Clinical Characteristics of and Treatment Strategy for Hydrocephalus in Patients With Severe Disorders of Consciousness.

Abstract Making an appropriate diagnosis and administering effective treatment for hydrocephalus in patients with severe disorders of consciousness (DOC) remains controversial and difficult. Given that the typical symptoms are usually concealed by the limited behavioral responsiveness of patients with severe DOC, hydrocephalus diagnosis is likely to be missed in the clinic. Even if not, the presence of hydrocephalus may reduce the likelihood of DOC recovery, posing a conundrum for clinicians. From December 2013 to January 2023, the clinical data and therapeutic schedule of hydrocephalus in patients with severe DOC at Huashan Hospital's Neurosurgical Emergency Center were studied retrospectively. Sixty-eight patients (mean age [± SD] 52.53 ± 17.03 years, 35 males and 33 females) with severe DOC were included. The hydrocephalus was discovered after computed tomography (CT) or magnetic resonance imaging (MRI) revealed enlarged ventricles in the patients. During hospitalization, patients underwent a surgical treatment that included a ventriculoperitoneal (V-P) shunt and/or cranioplasty (CP) implantation. Following the surgery, an individualized V-P pressure was established based on the patient's ventricle size and neurological function variation. To account for the improvement in consciousness in patients with severe DOC, Glasgow Coma Scale (GCS) and Coma Recovery Scale-Revised (CRS-R) assessments were performed before and after hydrocephalus treatment. All patients with severe DOC had varying degrees of ventricular enlargement, deformation, and poor brain compliance. Approximately 60.3% (41/68) of them had low- or negative-pressure hydrocephalus (LPH or NegPH). Of the patients, 45.5% (31/68) had a one-stage V-P shunt and CP operation performed concurrently, whereas the remaining 37 patients had a single V-P shunt operation performed independently. Besides two patients with DOC who developed surgical complications, 92.4% (61/66) of the survivors showed an improvement in consciousness after hydrocephalus treatment. In patients with severe DOC, LPH or NegPH was common. Secondary hydrocephalus in patients with DOC had been largely ignored, hampering their neurological rehabilitation. Even months or years after the onset of severe DOC, active treatment of hydrocephalus can significantly improve patients' consciousness and neurological function. This study summarized several evidence-based treatment experiences of hydrocephalus in patients with DOC.

Clinical Decision on Disorders of Consciousness After Acquired Brain Injury: Stepping Forward.

Major advances have been made over the past few decades in identifying and managing disorders of consciousness (DOC) in patients with acquired brain injury (ABI), bringing the transformation from a conceptualized definition to a complex clinical scenario worthy of scientific exploration. Given the continuously-evolving framework of precision medicine that integrates valuable behavioral assessment tools, sophisticated neuroimaging, and electrophysiological techniques, a considerably higher diagnostic accuracy rate of DOC may now be reached. During the treatment of patients with DOC, a variety of intervention methods are available, including amantadine and transcranial direct current stimulation, which have both provided class II evidence, zolpidem, which is also of high quality, and non-invasive stimulation, which appears to be more encouraging than pharmacological therapy. However, heterogeneity is profoundly ingrained in study designs, and only rare schemes have been recommended by authoritative institutions. There is still a lack of an effective clinical protocol for managing patients with DOC following ABI. To advance future clinical studies on DOC, we present a comprehensive review of the progress in clinical identification and management as well as some challenges in the pathophysiology of DOC. We propose a preliminary clinical decision protocol, which could serve as an ideal reference tool for many medical institutions.

Neuroinflammation Following Traumatic Brain Injury: Take It Seriously or Not.

Traumatic brain injury (TBI) is associated with high mortality and disability, with a substantial socioeconomic burden. With the standardization of the treatment process, there is increasing interest in the role that the secondary insult of TBI plays in outcome heterogeneity. The secondary insult is neither detrimental nor beneficial in an absolute sense, among which the inflammatory response was a complex cascade of events and can thus be regarded as a double-edged sword. Therefore, clinicians should take the generation and balance of neuroinflammation following TBI seriously. In this review, we summarize the current human and animal model studies of neuroinflammation and provide a better understanding of the inflammatory response in the different stages of TBI. In particular, advances in neuroinflammation using proteomic and transcriptomic techniques have enabled us to identify a functional specific delineation of the immune cell in TBI patients. Based on recent advances in our understanding of immune cell activation, we present the difference between diffuse axonal injury and focal brain injury. In addition, we give a figurative profiling of the general paradigm in the pre- and post-injury inflammatory settings employing a bow-tie framework.

ISO-alpha-acids improve the hematoma resolution and prevent peri-hematoma inflammations by transforming microglia via PPARgamma-CD36 axis in ICH rats.

OBJECTIVE: To elucidate the effects of ISO-α-acids (IAAs), a PPAR-γ agonist, on ICH rats and its potential mechanism. MATERIAL AND METHODS: The Sprague Dawley rats ICH model was induced by stereotactic injecting of 100 µl autologous artery blood. Ninety male rats were randomly allocated to five groups: autologous blood and IAAs (IAA); received autologous blood, IAAs and PPAR-γ inhibitor (IAA + GW9662); autologous blood and normal Saline (Saline); only autologous blood (Mock); and only needle injection (Sham). Neurological functions were assessed by mNSS. Hematoma volume, brain water content, surface proteins and inflammatory factors were detected. The microglia anti-inflammatory abilities were also evaluated. RESULTS: IAAs were able to significantly decrease ICH rat's mNSS scores, alleviate brain water content, improve hematoma resolution than Saline, Mock (p < 0.05). More "M2" microglial/macrophage can be induced by IAAs. The expression of CD 36 was statistically higher in IAA than other groups (p < 0.05). Injection of IAAs led to a greatly increasing in CD 11b and CD 206 double-positive anti-inflammatory type microglial/macrophage, moreover, a reduction of inflammatory cytokines expression (p < 0.05). Such protective effects can be relieved by GW9662. CONCLUSIONS: This is the first study to elucidate the relationship between IAAs and ICH. IAAs were able to accelerate hematoma absorption, alleviate brain edema, suppress peri-hematoma inflammations and finally improved the outcome of ICH rats. The phenotype was due to the IAAs induction of "M2" microglial/macrophage via activating of PPAR-γ and increasing CD 36 expression.

Intensive blood pressure control reduces the risk of progressive hemorrhage in patients with acute hypertensive intracerebral hemorrhage: A retrospective observational study.

OBJECTIVE: To investigate the impact of intensive blood pressure control on progressive intracerebral hemorrhage and outcome in patients with high blood pressure and intracerebral hemorrhage. PATIENTS AND METHODS: A retrospective study was conducted recruiting 659 patients with acute hemorrhagic stroke between Jan. 2012 and May 2018. Patients recruited before May 2015 were treated with a target systolic level of <180 mm Hg, while those recruited after May 2015 received intensive blood pressure control treatment with a target systolic level of <140 mm Hg within 1 h. Uni- and multi-variate analysis were conducted to illustrate the association between intensive blood pressure control and progressive intracerebral hemorrhage. Mortality, rates of operation, length of ICU stay, modified Rankin scores at 90 days, and the rate of serious adverse events were also compared between the two groups. RESULTS: A total of 351 and 308 patients with acute hypertensive intracerebral hemorrhage were recruited before and after May 2015, respectively. Progressive intracerebral hemorrhage was identified among 111 out of 659 patients. Patients who received intensive blood pressure control showed a statistically lower rate of hematoma enlarging (43 of 308, 13.9% vs. 74 of 351, 21.1%, p = 0.018). The rates of operation and modified Rankin scores at 90 days were statistically lower with intensive blood control, while the mortality, length of ICU stay and rate of serious adverse events were similar between the two groups. Intensive BP control is an independent factor in predicting hematoma growing, with a more favorable discrimination (AUC = 0.889; 95%CI, 0.859-0.917) than other two models (AUC = 0.821; 95%CI, 0.791-0.852; and AUC = 0.635; 95%CI, 0.588-0.682). CONCLUSION: Intensive blood pressure control reduce the risk of progressive intracerebral hemorrhage and improved functional outcomes in patients with acute hemorrhagic stroke.

Prognostic Value of Neutrophil-to-Lymphocyte Ratio in Predicting the 6-Month Outcome of Patients with Traumatic Brain Injury: A Retrospective Study.

BACKGROUND: Peripheral white blood cells are regularly analyzed on admission for patients with traumatic brain injury (TBI). The prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in predicting the 6-month outcome of patients with TBI is unclear. METHODS: We designed a single-center retrospective cohort study. Patients admitted to Fudan University Huashan Hospital within 6 hours after TBI were identified between December 2004 and December 2017. The primary outcome was 6-month Glasgow Outcome Scale score. Independent predictors of 6-month outcome were assessed using uni- and multivariate analyses. Three models based on admission characteristics were built to evaluate the prognostic value of the NLR in predicting the outcome of patients with TBI. The discriminative ability of predictive models was evaluated by the area under the curve (AUC). RESULTS: A total of 1291 patients with TBI were included. Multivariate analysis showed age, Glasgow Coma Scale scores at admission, subdural hematoma, intraparenchymal hemorrhage, traumatic subarachnoid hemorrhage, NLR (P < 0.001), and coagulopathy (P = 0.028) were independent predictors of 6-month outcome. The model combining the NLR and standard variables (AUC = 0.936; 95% confidence interval [CI], 0.923-0.949) was more favorable in predicting 6-month outcome of patients with TBI than the model without the NLR (AUC = 0.901; 95% CI, 0.883-0.919) and the model based only on the NLR (AUC = 0.827; 95% CI, 0.802-0.852). CONCLUSIONS: NLR is an independent prognostic factor of predicting 6-month outcome of patients with TBI. A high NLR in patients with TBI is associated with poor outcome. The prognostic value of the NLR in predicting 6-month outcome of patients with TBI is favorable.

Prognostic value of coagulation tests for in-hospital mortality in patients with traumatic brain injury.

BACKGROUND: Coagulopathy is commonly observed after traumatic brain injury (TBI). However, it is not known whether using the standard independent predictors in conjunction with coagulation tests would improve their prognostic value. We determined the incidence of TBI-associated coagulopathy in patients with isolated TBI (iTBI), evaluated the prognostic value of coagulation tests for in-hospital mortality, and tested their predictive power for in-hospital mortality in patients with iTBI. METHODS: We conducted a retrospective, observational database study on 2319 consecutive patients with iTBI who attended the Huashan Hospital Department of the Neurosurgery Neurotrauma Center at Fudan University in China between December 2004 and June 2015. Two models based on the admission characteristics were developed: model A included predictors such as age, Glasgow Coma Scale (GCS) score, pupil reactivity, type of injury, and hemoglobin and glucose levels, while model B included the predictors from model A as well as coagulation test results. A total of 1643 patients enrolled between December 2004 and December 2011 were used to derive the prognostic models, and 676 patients enrolled between January 2012 and June 2015 were used to validate the models. RESULTS: Overall, 18.6% (n = 432) of the patients developed coagulopathy after iTBI. The prevalence of acute traumatic coagulopathy is associated with the severity of brain injury. The percentage of platelet count <100 × 109/L, international normalized ratio (INR) > 1.25, the prothrombin time (PT) > 14 s, activated partial thromboplastin time (APTT) > 36 s, D-dimer >5 mg/L and fibrinogen (FIB) < 1.5 g/L was also closely related to the severity of brain injury, significance being found among three groups. Age, pupillary reactivity, GCS score, epidural hematoma (EDH), and glucose levels were independent prognostic factors for in-hospital mortality in model A, whereas age, pupillary reactivity, GCS score, EDH, glucose levels, INR >1.25, and APTT >36 s exhibited strong prognostic effects in model B. Discrimination and calibration were good for the development group in both prediction models. However, the external validation test showed that calibration was better in model B than in model A for patients from the validation population (Hosmer-Lemeshow test, p = 0.152 vs. p = 0.046, respectively). CONCLUSIONS: Coagulation tests can improve the predictive power of the standard model for in-hospital mortality after TBI.

Effects of Deferoxamine Mesylate on Hematoma and Perihematoma Edema after Traumatic Intracerebral Hemorrhage.

Deferoxamine mesylate can cross the blood-brain barrier and reduce iron accumulation in nervous tissue; moreover, it has a variety of neuroprotective functions in addition to complexing with iron ions. Such iron chelators are expected to become a new treatment option for intracerebral hemorrhage. This study evaluated the effects of deferoxamine mesylate on hematoma and edema absorption after traumatic intracerebral hemorrhage (TICH), and it provides clinical evidence for TICH treatment with deferoxamine mesylate. Patients with isolated TICH, confirmed by head computed tomography, were enrolled prospectively from January 2013 to December 2016. Patients were divided non-randomly into an experimental or control group as decided by the attending neurosurgeon. Patients in the experimental group received intravenous deferoxamine mesylate (20 mg/kg daily) from the day of admission for 5 consecutive days. We evaluated the impact of deferoxamine mesylate on the change in edema volume and the absorption of hematoma volume using a propensity score-matched analysis. In total, 190 patients were included. After matching, 94 patients were included in the final analysis (47 per group); no variable differed significantly between the two groups. The hematoma volume on the 7th day in the control group was higher than that at the same time-point in the experimental group (9.4 ± 7.2 vs. 5.2 ± 4.8 mL; p = 0.001). There was no difference in hematoma volume on Day 1 (12.6 ± 7.8 vs. 12.8 ± 6.4 mL; p = 0.896), Day 3 (12.4 ± 7.4 vs. 11.4 ± 4.9 mL; p = 0.442), and Day 14 (3.2 ± 3.0 vs. 2.5 ± 2.6 mL; p = 0.215) between the groups. The absorption of hematoma volume between the 1st and 3rd days and the 1st and 7th days in the experimental group was higher than that during the same periods in the control group. The edema volumes on the 3rd, 7th, and 14th days in the control group were higher than those at the same time-points in the experimental group. There was no difference in edema volume on the 1st day. The changes in edema volume between the 1st and 3rd days, the 1st and 7th days, and the 1st and 14th days in the control group were higher than those during the same periods in the experimental group. Deferoxamine mesylate may accelerate hematoma absorption and inhibit edema after TICH; however, further investigation is required to reach definitive conclusions.

Coagulopathy in Traumatic Brain Injury and Its Correlation with Progressive Hemorrhagic Injury: A Systematic Review and Meta-Analysis.

The association between coagulopathy and either isolated traumatic brain injury (TBI) or progressive hemorrhagic injury (PHI) remains controversial. The aims of this study were to evaluate whether isolated TBI induces pronounced coagulopathy, in comparison with non-TBI or TBI in conjunction with other injuries (TBI + other injuries), and to examine whether there is any evidence of a relationship between coagulopathy and PHI in patients who have experienced TBI. The MEDLINE(®) and Embase databases, and the Cochrane Central Register of Controlled Trials (Central), were trawled for relevant studies. Searches covered the period from the inception of each of the databases to June 2015, and were conducted using appropriate combinations of terms and key words based on medical subject headings (MeSH). Studies were included if they compared isolated TBI with a similar severity of injury to other body regions, or compared PHI with non-PHI, with regard to coagulation tests and the prevalence of coagulopathy. We extracted the means and standard deviations (SD) of coagulation test levels, as well as their ranges or the percentage of abnormal coagulation tests, in both cases and controls. A total of 19 studies were included in our systematic review and meta-analysis. Only the mean fibrinogen (FIB) in isolated TBI was found to be significantly higher than in TBI + other injuries (pooled mean difference [MD] 32.09; 95% confidence interval [CI] 4.92-59.25; p = 0.02); in contrast, it was also significantly higher than in non-TBI (pooled MD 15.44; 95% CI 0.28-30.59; p = 0.05). We identified 15 studies that compared coagulopathy between a PHI group and a non-PHI group. The PHI group had a lower platelet count (PLT) value (pooled MD -19.21; 95% CI: -26.99 to -11.44, p < 0.001) and a higher international normalized ratio (INR) value (pooled MD 0.07; 95% CI: 0.02-0.13, p = 0.006) than the non-PHI group, but no differences were observed in the mean activated partial thromboplastin time (APTT) and prothrombin time (PT) between the PHI and non-PHI patients. In addition, PHI was significantly associated with a higher percentage of INR >1.2 (pooled OR 3.49 [95% CI 1.97-6.20], p < 0.001), PLT <100 × 109/L (pooled OR 4.74 [95% CI 2.44-9.20], p < 0.001), and coagulopathy (pooled OR 2.52; 95% CI 1.88- 3.38; p < 0.001), compared with non-PHI. The current clinical evidence does not indicate that the prevalence of coagulopathy in TBI is significantly higher than in injuries of similar severity to other areas of the body, or in multiple injuries with TBI. With respect to the association between coagulopathy and PHI, the occurrence of coagulopathy, INR, and PLT was significantly associated with PHI, but APTT and PT were not found to be associated with PHI. In the future, high quality research will be required to further characterize the effects of coagulopathy on TBI and subsequent PHI.

Low-dose recombinant factor VIIa for reversing coagulopathy in patients with isolated traumatic brain injury.

PURPOSE: The purpose of this study was to investigate the role of low-dose recombinant factor VIIa (rFVIIa) (20 µg/kg) in reversing coagulopathy in patients with isolated traumatic brain injury (TBI). MATERIALS AND METHODS: Patients with isolated TBI and coagulopathy at admission were enrolled prospectively from January 2010 to December 2011. The patients were divided into 2 groups: the rFVIIa and the no-rFVIIa groups. In the rFVIIa group, patients received a single dose of 20 µg/kg rFVIIa intravenously to reverse their coagulopathy in addition to blood products. Patients in the no-rFVIIa group received only blood products to correct the coagulopathy. The clinical outcome variables evaluated included changes in coagulation parameters after administration for reversing coagulopathy, the occurrence of progressive hemorrhagic injury (PHI), intensive care unit length of stay, the incidence of thromboembolic complications, inhospital mortality, and 90-day Glasgow Outcome Scale. RESULTS: Eighty-seven patients were ultimately included in this study. Of them, 49 patients were treated with blood products alone, whereas 38 patients also received rFVIIa to reverse their coagulopathy. The improvement in international normalized ratio was greater in the rFVIIa group (0.26 [0.18-0.39]) than in the no-rFVIIa group (0.06 [-0.11 to 0.30]) (P = .001). In addition, the improvement in lactate was also greater in the rFVIIa group (0.33 [-0.18 to 0.54]) than in the no-rFVIIa group (0.04 [-0.25 to 0.20]) (P = .029). During the period after we began to correct the coagulopathy, PHI occurred in 19 patients (38.8%) in the no-rFVIIa group, which was significantly higher than that in the rFVIIa group (7, 18.4%; P = .040). The rate of cerebral infarction was similar in both groups (10.2% vs 5.3%). There was a trend indicating that low-dose rFVIIa therapy was associated with a lower mortality, but the association was not statistically significant (P = .266). CONCLUSIONS: The use of low-dose rFVIIa (20 µg/kg) is effective for correcting coagulopathy in patients with TBI without an increase in thromboembolic events. Moreover, it is more effective for preventing the occurrence of PHI.

[Role of small-dose recombinant human coagulation factor VIIa for coagulopathy in patients with isolated traumatic brain injury].

OBJECTIVE: To explore the role of small-dose recombinant human coagulation factor VIIa (rFVIIa) for coagulopathy in patients with isolated traumatic brain injury. METHODS: A total of 86 isolated traumatic brain patients with coagulopathy were treated at our neurosurgery intensive care unit (NICU) from January 2010 to December 2012. Their trauma registry data included mortality, pre-and post-rFVIIa coagulation parameters. Two-tailed paired t-test was used to determine significant changes in coagulation parameters and other major clinical parameters. RESULTS: Twenty-seven patients made up the low-dose rFVIIa (20 µg/kg) group. And the control group had 59 well-matched subjects. At admission, age, blood pressure, Glasgow coma scale score, hemoglobin, platelets and international normalize ratio were similar in both groups. After treatment, the INR of patients on rFVIIa was lower than that of the conventional treatment group (1.1 ± 0.2 vs 1.2 ± 0.2, P < 0.01) and it declined more in the rFVIIa group (0.3 ± 0.2 vs 0.1 ± 0.4, P = 0.05). No significant difference existed in mortality or length of stay between two groups.There was no occurrence of subsequent thromboembolic events. CONCLUSION: The application of small-dose rFVIIa can effectively reduce the value of INR and improve the coagulation status of patients. During the course of treatment, no major adverse events occur.

[Functional magnetic imaging of brain cortical activities in minimally conscious patients stimulated by visual presentation].

OBJECTIVE: To investigate whether a large-scale visual network and visual consciousness are still retained in the patients with minimally conscious state (MCT) and the possibility of promoting the rehabilitation of brain function by visual stimulation. METHODS: Fifteen standardized pictures provided by the International Affective Picture System (IAPS2005) were passively presented to 10 normal adult controls and 9 patients in MCT recovering from severe craniocerebral injury or cerebral hemorrhage. Functional magnetic imaging was conducted. The AFNI software was used to process the images thus collected. RESULTS: The primary visual cortex, occipital lobe, and the secondary visual cortexes, including temporal lobe, parietal lobe, fusiform gyrus, orbital gyrus, and prefrontal lobe were all activated in the 10 normal persons. Similar visual activation was found in 2 of the patients in MCS, however, with a smaller activation volume. Activation of partial visual network was found in 3 patients and the other 4 failed to be activated. CONCLUSION: It is feasible to promote the rehabilitation of brain function by visual stimulation in the patients in MCS.

Upregulated gene expression of local brain-derived neurotrophic factor and nerve growth factor after intracisternal administration of marrow stromal cells in rats with traumatic brain injury.

OBJECTIVE: To examine the effects of rat marrow stromal cells (rMSCs) on gene expression of local brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) after injection of rMSCs into Cistern Magnum of adult rats subjected to traumatic brain injury (TBI). METHODS: A modified Feeney's TBI model was created in 48 adult rats. rMSCs were harvested from 3-month-old rats, and injected into Cistern Magnum in 24 rats subjected to TBI (Group cell transplantation). Saline was given through Cistern Magnum to another 24 rats subjected to TBI (Group saline control). Animals were sacrificed 1, 2 and 3 weeks after intervention, and special brain tissue blocks were dissected for total RNA extraction from each block. BDNF and NGF mRNA were reverse-transcribed into cDNA and further expanded by polymerase chain reaction (PCR). The expression of target genes was evaluated using semi-quantitative methods. RESULTS: Group cell transplantation had higher BDNF and NGF gene expressions than Group saline control during a period of less than 3 weeks (P<0.05). CONCLUSIONS: rMSCs transplantation via Cistern Magnum in rats subjected to traumatic brain injury can enhance expressions of local brain NGF and BDNF to a certain extent.

Dynamically monitoring tissue factor and tissue factor pathway inhibitor following secondary brain injury.

OBJECTIVE: To study the altering rule of coagulation function at molecular level in patients with secondary brain injury (SBI). METHODS: Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) were studied in 32 patients 1, 2, 3 and 7 days after craniocerebral injury. Repeated cranial CT scans and platelet counts were made simultaneously. Same measurements were done in 30 normal adults except CT scan. RESULTS: No obvious difference was found in age, sex and platelet count between the injured and the normal groups. TFPI/TF decreased markedly in the first week after injury in patients with SBI, but only decreased on the 7th day in the patients without obvious SBI. For the patients who developed delayed intracranial hematoma (DIH) or hematoma enlargement, TF rose only 1 and 2 days after injury, but TFPI had a tendency to rise again after a fall on the 3rd day. For those patients who developed no DIH, TF rose all the time within the 1st week. CONCLUSIONS: Decrease of TFPI/TF for a long time, especially within 3 days after injury, may be one of the most important reasons for SBI. High expression of TF for a relative short time and increase of TFPI after a fall within 3 days may be one of the important reasons for DIH or hematoma enlargement.