) within the optic nerve sheath has a different composition from CSF surrounding the brain. Furthermore, fluctuations in CSF flow into the optic nerve sheath may be reduced by trabeculae within the sheath, and on standing intracranial pressure (ICP) within the sheath is stabilised at around 3 mmHg due to orbital pressure. Blood pressure has been linked both to glaucoma and ICP. These facts have led some to conclude that ICP does not play a role in glaucoma. However, according to stress formulae and Laplace's Law, stress within the lamina cribrosa is dependent on the forces on either side of it, (IOP and ICP), and its thickness. On lying flat at night, ICP between the brain and optic nerve sheath should equalise. Most evidence suggests ICP is lower in glaucoma than in control groups, and that the lamina cribrosa is thinner and more posteriorly displaced in glaucoma. Subjects who have had ICP reduced have developed signs of glaucoma. This review finds most evidence supports a role for low ICP in the pathogenesis of glaucoma. Caffeine, theophylline and vitamin A may increase ICP, and could be new candidates for an oral treatment.
Topics: Glaucoma; Humans; Intracranial Pressure; Intraocular Pressure; Optic Nerve; Tonometry, Ocular
PubMed: 31776450
DOI: 10.1038/s41433-019-0681-y -
Current Neurology and Neuroscience... Apr 2018A pressure difference between the intraocular and intracranial compartments at the site of the lamina cribrosa has been hypothesized to have a pathophysiological role in... (Review)
Review
PURPOSE OF REVIEW
A pressure difference between the intraocular and intracranial compartments at the site of the lamina cribrosa has been hypothesized to have a pathophysiological role in several optic nerve head diseases. This paper reviews the current literature on the translamina cribrosa pressure difference (TLCPD), the associated pressure gradient, and its potential pathophysiological role, as well as the methodology to assess TLCPD.
RECENT FINDINGS
For normal-tension glaucoma (NTG), initial studies indicated low intracranial pressure (ICP) while recent findings indicate that a reduced ICP is not mandatory. Data from studies on the elevated TLCPD as a pathophysiological factor of NTG are equivocal. From the identification of potential postural effects on the cerebrospinal fluid (CSF) communication between the intracranial and retrolaminar space, we hypothesize that the missing link could be a dysfunction of an occlusion mechanism of the optic nerve sheath around the optic nerve. In upright posture, this could cause an elevated TLCPD even with normal ICP and we suggest that this should be investigated as a pathophysiological component in NTG patients.
Topics: Eye; Glaucoma; Humans; Intracranial Pressure; Intraocular Pressure; Ocular Physiological Phenomena; Optic Nerve; Optic Nerve Diseases; Posture
PubMed: 29651628
DOI: 10.1007/s11910-018-0831-9