Arteriovenous and Cavernous Malformations

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• Publisher: Elsevier
• Year: 2017
• ISBN:
  9780444636430
• Topic: Medicine
• Subtopic: Neurology

Arteriovenous and Cavernous Malformations, Volume 143, is the latest addition in the ongoing HCN series, an evidence-based compendium which addresses both the scientific and clinical aspects of this unique disease process. The volume covers didactic aspects, such as the epidemiology, etiology, and diagnosis of AVMs, while also providing expert clinical information on the management and treatment of these lesions.

In addition, it provides coverage of modern-day advances in the genetics of cavernous malformations, as well as discussion regarding future open research questions. Readers from the laboratory bench to the bedside can expect a broad, yet objective, review of this pathology, with updates from the latest scientific literature and data supporting current practices.

• Offers an evidence-based focus with coverage of both the scientific and clinical aspects of cavernous malformations
• Addresses epidemiology, etiology, diagnosis, and genetics
• Contains clinical insights regarding indications for surgery, surgical techniques, outcomes, and prognostic factors drawn from the authors' extensive experiences
• Edited work with chapters authored by leaders in the field from around the globe – the broadest, most expert coverage available

Part I

Arteriovenous Malformations

Section 1

Cerebral arteriovenous malformations

Chapter 1

Epidemiology, genetics, pathophysiology, and prognostic classifications of cerebral arteriovenous malformations

Alp Ozpinar^1,*; Gustavo Mendez²; Adib A. Abla^{3 1} Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, USA
² Department of General Surgery, Rush University Medical Center, Chicago, IL, USA
³ Department of Neurological Surgery, University of Arkansas for Medical Sciences, Little Rock, AR, USA
^* Correspondence to: Alp Ozpinar, MD, Department of Neurological Surgery, University of Pittsburgh Medical Center, Suite B-400, 200 Lothrop Street, Pittsburgh PA, USA. Tel: [phone] email address: [email protected]

Abstract

Arteriovenous malformations (AVMs) are vascular deformities involving fistula formation of arterial to venous structures without an intervening capillary bed. Such anomalies can prove fatal as the high arterial flow can disrupt the integrity of venous walls, thus leading to dangerous sequelae such as hemorrhage. Diagnosis of these lesions in the central nervous system can often prove challenging as intracranial AVMs represent a heterogeneous vascular pathology with various presentations and symptomatology. The literature suggests that most brain AVMs (bAVMs) are identified following evaluation of the etiology of acute cerebral hemorrhage, or incidentally on imaging associated with seizure or headache workup. Given the low incidence of this disease, most of the data accrued on this pathology comes from single-center experiences. This chapter aims to distill the most important information from these studies as well as examine meta-analyses on bAVMs in order to provide a comprehensive introduction into the natural history, classification, genetic underpinnings of disease, and proposed pathophysiology. While there is yet much to be elucidated about AVMs of the central nervous system, we aim to provide an overview of bAVM etiology, classification, genetics, and pathophysiology inherent to the disease process.

Keywords

brain arteriovenous malformation; classification; pathophysiology

Introduction

Vascular disease entities manifest in various forms, and are particularly dangerous when high-flow arterial systems erroneously communicate directly with venous systems. Arteriovenous malformations (AVMs) are vascular deformities involving fistula formation of arterial to venous structures without an intervening capillary bed. Such anomalies can prove fatal as the high arterial flow can disrupt the integrity of venous walls, thus leading to sequelae such as hemorrhage. The central nervous system (CNS) is particularly sensitive to such insults as intracranial hemorrhage secondary to AVM rupture can prove profoundly disabling or deadly. Diagnosis of these lesions can prove challenging, as intracranial AVMs represent a heterogeneous vascular pathology with various presentations and symptomatology, as well as a wide variation in severity of the effect of an AVM on a patient's overall well-being. The literature suggests that most brain AVMs (bAVMs) are identified following evaluation of the etiology of acute cerebral hemorrhage, or incidentally on imaging associated with seizure or headache workup (Hofmeister et al., 2000; Conger et al., 2015). As reinforced by Conger et al. (2015), subsequent to detection of the AVM, history and physical examination coupled with critical imaging, including computed tomography (CT), magnetic resonance imaging (MRI), and catheter angiogram, allow neurosurgeons to form a clinical picture of the AVM patient as well as visualize the structure and hemodynamics of the vascular malformation (Conger et al., 2015).

To date, bAVM data have been derived from single-center experiences. From epidemiological studies, the incidence of AVMs ranges from 1.12 to 1.42 cases per 100 000 person-years, with 38–68% of new cases presenting as first-ever hemorrhage (Abecassis et al., 2014). Annual rates of hemorrhage in untreated bAVMs have been estimated at 2.10–4.12% (Abecassis et al., 2014). Various studies have tried to identify factors associated with increased risk of AVM rupture. Meta-analyses on the topic have found that increased risk of future rupture has been associated with factors such as previous rupture, location of AVM in deep brain structures, and exclusive deep venous drainage (Stapf et al., 2006; Gross and Du, 2013). Gross and Du (2013) calculated for observed AVMs an overall yearly risk of hemorrhage rate of 3.0%, with an annual rate of 2.2% for the unruptured subset and 4.5% for ruptured AVMs. Stapf et al. (2006) showed that the annual rate of rupture for an AVM is 35.5% when the AVM has the triad of deep venous drainage, deep location, and prior hemorrhage. The other large meta-analysis (Kim et al., 2014) examined four AVM cohorts and found an overall annual hemorrhage rate of 2.3%, with a rate of 1.3% for unruptured AVMs and 4.8% for the ruptured group. These estimates have held up as results of the multicenter prospective randomized trial ARUBA showed a 2.2% annual risk of rupture for unruptured bAVMs (Mohr et al., 2014).

Data for the natural history of ruptured AVMs are less prevalent as the decision to observe ruptured lesions is a riskier enterprise. Some studies (Kondziolka et al., 1995; Brown, 2000) have gone so far as to extrapolate lifetime risk of hemorrhage by using annual rates and applying the following equation:

$\mathrm{Annual}\mathrm{rupture}\mathrm{risk}=1-{\left(\mathrm{risk}\mathrm{of}\mathrm{no}\mathrm{hemorrhage}\right)}^{\left(\mathrm{life}\mathrm{expectancy}\right)}\mathrm{and}\mathrm{rupture}\mathrm{risk}=105-\mathrm{patient}\mathrm{age}$

While the aforementioned studies have shown concordance in estimates of annual risk of rupture, variability among lesions and patient populations presents inherent challenges to generalizability and comprehensively predicting risk of rupture, as illustrated in various studies on the natural history of bAVMs (Pollock et al., 1996; Stapf et al., 2001; Stefani et al., 2002; Fullerton et al., 2005; Kim et al., 2010; Laakso et al., 2010; Gross and Du, 2013).

Classification systems

Multiple scales have been formulated to predict the morbidity and mortality associated with AVMs and the associated risk of intervention. Spetzler and Martin (1986), in their seminal paper on bAVMs, proposed a grading system based on size, venous drainage, and eloquence of brain adjacent to the malformation. The five-point scale assigns a score as follows: for size, <3 cm=1 point, 3–6 cm=2 points, >6 cm=3 points; for location, eloquent brain=1 point, noneloquent=0 points; for venous drainage, deep venous drainage=1 point, not deep venous drainage=0 points. Applying this scheme, higher scores translate to higher Spetzler–Martin grade, which corresponds to greater risk of morbidity and mortality with microsurgical removal of the lesion. (See Figure 1.1 for an example of Spetzler–Martin grade 3 AVM on preoperative imaging, intraoperative photos, and intraoperative fluorescence angiography processing.)

Fig. 1.1 (A) A representative Spetzer–Martin grade 3 arteriovenous malformation (AVM) (3 points for size) of the right frontal operculum and premotor region is demonstrated on anterior–posterior angiography. (B) Intraoperative photo demonstrates the dilated draining veins of Labbe and Trolard on the surface of the AVM with the AVM nidus located deep to the draining veins. (C) Intraoperative flow 800 processing of indocyanine green angiography demonstrates the arrival time of dye to the AVM with red demonstrating the vessels that fill first (feeders). Seconds in the figure key indicates latency in arrival time of dye. (D) AVM nidus seen deep to the draining veins along the anterior noneloquent border of the AVM. (E) Intraoperative photo demonstrating the surgical bed following resection. Note the change in color of the draining veins which are no longer arterialized. Change in color from red (before resection) to blue (following resection). (F) Postoperative anterior–posterior cerebral angiography demonstrating complete resection of AVM.

While the Spetzler–Martin grade is the most-quoted benchmark/standard in determining outcome and management, other grading systems have been introduced as adjuncts. Lawton et al. proposed a supplementary and complementary system to the Spetzler–Martin grade in 2010 that takes into account age, hemorrhagic presentation, and diffuseness of lesion, and yields improved accuracy in predictability of neurologic outcome when combined with the Spetzler–Martin scale (Table 1.1). This supplementary scale in conjunction with Spetzler–Martin is a 10-point scale that takes the five-point Spetzler–Martin scheme and, in addition, accounts for the following: for age, <20 years=1 point, 20–40=2 points, >40=3 points; for hemorrhagic presentation, hemorrhage=0 points, no hemorrhage=1 point; for lesion nidus diffuseness, compact=0 points, diffuse=1 point. Lawton et al. (2010) have shown that application of their scale can help with preoperative risk prediction and extrapolation of outcome (Kim et al., 2014).

Table 1.1

Comparing the Spetzler...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Handbook of Clinical Neurology 3rd Series
• Foreword
• Preface
• Contributors
• Part I: Arteriovenous Malformations
• Part II: Cavernous Malformations
• Index