Risk factors for decompressive craniectomy after endovascular treatment in acute ischemic stroke.

Endovascular treatment (EVT) is safe and effective for acute ischemic stroke (AIS) caused by large artery occlusion in the anterior circulation. However, some patients require decompressive craniectomy (DC), despite having undergone a timely EVT. This study aimed to evaluate the risk factors for subsequent DC after EVT. This retrospective cohort study comprised 138 patients who received EVT between April 2015 and June 2019 at our center. The need for subsequent DC was defined as cerebral edema or/and hemorrhagic transformation caused by large ischemic infarction, with a ≥ 5-mm midline shift and clinical deterioration after EVT. The relationship between risk factors and DC after EVT was assessed via univariate and multivariable logistic regression. Thirty (21.7%) patients required DC. These patients tended to have atrial fibrillation (P = 0.037), sedation (P = 0.049), mechanical ventilation (P = 0.008), poorer collateral circulation (P = 0.003), a higher baseline National Institutes of Health Stroke Scale (NIHSS) score (P < 0.001), heavier thrombus burden (P < 0.001), a lower baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) (P < 0.001), and unsuccessful recanalization (P < 0.001). In the multivariate analysis, higher baseline NIHSS score [odds ratio (OR), 1.17; 95% confidence interval (CI), 1.03-1.32], heavier thrombus burden [OR, 1.35; 95% CI, 1.02-1.79], baseline ASPECTS ≤ 8 [OR, 7.41; 95% CI, 2.43-22.66], and unsuccessful recanalization [OR, 7.49; 95% CI, 2.13-26.36] were independent risk factors for DC after EVT. DC remains an essential treatment for some AIS patients after EVT, especially those with higher baseline NIHSS scores, heavier thrombus burden, baseline ASPECTS ≤ 8, and unsuccessful recanalization.

Neutrophil to Lymphocyte Ratio as a Novel Predictor of Outcome in Patients With Severe Traumatic Brain Injury.

OBJECTIVE: The neutrophil to lymphocyte ratio (NLR) has been reported to be a predictor of outcome in critical illness. Objective of this study was to investigate the changes of the NLR in patients with severe traumatic brain injury (TBI) and analyze the relationship between the NLR and TBI outcome. SETTING: China. PARTICIPANTS: A total of 855 patients with severe TBI from January 2007 to April 2012. DESIGN: Retrospective. MAIN MEASUREMENT: Data on the NLR and other indicators were collected. After follow-up until death or 1 year, the relationship between the NLR and TBI outcome was analyzed retrospectively. RESULTS: The final analysis included 688 patients. There were 508 (73.8%) who had an unfavorable outcome by 1 year after head trauma. The value of the NLR on admission was significantly higher in the unfavorable outcome group than in the favorable outcome group (P < .001). Multivariate logistic analysis showed that higher NLR was associated with an unfavorable outcome (odds ratio, 1.100; P < .001). Receiver operating characteristic curve analysis showed that the NLR had a sensitivity of 60.2% and a specificity of 71.1% for predicting unfavorable outcome at 1 year on the basis of the best threshold. CONCLUSION: The NLR might be useful as a novel predictor for 1-year outcome and mortality in severe TBI.

Cytokine cascades induced by mechanical trauma injury alter voltage-gated sodium channel activity in intact cortical neurons.

BACKGROUND: Traumatic brain injury (TBI) triggers both immediate (primary) and long-term (secondary) tissue damages. Secondary damages can last from hours to days or even a lifetime. Secondary damages implicate several mechanisms, including influence of inflammatory mediators, mainly cytokines, on excitability of ion channels. However, studies should further explore the effects of inflammatory cytokines on voltage-gated sodium channels (VGSCs) and excitability in distal intact neurons. METHODS: Mixed cultures of mouse cortical astrocytes and neurons were subjected to mechanical injury (trauma) to mimic TBI in vitro. Expression of various cytokines in these cultures were measured by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. A trauma-conditioned medium with or without brain-derived neurotrophic factor (BDNF) was added to mouse primary cortical neurons for 6 and 24 h to mimic combined effects of multiple inflammatory cytokines on VGSCs. Spike behaviors of distal intact neurons were examined by whole-cell patch-clamp recordings. RESULTS: Mechanical injury in mixed cortical neuron-astrocyte cultures significantly increased expression levels of multiple cytokines, including interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, chemokine (C-C motif) ligand-5, IL-10, and transforming growth factor-ß1, at 6 and 24 h after injury. Incubation in trauma-conditioned medium increased functional VGSCs in neuronal membranes and Na+ currents. Enhanced VGSCs were almost completely abolished by BDNF, and reinforcement of Na+ currents was also reduced in a dose-dependent manner. BDNF (30 ng/mL) also significantly reversed reduced neuronal cell viability, which was induced by medium conditioned at 6 h. At 6 and 24 h, trauma-conditioned medium significantly increased spike frequency but not spike threshold. CONCLUSIONS: In TBI, the combined effect of inflammatory cytokines is directly involved in VGSC, Na+ current, and excitability dysfunction in distal intact neurons. BDNF may partly exert neuroprotective effects by maintaining balance of VGSC function in distal intact neurons.

Neutrophil to lymphocyte ratio predicts early growth of traumatic intracerebral haemorrhage.

OBJECTIVE: The neutrophil to lymphocyte ratio (NLR) has been proposed to capture the inflammatory status of patients with various conditions involving the brain. This retrospective study aimed to explore the association between the NLR and the early growth of traumatic intracerebral haemorrhage (tICH) in patients with traumatic brain injury (TBI). METHODS: A multicentre, observational cohort study was conducted. Patients with cerebral contusion undergoing baseline computed tomography for haematoma volume analysis within 6 h after primary injury and follow-up visits within 48 h were included. Routine blood tests were performed upon admission, and early growth of tICH was assessed. Prediction accuracies of the NLR for the early growth of tICH and subsequent surgical intervention in patients were analysed. RESULTS: There were a total of 1077 patients who met the criteria included in the study cohort. Univariate analysis results showed that multiple risk factors were associated with the early growth of tICH and included in the following multivariate analysis models. The multivariate logistic regression analysis results revealed that the NLR was highly associated with the early growth of tICH (p < 0.001) while considering other risk factors in the same model. The prediction accuracy of the NLR for the early growth of tICH in patients is 82%. INTERPRETATION: The NLR is easily calculated and might predict the early growth of tICH for patients suffering from TBI.

TGF-ß1 Regulation of P-JNK and L-Type Calcium Channel Cav1.2 in Cortical Neurons.

Central nervous system (CNS) diseases can cause a series of neuronal lesions, which may be improved by the anti-apoptotic neuroprotection of transforming growth factor-beta 1 (TGF-ß1). In neurons, L-type Ca2+ channels (LTCC) are mainly composed of Cav1.2 subunits. Given the implication of TGF-ß1 in numerous CNS diseases, we examined the neuroprotective effects of TGF-ß1 on the Cav1.2 channel in the CNS. To simulate acute mechanical traumatic brain injury (TBI), we used a needle to create parallel scratches across plates, which were cultured for 9 h. Meanwhile, Fluo4-AM-loaded laser scanning confocal microscopy with a dual wavelength of 488 nm/530 nm was employed to determine intracellular calcium concentrations ([Ca2+]i). We found that MAPK inhibitors impede TGF-ß1-induced cell viability and that TGF-ß1 recovered from the trauma-induced cell viability in neurons. Cav1.2 production was significantly decreased in the TGF-ß1-treated (10 ng/mL) neurons. At this TGF-ß1 concentration, Cav1.2 was significantly down-regulated in a time-dependent manner after 12 h. Moreover, TGF-ß1 partially recovered the protein levels of Cav1.2 that were reduced by TBI. TGF-ß1 significantly inhibited the fluorescence intensity of [Ca2+]i increased by KCl and delayed the time of the peak [Ca2+]i. The observed effects of TGF-ß1 on Cav1.2 were regulated by MAPK inhibitors. The observed effects of TGF-ß1 on P-JNK were also impeded by pre-incubation with the LTCC inhibitor (10 µM) nimodipine in trauma-injured neurons. Altogether, TGF-ß1 regulated LTCCs through a mechanism dependent on MEK, JNK1/2 and p38 MAPK signal pathways in cortical neurons. Thus, we suggest the involvement of this mechanism in cell viability.

Early stage alterations of catecholamine and adrenocorticotropic hormone levels in posttraumatic acute diffuse brain swelling.

Posttraumatic acute diffuse brain swelling (PADBS) is characterized by serious brain bulk enlargement rapidly following trauma and is a major cause of elevated intracranial pressure and thus mortality. The pathogenesis of PADBS is not clearly understood, and the early stage alterations of catecholamine (CA) and adrenocorticotropic hormone (ACTH) levels in PADBS also remain largely unknown. The objective of this study was to investigate CA and ACTH levels in the patients with PADBS in the early stage and discuss the possible roles CA and ACTH in the pathogenesis of PADBS. It is a cross-sectional study. A group of patients with PADBS (n=10) was compared with a group of patients with severe brain injury (SBI) (n=33). A control group of healthy adults (n=25) was also included. Blood samples were obtained to measure levels of epinephrine (EPI), norepinephrine (NE), dopamine (DA), and ACTH as soon as the patients arrived at the neurosurgery department, which was done within 4h after trauma. Both SBI and PADBS groups of patients had higher levels of EPI, NE, DA, and ACTH than the control group. The PADBS group had significantly higher levels of EPI, NE, and ACTH than the SBI group. CA and ACTH levels are significantly increased in early stage PADBS. These results imply that CA and ACTH may play important roles in the pathogenesis of PADBS. To eliminate the effects of CA and ACTH at the early stage, and thereby protect the hypothalamus and brain stem, might be critical measures for treating patients with PADBS.

Paradoxical Herniation After Unilateral Decompressive Craniectomy Predicts Better Patient Survival: A Retrospective Analysis of 429 Cases.

Paradoxical herniation (PH) is a life-threatening emergency after decompressive craniectomy. In the current study, we examined patient survival in patients who developed PH after decompressive craniectomy versus those who did not. Risk factors for, and management of, PH were also analyzed. This retrospective analysis included 429 consecutive patients receiving decompressive craniectomy during a period from January 2007 to December 2012. Mortality rate and Glasgow Outcome Scale (GOS) were compared between those who developed PH (n = 13) versus those who did not (n = 416). A stepwise multivariate logistic regression analysis was carried out to examine the risk factors for PH. The overall mortality in the entire sample was 22.8%, with a median follow-up of 6 months. Oddly enough, all 13 patients who developed PH survived beyond 6 months. Glasgow Coma Scale did not differ between the 2 groups upon admission, but GOS was significantly higher in subjects who developed PH. Both the disease type and coma degree were comparable between the 13 PH patients and the remaining 416 patients. In all PH episodes, patients responded to emergency treatments that included intravenous hydration, cerebral spinal fluid drainage discontinuation, and Trendelenburg position. A regression analysis indicated the following independent risk factors for PH: external ventriculostomy, lumbar puncture, and continuous external lumbar drainage. The rate of PH is approximately 3% after decompressive craniectomy. The most intriguing findings of the current study were the 0% mortality in those who developed PH versus 23.6% mortality in those who did not develop PH and significant difference of GOS score at 6-month follow-up between the 2 groups, suggesting that PH after decompressive craniectomy should be managed aggressively. The risk factors for PH include external ventriculostomy, ventriculoperitoneal shunt, lumbar puncture, and continuous external lumbar drainage.

Neuroprotective effect of interleukin-6 regulation of voltage-gated Na(+) channels of cortical neurons is time- and dose-dependent.

Interleukin-6 has been shown to be involved in nerve injury and nerve regeneration, but the effects of long-term administration of high concentrations of interleukin-6 on neurons in the central nervous system is poorly understood. This study investigated the effects of 24 hour exposure of interleukin-6 on cortical neurons at various concentrations (0.1, 1, 5 and 10 ng/mL) and the effects of 10 ng/mL interleukin-6 exposure to cortical neurons for various durations (2, 4, 8, 24 and 48 hours) by studying voltage-gated Na(+) channels using a patch-clamp technique. Voltage-clamp recording results demonstrated that interleukin-6 suppressed Na(+) currents through its receptor in a time- and dose-dependent manner, but did not alter voltage-dependent activation and inactivation. Current-clamp recording results were consistent with voltage-clamp recording results. Interleukin-6 reduced the action potential amplitude of cortical neurons, but did not change the action potential threshold. The regulation of voltage-gated Na(+) channels in rat cortical neurons by interleukin-6 is time- and dose-dependent.