Thomas Geeraerts

Optic nerve sheath diameter used as ultrasonographic assessment of the incidence of raised intracranial pressure in preeclampsia: a pilot study.

Background: In some cases of severe preeclampsia/eclampsia, brain imaging displays signs compatible with raised intracranial pressure. We aimed to estimate the incidence of raised intracranial pressure in preeclampsia using ocular ultrasonography. Methods: Optic nerve sheath diameter (ONSD) measurements were compared in 26 preeclamptic and 25 healthy pregnant women. For each optic nerve, two measurements were made (transverse plane and sagittal plane) using a 7.5 MHz ultrasound linear probe. Preeclamptic patients were followed-up until postpartum day 7. Results: Median ONSD values were significantly greater in preeclamptic patients compared with healthy pregnant women at delivery (5.4 mm (95% CI: 5.2, 5.7) vs. 4.5 mm (95% CI: 4.3, 4.8), P < 0.0001). At delivery, 5/26 (19%) of preeclamptic patients had ONSD values above 5.8 mm (value associated in the literature with 95% risk of raised intracranial pressure) whereas none of the healthy pregnant group had such high ONSD values. In the preeclamptic group, ONSD decreased after the third postpartum day. ONSD values at day 7 were not significantly different from those obtained in the normal pregnancy group (P = 0.10). Conclusion: In about 20% of preeclamptic patients, ONSD reaches values compatible with intracranial pressure above 20 mmHg. Further work is needed to confirm this incidence and to better understand the diagnostic and therapeutic usefulness of this easy-to-do monitoring technique.

Fractalkine reduces N-methyl-d-aspartate-induced calcium flux and apoptosis in human neurons through extracellular signal-regulated kinase activation

Our purpose was to investigate in human neurons the neuroprotective pathways induced by Fractalkine (FKN) against glutamate receptor‐induced excitotoxicity. CX3CR1 and FKN are expressed constitutively in the tested human embryonic primary neurons and SK‐N‐SH, a human neuroblastoma cell line. Microfluorometry assay demonstrated that CX3CR1 was functional in 44% of primary neurons and in 70% of SK‐N‐SH. Fractalkine induced ERK1/2 phosphorylation within 1 min and Akt phosphorylation after 10 min, and both phosphorylation decreased after 20 min. No p38 and SAPK/JNK activation was observed after FKN treatment. Application of FKN triggered a 53% reduction of the NMDA‐induced neuronal calcium influx, which was insensitive to pertussis toxin and LY294002 an inhibitor of Akt pathway, but abolished by PD98059, an ERK1/2 pathway inhibitor. Moreover, FKN significantly reduced neuronal NMDA‐induced apoptosis, which was pertussis toxin insensitive and abolished in presence of PD98059 and LY294002. In conclusion, FKN protected human neurons from NMDA‐mediated excitotoxicity in at least two ways with different kinetics: (i) an early ERK1/2 activation which reduced NMDA‐mediated calcium flux; and (ii), a late Akt activation associated with the previously induced ERK1/2 activation.

Cerebral hemodynamic changes in severe head injury patients undergoing decompressive craniectomy.

Objective: To assess the intracranial hemodynamic modifications induced by a decompressive craniectomy (DC) after severe traumatic brain injury (TBI), using transcranial Doppler (TCD) ultrasonography and intracranial pressure (ICP) sensor. Mortality rate and neurological outcomes were also evaluated after this procedure. Design: A prospective study was carried out on 26 TBI patients, measuring transcranial Doppler and ICP before, immediately after, and 48 hours after the DC, allowing for statistical analysis of hemodynamic changes. The mortality rate and the neurological outcomes were assessed. Measurements and Results: After DC, ICP decreased from 37±17 to 20±13 mm Hg (P=0.0003). The global cerebral blood flow was modified with diastolic velocities rising from 23±15 to 31±13 cm/s (P=0.0038) and a pulsatility index decreasing from 1.70±0.66 to 1.18±0.37 (P=0.0012). This normalization of the global cerebral hemodynamics after the DC was immediate, symmetric, and constant during the first 48 hours. Outcome was evaluated at 6 months: good recovery or moderate disability was observed in 11 patients (42%), persistent vegetative state in 7 patients (27%), and 8 patients died (31%). Conclusions: The DC results in a significant, immediate, and durable improvement of ICP associated with a normalization of cerebral blood flow velocities in most TBI patients with refractory intracranial hypertension.

Optimal perioperative management of arterial blood pressure

Perioperative blood pressure management is a key factor of patient care for anesthetists, as perioperative hemodynamic instability is associated with cardiovascular complications. Hypertension is an independent predictive factor of cardiac adverse events in noncardiac surgery. Intraoperative hypotension is one of the most encountered factors associated with death related to anesthesia. In the preoperative setting, the majority of antihypertensive medications should be continued until surgery. Only renin-angiotensin system antagonists may be stopped. Hypertension, especially in the case of mild to moderate hypertension, is not a cause for delaying surgery. During the intraoperative period, anesthesia leads to hypotension. Hypotension episodes should be promptly treated by intravenous vasopressors, and according to their etiology. In the postoperative setting, hypertension predominates. Continuation of antihypertensive medications and postoperative care may be insufficient. In these cases, intravenous antihypertensive treatments are used to control blood pressure elevation.

Disruption of posteromedial large-scale neural communication predicts recovery from coma

Objective: We hypothesize that the major consciousness deficit observed in coma is due to the breakdown of long-range neuronal communication supported by precuneus and posterior cingulate cortex (PCC), and that prognosis depends on a specific connectivity pattern in these networks. Methods: We compared 27 prospectively recruited comatose patients who had severe brain injury (Glasgow Coma Scale score <8; 14 traumatic and 13 anoxic cases) with 14 age-matched healthy participants. Standardized clinical assessment and fMRI were performed on average 4 ± 2 days after withdrawal of sedation. Analysis of resting-state fMRI connectivity involved a hypothesis-driven, region of interest–based strategy. We assessed patient outcome after 3 months using the Coma Recovery Scale–Revised (CRS-R). Results: Patients who were comatose showed a significant disruption of functional connectivity of brain areas spontaneously synchronized with PCC, globally notwithstanding etiology. The functional connectivity strength between PCC and medial prefrontal cortex (mPFC) was significantly different between comatose patients who went on to recover and those who eventually scored an unfavorable outcome 3 months after brain injury (Kruskal-Wallis test, p < 0.001; linear regression between CRS-R and PCC-mPFC activity coupling at rest, Spearman ρ = 0.93, p < 0.003). Conclusion: In both etiology groups (traumatic and anoxic), changes in the connectivity of PCC-centered, spontaneously synchronized, large-scale networks account for the loss of external and internal self-centered awareness observed during coma. Sparing of functional connectivity between PCC and mPFC may predict patient outcome, and further studies are needed to substantiate this potential prognosis biomarker.

Increase in optic nerve sheath diameter induced by epidural blood patch: a preliminary report

BACKGROUND Post-dural puncture headache (PDPH) might be related to cerebrospinal fluid hypotension. Studies in brain-injured patients have shown a good relationship between optic nerve sheath diameter (ONSD) measured by ocular sonography and invasively measured intracranial pressure (ICP). The aim of this study was to evaluate changes in ONSD after lumbar epidural blood patch (EBP). METHODS Consecutive subjects receiving an EBP for PDPH were included. ONSD and pain measurements were performed before (T(0)), 10 min (M(10)), 2 h (H(2)), and 20 h (H(20)) after the EBP. RESULTS Ten subjects were included. ONSD [median (inter-quartile range)] increased with time after EBP, from 4.8 mm (4.5-5.1) at T(0) to 5.2 mm (4.9-5.7) at M(10) (P=0.005 vs T(0)), 5.5 mm (5.1-6.0) at H(2) (P=0.007 vs T(0)), and 5.8 mm (5.2-6.3) at H(20) (P=0.02 vs T(0)). EBP was clinically successful in nine of 10 subjects. In subjects in whom EBP was successful, ONSD significantly increased at M(10) and T(2) compared with T(0) (P=0.004 and 0.008, respectively) but did not reach statistical significance at H(20) (P=0.06). In the subject in whom EBP failed, a small increase in ONSD was observed over time. CONCLUSIONS In this preliminary report, EBP was followed by ONSD enlargement in subjects with successful EBP, but not in the subject with EBP failure. Since ONSD is a surrogate marker of ICP, this suggests that a sustained increase in ICP is associated with successful EBP.

Effects of SDF-1α and gp120IIIB on apoptotic pathways in SK-N-SH neuroblastoma cells

CXCR4, a chemokine receptor constitutively expressed in the brain, binds both ligands, the chemokine SDF-1alpha and the HIV envelope glycoprotein gp120(IIIB). There seem to be intracellular differences between the neuronal apoptosis induced by SDF-1alpha and that induced by gp120(IIIB), but the apoptotic pathways involved have not been compared in human neuronal cells. In this study, we characterized the apoptotic intracellular pathways activated by neurotoxic concentrations of SDF-1alpha and gp120(IIIB) in human neuroblastoma cells SK-N-SH. SDF-1alpha (10 nM) and gp120(IIIB) (2 nM) induced similar levels of apoptosis after 24 h of incubation (49 +/- 4% and 48 +/- 3%, respectively, of the neurons were apoptotic). SDF1alpha-induced apoptosis was completely abolished by the inhibition of Src phosphorylation by PP2. Exposure to SDF-1alpha (10 nM) triggered an increase in Src phosphorylation, with a maximum after 20 min of incubation (1.80 +/- 0.24 times higher than control, P = 0.01). NMDA calcium flux was enhanced only if cells were incubated with SDF-1alpha for 20 min before applying NMDA. By contrast, gp120(IIIB)-induced apoptosis was not affected by the inhibition of Src phosphorylation. Moreover, gp120(IIIB) enhanced NMDA calcium flux immediately, without modifying Src phosphorylation status. Finally, levels of phospho-JNK increased following exposure to gp120(IIIB) (by a factor of 1.46 +/- 0.4 at 120 min, P = 0.03), but not after exposure to SDF-1alpha. Thus, SDF-1alpha and gp120(IIIB) induced a similar level of neuronal apoptosis, but by activating different intracellular pathways. SDF-1alpha enhanced NMDA activity indirectly via Src phosphorylation, whereas gp120(IIIB) probably activated the NMDA receptor directly and phosphorylated JNK.

The Frontal Lobe and Thalamus Have Different Sensitivities to Hypoxia-Hypotension after Traumatic Brain Injury: A Microdialysis Study in Rats

After traumatic brain injury (TBI), lesions are anatomically heterogeneous, but the spatial heterogeneity of the post-traumatic brains vulnerability to hypoxia-hypotension (HH) has been poorly studied. Our objective was to compare the effect of HH after TBI on brain energy metabolism into two regions: the frontal lobe and the thalamus. Twenty-eight Sprague-Dawley rats were randomized into four groups: sham, TBI (brain trauma alone, impact acceleration, 450-g weight drop from 1.8 m), HH (blood depletion to mean arterial pressure 40 mm Hg, FiO(2) 10%, 15 min), and TBI-HH (TBI followed by HH, 45-min delay). Cerebral perfusion pressure (CPP) was continuously measured. Brain microdialysis and brain tissue oxygen partial pressure (PtiO(2)) probes were both inserted stereotaxically into the right thalamus and frontal lobe. Except during the HH period, CPP was always above 60 mm Hg. During the hour following the HH period, significant increases in cerebral lactate-pyruvate ratio, glycerol, and glutamate were observed, and were always higher in the frontal lobe than in the thalamus (p<0.001). In the TBI-HH group and in the frontal lobe, increases in glutamate and glycerol were significantly higher than in the HH group (p<0.001). During the 30 min following the HH phase (reperfusion), an increase in PtiO(2) was observed. In the TBI-HH group, this increase was significantly lower in the frontal lobe than in the thalamus. These findings demonstrate that in the early post-traumatic period, the metabolic cerebral response to HH is higher in the frontal lobe than in the thalamus, and is worsened by TBI, suggesting a higher vulnerability for the frontal lobes.

Oxygen challenge test in septic shock patients: prognostic value and influence of respiratory status.

ABSTRACT Transcutaneous oxygen pressure (PtcO2) value in response to an increase of FiO2 or oxygen challenge test (OCT) in ventilated patients has been reported to be related to peripheral perfusion and outcome during septic shock. However, patients with sepsis-related acute respiratory distress syndrome could demonstrate compromised arterial oxygenation with OCT impairment decoupled to circulatory failure. The aims of this study were to confirm the prognostic value of OCT and to explore the influence of respiratory status on OCT results. This was a prospective study set in an intensive care unit of a tertiary teaching hospital. Fifty-six mechanically ventilated patients with septic shock criteria were studied. Transcutaneous oxygen pressure was measured at baseline and after OCT, at intensive care unit admittance (T0), and 24 h later (T24). Survival at day 28 and hemodynamic and respiratory parameters were analyzed and compared according to outcome and respiratory status. Central hemodynamic parameters or static transcutaneous data did not differ between survivors and nonsurvivors at enrollment. The OCT was statistically different at T24 according to outcome (P < 0.001), but sensitivity was low (53%). Moreover, patients with low OCT results at T24 exhibited more severe respiratory failure (P < 0.01). The OCT at T24 is related to outcome but is influenced by the severity of respiratory failure. Our results suggest considering with caution hemodynamic management based on OCT in septic shock patients with altered pulmonary function.

COBI (COntinuous hyperosmolar therapy for traumatic Brain-Injured patients) trial protocol: a multicentre randomised open-label trial with blinded adjudication of primary outcome

Introduction Traumatic brain injury (TBI) is a major cause of death and severe prolonged disability. Intracranial hypertension (ICH) is a critical risk factor of bad outcomes after TBI. Continuous infusion of hyperosmolar therapy has been proposed for the prevention and the treatment of ICH. Whether an early administration of continuous hyperosmolar therapy improves long-term outcomes of patients with TBI is uncertain. The aim of the COBI study (number clinicaltrial.gov 03143751, pre-results stage) is to assess the efficiency and the safety of continuous hyperosmolar therapy in patients with TBI. Methods and analysis The COBI (COntinuous hyperosmolar therapy in traumatic Brain-Injured patients) trial is a multicentre, randomised, controlled, open-label, two-arms study with blinded adjudication of primary outcome. Three hundred and seventy patients hospitalised in intensive care unit with a TBI (Glasgow Coma Scale ≤12 and abnormal brain CT scan) are randomised in the first 24 hours following trauma to standard care or continuous hyperosmolar therapy (20% NaCl) plus standard care. Continuous hyperosmolar therapy is maintained for at least 48 hours in the treatment group and continued for as long as is necessary to prevent ICH. The primary outcome is the score on the Extended Glasgow Outcome Scale at 6 months. The treatment effect is estimated with ordinal logistic regression adjusted for prespecified prognostic factors and expressed as a common OR. Ethics and dissemination The COBI trial protocol has been approved by the ethics committee of Paris Ile de France VIII and will be carried out according to the principles of the Declaration of Helsinki and the Good Clinical Practice guidelines. The results of this study will be disseminated through presentation at scientific conferences and publication in peer-reviewed journals. The COBI trial is the first randomised controlled trial powered to investigate whether continuous hyperosmolar therapy in patients with TBI improve long-term recovery. Trial registration number Trial registration number is NCT03143751.