Vascular Malformations Overview

General Considerations

Cerebrovascular malformations (CVMs) of the brain are a

heterogeneous group of disorders that represent

morphogenetic errors affecting arteries, capillaries, veins, or

various combinations of vessels.

The presentation, natural history, and management

approaches to CVMs depend on their type, location, size, and

hemodynamic characteristics. Some CVMs, such as venous or

capillary malformations, are almost always clinically silent and

therefore usually identified at imaging or autopsy. Others,

such as arteriovenous malformations (AVMs) and cavernous

malformations, may hemorrhage unexpectedly and without

warning.

Terminology

Without a uniform consensus, there is much confusion

regarding the nomenclature of brain CVMs. They have

variously been called angiomas, hemangiomas,

developmental anomalies, malformations, and hamartomas.

For example, venous vascular malformations have been

termed venous angiomas, venous anomalies, venous

malformations, and developmental venous anomalies.

Cavernous malformations have been called cavernous

angiomas, cavernous hemangiomas, and "cavernomas" in the

literature.

Using accurate terminology when discussing brain vascular

malformations is important. Two major groups of vascular

anomalies are recognized: Vascular malformations and

hemangiomas. All CVMs ("angiomas") are malformative

lesions. In contrast, "hemangiomas" are true proliferating,

vasoformative neoplasms and, in the most recent WHO

classification "Blue Book," are included with the mesenchymal,

nonmeningothelial tumors.

Hemangiomas are benign vascular neoplasms, not

malformations, and can be capillary or cavernous. Most

intracranial hemangiomas are found in the skull, meninges,

and dural venous sinuses, whereas most vascular

malformations occur in the brain parenchyma. Therefore, the

term hemangioma should be reserved for vasoproliferative

neoplasms and not used to describe vascular malformations.

In this text, CVMs are included in this section; hemangiomas

are considered as neoplasms and included elsewhere.

Epidemiology

The overall prevalence of brain CVMs is difficult to estimate, as

accurate epidemiologic data are scarce. Cushing and Bailey

found that vascular anomalies constituted about 1% of all

intracranial tumors. Using ICD-9 codes, hospital admission

rates for CVMs have been calculated as ~ 1.5-1.8 cases per

100,000 person-years. CVMs are estimated to cause about 5%

of all nontraumatic intracranial hemorrhages.

With modern imaging, and especially with contrast-enhanced

MR, CVMs are found in up to 8-10% of imaged patients. Most

(venous and capillary malformations) are asymptomatic and

found incidentally.

Embryology

Development of the human fetal vascular system occurs via 2

related processes: Vasculogenesis and angiogenesis.

Vasculogenesis begins with de novo differentiation of

endothelial cells from mesoderm-derived precursors called

hemangioblasts. Islands of hemangioblasts form an outer rim

of endothelial cell precursors ("angioblasts") and an inner core

of hematopoietic stem cells.

Angioblasts form capillary-like tubules that constitute the

primitive vascular plexus. This embryonic vascular network is

then remodeled by a process of sprouting, progressive

anastomosis, and retrogressive differentiation. Endothelial

cells differentiate into arterial and venous types, preceded,

and guided by, migrating activated pericytes during definitive

organization of the growing vessel wall.

Angiogenesis is regulated by a number of intercell signaling

and growth factors. Some of these include Ang-1, Ang-2, Tie2,

VEGF, PDGF, and TGF-β1, among others. Mutations in

components of the angiogenetic system have been associated

with the development of various CVMs.

Classification

In general, CVMs have been traditionally classified by

histopathology and, more recently, by embryology and

molecular genetics. With the advent of neurovascular

interventional procedures, CVMs have also been classified by a

practical, more functional approach.

Histopathologic Classification

Most neuropathology texts classify CVMs into 4 major types:

(1) AVM, (2) venous angioma, (3) capillary telangiectasia, and

(4) cavernous malformation. This histopathologic classification

is used in this book.

Embryologic Classification

Some investigators have proposed an embryonic, "metameric"

approach to classifying vascular malformations that accounts

for the known relationship between some brain and

cutaneous vascular malformations. They termed these

"cerebral arterial metameric syndromes" or CAMS. For

example, a CAMS1 syndrome links AVMs in the

prosencephalon with those of the nose and orbit. Hence a