Development of cerebral vasospasm following traumatic intracranial hemorrhage: incidence, risk factors, and clinical outcomes.

OBJECTIVE: Limited evidence exists characterizing the incidence, risk factors, and clinical associations of cerebral vasospasm following traumatic intracranial hemorrhage (tICH) on a large scale. Therefore, the authors sought to use data from a national inpatient registry to investigate these aspects of posttraumatic vasospasm (PTV) to further elucidate potential causes of neurological morbidity and mortality subsequent to the initial insult. METHODS: Weighted discharge data from the National (Nationwide) Inpatient Sample from 2015 to 2018 were queried to identify patients with tICH who underwent diagnostic angiography in the same admission and, subsequently, those who developed angiographically confirmed cerebral vasospasm. Multivariable logistic regression analysis was performed to identify significant associations between clinical covariates and the development of vasospasm, and a tICH vasospasm predictive model (tICH-VPM) was generated based on the effect sizes of these parameters. RESULTS: Among 5880 identified patients with tICH, 375 developed PTV corresponding to an incidence of 6.4%. Multivariable adjusted modeling determined that the following clinical covariates were independently associated with the development of PTV, among others: age (adjusted odds ratio [aOR] 0.98, 95% CI 0.97-0.99; p < 0.001), admission Glasgow Coma Scale score < 9 (aOR 1.80, 95% CI 1.12-2.90; p = 0.015), intraventricular hemorrhage (aOR 6.27, 95% CI 3.49-11.26; p < 0.001), tobacco smoking (aOR 1.36, 95% CI 1.02-1.80; p = 0.035), cocaine use (aOR 3.62, 95% CI 1.97-6.63; p < 0.001), fever (aOR 2.09, 95% CI 1.34-3.27; p = 0.001), and hypokalemia (aOR 1.62, 95% CI 1.26-2.08; p < 0.001). The tICH-VPM achieved moderately high discrimination, with an area under the curve of 0.75 (sensitivity = 0.61 and specificity = 0.81). Development of vasospasm was independently associated with a lower likelihood of routine discharge (aOR 0.60, 95% CI 0.45-0.78; p < 0.001) and an extended hospital length of stay (aOR 3.53, 95% CI 2.78-4.48; p < 0.001), but not with mortality. CONCLUSIONS: This population-based analysis of vasospasm in tICH has identified common clinical risk factors for its development, and has established an independent association between the development of vasospasm and poorer neurological outcomes.

Ultra-Early Hemostatic Therapy for Acute Intracerebral Hemorrhage: An Updated Review.

Intracerebral hemorrhage (ICH) is the second most common type of stroke, accounting for approximately 10-20% of all strokes, and is linked to severe neurological disability and death. Since the most accurate predictor of outcome in patients with ICH is hematoma volume, there is a great need for pharmacologic therapy that can reduce hematoma expansion and resultant mass effect and edema. This is especially critical within the ultra-early window of 3-4 hours after the presentation. Hemostatic therapies are exceptionally important for those patients taking antiplatelet or anticoagulant medications to reverse the effects of these medications and therefore prevent hematoma expansion. Furthermore, the recent publication of the 2023 Guideline for the Management of Patients with Aneurysmal Subarachnoid Hemorrhage by the American Heart Association/American Stroke Association, the first update to the guidelines since 2012, underscores the importance of optimizing anticoagulation reversal for this population. The purpose of this selective, nonsystematic review is to examine current literature regarding the use of hemostatic therapies in ICH, with particular attention paid to antiplatelet, anticoagulation, and antifibrinolytic therapies.

Outcomes of heparin-induced thrombocytopenia type II in aneurysmal subarachnoid hemorrhage patients: A US nationwide analysis.

BACKGROUND: Despite the widespread use of heparin during and following endovascular procedures in the management of aneurysmal subarachnoid hemorrhage (SAH) patients, limited research has explored the incidence and impact of heparin-induced thrombocytopenia (HIT) on SAH. METHODS: Descriptive statistics, multivariate regressions, and propensity score-matching were employed to compare clinical characteristics, comorbidities, interventions, complications, and outcomes of HIT in SAH patients identified within the US National Inpatient Sample database from 2010 to 2019. RESULTS: Among 76 387 SAH patients from 2010 to 2019, 166 (0.22%) developed HIT. HIT was identified as a significant predictor of prolonged length of stay (OR 6.799, 95% CI 3.985 to 11.6, P<0.01) and poor functional outcomes (OR 2.541, 95% CI 1.628 to 3.966, P<0.01) after adjusting for relevant factors. HIT incidence was higher in patients with elevated SAH severity scores (1.42 vs 1.06, P<0.01), younger patients (58.04 vs 61.39 years, P=0.01), overweight individuals (0.4% vs 0.2%, P<0.01), those on long-term anticoagulants (10.84% vs 5.72%, P<0.01), or with a cerebrospinal fluid drainage device (external ventricular drain, ventriculoperitoneal shunt; P<0.01). HIT patients showed increased rates of endovascular coiling, ventricular drain placement, shunt placement, deep vein thrombosis, urinary tract infection, acute kidney injury, pulmonary embolism, venous sinus thrombosis, pneumonia, and cerebral vasospasm (all P<0.01). CONCLUSION: SAH patients with HIT exhibited various comorbidities and increased rates of complications, which may contribute to extended hospital stays. This nationwide study aids clinical suspicion and highlights HIT's impact on SAH patients.

Safety and efficacy of a novel robotic transcranial doppler system in subarachnoid hemorrhage.

Delayed cerebral ischemia (DCI) secondary to vasospasm is a determinate of outcomes following non-traumatic subarachnoid hemorrhage (SAH). SAH patients are monitored using transcranial doppler (TCD) to measure cerebral blood flow velocities (CBFv). However, the accuracy and precision of manually acquired TCD can be operator dependent. The NovaGuide robotic TCD system attempts to standardize acquisition. This investigation evaluated the safety and efficacy of the NovaGuide system in SAH patients in a Neuro ICU. We retrospectively identified 48 NovaGuide scans conducted on SAH patients. Mean and maximum middle cerebral artery (MCA) CBFv were obtained from the NovaGuide and the level of agreement between CBFv and computed tomography angiography (CTA) for vasospasm was determined. Safety of NovaGuide acquisition of CBFv was evaluated based on number of complications with central venous lines (CVL) and external ventricular drains (EVD). There was significant agreement between the NovaGuide and CTA (Cohen's Kappa = 0.74) when maximum MCA CBFv ≥ 120 cm/s was the threshold for vasospasm. 27/48 scans were carried out with CVLs and EVDs present without negative outcomes. The lack of adverse events associated with EVDs/CVLs and the strong congruence between maximal MCA CBFv and CTA illustrates the diagnostic utility of the NovaGuide.

Frailty is a risk factor for intracranial abscess and is associated with longer length of stay: a retrospective single institution case-control study.

BACKGROUND: Intracranial abscess (IA) causes significant morbidity and mortality. The impact of baseline frailty status on post-operative outcomes of IA patients remains largely unknown. The present study evaluated if frailty status can be used to prognosticate outcomes in IA patients. METHODS: We retrospectively reviewed all IA patients undergoing craniotomy at our institution from 2011 to 2018 (n =18). These IA patients were age and gender matched with patients undergoing craniotomy for intracranial tumor (IT), an internal control for comparison. Demographic and clinical data were collected to measure frailty, using the modified frailty index-11 (mFI-11), pre-operative American Society of Anesthesiologists Physical Status Classification System (ASA), and study their association with post-operative complications, as measured by the Clavien-Dindo Grade (CDG). RESULTS: No significant difference in mFI-11 or ASA score was observed between the IA and IT groups (p = 0.058 and p = 0.131, respectively). IA patients had significantly higher CDG as compared with the control IT patients (p < 0.001). There was a trend towards increasing LOS in the IA group as compared to the IT group (p = 0.053). Increasing mFI and ASA were significant predictors of LOS by multiple linear regression in the IA group (p = 0.006 and p = 0.001, respectively), but not in the control IT group. Neither mFI-11 nor ASA were found to be predictors for CDG in either group. Within this case-control group of patients, we found an increase for odds of having IA with increasing mFI (OR 1.838, CI 95% 1.016-3.362, p = 0.044). CONCLUSIONS: Frail IA patients tend to have more severe postoperative complications. The mFI-11 seems to predict increased resource utilization in the form of LOS. This study provides the initial retrospective data of another neurosurgical pathology where frailty leads to significantly worse outcomes. We also found that mFI may serve as a potential risk factor for severe disease.

Relation between brain natriuretic peptide and delayed cerebral ischemia in patients with aneurysmalsubarachnoid hemorrhage.

BACKGROUND: Brain natriuretic peptide (BNP), often used to evaluate degree of heart failure, has been implicated in fluid dysregulation and inflammation in critically-ill patients. Twenty to 30% of patients with aneurysmal subarachnoid hemorrhage (aSAH) will develop some degree of neurogenic stress cardiomyopathy (NSC) and in turn elevation of BNP levels. We sought to explore the association between BNP levels and development of delayed cerebral ischemia (DCI) in patients with aSAH. METHODS: We retrospectively evaluated the records of 149 patients admitted to the Neurological Intensive Care Unit between 2006 and 2015 and enrolled in an existing prospectively maintained aSAH database. Demographic data, treatment and outcomes, and BNP levels at admission and throughout the hospital admission were noted. RESULTS: Of the 149 patients included in the analysis, 79 developed DCI during their hospital course. We found a statistically significant association between DCI and the highest recorded BNP (OR 1.001, 95% CI-1.001-1.002, p = 0.002). The ROC curve analysis for DCI based on BNP showed that the highest BNP level during hospital admission (AUC 0.78) was the strongest predictor of DCI compared to the change in BNP over time (AUC 0.776) or the admission BNP (AUC 0.632). CONCLUSION: Our study shows that DCI is associated not only with higher baseline BNP values (admission BNP), but also with the highest BNP level attained during the hospital course and the rapidity of change or increase in BNP over time. Prospective studies are needed to evaluate whether routine measurement of BNP may help identify SAH patients at high risk of DCI.

Decision-Making for Patients With Cerebral Arteriovenous Malformations.

Cerebral arteriovenous malformations (AVMs) are a complex and heterogeneous pathology which require an understanding of the natural history of these lesions, as well as the potential treatment options in order to manage them safely. While treatment is the agreed upon strategy for most ruptured AVMs, the management of unruptured AVMs continues to be debated. More recently, this debate has been fueled by the A Randomized Trial of Unruptured Arteriovenous Malformations (ARUBA) trial which attempts to define the natural history and treatment risk of AVMs. However, the trial has significant shortcomings which limit its broad applicability. In addition, the breadth, efficacy, and safety of potential treatment options continue to improve. This review focuses on defining the natural history of cerebral AVMs, an overview of the ARUBA trial, and the most current treatment paradigm for cerebral AVMs.

Impact of pre-ictal antiplatelet therapy use in aneurysmal subarachnoid hemorrhage.

OBJECTIVE: There is limited evidence on the use of antiplatelet therapy (APT) to reduce the risk and morbidity of cerebral aneurysmal rupture. This analysis retrospectively assessed APT use in patients presenting to our institution with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We evaluated the records of 186 patients over 7 years of retrospective data from our tertiary care center and an existing database of patients with aSAH. A total of 18 cases with patients on APT and 168 patients not on APT (controls) were identified. Primary outcomes measured were clinical grade (Hunt and Hess score), radiographic grade (Fisher score), and presence of delayed cerebral ischemia (DCI). Secondary outcomes were modified Rankin score at discharge and at 3 months. DCI from cerebral vasospasm was defined as the occurrence of focal neurological impairment or a decrease in at least 2 points on the Glasgow Coma Scale. Logistic regression models were generated. RESULTS: We found that APT use did not appear to lead to statistically significant differences in initial presentation, including Hunt-Hess score and Fisher grade (2.91 vs 3.06, p = 0.66, and 3.23 vs 3.22, p = 0.96 respectively). In addition, APT use was not associated with increased rates of delayed cerebral ischemia (DCI) (OR 0.27 p = 0.12). Our analysis showed that increased Hunt Hess score and the presence of DCI are both associated with increased mRS at 90 days (OR 2.32 p < 0.001; OR 2.91 p = 0.002). CONCLUSION: The patients in this retrospective observational study did not demonstrate worse outcomes from their aSAH despite APT therapy. Larger prospective studies should be performed to see if this relationship holds and if decreased rates of DCI can be observed.

Body Mass Index and Overall Outcome Following Subarachnoid Hemorrhage: An Obesity Paradox?

BACKGROUND: Conventional understanding of obesity demonstrates negative consequences for overall health, whereas more modern studies have found that it can provide certain advantages. The current literature on the effect of body mass index (BMI) in subarachnoid hemorrhage (SAH) is similarly inconsistent. METHODS: cohort of 406 patients with SAH were retrospectively reviewed and stratified into 3 BMI categories: normal weight, 18.5-24.9 kg/m2; overweight, 25-29.9 kg/m2; and obese, >30 kg/m2. Neurologic status, the presence of clinical cerebral vasospasm, and outcome as assessed by the modified Rankin scale (mRS) were obtained. RESULTS: Statistical differences were evident for all outcome categories. A categorical analysis of the different groups revealed that compared with the normal weight group, the overweight group had an odds ratio (OR) for mortality of 0.415 (P = 0.023), an OR for poor mRS score at 90 days of 0.432 (P = 0.014), and an OR for poor mRS score at 180 days of 0.311 (P = 0.001), and the obese group had statistically significant ORs for poor mRS score at 90 days of 2.067 (P = 0.041) and at 180 days of 1.947 (P = 0.049). These significant ORs persisted in a multivariable model controlling for age and Hunt and Hess grade. CONCLUSIONS: The overweight group exhibited strikingly lower odds of death and poor outcome compared with the normal weight group, whereas the obese group demonstrated the opposite. These associations persisted in a multivariable model; thus, BMI can be considered an important predictor of outcome after SAH.

Pituitary Apoplexy Following Endoscopic Retrograde Cholangiopancreatography.

BACKGROUND: Pituitary apoplexy is an uncommon neurosurgical emergency that may be the initial presentation of undiagnosed pituitary adenomas. Though the exact pathogenesis is unclear, there appears to be an association between pituitary apoplexy and medical interventions that disturb the blood supply and venous drainage of the abnormal sellar region. We present the first case of pituitary apoplexy occurring after an endoscopic retrograde cholangiopancreatography (ERCP). CASE DESCRIPTION: A 43-year-old male who was several hours status post ERCP presented with a severe headache, bilateral ptosis, and multidirectional ophthalmoplegia. Computed tomography scan and magnetic resonance imaging of the brain revealed a hemorrhagic and necrotic sellar mass with suprasellar extension compressing the optic chiasm and bilateral extension displacing the cavernous carotid arteries laterally. The patient underwent emergent endoscopic endonasal transsphenoidal resection of the underlying pituitary tumor apoplexy with eventual resolution of his cranial nerve palsies. CONCLUSIONS: Although pituitary apoplexy has been recognized as a sequela of surgical and laparoscopic procedures, it should also be considered in less invasive gastrointestinal procedures which may alter the intraabdominal pressures, such as ERCP. Early detection of this unusual complication allows for rapid diagnosis and timely surgical intervention in select cases to prevent debilitating cranial nerve palsies, preserve visual function, and retain normal pituitary function.

Updates in the Management of Cerebral Infarctions and Subarachnoid Hemorrhage Secondary to Intracranial Arterial Dissection: A Systematic Review.

OBJECTIVE: Intracranial arterial dissection (IAD) is a rare cerebrovascular disease that is likely underdiagnosed because of the inherent difficulty of visualizing the subtle radiographic signs of the pathologic small intracranial arteries. No widespread consensus exists on the treatment of IAD, and thus it is often managed empirically because of the absence of major randomized controlled trials. In this study, we conducted a systematic review to evaluate the management and treatment options for IAD. METHODS: We performed a systematic review in accordance with the PRISMA guidelines using the following databases: MEDLINE (PubMed) and Cochrane Library. Included studies were limited to human patients with dissections in intracranial vessels only. RESULTS: A total of 82 studies were included in this systematic review. The most common complications of IAD were cerebral infarction and subarachnoid hemorrhage, and thus, patients with IAD can be subdivided into those presenting with either ischemia or hemorrhage, respectively. Those with ischemia were predominantly managed with antiplatelet therapy, whereas patients presenting with hemorrhage often were amenable to treatment with endovascular techniques. CONCLUSIONS: Given these findings, clinicians should prescribe antiplatelet therapy for patients with IAD presenting with ischemia and consider endovascular treatment for those presenting with hemorrhage. However, further investigation is required given the heterogeneity of methods and reporting outcomes in the investigated studies.

Admission neutrophil-lymphocyte ratio predicts delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) has a multifactorial pathophysiology, with immune dysregulation being an important component. The neutrophil-lymphocyte ratio (NLR) is an established prognostic marker in patients with cancer, cardiac disease, and sepsis. OBJECTIVE: To determine whether there is a relationship between NLR and DCI in patients with aSAH. METHODS: We evaluated 1067 patients with aSAH between 2006 and 2015 enrolled in a single-center, prospective, observational cohort study. Admission white blood cell differentials (NLR) were analyzed using a cut-off point of ≥5.9. DCI from cerebral vasospasm was defined as the occurrence of focal neurological impairment, or a decrease in at least two points on the Glasgow Coma Scale, which was not apparent immediately after aneurysm occlusion, and could not be attributed to other causes. Cerebral infarct was defined as a new infarct on CT that was not visible on the admission or immediate postoperative scan, when the cause was thought to be vasospasm by the research team. Logistic regression models were generated. RESULTS: We found that 768 (72%) patients had an admission NLR ≥5.9. In a multivariable model, elevated NLR was associated with poor admission Hunt-Hess grade (OR=1.6, 95% CI 1.2 to 2.6, p=0.005), Caucasian ethnicity (OR=2.6, 95% CI 1.9 to 3.7, p<0.001), anterior aneurysm location (OR=1.7, 95% CI 1.2 to 2.4, p=0.004), loss of consciousness at ictus (OR=1.4, 95% CI 1.0 to 2.0, p=0.055), and thick SAH (modified Fisher grade ≥3) (OR=1.8, 95% CI 1.3 to 2.4, p<0.001). Admission NLR predicted development of delayed cerebral ischemia (DCI) (OR=1.7; 95% CI 1.1 to 2.5, p=0.008) after controlling for known predictors such as age, poor admission clinical grade, thick SAH blood, and elevated admission mean arterial pressure. CONCLUSIONS: This study provides further evidence of the association between inflammation and DCI. Admission NLR is a readily available and convenient biomarker that may be a clinically useful tool for prognostication when evaluating aSAH.

Novel minimally invasive multi-modality monitoring modalities in neurocritical care.

Elevated intracranial pressure (ICP) following brain injury contributes to poor outcomes for patients, primarily by reducing the caliber of cerebral vasculature, and thereby reducing cerebral blood flow. Careful monitoring of ICP is critical in these patients in order to determine prognosis, implement treatment when ICP becomes elevated, and to judge responsiveness to treatment. Currently, the gold standard for monitoring is invasive pressure transducers, usually an intraventricular monitor, which presents significant risk of infection and hemorrhage. These risks made discovering non-invasive methods for monitoring ICP and cerebral perfusion a priority for researchers. Herein we sought to review recent publications on novel minimally invasive multi-modality monitoring techniques that provide surrogate data on ICP, cerebral oxygenation, metabolism and blood flow. While limitations in various forms preclude them from supplanting the use of invasive monitors, these modalities represent useful screening tools within our armamentarium that may be invaluable when the risks of invasive monitoring outweigh the associated benefits.

Novel management strategies for medically-refractory vasospasm following aneurysmal subarachnoid hemorrhage.

Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is an important cause of further morbidity and mortality after an already devastating condition. Though traditionally attributed to vasospasm of large capacitance arteries and the resulting down-stream disruption of cerebral blood flow, the pathogenesis of DCI has proven to be more complex with early brain injury, blood-brain barrier disruption, microthrombosis, cortical spreading depolarizations, and the failure of cerebral autoregulation as newly elucidated factors. Vasospasm is a known consequence of SAH. The standard of care includes close monitoring for neurological deterioration, most often with serial clinical examinations, transcranial Doppler ultrasonography, and vascular imaging (crucial for early detection of DCI and allows for prompt intervention). Nimodipine continues to remain an important pharmacological strategy to improve functional outcomes in patients with SAH at risk for developing vasospasm. The paradigm for first line therapy in patients with vasospasm of induced hypertension, hypervolemia, and hemodilution has recently been challenged. Current American Heart Association guidelines recommend targeting euvolemia and judicious use of the pharmacologically induced hypertension component. Symptomatic vasospasm patients who do not improve with this first line therapy require rescue intervention with mechanical or chemical angioplasty and optimization of cardiac output and hemoglobin levels. This can be escalated in a step-wise fashion to include adjunct treatments such as intrathecal administration of vasodilators and sympatholytic or thrombolytic therapies. This review provides a general overview of the treatment modalities for DCI with a focus on novel management strategies that show promising results for treating vasospasm to prevent DCI.

Emerging Markers of Early Brain Injury and Delayed Cerebral Ischemia in Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage is characterized by a highly complex pathophysiology and results in neurologic deterioration after the inciting bleed. Despite its significant consequences, prompt diagnosis can be elusive and treatment is often administered too late. Early brain injury, which occurs within the first 72 hours after ictus, may be an important factor for delayed cerebral ischemia and poor overall outcome. Here, we explore the purported clinical and pathologic manifestations of early brain injury to identify biomarkers that could have prognostic value. METHODS: We review the literature and discuss potential emerging markers of delayed cerebral ischemia in the context of early brain injury. RESULTS: The following clinical features and biomarkers were examined: global cerebral edema, ictal loss of consciousness, ultra early angiographic vasospasm, continuous electroencephalogram monitoring, systemic inflammatory response syndrome, cellular mediators of the inflammatory response, and hematologic derangements. CONCLUSIONS: Some of these markers possess independent value for determining the risk of complications after aneurysmal subarachnoid hemorrhage. However, their use is limited because of a variety of factors, but they do provide an avenue of further study to aid in diagnosis and management.