John Pile-Spellman

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.

MERCI 1 A Phase 1 Study of Mechanical Embolus Removal in Cerebral Ischemia

Background and Purpose— To report the result of the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) 1 study, a phase 1 trial to evaluate the safety and efficacy of mechanical embolectomy in the cerebral vasculature. Methods— MERCI 1 enrolled 30 patients in 7 US centers. Main inclusion criteria were: National Institutes of Health Stroke Scale score (NIHSS) ≥10; treatment performed within 8 hours from symptoms onset and contra-indication to intravenous thrombolysis; no large hypodensity on computed tomography; and occlusion of a major cerebral artery on the angiogram. Safety was defined by the absence of vascular injury or symptomatic intracranial hemorrhage. Efficacy was assessed by recanalization rate and clinical outcome at 1 month. Significant recovery was defined as 30-day modified Rankin of 0 to 2 in patients with baseline NIHSS 10 to 20 and 30-day modified Rankin of 0 to 3 in patients with baseline NIHSS >20. The procedures were performed with the Merci Retrieval System, a system specially designed for intracranial embolectomy. Results— Twenty-eight patients were treated. Median NIHSS was 22. Median time from onset to completion of treatment was 6 hours and 15 minutes. Successful recanalization with mechanical embolectomy only was achieved in 12 (43%) patients, and with additional intra-arterial tissue plasminogen activator in 18 (64%) patients. There was one procedure related technical complication, with no clinical consequence. Twelve asymptomatic and no symptomatic intracranial hemorrhages occurred. At 1 month, 9 of 8 revascularized patients and 0 of 10 nonrevascularized patients had achieved significant recovery. Conclusion— This phase 1 study shows that cerebral embolectomy with the Merci Retriever was safe and that successful recanalization could benefit a significant number of patients, even when performed in an extended 8-hour time window.

Risk of spontaneous haemorrhage after diagnosis of cerebral arteriovenous malformation

BACKGROUND A small proportion of strokes are caused by cerebral arteriovenous malformations (AVM). Treatment to prevent intracranial haemorrhage itself carries risks, and untreated AVM may in many cases have a good prognosis. We investigated the risk of subsequent symptomatic bleeding in the clinical course of AVM in patients with and without an initial haemorrhage. METHODS 281 unselected, consecutive, prospectively enrolled patients with cerebral AVM were grouped according to their initial clinical presentation--142 presented with and 139 without haemorrhage. The frequency of AVM haemorrhages during the subsequent clinical course (before the start of endovascular, surgical, or radiation treatment) in the two groups was compared by means of Kaplan-Meier life-tables, log-rank test, and multivariate proportional-hazards regression models. Haemorrhage was defined as a clinically symptomatic event with signs of acute bleeding on computed tomography or magnetic resonance brain imaging. FINDINGS During mean follow-up of 8.5 months for the haemorrhage group and 11.9 months for the non-haemorrhage group, haemorrhages occurred in 18 (13%) of the former patients and in three (2%) of the latter (p=0.0002). The annual risk of haemorrhage was 17.8% and 2.2%, respectively. In the multivariate regression model, the adjusted hazard ratio for haemorrhage at initial presentation was 13.9 (95% CI 2.6-73.8; p=0.002). Deep venous drainage (hazard ratio 4.1 [1.2-14.9], p=0.029) and male sex (9.2 [2.1-41.3], p=0.004) were also significantly associated with subsequent haemorrhage, but no significant association was found for age or AVM size. The annual rate of spontaneous haemorrhage was 32.6% for men and 10.4% for women in the haemorrhage group compared with 3.3% for men and 1.3% for women in the non-haemorrhage group. Among patients with haemorrhage at initial presentation, the risk of haemorrhage fell from 32.9% in year 1 to 11.3% in subsequent years (34.2% to 31.0% in men; 31.1% to 5.5% in women). INTERPRETATION In AVM, patients initially presenting with haemorrhage have a higher risk of subsequent bleeding than those presenting with other symptoms. The risk is higher in men than in women.

The New York Islands AVM Study Design, Study Progress, and Initial Results

Background and Purpose— Prospective population-based data on the incidence of brain arteriovenous malformation (AVM) hemorrhage are scarce. We studied lifetime detection rates of brain AVM and incident AVM hemorrhage in a defined population. Methods— The New York islands (ie, Manhattan Island, Staten Island, and Long Island) comprise a 9 429 541 population according to the 2000 census. Since March 15, 2000, all major New York islands hospitals have prospectively reported data on consecutive patients living in the study area with a diagnosis of brain AVM and whether the patient had suffered AVM hemorrhage. Patients living outside the ZIP code–defined study area were excluded from the study population. Results— As of June 14, 2002, 284 prospective AVM patients (mean±SD age, 35±18 years; 49% women) were encountered during 21 216 467 person-years of observation, leading to an average annual AVM detection rate of 1.34 per 100 000 person-years (95% CI, 1.18 to 1.49). The incidence of first-ever AVM hemorrhage (n=108; mean age, 31±19 years; 45% women) was 0.51 per 100 000 person-years (95% CI, 0.41 to 0.61). The estimated prevalence of AVM hemorrhage among detected cases (n=144; mean age, 33±19 years; 50% women) was 0.68 per 100 000 (95% CI, 0.57 to 0.79). Conclusions— Our prospective data, spanning 27 months, suggest stable rates for AVM detection and incident AVM hemorrhage. Approximately half of AVM patients may suffer intracranial hemorrhage.

Morbidity of Intracranial Hemorrhage in Patients With Cerebral Arteriovenous Malformation

To the Editor: The Columbia-Presbyterian Medical Center Arteriovenous Malformation Study Project has made, and continues to make, a significant contribution to our understanding of arteriovenous malformations of the brain. In the recent contribution of Hartmann et al,1 a number of interesting observations were made with regard to hemorrhage. The first is the high incidence among those that bleed of subarachnoid and intraventricular hemorrhage. Only 54% of initial hemorrhages and 49% of follow-up hemorrhage were intraparenchymal. This is at considerable variance with our experience at the Northern and Western Medical School, The University of Sydney, where we have followed all arteriovenous malformations (AVMs) seen since 1991, and of 114 patients presenting with hemorrhage, 82% have a significant intraparenchymal component. One is left with the feeling from this article that hemorrhage from AVMs is relatively benign. However, it must be borne in mind that this is a specially selected subset …

The influence of hemodynamic and anatomic factors on hemorrhage from cerebral arteriovenous malformations.

The physiological and anatomical aberrations that result in hemorrhage from cerebral arteriovenous malformations (AVMs) remain unclear. In an attempt to clarify which conditions may predispose to hemorrhage, we examined clinical and physiological indices on presentation groups of either hemorrhage or nonhemorrhage in a large cohort of patients (n = 449). Variables examined included AVM size, type of venous drainage, transcranial Doppler (TCD) velocities, feeding mean arterial pressure (FMAP), and draining vein pressure. TCD and pressure data were obtained before any treatment. Age (mean +/- standard deviation) at the time of presentation was 33 +/- 13 years and did not differ between groups. Patients with small (< or = 2.5 cm) AVMs presented more frequently with hemorrhage (90%) than did patients with medium (> 2.5 and < or = 5.0 cm; 52%) or large (> 5.0 cm; 50%) AVMs (P = 0.0001). The 48 of 94 AVMs (51%) with deep venous drainage were more likely to have hemorrhage (P = 0.0219) than were those with superficial drainage (24 of 73 [33%]). Deep drainage was a predictor of hemorrhage even in the subgroup of medium and large supratentorial AVMs (P = 0.005). There was no difference in draining vein pressure (n = 18) between groups (21 +/- 10 and 19 +/- 11 mm Hg, respectively; P = 0.7812). FMAP (n = 52) was higher in the hemorrhage than in the nonhemorrhage group (44 +/- 13 versus 34 +/- 10 mm Hg; P = 0.0007) but was only weakly related to the size of the lesion (largest dimension) (y = -0.74x + 40; r = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Reperfusion injury following cerebral ischemia: pathophysiology, MR imaging, and potential therapies.

IntroductionRestoration of blood flow following ischemic stroke can be achieved by means of thrombolysis or mechanical recanalization. However, for some patients, reperfusion may exacerbate the injury initially caused by ischemia, producing a so-called “cerebral reperfusion injury”. Multiple pathological processes are involved in this injury, including leukocyte infiltration, platelet and complement activation, postischemic hyperperfusion, and breakdown of the blood–brain barrier.Methods/results and conclusionsMagnetic resonance imaging (MRI) can provide extensive information on this process of injury, and may have a role in the future in stratifying patients’ risk for reperfusion injury following recanalization. Moreover, different MRI modalities can be used to investigate the various mechanisms of reperfusion injury. Antileukocyte antibodies, brain cooling and conditioned blood reperfusion are potential therapeutic strategies for lessening or eliminating reperfusion injury, and interventionalists may play a role in the future in using some of these therapies in combination with thrombolysis or embolectomy. The present review summarizes the mechanisms of reperfusion injury and focuses on the way each of those mechanisms can be evaluated by different MRI modalities. The potential therapeutic strategies are also discussed.

Feeding Artery Pressure and Venous Drainage Pattern Are Primary Determinants of Hemorrhage From Cerebral Arteriovenous Malformations

PURPOSE The purpose of this study was to define the influence of feeding mean arterial pressure (FMAP) in conjunction with other morphological or clinical risk factors in determining the probability of hemorrhagic presentation in patients with cerebral arteriovenous malformations (AVMs). METHODS Clinical and angiographic data from 340 patients with cerebral AVMs from a prospective database were reviewed. Patients were identified in whom FMAP was measured during superselective angiography. Additional variables analyzed included AVM size, location, nidus border, presence of aneurysms, and arterial supply and venous drainage patterns. The presence of arterial aneurysms was also correlated with site of bleeding on imaging studies. RESULTS By univariate analysis, exclusively deep venous drainage, periventricular venous drainage, posterior fossa location, and FMAP predicted hemorrhagic presentation. When we used stepwise multiple logistic regression analysis in the cohort that had FMAP measurements (n = 129), only exclusively deep venous drainage (odds ratio [OR], 3.7; 95% confidence interval [CI], 1.4 to 9.8) and FMAP (OR, 1.4 per 10 mm Hg increase; 95% CI, 1.1 to 1.8) were independent predictors (P < 0.01) of hemorrhagic presentation; size, location, and the presence of aneurysms were not independent predictors. There was also no association (P = 0.23) between the presence of arterial aneurysms and subarachnoid hemorrhage. CONCLUSIONS High arterial input pressure (FMAP) and venous outflow restriction (exclusively deep venous drainage) were the most powerful risk predictors for hemorrhagic AVM presentation. Our findings suggest that high intranidal pressure is more important than factors such as size, location, and the presence of arterial aneurysms in the pathophysiology of AVM hemorrhage.

Risk of Endovascular Treatment of Brain Arteriovenous Malformations

Background and Purpose— Independently assessed data on frequency, severity, and determinants of neurological deficits after endovascular treatment of brain arteriovenous malformations (AVMs) are scarce. Methods— From the prospective Columbia AVM Study Project, 233 consecutive patients with brain AVM receiving ≥1 endovascular treatments were analyzed. Neurological impairment was assessed by a neurologist using the Rankin Scale before and after completed endovascular therapy. Multivariate logistic regression models were used to identify demographic, clinical, and morphological predictors of treatment-related neurological deficits. The analysis included the components used in the Spetzler-Martin risk score for AVM surgery (AVM size, venous drainage pattern, and eloquence of AVM location). Results— The 233 patients were treated with 545 endovascular procedures. Mean follow-up time was 9.6 months (SD, 18.1 months). Two hundred patients (86%) experienced no change in neurological status after treatment, and 33 patients (14%) showed treatment-related neurological deficits. Of the latter, 5 (2%) had persistent disabling deficits (Rankin score >2), and 2 (1%) died. Increasing patient age [odds ratio (OR), 1.04; 95% confidence interval (CI), 1.01 to 1.08], number of embolizations (OR, 1.41; 95% CI, 1.16 to 1.70), and absence of a pretreatment neurological deficit (OR, 4.55; 95% CI, 1.03 to 20.0) were associated with new neurological deficits. None of the morphological AVM characteristics tested predicted treatment complications. Conclusions— From independent neurological assessment and prospective data collection, our findings suggest a low rate of disabling treatment complications in this center for endovascular brain AVM treatment. Risk predictors for endovascular treatment differ from those for AVM surgery.

The epidemiology of brain arteriovenous malformations.

OBJECTIVE Common estimates of the prevalence rate for pial arteriovenous malformations (AVMs) of the brain vary widely, and their accuracy is questionable. Our objective was to critically review the original sources from which these rates were derived and to establish best estimates for both the incidence and prevalence of the disease. METHODS We reviewed all of the relevant original literature: autopsy series, the Cooperative Study of Intracranial Aneurysms and Subarachnoid Hemorrhage and related analyses, and other population-based studies. We also modeled the confidence intervals of estimates for a process of low prevalence such as AVMs. RESULTS Many of the prevalence estimates (500-600/100,000 population) were based on autopsy data, a source that is inherently biased. Other estimates (140/100,000 population) originated from an inappropriate analysis of data from the Cooperative Study. The most reliable information comes from a population-based study of Olmsted County, MN, but prevalence data specific to AVMs was not found in that study. CONCLUSION The estimates for AVM prevalence that are published in the medical literature are unfounded. Because of the rarity of the disease and the existence of asymptomatic patients, establishing a true prevalence rate is not feasible. Owing to variation in the detection rate of asymptomatic AVMs, the most reliable estimate for the occurrence of the disease is the detection rate for symptomatic lesions: 0.94 per 100,000 person-years (95% confidence interval, 0.57-1.30/100,000 person-years). This figure is derived from a single population-based study, but it is supported by a reanalysis of other data sources. The prevalence of detected, active (at risk) AVM disease is unknown, but it can be inferred from incidence data to be lower than 10.3 per 100,000 population.