Global Cerebral Edema Research Articles

Systematic assessment of early brain injury severity at admission with aneurysmal subarachnoid hemorrhage

Early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH) has been increasingly recognized as a risk factor for delayed cerebral ischemia (DCI). While several clinical and radiological EBI biomarkers have been identified, no tool for systematic assessment of EBI severity has been established so far. This study aimed to develop an EBI grading system based on clinical signs and neuroimaging for estimation of EBI severity at admission. This is a retrospective observational study assessing imaging parameters (intracranial blood amount, global cerebral edema (GCE)), and clinical signs (persistent loss of consciousness [LOC]) representative for EBI. The intracranial blood amount was semi-quantitatively assessed. One point was added for GCE and LOC, respectively. All points were summed up resulting in an EBI grading ranging from 1 to 5. The estimated EBI severity was correlated with progressive GCE requiring decompressive hemicraniectomy (DHC), DCI-associated infarction, and outcome according to the modified Rankin scale (mRS) at 3-month-follow up. A consecutive cohort including 324 aSAH-patients with a mean age of 55.9 years, was analyzed. The probability of developing progressive GCE was 9% for EBI grade 1, 28% for EBI grade 2, 43% for EBI grade 3, 61% for EBI grade 4, and 89% for EBI grade 5. The EBI grading correlated significantly with the need for DHC (r = 0.25, p < 0.0001), delayed infarction (r = 0.30, p < 0.0001), and outcome (r = 0.31, p < 0.0001). An EBI grading based on clinical and imaging parameters allowed an early systematic estimation of EBI severity with a higher EBI grade associated not only with a progressive GCE but also with DCI and poor outcome.

Identifying the Preoperative Radiological Risk Features in Patients with Leptomeningeal Carcinomatosis Undergoing Cerebrospinal Fluid Drainage

Patients with leptomeningeal carcinomatosis (LMC) experience a poor prognosis and rapid progression, and cerebrospinal fluid drainage (CSFD) is used to manage intracranial hypertension and hydrocephalus in LMC patients. This study aims to describe a novel discovery of preoperative radiological features in patients who underwent CSFD for LMC. A retrospective review was conducted during the past 5 years of LMC patients with intracranial hypertension and hydrocephalus who underwent CSFD. We evaluated the patients' preoperative radiological features, clinical characteristics, and survival times. A total of 36 patients were included. Of the 36 patients, 34 underwent ventriculoperitoneal shunting, and 2 patients underwent only external ventricular drainage due to rapid progression. The median preoperative Karnofsky performance scale score was 40.0 (interquartile range [IQR], 20.0-40.0). The median survival time after surgery was 5 months (IQR, 0.00-10.43 months). Of the 36 patients, 24 (66.7%) had supratentorial cerebral edema before surgery, including 14 patients (38.9%) with features of disproportionately enlarged subarachnoid space hydrocephalus (DESH). Four patients (11.1%) exhibited cerebellar swelling and had a median survival time of 0.27 month (IQR, 0.00-0.56 month). Nine patients (25%) have enhancement lesions on the cerebellum. The survival curve analysis shows that patients with features of cerebellar enhancement have shorter survival times than other patients. Patients with DESH features have longer survival times compared with those with global cerebral edema. Patients with radiological features of cerebellar enhancement have shorter postoperative survival than other patients; however, those with supratentorial cerebral edema, especially features of DESH, could benefit from CSFD. Patients with cerebellar swelling should avoid undergoing CSFD.

Hemorrhage Volume Drives Early Brain Injury and Outcome in Poor-Grade Aneurysmal SAH.

Early brain injury is a major determinant of clinical outcome in poor-grade (World Federation of Neurosurgical Societies [WFNS] IV-V) aneurysmal SAH and is radiologically defined by global cerebral edema. Little is known, though, about the effect of global intracranial hemorrhage volume on early brain injury development and clinical outcome. Data from the multicentric prospective Poor-Grade Aneurysmal Subarachnoid Hemorrhage (POGASH) Registry of consecutive patients with poor-grade aneurysmal SAH admitted from January 1, 2015, to August 31, 2022, was retrospectively evaluated. Poor grade was defined according to the worst-pretreatment WFNS grade. Global intracranial hemorrhage volume as well as the volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH were calculated by means of analytic software in a semiautomated setting. Outcomes included severe global cerebral edema (defined by Subarachnoid Hemorrhage Early Brain Edema Score grades 3-4), in-hospital mortality (mRS 6), and functional independence (mRS 0-2) at follow-up. Among 400 patients (median global intracranial hemorrhage volume of 91 mL; interquartile range, 59-128), severe global cerebral edema was detected in 218/400 (54.5%) patients. One hundred twenty-three (30.8%) patients died during the acute phase of hospitalization. One hundred fifty-five (38.8%) patients achieved mRS 0-2 at a median of 13 (interquartile range, 3-26) months of follow-up. Multivariable analyses showed global intracranial hemorrhage volume as independently associated with severe global cerebral edema (adjusted OR, 1.009; 95% CI, 1.004-1.014; P < .001), mortality (adjusted OR, 1.006; 95% CI, 1.001-1.01; P = .018) and worse clinical outcome (adjusted OR, 0.992; 95% CI, 0.98-0.996; P < .010). The effect of global intracranial hemorrhage volume on clinical-radiologic outcomes changed significantly according to different age groups (younger than 50, 50-70, older than 70 year of age). Volumes of intracerebral hemorrhage, intraventricular hemorrhage, and SAH affected the 3 predefined outcomes differently. Intracerebral hemorrhage volume independently predicted global cerebral edema and long-term outcome, intraventricular hemorrhage volume predicted mortality and long-term outcome, and SAH volume predicted long-term clinical outcome. Global intracranial hemorrhage volume plays a pivotal role in global cerebral edema development and emerged as an independent predictor of both mortality and long-term clinical outcome. Aging emerged as a reducing predictor in the relationship between global intracranial hemorrhage volume and global cerebral edema.

Lower Serum Iron Level Predicts Postoperative Global Cerebral Edema Following Aneurysmal Subarachnoid Hemorrhage.

Iron plays an important role in neuronal injury and edema formation after intracranial hemorrhage. However, the role of serum iron in aneurysmal subarachnoid hemorrhage (aSAH) is yet to be well-established. This study aims to identify whether serum iron could predict postoperative global cerebral edema (GCE) and poor outcome in aSAH. 847 patients' aSAH clinical data were retrospectively collected at the First Affiliated Hospital of Fujian Medical University. Data on demographics, clinical characteristics, and laboratory values were collected and analyzed through univariate and multivariate analyses. Propensity score matching (PSM) analysis was performed to balance the baseline differences between the groups. The incidence of high-grade global cerebral edema (H-GCE) following aSAH was 12.99% (110/847). Serum iron levels [odds ratio (OR) = 1.143; 95% confidence interval (CI), (1.097-1.191); p < 0.001] were associated with the occurrence of H-GCE following aSAH in the univariate analysis. This association remained statistically significant even after adjusting for other variables in the multivariate model, with serum iron having an OR of 1.091 (95% CI, 1.043-1.141; p < 0.001) for GCE. After 1:1 PSM, serum iron levels ≤ 10.7 µmol/L remained a significant independent predictor of GCE (p = 0.002). The receiver operating characteristic (ROC) curve analysis determined that a serum iron cut-off value of ≤ 10.7 µmol/L was optimal for predicting H-GCE [Areas under the ROC curves (AUC) = 0.701, 95% CI, (0.669-0.732), p < 0.001; sensitivity, 67.27%; specificity, 63.77%] in patients with aSAH. Additionally, a trend was observed in which higher Hunt-Hess grades (HH grade) were associated with lower serum iron levels, and higher modified Fisher grades (mFisher grade) were associated with lower serum iron levels. In addition, the serum iron level was also associated with a 3-month functional neurological outcome (p < 0.001). The results of this study indicate that a decreased serum iron level serves as a clinically significant biomarker for the prediction of postoperative GCE and a poor outcome at 3-months in patients with aSAH.

Associations between clinical characteristics of cardiac arrest and early CT head findings of hypoxic ischaemic brain injury following out-of-hospital cardiac arrest

Background/ObjectivePost-cardiac arrest patients are vulnerable to hypoxic-ischaemic brain injury (HIBI), but HIBI may not be identified until computed tomography (CT) scan of the brain is obtained post-resuscitation and stabilization. We aimed to evaluate the association of clinical arrest characteristics with early CT findings of HIBI to identify those at the highest risk for HIBI. MethodsThis is a retrospective analysis of out-of-hospital cardiac arrest (OHCA) patients who underwent whole-body imaging. Head CT reports were analyzed with an emphasis on findings suggestive of HIBI; HIBI was present if any of the following were noted on the neuroradiologist read: global cerebral oedema, sulcal effacement, blurred grey-white junction, and ventricular compression. The primary exposure was duration of cardiac arrest. Secondary exposures included age, cardiac vs noncardiac etiology, and witnessed vs unwitnessed arrest. The primary outcome was CT findings of HIBI. ResultsA total of 180 patients (average age 54 years, 32% female, 71% White, 53% witnessed arrest, 32% cardiac etiology of arrest, mean CPR duration of 15 ± 10 minutes) were included in this analysis. CT findings of HIBI were seen in 47 (48.3%) patients. Multivariate logistic regression demonstrated a significant association between CPR duration and HIBI (adjusted OR = 1.1, 95% CI 1.01–1.11, p < 0.01). ConclusionSigns of HIBI are commonly seen on CT head within 6 hours of OHCA, occurring in approximately half of patients, and are associated with CPR duration. Determining risk factors for abnormal CT findings can help clinically identify patients at higher risk for HIBI and target interventions appropriately.

Acute Paraparesis Syndrome after a Ruptured Aneurysm of the Azygos Anterior Cerebral Artery (P12-5.016)

<h3>Objective:</h3> To describe a rare case of acute paraparesis syndrome (APS) after a ruptured aneurysm of the azygos anterior cerebral artery (ACA). <h3>Background:</h3> The incidence of APS within 24 hours after subarachnoid hemorrhage is very rare. Additionally, the pathophysiology of this syndrome remains poorly defined. Nonetheless, the literature suggests it could emerge from a bilateral ACA vasospasm, acute hydrocephalus, or global cerebral edema and can be associated with poor clinical status. The azygos ACA is a rare variant whose unique anatomy intensifies the hemodynamic stress on the arterial wall, making aneurysm formation closely associated with this anomaly. <h3>Design/Methods:</h3> A 72-year-old man with a past medical history of hypertension presented to the hospital with the complaint of acute paraparesis after a thunderclap headache and transitory loss of consciousness. The physical exam showed paraparesis with brisk patellar and Achilles reflexes and a neutral response to bilateral plantar stimulation. No abnormalities were noticed on the cranial nerves, coordination, and sensory examination. <h3>Results:</h3> Routine laboratory studies were normal. Brain computed tomography revealed an acute punctate hemorrhage of an aneurysm located in the frontal interhemispheric fissure. Magnetic Resonance Imaging (MRI) of the spine was unremarkable. Brain MRI showed unspecific white matter abnormalities, and an MR angiography showed a 4.3 mm saccular aneurysm in the right ACA A3 segment in the bifurcation of an azygos ACA. The patient underwent coiling of the aneurysm and was able to walk unassisted nine weeks after the procedure. <h3>Conclusions:</h3> Acute paraparesis syndrome is a rare manifestation of a ruptured anterior communicating artery or anterior cerebral artery aneurysm. Here, we present an atypical etiology of APS caused by a ruptured aneurysm of the azygos ACA. To the best of our knowledge, this is the first description of an APS after a ruptured aneurysm of the azygos ACA. <b>Disclosure:</b> Dr. Moreno-Zambrano has nothing to disclose. Dr. Jimenez Zambrano has nothing to disclose. Jose Francisco Ortega Tola, MD has nothing to disclose. Dr. Yepez has nothing to disclose. Wilson Cueva has nothing to disclose.

Peripheral eosinophil trends and clinical outcomes after non-traumatic subarachnoid hemorrhage.

Uncontrolled systemic inflammation after non-traumatic subarachnoid hemorrhage (SAH) is associated with worse outcomes. Changes in the peripheral eosinophil count have been linked to worse clinical outcomes after ischemic stroke, intracerebral hemorrhage, and traumatic brain injury. We aimed to investigate the association of eosinophil counts with clinical outcomes after SAH. This retrospective observational study included patients with SAH admitted from January 2009 to July 2016. Variables included demographics, modified Fisher scale (mFS), Hunt-Hess Scale (HHS), global cerebral edema (GCE), and the presence of any infection. Peripheral eosinophil counts were examined as part of routine clinical care on admission and daily for 10 days after aneurysmal rupture. Outcome measures included dichotomized discharge mortality, modified Ranked Scale (mRS) score, delayed cerebral ischemia (DCI), vasospasm, and need for ventriculoperitoneal shunt (VPS). Statistical tests included the chi-square test, Student's t-test, and multivariable logistic regression (MLR) model. A total of 451 patients were included. The median age was 54 (IQR 45, 63) years, and 295 (65.4%) were female patients. On admission, 95 patients (21.1%) had a high HHS (>4), and 54 (12.0%) had GCE. A total of 110 (24.4%) patients had angiographic vasospasm, 88 (19.5%) developed DCI, 126 (27.9%) had an infection during hospitalization, and 56 (12.4%) required VPS. Eosinophil counts increased and peaked on days 8-10. Higher eosinophil counts on days 3-5 and day 8 were seen in patients with GCE (p < 0.05). Higher eosinophil counts on days 7-9 (p < 0.05) occurred in patients with poor discharge functional outcomes. In multivariable logistic regression models, higher day 8 eosinophil count was independently associated with worse discharge mRS (OR 6.72 [95% CI 1.27, 40.4], p = 0.03). This study demonstrated that a delayed increase in eosinophils after SAH occurs and may contribute to functional outcomes. The mechanism of this effect and the relationship with SAH pathophysiology merit further investigation.

Sedation protocols in non-traumatic SAH (SPRINT-SAH): A cross-sectional survey among German-speaking neurointensivists.

In subarachnoid hemorrhage (SAH), titrating sedation to find a balance between wakefulness with the ability to perform valid clinical examinations on the one hand, and deep sedation to minimize secondary brain damage, on the other hand, is challenging. However, data on this topic are scarce, and current guidelines do not provide recommendations for sedation protocols in SAH. We designed a web-based, cross-sectional survey for German-speaking neurointensivists to map current standards for the indication and monitoring of sedation, duration of prolonged sedation, and biomarkers for the withdrawal of sedation. Overall, 17.4% (37/213) of neurointensivists answered the questionnaire. Most of the participants were neurologists (54.1%, 20/37) and exhibited a long-standing experience in intensive care medicine (14.9 years, SD 8.3). Among indications for prolonged sedation in SAH, the control of intracranial pressure (ICP) (94.6%) and status epilepticus (91.9%) were most significant. With regard to further complications in the course of the disease, therapy refractory ICP (45.9%, 17/37) and radiographic surrogates of elevated ICP, such as parenchymal swelling (35.1%, 13/37), were the most relevant topics for experts. Regular awakening trials were performed by 62.2% of neurointensivists (23/37). All participants used clinical examination for the therapeutic monitoring of sedation depth. A total of 83.8% of neurointensivists (31/37) used methods based on electroencephalography. As a mean duration of sedation before attempting an awakening trial in patients with unfavorable biomarkers, neurointensivists suggested 4.5 days (SD 1.8) for good-grade SAH and 5.6 days (SD 2.8) for poor-grade SAH, respectively. Many experts performed cranial imaging before the definite withdrawal of sedation [84.6% (22/26)], and 63.6% (14/22) of the participants required an absence of herniation, space-occupying lesions, or global cerebral edema. The values of ICP tolerated for definite withdrawal were smaller compared to that of awakening trials (17.3 mmHg vs. 22.1 mmHg), and patients were required to stay below the threshold value for several hours (21.3 h, SD 10.7). Despite the paucity of clear recommendations for sedation management in SAH in the pre-existing literature, we found some level of agreement indicating clinical efficacy for certain clinical practices. By mapping the current standard, this survey may help to identify controversial aspects in the clinical care of SAH and thereby streamline future research.

Poor Accuracy of Manually Derived Head Computed Tomography Parameters in Predicting Intracranial Hypertension After Nontraumatic Intracranial Hemorrhage.

The utility of head computed tomography (CT) in predicting elevated intracranial pressure (ICP) is known to be limited in traumatic brain injury; however, few data exist in patients with spontaneous intracranial hemorrhage. We conducted a retrospective review of prospectively collected data in patients with nontraumatic intracranial hemorrhage (subarachnoid hemorrhage [SAH] or intraparenchymal hemorrhage [IPH]) who underwent external ventricular drain (EVD) placement. Head CT scans performed immediately prior to EVD placement were quantitatively reviewed for features suggestive of elevated ICP, including temporal horn diameter, bicaudate index, basal cistern effacement, midline shift, and global cerebral edema. The modified Fisher score (mFS), intraventricular hemorrhage score, and IPH volume were also measured, as applicable. We calculated the accuracy, positive predictive value (PPV), and negative predictive value (NPV) of these radiographic features for the coprimary outcomes of elevated ICP (> 20mm Hg) at the time of EVD placement and at any time during the hospital stay. Multivariable backward stepwise logistic regression analysis was performed to identify significant radiographic factors associated with elevated ICP. Of 608 patients with intracranial hemorrhages enrolled during the study time frame, 243 (40%) received an EVD and 165 (n = 107 SAH, n = 58 IPH) had a preplacement head CT scan available for rating. Elevated opening pressure and elevated ICP during hospitalization were recorded in 48 of 152 (29%) and 103 of 165 (62%), respectively. The presence of ≥ 1 radiographic feature had only 32% accuracy for identifying elevated opening pressure (PPV 30%, NPV 58%, area under the curve [AUC] 0.537, 95% asymptotic confidence interval [CI] 0.436-0.637, P = 0.466) and 59% accuracy for predicting elevated ICP during hospitalization (PPV 63%, NPV 40%, AUC 0.514, 95% asymptotic CI 0.391-0.638, P = 0.820). There was no significant association between the number of radiographic features and ICP elevation. Head CT scans without any features suggestive of elevated ICP occurred in 25 of 165 (15%) patients. However, 10 of 25 (40%) of these patients had elevated opening pressure, and 15 of 25 (60%) had elevated ICP during their hospital stay. In multivariable models, mFS (adjusted odds ratio [aOR] 1.36, 95% CI 1.10-1.68) and global cerebral edema (aOR 2.93, 95% CI 1.27-6.75) were significantly associated with elevated ICP; however, their accuracies were only 69% and 60%, respectively. All other individual radiographic features had accuracies between 38 and 58% for identifying intracranial hypertension. More than 50% of patients with spontaneous intracranial hemorrhage without radiographic features suggestive of elevated ICP actually had ICP > 20mm Hg during EVD placement or their hospital stay. Morphological head CT findings were only 32% and 59% accurate in identifying elevated opening pressure and ICP elevation during hospitalization, respectively.

489: CEREBRAL VASCULOPATHY-ASSOCIATED ISCHEMIC STROKE IN THE SETTING OF BACTERIAL MENINGITIS

Introduction: Bacterial Meningitis is known to have high morbidity and mortality rates. A less recognized complication from this disease includes acute ischemic stroke, which conveys a worse prognosis. Description: A 37-year-old previously healthy woman presented to the hospital with progressive encephalopathy associated with ataxia and dysarthria. Her immediate past travel history revealed a trip to Europe where she endured a COVID19 infection three weeks before her admission. Nevertheless, she recovered without any complications. However, she developed fatigue and headaches, prompting a diagnosis of post-COVID19 syndrome by her primary care physician. Over the course of several days, her ability to carry out her normal daily activities and perform work-related duties deteriorated as she developed severe fatigue accompanied by a painless diffuse skin rash. She presented to the ED once she started having symptoms of dysarthria, abasia, and truncal ataxia. An emergently obtained CSF sample was consistent with bacterial meningitis. Standard empiric antibiotics and steroids were administered. The patient’s condition acutely decompensated soon after antibiotics administration. A follow-up head CT showed global cerebral edema and hydrocephalus, triggering an EVD placement for ICP monitoring. An MRI brain showed multiple bilateral acute ischemic strokes in the brainstem and basal ganglia. A head CT angiography showed diffuse narrowing of the cerebral arteries. The patient ultimately completed a course of antibiotics (Neisseria PCR was positive). We used TCD-guided blood pressure augmentation to prevent the progression of cerebral ischemia. The patient was discharged on long-term steroid therapy for presumed post-infectious vasculopathy. A follow-up MRI brain did not reveal a progression of cerebral ischemia. Discussion: Bacterial Meningitis is a severe disease with significant complications. One such complication is ischemic stroke. However, the exact pathophysiology is unknown. Understanding the risks of developing cerebral ischemia and the related pathophysiology could help improve patient outcomes with better treatment modalities. The interplay between COVID19 infection and conventional infectious pathogens is an ongoing area of interest.

Novel technique for ventriculoperitoneal shunt placement using a neurointerventional biplanar fluoroscopy suite: a technical note

BackgroundShunt dependent hydrocephalus is an increasingly common pathology in contemporary neurosurgery. While effective, ventriculoperitoneal shunt systems (VPS) carry a high rate of failure, most commonly secondary to proximal catheter failure and inaccurate placement has been cited an independent predictor of revision surgery. In this technical note, we describe a novel method of VPS placement in a hybrid operating room equipped with biplanar fluoroscopy with 3D-fluoroscopy capabilities to ensure appropriate proximal and distal catheter placements intraoperatively. MethodsA 27-year-old male with Human Immunodeficiency Virus and recently placed left parietooccipital VPS for cryptococcal meningitis presented to our facility with global cerebral edema with slit like ventricles. A right frontal VPS with intraoperative imaging in our hybrid operating room equipped with a Philips Azurion biplane unit (Philips, Amsterdam, Netherlands) was planned. ResultsA standard right frontal VPS was conducted under neuronavigation with open distal catheter placement. Following ventricular catheter insertion, spontaneous cerebrospinal fluid (CSF) return slowed significantly prompting concern for malposition. 3D-fluoro was performed using the biplane machine, confirming accurate placement of the proximal catheter about the foramen of Monroe. Plain static fluoroscopic images were then acquired to confirm the placement and integrity of the distal catheter. The patient had a non-complicated post-operative course and experienced total symptom resolution. ConclusionsProximal and distal catheter shunt failure secondary to malposition remains a significant etiology for revision in contemporary image guided neurosurgery. Biplanar fluoroscopic intraoperative confirmation may provide an efficient and effective modality in CSF diversion. Continued experience is necessary to validate our report.

Acute paraparesis syndrome after ruptured anterior communicating artery aneurysm.

Here, we describe a series of 7 patients who presented with acute paraparesis due to anterior communicating artery aneurysm rupture. This study aimed to assess the clinical and radiological factors associated with acute paraparesis syndrome caused by subarachnoid hemorrhage (SAH).Between June 2005 and December 2012, our institution consecutively treated 210 patients with anterior communicating aneurysm rupture within 24 hours after ictus. We divided the patients into 2 groups based on the presence (n = 7) and absence (n = 203) of acute paraparesis after anterior communicating aneurysm rupture.Diffusion-weighted magnetic resonance imaging revealed high intensity in the medial aspects of the bilateral frontal lobes in 3 patients. The mean third ventricular distance at the time of admission was 9.2 mm (range, 8–12.5 mm), and the mean bicaudate distance was 33.9 mm (range, 24–39 mm). There was a significant difference in the bicaudate distance (P = .001) and third ventricle distance (P = .001) between the 2 groups. Acute hydrocephalus and global cerebral edema (GCE) were confirmed radiologically in all patients in the acute paraparesis group. The presence of acute hydrocephalus (P = .001) and GCE (P = .003) were significantly different between the groups.Acute paraparesis syndrome after SAH is transient and gradually improves if the patient does not develop severe vasospasm. The present study demonstrates that acute paraparesis after SAH is associated with acute hydrocephalus and GCE.

Prospective Analysis of Cerebral Edema Admission and Clinical Outcome in Ruptured Intracranial Aneurysm.

To evaluate the association between global cerebral edema (GCE) after subarachnoid hemorrhage (SAH) and its impact on functional outcome evaluated by the modified Rankin scale (mRS). This is a prospective cohort study with patients who were admitted to the hospital due to SAH. During the period from January 2018 to November 2019, 107 patients with intracranial aneurysms were enrolled. Using univariate and multivariate analysis, we sought to identify predictors and evaluated the impact of GCE on outcome after 6 months using the mRS. GCE was present in 54 (50.5%) patients, of which 27 (25.2%) were mild, 20 (18.7%) moderate and 7 (6.5%) were severe. Univariate analysis identified high Hunt-Hess and Glasgow coma scale on clinical admission as predictors factors of GCE (p < 0.05), and higher modified Fisher scale as a radiological predictor of Glasgow coma scale (p < 0.05). Thirty-three (30.8%) patients were deceased at 6 months. Death or severe disability were predicted by higher age, poor clinical scale on admission and severe GCE (p < 0.05). GCE on admission is independently associated with poor clinical outcomes at discharge, and six months after SAH. Given its strong association with poor clinical grade on admission, GCE should be considered a straightforward and radiological important marker of early brain injury, with ominous implications.

Clusters Across Multiple Domains of Health-Related Quality of Life Reveal Complex Patient Outcomes After Subarachnoid Hemorrhage.

Patients with subarachnoid hemorrhage were prospectively identified. Clinical data were prospectively recorded. Health-related quality of life was prospectively assessed at 3-month follow-up using the National Institutes of Health Patient Reported Outcomes Measurement Information System and neuro-quality of life in the domains of mobility, cognitive function, satisfaction with social roles, and depression. We used k-means clustering to analyze prospectively recorded health-related quality of life data, identifying clusters of complex patient outcomes. Decision tree analysis identified index hospital stay factors predictive of a patient having a particular complex patient outcome at follow-up. Academic medical center. One hundred three survivors of subarachnoid hemorrhage. None. We analyzed 103 patients, of whom 75 (72.8%) were female, and mean age was 53.6 ± 13.4 years. There were three complex patient outcomes: health-related quality of life greater than 1 sd better than the U.S. mean across all domains (n = 23, 22.3%), health-related quality of life greater than 1 sd worse than U.S. mean across all domains (n = 26, 25.2%), and satisfaction with social roles greater than 0.5 sd worse than U.S. mean with cognitive function, depression, and mobility scores near the U.S. mean (n = 54, 52.4%). In decision tree analysis, hospital disposition and Hunt and Hess Grade were associated with complex patient outcome. Complex patient outcomes across multiple domains of health-related quality of life at follow-up after subarachnoid hemorrhage are distinct and may be predictable.

Time Course of Peripheral Leukocytosis and Clinical Outcomes After Aneurysmal Subarachnoid Hemorrhage.

Objective: Systemic inflammation after subarachnoid hemorrhage (SAH) is implicated in delayed cerebral ischemia (DCI) and adverse clinical outcomes. We hypothesize that early changes in peripheral leukocytes will be associated with outcomes after SAH.Methods: SAH patients admitted between January 2009 and December 2016 were enrolled into a prospective observational study and were assessed for Hunt Hess Scale (HHS) at admission, DCI, and modified Ranked Scale (mRS) at discharge. Total white blood cell (WBC) counts and each component of the differential cell count were determined on the day of admission (day 0) to 8 days after bleed (day 8). Global cerebral edema (GCE) was assessed on admission CT, and presence of any infection was determined. Statistical tests included student's t-test, Chi-square test, and multivariate logistic regression (MLR) models.Results: A total of 451 subjects were analyzed. Total WBCs and neutrophils decreased initially reaching a minimum at day 4–5 after SAH. Monocyte count increased gradually after SAH and peaked between day 6–8, while basophils and lymphocytes decreased initially from day 0 to 1 and steadily increased thereafter. Neutrophil to lymphocyte ratio (NLR) reached a peak on day 1 and decreased thereafter. WBCs, neutrophils, monocytes, and NLR were higher in patients with DCI and poor functional outcomes. WBCs, neutrophils, and NLR were higher in subjects who developed infections. In MLR models, neutrophils and monocytes were associated with DCI and worse functional outcomes, while NLR was only associated with worse functional outcomes. Occurrence of infection was associated with poor outcome. Neutrophils and NLR were associated with infection, while monocytes were not. Monocytes were higher in males, and ROC curve analysis revealed improved ability of monocytes to predict DCI and poor functional outcomes in male subjects.Conclusions: Monocytosis was associated with DCI and poor functional outcomes after SAH. The association between neutrophils and NLR and infection may impact outcomes. Early elevation in monocytes had an improved ability to predict DCI and poor functional outcomes in males, which was independent of the occurrence of infection.

Aneurysmal subarachnoid hemorrhage survivors show long-term deficits in spatial reference memory in a pilot study of a virtual water maze paradigm

BackgroundLimited data exists on the long-term effects of aneurysmal subarachnoid hemorrhage (SAH) on spatial memory. Herein, we used a computerized virtual water maze to evaluate the feasibility of spatial memory testing in pilot cohort of ten patients who survived previous SAH. MethodsTen SAH survivors (5.8 ± 5.1 years after initial hemorrhage) and 7 age-matched controls underwent testing in a virtual water maze computer program. Additional subgroup analyses were performed to evaluate spatial reference memory correlation for ventricular size on admission, placement of an external ventricular drain and placement of a shunt. ResultsWith respect to the spatial memory acquisition phase, there was no significant difference of pathway length traveled to reach the platform between SAH survivors and control subjects. During the probe trial, control subjects spent significantly longer time in target quadrants compared to SAH survivors (F(3, 24) = 10.32, p = 0.0001; Target vs. Right: Mean percent difference 0.16 [0–0.32], p = 0.045; Target vs. Across: Mean percent difference 0.35 [0.19–0.51], p < 0.0001; Target vs. Left: Mean percent difference 0.21 [0.05–0.37], p = 0.0094). Furthermore, patients who initially presented with smaller ventricles performed worse that those patients who had ventriculomegaly and/or required surgical management of hydrocephalus. ConclusionsOur data demonstrate that SAH survivors have persistent spatial reference memory deficits years after the hemorrhage. Hydrocephalus at presentation and external ventricular drainage were not found to be associated with poor spatial memory outcomes in this pilot cohort. Therefore, other causes such as global cerebral edema or magnitude of initial ICP spike, need to be considered to be examined as root cause as well in subsequent studies. The protocol described in this manuscript is able to demonstrate a spatial reference memory deficit and can be used to study risk factors for spatial memory impairment on a larger scale.

Abstract P392: Early Brain Injury and Soluble ST2 After Non-Traumatic Subarachnoid Hemorrhage

Intro: Early Brain Injury (EBI) after non-traumatic subarachnoid hemorrhage (SAH) is a significant mediator of neurological injury, but the injury pathways and markers are not well understood. We hypothesized that the inflammatory mediator soluble ST2 (sST2) is associated with markers of EBI. Methods: We studied two independent cohorts, including 190 SAH patients in a discovery cohort and 50 patients in a replication cohort. Clinical markers of EBI included early loss of consciousness, Glasgow Coma Scale (GCS) score at 24 hours, and neurological deterioration within the first 72 hours (defined as a decrease in GCS ≥ 2 points). Radiographic markers included bicaudate index, clinically significant hydrocephalus requiring external ventricular drainage (EVD), and global cerebral edema. Serial plasma sST2 level was measured at early (3.5 ± 1.2 days post-hemorrhage), intermediate (7.8 ± 1.3 days post-hemorrhage), and late (13 ± 2.3 days post-hemorrhage) time points in the discovery cohort and daily during post-hemorrhage days 1-9 in the replication cohort. In the discovery cohort, the relationship between EBI markers and poor functional outcome (90-day modified Rankin Scale; mRS ≥ 3) was assessed using multivariable logistic regression. The association between sST2 level and EBI markers was evaluated using repeated measures analysis. In the replication cohort, associations were examined using an analysis of response profiles. Results: Clinical and radiographic markers of EBI, except for global edema, were each associated with functional outcome in univariate analysis. Of these EBI markers, independent predictors of poor outcome included 24-hour GCS (OR=5.76, 95% CI 2.31-14.4, p&lt;0.001) and clinically significant hydrocephalus (OR=8.74, 95% CI 2.44-31.3, p=0.001). Elevated sST2 was associated with all markers of EBI except for global edema, and independently predicted poor outcome in a multivariate model that included EBI markers. These findings were further replicated in an independent cohort. Conc: Of the potential clinical and radiographic contributors to EBI, poor 24-hour GCS and clinically significant hydrocephalus remain independent predictors of poor outcome. Furthermore, soluble sST2 level is associated with EBI and poor outcome.

Automated Quantification of Reduced Sulcal Volume Identifies Early Brain Injury After Aneurysmal Subarachnoid Hemorrhage.

Early brain injury may be a more significant contributor to poor outcome after aneurysmal subarachnoid hemorrhage (aSAH) than vasospasm and delayed cerebral ischemia. However, studying this process has been hampered by lack of a means of quantifying the spectrum of injury. Global cerebral edema (GCE) is the most widely accepted manifestation of early brain injury but is currently assessed only through subjective, qualitative or semi-quantitative means. Selective sulcal volume (SSV), the CSF volume above the lateral ventricles, has been proposed as a quantitative biomarker of GCE, but is time-consuming to measure manually. Here we implement an automated algorithm to extract SSV and evaluate the age-dependent relationship of reduced SSV on early outcomes after aSAH. We selected all adults with aSAH admitted to a single institution with imaging within 72 hours of ictus. Scans were assessed for qualitative presence of GCE. SSV was automatically segmented from serial CTs using a deep learning-based approach. Early SSV was the lowest SSV from all early scans. Modified Rankin Scale score of 4 to 6 at hospital discharge was classified as a poor outcome. Two hundred forty-four patients with aSAH were included. Sixty-five (27%) had GCE on admission while 24 developed it subsequently within 72 hours. Median SSV on admission was 10.7 mL but frequently decreased, with minimum early SSV being 3.0 mL (interquartile range, 0.3-11.9). Early SSV below 5 mL was highly predictive of qualitative GCE (area under receiver-operating-characteristic curve, 0.90). Reduced early SSV was an independent predictor of poor outcome, with a stronger effect in younger patients. Automated assessment of SSV provides an objective biomarker of GCE that can be leveraged to quantify early brain injury and dissect its impact on outcomes after aSAH. Such quantitative analysis suggests that GCE may be more impactful to younger patients with SAH.

CT-Based Classification of Acute Cerebral Edema: Association with Intracranial Pressure and Outcome.

Brain edema after acute cerebral lesions may lead to raised intracranial pressure (ICP) and worsen outcome. Notwithstanding, no CT-based scoring system to quantify edema formation exists. This retrospective correlative analysis aimed to establish a valid and definite CT score quantifying brain edema after common acute cerebral lesions. A total of 169 CT investigations in 60 patients were analyzed: traumatic brain injury (TBI; n = 47), subarachnoid hemorrhage (SAH; n = 70), intracerebral hemorrhage (ICH; n = 42), and ischemic stroke (n = 10). Edema formation was classified as 0: no edema, 1: focal edema confined to 1 lobe, 2: unilateral edema > 1 lobe, 3: bilateral edema, 4: global edema with disappearance of sulcal relief, and 5: global edema with basal cisterns effacement. ICP and Glasgow Outcome Score (GOS) were correlated to edema formation. Median ICP values were 12.0, 14.0, 14.9, 18.2, and 25.9 mmHg in grades 1-5, respectively. Edema grading significantly correlated with ICP (r = .51; P<.0001) in focal and global cerebral edema, particularly in patients with TBI, SAH, and ICH (r = .5, P<.001; r = .5; P<.0001; r = .6, P<.0001, respectively). At discharge, 23.7% of patients achieved a GOS of 5 or 4, 65.0% reached a GOS of 3 or 2, and 11.9% died (GOS 1). CT-score of cerebral edema in all patients correlated with outcome (r = -.3, P = .046). The proposed CT-based grading of extent of cerebral edema significantly correlated with ICP and outcome in TBI, SAH, and ICH patients and might be helpful for standardized description of CT-images and as parameter for clinical studies, for example, measuring effects of antiedematous therapies.

Refeeding syndrome: multimodal monitoring and clinical manifestation of an internal severe neurotrauma

Refeeding syndrome (RFS) is a rare, potentially life-threatening, condition seen in malnourished patients starting refeeding. RFS may provoke seizures and acute encephalopathy and can be considered an internal severe neurotrauma in need of specific treatment. The objective was to describe course of disease, treatment and, for the first time, multimodal monitoring output in a comatose patient suffering RFS. After gastric-banding and severe weight loss, the patient initiated self-starving and was transferred to our intensive care unit (ICU) following rapid refeeding. At arrival, seizures, decrease in consciousness (GCS 7) and suspected acute encephalitis was presented. Serum albumin was 8 g/l. Intracranial pressure (ICP), invasive blood pressure and electrocardiography (ECG) were monitored. Pressure reactivity (PRx) and compliance (RAP) were calculated. The patient developed congestive heart failure, anuria and general oedema despite maximal neuro- and general ICU treatment. Global cerebral oedema and hypoperfusion areas with established ischemia were seen. ECG revealed massive cardiac arrhythmia and disturbed autonomic regulation. PRx indicated intact autoregulation (−0.06 ± 0.18, mean ± SD) and relatively normal compliance (RAP = 0.23 ± 0.13). After 15 days the clinical state was improved, and the patient returned to the primary hospital. RFS was associated with serious deviations in homeostasis, high ICP levels, ECG abnormalities, kidney and lung affections. It is of utmost importance to recognize this rare syndrome and to treat appropriately. Despite the severe clinical state, cerebral autoregulation and compensatory reserve were generally normal, questioning the applicability of indirect measurements such as PRx and RAP during neuro-intensive care treatment of RFS patients with cerebral engagement.