Henning Mast

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.

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.

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)

Mortality and causes of death after first ischemic stroke: The Northern Manhattan Stroke Study

Objective: To analyze the early and long-term causes of death after first ischemic stroke in the multiethnic northern Manhattan community. Methods: In the prospective, population-based Northern Manhattan Stroke Study, 980 patients with first ischemic stroke (mean age 70 years; 56% women; 49% Caribbean Hispanic, 31% black, 20% white) were followed for a mean of 3 years. Causes of death were classified as vascular (incident stroke, recurrent stroke, cardiac) or nonvascular. Life table analyses were used to assess mortality risks among different race-ethnic groups. Early (≤1 month) vs long-term (>1 month to 5 years) causes of death were compared. Results: Among the 980 patients followed, 278 (28%) died; 47 (5%) died during the first month. Cumulative mortality risk was 5% at 1 month, 16% after 1 year, 29% after 3 years, and 41% after 5 years. The proportion of vascular deaths among all deaths was 75% at 1 month and 43% thereafter (p = 0.001). Stroke, either incident (53%) or recurrent (4%), caused early deaths in 57% and long-term deaths in 14% (p = 0.001). Overall mortality risks did not differ significantly among race-ethnic groups. However, the proportion of incident stroke-related early deaths was 85% in Caribbean Hispanic patients, 33% in white patients, and 25% in black patients (p = 0.002). Conclusions: Among patients with first ischemic stroke, incident stroke is the leading cause of early deaths. A large proportion of long-term deaths are nonvascular in origin. Despite similar overall mortality rates in race-ethnic groups, our data suggest a higher incident stroke-related early mortality among Caribbean Hispanics.

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.

Clinical Outcome After First and Recurrent Hemorrhage in Patients With Untreated Brain Arteriovenous Malformation

Background and Purpose— The morbidity from spontaneous hemorrhage of untreated brain arteriovenous malformations (AVM) is not well described. Methods— The 241 consecutive AVM patients (mean age 37±16 years, 52% women) from the prospective Columbia AVM Databank initially presenting with hemorrhage were evaluated using the Rankin Scale (RS) and the National Institute of Health Stroke Scale (NIHSS). From the 241 AVM patients, 29 (12%) had subsequent intracranial hemorrhage during follow-up. For further comparisons, 84 non-AVM patients with intracerebral hemorrhage from the Northern Manhattan Study (NOMAS) served as a control group. Results— In 241 AVM patients presenting with hemorrhage the median RS was 2 and the median NIHSS was 1 (49% RS 0 to 1, 61% NIHSS <2). The median time between hemorrhage and clinical evaluation was 11 days (mean 219 days). Recurrent AVM hemorrhage during follow-up resulted in no significant increase in morbidity (median RS 2, P=0.004; median NIHSS 3, P=0.322; time between hemorrhage and study evaluation: median 55 days, mean 657 days). Among AVM-hemorrhage subtypes, parenchymatous AVM hemorrhage was associated with higher stroke morbidity (odds ratio, 2.9; 95% CI, 1.5 to 5.8 for NIHSS ≥2) than nonparenchymatous hemorrhages. Parenchymatous AVM hemorrhage had a significantly better outcome (median NIHSS 1) than non-AVM related hemorrhage (median NIHSS 12; P<0.0001). Conclusions— Hemorrhage, either at initial presentation or during follow-up of untreated AVM patients appears to carry a lower morbidity than intracranial hemorrhage from other causes. These findings support a careful weighing of risks from interventional treatment and natural history.

Hypertension and Diabetes Mellitus as Determinants of Multiple Lacunar Infarcts

BACKGROUND AND PURPOSE We investigated the relationship between hypertension, diabetes mellitus, and lacunes. METHODS From 1237 cases of ischemic stroke in the Stroke Data Bank of the National Institute of Neurological and Communicative Disorders and Stroke, data from 637 patients whose initial computed tomogram showed lacunar (n = 184) or nonlacunar infarcts (n = 453) were analyzed. The group with lacunar infarcts was further divided into subgroups according to whether the patients had multiple (n = 40) or single (n = 144) lacunar infarcts. The association of hypertension and diabetes mellitus with lacunar infarcts was investigated using logistic regression models that included age, sex, and cardiac disease. Similar models were used to analyze the effects of diastolic and systolic blood pressure. RESULTS Hypertension (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.1 to 6.0) and diabetes (OR, 2.3; 95% CI, 1.1 to 4.5) were significantly related to multiple but not to single lacunes. Cardiac disease was inversely associated with both single and multiple lacunes. Diastolic blood pressure significantly affected the probability of multiple lacunar infarcts (OR, 1.4; 95% CI, 1.04 to 1.9), whereas systolic pressure did not. CONCLUSIONS There may be etiologically distinct lacunar infarct subgroups, with multiple lacunes being strongly related to hypertension and diabetes mellitus. Other stroke risk factors may be more important in patients with single lacunes. Diastolic rather than systolic pressure seems to be a major determinant of multiple lacunes.

Invasive treatment of unruptured brain arteriovenous malformations is experimental therapy

Purpose of reviewBrain arteriovenous malformations (AVMs) are currently being treated in a variety of ways, including medical management, endovascular procedures, neurosurgery and radiotherapy. The widespread diffusion of these various treatment approaches is partially driven by the existence of variations in the perception about the risks of rupture, and how devastating such events would be. Recent findingsData from the most recent studies suggest the majority of AVM patients are diagnosed without signs of hemorrhage, further, that the natural history risk for the unruptured cohort is far more benign than for those presenting with rupture. In cases where hemorrhage occurs, the clinical syndrome is significantly less disabling than in patients with non-AVM related hemorrhage. For unruptured AVMs, current morbidity data suggest a higher risk for invasive management than for the natural history of untreated patients. SummaryNo randomized clinical trial data exist on the benefit of invasive AVM treatment, and the most contentious issue at present is whether intervention should be considered for AVMs that have not bled. In a scientific sense, invasive treatment for unruptured brain AVMs may be considered experimental therapy awaiting the results from ‘A Randomized Trial of Unruptured Brain AVMs’ (ARUBA), which is currently underway.