Page 69 - GPD-2-2

Gene & Protein in Disease Genetics of arteriovenous malformations

somatic gene mutations are linked to increased AVM surgical intervention. Spetzler did not recommend surgical
susceptibility and hemorrhage . Mullan noticed that intervention for Grade 4 or 5 lesions . Unofficially, there
[13]
[17]
venous malformations and bAVM shared some similarities, is also a Grade 6 that describes an inoperable AVM [3,5] .
and hypothesized that venous malformations and bAVM The Spetzler-Martin Grading System, initially published
could be developmentally linked and that bAVM were in 1986, is commonly used today, and at present, there
fistulized venous malformations that developed during are many variations and modifications which try to
embryogenesis . Mullan based the theory on the treatment compensate for the variability of Grade 3 AVM [17,25] . There
[23]
of venous malformations and bAVM because venous side have been many proposed classification systems to assess
occlusion is more curative than the arterial side in both the risk of endovascular and stereotactic radiosurgical
conditions . Approximately 95% of bAVM are sporadic approaches to treat bAVM. Pollock et al. compared five
[23]
while the rest can be linked to hereditary conditions, with AVM grading scales useful for predicting stereotactic
HHT being the most common condition . radiosurgical outcomes . Those grading scales were the
[16]
[26]
Spetzler-Martin grading scale, radiosurgery-based AVM
2.2. Diagnosis and treatment score (RBAS), Heidelberg score, virginia radiosurgery
Magnetic resonance imaging (MRI) and computed AVM scale (VRAS), and proton radiosurgery AVM scale
tomography (CT) are important tools for the (PRAS) . They found that continuous scores such as
[26]
characterization of bAVM. During 3D multidetector CT, RBAS and PRAS were more accurate than the Spetzler-
bAVM can show a spot sign which is seen when contrast Martin Grading System . Although there have been
[26]
leaks out the blood vessel wall . In contrast-enhanced, several proposed scales to use for endovascular surgery,
[13]
CT a key distinguishing feature is the “serpentine none have become widely popular . Jin et al. found
[25]
enhancement pattern .” MRI with MR angiography and that the Puerto Rico score did a better job of predicting
[13]
CT angiography is best for identifying the size, location, complications in endovascular surgery than the Spetzler-
history, and risk of hemorrhage, the mass effect of the Martin Grading system .
[27]
lesion, and prognosis . Treating bAVM tends to be Altogether, understanding the etiology, pathogenesis,
[24]
clinically challenging and requires a variety of resources . diagnosis, and treatment of AVM requires a multifunctional
[18]
Microsurgical resection, stereotactic radiosurgery, and perspective. A more detailed look at the cellular and molecular
endovascular embolization are options for treating bAVM physiology of AVM pathogenesis has more recently allowed
and may be used individually or in combination . The for the identification of key signaling mediators in AVM
[18]
complex nature of bAVM typically requires multiple angiogenesis, which we will discuss further.
imaging and treatment modalities for adequate clinical
care [13,18,24] . The goal of treating AVM is usually to prevent 3. Molecular characterization of AVM
hemorrhage and manage symptoms . Findings from a pathogenesis
[25]
meta-analysis indicated that all three treatment options
were associated with significant risks and low efficacy. 3.1. Pathogenesis
In addition, multi-modal approaches may be the safest The pathogenesis of bAVM is not fully understood.
option, but they are still associated with the combined risks Some well-known associated factors such as angiogenic
of each approach . factors and inflammatory cytokines likely influence the
[25]
[28]
Some may classify bAVM into three categories: development of bAVM . Chen et al. demonstrated that
Parenchymal AVM, pure dural AVM, and mixed inflammatory cells were present in bAVM, indicating that
parenchymal and dural AVM. In addition, parenchymal inflammation may be involved in disease progression
[29]
AVM includes four subcategories: Pial, subcortical, or pathogenesis . Molecular and histopathological
paraventricular, and combined . In this paper, we focus characterization of bAVM tissue showed increased
[17]
on parenchymal AVM. The Spetzler-Martin Grading expression of angiogenic factors, such as VEGF,
System was designed by Spetzler and Martin to associate angiopoietin-2, and matrix metalloproteinase (MMP)-9 as
major AVM characteristics with risks for surgical well as elevated expression of inflammatory factors, such as
intervention . The Spetzler-Martin Grading System has IL-6 and Myeloperoxidase (MPO) . Kim et al. speculated
[13]
[30]
three components: Size, eloquence of the adjacent brain, that bAVM develops from regions destined to become
[17]
and pattern of venous drainage . The scale ranges from 1 the AVM nidus and some inciting event would cause an
to 5, and the grade of the AVM is determined by adding the increase in angiogenic factors or inflammatory cytokines.
score of each component. You can receive up to 3 points Instead of stabilizing like normal vessels, this predestined
for the size of the AVM and up to 1 point for the other area undergoes a dysplastic response and over time will
components . Lower grades predict better success with eventually develop into bAVM nidus .
[17]
[30]
Volume 2 Issue 2 (2023) 3 https://doi.org/10.36922/gpd.0312