Interventional Treatment of Symptomatic Vasospasm in the Setting of Traumatic Brain Injury: A Systematic Review of Reported Cases.

Traumatic subarachnoid hemorrhage (tSAH) is frequently comorbid with traumatic brain injury (TBI) and may induce secondary injury through vascular changes such as vasospasm and subsequent delayed cerebral ischemia (DCI). While aneurysmal SAH is well studied regarding vasospasm and DCI, less is known regarding tSAH and the prevalence of vasospasm and DCI, the consequences of vasospasm in this setting, when treatment is indicated, and which management strategies should be implemented. In this article, a systematic review of the literature that was conducted for cases of symptomatic vasospasm in patients with TBI is reported, association with tSAH is reported, risk factors for vasospasm and DCI are summarized, and commonalities in diagnosis and management are discussed. Clinical characteristics and treatment outcomes of 38 cases across 20 studies were identified in which patients with TBI with vasospasm underwent medical or endovascular management. Of the patients with data available for each category, the average age was 48.7 ± 20.3 years (n = 31), the Glasgow Coma Scale score at presentation was 10.6 ± 4.5 (n = 35), and 100% had tSAH (n = 29). Symptomatic vasospasm indicative of DCI was diagnosed on average at postinjury day 8.4 ± 3.0 days (n = 30). Of the patients, 56.6% (n = 30) had a new ischemic change associated with vasospasm confirming DCI. Treatment strategies are discussed, with 11 of 12 endovascularly treated and 19 of 26 medically treated patients surviving to discharge. tSAH is associated with vasospasm and DCI in moderate and severe TBI, and patients with clinical and radiographic evidence of symptomatic vasospasm and subsequent DCI may benefit from endovascular or medical management strategies.

Glypican-1 may be a plasma biomarker for predicting the rupture of small intracranial aneurysms.

Currently, there are no effective methods for predicting the rupture of asymptomatic small intracranial aneurysms (IA) (<7 mm). In this study the aim was to identify early warning biomarkers in peripheral plasma for predicting IA rupture. Four experimental groups were included: ruptured intracranial aneurysm (RIA), unruptured intracranial aneurysm (UIA), traumatic subarachnoid hemorrhage control (tSAHC), and healthy control (HC) groups. Plasma proteomics of these four groups were detected using iTRAQ combined LC-MS/MS. Differentially expressed proteins (DEPs) were identified in RIA, UIA, tSAHC compared with HC. Target proteins associated with aneurysm rupture were obtained by comparing the DEPs of the RIA and UIA groups after filtering out the DEPs of the tSAHC group. The plasma concentrations of target proteins were validated using enzyme-linked immunosorbent assay (ELISA). The iTRAQ analysis showed a significant increase in plasma GPC1 concentration in the RIA group compared to the UIA group, which was further validated among the IA patients. Logistic regression analysis identified GPC1 as an independent risk factor for predicting aneurysm rupture. The ROC curve indicated that the GPC1 plasma cut-off value for predicting aneurysms rupture was 4.99 ng/ml. GPC1 may be an early warning biomarker for predicting the rupture of small intracranial aneurysms. SIGNIFICANCE: The current management approach for asymptomatic small intracranial aneurysms (<7 mm) is limited to conservative observation and surgical intervention. However, the decision-making process regarding these options poses a dilemma due to weighing their respective advantages and disadvantages. Currently, there is a lack of effective diagnostic methods to predict the rupture of small aneurysms. Therefore, our aim is to identify early warning biomarkers in peripheral plasma that can serve as quantitative detection markers for predicting intracranial aneurysm rupture. In this study, four experimental populations were established: small ruptured intracranial aneurysm (sRIA) group, small unruptured intracranial aneurysm (sUIA) group, traumatic subarachnoid hemorrhage control (tSAHC) group, and healthy control (HC) group. The tSAH group was the control group of spontaneous subarachnoid hemorrhage caused by ruptured aneurysm. Compared with patients with UIA, aneurysm tissue and plasma GPC1 in patients with RIA is significantly higher, and GPC1 may be an early warning biomarker for predicting the rupture of intracranial small aneurysms.

Classification, risk factors, and outcomes of patients with progressive hemorrhagic injury after traumatic brain injury.

BACKGROUND: According to the pathoanatomic classification system, progressive hemorrhagic injury (PHI) can be categorized into progressive intraparenchymal contusion or hematoma (pIPCH), epidural hematoma (pEDH), subdural hematoma (pSDH), and traumatic subarachnoid hemorrhage (ptSAH). The clinical features of each type differ greatly. The objective of this study was to determine the predictors, clinical management, and outcomes of PHI according to this classification. METHODS: Multivariate logistic regression analysis was used to identify independent risk factors for PHI and each subgroup. Patients with IPCH or EDH were selected for subgroup propensity score matching (PSM) to exclude confounding factors before evaluating the association of hematoma progression with the outcomes by classification. RESULTS: In the present cohort of 419 patients, 123 (29.4%) demonstrated PHI by serial CT scan. Of them, progressive ICPH (58.5%) was the most common type, followed by pEDH (28.5%), pSDH (9.8%), and ptSAH (3.2%). Old age (≥ 60 years), lower motor Glasgow Coma Scale score, larger primary lesion volume, and higher level of D-dimer were independent risk factors related to PHI. These factors were also independent predictors for pIPCH, but not for pEDH. The time to first CT scan and presence of skull linear fracture were robust risk factors for pEDH. After PSM, the 6-month mortality and unfavorable survival rates were significantly higher in the pIPCH group than the non-pIPCH group (24.2% vs. 1.8% and 12.1% vs. 7.3%, respectively, p < 0.001), but not significantly different between the pEDH group and the non-pEDH group. CONCLUSIONS: Understanding the specific patterns of PHI according to its classification can help early recognition and suggest targeted prevention or treatment strategies to improve patients' neurological outcomes.

Risk Factor-Guided Early Discharge and Potential Resource Allocation Benefits in Patients with Traumatic Subarachnoid Hemorrhage.

OBJECTIVE: We sought to develop screening criteria predicting the lack of poor neurologic outcomes in patients presenting with traumatic subarachnoid hemorrhage (tSAH) and to evaluate their potential to improve resource allocation in these cases. METHODS: We retrospectively reviewed patients presenting with tSAH to the emergency department (ED) of a tertiary-care institution from 2016 to 2018. We defined good neurologic outcomes as patients with stable/improving neurologic status, who did not require neurosurgical intervention, had no expanding bleed, and needed no hospital readmission. Univariate and multivariate models were generated to predict risk factors inversely associated with good neurologic outcome. RESULTS: A total of 167 patients presented with tSAH from 2016 to 2018. The presence of depressed skull fracture, concomitant spinal fracture, low Glasgow Coma Scale (GCS) score, cranial nerve palsies, disorientation, concomitant hemorrhages, midline shift, increased international normalized ratio (INR), and emergent medical intervention were inversely correlated with likelihood of good neurologic outcome on univariate analysis. Multivariate regression showed that midline shift (odds ratio [OR], 0.22; 95% confidence interval [CI], 0.05-0.89; P = 0.04), GCS score <13 (OR, 0.22; 95% CI, 0.05-0.99; P = 0.05), increased INR (OR, 0.18; 95% CI, 0.03-0.85; P = 0.04), and emergent medical intervention (OR, 0.18; 95% CI, 0.04-0.63; P = 0.01) were independently associated with lower likelihood of good neurologic outcome. Forty-six patients without any factors had good outcomes but were held in the ED or admitted to the hospital. These patients (if instead discharged directly) meant a potential cost savings of $179,172. CONCLUSIONS: In our study, we found multiple risk factors inversely associated with good neurologic outcome, namely low GCS score, midline shift, emergent medical intervention, and INR ≥1.4. Our findings may aid clinicians in determining which tSAH patients are candidates for safe early discharge.

White Matter Abnormalities in Traumatic Subarachnoid Hemorrhage: A Tract-Based Spatial Statistics Study.

BACKGROUND The pathophysiology of traumatic subarachnoid hemorrhage and brain injury has not been fully elucidated. In this study, we examined abnormalities of white matter in isolated traumatic subarachnoid hemorrhage patients by applying tract-based spatial statistics. MATERIAL AND METHODS For this study, 10 isolated traumatic subarachnoid hemorrhage patients and 10 age- and sex-matched healthy control subjects were recruited. Fractional anisotropy data voxel-wise statistical analyses were conducted through the tract-based spatial statistics as implemented in the FMRIB Software Library. Depending on the intersection between the fractional anisotropy skeleton and the probabilistic white matter atlases of Johns Hopkins University, we calculated mean fractional anisotropy values within the entire tract skeleton and 48 regions of interest. RESULTS The fractional anisotropy values for 19 of 48 regions of interest showed significant divergences (P<0.05) between the patient group and control group. The regions showing significant differences included the corpus callosum and its adjacent neural structures, the brainstem and its adjacent neural structures, and the subcortical white matter that passes the long neural tract. CONCLUSIONS The results demonstrated abnormalities of white matter in traumatic subarachnoid hemorrhage patients, and the abnormality locations are compatible with areas that are vulnerable to diffuse axonal injury. Based on these results, traumatic subarachnoid hemorrhage patients also exhibit diffuse axonal injuries; thus, traumatic subarachnoid hemorrhage could be an indicator of the presence of severe brain injuries associated with acute or excessive mechanical forces.

Putting 'CSF-Shift Edema' Hypothesis to Test: Comparing Cisternal and Parenchymal Pressures After Basal Cisternostomy for Head Injury.

BACKGROUND: Increased brain edema in head injury is due to shift of cerebrospinal fluid (CSF) from cisterns at high pressure to brain parenchyma at low pressure. By opening basal cisterns and decreasing the increased cisternal pressure, basal cisternostomy (BC) results in reversal of CSF shift from parenchyma to cisterns, leading to decreased brain edema. Though the CSF-shift edema hypothesis is based on pressure difference between cisterns and brain parenchyma, the relationship of these pressures has not been studied. METHODS: A prospective clinical study was conducted from November 2018 to March 2020 including adult patients with head injury who were candidates for standard decompressive hemicraniectomy (DHC). All patients had neurological assessment and head computed tomography preoperatively and postoperatively. All patients underwent BC with DHC. Postoperatively, parenchymal and cisternal pressures and neurological condition were monitored hourly for 72 hours. RESULTS: Nine (5 men, 4 women) patients with head injury (mean age, 45.7 years; range, 25-72 years) underwent DHC-BC. Median Glasgow Coma Scale score of patients at admission was 8 (range, 4-14), and median midline shift on computed tomography was 8 mm (range, 7-12 mm). There was a significant difference between opening (25.70 ± 10.48 mm Hg) and closing (11.30 ± 5.95 mm Hg) parenchymal pressures (t9 = 3.963, P = 0.003). Immediate postoperative cisternal pressure was 1-11 mm Hg and was lower than immediate postoperative parenchymal pressure in all except 1 patient. Postoperatively, if cisternal pressure remained low, parenchymal pressure also decreased, and patients showed clinical improvement. Patients showing increased cisternal pressure showed increased parenchymal pressure and clinical worsening. CONCLUSIONS: Our study supports the CSF-shift edema hypothesis. Following DHC-BC, cisternal pressure is lowered to near-atmospheric pressure, and its relationship to parenchymal pressure predicts the future course of patients by reversal or re-reversal of CSF shift.

The delayed detection of an acute neurological worsening increases traumatic brain injury lethality / [La detección tardía del deterioro neurológico agudo incrementa la letalidad por trauma craneoencefálico.]

Introduction: Traumatic brain injury is a leading worldwide cause of death and disability in young people. Severity classification is based on the Glasgow Coma Scale. However, the neurological worsening in an acute setting does not always correspond to the initial severity suggesting an underestimation of the real magnitude of the injury. Objective: To study the correlation between the initial severity according to the Glasgow Coma Scale and the patient outcome in the context of different clinical and tomography variables. Materials and methods: We analyzed a retrospective cohort of 490 patients with closed traumatic brain injury requiring a stay in the intensive care unit of two third-level hospitals in Barranquilla. The risk was estimated by calculating the OR (95% CI). The significance level was established at an alpha value of 0.05. Results: Forty-one percent of all patients required orotracheal intubation; 51.2% were initially classified with moderate trauma and 6,0% as mild. The delay in the aggressive management of the traumas affected mainly those patients with traumas classified as moderate in whom lethality increased to 100% when there was delay in the detection of the neurological worsening and in the establishment of the aggressive treatment beyond 4 to 8 hours while the lethality in patients who received this treatment within the first hour reduced to <20%. Conclusions: The risk of lethality in traumatic brain injury increases with the delayed detection of neurological worsening in an acute setting, especially when aggressive management is performed after the first hour post-trauma.

Introducción. El trauma craneoencefálico es una de las principales causas de muerte y discapacidad en adultos jóvenes. Su gravedad se define según la escala de coma de Glasgow. Sin embargo, el deterioro neurológico agudo no siempre concuerda con la gravedad inicial indicada por la escala, lo que implica una subestimación de la magnitud real de la lesión. Objetivo. Estudiar la correlación entre la gravedad inicial del trauma craneoencefálico según la escala de coma de Glasgow y la condición final del paciente, en el contexto de diferentes variables clínicas y de los hallazgos de la tomografía. Materiales y métodos. Se analizó una cohorte retrospectiva de 490 pacientes con trauma craneoencefálico cerrado que requirieron atención en la unidad de cuidados intensivos de dos centros de tercer nivel de Barranquilla. La estimación del riesgo se estableció con la razón de momios (odds ratio, OR) y un intervalo de confianza (IC) del 95 %. Se utilizó un alfa de 0,05 como nivel de significación. Resultados. El 41,0 % de los pacientes requirió intubación endotraqueal; el 51,2 % había presentado traumas inicialmente clasificados como moderados y, el 6,0 %, como leves. El retraso en la implementación de un tratamiento agresivo afectó principalmente a aquellos con trauma craneoencefálico moderado, en quienes la letalidad aumentó al 100 % cuando no se detectó a tiempo el deterioro neurológico y, por lo tanto, el tratamiento agresivo se demoró más de 4 a 8 horas. Por el contrario, la letalidad fue de menos de 20 % cuando se brindó el tratamiento agresivo en el curso de la primera hora después del trauma. Conclusiones. El riesgo de letalidad del trauma craneoencefálico aumentó cuando el deterioro neurológico se detectó tardíamente y el tratamiento agresivo se inició después de transcurrida la primera hora a partir del trauma.

Ratio of Optic Nerve Sheath Diameter to Eyeball Transverse Diameter by Ultrasound Can Predict Intracranial Hypertension in Traumatic Brain Injury Patients: A Prospective Study.

BACKGROUND: Measuring optic nerve sheath diameter (ONSD), an indicator to predict intracranial hypertension, is noninvasive and convenient, but the reliability of ONSD needs to be improved. Instead of using ONSD alone, this study aimed to evaluate the reliability of the ratio of ONSD to eyeball transverse diameter (ONSD/ETD) in predicting intracranial hypertension in traumatic brain injury (TBI) patients. METHODS: We performed a prospective study on patients admitted to the Surgery Intensive Care Unit. The included 52 adults underwent craniotomy for TBI between March 2017 and September 2018. The ONSD and ETD of each eyeball were measured by ultrasound and computed tomography (CT) scan within 24 h after a fiber optic probe was placed into lateral ventricle. Intracranial pressure (ICP) > 20 mmHg was regarded as intracranial hypertension. The correlations between invasive ICP and ultrasound-ONSD/ETD ratio, ultrasound-ONSD, CT-ONSD/ETD ratio, and CT-ONSD were each analyzed separately. RESULTS: Ultrasound measurement was successfully performed in 94% (n = 49) of cases, and ultrasound and CT measurement were performed in 48% (n = 25) of cases. The correlation efficiencies between ultrasound-ONSD/ETD ratio, ultrasound-ONSD, CT-ONSD/ETD ratio, and ICP were 0.613, 0.498, and 0.688, respectively (P < 0.05). The area under the curve (AUC) values of the receiver operating characteristic (ROC) curve for the ultrasound-ONSD/ETD ratio and CT-ONSD/ETD ratio were 0.920 (95% CI 0.877-0.964) and 0.896 (95% CI 0.856-0.931), respectively. The corresponding threshold values were 0.25 (sensitivity of 90%, specificity of 82.3%) and 0.25 (sensitivity of 85.7%, specificity of 83.3%), respectively. CONCLUSION: The ratio of ONSD to ETD tested by ultrasound may be a reliable indicator for predicting intracranial hypertension in TBI patients.

A case report of delayed cortical infarction adjacent to sulcal clots after traumatic subarachnoid hemorrhage in the absence of proximal vasospasm.

BACKGROUND: Cortical ischemic lesions represent the predominant pathomorphological pattern of focal lesions after aneurysmal subarachnoid hemorrhage (aSAH). Autopsy studies suggest that they occur adjacent to subarachnoid blood and are related to spasm of small cortical rather than proximal arteries. Recent clinical monitoring studies showed that cortical spreading depolarizations, which induce cortical arterial spasms, are involved in lesion development. If subarachnoid blood induces adjacent cortical lesions, it would be expected that (i) they also develop after traumatic subarachnoid hemorrhage (tSAH), and (ii) lesions after tSAH can occur in absence of angiographic vasospasm, as was found for aSAH. CASE PRESENTATION: An 86-year-old woman was admitted to our hospital with fluctuating consciousness after hitting her head during a fall. The initial computed tomography (CT) was significant for tSAH in cortical sulci. On day 8, the patient experienced a secondary neurological deterioration with reduced consciousness and global aphasia. Whereas the CT scan on day 9 was still unremarkable, magnetic resonance imaging (MRI) on day 10 revealed new cortical laminar infarcts adjacent to sulcal blood clots. Proximal vasospasm was ruled out using MR and CT angiography and Doppler sonography. CT on day 14 confirmed the delayed infarcts. CONCLUSIONS: We describe a case of delayed cortical infarcts around sulcal blood clots after tSAH in the absence of proximal vasospasm, similar to results found previously for aSAH. As for aSAH, this case suggests that assessment of angiographic vasospasm is not sufficient to screen for risk of delayed infarcts after tSAH. Electrocorticography is suggested as a complementary method to monitor the hypothesized mechanism of spreading depolarizations.

Effect of Mannitol Infusion on Optic Nerve Injury After Acute Traumatic Subarachnoid Hemorrhage and Brain Injury.

The primary aim of this paper is to investigate the neuroprotective and antiinflammatory effects of mannitol on optic nerve injury after acute traumatic subarachnoid hemorrhage and brain injury in rat models. Traumatic brain injury (TBI) and traumatic subarachnoid hemorrhage (tSAH) were produced by a custom-made weight-drop impact acceleration device. Thirty male Wistar rats were divided into 3 groups. Group I (n = 10) was the sham group, group II (n = 10) received TBI, and group III (n = 10) received TBI + mannitol (1 mg/kg intravenously). Optic nerve tissue glutathione peroxidase (GPx) and interleukin 1 beta (IL-1ß) levels were measured 4 hours after the trauma. The authors used Kruskal-Wallis variance analysis and Mann-Whitney U tests for statistical analysis. Optic nerve tissue GPx levels were significantly higher in group III than in groups I and II (P < 0.05). Optic nerve tissue IL-1ß levels were significantly lower in group III than in group II (P < 0.05) and higher than in group I (P < 0.05).Mannitol increased the antioxidant GPx levels and decreased the IL-1ß levels, which can protect the optic nerve from secondary injury after severe acute trauma. Mannitol plays an important role in the treatment of acute severe indirect optic nerve injury after TBI and tSAH.

Computed Tomography Indicators of Deranged Intracranial Physiology in Paediatric Traumatic Brain Injury.

OBJECTIVE: Computed tomography (CT) of the brain can allow rapid assessment of intracranial pathology after traumatic brain injury (TBI). Frequently in paediatric TBI, CT imaging can fail to display the classical features of severe brain injury with raised intracranial pressure. The objective of this study was to determine early CT brain features that influence intracranial or systemic physiological trends following paediatric TBI. MATERIALS AND METHODS: Thirty-three patients (mean age, 10 years; range, 0.5-16) admitted between 2002 and 2015 were used for the current analysis. Presence of petechial haemorrhages, basal cistern compression, subarachnoid blood, midline shift and extra-axial masses on the initial trauma CT head were assessed. ICP and arterial blood pressure (ABP) were then monitored continuously with an intraparenchymal microtransducer and an indwelling arterial line. Pressure monitors were connected to bedside computers running ICM+ software. Pressure reactivity was determined as the moving correlation between 30, 10-s averages of ABP and ICP (PRx). The mean ICP, ABP, cerebral perfusion pressure (CPP; ABP minus ICP) and PRx were calculated for the whole monitoring period for each patient. RESULTS: The presence of subarachnoid blood was related to higher ICP, higher ABP and a trend toward higher PRx. Smaller basal cisterns were related to increased ICP (R = -0.42, p = 0.02), impaired PRx (R = -0.5, p = 0.003). The presence of an extra-axial mass was associated with deranged PRx (-0.02 vs. 0.41, p = 0.003) and a trend toward higher ICP (14 vs. 40, p = 0.07). Interestingly the degree of midline shift was not related to ICP or PRx. CONCLUSIONS: The size of the basal cisterns, the presence of subarachnoid blood or an extra-axial mass are all related to disturbed ICP and pressure reactivity in this paediatric TBI cohort. Patients with these features are ideal candidates for invasive multimodal monitoring.

Pediatric Extracorporeal Cardiopulmonary Resuscitation Patient With Traumatic Subarachnoid Hemorrhage and Takotsubo Syndrome.

Takotsubo syndrome is rare in pediatric patients but must be considered in patients with subarachnoid hemorrhage with pulmonary edema and cardiomyopathy. A systematic, collaborative approach is needed to facilitate emergent transfer of patients where extracorporeal cardiopulmonary resuscitation (e-CPR) is used as a lifesaving measure. Extracorporeal membrane oxygenation (ECMO) use in transport requires preplanning, role delineation, resources, and research efforts to be successful. We present an unusual transport case of successful e-CPR/ECMO treatment of Takotsubo syndrome in a 12-year-old boy with an isolated traumatic intracranial injury, cardiomyopathy with pulmonary edema, and multiple cardiac arrests.

Occult Pneumomediastinum in the Deployed Setting: Evaluation and Management.

Pneumomediastinum can occur after both blunt and penetrating trauma. The greatest concern involving this finding in a trauma patient is an aerodigestive tract injury. Prompt evaluation, identification, and management of these injuries are extremely important. This case describes a soldier who was involved in an improvised explosive device blast with no evidence of cavity penetration. During the routine evaluation of his head and neck an occult pneumomediastinum was identified. The patient was asymptomatic and was further evaluated with computed tomography because of the absence of endoscopy and bronchoscopy in theatre. The imaging showed no evidence of esophageal or tracheobronchial injury. The patient was observed and when noted to be stable was transferred to the local Role 3 hospital for management of his other injuries.

Traumatic Entrapment of the Vertebral Artery Demonstrated by a 3D Angiographic Study.

BACKGROUND: Vertebrobasilar artery entrapment resulting from a clivus fracture is rare. The entrapped lesions are not radiographically depicted precisely because they are only identified by autopsy or completely occluded. In addition, no changes in the features have been revealed clearly because radiologic examinations were performed only in the acute stage. CASE DESCRIPTION: We report a case of traumatic entrapment of the vertebral artery depicted precisely by a three-dimensional angiographic study in the subacute stage, presenting the serial changes in the morphologic features and a review of the published cases. CONCLUSION: It is necessary to manage vertebrobasilar artery entrapment cautiously because it is suggested that the entrapped lesion is accompanied by arterial dissection.

Neuroprotective Effects of Valproic Acid on Blood-Brain Barrier Disruption and Apoptosis-Related Early Brain Injury in Rats Subjected to Subarachnoid Hemorrhage Are Modulated by Heat Shock Protein 70/Matrix Metalloproteinases and Heat Shock Protein 70/AKT Pathways.

BACKGROUND: Blood-brain barrier (BBB) disruption and neural apoptosis are thought to promote early brain injury (EBI) after subarachnoid hemorrhage (SAH). Previous studies have demonstrated that valproic acid (VPA) decreased brain injury in a prechiasmatic injection model of SAH in mice. It should be noted that the beneficial effects of VPA and the underlying mechanisms have not been fully elucidated. OBJECTIVE: To characterize the effects of VPA on BBB disruption and neural apoptosis and to determine mechanisms involved in EBI after SAH. METHODS: An endovascular perforation model was used to induce SAH in rats. VPA (300 mg/kg) was promptly administered after SAH induction, and the same dose was given 12 hours later. Quercetin (100 mg/kg), an inhibitor of heat shock protein 70 (HSP70), was injected into the peritoneum 2 hours before SAH induction. Mortality, SAH grades, neurological function, Evans Blue extravasation, brain edema, transmission electron microscopy, Western blot, double fluorescence labeling, and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling staining also were used. RESULTS: VPA treatment decreased BBB disruption and brain edema, attenuated neural apoptosis, and improved neurobehavioral functions in EBI after SAH. Double fluorescence labeling indicated that matrix metallopeptidase 9 (MMP-9) was located predominately in neurons and endothelial cells. VPA upregulated the expression of HSP70, effectively decreased the expression and activity of MMP-9, and reduced claudin-5 and occludin degradation. Meanwhile, VPA also upregulated the expression of phosphorylated Akt and bcl-2. Both the anti-BBB disruption and antiapoptotic effects of VPA were abolished by quercetin. CONCLUSION: VPA prevented BBB disruption and alleviated neural apoptosis after SAH. The action of VPA appeared to be mediated though the HSP70/MMPs and HSP70/Akt pathways. ABBREVIATIONS: BBB, blood-brain barrierEBI, early brain injuryHSP, heat shock proteinMMP, matrix metalloproteinasePBS, phosphate-buffered salineSAH, subarachnoid hemorrhageTUNEL, terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labelingVPA, valproic acid.

CSF Lumbar Drainage: A Safe Surgical Option in Refractory Intracranial Hypertension Associated with Acute Posttraumatic External Hydrocephalus.

INTRODUCTION: External lumbar drainage (ELD) of cerebrospinal fluid (CSF) in posttraumatic refractory intracranial hypertension (ICHT) is controversial. We report our experience of ELD in ICHT associated with acute disturbance of CSF flow within subarachnoid spaces (SASs). MATERIALS AND METHODS: Four adult patients admitted to the neurointensive care unit for severe TBI who presented with secondary ICHT are retrospectively reported. When refractory to second-tier therapy, if external ventricular drainage were not possible or failed, and in the absence of an indication for craniotomy to treat a mass lesion or decompressive craniectomy, we assessed the evolution of CSF volume within cranial SAS and checked the presence of basal cisterns and the absence of tonsillar herniation to evaluate interest in and the safety of ELD. RESULTS: As second-tier therapy failed to lower intracranial pressure (ICP; mean ICP 37 ± 5 mmHg), and computed tomography (CT) showed abnormally enlarged cranial SAS following traumatic subarachnoid hemorrhage, patients received ELD. ICP decreased, with immediate and long-term effect (mean ICP 5 mmHg ± 2 mmHg). There were no complications to report. DISCUSSION: Acute traumatic external hydrocephalus may explain some of the specific situations of secondary increased ICP, with a "normal" CT scan, that is refractory to medical treatment. In these situations, lumbar drainage should be considered to be a safe, minimally invasive, and effective surgical option.

"Solid Red Line": An Observational Study on Death from Refractory Intracranial Hypertension.

The index of cerebrovascular pressure reactivity (PRx) correlates independently with outcome after traumatic brain injury (TBI). However, as an index plotted in the time domain, PRx is rather noisy. To "organise" PRx and make its interpretation easier, the colour coding of values, with green when PRx <0 and red when PRx> 0.3, has been introduced as a horizontal colour bar on the ICM+ screen. In rare cases of death from refractory intracranial hypertension, an increase in intracranial pressure (ICP) is commonly preceded by values of PRx >0.3, showing a "solid red line".Twenty patients after TBI and one after traumatic subarachnoid haemorrhage (SAH) from six centres in Europe and Australia have been studied. All of them died in a scenario of refractory intracranial hypertension. In the majority of cases the initial ICP was below 20 mmHg and finally increased to values well above 60 mmHg, resulting in cerebral perfusion pressure less than 20 mmHg. In three cases initial ICP was elevated at the start of monitoring. A solid red line was observed in all cases preceding an increase in ICP above 25 mmHg by minutes to hours and in two cases by 2 and 3 days, respectively. If a solid red line is observed over a prolonged period, it should be considered as an indicator of deep cerebrovascular deterioration.