J Mocco, Carlton S. Prickett, Ricardo J. Komotar, E. Sander Connolly and Stephan A. Mayer
✓In an attempt to elucidate the pathophysiology and clinical significance of global cerebral edema (GCE) following aneurysmal subarachnoid hemorrhage (SAH), the authors explored potential mechanisms and reviewed findings associated with this phenomenon. Admission computed tomography (CT) scans show GCE in up to 20% of patients experiencing aneurysmal SAH. This edema is likely to have been initiated by transient global ischemia, as indicated by an association between ictal loss of consciousness and the development of edema. A further cascade of events, including a rise in intracranial pressure and compromise of the blood–brain barrier, are also likely contributors. Clinically, GCE on CT after aneurysmal SAH is predictive of a poor outcome. Further investigation is needed to gain a full understanding of edema development following SAH, with the hope that the knowledge can be used to influence treatment positively and improve outcome.
Shouri Lahiri, Mani Nezhad, Konrad H. Schlick, Brenda Rinsky, Axel Rosengart, Stephan A. Mayer and Patrick D. Lyden
Intravenous nicardipine is commonly used for blood pressure reduction in patients with acute stroke. However, few studies have described its effects on cerebrovascular hemodynamics as measured by transcranial Doppler (TCD) waveform analysis and pulsatility index (PI). In this study, the authors report examples of a consistent but paradoxical finding associated with nicardipine that suggests intracranial vasoconstriction, contrary to what is expected from a vasodilator.
The data presented are from a convenience sample of patients who underwent TCD monitoring before, after, or during nicardipine administration. In each case, TCD waveform morphologies and PIs were compared.
The TCD waveforms during nicardipine infusion are characterized by a prominent systolic peak and dicrotic notch. Systolic deceleration was more pronounced and PIs were significantly elevated in patients who were on nicardipine (p < 0.001). This finding was not evident when patients were not on nicardipine.
This study provides the first evidence of paradoxical intracranial vasoconstriction associated with intravenous nicardipine. In the authors' experience, this finding is consistently encountered in the vast majority of patients who are treated with intravenous nicardipine, and is contradictory to what is expected from a vasodilator. Future studies are needed to confirm this finding in larger populations and diverse clinical settings and to examine mechanisms that explain this phenomenon.
Stephan A. Mayer, Gregory K. Yim, Stephen T. Onesti, Timothy Lynch, Phyllis L. Faust and Karen Marder
✓ Neurosarcoidosis without systemic involvement is rare and difficult to diagnose. The case of a 27-year-old man with a 6-week history of headache, mental status changes, and polyradiculopathy attributable to hypoglycorrheic lymphocytic meningitis is presented. Extensive testing for occult systemic sarcoidosis was negative. The presence of noncaseating granulomatous inflammation was established by open brain biopsy, and the patient improved clinically with oral steroid therapy. In individuals with undiagnosed chronic meningitis, brain biopsy may be necessary to rule out isolated neurosarcoidosis.
William J. Mack, Ryan G. King, Andrew F. Ducruet, Kurt Kreiter, J Mocco, Ahmed Maghoub, Stephan Mayer and E. Sander Connolly Jr.
Elevated intracranial pressure (ICP) is an important consequence of aneurysmal subarachnoid hemorrhage (SAH) that often results in decreased cerebral perfusion and secondary clinical decline. No definitive guidelines exist regarding methods and techniques for ICP management following aneurysm rupture. The authors describe monitoring practices and outcome data in 621 patients with aneurysmal SAH admitted to their neurological intensive care unit during an 8-year period (1996–2003).
A fiberoptic catheter tip probe or external ventricular drain (EVD) was used to record ICP values. The percentage of monitored patients varied, as expected, according to admission Hunt and Hess grade (p < 0.0001). Intracranial pressure monitoring devices were used in 27 (10%) of 264 Grade I to II patients, 72 (38%) of 189 Grade III patients, and 134 (80%) of 168 Grade IV to V patients. There was a strong propensity to favor transduced ventricular drains over parenchymal fiberoptic bolts, with the former used in 221 (95%) of 233 cases. This tendency was particularly strong in the poor-grade cohort, in which EVDs were placed in 99% of monitored individuals. The rates of cerebrospinal fluid infection in patients in whom ICP probes (0%) and ventricular drains (12%) were placed accorded with those in the literature.
Following aneurysmal SAH, ICP monitoring prevalence and techniques differ with respect to admission Hunt and Hess grade and are associated with the patient's functional status at discharge.
E. François Aldrich, Randall Higashida, Abdel Hmissi, Elizabeth J. Le, R. Loch Macdonald, Angelina Marr, Stephan A. Mayer, Sébastien Roux and Nicolas Bruder
Aneurysmal subarachnoid hemorrhage (aSAH) is associated with significant morbidity and mortality. The presence of thick, diffuse subarachnoid blood may portend a worse clinical course and outcome, independently of other known prognostic factors such as age, aneurysm size, and initial clinical grade.
In this post hoc analysis, patients with aSAH undergoing surgical clipping (n = 383) or endovascular coiling (n = 189) were pooled from the placebo arms of the Clazosentan to Overcome Neurological Ischemia and Infarction Occurring After Subarachnoid Hemorrhage (CONSCIOUS)–2 and CONSCIOUS-3 randomized, double-blind, placebo-controlled phase 3 studies, respectively. Patients without and with thick, diffuse SAH (≥ 4 mm thick and involving ≥ 3 basal cisterns) on admission CT scans were compared. Clot size was centrally adjudicated. All-cause mortality and vasospasm-related morbidity at 6 weeks and Glasgow Outcome Scale–Extended (GOSE) scores at 12 weeks after aSAH were assessed. The effect of the thick and diffuse cisternal aSAH on vasospasm-related morbidity and mortality, and on poor clinical outcome at 12 weeks, was evaluated using logistic regression models.
Overall, 294 patients (51.4%) had thick and diffuse aSAH. Compared to patients with less hemorrhage burden, these patients were older (median age 55 vs 50 years) and more often had World Federation of Neurosurgical Societies (WFNS) grade III–V SAH at admission (24.1% vs 16.5%). At 6 weeks, all-cause mortality and vasospasm-related morbidity occurred in 36.1% (95% CI 30.6%–41.8%) of patients with thick, diffuse SAH and in 14.7% (95% CI 10.8%–19.5%) of those without thick, diffuse SAH. Individual event rates were 7.5% versus 2.5% for all-cause death, 19.4% versus 6.8% for new cerebral infarct, 28.2% versus 9.4% for delayed ischemic neurological deficit, and 24.8% versus 10.8% for rescue therapy due to cerebral vasospasm, respectively. Poor clinical outcome (GOSE score ≥ 4) was observed in 32.7% (95% CI 27.3%–38.3%) and 16.2% (95% CI 12.1%–21.1%) of patients with and without thick, diffuse SAH, respectively.
In a large, centrally adjudicated population of patients with aSAH, WFNS grade at admission and thick, diffuse SAH independently predicted vasospasm-related morbidity and poor 12-week clinical outcome. Patients with thick, diffuse cisternal SAH may be an important cohort to target in future clinical trials of treatment for vasospasm.
Neha S. Dangayach, Harpreet Singh Grewal, Gian Marco De Marchis, Roberta K. Sefcik, Rachel Bruce, Aarti Chhatlani, E. Sander Connolly, M. Cristina Falo, Sachin Agarwal, Jan Claassen, J. Michael Schmidt and Stephan A. Mayer
Being overweight or mildly obese has been associated with a decreased risk of death or hospitalization in patients with cardiovascular disease. Similarly, overweight patients admitted to an intensive care unit (ICU) have improved survival up to 1 year after admission. These counterintuitive observations are examples of the “obesity paradox.” Does the obesity paradox exist in patients with intracerebral hemorrhage (ICH)? In this study the authors examined whether there was an association between obesity and functional outcome in patients with ICH.
The authors analyzed 202 patients admitted to the neurological ICU (NICU) who were prospectively enrolled in the Columbia University ICH Outcomes Project between September 2009 and December 2012. Patients were categorized into 2 groups: overweight (body mass index [BMI] ≥ 25 kg/m2) and not overweight (BMI < 25 kg/m2). The primary outcome was defined as survival with favorable outcome (modified Rankin Scale [mRS] score 0–3) versus death or severe disability (mRS score 4–6) at 3 months.
The mean age of the patients in the study was 61 years. The mean BMI was 28 ± 6 kg/m2. The mean Glasgow Coma Scale score was 10 ± 4 and the mean ICH score was 1.9 ± 1.3. The overall 90-day mortality rate was 41%. Among patients with a BMI < 25 kg/m2, 24% (17/70) had a good outcome, compared with 39% (52/132) among those with a BMI ≥ 25 kg/m2 (p = 0.03). After adjusting for ICH score, sex, do-not-resuscitate code status, and history of hypertension, being overweight or obese (BMI ≥ 25 kg/m2) was associated with twice the odds of having a good outcome compared with patients with BMI < 25 kg/m2 (adjusted odds ratio 2.05, 95% confidence interval 1.03–4.06, p = 0.04).
In patients with ICH admitted to the NICU, being overweight or obese (BMI ≥ 25 kg/m2) was associated with favorable outcome after adjustment for established predictors. The reason for this finding requires further study.
Charles L. Francoeur, David Roh, J. Michael Schmidt, Stephan A. Mayer, M. Cristina Falo, Sachin Agarwal, E. Sander Connolly, Jan Claassen, Mitchell S. V. Elkind and Soojin Park
Rebleeding remains a frequent and catastrophic event leading to poor outcome after subarachnoid hemorrhage (SAH). Reduced platelet function after the initial bleed is associated with higher risk of early rebleeding. Desmopressin (DDAVP) is a well-known hemostatic agent, and recent guidelines already suggest its use in individuals exposed to antiplatelet drugs. The authors hypothesized that DDAVP administration in patients with SAH at admission would be associated with lower risks of rebleeding.
The authors performed an observational cohort study of patients enrolled in the Columbia University SAH Outcome Project between August 1996 and July 2015. The authors compared the rate of rebleeding between patients who were and those who were not treated with DDAVP. After adjustment for known predictors, logistic regression was used to measure the association between treatment with DDAVP and risks of rebleeding.
Among 1639 patients with SAH, 12% were treated with DDAVP. The main indication for treatment was suspected exposure to an antiplatelet agent. The overall incidence of rebleeding was 9% (1% among patients treated with DDAVP compared with 8% among those not treated). After adjustment for antiplatelet use and known predictors, treatment with DDAVP was associated with a 45% reduction in the risks of rebleeding (adjusted OR 0.55, 95% CI 0.27–0.97). DDAVP was associated with a higher incidence of hyponatremia but not with thrombotic events or delayed cerebral ischemia.
Treatment with DDAVP was associated with a lower risk of rebleeding among patients with SAH. These findings support further study of DDAVP as first-line therapy for medical hemostasis in patients with SAH.
J Mocco, William J. Mack, Grace H. Kim, Alan P. Lozier, Ilya Laufer, Kurt T. Kreiter, Robert R. Sciacca, Robert A. Solomon, Stephan A. Mayer and E. Sander Connolly Jr.
Object. Proinflammatory adhesion molecule expression has been demonstrated to be elevated in patients with aneurysmal subarachnoid hemorrhage (SAH). Recent studies have shown that elevations in soluble intercellular adhesion molecule—1 (ICAM-1) may be predictive of poor outcome in patients with good grade (Hunt and Hess Grades 1–2) aneurysmal SAH at delayed time points that correspond with the risk period for cerebral vasospasm. In addition, ICAM-1 is upregulated in experimental models of vasospasm. Unfortunately, the relationship of adhesion molecule expression to human vasospasm remains unclear. The authors hypothesized that the delayed elevation of soluble ICAM-1 in patients with aneurysmal SAH is associated with the development of cerebral vasospasm.
Methods. Eighty-nine patients with aneurysmal SAH were prospectively enrolled in a study and stratified according to the presence or absence of vasospasm, as evidenced by daily monitoring of transcranial Doppler (TCD) velocities (presence, > 200 cm/second; absence, ≤ 120 cm/second). Levels of soluble ICAM-1 were determined using enzyme-linked immunosorbent assay every other day for 12 days post-SAH. An analysis of covariance model was used to evaluate trends in soluble ICAM-1 levels from 2 days prior to 6 days after the occurrence of documented vasospasm. Two groups of patients, matched for admission admission Hunt and Hess grade, were compared: nine patients with TCD velocities greater than 200 cm/second and nine patients with TCD velocities less than 120 cm/second. From among the patients with TCD velocities greater than 200 cm/second six patients with angiographically documented vasospasm were selected. Patients with TCD velocities less than 120 cm/second and matched admission Hunt and Hess grades but without angiographically documented vasospasm were selected. Patients with TCD-demonstrated vasospasm showed a significant mean rate of rise (p < 0.01) in soluble ICAM-1 levels during the perivasospasm period, but admission Hunt and Hess grade—matched control patients did not (p = not significant [NS]). There was a significant difference between these groups' rates of soluble ICAM increase (p < 0.01). Patients with both TCD- and angiographically demonstrated vasospasm likewise showed a highly significant mean rate of increase in soluble ICAM-1 levels during the perivasospasm period (p < 0.01), whereas admission Hunt and Hess grade—matched controls did not (p = NS). The difference beween these groups' rates of increase was highly significant (p < 0.001).
Conclusions. These data suggest a role for ICAM-1 in the pathophysiology of cerebral vasospasm or its ischemic sequelae. As this relationship is further elucidated, adhesion molecules such as ICAM-1 may provide novel therapeutic targets in the prevention of vasospasm or its ischemic consequences.