Intracranial pressure

Cryptococcus neoformans ex vivo capsule size is associated with intracranial pressure and host immune response in HIV-associated cryptococcal meningitis

Authors: Robertson EJ, Najjuka G, Rolfes MA, Akampurira A, Jain N, Anantharanjit J, von Hohenburg M, Tassieri M, Carlsson A, Meya DB, Harrison TS, Fries B, Boulware DR, Bicanic T.

Background. The Cryptococcus neoformans polysaccharide capsule is a well-characterised virulence factor with immunomodulatory properties. The organism and/or shed capsule is postulated to raise intracranial pressure(ICP) in cryptococcal meningitis(CM) by mechanical obstruction of cerebrospinal fluid(CSF) outflow. Little is known regarding capsule phenotype in human cryptococcosis. We investigated the relationship of ex vivo CSF capsular phenotype with ICP and CSF immune response, as well as in vitro phenotype.Methods. 134 HIV-infected Ugandan adults with CM had serial lumbar punctures with measurement of CSF opening pressures, quantitative cultures, ex vivo capsule size and shedding, viscosity, and CSF cytokines. 108 had complete data. Induced capsular size and shedding were measured in vitro for 48 C. neoformans isolates.Results. Cryptococcal strains producing larger ex vivo capsules in the baseline(pre-treatment) CSF correlated with higher ICP(P=.02), slower rate of fungal clearance(P=.02), and paucity of CSF inflammation, including decreased CSF white blood cell(WBC) count(P<.001), interleukin(IL)-4(P=.02), IL-6(P=.01), IL-7(P=.04), IL-8(P=.03), and interferon-gamma(P=.03). CSF capsule shedding did not correlate with ICP. On multivariable analysis, capsule size remained independently associated with ICP. Ex vivo capsular size and shedding did not correlate with that of the same isolates grown in vitro.Conclusions. Cryptococcal capsule size ex vivo is an important contributor to virulence in human cryptococcal meningitis.

Intermittent Versus Continuous Cerebrospinal Fluid Drainage Management in Adult Severe Traumatic Brain Injury: Assessment of Intracranial Pressure Burden

Authors: Nwachuku EL, Puccio AM, Fetzick A, Scruggs B, Chang YF, Shutter LA, Okonkwo DO.

INTRODUCTION: There is clinical equipoise regarding whether neurointensive care unit management of external ventricular drains (EVD) in severe traumatic brain injury (TBI) should involve an open EVD, with continuous drainage of cerebrospinal fluid (CSF), versus a closed EVD, with intermittent opening as necessary to drain CSF. In a matched cohort design, we assessed the relative impact of continuous versus intermittent CSF drainage on intracranial pressure in the management of adult severe TBI.
METHODS: Sixty-two severe TBI patients were assessed. Thirty-one patients managed by open EVD drainage were matched by age, sex, and injury severity (initial Glasgow Coma Scale (GCS) score) to 31 patients treated with a closed EVD drainage. Patients in the open EVD group also had a parenchymal intracranial pressure (ICP) monitor placed through an adjacent burr hole, allowing real-time recording of ICP. Hourly ICP and other pertinent data, such as length of stay in intensive care unit (LOS-ICU), Injury Severity Score, and survival status, were extracted from our prospective database.
RESULTS: With age, injury severity (initial GCS score), and neurosurgical intervention adjusted for, there was a statistically significant difference of 5.66 mmHg in mean ICP (p < 0.0001) between the open and the closed EVD groups, with the closed EVD group exhibiting greater mean ICP. ICP burden (ICP ≥ 20 mmHg) was shown to be significantly higher in the intermittent EVD group (p = 0.0002) in comparison with the continuous EVD group.
CONCLUSION: Continuous CSF drainage via an open EVD seemed to be associated with more effective ICP control in the management of adult severe TBI.

Decreased risk of acute kidney injury with intracranial pressure monitoring in patients with moderate or severe brain injury

Authors: Zeng J, Tong W, Zheng P.

Object The authors undertook this study to evaluate the effects of continuous intracranial pressure (ICP) monitoring-directed mannitol treatment on kidney function in patients with moderate or severe traumatic brain injury (TBI). Methods One hundred sixty-eight patients with TBI were prospectively assigned to an ICP monitoring group or a conventional treatment control group based on the Brain Trauma Foundation guidelines. Clinical data included the dynamic changes of patients' blood concentrations of cystatin C, creatinine (Cr), and blood urea nitrogen (BUN); mannitol use; and 6-month Glasgow Outcome Scale (GOS) scores. Results There were no statistically significant differences with respect to hospitalized injury, age, or sex distribution between the 2 groups. The incidence of acute kidney injury (AKI) was higher in the control group than in the ICP monitoring group (p < 0.05). The mean mannitol dosage in the ICP monitoring group (443 ± 133 g) was significantly lower than in the control group (820 ± 412 g) (p < 0.01), and the period of mannitol use in the ICP monitoring group (3 ± 3.8 days) was significantly shorter than in the control group (7 ± 2.3 days) (p < 0.01). The 6-month GOS scores in the ICP monitoring group were significantly better than in the control group (p < 0.05). On the 7th, 14th, and 21st days after injury, the plasma cystatin C and Cr concentrations in the ICP-monitoring group were significantly higher than the control group (p < 0.05). Conclusions In patients with moderate and severe TBI, ICP-directed mannitol treatment demonstrated a beneficial effect on reducing the incidence of AKI compared with treatment directed by neurological signs and physiological indicators.

Methodology and Evaluation of Intracranial Pressure Response in Rats Exposed to Complex Shock Waves

Authors: Dal Cengio Leonardi A, Keane NJ, Hay K, Ryan AG, Bir CA, Vandevord PJ.

Studies on blast neurotrauma have focused on investigating the effects of exposure to free-field blast representing the simplest form of blast threat scenario without considering any reflecting surfaces. However, in reality personnel are often located within enclosures or nearby reflecting walls causing a complex blast environment, that is, involving shock reflections and/or compound waves from different directions. The purpose of this study was to design a complex wave testing system and perform a preliminary investigation of the intracranial pressure (ICP) response of rats exposed to a complex blast wave environment (CBWE). The effects of head orientation in the same environment were also explored. Furthermore, since it is hypothesized that exposure to a CBWE would be more injurious as compared to a free-field blast wave environment (FFBWE), a histological comparison of hippocampal injury (cleaved caspase-3 and glial fibrillary acidic protein (GFAP)) was conducted in both environments. Results demonstrated that, regardless of orientation, peak ICP values were significantly elevated over the peak static air overpressure. Qualitative differences could be noticed compared to the ICP response in rats exposed to simulated FFBWE. In the CBWE scenario, after the initial loading the skull/brain system was not allowed to return to rest and was loaded again reaching high ICP values. Furthermore, results indicated consistent and distinct ICP-time profiles according to orientation, as well as distinctive values of impulse associated with each orientation. Histologically, cleaved caspase-3 positive cells were significantly increased in the CBWE as compared to the FFBWE. Overall, these findings suggest that the geometry of the skull and the way sutures are distributed in the rats are responsible for the difference in the stresses observed. Moreover, this increase stress contributes to correlation of increased injury in the CBWE.

Effects of xenon and hypothermia on cerebrovascular pressure reactivity in newborn global hypoxic-ischemic pig model

Authors: Chakkarapani E, Dingley J, Aquilina K, Osredkar D, Liu X, Thoresen M.

Autoregulation of cerebral perfusion is impaired in hypoxic-ischemic encephalopathy. We investigated whether cerebrovascular pressure reactivity (PRx), an element of cerebral autoregulation that is calculated as a moving correlation coefficient between averages of intracranial and mean arterial blood pressure (MABP) with values between -1 and +1, is impaired during and after a hypoxic-ischemic insult (HI) in newborn pigs. Associations between end-tidal CO2, seizures, neuropathology, and PRx were investigated. The effect of hypothermia (HT) and Xenon (Xe) on PRx was studied. Pigs were randomized to Sham, and after HI to normothermia (NT), HT, Xe or xenon hypothermia (XeHT). We defined PRx >0.2 as peak and negative PRx as preserved. Neuropathology scores after 72 hours of survival was grouped as 'severe' or 'mild.' Secondary PRx peak during recovery, predictive of severe neuropathology and associated with insult severity (P=0.05), was delayed in HT (11.5 hours) than in NT (6.5 hours) groups. Seizures were associated with impaired PRx in NT pigs (P=0.0002), but not in the HT/XeHT pigs. PRx was preserved during normocapnia and impaired during hypocapnia. Xenon abolished the secondary PRx peak, increased (mean (95% confidence interval (CI)) MABP (6.5 (3.8, 9.4) mm Hg) and cerebral perfusion pressure (5.9 (2.9, 8.9) mm Hg) and preserved the PRx (regression coefficient, -0.098 (95% CI (-0.18, -0.01)), independent of the insult severity.Journal of Cerebral Blood Flow & Metabolism advance online publication, 31 July 2013; doi:10.1038/jcbfm.2013.123.

Lessons from the Intracranial Pressure Monitoring-Trial in TBI patients

Authors: Sarrafzadeh AS, Smoll NR, Unterberg AW.

BACKGROUND: Monitoring of intracranial pressure (ICP) has been used for decades in patients with severe traumatic brain injury (TBI) and is recommended in the Guidelines of the Brain Trauma Foundation. It is the standard of care in most industrialized countries.
METHODS: Chesnut et al. have now performed the first randomized trial of ICP monitoring in patients with severe TBI. Patients were randomly assigned to one of two specific protocols - ICP monitoring (n=157) or imaging and clinical exam (n=167). The study was conducted in Latin America, where ICP-monitoring is not the standard of care in most hospitals.
RESULTS: Six months after injury, patients groups had similar scores on functional status and cognition and similar cumulative mortality. Patients who underwent ICP monitoring had a significantly lower intensity of brain-specific treatment and received fewer treatments for intracranial hypertension.
CONCLUSION: The benefit of this study is that ICP-monitoring - and more advanced multimodal monitoring allows a tailored treatment avoiding an overtherapy of drugs with unfavorable side effects. For low income countries, the results of this trial are encouraging, though efforts should be done to further improve after ICU-care and outcome. However, we guard against the use of this data to reform European and North American treatment guidelines. The authors have proven that neurosurgery can be studied in an elegant fashion. Thanks to their team of neurosurgeons and neurointensivists, the outcome of TBI-patients will continue to improve, driven by clinical practice guidelines.

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