Arteries
Artery walls are composed of three layers: tunica intima, tunica media, and tunica adventitia. There are three types of arteries: elastic arteries, muscular arteries, and arterioles. Thickness of wall layers and differences in makeup of these layers – particularly the tunica media – are elements that further distinguish the different artery types from one another (Moore and Agur 1995)
Elastic arteries
Elastic arteries are the largest type of artery. They expand synchronously with heart contractions and resume their normal shape between contractions (Moore and Agur 1995)
Muscular arteries
These arteries distribute blood to various parts of the body, and for this they are often referred to as distributing arteries. Muscular artery walls consist of circularly disposed smooth muscle fibers. The smooth muscle fibers constrict their lumina upon contraction (Moore and Agur 1995)
Arterioles
Arterioles are the smallest of the arteries. They have a narrow lumina and thick muscular walls. The degree of tonus of the smooth muscle in arteriole walls is primarily responsible for arterial pressure (Moore and Agur 1995)
Capillaries
Capillaries connect arteries to veins. They are made of endothelial tubes and are arranged in a network known as capillary bed (Moore and Agur 1995). The makeup of a capillary wall consists of a single layer of endothelial cells that are surrounded by a thin basement membrane of the tunica intima. Some capillary walls consist of a single endothelial cell with no tunica of the tunica externa. Other capillaries contain oval windows known as fenestrations within the endothelial cells. A thin diaphragm covers the fenestrations (McCance and Huether 2002)
Veins
Vein wall are thinner than artery walls because of the lower blood pressure in the venous system. They are also fibrous and have a larger diameter. The tunica externa of veins has less elastic tissue than arteries, and as a result, veins do not possess the capacity to recoil as seen in arteries (McCance and Huether 2002). Valves work to permit blood to flow toward the heart and prevent blood from flowing in the opposite direction. There are three types of veins: small, medium, and large. The adventitia of large veins is composed of wide bundles of longitudinal smooth muscle. Venules are the smallest type of vein (Moore and Agur 1995). The smallest venules that are closest to capillaries have an inner lining made up of the endothelium of the tunica intima and surrounded by fibrous tissue. The largest venules that are furthest from the capillaries are made of a thin tunica media that consists of a few smooth muscle fibers (Moore and Agur 1995)
12.3 Cerebral Blood Supply
The cerebral circulation is composed of two very distinct circulatory systems: the arterial and venous systems. The two systems work in unison to maintain appropriate pressure and perfusion within the brain. There are many physiologic and pathologic factors that can affect blood flow in the arteries and veins of the brain, including acid-base balance, oxygen saturation, and systemic blood pressure. Under normal conditions of autonomic regulation, the mean arterial pressure is maintained at 0–10 cm H2O (McCance and Huether 2002). This ensures adequate perfusion of the cerebral capillary beds despite changes in systemic blood pressure.
12.3.1 Arterial Supply
Arterial blood enters the cranial cavity anteriorly (via the carotid arteries) and posteriorly (via the vertebral arteries). They feed into an anastomotic ring of vessels called the circle of Willis, which gives rise to all the major cerebral arteries (Fig. 12.1). The origin of the brain’s anterior arterial system is the right and left common carotids arising from the innominate artery and aortic arch, respectively. Each of these large vessels further branches into the external and internal carotid arteries. The external carotid is responsible for blood supply to the face and scalp. The internal carotid enters the base of the skull via the foramen lacerum. It then twists and divides into several segments (i.e., cervical, petrous) and terminates by dividing into the anterior cerebral artery and middle cerebral artery (MCA). Main branches include the ophthalmic artery, the posterior communicating artery, and the anterior choroidal artery (Hinkle et al. 2010). The cortical areas are supplied by the anterior and middle cerebral arteries, as well as the anterior choroidal arteries (Table 12.2).
Fig. 12.1
Circle of Willis. Principal arteries on the floor of the cranial cavity (From Waxman (2003))
Table 12.2
The cortical areas supplied by the major cerebral arteries
Middle cerebral artery | Supplies many deep lateral aspect of the cerebrum |
Anterior cerebral artery | Supplies the anterior frontal lobe and the medial aspects of the hemisphere |
Posterior cerebral artery | Supplies the occipital lobe and choroid plexus of the third and lateral ventricles and the lower surface of the temporal lobe |
Anterior choroidal artery | Supplies the choroid plexus of the lateral ventricles and the adjacent brain structures supplied by the major cerebral arteries |
The two vertebral arteries, which originate from the subclavian arteries, enter the skull through the foramen magnum and then unite at the level of the pons to form the basilar artery. The posterior inferior cerebellar arteries branch off the vertebrals and the anterior inferior cerebellar arteries, superior cerebellar arteries, and posterior cerebral arteries arise from the basilar artery (Fig. 12.1).
The posterior circulation, or the vertebral basilar system, supplies the brainstem, cerebellum, occipital lobe, and parts of the thalamus. The anterior circulation, as described above, supplies the reminder of the forebrain (Hinkle et al. 2010). Occlusion of a specific artery often leads to a characteristic clinical picture (Fig. 12.2). Each major artery supplies a certain territory which is separated from other territories by watershed areas (the border of two vascular territories lying adjacent to each other). The two anterior cerebral arteries are joined together by the anterior communicating artery. This allows for communication of the right and left hemispheres and is important in compensation for blood flow in the event of an occlusion of one of the carotid arteries.
Fig. 12.2
Arterial supply and homunculus
12.3.2 Venous System
The venous system of the brain and coverings is a network of drainage systems that include the veins of brain tissue, dural venous sinuses, dural meningeal veins, and veins between the skull tables (diploic veins). The majority of these veins communicate and, unlike systemic veins, have no valves.
The cerebral veins consist of the superficial cerebral veins and the deep cerebral veins. The superficial cerebral veins, also known as the cortical veins, drain blood from the outer surface of the brain into the large venous channels: the superior and inferior sagittal sinuses, the great cerebral vein of Galen, the straight sinus, and the tentorial veins. Blood from the cerebellar surface is drained by way of the cerebellar veins into the superior vermian vein and then into the great cerebral vein, straight sinus, and transverse sinuses. Blood from the inner regions of the brain is drained by the deep cerebral veins (or central veins). The inner regions include the hemispheric white matter, basal ganglia, corpus callosum, and choroid plexus. The deep cerebral veins also drain blood from several cortical areas (Moore and Agur 1995).
Blood supply from the brain drains into the dural venous sinuses and subsequently into the internal jugular veins. The dural venous sinuses are lined with endothelial cells and are found between the endosteal and meningeal layers of the dural mater (Moore and Agur 1995).
12.3.3 Pediatric Stroke
Stroke is the sudden occlusion or rupture of cerebral arteries or veins resulting in focal cerebral damage and clinical neurological deficits. A hemorrhagic stroke is one involving the rupture of a blood vessel, while ischemic stroke involves an occlusion that restricts the flow of blood to part of the brain, thus causing the tissue to die. Although it is commonly thought of as an “old person’s disease,” stroke also strikes infants and children and can occur in utero. Strokes in children are markedly different than strokes in adults, both in terms of risk factors and treatment, but the need to urgently recognize and treat within a short time period is vital for both populations.
The risk of stroke is greatest in the perinatal period, occurring in 1 out of every 4,000 live births (Lloyd-Jones et al. 2009), and the overall incidence of stroke in children is 1–6 per 100,000 children per year (Mallick et al. 2014). Breaking it down, the incidence of cerebral venous strokes is 0.5–1 per 100,000 children (Agrawal et al. 2009), 5.11/100,000 for hemorrhagic strokes (Giroud et al. 1995), and 2–13/100,000 for arterial ischemic strokes. The rates may even be higher as it remains an under-recognized disease entity in childhood. Boys are at greater risk of stroke than girls, and African American children are at greater risk than Caucasian and Asian children (Lloyd-Jones et al. 2009).
Neonatal risk factors include a maternal history of infertility, chorioamnionitis, premature rupture of membranes, and preeclampsia. In older children, sickle cell disease and congenital or acquired heart disease, head trauma, and major infections, such as encephalitis, meningitis, and stroke, are the most common risk factors (Roach et al. 2008), although arteriopathies, vasculitis, coagulopathies, and hematologic and metabolic disorders raise the risk as well. However, in the majority of children, strokes are idiopathic, with no underlying systemic disease found (Amlie-Lefond et al. 2009).
Symptoms of stroke in children are different than in adults and differ between age groups. Perinatal strokes that may occur anywhere from birth to 28 days after birth generally present less specifically as poor feeding, irritability, apnea, hypotonia, or with seizures (Kirton et al. 2011). Early handedness (before age 3 years) or developmental delay may also be a sign of perinatal stroke (Roach et al. 2008). As the child ages, focal neurological deficits are the more common presenting signs including hemiplegia or hemiparesis, an acute change in speech pattern, headaches, vomiting, hemianopsia, ataxia, or abrupt change in level of consciousness. The middle cerebral artery (MCA) is the most affected. Fifty to 80% of children who survive stroke will often have permanent neurological deficits, usually hemiplegia/hemiparesis – the most common symptom of cerebral palsy in term infants (Kirton and deVeber 2006).
A noncontrast CT may be performed in the acute presentation to rule out a hemorrhagic stroke, but within the first 12 hours of an acute ischemic stroke, the CT will likely be normal. Consequently, an MRI of the brain with diffusion-weighted imaging is considered the diagnostic gold standard.
Treatment of acute ischemic stroke is directed at minimizing further injury to prevent future developmental, cognitive, or functional impairment. Although there is a significant lack of pediatric data for the clear treatment of stroke, there are management guidelines available (Monagle et al. 2008; Roach et al. 2008). Generally, after hemorrhagic stroke has been ruled out, acute thrombotic treatment is recommended although the specific indications and type of therapy remain controversial. Anticoagulation with unfractionated heparin is safe for secondary prevention (Coutinho et al. 2011).
Children presenting with hemorrhagic stroke should have a thorough evaluation for vascular malformations and any arteriovenous malformations should be treated. Due to the significant chance of lifelong disability accompanied by the potential for considerable devastating effects on the family and society, pediatric stroke should be highly considered in the differential diagnosis. When the child presents with neurologic signs and symptoms, aggressive data collection should be performed to make an accurate diagnosis in this extremely significant disease entity (Gardner et al. 2010; Goldenberg et al. 2009; Perkins et al. 2009).
Pearls
Risk of stroke is greatest in the perinatal period.
Newborns with stroke present with:
Poor feeding
Irritability
Apnea
Hypotonia
Seizures
Early handedness (before age 3 years)
Developmental delay
Older children with stroke present with:
Hemiplegia or hemiparesis
Acute change in speech pattern
Headaches
Vomiting
Hemianopsia
Ataxia
Abrupt change in level of consciousness
Noncontrast CT may be used in the acute stage to rule out hemorrhagic stroke, but diffusion-weighted MRI is the gold standard for diagnosis.
Treatment is directed at minimizing further injury and may include thrombotic treatment and/or prolonged anticoagulation for cases of ischemic stroke.
Ronnie’s Story
Ronnie is a happy, healthy 13-year-old African American male who loves playing sports and hanging out with his friends. One summer morning, he began to experience a headache but decided it wasn’t bad enough to stay at home, so he went to the gym to play basketball with his friends. Once there though, his headache worsened and he experienced a syncopal episode. He was taken by EMS transport to the closest children’s hospital and diagnosed with an acute stroke. He was given tissue plasminogen activator (tPA), and his clot was embolized in the catheterization lab. He was diagnosed with dextrocardia as well as a moderate to large secundum atrial septal defect with left to right shunt. Surprisingly, he had been asymptomatic up to this event. Ronnie was discharged home with physical therapy secondary to his left-sided hemiparesis and placed on low-molecular-weight heparin (LMWH) until he could have surgical repair of his heart defect. Four months later, Ronnie underwent successful surgical intervention. He demonstrates minimal residual neurological deficits, and he is playing sports, going to school, and thankful for his life returning to normal.
12.4 Vein of Galen Aneurysmal Malformations
12.4.1 Pathophysiology
A vein of Galen aneurysmal malformation (VGAM) is a rare intracranial vascular anomaly typically found in neonates and infants but can also present in older children and adults. It accounts for approximately 1% of all cerebrovascular lesions overall (Huhn et al. 2006), although it is estimated to account for approximately 30% of all pediatric vascular malformations (Long et al. 1974). The vein of Galen, or great cerebral vein, lies under the cerebral hemispheres in the subarachnoid space dorsal to the midbrain and drains the anterior and central regions of the brain into the sinuses of the posterior cerebral fossa (Santos et al. 2005). The vein of Galen extends embryologically from the posterior segment of the median prosencephalic vein of Markowski (MProsV) and drains into the vein of Galen (Huhn et al. 2006). The MProsV can be identified between the 8th and 11th weeks of gestation, during which time the VGAM is thought to develop. The MProsV is the persistent embryonic channel that forms the aneurysmal or dilated component of the VGAM (Raybaud and Strother 1986). Most of the arterial supply of a VGAM comes from the choroidal arteries or feeders, which include the anterior and posterior choroidal arteries, the pericallosal artery, transmesencephalic branches from the basilar tip, and the proximal posterior cerebral arteries (Gailloud et al. 2005). The VGAM results from multiple fistulous connections or arteriovenous shunts that drain into the MProsV. It is still not known how these arteriovenous shunts actually form. Consequently, the MProsV becomes progressively dilated from the high-pressure flow from the choroidal feeders (Gailloud et al. 2005).
VGAMs can be classified into categories based on their angioarchitecture: choroidal and mural (Lasjaunias 1997). The simplest or choroidal type receives its arterial contribution from the choroidal arteries and a typical interposed network is present before opening into the large venous pouch. This choroidal type has been found mostly in neonates with poor clinical scores (Table 12.3). The second, or mural type, represents direct arteriovenous fistulas within the wall of the MProsV, and it can either be single or multiple. There may also be mixed forms when direct shunts and arterial networks combine (Hoang et al. 2009). Mural VGAMs tend to occur in infants with higher clinical scores. A score between 8 and 12 entails emergency endovascular management (Lasjaunias 1997).
Table 12.3
Vein of Galen aneurysmal malformation: neonatal evaluation scoring system
Score | Cardiac function | Cerebral function | Hepatic function | Respiratory function | Renal function |
|---|---|---|---|---|---|
5 | Normal | Normal | Normal | Normal | Normal |
4 | Untreated overload | Subclinical EEG abnormalities | Normal | Tachypnea but finishes bottle feed | Normal |
3 | Stable treated failure | Intermittent neurological signs | No hepatomegaly, normal function | Tachypnea, does not normally finish bottle feed | |
2 | Unstable treated failure | Isolated seizure | Hepatomegaly, normal function | Ventilated, normal saturations <25% added O2 | Transient anuria |
1 | Ventilated treated failure | Continuing seizures, neurological signs | Abnormal function | Ventilated, normal | Unstable |
0 | Resistant to treatment | Coagulopathy, raised enzymes | Ventilated, desaturated | Anuric |
12.4.2 Presenting Symptoms
The clinical features of VGAM differ characteristically with the age of presentation (Gold et al. 1964). The larger the arteriovenous shunt, the earlier the anomaly will manifest itself clinically. Symptomatic neonates can present with severe or progressive high-output congestive heart failure with cardiomegaly, as a result of the large volume of blood exerted by a VGAM with high-flow arteriovenous shunts (Gold et al. 1964; Fullerton et al. 2003). Severe pulmonary hypertension can also be a complication. Infants may present with an increasing head circumference secondary to hydrocephalus, seizures, and/or hemorrhage, albeit rare (Gold et al. 1964). Vein of Galen malformation should always be ruled out in neonates born with high-output cardiac failure (Hoang et al.2009).
A cerebral “steal” phenomenon, or the siphoning of blood flow away from adjacent brain tissue, can result in cerebral atrophy and periventricular leukomalacia (Pasqualin et al. 1982). The most severe form of the cerebral “steal” phenomenon is often referred to as the melting brain (Alvarez et al. 2007). Mild symptoms in the neonate may include feeding difficulties, tachycardia, and cardiomegaly on chest x-ray (Alvarez et al. 2007). More severe presentations include cardiorespiratory failure, hydrops, (a large amount of fluid buildup in the infant’s brain tissue), and renal failure (Gailloud et al. 2005).
Cardiac manifestation is typically milder in infants, and they are usually treated symptomatically with diuretics until the embolization procedure can be performed (Alvarez et al. 2007). Milder symptoms in this age group are usually due to a smaller shunt. Other symptoms may include failure to thrive, cranial bruits, dilated scalp veins, proptosis, prominent scalp veins, and epistaxis (Gailloud et al. 2005; Gulati and Kalra 2002; Gupta and Varma 2004). Noncommunicating hydrocephalus results from aqueductal obstruction or compression of the posterior third ventricle by the VGAM itself, whereas impaired cerebrospinal fluid absorption caused by subarachnoid hemorrhage (SAH) could contribute to communicating hydrocephalus (Jaegar et al. 1937). Intracranial venous hypertension induced by the VGAM has also been postulated to contribute to the development of hydrocephalus (Zerah et al. 1992).
In older children and adults, headaches tend to be the presenting symptom, which may be attributed to subarachnoid hemorrhage (Gold et al. 1964). Older children may also present with focal seizures and developmental delay. Poorer outcomes are demonstrated when prenatal diagnoses with ultrasound showed associated cardiomegaly and ventriculomegaly rather than isolated VGAM (Deloison et al. 2012). Preoperative sudden deaths in patients with VGAM have gradually declined, while the rate of emergency operations has gradually increased. Urgent medical attention to these malformations has demonstrated improved outcome (Yan et al.2016).
12.4.3 Diagnostic Tests
Transcranial ultrasound will help to localize or identify the lesion, and color Doppler studies can help to delineate the hemodynamics of the lesion (Deeg and Scarf 1990; Rodesch et al. 1994). A typical Doppler finding is that of a large, midline cystic structure with arterialized flow and visualization of the feeding arteries (Blaser et al. 2003). Cranial MRI and/or CT scan, with and without contrast administration, will help to establish the venous and arterial vascular anatomy of the lesion, as well as to confirm the diagnosis and define the degree of involvement (Fig. 12.3) (Blaser et al. 2003; Gailloud et al. 2005; Huhn et al. 2006). Imaging studies in infants will also help determine whether the patient has accompanying hydrocephalus.
Fig. 12.3
Magnetic resonance image (MRI) of the vein of Galen malformation
MR angiography (MRA) will be able to delineate feeding arteries, nidus, and draining veins, as well as distinguish the high-flow feeding vessels from the low-flow venous lesions (Blaser et al. 2003; Santos et al. 2006). CT angiogram is another modality of diagnostic imaging that may be helpful. In patients being considered for surgery or for endovascular therapy, cerebral angiography may be required to define the extent of aneurysmal dilatation and details for arterial feeders (Huhn et al. 2006). Angiography findings typically show anterior and posterior circulation fistulae supplying a markedly dilated vein of Galen (Blaser et al. 2003). However, cerebral angiography should only be undertaken as a prelude to therapeutic intervention and is not required purely for diagnosis, as the nature of the condition can be confirmed by MRI (Punt 2004). Cardiac ultrasound may be indicated to assess left ventricular function (Chevret et al. 2002).
12.4.4 Treatment Options
12.4.4.1 Endovascular Treatment
VGAMs have proven to be very difficult to treat using standard surgical procedures. Fortunately, this condition can now be treated with endovascular embolization, with improved neurodevelopmental outcomes (Chow et al. 2015). Endovascular embolization involves the injections of embolic agents, such as synthetic cyanoacrylate glue (N-butyl-cyanoacrylate or NBCA) or a variety of coils. Embolic agents encourage blood clotting and closure of the VGAM (Lasjaunias et al. 1991). Onyx (one of the more recently developed liquid embolic substances) has also been used to occlude the arteriovenous fistula on the arterial side (Gailloud et al. 2005; Jankowitz et al. 2008; Lasjaunias et al. 2006). The transarterial approaches are preferred over transvenous endovascular treatments. The literature clearly indicates an improved outcome and fewer complications associated with the arterial approach, such as potentially impairing normal deep venous pathways (Levrier et al. 2004; TerBrugge 1999, 2006). Using x-ray guidance, this procedure involves the insertion of a microcatheter through the femoral artery that is threaded through the arteries until the tip reaches the site of the arterial feeder. The embolic agent is then injected through the catheter. Sometimes several staged endovascular embolizations are required to help avoid the occurrence of parenchymal bleeds, secondary to “perfusion breakthrough phenomenon,” or massive venous thrombosis potentially endangering the normal venous supply (Gailloud et al. 2005). “Perfusion breakthrough” refers to a hemorrhage or swelling that develops from abnormal perfusion of the vessels surrounding the recently embolized lesion. Perfusion breakthrough is more prevalent in patients who are hypertensive. Given that most of these hemorrhages occur within the first week after treatment, strict management of the blood pressure in the days post-procedure is imperative.
Non-neurological complications related to embolization are rare (Lasjaunias 1997). Asymptomatic occlusion of the internal iliac artery and the microcatheter getting glued in place have been reported. Repeated punctures of the femoral artery do not seem to cause significant problems.
The timing of endovascular management is usually determined by the severity of the clinical presentation (Gupta and Varma 2004). Emergency embolization in the newborn is considered necessary in cases where congestive heart failure is present and does not respond to medical management (Gupta et al. 2006). Some clinicians feel that the therapeutic window for optimal endovascular management is between 4 and 6 months of age, as long as the infant is hemodynamically stable (Gailloud et al. 2005; TerBrugge 1999). However, excessive delay may lead to intractable hydrocephalus. There are a minority of patients who experience spontaneous thrombosis of the malformation (Cheng et al. 2003; Lasjaunias 1997; Lasjaunias et al. 1991).
12.4.4.2 Surgical Treatment
As a result of advances in endovascular management, surgical obliteration of a VGAM is now only considered in case of failure of, or as an adjunct to embolization (Gailloud et al. 2005; Huhn et al. 2006). Surgical interventions are indicated for the evacuation of intracranial hematomas and for the management of hydrocephalus. This can be treated either by endoscopic third ventriculostomy or insertion of a ventriculoperitoneal shunt (Gailloud et al. 2005). Shunt placement is associated with mortality and morbidity so should be considered if the treatment of the VGAM does not address the hydrocephalus.
12.4.5 Nursing Care
One of the primary goals of the nursing care for the neonate with a VGAM is maintaining optimal neurological function. Head circumference measurements should be obtained regularly and monitored carefully to detect hydrocephalus. Patients should be monitored for seizures and managed with antiepileptic medications. Usually, neonates are given phenobarbital and phenytoin. Respiratory interventions should include chest physiotherapy and suctioning to maintain the airway in the ventilated patient. Cardiac management of high-output heart failure is essential. Clinical care includes monitoring of physical activity, oxygen requirements, adequate caloric intake, and strict maintenance of input and output records. Pharmacological management can include inotropic agents (digoxin, dopamine, dobutamine), diuretics (loop diuretics, such as furosemide), and afterload-reducing agents (angiotensin-converting enzyme inhibitors such as captopril and enalapril). Other important nursing interventions include maintaining skin integrity, infection prevention and early recognition of sepsis, and providing comfort measures of frequent repositioning and pain medications as needed. Additionally, facilitation of parent-infant bonding, normal grieving and coping, and open communication are other means of providing holistic nursing care (TerBrugge 1999).
12.4.6 Family Education
Parents must face the ethically and morally difficult decision of whether or not to treat the child’s lesion, particularly for parents of children whose available medical information does not clearly indicate the benefit of one choice over the other (Gailloud et al. 2005). Parents may not fully understand the potentially devastating outcome of a child who is unresponsive to treatment, yet survives, and therefore are ill-prepared to adapt to life with a severely debilitated child. Problems include obtaining medical equipment, financial assistance, and certain support services often occur. It is of utmost importance that therapeutic decision-making is a shared process between the clinician and parents. All elements defining the child’s best interests must be considered and discussed.
12.4.7 Outcomes
Prior to the advent of endovascular embolization, the prognosis for patients presenting as neonates with congestive heart failure was poor. An earlier review reported mortality rates of 100% (9/9) for neonates, 68% (13/19) for infants, and 45% (5/11) for older children and adults (Gold et al. 1964). Modifications in the application of newer microcatheters, acrylic polymer NBCA, and neonatal care, such as modern imaging and intensive care environment, improved the outlook in a series of 11 patients (Friedman et al. 1993). No mortality had occurred, and 6 out of the 11 patients were functionally normal up to 30-month follow-up. In a series of 78 neonates, infants, and children that were treated and followed, seven of these patients died, but 66% of the 71 patients remaining were neurologically normal, 14% had transient neurological symptoms, 11.5% had mild permanent deficits, and 8.5% had severe permanent deficits (Lasjaunias et al. 1991). In a more recent series of 27 children undergoing endovascular treatment, four of whom died in hospital, 61% of the 23 surviving patients had no or minor developmental delay, and 64% had no or mild abnormalities on neurological examination (Fullerton et al. 2003).
Resolution of cardiac failure has also been achieved favorably with embolization. In a series of five symptomatic neonates, one died of intractable cardiac failure (20%), whereas control of cardiac failure was achieved by embolization without neurological symptoms in the surviving four patients. One of the patients (20%) demonstrated moderate developmental delay in follow-up (Mitchell et al. 2001). In a larger series of nine symptomatic neonates who underwent endovascular treatment, six patients (66%) obtained control of cardiac failure and normal neurological functioning, one patient died from intractable cardiac failure, and two patients (33%) died later as a result of severe hypoxic-ischemic neurological injury. At 6-month to 4-year follow-up, five infants had no evidence of either neurological or cardiac deficits, and one (11%) child had mild developmental delay (Frawley et al. 2002).
In another series with 15 patients who underwent embolization, 66% (10/15) had a complete obliteration of the fistula with an overall mortality rate of 20% (3/15) secondary to meningitis and intracranial hemorrhage. At 6-year follow-up, these patients were stable cognitively with overall improvement of their delayed developmental milestones (Gupta et al. 2006).
In a series of 233 patients, endovascular embolization was utilized via the transfemoral approach in patients where angiographic studies demonstrated a 90–100% occlusion in 55% of the patients. The neonatal mortality outcome was 52% (12/23), while the general mortality rate was 10.6% (23/216). Of note, only three of these deaths were caused by the embolization procedure. In the neonatal population, most of the deaths represented patients whose clinical presentation score was <8, and intervention was not expected to be successful. This study also demonstrated that persistent shunts, if small, can be tolerated and may even resolve spontaneously over time (Lasjaunias et al. 2006).
In a prospective review spanning 21 years, one large center treated 26 patients with VGAMs. At presentation, 12 of the patients presented with congestive heart failure, while ten presented with hydrocephalus. Five patients did not qualify for surgical interventions because of either mild or severe symptomatology. Of the remaining patients, 12 underwent embolization, and the remaining nine underwent endovascular surgery. Overall survival rate was 76.9% (20/26). Of the 21 patients who underwent endovascular treatment, 66/7% (14/21) went on to experience no delay in development. Those patients who were older at the time of embolization were noted to have more developmental delay as compared to those who were younger at the time of embolization (Li et al. 2010).
In summary, the more current reviews have shown improvement in both morbidity and mortality for the neonatal and pediatric populations. With continued advances in imaging and staged transarterial and transvenous embolizations, infants and children can have promising long-term cognitive and functional outcomes (Ellis et al. 2012).
12.5 Cerebral Arteriovenous Malformation in Children
12.5.1 Etiology
Cerebral arteriovenous malformation (AVM) is a relatively uncommon vascular lesion. Within the general population, the prevalence is estimated to be between 1.34 and 18 cases per 100,000 (Boone et al. 2016). Although AVMs are considered to be congenital in origin, few are diagnosed in the first two decades of life. The average age of presentation is 32–40 years old. In the less than 20-year-old age group, rate of occurrence is between 0.014% and 0.028%. This translates to a 20% rate of all AVMs diagnosed (Darsaut et al. 2011; Singhal et al. 2011; Foy et al. 2010; Buckley and Hickey 2014; Boone et al. 2016). The main difference between adults and children with regard to this lesion is the dramatic presentation of spontaneous hemorrhage as the initial symptom. This is as high as 80–85% in the pediatric population versus 50–65% in adults (Niazi et al. 2010) and accounts for more than half of the various presentation symptoms. Despite improvement of medical and surgical management, there is still a high mortality rate of 20–25% in children due to this phenomenon (Boone et al. 2016).
The majority of cerebral AVMs occur sporadically, are generally single lesions, and have no predilection for race or gender. Multiple AVM (MAVM) has been reported in the literature. These are two or more nidi that are separated by brain parenchyma and often present with neurological findings versus hemorrhage (Boone et al. 2016). Additionally, familial cases have been documented but are very rare (Yokoyama et al. 1991). AVMs are known to be associated with a few syndromes, specifically hereditary hemorrhagic telangiectasia (HHT) or Osler-Weber-Rendu disease. About 3.4% of children with AVM have HHT (Smith 2015). Recent investigations into this comorbid phenomenon have implicated a genetic mutation process along the transforming growth factor-beta signaling pathway causing AVM development (Smith 2015). In children diagnosed with multiple AVMs, HHT should be considered (Griffiths et al. 1998; Horgan et al. 2006; Roach and Riela 1995). Additionally, Wyburn-Mason syndrome (Bonnet-Dechaume-Blanc) is a rare congenital, nonhereditary disorder characterized by multiple cutaneous nevi and brain and retinal AVM (Roach and Riela 1995).
12.5.2 Pathophysiology
AVMs are often very complex neurovascular lesions. They are defined as a cluster of arteries and veins in the brain or on its surface that directly shunts arterial blood to the venous system. There is an absence of normal intervening capillary beds between the two systems causing the vessels to become dilated and tortuous forming a central nidus (Ali et al. 2003; Kondziolka et al. 1999; Roach and Riela 1995).
There is no brain parenchyma contained within the nidus. The tangled nidus of the AVM receives direct high-flow arterial blood from multiple feeding arteries. Blood is then shunted straight into the venous drainage system, which is subserved by veins that vary considerably in number, size, and configuration. The blood vessels become progressively dilated, thereby increasing the risk of rupture and subsequent spontaneous intracranial hemorrhage. In addition to dilatation, blood vessels are further weakened by dynamic remodeling of the structure from inflammatory and angiogenic processes (Smith 2015).
AVMs have been predominantly described as congenital abnormalities arising from persistent embryonic patterns with failure of normal involution of blood vessel networks (Buckley and Hickey 2014). It is hypothesized that a defect in the formation of the normal arteriolar capillary network occurs somewhere around the third to 12th week of embryogenesis which leads to the malformation (Niazi et al. 2010). Others postulate that AVMs are a consequence of stimulation of vascular growth by blood shunting, genetic errors, and mutations in the genes controlling angiogenesis (Zaidat and Alexander 2006). They may enlarge in childhood through early adulthood when new blood vessels are recruited during brain growth and development (Buckley and Hickey 2014).
These factors result in a propensity for AVM hemorrhage. The annual incidence of AVM rupture in children is 2–4% per year (Niazi et al. 2010; Yen et al. 2010; Darsaut et al. 2011). Mortality rate for children is 25% versus 6–10% in adults. Often AVMs in children are located in the posterior fossa or are deep seated in areas such as the basal ganglia or thalamus. Hemorrhages in these regions are generally less tolerated because of the valuable “real estate” in these areas than in the supratentorial areas seen as common AVM sites for adults. It is suspected that AVMs in children may be prone to bleeding due to a more active angiogenesis mediated by vascular endothelial growth factor (VEGF) as opposed to their adult counterparts (Niazi et al. 2010).
Tissues adjacent to the AVM may also be mildly hypoxic as the malformation may be stealing blood from the bordering healthy tissue causing chronic ischemia (Roach and Riela 1995; Smith and Sinson 2006). This steal phenomenon results in less devastating neurological symptoms initially but may herald an impending bleed. This phenomenon is generally not seen in children.
Secondary pathological changes can occur and include cerebral aneurysms; approximately 7% of patients with an AVM develop an aneurysm (Smith and Sinson 2006). Most commonly, aneurysms are found on the artery feeding the AVM and are considered pre-nidal. Aneurysms may also occur within the nidus or post-nidal veins. It has been reported that associated aneurysms are higher in adults with AVM than children −41% versus 26% in one series (Niazi et al. 2010).
12.5.3 Presenting Symptoms
Mentioned earlier, the primary symptom of AVM in the pediatric population is intracranial hemorrhage (ICH) (Griffiths et al. 1998; Horgan et al. 2006; Humphreys et al. 1996; Kondziolka et al. 1992, 1999; Muszynski and Berenstein 2001; Punt 2004; Zaidat and Alexander 2006). These lesions account for 30–50% of hemorrhagic stroke in children (Buckley and Hickey 2014). Since the majority of AVMs lie within the cerebral parenchyma, hemorrhages usually present as a subarachnoid or intraparenchymal bleeds. Clinical symptoms of an intracranial hemorrhage include sudden and severe headache that is often described as the “worst headache ever,” nausea and vomiting, neck stiffness, progressive neurological decline, and rapidly progressing coma (Punt 2004).
Some patients with AVMs may have intermittent or progressive symptoms rather than a single catastrophic event. Occasionally, the evolution may be more gradual and characterized by episodes of moderate headache, followed by focal neurological features over the next several hours. Hemiparesis, hemianopsia, and focal seizures are typically seen. This presentation may lead clinicians to believe that the child has sustained a characteristic occlusive episode rather than a hemorrhagic one (Punt 2004). It may, in fact, be periodic small hemorrhages that have occurred or thrombosis of a portion of the AVM, causing an infarct in the surrounding brain parenchyma (Roach and Riela 1995).
Some patients develop progressive neurological deficits over time without evidence of hemorrhage. This presentation may be attributed to the steal phenomenon mentioned earlier. In one series, other than ICH (71.6%), children presented with seizures (15.6%), headache (5.9%), and other neurological deficits including cranial nerve palsies (4.3%). Approximately 2.7% children were asymptomatic with the AVM found incidentally in this same series (Niazi et al. 2010).
Seizures without features of spontaneous intracranial hemorrhage or fixed neurological deficit are seen in 14–20% of patients (Humphreys et al. 1996; Kondziolka et al. 1999; Punt 2004). The seizures are presumably a result of gliosis of the brain due to chronic ischemia adjacent to the AVM (Kondziolka et al. 1999; Punt 2004). Very large AVMs may produce audible cranial bruits. AVMs with large arteriovenous shunts can also present with heart failure in the neonatal and infant populations (Elixson 1992; Levy et al. 2000; Punt 2004). Those located in the basal ganglia may produce movement disorders (Punt 2004). Macrocephaly and prominent scalp veins may also be evident.
12.5.4 Diagnostic Imaging
Upon initial presentation of a symptomatic ICH, CT scan should be the first radiological study completed. It is readily available at most hospitals, takes a few minutes to complete, and is most appropriate for identification of hemorrhage and any resulting hydrocephalus or mass effect. A noncontrast CT may also suggest the presence of an AVM if calcifications or dilated vessels are seen. Contrast CT (Horgan et al. 2006; Kondziolka et al. 1999; Meyer et al. 2000), specifically CT angiogram or CTA, will often reveal the vascular nature of the lesion. It will give a rough estimate of the location, size, and drainage of the lesion that is especially useful if other imaging such as MRI/MRA or cerebral angiography cannot be done due to emergent nature of surgical intervention (Niazi et al. 2010; Smith 2015).
When clinically feasible, MRI and MRA imaging may prove very helpful in diagnosis and planning management strategies. The higher resolution of this technique compared to CT is more specific regarding size and location, as well as helping differentiate from other sources of bleeding such as tumor or cavernoma. MRA may identify anatomy of the feeding arteries, possible aneurysms, venous drainage patterns, and nidal location/characteristics. Lastly, MRI/MRA technology preoperatively can assist with stereotactic guidance intraoperatively (Niazi et al. 2010).
The gold standard for AVM diagnosis is conventional four-vessel cerebral angiography. Angiography of an AVM will show abnormally dilated feeding arteries, draining veins, and the location of the tangle nidus (Horgan et al. 2006; Wolfe et al. 2009). Additionally, the presence of associated aneurysm or venous anomalies such as ectasia or varices can be identified. Dynamic blood flow through and around the AVM can be evaluated by angiography and helps the medical team determine feasibility of treatments such as endovascular therapy, surgery options, and radiosurgery (Buckley and Hickey 2014). The presence of a hematoma may lead to failure to visualize all of the malformation and its feeding vessels. The hematoma may compress and obscure the AVM, so for this reason, it is advisable to perform angiography once the clot retracts/dissolves (Punt 2004; Niazi et al. 2010).
12.5.5 Treatment
The primary goals of treatment of AVMs in children are to eliminate the risk of future hemorrhage, control seizures, and relieve symptoms related to vascular steal (Horgan et al. 2006). Hemorrhage rates for children are close to 4% the first year after an initial hemorrhage and 2–4% annually thereafter (Smith 2015). Some literature shows the rebleeding rate higher in the first 1–3 years, from 6% to 17% (Buckley and Hickey 2014). The success of treatment is dependent on the size of the AVM, its location, and vascular tendencies. The clinical condition of the patient at the time of diagnosis also plays a major role (Niazi et al. 2010). Treatment options of AVMs include microsurgical resection, radiosurgery, endovascular embolization, or a combination of treatment modalities. The focus of a recent investigation of AVMs in the adult population during the ARUBA study (A Randomized Trial of Unruptured Brain AVMs) was examination of the best outcomes of interventional versus conservative treatments 5 years from discovery of the unruptured lesion. Many AVMs in adults are found incidentally and don’t have the propensity for hemorrhage like those in children (Buckley and Hickey 2014). The option for conservative management of AVM in children is essentially not recommended, except where high morbidity risk or ineffective treatment is determined (Darsaut et al. 2011; Niazi et al. 2010; Ali et al. 2003; Horgan et al. 2006; Kondziolka et al. 1999; Zaidat and Alexander 2006).
The Spetzler-Martin (SM) grading system (Table 12.4) is a scale that was developed to predict the results of surgical intervention in adults (Spetzler et al. 2002). It is used in pediatric patients and has also been helpful in predicting outcomes of surgical and other interventions (Darsaut et al. 2011). This grading system assigns points to three features of an AVM: the size, area of the brain (eloquent and non-eloquent), and the presence or absence of deep venous drainage. The sum of the points determines the grading. Figure 12.4 is the proposed Spetzler-Martin grading scale with visual depictions of each grade.
Graded feature | Point assigned |
|---|---|
Size of AVM | |
Small (<3 cm) | 1 |
Medium (3.1–6 cm) | 2 |
Large (>6 cm) | 3 |
Eloquence of adjacent brain | |
Non-eloquent | 0 |
Eloquenta | 1 |
Deep venous drainage | |
Not present | 0 |
Presentb | 1 |
Lesions with SM grades I-III tend to have acceptable surgical outcomes: a rate of 86-100% radiographic obliteration (Smith 2015), average complication rate of 10%, and low mortality rate (0-8%) (Yen et al 2010). Patients who receive SM scores of IV and V should only be considered for surgery when significant repetitive hemorrhage occurs since rates of morbidity and mortality are proportionately higher. The high mortality rate in pediatric AVM is mainly associated with the initial sudden and catastrophic bleeding (Smith 2015). Hence, children who present with an acute intracerebral hemorrhage and associated progressive neurological deficit and/or brainstem compression require immediate surgery (Horgan et al. 2006; Kondziolka et al. 1992). The main goal of the surgery in acute presentation is to relieve the immediate increased intracranial pressure by evacuation of hematoma and removal of the AVM if possible. Patients often require a cerebral spinal fluid (CSF) diversionary procedure, specifically insertion of an external ventricular drain at the time of evacuation.
Ideally, surgical resection of the AVM should be delayed for 2–4 weeks post hemorrhage if a child is clinically stable (Horgan et al. 2006). This allows for resolution of the hematoma and the opportunity for a complete diagnostic workup to be done. MRI/MRA including navigation imaging and cerebral angiogram prior to surgery assists the surgeon in locating the nidus and feeding and draining vasculature that may have been previously occult due to the hematoma.
Surgery eliminates the risk of immediate bleeding and improves seizure control (Ali et al. 2003; Hoh et al. 2000; Horgan et al. 2006; Smith and Sinson 2006). Adjuncts to surgery that assist the neurosurgical team with planning and limit surgical complications are stereotactic localization, functional testing, and cortical localization. Monitoring of the patient during the procedure with somatosensory evoked potential (SSEP), motor evoked potential (MEP), electroencephalogram (EEG), and/or brainstem auditory evoked response (BAER) is indicated, especially in higher grade lesions where the potential for significant deficit exists (Darsaut et al. 2011). Intraoperative complications include hemorrhage, parenchymal injury due to sacrificing of vessels or retraction, and incomplete resection. Intraoperative angiography should be considered to assess for residual AVM during the procedure, but it isn’t always readily available.
Immediate complications related to surgical excision of an AVM are hemorrhage, seizures, vasospasm, and retrograde vascular occlusion, with either an arterial or venous thrombosis within the first 12–24 h after surgery (Horgan et al. 2006). These children will require postoperative management in the pediatric intensive care setting. Postoperative hemorrhage may be due to residual malformation or insufficient occlusion of the major arterial inputs and normal perfusion breakthrough phenomenon (Horgan et al. 2006; Smith and Sinson 2006). Normal perfusion breakthrough can occur after AVM resection, when blood flow that was directed through the AVM is now redistributed. If the perfusion pressure is greater than the autoregulatory capacity of the surrounding brain, swelling or hemorrhage may occur (Horgan et al. 2006).
Stereotactic radiosurgery (SRS) is a treatment modality utilized in children that uses high-energy radiation aimed directly on the nidus of the AVM. The radiation induces sclerosis or thickening of the blood vessel walls and ultimately obliterates the AVM by proliferation and thrombosis (Roach and Riela 1995; Niazi et al. 2010; Darsaut et al. 2011). SRS is a noninvasive procedure that is usually done in the outpatient setting. It is often administered in a single session, but depending on age of the child, location, and size of the lesion, the treatment may be staged to deliver smaller doses at intervals rather than one larger dose.
Whereas microsurgical intervention has the advantage of immediate and definitive treatment in lower SM grade lesions, SRS is recommended for AVMs in deep brain locations and eloquent cortical areas where safe surgical resection is questionable (Niazi et al. 2010; Yen et al. 2010; Darsaut et al. 2011; Buckley and Hickey 2014). There is also a role for radiosurgery for recurrent AVM and as part of a combined treatment approach for multiple AVMs (Boone et al. 2016). The main disadvantage of SRS is that obliteration of the malformation occurs over 3–5 years. During this period of time, the child continues to be at risk for recurrent hemorrhage (Hoh et al. 2000; Levy et al. 2000; Punt 2004; Smith and Sinson 2006; Smyth et al. 1997). An interesting finding over the last several years is that when total low-dose treatments are utilized in children to minimize radiation, there have been reported rebleed rates as high as 25% at 5 years versus a less than 2% annual rate (Smith 2015).
Because of the need for placement of a stereotactic frame utilizing some radiotherapy systems, children under 13–16 years of age often do best with sedation or anesthesia initiated prior to frame placement. Stereotactic MRI and/or biplanar stereotactic angiography is then utilized for dose planning. There are several SRS delivery systems, including Gamma Knife© (GKS), CyberKnife©, and linear accelerator (LINAC) (Darsaut et al. 2011; Niazi et al. 2010) and more recently greater use of proton beam (Smith 2015).
Over the last two decades, there have been several studies that retrospectively examined the clinical outcomes of SRS treatment. Radiosurgery has proven to be most efficacious in smaller lesions (less than 3 cm in size) and in those that receive a mean marginal dose of 20 Gy. Complete obliteration of AVM for these select patients has been reported in the 65–88% range (Levy et al. 2000; Smith 2015). With proton beam, these numbers are slightly less (Smith 2015). Surveillance of the lesion after treatment varies by center. Typically, angiogram is performed immediately to and within the first year of the procedure, followed by annual MRI until the nidus is no longer visualized. At that juncture, or by at least year 5, another angiogram is performed to assess the AVM. Retreatment or alternate treatment should be considered if there is obliteration failure or rebleeding in this time period (Niazi et al. 2010; Foy et al. 2010).
Radiosurgery is seldom performed in children under 2 years of age (Niazi et al. 2010; Levy et al. 2000). Side effects associated with radiation that present around the time of treatment are at a rate of 15%, are often transient, and are due to cerebral edema. AVM size, radiation dose, and AVM location also may influence presence and severity of symptoms (Levy et al. 2000). After radiosurgery has been performed, patients may present with headache, nausea, vomiting, and new onset or increase of seizure activity. Treatment with corticosteroids in the post-procedure phase may help with symptom management, but a small percentage (1–6%) of these issues may become permanent. Additionally, there have been a few cases of cyst formation and meningioma identification in follow-up (Yen et al. 2010; Darsaut et al. 2011).
The delayed effects of radiation on children can occur weeks to years after treatment. Although there is limited data available given the short history of this treatment modality, complications include hemorrhage, progressive edema, radionecrosis, seizures, and neurological deterioration (Friedlander 2007). So far, the rate of developing neoplasia status post-treatment seems to be less than 1% (Yen et al. 2010).
Embolization is rarely a solitary treatment option for children with AVMs (Roach and Riela 1995). It is usually an adjunct therapy prior to a surgical resection (Roach and Riela 1995; TerBrugge 1999), and it is helpful in removing the deep vessels that feed the malformation by inducing partial thrombosis of the malformation. By occluding the flow through the malformation, embolization helps to prevent excessive blood loss during surgery and avoid normal perfusion pressure breakthrough postoperatively (Horgan et al. 2006; Zaidat and Alexander 2006). In large AVMs, complete embolization in one session carries a higher risk of embolization-related hemorrhage so a staged treatment approach is recommended (Roach and Riela 1995; Zaidat and Alexander 2006; Buckley and Hickey 2014).
During embolization, a catheter is placed inside the blood vessel and blocks off the abnormal vessels supplying the AVM. Various materials can be used for this procedure, including thrombogenic coils, silk threads, polyvinyl alcohol (PVA) particles, N-butyl cyanoacrylate (NBCA) glue, and Onyx-34 liquid embolic. In some institutions, interventionalists use combinations of coils and glue (Lv et al. 2009). The chance of complete obliteration by this method alone is anywhere from 5% to 20% in recent series, with Onyx showing early promise for higher success rates (Darsaut et al. 2011; Yen et al. 2010; Friedlander 2007). Onyx has theoretical slower filling times allowing for a more solid cast to occlude the vessel than other agents. As with many treatments in pediatrics, it is approved for adults and is off-label in pediatrics. In a recent study by Soltanolkotabi et al. (2013), of 38 embolizations, 12% had complete obliteration, while 88% had partial obliteration. Preoperative devascularization occurred in 72% of patients which made surgery safer.
For all endovascular methods, low obliteration rates result from the inability to embolize all vessels, and over time, AVMs can recanalize, recruit new vasculature, and reestablish AV shunting. Although the patient may have relief of some of the symptoms caused by the AVM after embolization, it is important to keep in mind that the risk of hemorrhage in a partially treated AVM may be reduced but not eliminated (Niazi et al. 2010).
The advantages of embolization over radiosurgery are the elimination of brain edema from radiation and a more immediate effect of lesion reduction prior to surgery. There is, however, a reported complication rate of almost 8% with embolization, including hemorrhage and other unexpected neurological deficits (Darsaut et al. 2011). AVMs in eloquent areas may have negative outcomes from vessel thrombosis. Some centers perform sodium amytal assessment prior to embolization or opt for radiosurgery instead.
Mentioned earlier, rare conservative management is used only in cases where the AVM is not treatable due to size or location and is generally associated with poor outcome (Zaidat and Alexander 2006). Patients and families should be counseled to have the child avoid activities that elevate blood pressure excessively, avoid medications or alternative therapies that may have blood thinning properties, and have regular medical monitoring and follow-up. Infants with congestive heart failure from shunting through the low-resistance AVM should be stabilized. Seizures should be treated with anticonvulsant medication. All treatment modalities require angiographic follow-up at appropriate intervals to confirm successful and complete obliteration (Ali et al. 2003; Punt 2004).
12.5.6 Outcomes
In the general population, nontreated lesions carry a 10–15% mortality and 30–50% morbidity rates (Horgan et al. 2006; TerBrugge 1999). Risk of hemorrhage from an unruptured AVM is 2–4% per year, which translates into a 30–40% risk of serious morbidity and a 10–15% risk of mortality per decade (Horgan et al. 2006; Levy et al. 2000; Maity et al. 2004; Roach and Riela 1995; Smith and Sinson 2006). The greatest risk to a child with an AVM is hemorrhage. Without treatment, the risk for re-hemorrhage is nearly 6% or higher in the first year after the initial hemorrhage, with a return to 1.5–3% per year thereafter. Hemorrhage results in damage to normal brain tissue that can lead to loss of normal functional abilities which may be temporary or permanent. The impact of a hemorrhage depends on the location and the extent of associated brain injury. Successful management depends on many factors, including presentation, clinical condition, the age of the child, and neuroanatomical features (size, location, and angioarchitecture) of the lesion (Horgan et al. 2006). Complete surgical excision of the AVM eliminates the risk of bleeding almost immediately. Nearly 50% of patients with preoperative seizures are eventually seizure-free and off anticonvulsants after resection of the AVM (Horgan et al. 2006).
Excellent or good outcomes can now be achieved in 95% of children with AVMs who survive a hemorrhagic event with complete angiographic obliteration achieved in over 90% (Horgan et al. 2006). A multidisciplinary approach to these malformations, with selection of appropriate treatment modalities done on a case-by-case basis by comprehensive teams, has proved invaluable in these successes. Additionally, young children have brain plasticity and the ability to overcome initially poor neurological presentations better than adults (Niazi et al. 2010).
It is imperative that radiological evaluation in the posttreatment period is completed, as there is a risk of incomplete resection or recurrence. Severe complications are reported in approximately 10% of children, and operative mortality is between 0% and 8% (Horgan et al. 2006; Roach and Riela 1995). Despite the recent advances in treatment options approximately 10% of cases are unable to utilize these options. Prognosis for these children continues to be poor (Horgan et al. 2006; Singhal et al. 2011).
Pearls
AVM in pediatrics is rare, but up to 85% present with hemorrhage with a mortality rate of up to 25% in this population.
Congenital and complex lesions with direct shunting of arterial blood into venous system and have rate of rupture 2–4% per year.
Imaging includes CTA and MRI, with cerebral angiogram as the gold standard.
Treatments
Aggressive in children due to high risk for bleeding over lifetime.
Conservative management only in very high-risk patients.
Endovascular embolization
Used mainly as adjunct therapy for many years prior to surgical resection by occluding deep vessels and limiting bleeding during surgery.
Incomplete obliteration may encourage reestablishment of AV shunting over time.
Solitary therapy for AVM that is surgically risky or inaccessible.
Surgery
May be required urgently to evacuate large hematoma after rupture.
Ideally surgical resection after rupture planned with angiogram, embolization prior to surgery.
Stereotactic radiosurgery
Not used in children under 2 years old.
Delayed obliteration (up to 5 years later), brain edema after treatment risks of treatment.
May be used for deep AVM or in eloquent brain area.
Outcomes
Up to 90% of children who survive initial rupture achieve obliteration of AV.
Brain plasticity in young children leads to better outcomes.
Ten percent of AVM patients have poor outcome due to eloquent, deep location of lesion, rebleeding, and morbidity of survivors.
Mariana’s Story
Mariana is an 11-year-old girl who suffered a sudden and severe headache after playing a soccer game. She was taken by her parent to the local emergency room where she proceeded to display worsening neurological symptoms. Brain CT was positive for a large left temporal/parietal hemorrhage. She was immediately airlifted to a major children’s hospital where upon arrival her right pupil became dilated and fixed. She was immediately taken for a craniectomy and evacuation of the hematoma, and a ventricular drain was placed. Postoperatively, she had expressive aphasia and right hemiparesis but was stabilized hemodynamically and neurologically. Although an AVM was suspected, because of the urgency of surgery to decompress her, MRI/MRA and cerebral angiogram was done postoperatively. These studies confirmed an AVM as the source of her hemorrhage. After several days, she was able to utter some words, but this was not consistent for several weeks. During that time period, she began to increase her motor function on her right side and her speech improved. The neurosurgical plan was to do another angiogram electively in 6–8 weeks to determine the status of the AVM and attempt embolization of an accessible vessel. It was deemed to not be safe to embolize any vessels so the neurosurgeon performing the resection had to do so surgically. The surgery resulted in complete removal of the AVM that was confirmed on postoperative angiogram.
Mariana has taken about a year to regain the majority of her motor strength with some fine motor deficits of her right hand that she has ongoing therapy for. Her expressive aphasia has dramatically improved, but she still needs speech therapy for continued achievement. Her 1-year anniversary after AVM rupture is bittersweet for her parents: an emotional reminder as to how close she was to death and her long journey back to baseline combined with one of pure joy and thankfulness for the team that gave Marianna and her family all the care and support through this crisis.
12.6 Cerebral Arteriovenous Fistulas in Children
12.6.1 Etiology
Cerebral arteriovenous fistulas (AVFs), excluding the vein of Galen malformation (VGAM), are extremely rare and account for only 1.6–4.7% of all brain AV malformations in the general public (Lv et al. 2009). Among all intracranial arteriovenous lesions in children, AVFs account for approximately 10% (Horgan et al. 2006; Zaidat and Alexander 2006). Arteriovenous fistulas can be acquired or congenital in origin (Hoh et al. 2000; Horgan et al. 2006). The exact etiology is unknown, but most AVFs are thought to be multifactorial. Conditions associated with dural AVFs include intracranial venous hypertension, previous sinus thrombosis, thrombophlebitis, tumor, previous neurosurgical intervention, and cranial trauma. Much like arteriovenous malformations, AVFs have a relationship to some childhood syndromes, including hereditary hemorrhagic telangiectasia (HHT) (Osler-Weber-Rendu disease), Wyburn-Mason syndrome (Bonnet-Dechaume-Blanc), and Klippel-Trenaunay-Weber syndrome (Hoh et al. 2000; Horgan et al. 2006).
12.6.2 Pathophysiology
Arteriovenous fistulas are abnormal connections between a dural arterial supply and a dural venous channel. There is no intervening capillary channel between the arterial and venous supply which creates conditions for rapid high flow through the vessels (Lv et al. 2009). Unlike the AVM, which has a well-circumscribed discrete nidus, AVFs are composed of a diffuse network of numerous arteriovenous microfistulae (Kondziolka et al. 1992; Zaidat and Alexander 2006). Arteriovenous fistulas are commonly found in the sigmoid-transverse sinus, cavernous sinus, and superior sagittal sinus (Horgan et al. 2006; Kondziolka et al. 1992). Approximately 50% of all dural AVFs are found in the occipital-suboccipital region (Kondziolka et al. 1992).
In children, AVFs are often solitary entities, but they may also be multiple entities with multiple feeding arteries (Horgan et al. 2006; Kondziolka et al. 1992). Arterial supply and venous drainage patterns vary depending on the location of the fistula (Zaidat and Alexander 2006). Transverse-sigmoid dural AVFs are usually supplied by the ipsilateral occipital artery, with additional supply from the anterior and posterior division of middle meningeal arteries, posterior auricular artery, neuromeningeal trunk of the ascending pharyngeal artery, posterior meningeal branches of the ipsilateral vertebral artery, and possibly the meningohypophyseal trunk from the internal carotid artery (ICA) (Zaidat and Alexander 2006). Venous drainage is variable and can involve the ipsilateral sinus, depending on the degree of sinus obstruction into the contralateral transverse sigmoid sinus or cortical veins (Zaidat and Alexander 2006). Arterial supply from the coronal segments of either or both middle meningeal arteries or superficial temporal artery primarily supplies fistulas that are found in the superior sagittal sinus. Additional supply may be from the anterior falcine artery of the ophthalmic artery and the posterior meningeal branch of the vertebral artery.
Ethmoidal dural AVFs are those along the anterior cranial fossa floor, are primarily fed by anterior and posterior ethmoidal branches of the ophthalmic artery, and receive a secondary supply from the internal maxillary artery. Venous drainage is usually via a pial vein commonly associated with a venous varix that is directed toward the superior sagittal sinus (Horgan et al. 2006). Cavernous dural AVFs are rarely found in the pediatric population. These fistulas receive arterial supply from dural branches of the cavernous segment of the internal carotid artery and also from distal internal maxillary artery branches, middle/accessory meningeal arteries, and distal branches of the ascending pharyngeal artery. Venous drainage is via superior ophthalmic vein, cavernous sinus, or cortical veins.
Pial AVFs occur in the subpial space. These lesions are mainly congenital but can be associated with trauma or iatrogenic factors. They resemble AVMs in structure with direct arterial connection to a pial venous channel, although without a nidus that is distinctive of AVM. They are located most often in the supratentorial area of the brain (Paramasivam et al. 2013). There is up to 25% association with HHT – hemorrhagic hereditary telangiectasia – reported in the literature (Walcott et al. 2013). This association has led to the hypothesis that this anomaly results from failure of the primitive endothelial tubes of venous development to regress as proper capillary networks are developed. The abnormally dilated capillary nets form fistulas that persist. In HHT, the auxiliary receptor for normal vascular development and maintenance, endoglin, is deficient. Especially in cases where multiple pial AVFs are present, this deficiency is suspect (Paramasivam et al. 2013).
12.6.3 Presenting Symptoms
Clinical presentation in children with AVFs is variable and specific to age, location, size of the fistula, and the presence of other vascular lesions (Hoh et al. 2000; Horgan et al. 2006; Kondziolka et al. 1992). Location and pattern of drainage are key components of the clinical presentation. Cardiac involvement is absent in the adult population, but in children it is often seen and may be the sole presenting feature (Zaidat and Alexander 2006). Neonates typically present with symptoms of heart failure, cyanosis, and cranial bruits, whereas children outside of the neonate period present with neurological symptoms (Hoh et al. 2000; Horgan et al. 2006; Kondziolka et al. 1992). Children between 1 and 15 months of age are the largest group of patients, with hydrocephalus and macrocrania, increased intracranial pressure (ICP), developmental delay, seizures, and subarachnoid hemorrhage (SAH) as typical symptmology (Horgan et al. 2006). In one series reporting on pial AVF, 8 out of 16 cases were diagnosed before 1 year of age, and 80% had congestive heart failure (Paramasivam et al. 2013). If a child is 2–15 years of age at time of presentation, their clinical symptoms would often include headaches, focal neurological deficits, syncope, seizures, and SAH (Horgan et al. 2006; Parmasivam et al. 2013; Hacein-Bey et al. 2014).
Hemorrhage from an AVF is relatively uncommon (Hoh et al. 2000; Kondziolka et al. 1992). In one series of 41 patients with 63 AVFs, there was a 17.1% hemorrhage rate (Weon et al. 2004). Anterior cranial fossa and tentorial dural AVFs almost always drain into a cortical vein and are associated with a high degree of intracranial hemorrhage (Zaidat and Alexander 2006). Pial AVFs also are high risk for bleeding due to high-flow shunting and the absence of varix (Paramasivam et al. 2013). A dural AVF occurring in the cavernous sinus usually presents with proptosis, cranial bruit, increased intraocular pressure, diplopia, or diminished visual acuity (Kondziolka et al. 1992; Zaidat and Alexander 2006).
AVFs can be classified into three types (Djindjian system):
Type 1 (least risk): Drain via the ipsilateral sinus; these usually present with headaches and bruits but rarely with neurological deficits or hemorrhage.
Type 2 (higher risk): Drain toward the contralateral sinus; these present with more severe symptoms mostly related to increased ICP or papilledema.
Type 3 (highest risk): Drain via cortical veins; these are at greatest risk of ICH or venous infarction.
Some dural AVFs can spontaneously progress from type 1 to either type 2 or 3 (Zaidat and Alexander 2006).
Alternatively, the Cognard classification system adds two additional types of lesions to this grading system (Buckley and Hickey 2014):
Type 4: Drainage into cortical veins with venous dilatation (ectasia).
Type 5: Drainage into spinal perimedullary veins, associated with progressive myelopathy – spinal AVF will be discussed later in this chapter.
12.6.4 Diagnostic Imaging
Conventional cerebral angiography remains the preferred diagnostic test for AVFs. Additionally, this is necessary for treatment planning especially in complex anatomical areas of the brain (Hacien-Bey et al. 2014). A complete evaluation of head and neck vasculature is required (Zaidat and Alexander 2006). Plain chest x-rays are utilized to screen for signs of congestive heart failure: cardiomegaly, pulmonary vascular congestion, and edema.
CT angiogram (CTA) is newer technology that has recently been enhanced by four-dimensional renderings. This imaging modality not only diagnoses the lesion but can also have a role in visualizing major arterial feeders to the lesion. If a cerebral angiogram is still indicated for treatment, this test does add more radiation exposure to a young child – it has about two-thirds the amount of radiation as cerebral angiography – and would not add additional information to the cerebral angiography. Therefore, it should not be utilized in this situation.
CT scan is generally not the best imaging for diagnosing AVF; however, features that may raise suspicion include prominent enlargement of arteries or veins, a large varix, and the lack of an obvious nidus (Horgan et al. 2006; Buckley and Hickey 2014). CT is valuable for assessing ventricular size or the presence of ischemic infarctions and is also used to rule out parenchymal edema related to venous hypertension, SAH, subdural hematoma, and intraparenchymal hemorrhage (Horgan et al. 2006). Pediatric dural AVFs can have rather large draining sinuses or veins. Sometimes, the draining sinus may be so massive on imaging that it can be misinterpreted as an extra-axial mass (Zaidat and Alexander 2006).
MRI or cranial ultrasound can adequately establish diagnosis of these lesions. MRI is preferred and can delineate abnormally enlarged dural arteries, normal pial arteries, thrombosis of the dural sinus, venous varix, possible feeders, and multiple parenchymal serpentine vessels without a vascular nidus (Zaidat and Alexander 2006; Paramasivam et al. 2013). MRI is also effective in delineating cerebellar tonsillar prolapse and cerebralmalacia. This is important when assigning prognosis – diffuse cerebralmalacia equates to poor outcomes since it is irreversible (Paramasivam et al. 2013). MRA may demonstrate flow-related enhancement of serpentine vessels. High-field 3-tesla time-resolved MRA has been reported to have excellent sensitivity and specificity in screening for and follow-up of AVF (Hacein-Bey et al. 2014). The role of MRV is to evaluate for the presence of a thrombosis in the recipient sinus (Zaidat and Alexander 2006) (Fig. 12.4).
Fig. 12.4
Proposed Grading System for Arteriovenous Malformations (Spetzler and Martin 1986)
12.6.5 Treatment
Therapy for dural AVFs in the pediatric population must be performed with the understanding that they are potentially life-threatening lesions. The goal of treatment is to interrupt all the feeding arteries as closely as possible to the fistula while leaving the venous drainage intact, thereby obliterating the fistula (Hoh et al. 2000). Medical management with inotropic agents and diuretics is often vital at the onset of cardiac manifestations (Kondziolka et al. 1992).
Treatment options for the AVF include surgical resection, endovascular treatment, or a combination of treatment modalities. Surgery has traditionally been the treatment approach but has been replaced more and more by endovascular embolization. Many brain AVFs are deep and located in eloquent areas that carry high risk for neurological morbidity when addressed surgically. There has been significant improvement of microcatheters, guidewires, and experience by endovascular practitioners over the last two decades that have resulted in better outcomes. Reported in a literature review by Yang and associates (2011), obliteration in endovascular treatment is 86.5%. Although obliteration rate in surgical resection in the same review was 96.9%, caution was given since many were superficial AVF (Paramasivam et al. 2013).
Because there may often be several arterial connections for a single venous channel, endovascular embolization is often done as a staged transarterial approach (Lv et al. 2009). The use of various agents has been employed, such as balloons, coils, glue, and Onyx-34. The procedure is generally done under general anesthesia via a percutaneous femoral puncture (Weon et al. 2004). Complications that may occur include arterial collateral recruitment from an occlusion too proximal or decreased venous outflow and venous hypertension from an occlusion too distal. Other complications include cerebral edema and hemorrhage. Radiation has been utilized in adults with localized slow flow dural lesions but is not an appropriate treatment in infants or children with extensive dural AVFs (Kondziolka et al. 1992). Depending on the complexity of the fistula, treatment may be either palliative for symptom relief or curative.
12.6.6 Outcomes
Irreversible brain injury was found in cases where dural AVFs were undiagnosed and where cerebral venous hypertension went unchecked for a long period of time. In cases of early presentation in neonates, no presence of lasting radiological or clinical deficits was seen (Kondziolka et al. 1992).
Posttreatment hydrocephalus has been documented in the literature and should be evaluated during scheduled medical follow-up (Walcott et al. 2013).
Pearls
AVFs are rare in children but usually present within the first 1–5 years of life.
Conventional diagnostic cerebral angiography remains the gold standard for certain vascular malformations including AVF and AVM when complete and thorough evaluation of head and neck vasculature is required.
The goal of treatment (endovascular and surgery) is to interrupt all the feeding arteries as close as possible to the fistula while leaving the venous drainage intact.
12.7 Intracranial Aneurysms
12.7.1 Incidence
The incidence of intracranial aneurysms in children under the age of 18 years has been estimated between 0.5% and 4.6% (Asaithambi et al. 2014). There is a bimodal age pattern, with a peak occurring in the first 2–6 years of life and the second peak occurring in the second decade. The mean age of diagnosis in the pediatric population is 7.6 years (Beez et al. 2016). Intracranial aneurysms occur predominantly in males, with a male to female ratio of 1.8:1 (Buckley and Hickey 2014). A recent review of the literature found that pediatric aneurysms account for 5% of all aneurysms. Cerebral aneurysms are very rare in patients 18 years old or younger but are even rarer in the infant and toddler age group (Huang et al. 2005).
In the adult population where aneurysms are more commonly seen, there is high-quality research that has evaluated the natural history of aneurysms (The International Study of Unruptured Intracranial Aneurysms and the Unruptured Cerebral Aneurysm Study). The International Subarachnoid Aneurysm Trial, a multicenter randomized trial, evaluated aneurysm treatments specifically endovascular coiling and neurosurgical clipping. The findings of these studies have improved care in adults with these lesions. For pediatric patients, data has been mostly case studies and reports in the literature. In a comprehensive review of the literature by Beez et al. (2016), current management of pediatric aneurysms is reviewed. They caution, however, that neither generalizations from adult data nor information from the review can replace research, and they encourage multicenter registries and clinical trials in children for the future.
Features of childhood aneurysms which are different than those of adults include:
- 1.
A predominant incidence in males versus females
- 2.
A higher incidence of unusual sites, specifically the posterior circulation, and especially the carotid bifurcation location
- 3.
A predominance of complex aneurysms with giant aneurysms accounting for 20% of the aneurysm types seen in children
- 4.
A lower incidence of multiple aneurysms
- 5.
A higher incidence of posttraumatic and infectious causes
- 6.
A tendency toward a higher frequency of spontaneous thrombosis aneurysms
- 7.
12.7.2 Aneurysm Subtypes
There are four different subtypes of aneurysms that are defined by their shape and form: saccular aneurysms (berry aneurysms), fusiform aneurysms (including giant aneurysms), infectious or mycotic aneurysms, and traumatic aneurysms.
12.7.2.1 Saccular Aneurysms (Berry Aneurysms)
Saccular aneurysms are nontraumatic, noninfectious lesions. They are often round with a well-defined neck that connects to a parent artery but also can be broad-based with no stalk or cylindrical. Thought likely to be a result of congenital abnormalities in the media of the arterial wall, saccular aneurysms occur more commonly in the general population, up to 80% of all aneurysms in some literature (Hinkle et al. 2010). They occur less so in children, but overall have a high incidence of spontaneous rupture or hemorrhage. Statistics of this phenomenon range from 35% to 75% (Jian et al. 2010).
12.7.2.2 Fusiform Aneurysms
Fusiform aneurysms are circumferential dilatations involving the arterial wall. They occur in cerebral arteries, as well as other parts of the body. Often called “dissecting aneurysms,” these lesions have a lower incidence of hemorrhage than saccular aneurysms, but their neurological impact is commonly embolic stroke as acute and subacute dissection events in the vessel wall occur (Hinkle et al. 2010). Although they only account for approximately 5% of intracranial aneurysms in the general population, fusiform lesions occur more frequently in children. A recent review showed 16% incidence of fusiform lesions in pediatrics (Beez et al. 2016). In children, they are associated with connective tissue disorders, radiation to the pituitary region, and after resection of craniopharyngiomas (Hetts et al. 2009). Fusiform aneurysms are commonly found in the basilar arteries or terminal portions of the internal carotid arteries and often result from diffuse arteriosclerotic changes.
“Giant aneurysm” is a term given to lesions that are >25 mm in size. They are rare in adults but were documented in 11–23% of the cases in the literature (Kakarla et al. 2010). Common sites were the basilar artery and the terminal portions of the ICAs and represent the largest subgroup (54%) of posterior circulation aneurysms in literature review (Beez et al. 2016). They also tend to produce symptoms typical of space-occupying lesions due to their potential size and can be mistaken for a tumor on neuroimaging (McCance and Huether 2002; Jian et al. 2010; Hetts et al. 2009).
12.7.2.3 Mycotic or Infectious Aneurysms
Mycotic aneurysms are rare and result from arteritis caused mainly by bacterial emboli, although fungal infections can also be a source (McCance and Huether 2002). These lesions tend to have a lower hemorrhage potential as compared to saccular and fusiform aneurysms. Associated infections include endocarditis and meningoencephalitis and immunodeficiencies, both congenital and acquired (Hetts et al. 2009; Lasjaunias et al. 2006; Buckley and Hickey 2014). In addition to endovascular and surgical management of these aneurysms, treatment of the underlying infectious process with appropriate systemic antibiotic therapy is indicated (Jian et al. 2010; Hetts et al. 2009).
12.7.2.4 Traumatic Aneurysms
Traumatic aneurysms occur as a result of sustained trauma to the arterial wall, causing a fracture that weakens the wall (McCance and Huether 2002). As would be expected given the mechanism of injury, these aneurysms are commonly seen in vessels near the skull base versus the supratentorium.
12.7.3 Etiology
The risk factors of aneurysms in the pediatric population differ from the classic risks seen in adults. In adults, these potentially modifiable risk factors include hypertension, shear stress, high fat and high cholesterol diets, oral contraceptive use and cocaine, and alcohol and tobacco use (Khoo et al. 1999; Lasjaunias et al. 2006). In addition, typical diseases of the vascular system seen during the fifth, sixth, and seventh decade of life, such as atheromatosis and degenerative vascular conditions, account for aneurysm peak during these age groups in adults. For this reason, it has been proposed that a vasculopathy (congenital or acquired) predisposes the cerebral vasculature to aneurysm development (Hinkle et al. 2010). Associated conditions of intracranial aneurysms in children include vascular anomalies, cardiac lesions, connective tissue abnormalities (Ehlers-Danlos most often), hematological disorders (with sickle cell predominance), infections, immunodeficiencies, and phakomatoses syndromes (e.g., neurofibromatosis type I and tuberous sclerosis) (Beez et al. 2016). Other miscellaneous causes, such as surgical complications, penetrating head injuries, and radiation therapy, have been reported. As with their adult counterparts, intracerebral aneurysms in children may be due to a combination of genetic and acquired factors (Khoo et al. 1999). Refer to Table 12.5 for a list of causes and pathologies that may be associated with intracranial aneurysms in childhood.
Table 12.5
Causes and associated pathologies of intracranial aneurysms
Vascular anomalies |
Cerebral AVM |
Moyamoya |
Cardiac lesions |
Coarctation of the aorta |
Bacterial endocarditis |
Atrial myxoma |
Connective tissue abnormalities |
Marfan’s syndrome |
Ehlers-Danlos type IV syndrome (rarely in types I and IV) |
Fibromuscular dysplasia |
Pseudoxanthoma elasticum |
Hematological disorders |
Sickle cell disease |
G-6-PD deficiency |
Thalassemia |
Infections and immunodeficiency |
HIV/AIDS |
Syphilis |
Severe combined immunodeficiency |
X-linked immunodeficiency |
Phakomatoses |
NF-1 (especially after radiation therapy) |
Tuberous sclerosis
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