Anti-HMGB1 mAb Therapy Reduces Epidural Hematoma Injury.

Epidural and subdural hematomas are commonly associated with traumatic brain injury. While surgical removal is the primary intervention for these hematomas, it is also critical to prevent and reduce complications such as post-traumatic epilepsy, which may result from inflammatory responses in the injured brain areas. In the present study, we observed that high mobility group box-1 (HMGB1) decreased in the injured brain area beneath the epidural hematoma (EDH) in rats, concurrent with elevated plasma levels of HMGB1. Anti-HMGB1 monoclonal antibody therapy strongly inhibited both HMGB1 release and the subsequent increase in plasma levels. Moreover, this treatment suppressed the up-regulation of inflammatory cytokines and related molecules such as interleukin-1-beta (IL-1ß), tumor necrosis factor-alpha (TNF-α), and inducible nitric oxide synthase (iNOS) in the injured areas. Our in vitro experiments using SH-SY5Y demonstrated that hematoma components-thrombin, heme, and ferrous ion- prompted HMGB1 translocation from the nuclei to the cytoplasm, a process inhibited by the addition of the anti-HMGB1 mAb. These findings suggest that anti-HMGB1 mAb treatment not only inhibits HMGB1 translocation but also curtails inflammation in injured areas, thereby protecting the neural tissue. Thus, anti-HMGB1 mAb therapy could serve as a complementary therapy for an EDH before/after surgery.

Prophylactic levetiracetam-induced pancytopenia with traumatic extra-dural hematoma: Case report.

BACKGROUND: Pancytopenia has only rarely been reported with Levetiracetam use. It is a potentially life threatening adverse effect that requires cessation of therapy. CASE DESCRIPTION: We describe a case of an otherwise well thirty-two-year-old man who underwent an emergent craniotomy for evacuation of a traumatic extra-dural haematoma. Post-operatively, he developed pancytopenia which corrected with cessation of levetiracetam. CONCLUSION: This report aims to increase awareness of this rare side effect and reiterates the judicious use of prophylactic levetiracetam in brain trauma.

Intravenous Tranexamic Acid for Subdural and Epidural Intracranial Hemorrhage: Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Recovery of patients with traumatic brain injury largely depends on the reduction in secondary brain damage. The present study aims at investigating the effect of Tranexamic Acid (TXA) administration within the first hours of brain trauma in the emergency department (ED). METHODS: This randomized, double-blind, placebo-controlled clinical trial was carried out in patients with subdural and epidural hemorrhage. Patients with any type of bleeding were assigned into two groups of TXA and 0.9% normal saline as placebo. The rate of intracranial hemorrhage after surgery was assessed by CT-scan and amount of hemoglobin (Hb) was measured immediately before surgery and after 6 hours of surgery. RESULTS: A total of 80 participants were randomly assigned into four groups of 20 people. There was a significant difference in the mean of intraoperative bleeding during surgery in patients receiving TXA and placebo in both SDH (Subdural hematoma) and EDH (Epidural Hemorrhage) groups (P= 0.012). The Hb drop amount had no significant difference with placebo (P< 0.0001). No complications were observed in any of the intervention and control groups during the study as well. CONCLUSION: The use of TXA may reduce bleeding, however, based on the results of this study, such effect was not statistically significant in controlling the epidural and subdural hemorrhage, but clinical trials with a higher sample size are suggested for further investigation in this regard.

Fibrinolytic Therapy Improves Outcomes in Patients with Epidural Hematomas Following Cranioplasty: A Pilot Study.

BACKGROUND AND STUDY AIMS: Cranioplasty is a cosmetic procedure utilized to reconstruct cranial defects in patients following decompressive craniectomy. Epidural hematomas are a common complication of cranioplasty and often require surgical drainage. However, repeated surgery compromises patient safety and delays recovery. MATERIAL AND METHODS: We investigated the development of epidural hematomas among 131 patients who underwent cranioplasty. Then we explored the efficacy of urokinase (UK) injection for the noninvasive treatment of epidural hematomas. We observed that 15 patients presented with epidural hematoma following cranioplasty. UK (30,000 IU/3 mL) was injected into the hematoma cavity twice every 12 hours in the first postoperative day. Next we closed the subgaleal drain for 1.5 hours and connected it with a negative-pressure ball on full vacuum to allow drainage. Binary logistic regression analysis was used to evaluate the risk factors associated with the development of epidural hematomas. RESULTS: Our findings demonstrated that a sunken skin flap was a risk factor for epidural hematoma formation (p = 0.006). The decrease in epidural hematoma volume was 35.27 ± 7.27 mL in the first 12 hours on postoperative day 1 after UK treatment. All treated patients whose Glasgow Coma Scale score did not significantly change despite the epidural hematoma had an uneventful recovery without additional complications and were discharged from the hospital, except for one patient. CONCLUSION: Fibrinolytic therapy can be considered an optional treatment for postoperative epidural hematoma associated with cranioplasty, especially in patients who refused further operative treatment or who are not optimal candidates for a second surgery.

Novel Minimally Invasive Treatment Strategy for Acute Traumatic Epidural Hematoma: Endovascular Embolization Combined with Drainage Surgery and Use of Urokinase.

BACKGROUND: Hematoma evacuation is regular treatment for acute traumatic epidural hematoma (ATEDH) patients meeting with surgery indications. However, it is an invasive approach performed under general anesthesia. Here, a novel minimally invasive method of endovascular embolization with subsequent drainage surgery and use of urokinase was established to treat ATEDH under local anesthesia. METHODS: A novel minimally invasive method of endovascular embolization with subsequent drainage surgery and use of urokinase was established to treat ATEDH under local anesthesia. Firstly, 23 ATEDH patients with hematomas in the temporal area underwent digital subtraction angiography detecting the bleeding point. Next, embolization was performed. After embolization, drainage surgery was taken and urokinase was injected into the hematoma cyst by drainage tube to lyse hematoma twice per day. RESULTS: The results showed that the middle meningeal artery was the bleeding source. Embolization immediately ceased bleeding. Most clots were resolved and drained after treatment. No recurrence of hematoma or infection was observed. CONCLUSION: The findings suggest that the combined treatments can be an alternative minimally invasive option for ATEDHs, especially for elderly patients or those contraindicated for general anesthesia.

Post-Traumatic Bifrontoparietal Extradural Hematoma with Superior Sagittal Sinus Detachment: A Case Report and Review of the Literature.

OBJECTIVE: To present, to our knowledge, the first case of a single bilateral extradural hematoma due to superior sagittal sinus detachment that was treated conservatively with an excellent outcome. METHODS: Bilateral extradural hematomas are a rare condition, accounting for only 2%-5% of all extradural hematomas. They can be either 2 distinct hematomas on either side or 1 single bilateral hematoma mostly due to sagittal sinus injury, with the latter being the most rare owing to the firm attachment of the sinus to its subperiosteal loggia. These hematomas usually require immediate surgical evacuation, as patients present with decreased level of consciousness, and have good postoperative outcomes. We present a bilateral extradural hematoma due to superior sagittal sinus injury, which was treated conservatively. RESULTS: The patient had an excellent recovery, with no residual neurological deficits and a Glasgow outcome scale of 5 on discharge. CONCLUSION: Bilateral extradural hematomas due to superior sagittal sinus injury almost always require surgical intervention. We present a patient who was treated conservatively with an excellent outcome and we also perform a review of the current literature.

In-hospital mortality after pre-treatment with antiplatelet agents or oral anticoagulants and hematoma evacuation of intracerebral hematomas.

Pre-treatment with antiplatelet agents is described to be a risk factor for mortality after spontaneous intracerebral hemorrhage (ICH). However, the impact of antithrombotic agents on mortality in patients who undergo hematoma evacuation compared to conservatively treated patients with ICH remains controversial. This analysis is based on a prospective registry for quality assurance in stroke care in the State of Hesse, Germany. Patients' data were collected between January 2008 and December 2012. Only patients with the diagnosis of spontaneous ICH were included (International Classification of Diseases 10th Revision codes I61.0-I61.9). Predictors of in-hospital mortality were determined by univariate analysis. Predictors with P<0.1 were included in a binary logistic regression model. The binary logistic regression model was adjusted for age, initial Glasgow Coma Score (GCS), the presence of intraventricular hemorrhage (IVH), and pre-ICH disability prior to ictus. In 8,421 patients with spontaneous ICH, pre-treatment with oral anticoagulants or antiplatelet agents was documented in 16.3% and 25.1%, respectively. Overall in-hospital mortality was 23.2%. In-hospital mortality was decreased in operatively treated patients compared to conservatively treated patients (11.6% versus 24.0%; P<0.001). Patients with antiplatelet pre-treatment had a significantly higher risk of death during the hospital stay after hematoma evacuation (odds ratio [OR]: 2.5; 95% confidence interval [CI]: 1.24-4.97; P=0.010) compared to patients without antiplatelet pre-treatment treatment (OR: 0.9; 95% CI: 0.79-1.09; P=0.376). In conclusion a higher rate of in-hospital mortality after pre-treatment with antiplatelet agents in combination with hematoma evacuation after spontaneous ICH was observed in the presented cohort.

Postoperative Epidural Hematomas in the Lumbar Spine.

Postoperative epidural hematomas are rare complications following lumbar spine surgery, but if they are not quickly identified and treated they can lead to permanent neurological deficits. Epidural hematomas occur in approximately 0.10%-0.24% of all spine surgeries, and despite the fact that multiple large studies have been performed attempting to identify risk factors for this complication, there is still significant debate about the effect of subfascial drains, postoperative anticoagulation, and antiplatelet medication on the incidence of postoperative hematoma. The purpose of this manuscript is to review the epidemiology, etiology, diagnosis, and treatment of patients who develop a postoperative lumbar epidural hematoma.

Effects of timing of dexamethasone treatment on the outcome of collagenase-induced intracerebral hematoma in rats.

The effect of timing in providing dexamethasone treatment after intracerebral hematoma was evaluated in rats with hematoma induced by a subcortical collagenase injection. Male Sprague-Dawley rats (n = 30; body weight, 185 to 230 g) received dexamethasone (1 mg/kg) intraperitoneally at 2 h, 4 h, or 6 h (1 group per time point) after intracerebral collagenase injection, with another dose (1 mg/kg) administered at 24 h after collagenase injection. Neurologic examinations and rotarod treadmill tests were used to evaluate motor behavior before and at 24 and 48 h after intracerebral injection. Rats were euthanized after the last behavioral test. Brains were evaluated for hematoma size, number of penumbral necrotic neurons, neutrophils within the hematoma, and astrocytic response. Compared with the control and other treatment groups, rats treated with dexamethasone at 2 and 24 h after intracerebral collagenase injection scored significantly better on neurologic exams and rotarod tests. Hematoma volume was significantly smaller in all treated groups than in the control group but did not differ between treatment groups. Fewer neutrophils were seen in the perihematoma region of all treated rats compared with controls, but the number of necrotic neurons was decreased significantly only in the group treated with dexamethasone at 2 and 24 h. These results indicate that a 1-mg/kg dose of dexamethasone is beneficial for treatment of intracerebral hemorrhage, particularly if administered early after the hemorrhagic insult.

Management of prehospital antiplatelet and anticoagulant therapy in traumatic head injury: a review.

Trauma and emergency department clinicians encounter a growing number of patients admitted with traumatic head injury on prehospital antithrombotic therapies. These patients appear to be at increased risk of developing life-threatening intracranial hemorrhage. It is imperative that trauma clinicians understand the mechanism and duration of commonly prescribed outpatient antithrombotics in order to appropriately assess and treat patients who develop intracranial hemorrhage. This review summarizes current literature on the morbidity and mortality associated with premorbid non-steroidal anti-inflammatory drugs, aspirin, clopidogrel, warfarin, and heparinoids in the setting of traumatic head injury, and also examines the current strategies for reversal of these therapies.

Recently published papers: Renal replacement therapy: which route and how much? Intracerebral haematomas: does the size matter? Beta blockers and steroids: will we ever know?

Femoral access for renal replacement therapy appears to have a similar infection rate to jugular access. High-intensity renal support does not seem to improve mortality or length of hospital stay. Acute kidney injury as defined by Acute Kidney Injury Network predicts increased hospital mortality. Recombinant factor VIIa reduces growth of volume of intracerebral haematoma but does not affect clinical outcome. Sustained released metoprolol reduces perioperative cardiac events in non-cardiac surgery but leads to more deaths and strokes. Steroids are probably not beneficial in either children with non-Haemophilus influenzae type b bacterial meningitis, or in prophylaxis of acute respiratory distress syndrome (ARDS), but could be beneficial in the treatment of ARDS.

Drilling skull plus injection of urokinase in the treatment of epidural haematoma: a preliminary study.

PRIMARY OBJECTIVE: This study was performed to evaluate the effectiveness of a minimally invasive approach to manage patients with epidural haematoma (EDH). The surgical indication and key points were investigated. RESEARCH DESIGN: Descriptive, retrospective study. METHODS AND PROCEDURES: Twenty-one patients with traumatic EDH were treated through the following method: After anaesthesia, twist drill trepanations were performed followed by a placement of drainage tubes. Twenty ku urokinase in 3 ml saline was injected into the haematoma cyst through the tube, which was closed for 3 hours before connection to a vacuum ball with negative pressure. The injection was repeated three times a day after operation. The fibrinolytic agents were not used in the 'acute group' because of the risk of rebleeding. CT scans were performed according to the changes of clinical manifestations. MAIN OUTCOMES AND RESULTS: The drainage tubes were left for 3-5 days before most clots were resolved. The patients discharged after 7 days' hospitalization on average. No infections or recurrence of EDHs were observed in this series. CONCLUSION: Drilling skull plus injection of urokinase through drainage tube is a safe and effective method with less injury in the treatment of a selected part of patients with EDHs.

Thrombolytic evacuation of post-craniotomy epidural haematomas using closed suction drains: a pilot study.

BACKGROUND: As an effective treatment for post-craniotomy epidural haematomas (EDHs), a novel method of urokinase instillation using a closed suction drain is presented and the procedure feasibility and outcomes assessed. METHOD: A closed system, comprising a closed suction drain with a three-spring 200 mL evacuator, fluid bag with urokinase, and syringe, was constructed to instill urokinase and evacuate a postoperative EDH. Nine patients with a symptomatic, localised EDH under a bone flap after a craniotomy underwent successive urokinase instillation following the proposed protocol. Measurement of the EDH volume and clinical evaluation were performed. FINDINGS: An improvement of computerised tomography findings and clinical state after urokinase instillation was observed in all patients. Six urokinase instillations lasting 12 h in 6 patients with an EDH (18.2 +/- 2.4 mL) and 12 urokinase instillations lasting 24 h in the other 3 patients with an EDH (33.0 +/- 7.9 mL) succeeded in achieving a minimal residual EDH (6.1 +/- 2.8 mL). The EDH volume decreased at a rate of 13.0 +/- 2.3 mL/12 h. The GCS scores increased immediately after thrombolytic evacuation of the EDHs in 6 out of the 9 patients. For the other three patients who did not show a change of GCS score, the severe headaches were improved. All the patients were successfully treated using the proposed technique with no procedural complications such as haemorrhage or infection in the operative wound. CONCLUSIONS: This pilot study demonstrated that thrombolytic evacuation of a post-craniotomy EDH using a closed suction drain is feasible without complications and may be associated with better outcomes.

Survey of management of severe head injury in Canada.

OBJECTIVE: To determine: 1. the degrees of consensus and disagreement among Canadian critical care clinicians regarding the appropriateness (benefit exceeding risk) of common therapeutic manoeuvres in patients with severe closed head injury (CHI), and 2. the frequency with which clinicians employed these manoeuvres. METHODS: The study design was a systematic scenario-based survey of all neurosurgeons and critical care physicians treating patients with severe CHI in Canada. RESULTS: In the scenario of acute epidural hematoma with mass effect, respondents agreed very strongly that surgery was appropriate. Clinicians reported mannitol and hypertonic saline as appropriate. Beyond these two interventions, agreement was less strong, and the use of the extraventricular drain (EVD), phenytoin, cooling, hyperventilation, nimodipine, and jugular venous oximetry (JVO) were of uncertain appropriateness. Steroids were considered inappropriate. In a scenario of diffuse axonal injury (DAI), clinicians agreed strongly that fever reduction, early enteral feeding, intensive glucose control, and cerebral perfusion pressure (CPP)-directed management were appropriate. The use of mannitol, hypertonic saline, EVD, JVO, narcotics and propofol were also appropriate. Neuromuscular blockade, surgery, and hyperventilation were of uncertain appropriateness. The appropriateness ratings of the interventions considered in the scenario of an intracranial contusion mirrored the DAI scenario. In general, correlations between the reported appropriateness and frequency of use of each intervention were very high. An exception noted was the use of the JVO. The correlation between CPP-guided therapy and the use of the EVD was weak. CONCLUSIONS: This survey has described current practice with regard to treatment of patients with severe CHI. Areas of variation in perceived appropriateness were identified that may benefit from further evaluation. Suggested priorities for evaluation include the use of osmotic diuretics, anticonvulsants, and intracranial manometry.

Utilization of recombinant activated factor VII for intracranial hematoma evacuation in coagulopathic nonhemophilic neurosurgical patients with normal international normalized ratios.

BACKGROUND: Recombinant activated Factor VII (rFVIIa) has recently gained popularity for rapid reversal of coagulopathy during operative neurosurgery. Patients undergoing chronic subdural hematoma (CSDH) or epidural hematoma (EDH) evacuation often have their coagulation status judged by preoperative international normalized ratio (INR). We present our experience in two patients with significant clinical coagulopathy who were successfully reversed with rFVIIa in the setting of normal INR. METHODS: Patient one was a 79-year-old man with history of prostate cancer and three previous operative left CSDH evacuations, each complicated by coagulopathic bleeding, who presented with new-onset left EDH. Patient two was a 27-year-old woman with relapsed acute myelogenous leukemia with bilateral CSDH and mass effect on MRI. Neither patient had hemophilia, and preoperative INR was 1.2 in each case. Both patients underwent evacuation in the operating room, preceded by rFVIIa administration. RESULTS: Patient one underwent removal of his previous craniotomy flap followed by EDH evacuation. In patient two, coagulopathic bleeding upon surgical approach necessitated an additional dose of rFVIIa. Burrhole evacuation was well-tolerated with visible brain re-expansion following irrigation. Each case occurred with minimal blood loss and relatively easy hemostasis, with postoperative CT and clinical course revealing adequate evacuation. Neither patient experienced thromboembolic complications or required re-operation. CONCLUSION: These two patients are the first to be examined for the use of rFVIIa for reversal of clinical coagulopathy in the setting of normal INR. Our experience suggests that normal INR should not be a deterrent for patients to receive rFVIIa in the setting of strong neurosurgical suspicion for underlying clinical coagulopathy.

Serum cellular fibronectin and matrix metalloproteinase-9 as screening biomarkers for the prediction of parenchymal hematoma after thrombolytic therapy in acute ischemic stroke: a multicenter confirmatory study.

BACKGROUND AND PURPOSE: Plasma levels of cellular fibronectin (c-Fn) > or =3.6 microg/mL and of matrix metalloproteinase-9 (MMP-9) > or =140 ng/mL have been associated with parenchymal hematoma (PH) after treatment with tissue-type plasminogen activator (t-PA) in patients with acute ischemic stroke. In this prospective study, we sought to validate the predictive capacity of the preestablished cutoff values of these biomarkers for PH in a larger series of patients. METHODS: We studied 134 patients treated with t-PA within 3 hours from symptom onset according to the SITS-MOST criteria (median time to infusion, 152 minutes; median National Institutes of Health Stroke Scale score, 14) in 4 university hospitals. Hemorrhagic transformation was classified according to the European-Australasian Acute Stroke Study II definitions on computed tomography scans performed 24 to 36 hours after treatment. Relevant hemorrhagic transformation was defined as hemorrhagic infarction type 2 or any PH. Serum c-Fn and MMP-9 levels were determined by an ELISA om blood samples obtained before treatment. RESULTS: Cranial computed tomography showed hemorrhagic transformation in 27 patients (20%), hemorrhagic infarction in 15 (type 2 in 8 patients), and PH in 12 patients (symptomatic in 4). Serum c-Fn and MMP-9 concentrations at baseline were significantly higher in patients with relevant hemorrhagic transformation and PH than in those without (all P<0.001). The sensitivity, specificity, and positive and negative predictive values for PH by c-Fn levels > or =3.6 microg/mL were 100%, 60%, 20%, and 100%, respectively, whereas corresponding values were 92%, 74%, 26%, and 99% for MMP-9 levels > or =140 ng/mL. When both biomarkers were at levels above the cutoff points, specificity increased to 87% and the positive predictive value increased to 41%. CONCLUSIONS: This prospective study confirmed the high sensitivity and negative predictive value, with retained good specificity, of c-Fn and MMP-9 for the prediction of PH in patients treated with t-PA. Development of faster analytic methods will prove the applicability of these biomarkers in routine clinical practice.

Hematoma epidural dorsal tras implante de neuroestimulador dorsal / Dorsal epidural hematoma after implantation of a dorsal nerve simulation

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The use of recombinant activated factor VII in three patients with central nervous system hemorrhages associated with factor VII deficiency.

BACKGROUND: Recombinant activated factor VII (rFVIIa) is being tested to improve hemostasis in a variety of bleeding disorders. Clinical indications and efficacy are still being evaluated for this product. CASE REPORT: Over a 17-month period, rFVIIa was used to treat central nervous system hemorrhage in three patients who were found to have isolated FVII deficiency (21%, 40%, 27%). Patient A fell 30 feet, Patient B suffered a motor vehicle accident, and Patient C had a spinal cord hematoma. None of the patients had a history of bleeding diathesis. All three patients received rFVIIa after failing initial treatment with fresh-frozen plasma. RESULTS: Patient A was treated with 11 doses (initial dose 95 microg/kg; subsequent doses 8-38 microg/kg) over 10 days; Patient B received 13 doses (45-60 microg/kg) over 13 days; and Patient C received 5 doses (12-24 microg/kg) over 4 days. The prothrombin time corrected from 16.2 +/- 1.8 (mean +/- SD) to 11.2 +/- 1.6 seconds after infusion of rFVIIa, but returned to pretreatment level in 14 +/- 4 hours. At the cessation of therapy, all patients showed neurologic improvement. No complications related to the infusion of rFVIIa occurred. CONCLUSION: The use of rFVIIa may be of value both for its general effect on hemostasis, and specifically in the setting where there is a documented reduction in FVII. Doses lower than those used in patients with FVIII inhibitors appear to be effective in the setting of central nervous system hemorrhage.