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Hemorrhage in the central nervous system (CNS), including intracerebral hemorrhage (ICH), intraventricular hemorrhage (IVH), and aneurysmal subarachnoid hemorrhage (aSAH), remains highly morbid. Trials of medical management for these conditions over recent decades have been largely unsuccessful in improving outcome and reducing mortality. Beyond its role in creating mass effect, the presence of extravasated blood in patients with CNS hemorrhage is generally overlooked. Since trials of surgical intervention to remove CNS hemorrhage have been generally unsuccessful, the potent neurotoxicity of blood is generally viewed as a basic scientific curiosity rather than a clinically meaningful factor. In this review, we evaluate the direct role of blood as a neurotoxin and its subsequent clinical relevance. We first describe the molecular mechanisms of blood neurotoxicity. We then evaluate the clinical literature that directly relates to the evacuation of CNS hemorrhage. We posit that the efficacy of clot removal is a critical factor in outcome following surgical intervention. Future interventions for CNS hemorrhage should be guided by the principle that blood is exquisitely toxic to the brain.

In cervical traumatic spinal cord injury (TSCI), the therapeutic effect of timing of surgery on neurological recovery remains uncertain. Additionally, the relationship between extent of decompression, imaging biomarker evidence of injury severity, and outcome is incompletely understood. We investigated the effect of timing of decompression on long-term neurological outcome in patients with complete spinal cord decompression confirmed on postoperative magnetic resonance imaging (MRI). American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade conversion was determined in 72 AIS grades A, B, and C patients 6 months after confirmed decompression. Thirty-two patients underwent decompressive surgery ultra-early (< 12 h), 25 underwent decompressive surgery early (12–24 h), and 15 underwent decompressive surgery late (> 24–138.5 h) after injury. Age, gender, injury mechanism, intramedullary lesion length (IMLL) on MRI, admission ASIA motor score, and surgical technique were not statistically different among groups. Motor complete patients (p = 0.009) and those with fracture dislocations (p = 0.01) tended to be operated on earlier. Improvement of one grade or more was present in 55.6% of AIS grade A, 60.9% of AIS grade B, and 86.4% of AIS grade C patients. Admission AIS motor score (p = 0.0004) and pre-operative IMLL (p = 0.00001) were the strongest predictors of neurological outcome. AIS grade improvement occurred in 65.6%, 60%, and 80% of patients who underwent decompression ultra-early, early, and late, respectively (p = 0.424). Multiple regression analysis revealed that IMLL was the only significant variable predictive of AIS grade conversion to a better grade (odds ratio, 0.908; confidence interval [CI], 0.862–0.957; p < 0.001). We conclude that in patients with post-operative MRI confirmation of complete decompression following cervical TSCI, pre-operative IMLL, not the timing of surgery, determines long-term neurological outcome.

A growing body of clinical literature emphasizes the impact of cerebral edema in early brain injury following aneurysmal subarachnoid hemorrhage (aSAH). Aneurysm rupture itself initiates global cerebral edema in up to two thirds of cases. Although cerebral edema is not a universal feature of aSAH, it portends a poor clinical course, with quantitative analysis revealing a direct correlation between cerebral edema and poor outcome, including mortality and cognitive deficits. Mechanistically, global cerebral edema has been linked to global ischemia at the time of aneurysm rupture, dysfunction of autoregulation, blood breakdown products, neuroinflammation, and hyponatremia/endocrine abnormalities. At a molecular level, several culprits have been identified, including aquaporin-4, matrix metalloproteinase-9, SUR1-TRPM4 cation channels, vascular endothelial growth factor, bradykinin, and others. Here, we review these cellular and molecular mechanisms of global cerebral edema formation in aSAH. Given the importance of edema to the outcome of patients with aSAH and its status as a highly modifiable pathological process, a better understanding of cerebral edema in aSAH promises to hasten the development of medical therapies to improve outcomes in this frequently devastating disease.

Abstract BACKGROUND Patients who survive aneurysmal subarachnoid hemorrhage (aSAH) are at risk for delayed neurological deficits (DND) and cerebral infarction. In this exploratory cohort comparison analysis, we compared in-hospital outcomes of aSAH patients administered a low-dose intravenous heparin (LDIVH) infusion (12 U/kg/h) vs those administered standard subcutaneous heparin (SQH) prophylaxis for deep vein thrombosis (DVT; 5000 U, 3 × daily). OBJECTIVE To assess the safety and efficacy of LDIVH in aSAH patients. METHODS We retrospectively analyzed 556 consecutive cases of aSAH patients whose aneurysm was secured by clipping or coiling at a single institution over a 10-yr period, including 233 administered the LDIVH protocol and 323 administered the SQH protocol. Radiological and outcome data were compared between the 2 cohorts using multivariable logistic regression and propensity score-based inverse probability of treatment weighting (IPTW). RESULTS The unadjusted rate of cerebral infarction in the LDIVH cohort was half that in SQH cohort (9 vs 18%; P = .004). Multivariable logistic regression showed that patients in the LDIVH cohort were significantly less likely than those in the SQH cohort to have DND (odds ratio (OR) 0.53 [95% CI: 0.33, 0.85]) or cerebral infarction (OR 0.40 [95% CI: 0.23, 0.71]). Analysis following IPTW showed similar results. Rates of hemorrhagic complications, heparin-induced thrombocytopenia and DVT were not different between cohorts. CONCLUSION This cohort comparison analysis suggests that LDIVH infusion may favorably influence the outcome of patients after aSAH. Prospective studies are required to further assess the benefit of LDIVH infusion in patients with aSAH.

Abstract BACKGROUND Subarachnoid hemorrhage (SAH) is most commonly caused by a ruptured vascular lesion. A significant number of patients presenting with SAH have no identifiable cause despite extensive cerebrovascular imaging at presentation. Significant neurological morbidity or mortality can result from misdiagnosis of aneurysm. OBJECTIVE To generate a model to assist in predicting the risk of aneurysm in this patient population. METHODS We conducted a retrospective study of all patients aged ≥18 yr admitted to a single center from March 2008 to March 2018 with nontraumatic SAH (n = 550). Patient information was compared between those with and without aneurysm to identify potential predictors. Odds ratios obtained from a logistic regression model were converted into scores which were summed and tested for predictive ability. RESULTS Female sex, higher modified Fisher or Hijdra score, nonperimesencephalic location, presence of intracerebral hemorrhage, World Federation of Neurosurgical Societies (WFNS) score ≥3, need for cerebrospinal fluid diversion on admission, and history of tobacco use were all entered into multivariable analysis. Greater modified Fisher, greater Hijdra score, WFNS ≥3, and hydrocephalus present on admission were significantly associated with the presence of an aneurysm. A model based on the Hijdra score and SAH location was generated and validated. CONCLUSION We show for the first time that the Hijdra score, in addition to other factors, may assist in identifying patients at risk for aneurysm on cerebrovascular imaging. A simple scoring tool based on patient sex, SAH location, and SAH burden can assist in predicting the presence of an aneurysm in patients with nontraumatic SAH.

BackgroundThe first pass effect has been recently reported as a predictor of good clinical outcome after stroke thrombectomy. We evaluate the first pass effect on outcome and the influence of revascularization in these and other patients.MethodsWe performed a retrospective analysis of a prospectively maintained database on anterior cerebral circulation stroke thrombectomy cases from April 2012 to April 2018. Data compiled included patient demographics, presenting National Institutes of Health Stroke Scale score, vessel occlusion site, thrombectomy procedural details, and 90 day modified Rankin Scale scores.Results205 patients were included. The numbers of patients who underwent one, two, three, four, five, and six passes were 69, 70, 55, 9, 1, and 1, respectively. Successful revascularization was achieved in 87%, 83%, and 64% of patients in the one, two, and 3 or more passes groups, respectively (p=0.002). Good functional outcome was inversely correlated with number of passes when comparing the one, two, and three or more passes groups (54%, 43%, 29%; P=0.014). In patients with full revascularization, there was no significant difference in good functional outcomes between the one, two, and three or more passes groups (64%, 65%, 50%; P=0.432). Number of passes was not an independent negative predictor of good clinical outcome (OR 1.66, 95% CI 0.82 to 3.39; P=0.165).ConclusionsFirst pass thrombectomy patients have better functional outcomes compared with beyond-first pass patients. This effect is related at least in part to a higher rate of revascularization in one pass patients. Revascularization beyond the first pass should continue to be the goal of stroke thrombectomy.

ObjectiveFlow diversion using the Pipeline embolization device (PED) has become a widely used treatment method for intracranial aneurysms. However, a subset of aneurysms will fail to occlude following treatment and the factors that influence the efficacy of flow diversion remain uncertain. As smaller diameter PEDs inherently have greater metal density than larger devices, we elected to investigate whether PED diameter influences treatment efficacy when using a single device. We also evaluated other factors that may influence treatment outcomes with PED.MethodsWe retrospectively evaluated all patients treated for an intracranial saccular aneurysm at our institution with a single PED at least 12 months prior to the time of data collection. Patients treated with multiple devices, adjunctive coiling, traumatic and fusiform target aneurysms, as well as patients with inadequate imaging follow-up (<12 months) were excluded.Results158 aneurysms in 124 patients (128 treatments) met the inclusion criteria for our study. 123 aneurysms (80%) were occluded over an average follow-up of 26.6 months. Multivariable logistic regression showed that branch vessel incorporation into the target aneurysm sac (p<0.001, OR=0.15) was significantly associated with aneurysm persistence, while smaller PED diameter was significantly associated with aneurysm occlusion (p=0.008; OR=0.30).ConclusionsPED diameter significantly impacts outcomes when using a single device for the treatment of small anterior circulation intracranial saccular aneurysms, most likely due to the inherent greater metal density of smaller devices. This factor should be taken into account when planning endovascular aneurysm treatment with PED.

Patients with spontaneous intracranial hemorrhage (sICH) are associated with high mortality and require early neurosurgical interventions. At our academic referral center, the neurocritical care unit (NCCU) receives patients directly from referring facilities. However, when no NCCU bed is immediately available, patients are initially admitted to the critical care resuscitation unit (CCRU). We hypothesized that the CCRU expedites transfer of sICH patients and facilitates timely external ventricular drain (EVD) placement comparable to the NCCU. This is a pre-post study of adult patients transferred with sICH and EVD placement. Patients admitted between January 2011-July 2013 (2011 Control) were compared with patients admitted either to the CCRU or the NCCU (2013 Control) between August 2013-September 2015. The primary outcome was time interval from arrival at any intensive care units (ICU) to time of EVD placement (ARR-EVD). Secondary outcomes included time interval from emergency department transfer request to arrival, and in-hospital mortality. We assessed clinical association by multivariable logistic regressions. We analyzed 259 sICH patients who received EVDs: 123 (48%) CCRU; 81 (31%) 2011 Control; and 55 (21%) in the 2013 Control. The groups had similar characteristics, age, disease severity, and mortality. Median ARR-EVD time was 170 minutes [106-311] for CCRU patients; 241 minutes [152-490] (p < 0.01) for 2011 Control; and 210 minutes [139-574], p = 0.28) for 2013 Control. Median transfer request-arrival time for CCRU patients was significantly less than both control groups. Multivariable logistic regression showed each minute delay in ARR-EVD was associated with 0.03% increased likelihood of death (odds ratio 1.0003, 95% confidence interval, 1.0001-1.006, p = 0.043). Patients admitted to the CCRU had shorter transfer times when compared to patients admitted directly to other ICUs. Compared to the specialty NCCU, the CCRU had similar time interval from arrival to EVD placement. A resuscitation unit like the CCRU can complement the specialty unit NCCU in caring for patients with sICH who require EVDs.

Background: Spontaneous intracranial hemorrhage (sICH) is associated with high mortality. Little information exists to guide initial resuscitation in the emergency department (ED) setting. However, blood pressure variability (BPV) and mechanical ventilation (MV) are known risk factors for poor outcome in sICH. Objectives: The objective was to examine the associations between BPV and MV in ED (EDMV) and between two ED interventions - post-MV sedation and hyperosmolar therapy for elevated intracranial pressure - and BPV in the ED and in-hospital mortality. Methods: We retrospectively studied adults with sICH and external ventricular drainage who were transferred to a quaternary academic medical center from other hospitals between January 2011 and September 2015. We used multivariable linear and logistic regressions to measure associations between clinical factors, BPV, and outcomes. Results: We analyzed ED records from 259 patients. There were 143 (55%) EDMV patients who had more severe clinical factors and significantly higher values of all BPV indices than NoEDMV patients. Two clinical factors and none of the severity scores (i.e., Hunt and Hess, World Federation of Neurological Surgeons Grades, ICH score) correlated with BPV. Hyperosmolarity therapy without fluid resuscitation positively correlated with all BPV indices, whereas propofol infusion plus a narcotic negatively correlated with one of them. Two BPV indices, i.e., successive variation of blood pressure (BPSV) and absolute difference in blood pressure between ED triage and departure (BPDepart − Triage), were significantly associated with increased mortality rate. Conclusion: Patients receiving MV had significantly higher BPV, perhaps related to disease severity. Good ED sedation, hyperosmolar therapy, and fluid resuscitation were associated with less BPV and lower likelihood of death.

Background The authors present a case of cervical myelopathy and radiculopathy in the setting of multiple Klippel-Feil syndrome abnormalities treated surgically with a single-level C3–C4 anterior cervical discectomy and fusion. We discuss the clinical presentation, radiographic findings, and various treatment options for cervical spine abnormalities in Klippel-Feil syndrome. Case Presentation This 22-year-old female with Klippel-Feil syndrome presented with intermittent neck pain, left upper extremity weakness, and paresthesias. Preoperative MRI, CT, and X-rays of the cervical spine revealed anterolisthesis at C3/4 with unstable movement on flexion and extension imaging. In addition, there were multiple segmental fusion abnormalities including hemivertebrae and other congenital fusion abnormalities. A C3–C4 anterior cervical discectomy and fusion was performed with intervertebral disc spacer. Adequate decompression was achieved with postoperative resolution of the patient’s symptoms and improvement in neurological exam. Conclusions Single-level anterior cervical discectomy and fusion can be utilized for treatment of cervical myelopathy and radiculopathy in the setting of multiple congenital Klippel-Feil syndrome abnormalities.