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3.14 Objectives and Methods of Treatment
3.14.1 General Remarks
The aim is for a child to develop normally without neurological sequelae.
To achieve this, normal cerebral development does not require,in all cases
or at all times, rapid morphological disappearance of the AV shunt or rapid
shrinkage of the ectasia. However, disappearance of the ectasia over time
will result from a successful transarterial approach. We have never observed regrowth of a shrunken VGAM. To reach the objectives mentioned
above, similar to other teams (Berenstein 1992; Seindenwurm et al. 1991),
we favor transarterial embolization using the femoral approach with glue
(N-butyl cyanoacrylate, NBCA) as the primary embolic agent.This method
has proven reliable and predictable results.The perioperative technical aspects and results will be discussed below (see also Vol. 2, Chap. 14).
We have chosen not to use coils, balloons, or particles as first-line
agents, as they are inappropriate materials for the treatment of these
high-flow lesions. We cannot comment on the transvenous approach,
which has not yet been reported to provide reliable benefit as a primary
form of treatment in children as compared to the transarterial approach.
The available results regarding the long-term neurological outcome
(Mickle and Quisling 1986; Mickle and Peters 1993) and the unpublished
morbidity and mortality rates with the transtorcular and transjugular
venous approaches confirm the doubts expressed in the mid 1980 s when
this technique was first introduced.In any case,the treatment goal being
good clinical outcome, our discussion will be based on the results observed from the consistent management of 300 VGAM patients during
the past 20 years.
3.14.2 Neonates
The idea that a neonate with severe multiorgan failure would do well if
the VGAM were to be excluded is wrong; there is evidence in the literature
that in neonates following properly performed emergency embolization,
the neurological outcome was disastrous, despite apparently normal
pretherapeutic brain imaging (ultrasound or CT). This emphasizes the
importance of a thorough analysis in order to best predict the degree of
cerebral tissue impairment not evident on diagnostic imaging. We are
very aware of the difficulty of making these observations and decisions,
and this is actually the basis and purpose of the VGAM neonatal score.
The relationship with the parents and fair information on the disease and
results of the therapeutic team are crucial in the decision-making
process. Thus we do not perform embolization in a neonate with evidence of severe cerebral damage (25/140 neonates) or severe multiorgan
failure (score of less than 8, 17/140 neonates) in whom embolization
would only be a technical challenge without any hope of acceptable clinical benefit. This was the case in 17% of the patients referred to us with
VGAM,representing 42 out of 140 neonates (30%).This group thus forms
the most seriously ill group with a high spontaneous mortality rate.
191Neonates
Prenatal diagnosis is not by itself an indication to perform early delivery,interruption of pregnancy,or caesarian section at term. Few prenatal
manifestations have thus far shown prognostic value that are today an indication for abortion (3/93): in utero cardiac failure and cerebral damage.
In both in utero instances,these findings are associated with severe irreversible multiorgan failure at birth.Cardiac manifestations have been reviewed for neonates (Garcia Monaco 1991b; Chevret et al. 2002; Frawley
et al. 2002) and for prenataly diagnosed VGAMs (Rodesch et al. 1994).
Over 140 neonates (including the prenatally diagnosed cases referred)
only 23 (among the 95 cases that were felt to likely have an acceptable
neurological prognosis) needed to be embolized at neonatal age.Yet half
of these patients died despite treatment.
The role of the pediatric intensive care physician is crucial in the
neonatal age management of VGAMs.We rely heavily on their analysis of
the controllability of the various disorders and their therapeutic choices.
The following information will be useful in the management strategy
(Chevret et al. 2002):
Clinical evaluation of the baby and documentation of all the possible
events that have occured since birth (convulsions,for example, do not
occur in VGAM at this age unless brain damage has already taken
place)
Evaluation of renal and liver function
Tr a ns f on tanellar ultrasound
Evaluate for possible encephalomalacia
Research cerebral arterial flow reversal
Cardiac ultrasound to evaluate hemodynamic status: (Fig. 3.62)
– Right and left end diastolic diameters
– Left ventricular shortening
– Stroke volume
– Left ventricular output
– Systolic arterial pressure
– Research of patent ductus arteriosus and foramen ovale
– Ductal flow if present
– Search for descending aortic flow reversal
– Shape of the interventricular septum
– Search for associated cardiac malformation that might require spe-
cific treatment
Good-quality MRI to provide all necessary morphological informa-
tion regarding the lesions and the status of the brain tissue
Electroencephalogram to evaluate neurologic maturation and elimi-
nate seizures
Cerebral AV shunts result in a hemodynamic hyperkinetic state charac-
terized by a high cardiac output and a decrease in vascular systemic resistances. The hemodynamic consequences are of variable intensity, ranging from mild cardiac overload to cardiogenic shock. AV fistulas lead to
an increase in venous return and subsequent right heart overload. The
result is right heart dilatation, pulmonary arterial hypertension and increased pulmonary blood flow. The resultant greater pulmonary venous
return to the left heart increases left ventricular diastolic volume, which
3Vein of Galen Aneurysmal Malformation192
may be further increased by a possible persistent arterial duct. The consequence of the increased left ventricular preload is an increase in stroke
volume and stroke work.Excessive stroke work results in increased myocardial oxygen requirements. Coronary perfusion to the left ventricle
occurs mainly during diastole and depends on the systemic arterial
intramyocardial diastolic pressure difference as well as the duration of
diastole.Therefore,a reduction in arterial diastolic pressure (as observed
in AV shunt),an increase in end diastolic pressure (due to increased preload), and a reduction in diastolic period (due to tachycardia) are all
detrimental to myocardial perfusion,and hence oxygen delivery,and may
precipitate left ventricular failure. Thus, even if only the right ventricle
193Neonates
Fig. 3.62A–D. Cardiac ultrasound evaluation.A Right
cardiac failure with rightchamber dilatations; B dilated
pulmonary arteries;
C,D see p. 194
fails initially, biventricular failure frequently follows depending on the
size of the left to right shunt.
Several mechanisms are involved in the attempt to maintain myocardial performance, normal systemic output,and adequate tissue oxygenation in the event of cerebral AV fistulas. One of them is increased catecholamine release.As a result,there are increases in heart rate and in the
force of contraction of the myocardium. It should be noted that catecholamine release also has a detrimental effect on heart work by increasing left ventricular afterload. In the neonatal period, such compensatory
mechanisms are limited, because the sympathetic nervous system is immature at birth and because myocardial reserves are limited. The limitation in myocardial reserves is anatomic and functional.
3Vein of Galen Aneurysmal Malformation194
Fig. 3.62. (continued)
C suprasystemic arterial pul-
monary hypertension with
tricuspid regurgitation;
D type 3 interventricular
septum pattern
The neonatal heart contains a high proportion of noncontractile
fibers. Moreover, all functional cardiac reserves are mobilized to deal
with adaptation to extrauterine life, and the resting cardiac output required to provide oxygen to the tissues is at its maximum level. Consequently, the heart is limited in its reserve capabilities and cannot cope
with the extra work imposed by the fistula. These factors explain the
rapid progression toward cardiogenic shock observed in neonates with
high-flow fistulas. Furthermore, the transition from a fetal circulatory
pattern to an adult circulatory pattern is complex, and both pulmonary
and systemic circulations remain highly unstable during the 1st week
after birth. This can explain a persistent transitional circulation with
shunts through the ductus arteriosus and the oval foramen and a pulmonary hypertension,which worsen the systolic and diastolic wall stress.
Pulmonary edemais linked to high pulmonary blood flow and to left
ventricular failure. Pulmonary edema creates a reduction in distal ventilation. Consequently, arterial oxygen content and therefore also oxygen
delivery decrease, leading to the shock. Right heart failure secondary to
increased venous return creates congestion in the suprahepatic veins and
secondary retrograde congestion in the centrolobular region of the liver.
In patients in whom cardiogenic shock supervenes, reduction in hepatic
arterial blood flow may precipitate centrolobular necrosis.These are the
regions that are most sensitive to ischemia, but in the majority of cases
the double vascular supply to the liver (portal vein and hepatic artery)
protects the liver from ischemia, and hepatic dysfunction is only reflected in mild biological changes.
A reduction in cardiac output and mean arterial blood pressure can
reduce the glomerular perfusion pressure. This may cause oliguria or
anuria and activation of the renin-angiotensin system. This situation
worsens the working conditions of the heart. The renin-angiotensin system activation increases left ventricular afterload by vasoconstriction
and the preload of the right ventricle by increased circulation volume and
increased sodium and water reabsorption (through associated secondary
hyperaldosteronism). Thus diuretics play a critical role in management.
The role of the atrial natriuretic factor has not been documented in this
situation, but from experimental studies we have seen that it is probable
that its influence is modest. There is often aortic and middle cerebral
steal of the diastolic flow assessed by echo Doppler.This steal usually has
no consequences on whole brain maturation, which is more dependent
on hydrocephalus and heart failure.
The clinical presentation depends on the size of the left-to-right shunt
and tolerance. If the shunt is not large, cardiovascular manifestations are
usually mild.Major symptoms are sweating, feeding difficulties, and poor
weight gain. Major signs are continuous murmur with a dancing carotid
pulse and distended jugular veins.There is tachycardia,and the peripheral pulses are also bounding. Systolic arterial pressure is normal,but diastolic pressure is low. The liver is always enlarged. Patients with cardiogenic shock present with respiratory distress, pallor, and often coma. All
pulses except the carotid pulses are feeble. Systemic arterial blood pressure has a tendency to drop. The capillary refilling time is prolonged to
over 3 s. Pulmonary edema is indicated by respiratory distress, tachyp-
195Neonates
nea, and rales on auscultation of the lungs. The patient is oliguric or
anuretic, and metabolic and lactic acidosis are present. Chest radiography demonstrates cardiomegaly,especially of the right heart. The superior vena cava is generally markedly dilated,and there may be signs of pulmonary edema. Electrocardiographic evidence of atrial and ventricular
hypertrophy depends on the duration and magnitude of the shunt and
the degree of heart failure. Echocardiography is the best method of assessing the cardiac consequences of the fistula; it demonstrates right ventricular dilatation.The distensibility and compliance of the right ventricular wall are compromised.The left ventricle is hyperkinetic with a shortening fraction of greater than 40%, a normal shortening fraction
indicating a left ventricle failure. Echocardiography and Doppler ultrasound can measure pulmonary hypertension, ejection fraction, stroke
volume and cardiac output and can detect a tricuspid insufficiency.
Echocardiography is also useful for the diagnosis of persistent ductus
arteriosus or a cardiac malformation,which must be corrected before any
decision is made concerning endovascular treatment of the AV shunt
itself (Tables 3.3,3.4; Chevret et al. 2002).
The aims of symptomatic therapy are to improve oxygen delivery to
the tissues and decrease tissue oxygen consumption. If cardiac failure
cannot be controlled by these measures, embolization of the AV shunt
should be considered.
3Vein of Galen Aneurysmal Malformation196
Ta ble 3.3. Cardiac parameters before the first endovascular embolization of the
VGAM
Ultrasound parameters Death (n=12) Survivalb(n=12) P
PDA (right-to-left 10 (83.3%) 4 (33%) 0.003
shunting, %)
LVEDD (mm) 20 (10–23) 20 (15–27) 0.23
LV SF (%) 47 (30–55) 39.5 (31–53) 0.68
RVEDD (mm) 16 (11–25) 15.5 (8–18) 0.82
SIV pattern 1 /2 / 3 (n)
a
0 /2 /8 4 / 3 / 2 0.005
Cardiac output 395.5(265–650) 325.5 (224–500) 0.29
(ml:min.kg
–1
)
Systemic arterial 67.5 (44–85) 65 (40–90) 0.19
pulmonary pressure
(mmHg)
Suprasystemic arterial
pulmonary pressure (%) 70% 20% 0.031
Descending aortic
diastolic reverse flow (n)
a
81 0.0007
LV SF,left ventricular shortening fraction; LVEDD, left ventricular end-diastolic
diameter; RVEDD, right ventricular end-diastolic diameter; SIV, interventricular
septum; PDA, patent ductus arteriosus; VGAM vein of Galen aneurysmal
malformation.
a
Missing data in three survival and two dead infants.
b
Missing datain four survival and two dead infants.
3.14.2.1 Reducing Oxygen Consumption
In patients with severe distress, tracheal intubation and mechanical ventilation reduce oxygen consumption and improve myocardial performance by limiting right heart overload. Oxygen consumption can also be
reduced by providing good external warmth for small infants and by
prescribing bed rest and sedation.
3.14.2.2 Improving Oxygen Delivery
Oxygen transport is determined by three factors: arterial oxygen saturation, hemoglobin concentration, and cardiac output. Measures that improve the patient’s effective ventilation, arterial oxygen saturation, and
hematocrit should therefore be the first steps taken to treat patients with
heart failure. Endotracheal intubation and adjustments of fractional inspired oxygen concentration on mechanical ventilation are often necessary to obtain an adequate arterial saturation. The goal is to obtain an
arterial saturation equal to 100%. Hemoglobin concentration should be
maintained between 10 and 12 g/dl, and the hematocrit level at about
30%. A higher concentration of hemoglobin may induce blood hyperviscosity and hence a decrease in oxygen transport.
Since cardiac output is determined by preload, afterload, contractility,
and heart rate, effective drug therapy influences one of these factors.
197Improving Oxygen Delivery
Ta ble 3.4. Clinical characteristics of newborns with VGAM and severe cardiac failure (Chevret 2002)
a, b
All Death Survival P
n 24 12 12
Sex ratio F (%) 37.5 42 33.3 1
Gestational age (weeks) 40 (36–42.7) 40 (36.7–41) 39 (36–42.7) 0.58
Birth weight (percentile) 75
th
75
th
75
th
1
Head circumference (>95
th
percentiles) 50% 50% 50% 1
VGAM diagnosis (days of life) 2.5 (0–15) 1.5 (0–15) 3 (0–8) 0.1
CCF diagnosis (days of life) 1.5 (0–14) 2 (0–14) 1 (0–5) 0.2
MV onset (days of life) 3 (0–19) 2.5 (1–19) 3 (0–17) 0.47
Bicêtre PICU admission (days of life) 12 (0–25) 12 (2–22) 11.5 (0–25) 0.56
Inotropic drugs use 54% 100% 8.3% <0.0001
Endovascular treatment
Ye s 75% 50% 100% 0.014
First session (days) 21 (7–38) 20 (11–29) 26 (7–38) 0.68
Neurological outcome
Developmental delay 66.7%
Epilepsy 27.3%
VGAM, vein of Galen malformation; MV, mechanical ventilation; CCF, clinical cardiac failure; PICU, pediatric intensive
care unit.
a
Results are expressed as percentage or median (range) as appropriate.
b
Fischer’s exact test and Wilcoxon rank sum test are used for statistical analysis.
Diuretics are the first step for reducing preload.They are given to eliminate excess salt and water and to prevent their reaccumulation. Furosemide is the most powerful agent (2–4 mg/kg per day in four IV injections or orally). Diuresis is often more rapid and effective if the drug is
given intravenously. This diuretic tends to eliminate potassium; thus
serum potassium must be measured periodically and potassium supplements may be needed.One alternative to the use of diuretics is to attempt
to restrict sodium and fluid intake. Water intake may be reduced to
60%–80% of maintenance levels.
Cardiac output can be improved by increasing cardiac contractility
with inotropic agents.Digoxin is the main agent used for increasing myocardial contractility.However,its use in hyperkinetic states due to AV fistulas remains controversial: pretreatment myocardial function indices
may already be above normal, and there is no clear evidence that their
further increase has any clinical benefit. Theoretically,when left ventricular dysfunction from chronic volume overload occurs, digoxin should
be beneficial. Digoxin also slows conduction, thus beneficially lowering
ventricular rates and improving myocardial perfusion. The oral loading
dose of digoxin is 30 mg/kg in newborns, and the maintenance dose is
10 mg/kg per day. In situations of severely compromised cardiac output,
catecholamines are powerful boosters of myocardial contractility.Dobutamine and dopamine can be used. These agents should be administered
under close supervision, optimally with monitoring of arterial pressure,
central venous pressure, heart rate, and urinary output. Dobutamine is
less chronotropic and arrhythmogenic than dopamine, and it may have a
more direct effect on enhancement of coronary flow. These drugs can be
used in concert with other agents, such as afterload-reduction drugs.
Amrinone, an inhibitor of myocardial cyclic adenine monophosphate
(cAMP) phosphodiesterase activity, is the most recent drug proposed in
cardiogenic failure without drop of systemic arterial pressure. This drug
has the combined effects of inotropic support and peripheral vasodilation. However,pediatric experience is limited.
Cardiac output can also be improved by decreasing ventricular afterload. However, vasodilators should be used with caution, because vasodilation can produce severe hypotension, decrease coronary perfusion,
and cause myocardial ischemia. Vasodilators are obviously contraindicated if systemic arterial pressure is low. For chronic vasodilation, an
angiotensin-converting enzyme inhibitor can be used (0.1–0.4 mg
enalapril/kg per day in one or two doses; 0.1mg captopril/kg per day in
one or two doses with a progressive increase to 2 mg/kg per day). When
sodium is depleted secondary to initial measures, it is important to start
with low doses,monitoring for a possible drop in arterial blood pressure.
Part of this neonatal VGAM group with CCF is identified as carrying
harmful manifestations such as suprasystemic pulmonary hypertension
resistant to NO (Chevret et al. 2002). This group was not identified
10 years ago and this raises the possible deleterious side effects of active
ICU management and oxygen therapy on postnatal lung vascular maturation (pericytic vascular coverage).
There is now experimental evidence to suggest that increased pulmonary blood flow and pulmonary hypertension can alter normal post-
3Vein of Galen Aneurysmal Malformation198
natal vascular remodeling, preventing a fall in pulmonary vascular resistance, even once the cause of pulmonary overflow is removed (Reddy
1995; Jouannic 2003). A recent fetal model with high pulmonary blood
flow,obtained by aortopulmonary shunt placement,provided for an alteration of the endothelin cascade by earlier upregulation of gene expression,
contributing to vascular remodeling and enhancement of pulmonary vascular reactivity (Black 2000). In severe situations with mechanical ventilation and a high level of pulmonary hypertension,fine evaluation of hemodynamic parameters (see Sect.3.15) should be decisive so as to provide
the best medical treatment associated with diuretics and fluid restriction:
Reopen ductus arteriosus with prostaglandin E1, alprostadil (Pro-
stineVR“) (in case of closed ductus arteriosus with dilatation of right
chambers)
Use other inotropic agents: amrinone (with vasodilatation effect bene-
fit to pulmonary pressure),dobutamine or dopamine.
Agents used in pulmonary hypertension (PHT) of other diseases:
nitric oxide (NO)or prostacycline.
The indication to reopen is typically in VGAM neonate with CCF associated with iso or suprasystemic PHT.Alprostadil is used in perfusion and
starts at 0.1 g/kg per min until response is obtained then doses will de-
creased until 0.01 g/kg per min to find the smallest efficient dosage. The
main secondary effects are tachycardia fever, apneas, and cutaneous
flush. Alprostadil is used to temporarily relieve the right ventricle, in
order to fully evaluate the consequences of the CCF and to decide on
whether early endovascular management is needed.
Two-thirds of neonates referred could be treated in infancy; if we add
the patients who were diagnosed at that age, three-quarters of VGAM
babies could be treated at the time of the optimal therapeutic window.
In neonates, the immediate goal is to not only to restore a satisfactory
systemic physiology and to gain time (Abbit et al. 1990; Garcia Monaco
1991a; Gomez et al. 1963; Norman and Becker 1974), but also to recreate
the conditions enabling postmaturation of the various vascular systems.
It is apparent that the VGAM neonatal score used during the first few days
of life varies from one day to the next depending on the response to medical treatment. Failure to observe a response to ICU management (or
stagnation) leads to early embolization at neonatal age. The end point of
partial embolization is usually the reduction by one-third to one-half of
the AV shunt for a significant systemic impact.This is still very subjective;
however, we use endovascular or follow-up hemodynamic tools that allow these changes induced by embolization to be quantified (Moersdorf
and Lasjaunias 1996). Immediate clinical evaluation with cardiac ultrasound demonstrates the response to the embolization and the possible
need to repeat the intervention.
Wa iting till the 5th month of age to perform the first diagnostic and
therapeutic angiogram is the optimal timing whenever feasible.If the parameters that have been chosen during that period are not reached, then
the date of this session is brought forward. In some small VGAMs,unusually severe CCF or PHT may be noted. Lack of response to drugs must lead
to a careful search for an associated cardiac malformation, primary pul-
199Improving Oxygen Delivery
monary disease, or an undesired persistent ductus arteriosus. The latter
should regress rapidly and spontaneously; if this is not noted and before
embolization, thorascopic clipping should be discussed. A high-quality
cardiac ultrasound study can show the role played by the present fetal circulation in persistent CCF. The physiopathology of such CCF, mimicking
fetal persistant circulation in its most severe forms, is better known.
3.14.3 Infants and Children
In infants and children, the immediate goal is to preserve the hydrovenous equilibrium and normal development and at the same time to exclude the lesion. Our concern in patients of this age is to anticipate the
natural history in order to avoid ventricular shunting (Andeweg 1989;
Del Bigio et al. 1985; Sainte Rose et al.1984; Zerah et al.1992; Girard et al.
1994; Gibson et al. 1959). Understanding the mechanisms of clinical
expression (Scheme 3.1A–F) and their reversibility with appropriate
treatment is the basis for a coherent management policy for this disorder.
The concept of a therapeutic window derived from this understanding
helps us optimize treatment management and timing (Fig. 3.63).
Premature attempts to exclude an asymptomatic lesion or taking
significant technical risks to exclude,in a single session,a VGAM that presents no immediate cerebral danger and can be eradicated in two or three
sessions should not be encouraged. Conversely,a decision not to treat on
the assumption that an asymptomatic lesion is well tolerated is certainly
naive and dangerous.At this age, reliance on the parameters and scores
presented above is recommended. Pediatric neurologists will provide all
the necessary information on the progression of the child and the need to
improve the capacity for normal development.
In the series used in this chapter, the treatment was declined in 9 out of
125 young infants and 3 out of 52 older children who presented severe
brain damage. In others,referred late with already permanently impaired
functions or severe developmental delays, treatment attempted to improve the quality of life. Under these circumstances, endovascular treatment has also proven to achieve satisfactory results,even with incomplete
exclusion of the lesion. Endovascular endpoints will be directed to the
draining pattern of the brain dependent upon the presence and degree of
cavernous sinus capture, jugular bulb maturation, parietal convexity
sump effect, venous stagnation from sinus congestion,pial reflux,superior petrosal to lateral mesencephalic reflux and posterior fossa venous
congestion,subependymal veins reflux,etc.
Although the volume of the ectatic vein does not seem to be mechanically responsible for brain stem compression, shrinkage of the pouch is
always a welcome reward for an effective transarterial embolization. As
mentioned in the analysis of the natural history, the fact that a given
VGAM has transformed into a VGAM draining into pial veins necessitates complete exclusion, as a formal goal, in order to eliminate the risk of
hemorrhage. In this situation, the strategy and timing may be similar to
that in any nonruptured, deep-seated lesion in which embolization and
combined approaches can be contemplated.
3Vein of Galen Aneurysmal Malformation200
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