Evan R. Ransom

Preoperative prediction of long-term outcome in poor-grade aneurysmal subarachnoid hemorrhage

OBJECTIVE:To evaluate which presentation indices, demographics, and clinical information predict 12-month outcome in poor-grade aneurysmal subarachnoid hemorrhage (SAH), and to provide a preoperative index of prognosis. METHODS:Data were obtained on all patients with poor-grade (Hunt and Hess Grades IV and V) aneurysmal SAH from a prospectively maintained SAH database and health outcomes project. Demographics, medical history, presenting clinical condition, and health outcomes were analyzed. Survival analysis was performed and Kaplan-Meier curves were generated. Multivariable logistic regression analysis was used to identify significant predictors of poor outcome at 12 months after hemorrhage, as measured by the modified Rankin disability scale. RESULTS:Survival curves for open surgery and endovascular treatment did not differ significantly. Overall, 40% of the 98 definitively treated patients had a favorable outcome at 12 months. Multivariable analysis identified patient age older than 65 years (P < 0.001), hyperglycemia (P < 0.03), worst preoperative Hunt and Hess Grade V (P < 0.0001), and aneurysm size of at least 13 mm (P < 0.002) as significant predictors of poor outcome. These variables were weighted and used to compute a poor-grade aneurysmal SAH Prognosis Score (hereafter, Prognosis Score) for each patient. A Prognosis Score of 0 was associated with a 90% favorable outcome; Prognosis Score of 1 with 83%; Prognosis Score of 2 with 43%; Prognosis Score of 3 with 8%; Prognosis Score of 4 with 7%; and a Prognosis Score of 5 with 0%. CONCLUSION:Outcome in poor-grade aneurysmal SAH is strongly predicted by patient age, worst preoperative Hunt and Hess clinical grade, and aneurysm size. Hyperglycemia on admission after poor-grade aneurysmal SAH increases the likelihood of poor outcome, and is a potentially modifiable risk factor. The Prognosis Score is a useful tool for preoperatively assessing the likelihood of a favorable outcome for poor-grade aneurysmal SAH patients.

Herniation Secondary to Critical Postcraniotomy Cerebrospinal Fluid Hypovolemia

OBJECTIVE:Cerebrospinal fluid hypovolemia resulting in postural headaches is a well-known clinical entity, but severe forms of cerebrospinal fluid hypovolemia with altered mental status and signs of transtentorial herniation (“brain sag”) have rarely been reported. This article describes the clinical features of brain sag after craniotomy in an attempt to increase recognition of this syndrome. METHODS:Between April 2001 and January 2003, 220 consecutive patients with subarachnoid hemorrhage were prospectively enrolled in the Columbia Subarachnoid Hemorrhage Outcomes Project; 137 underwent craniotomy for aneurysm clipping. Among these patients, the diagnosis of brain sag was made when all three of the following criteria were present: clinical signs of transtentorial herniation, head computed tomographic scans revealing effacement of the basal cisterns with an oblong brainstem, and improvement of symptoms after placement of the patient in the Trendelenburg position (–15 to –30 degrees). For each patient, the symptoms, clinical course, and subsequent response to treatment were characterized. In addition, brainstem dimensions were measured on computed tomographic scans taken before, during, and after resolution of brain sag. A “sag ratio” was generated for these time points by dividing the maximum anteroposterior distance by the maximum bipeduncular distance. RESULTS:Eleven (8.0%) of 137 aneurysmal subarachnoid hemorrhage patients treated by craniotomy and an intraoperative spinal drain met the criteria for brain sag. Signs of transtentorial herniation developed most commonly between 2 and 4 days postoperatively. Pupillary asymmetry was noted in 10 (91.0%) of 11 patients, whereas the other patient demonstrated extensor posturing. The Trendelenburg position reversed the symptoms in all patients. The mean sag ratios before, during, and after resolution of brain sag were 0.91 ± 0.03 (mean ± standard error), 1.18 ± 0.03, and 0.91 ± 0.03, respectively. This represented a 30.9% elongation of the brainstem during sag (P < 0.001) and a 23.6% change back to baseline after resolution of the syndrome (P < 0.002). There was no significant difference between the presag and postsag ratios. CONCLUSION:Severe cerebrospinal fluid hypovolemia after craniotomy may produce a dramatic herniation syndrome that is completely reversed by the Trendelenburg position. Brain sag should be included in the differential diagnosis for acute postoperative clinical deterioration in this patient population.

Racial Differences in Cerebral Vasospasm: A Systematic Review of the Literature

OBJECTIVE: Despite a significant body of clinical research and the widespread use of early intervention with aggressive postoperative management, cerebral vasospasm (CV) continues to contribute significantly to the morbidity and mortality of aneurysmal subarachnoid hemorrhage (aSAH). Many studies have evaluated predictive factors, although none to date has investigated a possible difference in the incidence of CV between Asian and white patients. We present a review of the modern aSAH literature to examine the incidence of CV in Japan and Europe, two highly researched populations. METHODS: A literature search was performed using the Medline and PubMed databases. Studies conducted in Japan or Europe published between 1990 and 2004 that reported an incidence of CV after aSAH were subjected to a thorough review. Data from included studies were categorized by origin (Japan or Europe) and method of CV diagnosis (angiography, delayed ischemic neurological deficit, or new infarct attributable to CV), and then were combined. Recorded incidences then were compared using a &khgr;2 test, and estimates of the relative risk of vasospasm were computed. RESULTS: The initial literature search identified 102 studies, and 32 studies met all inclusion criteria. The incidence of vasospasm diagnosed by angiography, delayed ischemic neurological deficit, and computed tomography was significantly greater in Japanese studies (all P < 0.001). The relative risks for Japanese patients as compared with European patients were 2.04, 2.07, and 1.53 for angiographic CV, delayed ischemic neurological deficit, and new infarct, respectively. CONCLUSION: Patients in Japanese studies were more likely to experience CV after aSAH across diagnostic methods. This may be a manifestation of genetic differences between Japanese and European populations. Clinicians should consider possible patient differences when interpreting CV research conducted in these populations.

Serial magnetic resonance imaging in experimental primate stroke: Validation of MRI for pre-clinical cerebroprotective trials

Abstract Precise assessment of stroke outcome is critical for pre-clinical testing of cerebroprotective strategies. Differences in stroke volume measured by various magnetic resonance imaging (MRI) techniques are documented in humans, but not well described in experimental primate stroke. This study characterizes changes in stroke volume using serial MRI scans in a baboon model of reperfused cerebral ischemia. The location/area of hyperintensity on MRI corresponded with the TTC-stained infarct region. T2-weighted fast spin echo (T2W FSE), fluid attenuated inversion recovery (FLAIR), and diffusion weighted imaging (DWI) showed a decrease in infarct volume between 72 h and nine days post-ischemia (p = ns, p = 0.029, and p = 0.006). T2W FSE and FLAIR demonstrated an increase in infarct volume from 24 h to nine days postischemia, while DWI displayed a decrease over the same period. While early T2W FSE, FLAIR, and DWI all correlated with late infarct volume (p < 0.001), 72 h T2W FSE was the best direct measure (2.39% ± 1.40% unity deviation). Serial MRI in a nonhuman primate model of focal cerebral ischemia recapitulates findings in clinical stroke. MRI at 72 h accurately predicts late infarct volume.

Critical postcraniotomy cerebrospinal fluid hypovolemia: risk factors and outcome analysis.

OBJECTIVE:Critical cerebrospinal fluid (CSF) hypovolemia may cause acute postoperative clinical deterioration in aneurysmal subarachnoid hemorrhage patients after craniotomy for microsurgical aneurysm clipping. We sought to identify risk factors for critical CSF hypovolemia and determine this syndrome’s effect on clinical outcome. METHODS:Between April 2001 and June 2004 at Columbia University Medical Center, 16 aneurysmal subarachnoid hemorrhage patients were diagnosed with postoperative critical CSF hypovolemia, whereas 151 patients who underwent craniotomy for clipping were not. The demographics, as well as the presenting radiographic and clinical characteristics, of these groups were evaluated. In addition, a 2:1 matched case-control comparison of patients with and without critical CSF hypovolemia was completed using clinical data, operative variables, and outcome data. Outcome analysis was performed with a battery of tests designed to assess global outcome, cognitive function, independence, and quality of life. RESULTS:There was no difference in clinical grade, Fisher score, age, and sex distribution between patients diagnosed with critical CSF hypovolemia and the general aneurysmal subarachnoid hemorrhage population at Columbia University Medical Center. Subsequent 2:1 matched case-control comparison demonstrated a higher incidence of global cerebral edema on admission computed tomographic scans (75 versus 31%; P < 0.01) and a significantly longer operative time for patients with critical CSF hypovolemia (5 h 18 min versus 4 h 22 min; P < 0.03). No significant differences were observed between groups in outcome assessments at the time of hospital discharge or the 3-month follow-up examination. CONCLUSION:Risk factors associated with an increased incidence of critical CSF hypovolemia after aneurysm surgery include the presence of global cerebral edema on admission head computed tomographic scans and prolonged operative time. In such patients, heightened suspicion of CSF hypovolemia is crucial because rapid and appropriate management obviates excess morbidity and mortality.

Shunt failure in idiopathic intracranial hypertension presenting with spontaneous cerebrospinal fluid leak

A case of spontaneous cerebrospinal (CSF) fluid leak after ventriculoperitoneal shunt (VPS) failure in a patient with idiopathic intracranial hypertension (IIH) is reported. This is the first report of spontaneous CSF leak in an IIH patient without a history of trauma, sinus surgery, or intracranial surgery. The diagnosis was confirmed using thin-sliced post-contrast computed tomography, which revealed a micro-dehiscence of the cribiform plate at the superior aspect of the ethmoid sinus. The patient underwent VPS revision without complication, resulting in complete amelioration of symptoms and cessation of CSF rhinorrhoea at 1 year follow up.

Internet-based neuro-oncology patient recruitment.

THE PRIVACY RULE, as part of the Health Insurance Portability and Accountability Act, was implemented in 2003 as a response to public concern over potential abuses of private health information. Although the Privacy Rule was not intended to place limits on clinical research, its complexity has caused much confusion throughout the academic medicine and research communities. Many clinical and translational researchers have created clinical databases or human tissue banks to facilitate future research. Maintenance of such databases is considered a research activity under the Privacy Rule, and researchers are, therefore, subject to its regulations. We present a novel Internet-based method to generate and maintain a neurooncology patient registry and human tissue bank. Through our web site, we secure both Health Insurance Portability and Accountability Act research authorization and informed consent, enabling us to contact the treating physician for clinical data and pathological specimens. Considering the importance of continued use of clinical databases and tissue banks in the genetic era of medicine, our method offers one way for researchers to adapt to the changing world of clinical research.

2-Hexyl Cyanoacrylate (Neuracryl M) Embolization of Cerebral Arteriovenous Malformations

OBJECTIVE: Neuracryl M is a newly designed liquid embolic agent. In an attempt to verify the safety and efficacy of neuracryl M, we participated in the PROVASIS Trial, a pilot study using this agent in the preoperative treatment of cerebral arteriovenous malformations (AVMs). Because the trial was prematurely terminated by the sponsoring company because of financial considerations, we now present our data as a single center series. METHODS: Between November 2002 and December 2003, six patients were enrolled in the PROVASIS trial at our institution, and four of these patients were randomized to treatment with neuracryl M. The patients were a 30-year-old man with a right frontal lobe AVM, a 20-year-old man with a right cerebellar AVM, a 26-year-old woman with a midline cerebellar AVM, and a 47-year-old man with a left parietotemporal lobe AVM. All patients underwent AVM embolization with neuracryl M, followed by definitive treatment, either open surgery or radiosurgery. RESULTS: In each case, there were no permanent complications, and blood loss was minimal. Follow-up imaging demonstrated either complete AVM obliteration (open surgery) or substantial diminution in AVM size (radiosurgery). CONCLUSION: Our data provide preliminary evidence supporting the thesis that neuracryl M is a safe and effective liquid embolic agent for the preoperative embolization of cerebral AVMs. Larger trials and continued experience using this novel liquid embolic agent are warranted.

Co-registration of radiographic and pathologic infarct territory in a non-human primate model of stroke

Abstract Objectives: Infarct volume correlation using magnetic resonance imaging (MRI) and pathology specimens enables exact tissue localization of cerebral injury following experimental stroke. We describe a protocol that enables co-registration of radiographic signal change and histologic ischemia in a non-human primate model of stroke. Methods: One male baboon underwent left middle cerebral artery territory occlusion/reperfusion. MRI [5 mm axial T2 weighted (T2W) slices] was carried out 9 days post-ischemia after which the animal was killed. Immediately post-mortem, the whole brain was perfused and fixed in paraformaldehyde and sliced into 5 mm axial sections that corresponded to those demonstrated on MRI. Slices (40 μm) were obtained from each section and were then stained using Luxol hematoxylin and eosin. Results: The relative area of hyperintensity demonstrated on T2W MRI approximates, in size and location, the region of infarct on gross pathology. This was confirmed microscopically. Discussion: With the use of advanced imaging modalities, this co-registration technique affords the capacity to differentiate ischemic core, penumbra, and uninjured cortex following experimental stroke. Such a precise delineation enables immunohistochemical analysis of a wide variety of substrates in each of the aforementioned regions.

Critical postcraniotomy cerebrospinal fluid hypovolemia: Risk factors and outcome analysis - Commentary

OBJECTIVE:Critical cerebrospinal fluid (CSF) hypovolemia may cause acute postoperative clinical deterioration in aneurysmal subarachnoid hemorrhage patients after craniotomy for microsurgical aneurysm clipping. We sought to identify risk factors for critical CSF hypovolemia and determine this syndrome’s effect on clinical outcome. METHODS:Between April 2001 and June 2004 at Columbia University Medical Center, 16 aneurysmal subarachnoid hemorrhage patients were diagnosed with postoperative critical CSF hypovolemia, whereas 151 patients who underwent craniotomy for clipping were not. The demographics, as well as the presenting radiographic and clinical characteristics, of these groups were evaluated. In addition, a 2:1 matched case-control comparison of patients with and without critical CSF hypovolemia was completed using clinical data, operative variables, and outcome data. Outcome analysis was performed with a battery of tests designed to assess global outcome, cognitive function, independence, and quality of life. RESULTS:There was no difference in clinical grade, Fisher score, age, and sex distribution between patients diagnosed with critical CSF hypovolemia and the general aneurysmal subarachnoid hemorrhage population at Columbia University Medical Center. Subsequent 2:1 matched case-control comparison demonstrated a higher incidence of global cerebral edema on admission computed tomographic scans (75 versus 31%; P < 0.01) and a significantly longer operative time for patients with critical CSF hypovolemia (5 h 18 min versus 4 h 22 min; P < 0.03). No significant differences were observed between groups in outcome assessments at the time of hospital discharge or the 3-month follow-up examination. CONCLUSION:Risk factors associated with an increased incidence of critical CSF hypovolemia after aneurysm surgery include the presence of global cerebral edema on admission head computed tomographic scans and prolonged operative time. In such patients, heightened suspicion of CSF hypovolemia is crucial because rapid and appropriate management obviates excess morbidity and mortality.