Clinicoradiological review: bilateral ethmoidal artery dural arteriovenous fistulas.
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Publications and source records attributed to E Sander Connolly.
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BACKGROUND: While efforts have been made to document short-term outcomes following poor grade aneurysmal subarachnoid hemorrhage (aSAH), no data exist concerning the degree of delayed improvement in neurological function. Here we assess cognitive function, level of independence, and quality of life (QoL) over 12 months following poor grade aSAH. METHODS: Data on definitively treated poor grade patients (Hunt and Hess grade IV or V) surviving 12 months post-aSAH were obtained through a prospectively maintained SAH database. Demographic information, medical history, and clinical course were analyzed. Health outcomes assessments completed by surviving patients at discharge (DC), three months (3 M) and 12 months (12 M) follow-up, including the Telephone Interview for Cognitive Status (TICS), Barthel Index (BI), and Sickness Impact Profile (SIP), were used to evaluate cognitive function, level of independence, and QoL. FINDINGS: Fifty-six poor grade patients underwent aneurysm-securing intervention and survived at least 12 months post-aSAH. Thirty-five (63%) surviving patients underwent health outcomes assessments at DC, 3 M and 12 M post-aSAH. A majority of patients had improved scores on the TICS (DC to 3 M: 91%; 3 M to 12 M: 82%), BI (DC to 3 M: 96%; 3 M to 12 M: 92%), and SIP (3 M to 12 M: 80%) following aSAH. Using paired-sample analyses, significant improvement on each test was observed. CONCLUSION: A substantial portion of patients experience cognitive recovery, increased independence, and improved QoL following poor grade aSAH. Delayed follow-up assessments are necessary when evaluating functional recovery in this population. These findings have the potential to impact poor grade aSAH management and prognosis.
In an effort to help clarify the current state of medical therapy for cerebral vasospasm, the authors reviewed the relevant literature on the established medical therapies used for cerebral vasospasm following aneurysmal subarachnoid hemorrhage (SAH), and they discuss burgeoning areas of investigation. Despite advances in the treatment of aneurysmal SAH, cerebral vasospasm remains a common complication and has been correlated with a 1.5- to threefold increase in death during the first 2 weeks after hemorrhage. A number of medical, pharmacological, and surgical therapies are currently in use or being investigated in an attempt to reverse cerebral vasospasm, but only a few have proven to be useful. Although much has been elucidated regarding its pathophysiology, the treatment of cerebral vasospasm remains a dilemma. Although a poor understanding of SAH-induced cerebral vasospasm pathophysiology has, to date, hampered the development of therapeutic interventions, current research efforts promise the eventual production of new medical therapies.
The complement cascade has been implicated in ischemia/reperfusion injury, and recent studies have shown that complement inhibition is a promising treatment option for acute stroke. The development of clinically useful therapies has been hindered, however, by insufficient understanding of which complement subcomponents contribute to post-ischemic injury. To address this issue, we subjected mice deficient in selected complement proteins (C1q, C3, C5) to transient focal cerebral ischemia. Of the strains investigated, only C3-/- mice were protected, as demonstrated by 34% reductions in both infarct volume (P<0.01) and neurological deficit score (P<0.05). C3-deficient mice also manifested decreased granulocyte infiltration (P<0.02) and reduced oxidative stress (P<0.05). Finally, administration of a C3a-receptor antagonist resulted in commensurate neurological improvement and stroke volume reduction (P<0.05). Together, these results establish C3 activation as the key constituent in complement-related inflammatory tissue injury following stroke and suggest a C3a anaphylatoxin-mediated mechanism.
The Adhesive Removal (sticky-tape) test is a commonly used test of somatosensory dysfunction following cerebral ischemia in rats. This test requires several days of pre-training prior to surgery, which can be time consuming. We present our results with an improved version of the sticky-tape test. Male Wistar rats were subjected to either sham surgery (n = 4) or right middle cerebral artery occlusion (rMCAo) using an intraluminal filament (n = 9), followed by a 10-day survival period. On post-operative days (POD) 1, 3, 7, and 10 animals underwent both the conventional sticky-tape test (CST) with measurement of the time to remove the stimulus (trs), as well as a modified sticky-tape test (MST), in which a non-removable tape sleeve was placed around the animal's paw. Time spent attending to this stimulus (tas) was recorded. Despite 3 days of pre-training, animals undergoing baseline CST still exhibited marked variability in pre-operative baseline test performance (trs range 1-60s). In contrast, animals undergoing MST for the first time demonstrated nearly uniformly excellent performance (% tas range 91.5-98.5% of the 30s testing period). Although, affected (left) limb performance on both CST (6.8-fold increase in trs on POD 1 compared to baseline) and MST (100% decrease in tas on POD 1 compared to baseline) was markedly altered by rMCAo, CST performance declined bilaterally, and no significant differences in the ratio of affected (left) and unaffected (right) limb performance between sham-operated and rMCAo animals were observed at any time point. In contrast, the ratio of left to right performance on the MST was significantly different at all time points (P<0.01). In conclusion, we present a simple modification of the widely used Adhesive Removal test and provide evidence that this test can accurately assess neurological dysfunction in rodents, not only with minimal pre-training, but also with improved localization of the side of injury.
Recent studies have focused on elucidating the contribution of individual complement proteins to post-ischemic cellular injury. As the timing of complement activation and deposition after cerebral ischemia is not well understood, our study investigates the temporal pattern of C1q accumulation after experimental murine stroke. Brains were harvested from mice subjected to transient focal cerebral ischemia at 3, 6, 12, and 24 hr post reperfusion. Western blotting and light microscopy were employed to determine the temporal course of C1q protein accumulation and correlate this sequence with infarct evolution observed with TTC staining. Confocal microscopy was utilized to further characterize the cellular localization and characteristics of C1q deposition. Western Blot analysis showed that C1q protein begins to accumulate in the ischemic hemisphere between 3 and 6 hr post-ischemia. Light microscopy confirmed these findings, showing concurrent C1q protein staining of neurons. Confocal microscopy demonstrated co-localization of C1q protein with neuronal cell bodies as well as necrotic cellular debris. These experiments demonstrate the accumulation of C1q protein on neurons during the period of greatest infarct evolution. This data provides information regarding the optimal time window during which a potentially neuroprotective anti-C1q strategy is most likely to achieve therapeutic success.
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OBJECTIVE: Medical complications occur frequently after subarachnoid hemorrhage (SAH). Their impact on outcome remains poorly defined. DESIGN: Inception cohort study. PATIENTS: Five-hundred eighty patients enrolled in the Columbia University SAH Outcomes Project between July 1996 and May 2002. SETTING: Neurologic intensive care unit. INTERVENTIONS: Patients were treated according to standard management protocols. MEASUREMENTS AND MAIN RESULTS: Poor outcome was defined as death or severe disability (modified Rankin score, 4-6) at 3 months. We calculated the frequency of medical complications according to prespecified criteria and evaluated their impact on outcome, using forward stepwise multiple logistic regression after adjusting for known predictors of poor outcome. Thirty-eight% had a poor outcome; mortality was 21%. The most frequent complications were temperature>38.3 degreesC (54%), followed by anemia treated with transfusion (36%), hyperglycemia>11.1 mmol/L (30%), treated hypertension (>160 mm Hg systolic; 27%), hypernatremia>150 mmol/L (22%), pneumonia (20%), hypotension (<90 mm Hg systolic) treated with vasopressors (18%), pulmonary edema (14%), and hyponatremia<130 mmol/L (14%). Fever (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1-3.4; p=.02), anemia (OR, 1.8; 95% CI, 1.1-2.9; p=.02), and hyperglycemia (OR, 1.8; 95% CI, 1.1-3.0; p=.02) significantly predicted poor outcome after adjustment for age, Hunt-Hess grade, aneurysm size, rebleeding, and cerebral infarction due to vasospasm. CONCLUSIONS: Fever, anemia, and hyperglycemia affect 30% to 54% of patients with SAH and are significantly associated with mortality and poor functional outcome. Critical care strategies directed at maintaining normothermia, normoglycemia, and prevention of anemia may improve outcome after SAH.
INTRODUCTION: Although magnesium provides cerebral protection in animal stroke models, magnesium therapy has significant side effects in humans. Therefore, we sought to examine the incidence of alpha-agonist treated hypotension in our ongoing, prospective, randomized, double-blind, placebo-controlled Phase I/IIa dose escalation study of magnesium therapy in patients undergoing carotid endarterectomy. METHODS: Eighty patients undergoing elective carotid endarterectomy were randomly assigned to a placebo control group (n = 38) or to one of the three intravenous magnesium groups. Magnesium levels were obtained before induction, and then 15 minutes, 1 hour, 2 hours, 6 hours, 12 hours, and 24 hours after a loading dose and infusion. After surgery, a target systolic blood pressure range was chosen, and the amount and duration of phenylephrine needed to maintain that pressure was compared across treatment groups. RESULTS: All treatment groups achieved levels significantly different from baseline at 12 and 24 hours (P < 0.01). Magnesium treatment did not significantly increase the proportion of patients requiring pressure support. For those requiring pressure support, the amount and average duration of phenylephrine required was not different between control patients and those receiving magnesium, even when the individual minimum systolic blood pressures required were subdivided on the basis of dose of magnesium administered. CONCLUSION: There were no significant differences detected in the 1) percentage of patients requiring pressor support, 2) the duration of postoperative pressor support, or 3) the amount of phenylephrine support needed between controls and magnesium treated patients. The percentage of patients requiring pressure support depended on the minimum systolic blood pressure ordered after surgery.
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 chi 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.
OBJECTIVE: Neurocognitive dysfunction has been shown to occur in roughly 25% of patients undergoing carotid endarterectomy (CEA). Despite this, little is known about the mechanism of this injury. Recently, several groups have shown that new diffusion weighted imaging (DWI)-positive lesions are seen in 20% of patients undergoing CEA. We investigated to what degree neurocognitive dysfunction was associated with new DWI lesions. METHODS: Thirty-four consecutive patients undergoing CEA were subjected to pre- and postoperative cognitive evaluation with a battery of neuropsychological tests. Postoperative magnetic resonance imaging was performed in all patients within 24 hours of surgery. Lesions that showed high signal on DWI and restricted diffusion on apparent diffusion coefficient maps but no abnormal high signal on the fluid-attenuated inversion recovery images were considered hyperacute. RESULTS: Cognitive dysfunction was seen in eight (24%) patients. New hyperacute DWI lesions were seen in three (9%). Only one (13%) of the patients with cognitive dysfunction had a new DWI lesion. Two thirds of the new DWI lesions occurred in the absence of cognitive deterioration. Patients with cognitive dysfunction had significantly longer carotid cross-clamp times. CONCLUSION: Neurocognitive dysfunction after CEA does not seem to be associated with new DWI positive lesions.
Intracranial atherosclerosis is responsible for a significant number of strokes. Medical therapy for this condition may fail, leaving patients at high risk for cerebral infarction and death. With advances in endovascular techniques on the horizon, understanding the prognosis of conservative treatment is essential for appropriate patient management. Although several small studies have attempted to address this issue, a comprehensive review regarding the natural history of intracranial atherosclerosis in a vessel-specific manner is lacking. Owing to heterogeneity in vascular anatomy and physiology, atherosclerosis in different vessels may represent diseases with fundamentally distinct courses. Therefore, it is important to distinguish vascular territories when studying the natural history of this condition. To this end, we critically review the literature investigating medical management of patients with intracranial atherosclerosis, segregating our findings by vessel. Analysis by this method suggests that middle cerebral artery atherosclerosis carries a lower mortality rate than stenoses involving other intracranial vessels, and that asymptomatic disease follows a more benign course. In addition, plaque progression and transcranial Doppler-detected microemboli seem to predict outcome according to limited data. This comprehensive review may help guide clinical decision-making and therapeutic developments in this patient population.
OBJECTIVE: Although the incidence of stroke after carotid endarterectomy (CEA) is low (1-3%), approximately 25% of patients experience subtle declines in postoperative neuropsychometric function. No studies have investigated the risk factors for this neurocognitive change. We sought to identify predictors of postoperative neurocognitive dysfunction. METHODS: We enrolled 186 CEA patients, with both symptomatic and asymptomatic stenosis, to undergo a battery of neuropsychometric tests preoperatively and on postoperative Days 1 and 30. Neurocognitive dysfunction was defined as a two standard deviation decline in performance compared with a similarly aged control group of lumbar laminectomy patients. Univariate logistic regression was performed for age, sex, obesity, smoking, symptomatology, diabetes mellitus, hypertension, hypercholesterolemia, use of statin medication, previous myocardial infarction, previous CEA, operative side, duration of surgery, duration of carotid cross-clamp, and weight-adjusted doses of midazolam and fentanyl. Variables achieving univariate P < 0.10 were included in a multivariate analysis. Data is presented as (odds ratio, 95% confidence interval, P-value). RESULTS: Eighteen and 9% of CEA patients were injured on postoperative Days 1 and 30, respectively. Advanced age predicted neurocognitive dysfunction on Days 1 and 30 (1.93 per decade, 1.15-3.25, 0.01; and 2.57 per decade, 1.01-6.51, 0.049, respectively). Additionally, diabetes independently predicted injury on Day 30 (4.26, 1.15-15.79, 0.03). CONCLUSIONS: Advanced age and diabetes predispose to neurocognitive dysfunction after CEA. These results are consistent with risk factors for neurocognitive dysfunction after coronary bypass and major stroke after CEA, supporting an underlying ischemic pathophysiology. Further work is necessary to determine the role these neurocognitive deficits may play in appropriately selecting patients for CEA.
OBJECTIVE: Stroke is a leading cause of morbidity and mortality in the United States. Recent animal studies have implicated the complement system in cerebral ischemia/reperfusion injury and suggest that complement inhibition may improve stroke outcomes. To assess the applicability of these findings to humans, we evaluated the characteristics and time course of human complement activation after stroke. METHODS: We compared peripheral blood levels of complement factor 3a (C3a), 5a (C5a), and sC5b-9 drawn from 15 patients on poststroke Days 1, 2, 3, 7, 14, 21, and 28 to age-, race/ethnicity-, and sex-matched controls from the same population. Statistical analysis was performed using unpaired Mann-Whitney nonparametric tests with Bonferroni correction. All data is presented as the mean +/- standard deviation. RESULTS: Mean C3a concentrations showed significant early elevations in stroke patients relative to matched controls (controls: 1080 +/- 189 ng/ml; Day 1: 1609 +/- 422 ng/ml, P = 0.0008; Day 3: 1520 +/- 317 ng/ml, P = 0.0005; Day 7: 1526 +/- 386 ng/ml, P = 0.001). C3a was also significantly elevated on Day 28 (1448 +/- 386 ng/ml, P = 0.004). Before poststroke Day 7, mean C5a levels did not differ significantly from controls. However, beginning on Day 7 and continuing through Day 14, there were significant elevations in C5a (controls: 3.33 +/- 2.1 ng/ml; day 7: 6.86 +/- 3.5 ng/ml, P = 0.005; Day 14: 7.65 +/- 4.6 ng/ml, P = 0.004). Mean sC5b-9 concentrations showed early depressions that reached significance on Days 1 and 2 (controls: 275.6 +/- 107 ng/ml; Day 1: 167.0 +/- 108 ng/ml, P = 0.006; Day 2: 156.3 +/- 80.0 ng/ml, P = 0.005) and did not differ significantly from controls at any other time point. CONCLUSION: C3a is acutely elevated after human ischemic stroke, C5a shows delayed elevations 7 to 14 days after cerebral ischemia, and sC5b-9 is acutely depressed after stroke. Together, these data confirm complement activation after stroke and suggest that this activation is a heterogeneous process, with varying responses for different components.
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.
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.
OBJECTIVE: Oxidative damage has been implicated in the pathogenesis of cerebral ischemia. We previously demonstrated that exogenously supplied dehydroascorbic acid (DHA), an oxidized, blood-brain barrier transportable form of the antioxidant ascorbic acid (AA), improves outcome after experimental stroke. METHODS: To investigate the neuroprotective effect of DHA therapy, we measured cerebral AA levels using a novel assay, quantified markers of lipid peroxidation, and evaluated infarct volume after reperfused stroke in a murine model. All experiments were performed using a new citrate/sorbitol-stabilized DHA formulation to improve the stability of the compound. RESULTS: Intraparenchymal AA levels declined after cerebral ischemia/reperfusion and were repleted in a dose-dependent fashion by postischemic administration of intravenous DHA (P < 0.01). Repletion of these levels was associated with reductions in cerebral malondialdehyde levels (P < 0.05), which were also elevated after reperfused stroke. DHA repletion of interstitial AA levels and reduction in cerebral lipid peroxidation was associated with dose-dependent reductions in infarct volume (P < 0.05). CONCLUSION: Together, these results indicate that an intravenous cerebroprotective dose of citrate/sorbitol-stabilized DHA is correlated with increased brain ascorbate levels and a suppression of excessive oxidative metabolism.
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.