Neuroprotective Effect of an Antioxidant, Ebselen, in Patients with Delayed Neurological Deficits after Aneurysmal Subarachnoid Hemorrhage

Abstract OBJECTIVE After aneurysmal subarachnoid hemorrhage, approximately 30% of patients experience delayed neurological deficits, related in part to arterial vasospasm and dysautoregulation. Transcranial Doppler (TCD) ultrasonography is commonly used to noninvasively detect arterial vasospasm. We studied cerebral perfusion patterns and associated TCD indices for 25 patients who developed clinical signs of delayed neurological deficits. METHODS Patients were treated in a neurosurgical intensive care unit and were studied if they exhibited delayed focal or global neurological deterioration. Positron emission tomographic cerebral blood flow (CBF) studies and TCD studies measuring the mean flow velocity (FV) of the middle cerebral artery and the middle cerebral artery FV/internal carotid artery FV ratio (with the internal carotid artery FV being measured extracranially at the cranial base) were performed. Glasgow Outcome Scale scores were assessed at 6 months. RESULTS A markedly heterogeneous pattern of CBF distribution was observed, with hyperemia, normal CBF values, and reduced flow being observed among patients with delayed neurological deficits. TCD indices were not indicative of the cerebral perfusion findings. The mean CBF value was slightly lower for patients who did not survive (32.3 ml/100 g/min), compared with those who did survive (36.0 ml/100 g/min, P= 0.05). CONCLUSION Among patients who developed delayed neurological deficits after aneurysmal subarachnoid hemorrhage, a wide range of cerebral perfusion disturbances was observed, calling into question the traditional concept of large-vessel vasospasm. Commonly used TCD indices do not reflect cerebral perfusion values.

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Use of the Extracranial-Intracranial Arterial Bypass in the Management of Refractory Vasospasm: A Case Report

Neurosurgery ◽

10.1227/00006123-198509000-00013 ◽

1985 ◽

Vol 17 (3) ◽

pp. 474-479 ◽

Cited By ~ 6

Author(s):

Jacob Rosenstein ◽

Hunt H. Batjer ◽

Duke S. Samson

Keyword(s):

Case Report ◽

Subarachnoid Hemorrhage ◽

Arterial Hypertension ◽

Volume Expansion ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Morbidity And Mortality ◽

Neurological Deficits ◽

Collateral Flow ◽

Intravascular Volume ◽

Arterial Vasospasm

Abstract Cerebral arterial vasospasm after aneurysmal subarachnoid hemorrhage remains one of the major causes of morbidity and mortality in patients surviving the initial hemorrhage. Once established, no known method has been shown to reverse this process in humans. Although intravascular volume expansion and induced arterial hypertension have been shown to be effective in the reversal of neurological deficits secondary to vasospasm, a large proportion of patients remain refractory to these methods. We report one such case successfully managed by the estalishment of an extracranial-intracranial anastomosis in an attempt to augment collateral flow.

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Delayed neurological deficits detected by an ischemic pattern in the extracellular cerebral metabolites in patients with aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/jns.2004.100.1.0008 ◽

2004 ◽

Vol 100 (1) ◽

pp. 8-15 ◽

Cited By ~ 101

Author(s):

Jane Skjøth-Rasmussen ◽

Mette Schulz ◽

Soren Risom Kristensen ◽

Per Bjerre

Keyword(s):

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Cerebral Metabolism ◽

Brain Infarction ◽

Neurological Deficits ◽

Parent Artery ◽

Glycerol Concentration ◽

Microdialysis Probe ◽

Content Type ◽

Fine Print

Object. In the treatment of patients with aneurysmal subarachnoid hemorrhage (SAH), early occlusion of the aneurysm is necessary as well as monitoring and treatment of complications following the primary bleeding episode. Monitoring with microdialysis has been studied for its ability to indicate and predict the occurrence of delayed ischemic neurological deficits (DINDs) in patients with SAH. Methods. In 42 patients with aneurysmal SAH microdialysis monitoring of metabolites was performed using a 0.3-µl/minute perfusion flow over several days, and the results were correlated to clinical events and to brain infarction observed on computerized tomography scans. The microdialysis probe was inserted into the territory of the parent artery of the aneurysm. The authors defined an ischemic pattern as increases in the lactate/glucose (L/G) and lactate/pyruvate (L/P) ratios that were greater than 20% followed by a 20% increase in glycerol concentration. This ischemic pattern was found in 17 of 18 patients who experienced a DIND and in three of 24 patients who did not experience a delayed clinical deterioration. The ischemic pattern preceded the occurrence of a DIND by a mean interval of 11 hours. Maximum L/G and L/P ratios did not correlate with the presence of DIND or outcome, and there was no association between the glycerol level and subsequent brain infarction. Conclusions. Microdialysis monitoring of the cerebral metabolism in patients with SAH may predict with high sensitivity and specificity the occurrence of a DIND. Whether an earlier diagnosis results in better treatment of DINDs and, therefore, in overall better outcomes remains to be proven, as it is linked to an efficacious treatment of cerebral vasospasm.

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Correlation Among Systemic Inflammatory Parameter, Occurrence of Delayed Neurological Deficits, and Outcome After Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽

10.1227/neu.0b013e31828048ce ◽

2012 ◽

Vol 72 (3) ◽

pp. 367-375 ◽

Cited By ~ 48

Author(s):

Carl Muroi ◽

Michael Hugelshofer ◽

Martin Seule ◽

Ilhan Tastan ◽

Masayuki Fujioka ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Confidence Interval ◽

Early Phase ◽

Odds Ratio ◽

Time Course ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Unfavorable Outcome ◽

Neurological Deficits ◽

Inflammatory Parameters ◽

Leukocyte Counts

Abstract BACKGROUND: The role and impact of systemic inflammatory response after aneurysmal subarachnoid hemorrhage remain to be elucidated. OBJECTIVE: To assess the time course and correlation of systemic inflammatory parameters with outcome and the occurrence of delayed ischemic neurological deficits (DINDs) after subarachnoid hemorrhage. METHODS: Besides the baseline characteristics, daily interleukin-6 (IL-6), procalcitonin, C-reactive protein levels, and leukocyte counts were prospectively measured until day 14 after subarachnoid hemorrhage. Occurrence of infectious complications and application of therapeutic hypothermia were assessed as confounding factors. The primary end point was outcome after 3 months, assessed by Glasgow Outcome Scale; the secondary end point was the occurrence of DINDs. RESULTS: During a 3-year period, a total of 138 patients were included. All inflammatory parameters measured were higher in patients with unfavorable outcome (Glasgow Outcome Scale score, 1-3). After adjustment for confounding factors, elevated IL-6 and leukocyte counts remained significant risk factors for unfavorable outcome. The odds ratio for log IL-6 was 4.07 (95% confidence interval, 1.18 to 14.03; P = .03) and for leukocyte counts was 1.24 (95% confidence interval, 1.06-1.46, P = .008). The analysis of the time course established that IL-6 was the only significantly elevated parameter in the early phase in patients with unfavorable outcome. Higher IL-6 levels in the early phase (days 3-7) were associated with the occurrence of DINDs. The adjusted odds ratio for log IL-6 was 4.03 (95% confidence interval, 1.21-13.40; P = .02). CONCLUSION: Higher IL-6 levels are associated with worse clinical outcome and the occurrence of DINDs. Because IL-6 levels were significantly elevated in the early phase, they might be a useful parameter to monitor.

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Characterization of perioperative seizures and epilepsy following aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/jns.2003.99.6.0978 ◽

2003 ◽

Vol 99 (6) ◽

pp. 978-985 ◽

Cited By ~ 99

Author(s):

Chih-Lung Lin ◽

Aaron S. Dumont ◽

Ann-Shung Lieu ◽

Chen-Po Yen ◽

Shiuh-Lin Hwang ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Predictive Factors ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Neurological Deficits ◽

Loss Of Consciousness ◽

Content Type ◽

Fisher Grade ◽

The Mean ◽

Fine Print

Object. The reported incidence, timing, and predictive factors of perioperative seizures and epilepsy after subarachnoid hemorrhage (SAH) have differed considerably because of a lack of uniform definitions and variable follow-up periods. In this study the authors evaluate the incidence, temporal course, and predictive factors of perioperative seizures and epilepsy during long-term follow up of patients with SAH who underwent surgical treatment. Methods. Two hundred seventeen patients who survived more than 2 years after surgery for ruptured intracranial aneurysms were enrolled and retrospectively studied. Episodes were categorized into onset seizures (≤ 12 hours of initial hemorrhage), preoperative seizures, postoperative seizures, and late epilepsy, according to their timing. The mean follow-up time was 78.7 months (range 24–157 months). Forty-six patients (21.2%) had at least one seizure post-SAH. Seventeen patients (7.8%) had onset seizures, five (2.3%) had preoperative seizures, four (1.8%) had postoperative seizures, 21 (9.7%) had at least one seizure episode after the 1st week postoperatively, and late epilepsy developed in 15 (6.9%). One (3.8%) of 26 patients with perioperative seizures (onset, preoperative, or postoperative seizure) had late epilepsy at follow up. The mean latency between the operation and the onset of late epilepsy was 8.3 months (range 0.3–19 months). Younger age (< 40 years old), loss of consciousness of more than 1 hour at ictus, and Fisher Grade 3 or greater on computerized tomography scans proved to be significantly related to onset seizures. Onset seizure was also a significant predictor of persistent neurological deficits (Glasgow Outcome Scale Scores 2–4) at follow up. Factors associated with the development of late epilepsy were loss of consciousness of more than 1 hour at ictus and persistent postoperative neurological deficit. Conclusions. Although up to one fifth of patients experienced seizure(s) after SAH, more than half had seizure(s) during the perioperative period. The frequency of late epilepsy in patients with perioperative seizures (7.8%) was not significantly higher than those without such seizures (6.8%). Perioperative seizures did not recur frequently and were not a significant predictor for late epilepsy.

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Influence of Fever and Hospital-Acquired Infection on the Incidence of Delayed Neurological Deficit and Poor Outcome after Aneurysmal Subarachnoid Hemorrhage

Neurology Research International ◽

10.1155/2012/479865 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 18

Author(s):

G. Logan Douds ◽

Bi Tadzong ◽

Akash D. Agarwal ◽

Satish Krishnamurthy ◽

Erik B. Lehman ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Neurological Deficits ◽

Multivariate Logistic Regression ◽

Hospital Acquired Infection ◽

Poor Outcome ◽

Independent Association ◽

Hospital Acquired ◽

The Relationship ◽

Retrospective Database

Although fever and infection have been implicated in the causation of delayed neurological deficits (DND) and poor outcome after aneurysmal subarachnoid hemorrhage (SAH), the relationship between these two often related events has not been extensively studied. We reviewed these events through of our retrospective database of patients with SAH. Multivariate logistic regression was used to determine independent predictors of DND and poor outcome. A total of 186 patients were analyzed. DND was noted in 76 patients (45%). Fever was recorded in 102 patients (55%); infection was noted in 87 patients (47%). A patient with one infection was more likely to experience DND compared to a patient with no infections (adjusted OR 3.73, 95% CI 1.62, 8.59). For those with more than two infections the likelihood of DND was even greater (adjusted OR 4.24, 95% CI 1.55, 11.56). Patients with 1-2 days of fever were less likely to have a favorable outcome when compared to their counterparts with no fever (adjusted OR 0.19, 95% CI 0.06, 0.62). This trend worsened as the number of days febrile increased. These data suggest that the presence of infection is associated with DND, but that fever may have a stronger independent association with overall outcome.

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Observations on the perioperative management of aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/jns.1986.65.1.0048 ◽

1986 ◽

Vol 65 (1) ◽

pp. 48-62 ◽

Cited By ~ 64

Author(s):

S. Sam Finn ◽

Sigurdur A. Stephensen ◽

Carole A. Miller ◽

Laura Drobnich ◽

William E. Hunt

Keyword(s):

Subarachnoid Hemorrhage ◽

Neurological Deficit ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Surgical Complication ◽

Neurological Deficits ◽

Arterial Line ◽

Postoperative Patient ◽

Content Type ◽

Wedge Pressure ◽

Fine Print

✓ Thirty-two patients with aneurysmal subarachnoid hemorrhage (SAH) were managed according to a protocol based on pain control and hemodynamic manipulation, monitored by an arterial line and Swan-Ganz catheter. Hemodynamic parameters were adjusted to four clinical situations. 1) For the unoperated patient with no neurological deficit, the regimen aims to maintain pulmonary wedge pressure (PWP) at 10 to 12 mm Hg, and the cardiac index (CI) and blood pressure (BP) at normal levels. 2) For the unoperated patient presenting with or developing neurological deficit, the PWP is increased until the deficit is reversed or the CI falls; the CI is high, and the BP normal. 3) For the postoperative patient with no neurological deficit, the PWP is maintained at 12 to 14 mm Hg, the CI is a high normal, and the BP is normal. 4) For the postoperative patient developing neurological deficit but showing no surgical complication on the computerized tomography scan, the PWP is increased until the deficit is reversed or the CI falls; the CI is high and the BP is increased with vasopressors if necessary. Fourteen patients developed neurological deficits either preoperatively, postoperatively, or both. Neurological deficits were repeatedly reversed by increasing the PWP, as measured hourly. In several patients an optimal wedge pressure was determined, below which deficits would reappear. In one patient whose neurological deficit was reversed on several occasions by increasing the PWP, the optimal PWP rose after each episode until it reached 22 mm Hg. Detailed event-related analysis of these patients' course illustrates these phenomena well. The optimal PWP varied from patient to patient, but ranged most frequently from 14 to 16 mm Hg. Meticulous monitoring of the patients' neurological status coupled with prompt correction of low PWP (assuming an adequate CI) has proven to be an effective way to prevent and reverse neurological deficits following aneurysmal SAH.

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