The Relationship between Serum Sodium, Serum Osmolality, and Intracranial Pressure in Patients with Traumatic Brain Injury Treated with Hyperosmolar Therapy.

BACKGROUND: Treatment of elevated intracranial pressure (ICP) in traumatic brain injury (TBI) is controversial. Hyperosmolar therapy is used to prevent cerebral edema in these patients. Many intensivists measure direct correlates of these agents-serum sodium and osmolality. We seek to provide context on the utility of using these measures to estimate ICP in TBI patients. MATERIALS AND METHODS: Patients admitted with TBI who required ICP monitoring from 2008 to 2012 were included. Intracranial pressure, serum sodium, and serum osmolality were assessed prior to hyperosmotic therapy then at 6, 12, 18, 24, 48, and 72 hours after admission. A linear regression was performed on sodium, osmolality, and ICP at baseline and serum sodium and osmolality that corresponded with ICP for 6-72-hour time points. RESULTS: 136 patients were identified. Patients with initial measures were included in the baseline analysis (n = 29). Patients who underwent a craniectomy were excluded from the 6-72-hour analysis (n = 53). Initial ICP and serum sodium were not significantly correlated (R2 .00367, P = .696). Initial ICP and serum osmolality were not significantly correlated (R2 .00734, P = .665). Intracranial pressure and serum sodium 6-72 hours after presentation were poorly correlated (R2 .104, P < .0001), as were ICP and serum osmolality at 6-72 hours after presentation (R2 .116, P < .0001). DISCUSSION: Our results indicate initial ICP is not correlated with serum sodium or osmolality suggesting these are not useful initial clinical markers for ICP estimation. The association between ICP and serum sodium and osmolality after hyperosmolar therapy was poor, thus may not be useful as surrogates for direct ICP measurements.

The role and importance of auxiliary tests in differential diagnosis in patients with mildly high basal 17-OH-progesterone levels in the evaluation of hirsutism

Background/aim: In the differential diagnosis of hirsutism, early follicular basal 17-OH-progesterone levels sometimes overlap with the diagnosis of late onset congenital adrenal hyperplasia (LOCAH) and other causes of hyperandrogenism. This study aims to investigate the role of some common tests and clinical findings in differential diagnosis in such cases. Materials and methods: One hundred seventy-five female patients with hirsutism and mildly high initial 17-OH-progesterone levels (2-10 ng/mL) were included in the study. The cases were divided into three groups according to their diagnosis: LOCAH (n = 16, mean age = 26.1 ± 6.9), polycystic ovary syndrome (PCOS) (n = 122, mean age = 23.9 ± 5.1), and intracranial hypertension (IH) (n = 37, mean age = 25.2 ± 7.3). Clinical signs and symptoms, such as menstrual irregularity and hirsutism score, and hormone levels including total testosterone and dehydroepiandrosterone sulfate (DHEAS), were compared between the groups. Results: There was no difference between the groups with PCOS, LOCAH, and IH for total testosterone level results (P = 0.461). The DHEAS level was higher in the PCOS group than in the LOCAH group (449.6 ± 151.14 vs. 360.31 ± 152.40, P = 0.044). While there was no difference between the PCOS and LOCAH groups in terms of menstrual irregularity (P = 0.316), the hirsutism score for IH was significantly lower than those of PCOS and LOCAH (9.2 vs. 12.2 and 11.1, respectively; P < 0.001). Basal 17-OH-progesterone levels were higher in the LOCAH group than in the other groups (P = 0.016). Conclusion: While DHEAS level was lower in LOCAH than in PCOS, it was not different from that in IH. While the severity of hirsutism was higher in LOCAH than in IH, it was not different from that in PCOS. Menstrual irregularity was similar between PCOS and LOCAH. According to these results, although the auxiliary tests and clinical findings for the diagnosis of LOCAH contribute to the clinical interpretation, they are not superior to the 17-OH-progesterone level for diagnosis.

Comparison of paired cerebrospinal fluid and serum cell-free mitochondrial and nuclear DNA with copy number and fragment length.

BACKGROUND: Most studies on cell-free DNA (cfDNA) were only for single body fluids; however, the differences in cfDNA distribution between two body fluids are rarely reported. Hence, in this work, we compared the differences in cfDNA distribution between cerebrospinal fluid (CSF) and serum of patients with brain-related diseases. METHODS: The fragment length of cfDNA was determined by using Agilent 2100 Bioanalyzer. The copy numbers of cell-free mitochondrial DNA (cf-mtDNA) and cell-free nuclear DNA (cf-nDNA) were determined by using real-time quantitative PCR (qPCR) and droplet digital PCR (ddPCR) with three pairs of mitochondrial ND1 and nuclear GAPDH primers, respectively. RESULTS: There were short (~60 bp), medium (~167 bp), and long (>250 bp) cfDNA fragment length distributions totally obtained from CSF and serum using Agilent 2100 Bioanalyzer. The results of both qPCR and ddPCR confirmed the existence of these three cfDNA fragment ranges in CSF and serum. According to qPCR, the copy numbers of long cf-mtDNA, medium, and long cf-nDNA in CSF were significantly higher than in paired serum. In CSF, only long cf-mtDNA's copy numbers were higher than long cf-nDNA. But in serum, the copy numbers of medium and long cf-mtDNA were higher than the corresponding cf-nDNA. CONCLUSION: The cf-nDNA and cf-mtDNA with different fragment lengths differentially distributed in the CSF and serum of patients with brain disorders, which might serve as a biomarker of human brain diseases.

Standardized Volume Dosing Protocol of 23.4% Hypertonic Saline for Pediatric Critical Care: Initial Experience.

Background: Standardized volume dosing of 23.4% hypertonic saline (HTS) exists for adults, but the concentration, dosing and administration of HTS in pediatrics is variable. With emerging pediatric experience of 23.4% HTS, a standard volume dose approach may be helpful. Objective: To describe initial experience with a standardized 23.4% HTS weight-based volume dosing protocol of 10, 20, or 30 mL in the pediatric intensive care unit. Methods: Standard volume doses of 23.4% HTS were developed from weight dosing equivalents of 3% HTS. Pre and post sodium and intracranial pressure (ICP) measurements were compared with paired t-test or Wilcoxon rank-sum test. The site of administration and complications were noted. Results: A total of 16 pediatric patients received 37 doses of 23.4% HTS, with the smallest patient weighing 11 kg. For protocol compliance, 17 doses (46%) followed recommended dosing, 19 were less volume than recommended (51%), and 1 dose (3%) was more than recommended. Mean increase in sodium was 3.5 mEq/L (95% CI = 2-5 mEq/L); P < 0.0001. The median decrease in ICP was 10.5 mm Hg (interquartile range [IQR] 8.3-19.5) for a 37% (IQR 25%-64%) reduction. Most doses were administered through central venous access, although peripheral intravenous administrations occurred in 4 patients without complication. Conclusion and Relevance: Three standard-volume dose options of 23.4% HTS based on weight increases sodium and reduces ICP in pediatric patients. Standard-volume doses may simplify weight-based dosing, storage and administration for pediatric emergencies, although the optimum dose, and safety of 23.4% HTS in children remains unknown.

High intracranial pressure may be the initial inducer of elevated plasma D-dimer level after aneurysmal subarachnoid haemorrhage.

Objective: The plasma D-dimer has been regarded as a poor prognosis factor in aneurysmal subarachnoid haemorrhage (aSAH) patients, but the reason of elevated D-dimer level has not been revealed. In this study, we retrospectively explored the potential clinical parameters which might be related to D-dimer level and further attempted to explain the pathological process of D-dimer level elevation in aSAH patients. Patients and methods: The qualified patients with aSAH were recruited and treated in Sichuan Provincial People's Hospital from 1 October 2015 to 28 February 2018. All clinical data were collected, the blood samples were gathered on admission and the levels of D-dimer were detected by the clinical laboratory. The χ2-test, univariate and multiple linear regression analysis were used to seek the relationship between clinical variables and D-dimer level.Results: Total 98 aSAH patients were enrolled. The χ2-test showed a significant difference in clinical characteristics of gender, hyperlipidaemia and ICP between the patients with normal D-dimer level and the others with a high D-dimer level (p < .05). The univariate linear regression analysis and the multiple linear regression analysis showed the combined CCT and ICP were still significantly related to D-dimer level (p < .05). Conclusion: Besides the other related factors, the increased ICP was obviously associated with the elevated plasma D-dimer level. It may indicate that the high ICP acted as the initial role, then led to poor perfusion, even induced the microthrombosis and activated the fibrinolytic system, which eventually contributed to D-dimer level increasing in aSAH patients.

Examining the Effect of Hypertonic Saline Administered for Reduction of Intracranial Hypertension on Coagulation.

BACKGROUND: Hypertonic saline (23.4%, HTS) bolus administration is common practice for refractory intracranial hypertension, but its effects on coagulation are unknown. We hypothesize that 23.4% HTS in whole blood results in progressive impairment of coagulation in vitro and in vivo in a murine model of traumatic brain injury (TBI). STUDY DESIGN: For the in vitro study, whole blood was collected from 10 healthy volunteers, and citrated native thrombelastography was performed with normal saline (0.9%, NS) and 23.4% HTS in serial dilutions (2.5%, 5%, and 10%). For the in vivo experiment, we assessed the effects of 23.4% HTS bolus vs NS on serial thrombelastography and tail-bleeding times in a TBI murine model (n = 10 rats with TBI and 10 controls). RESULTS: For the in vitro work, clinically relevant concentrations of HTS (2.5% dilution) shortened time to clot formation and increased clot strength (maximum amplitude) compared with control and NS. With higher HTS dosing (5% and 10% blood dilution), there was progressive prolongation of time to clot formation, decreased angle, and decreased maximum amplitude. In the in vivo study, there was no significant difference in thrombelastography measurements or tail-bleeding times after bolus administration of 23.4% HTS compared with NS at 2.5% blood volume. CONCLUSIONS: At clinically relevant dilutions of HTS, there is a paradoxical shortening of time to clot formation and increase in clot strength in vitro and no significant effects in a murine TBI model. However, with excess dilution, caution should be exercised when using serial HTS boluses in TBI patients at risk for trauma-induced coagulopathy.

Acute Disseminated Encephalomyelitis (ADEM) and Increased Intracranial Pressure Associated With Anti-Myelin Oligodendrocyte Glycoprotein Antibodies.

BACKGROUND: Antibodies to the myelin oligodendrocyte glycoprotein (MOG) have been identified in about 40% of children with acute disseminated encephalomyelitis (ADEM). The objective of this report is to describe three individuals with fulminant ADEM complicated by increased intracranial pressure associated with the presence of the anti-MOG antibodies. METHODS: This is a retrospective case series. Informed consent was obtained from the concerned patients or caregivers. RESULTS: High intracranial pressure associated with ADEM in the presence of MOG antibodies can result in cerebral edema, herniation, prolonged hospital stay (average intensive care unit stay: 22 days, average hospital stay: 50.6 days), and long-term disability. CONCLUSION: Increased intracranial pressure complicating MOG antibody-related ADEM is a unique finding in our cases. This can complicate the clinical picture of ADEM and confers high morbidity. Long-term immunosuppression is warranted in selected cases with persistent seropositivity.

Antidiuretic hormone release associated with increased intracranial pressure independent of plasma osmolality.

OBJECTIVE: Introduce and evaluate a new model which explains the release of brain antidiuretic hormone (ADH) independent of plasma osmolality. METHODS: Systematic review and critical analysis of the professional literature. RESULTS: Primary electronic database searches using key terms revealed 57,432 hits. Secondary searches with application of specific inclusion and exclusion criteria and manual inspection for completeness reduced the total number of studies to fourteen (N = 14). Twelve (N = 12) studies investigated human subjects in the hospital settings, and two (N = 2) studies investigated animals (rhesus monkeys and dog) under invasive experimental conditions. All fourteen studies included direct or indirect indicators of intracranial pressure (ICP), measurements of plasma ADH, and plasma osmolality or urine osmolality. Findings, in brief, reveal a stable and positive association between increased intracranial pressure (ICP) and increased ADH release, in patients with low or normal blood osmolality. Findings are reliable and reproducible across human and animal populations. CONCLUSIONS: Findings support the proposed model, which explains increase secretion of brain ADH when plasma osmolality is low or within normal limits. Mechanical pressures exerted on hypothalamic nuclei, especially paraventricular and supra-optic nuclei, as a consequence of increased intracranial pressure, produce release of ADH, independent of plasma osmolality. The mechanical pressure model explains release of ADH previously unexplained by traditional plasma osmolality models. Findings have important clinical implications for the medical and surgical management of patients.

Correlation of Circulating T Lymphocytes and Intracranial Hypertension in Intracerebral Hemorrhage.

BACKGROUND: The close correlation between intracerebral pressure (ICP) and immunologic responses has been well described, but the role of T lymphocytes in this process remains unknown. This study targeted the relationship of circulating T lymphocytes and ICP in patients with intracerebral hemorrhage (ICH). METHODS: Between October 2015 and October 2016, consecutive patients age 18-65 years with ICH were enrolled. ICP values were recorded hourly for 5 days, and the screened patients were divided into 2 groups based on ICP: the elevated ICP group (ICP >20 mmHg) and normal ICP group (ICP ≤20 mmHg). Peripheral blood was collected on admission and T lymphocyte subpopulations were analyzed by flow cytometry. Glasgow Coma Scale score on admission and Glasgow Outcome Scale (GOS) score at 30 days after ICH were analyzed. RESULTS: A total of 44 patients were enrolled, including 18 patients in the elevated ICP group and 26 in the normal ICP group. Both CD3+ and CD4+ T lymphocyte counts were higher in the elevated ICP group (P = 0.004 and 0.000, respectively). The CD8+ T lymphocyte count was not significantly different between the 2 groups (P = 0.751). There were correlation trends between the maximum ICP value and CD3+ lymphocyte count (P = 0.003), CD4+ T lymphocyte count (P = 0.000), and the CD4+/CD8+ T lymphocyte ratio (P = 0.000). The area under the curve (AUC) of CD4+/CD8+ T lymphocyte ratio was the largest among them (P = 0.011 and 0.033), with a significant cutoff value and good specificity and sensitivity. There was a close correlation between the CD4+/CD8+ T lymphocyte ratio and the 30-day GOS score (P = 0.003, AUC = 0.812). CONCLUSIONS: The CD4+/CD8+ T lymphocyte ratio may be a valuable indicator for predicting postoperative ICP and the short-term prognosis after ICH.

Comparison of the effects of 7.2% hypertonic saline and 20% mannitol on whole blood coagulation and platelet function in dogs with suspected intracranial hypertension - a pilot study.

BACKGROUND: Hyperosmolar therapy with either mannitol or hypertonic saline (HTS) is commonly used in the treatment of intracranial hypertension (ICH). In vitro data indicate that both mannitol and HTS affect coagulation and platelet function in dogs. The aim of this study was to compare the effects of 20% mannitol and 7.2% HTS on whole blood coagulation using rotational thromboelastometry (ROTEM®) and platelet function using a platelet function analyzer (PFA®) in dogs with suspected ICH. Thirty client-owned dogs with suspected ICH needing osmotherapy were randomized to receive either 20% mannitol (5 ml/kg IV over 15 min) or 7.2% HTS (4 ml/kg IV over 5 min). ROTEM® (EXTEM® and FIBTEM® assays) and PFA® analyses (collagen/ADP cartridges) were performed before (T0), as well as 5 (T5), 60 (T60) and 120 (T120) minutes after administration of HTS or mannitol. Data at T5, T60 and T120 were analyzed as a percentage of values at T0 for comparison between groups, and as absolute values for comparison between time points, respectively. RESULTS: No significant difference was found between the groups for the percentage change of any parameter at any time point except for FIBTEM® clotting time. Within each group, no significant difference was found between time points for any parameter except for FIBTEM® clotting time in the HTS group, and EXTEM® and FIBTEM® maximum clot firmness in the mannitol group. Median ROTEM® values lay within institutional reference intervals in both groups at all time points, whereas median PFA® values were above the reference intervals at T5 (both groups) and T60 (HTS group). CONCLUSIONS: Using currently recommended doses, mannitol and HTS do not differ in their effects on whole blood coagulation and platelet function in dogs with suspected ICH. Moreover, no relevant impairment of whole blood coagulation was found following treatment with either solution, whereas a short-lived impairment of platelet function was found after both solutions.

The effect of hypertonic saline and mannitol on coagulation in moderate traumatic brain injury patients.

BACKGROUND: Hyperosmolar therapy, using either hypertonic saline (HTS) or mannitol (MT), is considered the treatment of choice for intracranial hypertension, a disorder characterized by high intracranial pressure (ICP). However, hyperosmolar agents have been postulated to impair coagulation and platelet function. The aim of this study was to identify whether HTS and MT could affect coagulation in moderate traumatic brain injury (TBI) patients. METHODS: In this prospective and randomized double-blind study, we included adult patients with moderate TBI. Patients were divided into two groups according to the type of hypertonic solution administered. Group A patients received 20% MT and group B patients received 3% HTS. Rotational thromboelastometry (ROTEM) parameters were used to assess coagulation and platelet function. RESULTS: ROTEM parameters included CT (clotting time), CFT (clot formation time), maximum clot firmness (MCF) measured by MCF (EXTEM and INTEM), MCF (FIBTEM) and standard coagulation tests (p>0.05). No significant differences were found between the two groups. Moreover, ROTEM parameters did not show significant changes at different time points after administration of the hyperosmolar solutions (p>0.05). Conclusions Overall, use of 3% HTS and 20% MT for the control of ICP did not significantly affect patients' coagulation function. Therefore, hyperosmotic solution is safe and does not increase the risk of intracranial rebleeding.

Cerebral haemodynamics during experimental intracranial hypertension.

Intracranial hypertension is a common final pathway in many acute neurological conditions. However, the cerebral haemodynamic response to acute intracranial hypertension is poorly understood. We assessed cerebral haemodynamics (arterial blood pressure, intracranial pressure, laser Doppler flowmetry, basilar artery Doppler flow velocity, and vascular wall tension) in 27 basilar artery-dependent rabbits during experimental (artificial CSF infusion) intracranial hypertension. From baseline (∼9 mmHg; SE 1.5) to moderate intracranial pressure (∼41 mmHg; SE 2.2), mean flow velocity remained unchanged (47 to 45 cm/s; p = 0.38), arterial blood pressure increased (88.8 to 94.2 mmHg; p < 0.01), whereas laser Doppler flowmetry and wall tension decreased (laser Doppler flowmetry 100 to 39.1% p < 0.001; wall tension 19.3 to 9.8 mmHg, p < 0.001). From moderate to high intracranial pressure (∼75 mmHg; SE 3.7), both mean flow velocity and laser Doppler flowmetry decreased (45 to 31.3 cm/s p < 0.001, laser Doppler flowmetry 39.1 to 13.3%, p < 0.001), arterial blood pressure increased still further (94.2 to 114.5 mmHg; p < 0.001), while wall tension was unchanged (9.7 to 9.6 mmHg; p = 0.35).This animal model of acute intracranial hypertension demonstrated two intracranial pressure-dependent cerebroprotective mechanisms: with moderate increases in intracranial pressure, wall tension decreased, and arterial blood pressure increased, while with severe increases in intracranial pressure, an arterial blood pressure increase predominated. Clinical monitoring of such phenomena could help individualise the management of neurocritical patients.

Oxidative stress response to acute hypobaric hypoxia and its association with indirect measurement of increased intracranial pressure: a field study.

High altitude is the most intriguing natural laboratory to study human physiological response to hypoxic conditions. In this study, we investigated changes in reactive oxygen species (ROS) and oxidative stress biomarkers during exposure to hypobaric hypoxia in 16 lowlanders. Moreover, we looked at the potential relationship between ROS related cellular damage and optic nerve sheath diameter (ONSD) as an indirect measurement of intracranial pressure. Baseline measurement of clinical signs and symptoms, biological samples and ultrasonography were assessed at 262 m and after passive ascent to 3830 m (9, 24 and 72 h). After 24 h the imbalance between ROS production (+141%) and scavenging (-41%) reflected an increase in oxidative stress related damage of 50-85%. ONSD concurrently increased, but regression analysis did not infer a causal relationship between oxidative stress biomarkers and changes in ONSD. These results provide new insight regarding ROS homeostasis and potential pathophysiological mechanisms of acute exposure to hypobaric hypoxia, plus other disease states associated with oxidative-stress damage as a result of tissue hypoxia.

Monro-Kellie 2.0: The dynamic vascular and venous pathophysiological components of intracranial pressure.

For 200 years, the 'closed box' analogy of intracranial pressure (ICP) has underpinned neurosurgery and neuro-critical care. Cushing conceptualised the Monro-Kellie doctrine stating that a change in blood, brain or CSF volume resulted in reciprocal changes in one or both of the other two. When not possible, attempts to increase a volume further increase ICP. On this doctrine's "truth or relative untruth" depends many of the critical procedures in the surgery of the central nervous system. However, each volume component may not deserve the equal weighting this static concept implies. The slow production of CSF (0.35 ml/min) is dwarfed by the dynamic blood in and outflow (∼700 ml/min). Neuro-critical care practice focusing on arterial and ICP regulation has been questioned. Failure of venous efferent flow to precisely match arterial afferent flow will yield immediate and dramatic changes in intracranial blood volume and pressure. Interpreting ICP without interrogating its core drivers may be misleading. Multiple clinical conditions and the cerebral effects of altitude and microgravity relate to imbalances in this dynamic rather than ICP per se. This article reviews the Monro-Kellie doctrine, categorises venous outflow limitation conditions, relates physiological mechanisms to clinical conditions and suggests specific management options.

Efficacy and Safety of Continuous Micro-Pump Infusion of 3% Hypertonic Saline combined with Furosemide to Control Elevated Intracranial Pressure.

BACKGROUND: Elevated intracranial pressure is one of the most common problems in patients with diverse intracranial disorders, leading to increased morbidity and mortality. Effective management for increased intracranial pressure is based mainly on surgical and medical techniques with hyperosmolar therapy as one of the core medical treatments. The study aimed to explore the effects of continuous micro-pump infusions of 3% hypertonic saline combined with furosemide on intracranial pressure control. MATERIAL AND METHODS: We analyzed data on 56 eligible participants with intracranial pressure >20 mmHg from March 2013 to July 2014. The target was to increase and maintain plasma sodium to a level between 145 and 155 mmol/L and osmolarity to a level of 310 to 320 mOsmol/kg. RESULTS: Plasma sodium levels significantly increased from 138±5 mmol/L at admission to 151±3 mmol/L at 24 h (P<0.01). Osmolarity increased from 282±11 mOsmol/kg at baseline to 311±8 mOsmol/kg at 24 h (P<0.01). Intracranial pressure significantly decreased from 32±7 mmHg to 15±6 mmHg at 24 h (P<0.01). There was a significant improvement in CPP (P<0.01). Moreover, central venous pressure, mean arterial pressure, and Glasgow Coma Scale slightly increased. However, these changes were not statistically significant. CONCLUSIONS: Continuous infusion of 3% hypertonic saline + furosemide is effective and safe for intracranial pressure control.

Hypertonic saline in paediatric traumatic brain injury: a review of nine years' experience with 23.4% hypertonic saline as standard hyperosmolar therapy.

We describe the protocolised use of 23.4% hypertonic saline solution (HTS) for intracranial hypertension in the context of traumatic brain injury in the paediatric population. This study represents the largest published data on the use of 23.4% HTS in the paediatric population. In this retrospective cohort, we focus on the efficacy, biochemical and metabolic consequences of 23.4% HTS administration in a Level 1 paediatric trauma centre. Mortality in the first seven days was 6% (2/32) with a mean intensive care unit length-of-stay of ten days (range 2 to 25, standard deviation [SD] 6). All-cause hospital mortality was 6%, with no deaths after the seven-day study period. Mean intracranial pressure (ICP) response to HTS was 10 mmHg (range 1 to 30, SD 8). For biochemistry data, the mean highest daily serum sodium was 148 mmol/l (139 to 161, SD 6), mean highest serum chloride was 115 mmol/l (range 101 to 132, SD 8) with matched mean serum base excess of -1.5 mmol/l (range 2 to -8, SD 3) and mean peak serum creatinine was 73 mmol/l (range 32 to 104, SD 32). Glasgow outcome scores of >3 (independent function) were achieved in 74% of patients. We describe the use of 23.4% HTS, demonstrating it to be a practical and efficacious method of delivering osmoles and may be advantageous in minimising total fluid volume. Thus, the bolus versus infusion debate may best be served via combining both approaches.

Oligoclonal bands and increased cytokine levels in idiopathic intracranial hypertension.

OBJECTIVES: The pathogenesis of idiopathic intracranial hypertension (IIH) is currently unknown and there are speculations about the contribution of some immunologic factors. The aim of this study is to investigate the presence of oligoclonal bands (OCBs) and cerebrospinal fluid (CSF) and/or serum cytokine levels in patients with IIH. METHODS: Patients fulfilling revised diagnostic criteria for IIH were included. Their demographic, clinical, ophthalmologic and laboratory features were examined. Serum and CSF samples were detected by isoelectric focusing and immunoblotting for OCBs. The samples of IIH patients and control groups were investigated by ELISA for cytokine levels. RESULTS: We detected OCBs in eight (30.77%) patients diagnosed with IIH. There were no other obvious clinical and laboratory differences of IIH profiles between the patients with and without OCBs, but frequency of vision loss was significantly higher in the group with OCBs in comparison to OCB negatives (p = 0.038). Patients with IIH had highly elevated TNF-α, IFN-γ, IL-4, IL-10, IL-12, IL-17 in their sera compared to patients with multiple sclerosis (MS) and healthy controls. Furthermore, all cytokines except TNF-α in the CSF were found significantly higher in IIH patients compared to MS controls. CONCLUSION: The presence of OCBs and elevated cytokine levels in IIH patients may support an immunologic background in the pathophysiological pathway of this disorder.

Uptake of the antisecretory factor peptide AF-16 in rat blood and cerebrospinal fluid and effects on elevated intracranial pressure.

BACKGROUND: AF-16 is a 16-amino-acid-long peptide derived from the amino-terminal part of the endogenous protein, antisecretory factor (AF). AF-16 in vivo has been shown to regulate dysfunctions in the water and ion transport system under various pathological conditions and also to counteract experimentally increased tissue pressure. METHODS: Rats were subjected to a cryogenic brain injury in order to increase the intracranial pressure (ICP). The distribution of AF-16 in blood and CSF after intravenous or intranasal administration was determined in injured and control rats. ICP was monitored in freely moving, awake rats, by means of an epidural pressure transducer catheter connected to a wireless device placed subcutaneously on the skull. The continuous ICP registrations were achieved by means of telemetry. RESULTS: Intranasal administration of AF-16 resulted in a significantly higher CSF concentrations of AF-16 in injured than in control rats, 1.3 versus 0.6 ng/ml, whereas no difference between injured and control rats was seen when AF-16 was given intravenously. Rats subjected to cryogenic brain injury developed gradually increasing ICP levels. Intranasal administration of AF-16 suppressed the increased ICP to normal values within 30 min. CONCLUSION: Optimal AF-16 concentrations in CSF are achieved after intranasal administration in rats subjected to a cryogenic brain injury. The ability of AF-16 to suppress an increased ICP was manifested.

[Efficiency of high-volume hemofiltration in patients with severe sepsis and intracranial hypertension].

We performed a retrospective study in 68 patients (144 procedures) with severe sepsis and intracranial hypertension measured by the pressure in the central retinal vein. The patients underwent high-volume hemofiltration (HV-HF) for extrarenal indications. Increased pressure in the central retinal vein was accompanied by critical points of cerebral perfusion pressure and the growth of neurological deficit with inhibition level of consciousness to coma 1. In this case, IHV-HF may be associated with the formation of the critical points of cerebral perfihsion and severe disorders of microcirculation and the lack of resolution of tissue hypoperfusion. In case of intracranial hypertension IHV-HF is not effective in the category of patients where there is a combination ΔpCO2 > 5.9 mm Hg level and GCS <10 points.

Posttraumatic refractory intracranial hypertension and brain herniation syndrome: cerebral hemodynamic assessment before decompressive craniectomy.

BACKGROUND: The pathophysiology of traumatic brain swelling remains little understood. An improved understanding of intracranial circulatory process related to brain herniation may have treatment implications. OBJECTIVE: To investigate the cerebral hemodynamic changes associated with brain herniation syndrome due to traumatic brain swelling. METHODS: Nineteen head-injured patients with evidence of refractory intracranial hypertension and transtentorial herniation were prospectively studied. Cerebral hemodynamic assessment by transcranial Doppler (TCD) ultrasonography was performed prior to decompressive craniectomy. Patients and their cerebral hemispheres were classified according to TCD-hemodynamic patterns, and the data correlated with neurological status, midline shift on CT scan, and Glasgow outcome scale scores at 6 months after injury. RESULTS: A wide variety of cerebral hemodynamic findings were observed. Ten patients (52.7%) presented with cerebral oligoemia, 3 patients (15.8%) with cerebral hyperemia, and 6 patients with nonspecific circulatory pattern. Circulatory disturbances were more frequently found in the side of maximal cerebral swelling than in the opposite side. Pulsatility index (PI) values suggested that ICP varied from acceptable to considerably high; patients with increased PI, indicating higher microvascular resistance. No correlation was found between cerebral hemodynamic findings and outcome. CONCLUSIONS: There is a marked heterogeneity of cerebral hemodynamic disturbances among patients with brain herniation syndrome.