Connolly Es

Predictors of hemorrhage in patients with untreated brain arteriovenous malformation

Background: Intracranial hemorrhage is a serious possible complication in patients with brain arteriovenous malformation (AVM). Several morphologic factors associated with hemorrhagic AVM presentation have been established, but their relevance for the risk of subsequent AVM hemorrhage remains unclear. Methods: The authors analyzed follow-up data on 622 consecutive patients from the prospective Columbia AVM database, limited to the period between initial AVM diagnosis and the start of treatment (i.e., any endovascular, surgical, or radiation therapy). Univariate and multivariate logistic regression and Cox proportional hazard models were applied to analyze the effect of patient age, gender, AVM size, anatomic location, venous drainage pattern, and associated arterial aneurysms on the risk of intracranial hemorrhage at initial presentation and during follow-up. Results: The mean pretreatment follow-up was 829 days (median: 102 days), during which 39 (6%) patients experienced AVM hemorrhage. Increasing age (hazard ratio [HR] 1.05, 95% CI 1.03 to 1.08), initial hemorrhagic AVM presentation (HR 5.38, 95% CI 2.64 to 10.96), deep brain location (HR 3.25, 95% CI 1.30 to 8.16), and exclusive deep venous drainage (HR 3.25, 95% CI 1.01 to 5.67) were independent predictors of subsequent hemorrhage. Annual hemorrhage rates on follow-up ranged from 0.9% for patients without hemorrhagic AVM presentation, deep AVM location, or deep venous drainage to as high as 34.4% for those harboring all three risk factors. Conclusions: Hemorrhagic arteriovenous malformation (AVM) presentation, increasing age, deep brain location, and exclusive deep venous drainage appear to be independent predictors for AVM hemorrhage during natural history follow-up. The risk of spontaneous hemorrhage may be low in AVMs without these risk factors.

Procedural and Strain-related Variables Significantly Affect Outcome in a Murine Model of Focal Cerebral Ischemia

The recent availability of transgenic mice has led to a burgeoning number of reports describing the effects of specific gene products on the pathophysiology of stroke. Although focal cerebral ischemia models in rats have been well described, descriptions of a murine model of middle cerebral artery occlusion are scant and sources of potential experimental variability remain undefined. We hypothesized that slight technical modifications would produce widely discrepant results in a murine model of stroke and that controlling surgical and procedural conditions could lead to reproducible physiological and anatomic stroke outcomes. To test this hypothesis, we established a murine model that would permit either permanent or transient focal cerebral ischemia by intraluminal occlusion of the middle cerebral artery. This study provides a detailed description of the surgical technique and reveals important differences among strains commonly used in the production of transgenic mice. In addition to strain-related differences, infarct volume, neurological outcome, and cerebral blood flow appear to be importantly affected by temperature during the ischemic and postischemic periods, mouse size, and the size of the suture that obstructs the vascular lumen. When these variables were kept constant, there was remarkable uniformity of stroke outcome. These data emphasize the protective effects of hypothermia in stroke and might help to standardize techniques among different laboratories to provide a cohesive framework for evaluating the results of future studies in transgenic animals.

Global and domain-specific cognitive impairment and outcome after subarachnoid hemorrhage.

Background: Cognitive dysfunction is the most common form of neurologic impairment after subarachnoid hemorrhage (SAH). Objective: To evaluate the impact of global and domain-specific cognitive impairment on functional recovery and quality of life (QOL) after SAH. Methods: One hundred thirteen patients (mean age 49 years; 68% women) were evaluated 3 months after SAH. Three simple tests of global mental status and neuropsychological tests to assess seven specific cognitive domains were administered. Four aspects of outcome (global handicap, disability, emotional status, and QOL) were compared between cognitively impaired and unimpaired patients with analysis-of-covariance models controlling for age, race/ethnicity, and education. Multiple linear regression was used to evaluate the relative contribution of global and domain-specific cognitive status for predicting concurrent modified Rankin Scale (mRS) and Sickness Impact Profile (SIP) scores. Results: Impairment of global mental status on the Telephone Interview of Cognitive Status (TICS) was associated with poor performance in all seven cognitive domains (all p < 0.0005) and was the only cognitive measure associated with poor recovery in all four aspects of outcome (all p ≤ 0.005). Cognitive impairment in four specific domains was also associated with functional disability or reduced QOL. After accounting for global cognitive impairment with the TICS, however, neuropsychological testing did not contribute additional predictive value for concurrent mRS or SIP total scores. Conclusions: Cognitive impairment impacts broadly on functional status, emotional health, and QOL after SAH. The TICS may be a useful alternative to more detailed neuropsychological testing for detecting clinically relevant global cognitive impairment after SAH.

Nonconvulsive status epilepticus after subarachnoid hemorrhage.

OBJECTIVE Although in-hospital seizures have been reported for 3 to 24% of patients with aneurysmal subarachnoid hemorrhage (SAH), nonconvulsive status epilepticus (NCSE) has not been previously described. We sought to determine the frequency and clinical features of NCSE among comatose patients with SAH. METHODS Between November 1997 and February 2000, we performed continuous electroencephalographic (cEEG) monitoring for at least 24 hours for all patients with aneurysmal SAH who were treated in our neurological intensive care unit and exhibited unexplained coma or neurological deterioration. NCSE was diagnosed when cEEG monitoring demonstrated continuous or repetitive electrographic seizures exceeding 1 hour in duration. Refractory NCSE was treated aggressively with intravenous anticonvulsant administration and continuous-infusion midazolam therapy. RESULTS Of 233 patients with SAH who survived the first 48 hours of hospitalization, 101 were stuporous or comatose at some point during their hospitalization. Twenty-six of those patients underwent cEEG monitoring, and eight were diagnosed as having NCSE, an average of 18 days (range, 5–38 d) after SAH. All eight patients were receiving prophylactic anticonvulsant therapy. Four patients were persistently comatose and four demonstrated deterioration to stupor or coma; only one exhibited overt tonicoclonic activity. A worst Hunt and Hess grade of IV or V, older age, ventricular drainage, and cerebral edema on computed tomographic scans were identified as risk factors for NCSE (all P < 0.01). NCSE was successfully terminated for five patients (63%), but only one experienced clinical improvement, which was transient; all eight patients eventually died after a period of prolonged coma. CONCLUSION cEEG monitoring detected NCSE for 8% of patients with SAH and otherwise unexplained coma or neurological deterioration. The seizures were highly refractory to therapy, and the prognosis for these patients was extremely poor. Routine postoperative cEEG monitoring of patients with SAH who are at high risk for NCSE, allowing earlier diagnosis and treatment, offers the best chance of improving the outcomes for patients with this disorder.

Predictors and clinical impact of epilepsy after subarachnoid hemorrhage

Objective: To determine the frequency, predictors, and impact on outcome of epilepsy developing during the first year after subarachnoid hemorrhage (SAH). Methods: The authors prospectively analyzed 247 of 431 patients with SAH treated over a period of 5 years who were alive with follow-up at 12 months. Epilepsy was defined as two or more unprovoked seizures after hospital discharge. Results: New-onset epilepsy occurred in 7% (n = 17) of patients; an additional 4% (n = 10) had only one seizure after discharge. Independent predictors of epilepsy included subdural hematoma (OR 9.9, 95% CI 1.9 to 52.8) and cerebral infarction (OR 3.9, 95% CI 1.4 to 11.3). Unlike those without seizures, patients who developed epilepsy failed to experience functional recovery on the modified Rankin Scale (mRS) between 3 and 12 months after SAH. At 12 months epilepsy was independently associated with severe disability (score ≥ 3) on the mRS (OR 10.3, 95% CI 2.5 to 42.0), increased instrumental disability on the Lawton Instrumental Activities of Daily Living scale (OR 4.9; 95% CI 1.1 to 22.2), reduced quality of life on the Sickness Impact Profile (OR 4.5; 95% CI 1.1 to 18.0), and increased state anxiety on the Spielberger Anxiety Inventory (OR 4.8; 95% CI 1.1 to 20.4). Epilepsy was not associated with cognitive impairment, depression, or subjective life satisfaction. Conclusion: Epilepsy occurred in 7% of patients with SAH, was predicted by subdural hematoma and cerebral infarction, and was associated with poor functional recovery and quality of life. Our findings indicate that focal pathology, rather than diffuse injury from hemorrhage, is the principal cause of epilepsy after SAH.

Surgical Management of High-grade Intracranial Dural Arteriovenous Fistulas: Leptomeningeal Venous Disruption without Nidus Excision

OBJECTIVE Of intracranial dural arteriovenous malformations (AVMs), those with cortical venous drainage pose the greatest risk of hemorrhaging. Given recent advances in endovascular, surgical, and radiosurgical techniques, the optimal management of these dural AVMs is controversial. For surgical candidates, the choice of intraoperative techniques remains unclear. Several authors have suggested that surgical clipping of the draining vein close to the nidus of dural AVMs can provide adequate treatment for some lesions. However, recent reports have also promoted partial or complete surgical resection of these lesions. METHODS We present five cases of dural AVMs with cortical venous drainage that were surgically treated by the senior author between 1993 and 1996, and we review their management. Our series includes two frontal, one temporal, and two occipital lesions. Three patients presented with intracerebral hemorrhages, one with headache and eye pain, and one without symptoms. All five patients demonstrated venous aneurysms associated with the AVMs. Two patients underwent incomplete endovascular embolization before surgery. Operative management in all cases involved clipping of the draining vein as close as possible to the AVMs, together with extensive cautery of the surrounding dura. RESULTS Postoperative angiography demonstrated complete angiographic obliteration in all cases. The four symptomatic patients all experienced clinical improvement postoperatively. The asymptomatic patient remained asymptomatic. With a mean follow-up period of 29 months, no patient has developed recurrent symptoms. CONCLUSION Surgical clipping of the draining vein close to dural AVMs has proven safe and effective in our experience. Given the highly vascular nature of dural AVMs, often near major dural sinuses, surgical resection of these lesions may not be indicated.

Decompressive hemicraniectomy for poor-grade aneurysmal subarachnoid hemorrhage patients with associated intracerebral hemorrhage: clinical outcome and quality of life assessment.

OBJECTIVE:Decompressive hemicraniectomy has been proposed as a potential treatment strategy in patients with poor-grade aneurysmal subarachnoid hemorrhage presenting with focal intracerebral hemorrhage causing significant mass effect. Although hemicraniectomy improves overall survival rates, the long-term quality of life (QoL) for survivors in this patient population has not been reported. METHODS:Using adjudicated outcome assessments, we compare long-term clinical outcomes and QoL between a group of patients with poor-grade aneurysmal subarachnoid hemorrhage receiving decompressive hemicraniectomy (n = 12) and a control group of similar patients managed more conservatively (n = 10). RESULTS:Patients receiving decompressive hemicraniectomy experienced a statistically insignificant decrease in short-term mortality compared with controls (25 versus 42%); however, long-term QoL in hemicraniectomy survivors was generally poor. Furthermore, hemicraniectomy patients did not experience an increase in mean quality-adjusted life years over control patients (2.31 versus 2.22 yr). CONCLUSION:Decompressive hemicraniectomy prolongs short-term survival in patients with poor-grade aneurysmal subarachnoid hemorrhage with associated intracerebral hemorrhage; however, this trend is not statistically significant, and the overall QoL experienced by survivors is poor. Decompressive hemicraniectomy may be indicated if performed early in a select subset of patients. On the basis of our preliminary data, large prospective studies to investigate this issue further may not be warranted.

Neuropsychological dysfunction in the absence of structural evidence for cerebral ischemia after uncomplicated carotid endarterectomy.

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.

Treatment of inoperable carotid aneurysms with endovascular carotid occlusion after extracranial-intracranial bypass surgery.

OBJECTIVE Hunterian ligation of the internal carotid artery (ICA) is an accepted treatment for inoperable carotid aneurysms. Preliminary extracranial-intracranial (EC-IC) bypass surgery is required in some patients. The reported incidence of thromboembolic and ischemic complications remains significant for these patients, despite a variety of advocated management strategies. We present our treatment paradigm. METHODS Between April 1992 and March 1997, nine patients with inoperable ICA aneurysms were treated using EC-IC bypass surgery and then permanent endovascular ICA occlusion. All of the patients except one had been selected for bypass surgery on the basis of failing results of the ICA test occlusion with hypotensive challenge. ICA occlusion was performed by endovascular means and was delayed after bypass surgery was performed by a mean of 6 days (range, 2-20 d). All patients were managed in the intensive care unit after ICA occlusion. RESULTS Clinical improvement was noted in all patients (mean follow-up, 21 mo; range, 3-42 mo). There were no major complications. Aneurysmal thrombosis was confirmed in all patients. Although ICA occlusion was delayed after bypass surgery, only one bypass was noted to be occluded. The occluded bypass occurred in a patient who subsequently underwent successful ICA occlusion. This patient was thought to have been improperly selected for bypass surgery. CONCLUSION Certain carotid aneurysms can be effectively managed with hunterian ICA ligation. After preliminary identification of patients with borderline cerebrovascular reserve as candidates for EC-IC bypass surgery, close attention to the following points may help enhance clinical outcome: 1) excellence in surgical technique for EC-IC bypass surgery, 2) occlusion of the parent vessel as close to the aneurysm neck as possible by endovascular means, and 3) judicious postoperative combination of anticoagulation, fluid, and pressure management.

APOE-ε4 predisposes to cognitive dysfunction following uncomplicated carotid endarterectomy

Background: Between 9% and 23% of patients undergoing otherwise uncomplicated carotid endarterectomy (CEA) develop subtle cognitive decline 1 month postoperatively. The APOE-ε4 allele has been associated with worse outcome following stroke. Objective: To investigate the ability of APOE-ε4 to predict post-CEA neurocognitive dysfunction. Methods: Seventy-five patients with CEA undergoing elective CEA were prospectively recruited in this nested cohort study and demographic variables were recorded. Patients were evaluated before and 1 month after surgery with a standard battery of five neuropsychological tests. APOE genotyping was performed by restriction fragment length polymorphism analysis in all patients. Neuropsychological deficits were identified by comparing changes (before to 1 month post-operation) in individual performance on the test battery. Logistic regression was performed for APOE-ε4 and previously identified risk factors. Results: Twelve of 75 (16%) CEA patients possessed the APOE-ε4 allele. Eight of 75 (11%) patients experienced neurocognitive dysfunction on postoperative day 30. One month post-CEA, APOE-ε4–positive patients were more likely to be cognitively injured (42%) than APOE-ε4–negative patients (5%) (p = 0.002). In multivariate analysis, the presence of the APOE-ε4 allele increased the risk of neurocognitive dysfunction at 1 month 62-fold (62.28, 3.15 to 1229, p = 0.007). Diabetes (51.42, 1.94 to 1363, p = 0.02), and obesity (24.43, 1.41 to 422.9, p = 0.03) also predisposed to injury. Conclusion: The APOE-ε4 allele is a robust independent predictor of neurocognitive decline 1 month following CEA.