Chapter 111- Vascular Malformations, Intracerebral Hemorrhage, and

Subarachnoid Hemorrhage in Infants and Children

Introduction and Epidemiology

 The advent of computed tomography (CT) and magnetic resonance imaging (MRI) in
the past three decades has given clinicians the opportunity to understand better the
underlying causes of different types of acute neurologic symptoms in neonates,
infants, and children.
 As such, there has been increasing attention and recognition of intracerebral
hemorrhage and subarachnoid hemorrhage as an important contributors to these
acute injuries.
 Intracerebral hemorrhage (ICH) refers to bleeding into the brain parenchyma and/or
ventricles, whereas SAH refers to bleeding into the subarachnoid space.
 Previous studies suggest that approximately half of childhood strokes are caused by
ICH and SAH.
 The incidences of ICH and SAH in pediatric patients obtained from a California-wide
discharge database are 0.8/100,000/year and 0.4/100,000/year, respectively.
 ICH and SAH also may occur after traumatic brain injuries, but this chapter focuses on
nontraumatic or spontaneous ICH and SAH.
 Hypertension and amyloid angiopathy are the most common causes of primary adult
ICH.
 Although hypertension has been reported as a risk factor for ICH in children, most
childhood spontaneous ICH and SAH are caused by secondary causes such as
ruptured vascular malformations, tumors, cerebral infections, or hematological
abnormalities.
 Even after a complete workup, 9% to 23% of childhood ICH/SAH remains idiopathic.

 This chapter will focus on ICH and SAH caused by ruptured vascular malformations.
 Depending on the series, vascular malformations are responsible for approximately
17.5% to 73.5% of pediatric ICH 4 6 , arteriovenous malformations (AVMs) 7 are more
common than cavernous malformations (cavernomas or cavernous angiomas) or
aneurysms.
 The prevalence of intracranial aneurysms in children ranges from 0.5% to 4.6%, and
most do not present with acute rupture.

Presentation
 Common presenting signs and symptoms include headache, altered mental status,
focal deficits like hemiparesis, seizures, and nausea and vomiting.
 Headache is the most common presenting symptom and is present in 50% to nearly
80%.
 Headache is classically sudden onset and severe and often accompanied by nausea
and vomiting, but some patients may have no headache or mild headache or
headache that builds more slowly.
 Neck pain and/or stiffness can also occur, particularly in the settings of SAH or IVH.
 Altered mental status is present in 50% or more and can range from subtle changes in
mentation to coma.
 Focal deficits are present in 50% or more of children with ICH and are typically
referable to ICH location.
 Posterior fossa hemorrhages can present with cerebellar findings, cranial nerve
palsies, and rapid progression to coma. In one prospective cohort, over 40% of
children with ICH presented with seizures.
 Presentation in children with ICH and SAH can be rapid, occurring over minutes to
hours, or insidious over hours to days.
 In a cohort of children with intraparenchymal hemorrhage, the median time to hospital
presentation was 70 minutes, but nearly a quarter presented after 24 hours.
 Those with altered mental status, severe headache, or focal neurologic deficits likely
present more quickly, whereas those with milder headache and without substantial
focal deficits may take longer to seek medical attention or to be diagnosed.

Differential Diagnosis

 The differential diagnosis for ICH and SAH includes other stroke syndromes such as
arterial ischemic stroke and cerebral venous sinus thrombosis, tumors, metabolic and
mitochondrial disease, cerebral infections, demyelinating diseases, and complicated
migraine syndromes, among others.
 Imaging studies can quickly determine whether the presenting signs and symptoms
are caused by hemorrhage or by another etiology.

Initial Studies

 Initial studies are focused on diagnosis of hemorrhage and possible vascular

abnormalities as well as detection of hematological abnormalities that must be
corrected. Typically, brain CT is the initial imaging of choice because it is rapid, is
widely available, and can be performed without sedation if the child has preserved
airway reflexes.
 CT diagnoses almost all acute ICH. In adult studies, CT misses about 5% of acute
SAH.
 17-19If SAH is suspected and a CT does not demonstrate hemorrhage, a lumbar
puncture should be performed unless there is a contraindication.
 A spun-down sample of cerebrospinal fluid (CSF) can be examined for the presence
of xanthochromia (yellow discoloration of CSF secondary to bilirubin) to differentiate
SAH from venous blood from a "traumatic tap."
 Acute laboratory studies should include electrolytes, complete blood count with
platelets, prothrombin time or international normalized ratio, activated partial
thromboplastin time, fibrinogen level, and type and screen.
 A more detailed hematological workup may be necessary in some children with
suspected bleeding diatheses, but this information will be covered elsewhere in the
text.
 It is critical to evaluate the child with spontaneous ICH or SAH for vascular
malformations because some may require urgent stabilization and treatment.
 In the stable patient, MRI with magnetic resonance angiography (MRA) can be helpful.
 In a less stable patient, CT angiography (CTA) may be more feasible in the acute
setting as a first screen for vascular malformations.
 The MRI will show parenchymal damage (gradient echo and susceptibilityweighted
imaging are extremely sensitive for blood) and cavernous malformations, whereas the
MRA may show AVMs or aneurysms.
 However, once an AVM or aneurysm is found, or if an MRI does not demonstrate a
vascular malformation, most neurosurgeons will recommend a conventional
angiogram.
 The American Heart Association guidelines for pediatric stroke recommend that a
conventional catheter angiogram be obtained when no cause for hemorrhage is
identified.
 Furthermore, conventional angiograms are often used for surgical planning or to treat
vascular malformations by administering embolization material for an AVM or coils for
an aneurysm.
 See sections on AVM and aneurysms for more detailed treatment options.

Initial Management

 Stabilization of the patient and minimization of secondary brain injury are the goals of
acute management, which include assessments for ongoing seizures, elevated
intracranial pressure (ICP), and herniation syndromes.
 Childhood guidelines for management are based on adult practice guidelines or
cohort studies because no pediatric trials exist.
 A neurosurgeon should be consulted promptly upon diagnosis of ICH or SAH.
 Basic management includes frequent neurologic examinations to assess for
deterioration, maintenance of the head of the bed at least 30 degrees above the
tragus to facilitate venous drainage, isotonic fluid administration, and maintenance of
normoglycemia and normothermia. Children with seizures should be treated with
anticonvulsants; there is no evidence that prophylaxis with anticonvulsants is effective.
 Treatment of hypertension in adults with ICH may prevent expansion of the cerebral
hematoma; 23 a recent meta-analysis demonstrated a nonstatistically significant trend
toward fewer adult patients with death or dependency at 3 months among those with
intensive blood pressure-lowering treatment compared with patients provided
"standard" treatment.
 Although adult ICH guidelines discuss management of hypertension, there are no data
for treatment in children with ICH.
 It may be a reasonable goal to lower blood pressure to the 95th percentile for age and
sex, but this is not evidence based.
 Elevated blood pressure in the setting of ICH can be an autoregulatory mechanism to
maintain cerebral perfusion. Therefore caution must be utilized when lowering blood
pressure in a child with ICH so that secondary ischemia is not caused, and ICP
monitoring should be considered.
 Antihypertensive medications should be chosen with care. Vasodilators can reduce
systemic blood pressure, thereby compromising cerebral perfusion pressure.
 Use of beta adrenergic blocking agents may be preferable because they do not have
cerebral vasodilatory effects.

Acute Medical and Surgical Monitoring and Management

Increased Intracranial Pressure: Signs, Symptoms, and Monitoring

 Increased ICP can occur as a result of direct mass effect from an ICH or from
intraventricular hemorrhage and hydrocephalus that can occur with ICH or SAH.
 In patients with intraparenchymal hemorrhage, increased ICP may occur acutely
because of mass effect from the hemorrhage.
 Increased ICP can be acute or can develop over hours to days. Monitoring for
increased ICP should be considered in any pediatric patient with ICH or SAH with
abnormal or deteriorating mental status.
 Signs and symptoms of increased ICP include worsening or refractory headache
(usually worse when supine), emesis, combativeness or agitation, sixth nerve palsies,
and papilledema. Cushing's triad of hypertension, bradycardia, and irregular
respirations is typically a late finding.
 An intraventricular catheter (IVC), also called an external ventricular drain (EVD), is
often the monitoring tool of choice because it can be used to measure ICP as well as
to manage ICP via drainage of CSF or intraventricular blood.
 In one series, more than a quarter of children with intraparenchymal hemorrhage had
a ventriculostomy. A subdural bolt can be used to measure ICP if an IVC is not an
option.

Increased ICP: Medical Management

 Medical management for reducing ICP acutely is typically temporizing and includes
hyperventilation to a PC02 of 25 to 30 mm Hg, maintenance of the patient's head
midline and elevated to at least 30 degrees above the tragus to facilitate venous
drainage, and hyperosmolar therapy with either hypertonic saline or mannitol.
 Plasma osmoles and electrolytes must be monitored frequently when osmotic agents
are used to avoid hypovolemia, hypotension, and renal failure.
 Sedation is sometimes needed to help manage elevated ICP, but this need must be
balanced with the need for monitoring the patient's mental status and neurologic
examination.
 Corticosteroids have not been helpful in adult randomized trials, and hyperglycemia
that may be caused by corticosteroids or the stress of illness and acute brain injury is
associated with poorer outcomes.

Increased ICP: Surgical Management

Evacuation of Intraparenchymal Hemorrhage

 Emergent evacuation of supratentorial hematomas did not improve outcomes in adults
with spontaneous ICH in the Surgical Trial in Intracerebral Hemorrhage (STICH), but
few young adults were enrolled.
 A small retrospective series reported that young adults with lobar hemorrhages with
clinical deterioration caused by mass effect benefited from early surgical intervention.
 The 2010 guidelines for spontaneous ICH management in adults state that patients
with cerebellar hemorrhage with clinical deterioration, brainstem compression, or
obstructive hydrocephalus from compression of the ventricles should undergo surgical
hemorrhage evacuation.
 Children, who are less likely to have cerebral atrophy than older adults and who
typically have lobar hemorrhages rather than deep hemorrhages, may require urgent
hematoma evacuation to reduce mass effect and to prevent or relieve herniation
syndromes.
 Children with cerebellar ICH may warrant evacuation to prevent herniation.

Hemicraniectomy

 Decompressive craniectomy may be life-saving and function-sparing when there is

rapid deterioration in the setting of a large arterial ischemic stroke or ICH in adult
trials.
 In a series of 10 children with malignant MCA infarction, 7 underwent
hemicraniectomy and all survived and had moderately good recovery.
 Death in three children occurred because of elevated ICP; those three patients did not
undergo hemicraniectomy.
 In a pediatric prospective cohort, 3 of 22 children with ICH had decompressive
craniectomies; all were functionally independent.

Seizures: Monitoring and Treatment

 Seizures are a common presenting symptom and sequela of ICH and SAH. For those
who present with seizures, it is reasonable to acutely treat the child with an
anticonvulsant.
 Although prophylactic anticonvulsants are sometimes used in the setting of ICH or
SAH, the American Heart Association pediatric stroke guidelines recommend against
prophylactic anticonvulsant use in the setting of ischemic stroke and do not make
recommendations for children with ICH.
 A study that analyzed prophylactic anticonvulsant use in the Cerebral Hematoma And
NXY Treatment (CHANT) trial for neuroprotection in adults with ICH showed that
prophylactic use was associated with a poor outcome; only 8% of study participants
were treated with prophylactic anticonvulsant medication.
 In another adult prospective observational study, phenytoin use was associated with
longer hospitalizations and worse modified Rankin Scale scores.
 In both adult studies, there was selection bias because the sickest patients with the
largest hemorrhages were also the most likely to have prophylactic anticonvulsants
administered.
 In a pediatric prospective cohort of children and neonates with ICH, the 1- and 2-year
seizure-free survival rates were 82% and 67%, respectively.
 Discharge on anticonvulsants was not protective against developing seizures during
follow up, but that result must be interpreted with caution because the decision about
whether to discharge a child on an anticonvulsant was clinically based.
 To detect seizures in the acute ICH and SAH settings, continuous EEG monitoring is
used.
 A study of 100 children with continuous EEG monitoring for diverse indications,
including some children with ICH, reported that EEG monitoring led to the initiation or
escalation of anticonvulsants in over 40% of patients because of seizure detection.
 Many of these children had prolonged unresponsiveness after a seizure as the
indication for EEG monitoring, and the application of these data to children with acute
ICH is unclear.
 Continuous EEG monitoring should be considered in children with ICH or SAH who
have 1) persistently altered mental status or 2) movements or vital sign changes that
are suggestive of seizures that cannot be captured on a routine EEG.
 Although continuous EEG has been used in children in the setting of SAH to detect
vasospasm and is often used for vasospasm detection in adults, there are no studies
to demonstrate its utility for this indication in children.

Recurrent Hemorrhage

 Few pediatric studies report the incidence of recurrent hemorrhage.

 In one small retrospective cohort from Switzerland of 34 children presenting between
1990 and 2000, recurrent ICH occurred in 3 children All recurrences were within the
first year after the incident ICH and were in children with unknown cause of
hemorrhage (1 subject) or in children with unrepaired vascular anomalies (2 subjects).
 In a population-based cohort of 116 children with ICH in Northern California
presenting between January 1993 to December 2004, 11 (9.5%) had recurrent ICH at
a median of 3.1 months from the initial hemorrhage.
 Nine of 11 recurrences were in children with vascular malformations, 6 of whom were
not treated.
 The two children with medical etiologies of ICH recurred within 1 week of the incident
hemorrhage.
 Children with vascular malformations should therefore have close follow up,
particularly if the malformation cannot be treated or if they will be monitored and
treated in a subacute setting.
 ICH and SAH caused by an aneurysm have an increased risk of rebleeding
immediately after hemorrhage.
 Aneurysms should be managed with prompt surgical and/or endovascular treatment.
 In adults with aneurysmal hemorrhage, 4% rebleed on day 1; the highest risk of
rebleeding is in the first 6 hours.
 In the first 2 weeks after the initial bleed, 15% to 20% of adult patients have
rebleeding, and 50% have rebleeding within 6 months.
 Outcomes

 Estimates of mortality after childhood ICH range from 5% to 54%.3,14,41 According to

data from the Kids' Inpatient Database, mortality from ICH was 15.4% in 2003 and
12.8% in 2009.
 In the Kids' Inpatient Database pooled sample from 2003, 2006, and 2009, predictors
of mortality in multivariable analysis included Hispanic ethnicity, older age at
presentation (11 to 18 years vs. 1 to 10 years), coagulopathy, and coma.
 Poorer outcomes have been associated with infratentorial location, Glasgow Coma
Score (GCS) at admission, aneurysmal cause of hemorrhage, age <3 years at the
time of ICH, and underlying hematological disorders.
 Another retrospective study showed that ICH volume predicted poor outcome in
children.
 A prospective childhood ICH study found that ICH volume and altered mental status
within 6 hours of hospital presentation were risk factors for short-term functional
disability.
 These findings are consistent with adult studies that show that larger ICH volume and
GCS <9 at the time of presentation are strong predictors of 30-day mortality.
 Bedside estimates for hemorrhage volume in children exist and can be used for
clinical outcome prediction.
 These methods use the equation for an ellipsis to measure hemorrhage volume and
total brain volume and express ICH volume as a percent of total brain volume.
 Little information exists on cognitive outcomes after ICH in children.
 Thirteen of 21 surviving subjects (62%) in a prospective cohort had cognitive and/or
behavioral deficits at a median of 3.5 months after hemorrhage.
 One retrospective cohort study of 56 Dutch children <16 years of age at onset of ICH
who received care at a single medical center between 1978 and 1998 had long-term
follow-up (mean 10.3 years) on all 36 surviving patients.

Mean Full Scale

 Intelligence Quotient (IQ) of the 31 subjects who underwent cognitive testing was not
below average (IQ 106, SD 20, n = 28), but the large standard deviation indicates a
range of IQs.
 Fifteen of 31 patients (48%) had signs of cognitive deficits when their performance
was compared with their premorbid academic abilities or to those of their parents.
Moderate to severe cognitive deficits were present in 7 patients (23%).
 Seizures and epilepsy are another concern after ICH and SAH.
 In one prospective cohort of 72 children and neonates with ICH, the 1- and 2-year
seizure-free survival rates were 82% and 67%, respectively, and the 1- and 2-year
epilepsy-free survival rates were 96% and 87%, respectively.
 ICP that required urgent intervention was a risk factor for remote symptomatic
seizures and the development of epilepsy.
 There are few reports on health status or quality of life after childhood ICH. In one
report of children with arterial ischemic stroke or ICH, epilepsy and degree of
hemiparesis were associated with worse health status at follow-up.
 More data are needed to determine the factors that influence quality of life in children
after ICH and SAH.

High Flow Lesions

Arteriovenous Malformations

 Cerebral AVMs are characterized by an abnormal connection of arteries and veins in

the brain without intervening capillaries.
 AVMs are typically congenital lesions that are a result of failure of venous and
capillary development in the third week of gestation.
 The resulting direct connections between arteries and veins create a high-flow lesion
and arterialization of the veins.

Epidemiology

 The incidence of cerebral AVMs has been estimated at 1 per 100,000 per year. 49
 Although the lesions are thought to be congenital, in one series of over 2000 patients
with AVMs, only 8.
 4% presented at age 10 years or younger.
 Other estimates are that 18% to 20% of cerebral AVMs present in the pediatric
population.
 Hemorrhage is the most frequent presentation in children and adults, but children
seem to present with hemorrhage even more commonly than do adults.
 Seizures and headache are other common presenting symptoms.
 Some may present with progressive neurologic deficits even when there is no
hemorrhage, presumably related to the steal of blood flow from healthy brain by a
high-flow AVM.

Associated Conditions and Genetic Syndromes

 Certain genetic syndromes can have cerebral AVMs as a prominent feature (Table
111-1 @).
 Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant condition
characterized by AVMs of the skin (telangiectasias), nose, lungs, and brain. Cerebral
AVMs can be multiple.
 In families in which the diagnosis is known or in young patients, it is unclear when
screening for cerebral AVMs should begin.
 However, children with HHT can present in early childhood with hemorrhage.
 Patients with brain AVMs should have a skin examination to assess for telangiectasias
and should be asked about frequent severe nosebleeds, which are often an early sign
of HHT.
 If there is concern for HHT, patients should be referred to a center or provider with
HHT expertise for comprehensive evaluation.

TABLE 111-1 Genetic Disorders Associated with AVMs/AVFs, Cerebral

Cavernous Malformations, and Aneurysms

Evaluation

 When a child presents with either seizures or hemorrhage, CT or MRI is often the first
diagnostic images obtained.
 MRI is helpful in children with hemorrhage because the underlying parenchyma can
be assessed.
 MRA or CTA is often performed with the initial parenchymal imaging and can
diagnose or suggest AVM in many cases.
 However, conventional catheter angiogram (CCA) is more sensitive and should be
considered when an underlying vascular malformation is not seen on brain MRI when
hemorrhage is the presentation.
 Even when MRA or CTA diagnosis of AVM is made, a CCA should still be performed
to characterize the lesion better and to assess for associated aneurysms, which often
influence the rapidity of treatment.
 Even when a CCA is negative in the acute setting after a hemorrhage, a follow-up
CCA should be considered because the hematoma can compress and obscure an
AVM, which might only become evident months to even a year or more later.

Treatment

 The risk of hemorrhage from a cerebral AVM in children has been estimated at 2% per
year, so most should be evaluated for treatment.
 However, some AVMs may not be treatable because of their location or size.
 In a patient who presents with hemorrhage and is stable, it may be reasonable to wait
a month or more for the hematoma to regress before definitive AVM treatment as long
as there is not an associated aneurysm.
 In a comatose or deteriorating patient with an AVM, treatment may be required in the
acute setting.
 The timing of AVM treatment after a hemorrhage is often dependent on the
interventionalist and the surgeon.
 The Spetzler—Martin grading system grades AVMs based on their characteristics in
order to predict risk of neurologic morbidity from surgery.
 AVMs are graded on size (under 3 cm = 1 point, 3 to 6 cm = 2 points, over 6 cm = 3
points), adjacent eloquent cortex (noneloquent = O points, eloquent = 1 point), and
draining veins (superficial only = O points, deep veins = 1 point).
 The total score ranges from 1 to 5 points with greater scores conferring greater risk of
neurologic morbidity.
 One study that compared children to adults found that children have better outcomes
than adults after microsurgical resection of AVMs, which is not explained by
hemorrhage rates or AVM characteristics.
 Therefore, surgical resection should be carefully considered in each pediatric case.

 Treatment options include surgical resection, embolization, and stereotactic

radiosurgery (Figure 111-1 @). Often a combination of treatments is required.
 Embolization may completely obliterate some AVMs, but is more often used as an
adjunct therapy to surgical resection or radiosurgery.
 There are pediatric data suggesting that embolization alone as a treatment for AVMs
may increase the rate of posttreatment hemorrhage relative to the natural history.
 Embolization before operative resection serves to reduce flow to the AVM, thereby
reducing the risk of bleeding during the surgery.
 Moreover, preoperative embolization in highflow lesions may provide a staged
reduction in blood flow over 24 to 48 hours (between embolization and subsequent
surgical resection), potentially reducing the risk of intraparenchymal hemorrhage that
can occur from rapid rerouting of blood flow from a (now resected) low-resistance
AVM into higher resistance normal vasculature (unused to handling the high flow
previously running through the AVM), the so-called "normal-perfusion breakthrough
syndrome".
 Embolization may also facilitate subsequent radiosurgery by reducing the volume of
the nidus and immediately addresses the risks related to AVMassociated intranidal
and extranidal aneurysms.
 In one study, 75% of children underwent presurgical embolization, and 3% underwent
preoperative radiosurgery.
 Another study utilized preoperative embolization in 21% of patients and highlighted
the utility of intraoperative angiography to demonstrate complete resection of the
AVM.

FIGURE 111-1 @ Left frontal arteriovenous malformation with hemorrhage. A,

Noncontrast. ..

 Surgical approach (microsurgery vs. radiosurgery) is typically based on both AVM

location and AVM anatomy.
 Multidisciplinary review of cases with inclusion of neurosurgery, interventional
radiology, and radiation therapy physicians is helpful in determining the need for
treatment and the best approach for a given patient.
 In children, evidence supports the use of surgical resection (with or without
embolization) as a first-line therapy in the majority of low- to moderate-risk AVMs
(Spetzler-Martin 1-111), contrary to the more controversial data in adult patients from
the ARUBA trial.

Outcome

 In a small series, intraoperative CCA was helpful because it detected residual AVM in
4/18 children who underwent intraoperative CCA, which resulted in immediate repeat
resections.
 In this series, recurrent AVMs were found in 4/28 children with a recurrence risk of
0.08 per person-year.
 Recurrence was associated with a lower AVM compactness score (indicating diffuse
AVM), but the score's utility has not been tested in an independent and prospective
cohort.
 Although no recurrent AVMs were found after 15 months from the initial resection and
no child with a negative I-year CCA had recurrence on a 5 -year CCA study or one at
18 years of age, not all children had CCAs at later time points.
 In a different series, 2 children had recurrent AVM at later time points at 3 and 5
years, respectively.
 A third series demonstrated that intraoperative catheter angiography reduced
postoperative residual/recurrent AVM rates from 14% to 0% in a cohort of 117 patients
and that 1- and 5-year follow-up data indicated an overall annual hemorrhage rate of
0.3% and a recurrence rate of 0.90/0.
 Therefore, even though the duration and interval of long-term follow up for pediatric
AVMs is not clear, data suggest that at least 5 years of imaging surveillance may be
justified.
 Compared with adults, outcome after AVM resection seems to be more favorable in
children.
 In one study, children were 78% less likely to have a poor neurologic outcome and
86% less likely to have suffered neurologic deterioration.
 In this study, presentation with hemorrhage did not affect outcome, and over 90% of
children had good outcomes defined as a modified Rankin scale (mRS) score of 0 to 2
(living independently).
 Almost 94% of children had mRS scores that improved or were unchanged after
surgery.

Arteriovenous Fistulas

 Arteriovenous fistulas (AVFs) represent the least structurally complex variation of

AVMs.
 They consist of direct arterial-to-venous connections without intervening capillaries
and can occur in the cerebral hemispheres, brainstem, and spinal cord.
 Connections can be single ("singlehole") or multiple ("multihole") between an artery
and vein.
 They differ from AVMs by the absence of a discrete nidus between the arterial feeder
and draining vein.
 Two subtypes of AVFs exist, defined by their location as either pial or dural.
 Pial AVFs are communications between cortical branches of the internal carotid,
vertebral, or spinal arteries and pial veins on the cortical or spinal surface.
 In contrast, duralAVFs are direct connections between an artery and a dural-based
venous structure, such as a sinus.
 The arterial supply can be from any source, including the middle meningeal artery
(from the external carotid artery), the internal carotid artery (as is the case in a carotid-
cavernous fistula, CCF), or a radicular spinal artery.
 It is worth noting a particular type of AVF, the vein of Galen malformation (VOGM or
VGAM [vein of Galen aneurysmal malformation]).
 These are a subtype of high-flow AVFs that are commonly encountered prenatally,
perinatally, or in infants.
 Though they are technically a subtype of AVF, they often present as distinct clinical
entities, given their relatively high prevalence, specific anatomic structure, and unique
management issues.
 Consequently, VOGM merits its own section and will be discussed later in this
chapter.

Pathogenesis

 AVFs can be congenital or acquired. Impaired blood vessel segregation and

patterning during development are considered to be causative mechanisms of AVF
formation.
 Animal models have supported the hypothesis that genetic cues determine endothelial
arterial or venous identity by expression of distinct molecular signaling pathways.
 Although numerous molecules have been implicated in this process (including sonic
hedgehog, vascular endothelial growth factor, notch, chicken ovalbumin upstream-
transcription factor Il, and the ephrin family), it appears that the ephrin ligand—
receptor pathway is one of the most dominant regulators of vascular assembly,
differentiation, and boundary formation.
 The genetics of these lesions remain incompletely characterized, but a number of
associations have been described and are outlined below.
 AVFs can also be acquired. Dural AVFs can result from venous sinus thrombosis
(including thrombosis secondary to infection, particularly near the transverse sinus
with mastoiditis) or as a response to venous sinus hypertension.
 Evidence supporting the role of sinus thrombosis and sinus hypertension in the
development of dural AVFs has been robustly demonstrated in a rat model.
 Dural AVFs also have been reported in the setting of hypercoagulable states leading
to sinus thrombosis.
 Although largely outside the scope of this chapter, trauma can also cause AVFs,
including skull-based fractures and penetrating skull injuries.

Epidemiology

 The rarity of AVFs makes reliable epidemiologic data difficult to obtain.

 The estimated prevalence of pial AVFs ranges between 0.1/100,000 and 1/100,000
with no clear sex predilection.
 Pial AVFs often present between 3 and 15 years of age, with increasing prevalence in
young adulthood.
 They comprise about 4% of pediatric cerebral vascular malformations.
 General estimates suggest that 0.3/100,000 dural AVFs are detected annually in
adults, but it is unclear how that may translate to the pediatric population.
 The cavernous sinus is the most common site for a dural AVF, followed by the
transverse and sigmoid sinuses.65,84 Involvement of the superior sagittal sinus and
straight sinuses is rare.
 In young children, the posterior dural sinuses are the most frequent location.
 Only 7% of dural arteriovenous lesions are multiple.

Associated Conditions and Genetic Syndromes

 Several mutations have been found in association with AVFs (Table 111-1 @).
 It has been estimated that up to 25% of patients with HHT (Online Mendelian
Inheritance in Man [OMIM] No. 187300) may also have AVFs, although more recent
studies have markedly reduced this prevalence to just 0.5%.
 Mutations in the RASA-I gene have been linked to pial AVFs, with one series
demonstrating that 29% of pediatric patients with AVFs also had RASA-I mutations.
 The capillary malformation—AVM (CM-AVM; OMIM No. 608354) syndrome has a
RASA-I mutation and is associated with AVFs of the central nervous system (CNS).
 Specific to dural AVFs, isolated reports exist of associations with PHACE (OMIM No.
606519) and PTEN-associated syndrome/Bannayan—Riley—Ruvalcaba syndrome
(OMIM No. 153480).
 Lastly, patients with CLOVES syndrome (congenital lipomatous overgrowth, vascular
malformations, epidermal nevi, and skeletal/scoliosis/spinal anomalies) commonly
exhibit vascular malformations of the CNS, including AVFs.
 CLOVES is caused by a mutation in PIK3CA and, unlike RASA-I or HHT, manifests as
a sporadic, postzygotic activating mutation that is nonheritable.

Presentation

 AVFs pose a high risk of intracranial hemorrhage in addition to brain and spine injury
secondary to high flow.
 Dural AVFs may also present with hemorrhagic venous infarctions secondary to
venous outlet restriction.
 Overall, the risk of hemorrhage has been reported at 1.5% annually, with specific risk
factors including fistulas at the vein of Galen, petrosal or straight sinus, venous
varices (especially with aneurysmal dilation), and extensive cortical venous drainage.
 In particular, leptomeningeal venous drainage in dural AVFs has a 20-fold greater risk
of hemorrhage compared with dural AVFs without leptomeningeal involvement.
 Prenatal diagnosis of AVFs may occur in the setting of fetal ultrasonography.
 Specific to the pediatric population, AVFs may present with high-output cardiac failure,
developmental delay, cognitive impairment, macrocrania, seizures, or with focal
neurologic deficits from large venous varices 101 exerting mass effect.

 In general, multihole, high-flow AVFs are more commonly found in infants (with
concomitant higher rates of symptomatic heart failure), whereas single-hole lesions
are more common after 2 to 3 years of age. 77 Infants with congestive cardiac failure
caused by a large AVF may present with tachycardia, respiratory distress, poor
systemic perfusion, and cyanosis. With high-flow lesions, an audible murmur or cranial
bruit may be heard on auscultation. 102 Prominent scalp veins are often present,
representing collateral cerebral drainage.
 Venous congestion may impair CSF absorption, leading to hydrocephalus.
 On physical examination in the case of CCFs, proptosis, chemosis, and loss of cranial
nerve Il—VI function may be present.

Evaluation

 Catheter angiography remains the gold standard for evaluation of AVFs.

 Seminal to the diagnosis is evidence of arteriovenous shunting directly into a dural
sinus from meningeal branches of the external and internal carotid and vertebral
arteries or a direct connection into a pial vein.
 If a dural AVF is suspected, selective injection of the external branches of the carotid
artery (or spinal radicular vessels) is critical.
 A frequently used grading scheme delineates five types of dural AVFs according to
their venous drainage, with risk of intracranial hemorrhage increasing with higher
grade.
 Important findings derived from angiography include the feeding artery anatomy, the
status of the venous outflow of the shunt (including any stenosis), and the severity of
arterial "steal" from the cerebral circulation.
 In cases of dural AVFs, sinus occlusion is common and often progressive, particularly
in children.
 Intimal damage from the supraphysiologic flow promotes progressive thrombosis and
hyperplasia of the draining venous system, producing venous hypertension and
ischemia.
 MRI is useful in the evaluation of AVFs, but has limitations.
 Cross-sectional imaging may be nondiagnostic or may show only sinus thrombosis or
dilated vessels.
 Cortical venous reflux may manifest as engorged cortical vessels without a clear
fistulous connection.
 Cerebral venous hypertension may produce other findings, such as cerebral edema,
hydrocephalus, and ischemic infarction or atrophy (the so-called "melting brain").
 Large veins may exert local mass effect.
 Dilated ophthalmic vessels are characteristic of CCFs. Dural AVFs in the spine are
more common in adults and are believed to be secondary to veno-occlusive disease
of the medullary veins, in which segmental arteries connect to tortuous medullary
veins.
 MRI may not show the fistula directly, but may demonstrate edema in the affected
cord because of venous hypertension and may reveal enlarged venous structures
near the fistula.
 Hematological tests may include evaluation for hypercoagulable states, including
specific assessment for elevated levels of beta-2 glycoprotein-I antibody and
decreased levels of protein S.
 Consultation with a geneticist may be useful.
 As noted, there are associations with a number of heritable conditions and mutations,
including HHT, RASA-I, PIK3CA, PTEN, and PHACE.
 There are no specific guidelines for screening, but at-risk populations (including
children with the CM-AVM, CLOVES, PHACE, RASA-I mutations, HHT, and PTEN-
associated syndrome) and patients with recent histories of sinus thrombosis or head
trauma involving potential arterial injury should be considered as potential imaging
candidates.

Treatment

 Indications for treatment and recommendations for timing of treatment have evolved
with development of novel technologies.
 In general, any symptomatic, high-flow lesion should be considered for treatment.In
particular, anterior cranial fossa lesions and evidence of leptomeningeal venous
drainage are factors predictive of greater risk of hemorrhage.
 However, one area of controversy centers on the aggressive treatment of critically ill
neonates.
 Some authors have voiced concern over injudicious use of therapy resulting in
survival of profoundly impaired infants.
 In response, analysis of outcomes led to a scoring system used to predict more
effectively appropriate candidates for treatment in the subset of high-output AVF
cases in infants (including vein of Galen lesions).
 In general, treatment may not be recommended for neonates with microcephaly,
evidence of extensive cerebral ischemic damage, such as encephalomalacia and
infarction, or evidence of multiorgan failure.
 Dural AVFs involving the cavernous sinus (CCF) and transverse sinuses are distinct
groups of AVFs relative to indications for treatment.
 Slow-flow, smaller lesions with minimal or absent symptoms may be followed with
observation, as there is a possibility of spontaneous closure.
 However, high-flow lesions, or CCF with symptoms—particularly visual deterioration—
are high risk and warrant aggressive treatment.
 Successful treatment of pediatric AVFs requires a team approach, usually involving
collaboration of specialists with expertise in pediatric neurosurgery, neurology,
interventional neuroradiology, and occasionally ophthalmology to assess for
papilledema if there is increased ICP or to assess visual acuity after treatment of a
CCF.
 In the more rare cases presenting with cardiac failure in infants with high-flow lesions,
cardiology and pediatric critical care teams are also helpful.
 The goal of treatment for the child with an AVF involves endovascular or microsurgical
techniques to close the fistulous connection (with isolated reports of radiation therapy
for some cases).
 Given their rarity, overall experience with treating pediatric patients is limited.
 In general, endovascular techniques have emerged as a primary method of treatment
for pediatric AVFs.
 However, surgical treatment remains an option in some patients, particularly when the
risk of nontarget embolization to eloquent brain cortex is high.
 Recent data from pediatric AVF series suggest that dural AVFs have a higher
likelihood of successful treatment using solely endovascular techniques (85%),
whereas pial AVFs have a greater probability of combined endovascular and open
surgical approaches (71%).
 The advent of the embolic agent Onyx (ethylene vinyl alcohol copolymer), in
conjunction with the use of detachable coils, has markedly increased the therapeutic
efficacy of endovascular approaches for AVFs.
 Endovascular treatment can be transarterial or transvenous.
 Transarterial embolization is generally most effective for pial AVFs, whereas venous
side occlusion is useful in many dural AVFs, particularly in transverse and sigmoid
sinus disease.
 Venous occlusion is best tolerated when alternative routes for normal venous
drainage exist and when absolute occlusion of the affected fistulous area is to be
achieved.
 Venous infarction is a potential complication in cases that do not have adequate
rerouting of normal drainage.

Outcome
 Outcomes for children with AVFs are strongly related to the age at time of treatment.
 For those older than 2 years of age, 72% had a good clinical outcome, whereas
children under age 2 had far higher complication rates and more frequent need of
multiple procedures.
 Current reports of AVF treatment suggest high rates of lesional obliteration (86%),
with ageappropriate outcome scores at an average of 16 months of follow up.
 Complications related to AVF treatment include venous infarction, migration of
embolic agents into unintended vessels (arterial stroke or venous occlusion), guide
wire rupture of vessels during embolization (especially thin-walled veins in
transvenous approaches), posttreatment thrombosis of veins (secondary to reduced
flow), hyperperfusion ("normal perfusion pressure breakthrough") syndrome (from
rerouted arterial flow in larger lesions), and hydrocephalus.
 Overall, the risk of catastrophic complications from treatment has been reported in the
range of 3% for adults, but the risk seems much higher in children, with procedural
complication rates of up to 60% and major complications (and death) in the range of
10% to 12%.
 These risks are related most strongly to age, with children under 1 year having very
high complication rates (up to 85%), and children older than 2 years of age having
much lower complication rates (closer to 33%).
 After treatment of AVFs, patients should be monitored for the development of
hydrocephalus, which may be the result ofvenous thrombosis, altered venous outflow,
or deranged CSF dynamics secondary to shifts in blood flow.
 In series of patients who underwent endovascular treatment for pial AVFs, 14% to
19% experienced postprocedural hydrocephalus.
 Genetic screening and evaluation for hypercoagulable disorders are indicated,
particularly when other vascular anomalies or venous sinus thrombosis exist.

Vein of Galen Malformations

 As noted previously, VOGMs are a specific type of arteriovenous fistula (Fig. 111-2
@).
 Although they share the direct connection between arteries and veins without an
intervening nidus that is common to the biology of all AVFs, the historical precedent in
considering VOGMs as a distinct entity coupled with the unique clinical issues posed
by patients with VOGMs justifies discussion of their management independent from
other AVF subtypes.

FIGURE 111-2 @ Vein of Galen malformation (VOGM). A, T2-weighted axial

magnetic resona...

Pathogenesis

 There is abnormal development of cerebral midline venous structures.

 The choroidal arteries drain into a dilated vein, the median prosencephalic vein of
Markowski, which is the embryonic precursor of the vein of Galen.
 Normally, this vein is present from 8 to 11 weeks of gestation, and then the anterior
two thirds of this vein regress and the posterior one third persists as the normal vein of
Galen.
 This regression does not occur in VOGM.
 Instead, arteriovenous shunts are present and the anterior segment of the median
prosencephalic vein does not regress and instead progressively enlarges under the
stress produced by highpressure inflow from the choroidal feeders.
 Therefore a VOGM is a cluster of arteriovenous fistulas draining into a persistent and
dilated median prosencephalic vein of Markowski.
 There are two types of VOGM, choroidal and mural.
 The choroidal type involves multiple feeders, including thalamoperforating, choroidal,
and pericallosal arteries that are located in the subarachnoid space in the choroidal
fissure.
 These vessels converge on a fistula site at the anterior aspect of the median
prosencephalic vein and have little outflow restriction.
 This type of direct fistula has multiple shunts and tends to be seen in neonates with
severe symptoms.
 The mural type corresponds to interposition of an arterial network between the arterial
feeders and the venous structure.
 These fistulas may be single or, more often, multiple and converge into a single
venous chamber or into multiple venous pouches.
 Presentation of the mural type is often with macrocephaly and is less severe.
 Combined or mixed types also exist.

Epidemiology

 VOGMs are rare.

 Incidence and prevalence data are not available.
 Many tertiary children's medical centers in the United States will only treat 1 to 2
children per year.

Presentation

 There are three main presentations of VOGM. 1) neonates with high-output cardiac
failure, 2) infants and young children with macrocephaly and hydrocephalus with or
without seizures, and 3) older children or adults with macrocephaly, headaches, and
sometimes SAH.
 Symptoms in nonneonates are usually related to abnormal cerebral venous drainage
and altered CSF flow.
 Occasionally, VOGMs are diagnosed in utero.

Evaluation

 Ultrasonography is a helpful bedside technique for monitoring VOGM flow in an ill

neonate.
 Ultrasonography is limited in the evaluation of brain parenchyma. MRI of the brain can
assess the brain parenchyma for evidence of cerebral atrophy or ischemia that may
be due to a CBF steal phenomenon by the VOGM.
 Echocardiography can assess cardiac function and is helpful in determining whether
there is a high-output cardiac state and/or cardiac failure.
 Renal and liver function tests will assess for additional injury in the pretreatment
phase.

Treatment

 Urgent treatment in the neonatal period is necessary when a child has heart failure
that cannot be managed medically.
 In neonates, high-output cardiac failure can lead to renal or hepatic insufficiency, and
rarely myocardial ischemia.
 In infants and older children, treatment is to prevent cerebral atrophy and cognitive
delays.
 Endovascular treatment is the treatment of choice.
 The endovascular approach is typically staged.
 Technically, the VOGM may be targeted either through a transarterial or transvenous
approach.
 In the modern era, transarterial embolization is preferred at most centers, reserving
transvenous embolization for instances in which transarterial embolization has been
exhausted.
 In the neonate, the goal of treatment is to reduce flow through the VOGM so that heart
failure can be medically managed; some authors have indicated that this typically
requires reducing flow by about 30%.
 If the patient is stable, additional treatment is usually completed after 5 months of age.
 Hydrocephalus can be treated with CSF diversion either through shunting or by
endoscopic third ventriculostomy.
 However, hydrocephalus can significantly improve with embolization of the VOGM.
 Therefore, if possible, embolization should precede hydrocephalus treatment.
 In rare cases of transtorcular embolization, a surgical window is created to provide
venous access.
 Primary surgical repair of VOGM is not indicated.

Outcome

 In a series of 27 children treated at a single center, outcome was worse for those with
choroidal VOGMs (3/13 died; 5/13 had significant delay) than for those with mural
VOGMs (none died; 2/10 had significant delay).
 Of the survivors, 61% had no or minor delays. Features associated with worse
outcome were perinatal presentation, presence of CHF, and choroidal
angioarchitecture.
 In a series of 13 children treated at a single center, of 7 patients presenting in the first
2 weeks of life, 3 died.
 There were no deaths in the 6 children presenting after 2 weeks of age.
 Five patients had hydrocephalus and four required postembolization shunting.
 In 2006 Lasjaunias and colleagues reported a series of 233 patients with VGOM
treated with embolization, which is currently the largest reported experience.
 Overall mortality was 10.6%.
 Young age was a risk factor for death; neonates had a mortality of 52% compared
with infants (7.2%) and older children (0%).
 In addition, 74% of surviving children were neurologically normal, 15.6% were
moderately developmentally delayed, and 10.4% were noted to have severe
developmental delays with a median follow-up time of 4.4 years.
 Obliteration of 90% to 100% of the malformation was achieved in 55% of patients;
complete obliteration of a VOGM is not necessary in all cases to achieve clinical
improvement.

Low Flow Lesions

Cavernous Malformations

 Cavernous malformations (CMS) consist of dilated sinusoidal vessels lined by

endothelium without intervening neural parenchyma.
 They are low-flow lesions that can range in size from submillimeter to several
centimeters in diameter.
 Historically, they have been called cavernomas, cavernous angiomas, or cavernous
hemangiomas (Fig. 111-3 @

FIGURE 111-3 @ Cavernous malformation. A, T2-weighted axial magnetic

resonance imagin...

Pathogenesis

 Pathologically, CMS are a compact mass of sinusoidal vessels contiguous with one
another without intervening normal parenchyma.
 These well-circumscribed, unencapsulated masses are identified grossly as having a
dark red or violet lobulated "mulberry" appearance. Calcifications may be present,
both grossly and microscopically.
 Cysts containing old hemorrhagic products may be present and may facilitate growth
of these lesions by providing a substrate for neovascularization.
 The underlying pathology of CMS includes dysfunctional endothelial cell connections,
contributing to the "leaking" of blood into surrounding tissue.
 Adjacent brain may be gliotic, may contain focal calcifications, and frequently is
stained with hemosiderin from prior hemorrhage.

Epidemiology
 CMS occur most commonly as sporadic lesions (50% to 80% of cases), but also can
manifest as an autosomal dominant inherited form characterized by multiple lesions in
children.
 There also is a known association between CM formation and previous exposure to
intracranial radiation.
 A single CM is found in 75% of sporadic cases and only 8% to 19% of familial cases.
 In contrast, the presence of multiple CMS is strongly suggestive of a familial CM
syndrome; approximately 75% of patients with multiple lesions ultimately are found to
have affected relatives.
 Only 10% to 25% of individuals with multiple lesions will be sporadic cases, with the
remainder of patients with multiple CMS often attributed to the secondary effects of
radiation therapy.
 CMS are found with a prevalence of about 0.5% in autopsy studies.
 An incidence of 0.43 diagnoses per 100,000 people per year has been reported.
 There is no difference in incidence between males and females.
 Symptomatic lesions manifest in all age groups.
 The peak incidence at presentation is usually in the third to fourth decade.
 Affected children appear to be clustered into two age groups: infants and toddlers
under the age of 3 years, and children in early puberty, age 12 to 16 years.

Genetic Syndromes

 The cause of CMS remains under investigation.

 Recent advances have been made in the understanding of the contribution that
specific mutations play in the development of these lesions.
 In particular, three genes (see Table 111-1 @) have been associated with the
formation of cerebral CMs—CCM1 (also known as KRITI [Krev-l interaction trapped
1], found on chromosome 7q); CCM2 (also known as malcaverin, found on 7p); and
CCM3 (also known as Programmed Cell Death 10, on 3p).
 Molecular studies of CCMI have revealed that its protein is essential for normal
embryonic vascular development. Mutations in this gene, found in hereditary CM
cases, result in loss of function.
 In patients with these CCMI mutations, nearly all will have radiographic evidence of
multiple CMS, but only about 60% of patients will develop symptoms.
 Patients with familial CMS are prone to developing new lesions throughout their
lifetime.
 The CCMI genotype is associated with a higher number of lesions with increasing age
than the CCM2 or CCM3 genotypes.
 CCM3 mutations may confer a higher risk of hemorrhage during childhood.
 Up to 50% of patients with CCM3 mutations become symptomatic before age 15, and
53% of patients with CCM3 mutations who were symptomatic presented with
hemorrhage.
 Periodic MRI studies are recommended to follow patients known to be affected.
 Screening of family members, both genetically and radiographically, remains
controversial but may be helpful for genetic counseling and risk evaluation.
 Other systems may be affected, including skin, eyes, and visceral organs—most
commonly found with CCMI mutations.
 It is common practice to refer patients with multiple CMS for a genetics evaluation,
including mutational testing and counseling.

Presentation

 CMS may never cause symptoms and may be discovered incidentally or may be
responsible for a variety of neurologic complaints.
 The neurologic findings of symptomatic CMS correlate with the site of the CM and age
at presentation.
 CMS can occur anywhere in the CNS, with symptomatic lesions most commonly
presenting with symptoms associated with acute hemorrhage, seizures, headaches,
or focal neurologic deficits.
 Intracranial CMS often cause symptoms because of hemorrhage (usually low-
pressure relative to high-flow vascular lesions) that exerts mass effect on the
surrounding brain.
 Headache may occur either as a consequence of this mass effect deforming the dura
or of local blood products irritating the meninges.
 Extravasation of blood into brain parenchyma creates a hemosiderin ring that may
predispose susceptible tissue to seizures.
 New seizure rates after the diagnosis of CMS range from 1.5% to 4.3% per
patient/year, and a history of previous seizure increases this rate to 5.5% per
patient/year.
 Children with CMS may also have headache as a symptom, presumably secondary to
mass effect or irritation of dural nociceptors from hemorrhage products.

Evaluation

 Evaluation of CMS usually begins with CT or MRI.

 CMS are generally poorly visualized with angiography, and CCA is not normally
indicated.
 CT demonstrates a well-defined collection of multiple, rounded densities showing
minor contrast enhancement.
 Often, calcifications are present.
 Hemorrhage may or may not be present. MRI studies are distinctive with a typical
"popcorn" appearance and associated "bloom" on susceptibility-weighted imaging,
suggesting hemosiderin deposition.
 The majority of CMS are supratentorial lobar lesions (76%), with the remainder
infratentorial or intraventricular.
 If multiple CMS are seen on imaging, then a familial or postradiation etiology should
be considered.
 As discussed previously, referral of patients with multiple lesions for genetic
consultation should be considered.
 Of particular note is the high rate of finding a developmental venous anomaly (DVA) in
association with a CM, approaching 100% in some series.
 This is critical to planning surgical therapy as these DVAs provide venous drainage to
normal brain, and should be preserved if possible.
 In patients presenting with acute hemorrhage, it may be difficult to ascertain the
diagnosis.
 Strong consideration must be given to the possibility of an AVM, which is oun common
y in children.
 In this particular clinical scenario (unlike general screening as previously discussed),
angiography is extremely helpful in distinguishing between these entities.
 In children presenting with cystic or calcified lesions, the differential diagnosis may
include tumors, and susceptibility-weighted imaging may aid in identifying previous
hemorrhage or other CMS.

Treatment

 The natural history of CMS can be difficult to predict.

 Depending on various authors' definitions of hemorrhage, annual rates of hemorrhage
from CMS vary between near undetectable to about 3% for lesions that are found
incidentally and range between less than 4% to greater than 23% for lesions that were
found after a hemorrhage.
 In general, hemorrhage from CMS is better tolerated with regard to mortality than from
high-flow lesions, such as AVMs.
 However, fatal hemorrhage from CMS is a well-known occurrence— particularly if the
lesion is in a high-risk location, such as the posterior fossa.
 Of those children who have symptomatic hemorrhage, many can be at risk for
clustering of hemorrhages in a short period of time with a rate of up to approximately
2% per lesion per month and 24%/year.
 Even though there is no consensus or evidence-based guidelines delineating
indications for treatment in children with CMS, data generally support surgical excision
of symptomatic lesions (seizure, focal headache, neurologic deficits), lesions with
recurrent hemorrhage, or lesions with high risk of neurologic deficits (e.g., large
lesions or those located in the posterior fossa).
 There has been debate regarding the utility of extirpation of asymptomatic lesions.
 The decision to intervene is especially difficult in the patient who presents with
symptoms and has multiple lesions.
 If symptoms can be localized to a single lesion, which is amenable to surgical
resection, then that lesion should generally be removed.
 Smaller (<1 cm) asymptomatic lesions or those in surgically inaccessible locations
may warrant observation.
 If treatment is planned for a CM, surgical resection is the preferred option.
 Radiation therapy is controversial and generally reserved for surgically inaccessible
lesions with a demonstrated malignant natural history.
 Radiosurgery has been reported to reduce the frequency of hemorrhage in these
lesions from 17.3%/year to 4.5%/year.
 However, this decreased rate of hemorrhage comes at the cost of increased
complications, including a 16% incidence of new permanent neurologic deficits and a
3% mortality rate.

Outcome
 Outcomes after surgical therapy have been remarkably good, with most series
reporting a near 0% mortality rate and a 4% to 5% rate of new permanent deficits.
 It is important to note that risks greatly increase in sensitive locations such as the
brainstem with rates of new, permanent postoperative deficits ranging from 12% to
25%, suggesting a need to approach lesions in these areas with caution.
 Surgical resection of the most common type of CM in children, supratentorial lobar
lesions, provides high rates of symptomatic improvement and durable, long-term
treatment efficacy.
 With nearly 5 years of follow up, one large series demonstrated a 98% resection rate,
no rebleeding in completely resected lesions, and abrogation of seizures in 96% of
patients, with a 5% complication rate (with all complications limited only to CMS within
eloquent cortex).

 Close follow up is indicated in patients who have undergone surgical resection of a

CM. CMS can recur if not excised in toto and generation of new lesions has been
documented, particularly in the setting of radiation-induced lesions and in familial
cases.
 In most patients, a postoperative MRI is obtained, usually 6 weeks to 6 months
postoperatively to assess the extent of resection and to serve as a new baseline for
comparison to future studies.
 The length and frequency of monitoring with imaging remains a topic of debate; many
institutions perform annual MRI studies for the first 3 to 5 years after surgery and at
greater intervals thereafter.

Developmental Venous Anomalies

 DVAs, also known as venous angiomas, are composed of a radially arranged

configuration of medullary veins ("caput medusae") separated by normal brain
parenchyma (most commonly white matter) that converge on a larger collecting vein.
 They are considered extreme variations in the normal venous drainage of the brain.
 Though they are a common finding in association with CMS, they are also identified
as isolated structures, in the absence of any pathologic lesions.

Epidemiology

 DVAs are the most frequently encountered cerebral vascular malformation, with an
incidence of up to 2.6% reported in a series of 4069 brain autopsies.
 They are often incidentally noted during routine parenchymal brain imaging.
 DVAs are seen both in the pediatric and in adult populations, with a slight male
predominance.

Associated Conditions and Genetic Syndromes

 DVAs are associated with one or more cerebral CMS in 13% to 40% of the cases.
 There is also a strong association between DVAs and superficial venous
malformations of the head and neck, with DVAs seen in up to 20% of patients with a
large superficial venous malformation.
Presentation

 Typically, DVAs are asymptomatic. Rarely, hemorrhagic and/or ischemic infarction, or

reversible cerebral edema around a DVA may result from acute thrombosis of the
collecting vein.

Evaluation

 MRI and angiography typically show medullary veins converging on the dilated
collecting vein.
 T I-weighted post-contrast images and gradient echo or susceptibility-weighted
sequences should be included to increase sensitivity for detecting the DVA and
associated CMs.
 White matter abnormalities and/or calcifications may be observed in the parenchyma
surrounding the DVA. MR venography may show dilated venous channels with
variable depiction of the smaller medullary veins.
 Although angiography remains the gold standard in vascular imaging, cerebral
angiography usually is not needed for the diagnosis of DVAs because axial imaging
sequences on MRI often suffice to establish the diagnosis.
 In atypical cases, angiographic findings are pathognomonic; during the late capillary
or venous phase, there is a paucity of normal veins in the region of the lesion, and a
characteristic "caput medusae" appearance of the radially arranged small medullary
veins is observed.
 The arterial phase of cerebral angiography is usually normal for a DVA; however, so-
called "arterialized DVAs" have been described with early opacification of a DVA in
the mid to late arterial phase on angiography and/or enlarged arterial feeder vessels.
 These lesions are more similar to an AVM and sometimes a DVA is the venous
drainage for an AVM.
 These unusual lesions may have a bleeding risk that is more similar to an AVM, but
are not typically treatable.

Treatment

 Most DVAs follow a benign clinical course and do not require follow-up imaging or
specific treatment.
 The frequent association of DVAs with other vascular malformations, in particular with
cerebral CMS, usually explains cerebral hemorrhage or seizure activity (because of
CCM, not DVA).
 Rarely, a DVA may be responsible for neurologic complications secondary to
thrombosis of its collecting system.
 Thrombosed DVAs should be managed like a cortical or dural venous sinus
thrombosis.
 Venous infarction has been reported with DVA resection200 because DVAs drain
venous blood from brain parenchyma.
 In patients with cerebral hematomas or edema requiring surgical management,
particular care must be taken to preserve the collecting vein of the DVA in order to
avoid cerebral venous infarction.

Outcome
 Most DVAs follow a benign clinical course and do not require follow-up imaging or
specific treatment or management.

Aneurysms
 Aneurysms are one of the most common vascular anomalies of the CNS, but are far
less common in children than in adults.
 These structurally abnormal areas of arterial wall can cause bleeding, compression of
adjacent structures, and concomitant loss of neurologic function.

Pathogenesis

 Aneurysms are typically defined as saccular (a focal outpouching of a vessel wall,

usually at a bifurcation) or dissecting (caused by an injury to the vessel wall, leading to
loss of integrity and dilatation of a vessel, commonly along the axial length of a
segment).
 Mycotic aneurysms are caused by infection (or, rarely, tumor) and often appear similar
to dissecting lesions on angiogram.
 The etiology of aneurysms in the pediatric population shifts with increasing age.
 Younger children, particularly under 5 years of age, typically have dissecting, fusiform
aneurysms, whereas older children have saccular aneurysms.
 There are many causes of pediatric aneurysms.
 The most common aneurysms in children are saccular (46% to 70%), followed by
posttraumatic aneurysms (5% to 40%).
 Infectious (mycotic) aneurysms comprise 5% to 15% of cases, and are often seen in
conjunction with cardiac disease or severe systemic infection (often with
Staphylococcus species).
 There are also a number of genetic conditions associated with intracranial aneurysms
(Table 111-1 Rarely, aneurysms occur secondary to high-flow lesions, such as
aneurysms seen proximal to large AVMs.

Epidemiology

 It is estimated that the general prevalence of unruptured, asymptomatic intracranial

aneurysms (across all ages) is 3.2%, and only 0.5% to 4.6% of these are present in
children.
 Ruptured aneurysms in the pediatric population are also rare, with 0.6% of all
aneurysmal SAH comprising patients under 19 years of age.
 Given a total of approximately 18,300 SAH cases annually, this means that there are
only about 100 aneurysmal SAH cases each year in children.
 Intracranial aneurysms are more common in males than in females (especially in
prepubertal children) at 2.7 : 1, with a shift to a female preponderance (similar to
adults) at 3 to 5 : 1 in the postpubertal population.
 Location and size of aneurysms in children differ compared with adults.
 Children are more likely to harbor aneurysms in the posterior circulation (25% in
children vs. 8% in adults), less likely to have anterior cerebral artery aneurysms (5%
to 10% in children vs. 34% in adults), and are roughly the same for internal carotid
artery and middle cerebral artery lesions.
 Children are less likely than adults to have multiple aneurysms and 2 to 4 times more
likely to have giant (>2.5 cm) aneurysms than adults.

Associated Conditions and Genetic Syndromes

 Familial aneurysms are very rare, accounting for 5% to 20% of all reported cases in
children and young adults, but less than 5% of prepubertal cases.
 Genetic conditions associated with pediatric intracranial aneurysms include polycystic
kidney disease, fibromuscular dysplasia, Marfan syndrome, Ehlers—Danlos
syndrome, HHT, and Klippel—Trenaunay—Weber syndrome.
 Up to 15% of older children with aneurysms have multiple lesions, particularly those
with underlying genetic disorders.

Presentation

 Most aneurysms are asymptomatic and often are never detected.

 For those individuals who are symptomatic, headache is the most common symptom
(80%), followed by loss of consciousness (25%), seizures (20%), focal neurologic
deficits (20%), and visual changes (10%).
 In one series, over half of patients with pediatric aneurysm presented with SAH, 33%
presented with mass effect symptoms, and 11% had previous trauma.
 Children with SAH from aneurysm often present with less severe symptoms compared
with adults (as measured by the Hunt—Hess grade [see Box 111-1 usually 1 to 3 in
the pediatric population).

Evaluation

 Evaluation of patients with a suspected SAH from an aneurysm includes obtaining a

history, performing a neurologic and physical examination, and acquiring imaging
studies to define the lesion's anatomy.
 Up to 80% of all nontraumatic SAH in children results from a structural lesion.
 These patients should be screened with CT, and if a vascular lesion is suspected,
CTA can be used to identify the presence of an aneurysm.
 Although lacking the detail of a catheter-based arteriogram, CTA affords the treating
physician an immediate image outlining key anatomic features of the lesion,
information of critical importance in the setting of an acutely ill child.
 Patterns of hemorrhage in pediatric aneurysm CT studies include SAH (60%),
intraventricular hemorrhage (10% to 15%), and intraparenchymal (10% to 15%), or
subdural (1% to 3%) hemorrhage.
 MR1 is also useful in the diagnosis and delineation of the three-dimensional anatomy
of an aneurysm, particularly with MR angiography.
 In contrast, use of catheter-based digital subtraction angiography (DSA)—the "gold
standard" of imaging in aneurysm—was able to identify lesional pathology in 97% of
patients, versus 80% of the time without DSA.
 Angiography generally includes bilateral injections of the internal and external carotid
arteries and vertebral arteries in order to visualize all intracranial and neck vessels.
 Three-dimensional angiography with computer-generated reconstruction is
increasingly employed to depict lesional anatomy.
 With catheter angiography, a recent analysis of 241 consecutive pediatric patients
revealed a 0% complication rate during the procedure and a 0.4% postprocedural
complication rate.
 Evaluation should look for lesion size, orientation and location, neck anatomy,
daughter blisters, and other aneurysms (especially important with infectious lesions).
 If the aneurysm is fusiform, the segment of vessel involved, delineation of normal
borders, and involvement of perforators are important.
 Standard preoperative laboratory studies (complete blood count), clotting times
(PT/PTT/INR), type and cross for blood bank, and a chemistry panel should be
acquired.

Treatment

 The decision to treat or observe a given aneurysm can be complex and is best made
by a multidisciplinary team including neurosurgeons, endovascular specialists, and
neurologists.
 If treatment is planned, success is predicated on removing the lesion while preserving
normal brain blood flow.
 This can be achieved by open surgery, endovascular techniques, or a combination of
approaches.
 The advent of endovascular therapy has revolutionized the treatment of pediatric
aneurysms, providing options unavailable to earlier generations of physicians.
 The relatively noninvasive nature of the approach is particularly attractive in children.
 It is important to note that there is a great deal of evolution of this field, limiting long-
term outcome data.
 Consequently, it is important, when possible, to have cases reviewed at institutions
that offer both endovascular and open techniques in order to provide a balanced
approach to formulating care plans.
 The rarity of pediatric aneurysms preclude firm guidelines for treatment indications.
 In general, aneurysms that have ruptured or that demonstrate enlargement over time
or symptomatic lesions should be considered for treatment.
 Depending on location and patient status, it may be reasonable to treat any aneurysm
greater than 3 mm in size, particularly given the anticipated longer life expectancy of
children.
 Mycotic aneurysms sometimes will regress with effective antibiotic therapy, obviating
the need for other interventions.
 In addition, flow-related aneurysms located proximal to a lesion like an AVM may
regress after definitive treatment of the primary lesion (such as resection of the AVM),
demonstrating another situation in which direct aneurysm treatment may not be
required.
 Although debatable, lesions 2 mm or smaller in size and those located outside the
subarachnoid space are sometimes followed.
 Even though aneurysms over 10 mm are often treated, management of the "middle-
sized lesions," those 2 to 10 mm, in children remains a topic of debate.
 Much controversy surrounds the large study of unruptured aneurysms published in
1998, but it is important to recognize that these patients were predominantly adults,
with questionable relation to the pediatric population, given the differences in lifespan,
aneurysm etiology, and risk factors.
 Outcome

 Overall treatment morbidity and mortality vary widely dependent on age, aneurysm
type, and presentation. Recent series describe average mortality rates of 1% to 3%
and morbidity rates of 8% to 14%.
 It is important to note that treatment of aneurysms often includes management of
posttreatment and posthemorrhage issues.
 These can include stroke, hydrocephalus, vasospasm, and electrolyte derangements.
 Stroke may occur from perforator/parent vessel occlusion or emboli/dissection caused
by injury to the arterial tree during manipulation (6% to 8%).
 Hydrocephalus can result from blood in the subarachnoid space or ventricles
Vasospasm can occur after SAH (21% of pediatric cases).
 Cerebral salt wasting is an often underrecognized consequence of SAH and should be
considered in the posthemorrhage period if major fluid or sodium shifts are observed.
 In general, most patients will spend a period of time after treatment in the critical care
unit.
 For patients with SAH, the first week or so after presentation is the key period for
developing hydrocephalus, vasospasm, and cerebral salt wasting.
 Frequent neurologic examinations should be supplemented with imaging (CT/MRI for
hydrocephalus and CTA/MRA/transcranial Doppler/angiography for vasospasm).
 Some patients may benefit from the so-called "triple-H" therapy—hypertension,
hypervolemia, and hemodilution—in order to reduce the risk of vasospasm (only after
aneurysm treatment).
 The benefit of calcium channel blocking agents, such as nimodipine, is unclear in
children.
 There is a wide range of reported outcomes for pediatric aneurysms, with "good"
posttreatment outcomes ranging from 13% to 95% and treatment-related mortality
ranging from 3% to 1000/0.
 Shunting will be required for 14% of patients with hydrocephalus after SAH.
 Overall, of patients who survive treatment, 91% (with a mean of 25 years' follow up)
enjoy independent living, with high rates of university graduation and employment.
 Radiographically, one study reviewed a group of 59 patients with aneurysms who
were treated in childhood.
 Average follow up was 34 years.
 In this series, 41% developed recurrent or only risk factor identified for recurrent or de
novo aneurysm development was smoking.
 These data, though obviously limited in part by the absence of current imaging
technologies and surgical techniques at the time of patient treatment, nonetheless
underscore the need for continued follow up in pediatric intracranial aneurysm
patients.
 Follow up will frequently consist of an office visit about 1 month
postoperatively/postembolization and then annually thereafter.
 In addition to the periprocedural angiogram to confirm obliteration of the aneurysm, an
MRI/A at 6 months may be helpful as a baseline study, to be compared with
subsequent annual studies.
 Imaging is performed annually for 5 years, if feasible, with some centers suggesting
lifetime imaging every 3 to 5 years thereafter.
 An angiogram (DSA) is often performed at 1 year postoperatively to confirm cure.