Definition and cause

VGAM (see Figs. 2 and 3 ) can be defined as a congenital AV shunt, centered on the tela choroidea of the third ventricle, supplied predominantly by choroidal arteries, and usually draining into an aberrant falcine sinus. In VGAMs, the thalamostriate and internal cerebral veins do not communicate with the vein of Galen but instead drain into the posterior and inferior thalamic veins, and either join a subtemporal vein or, more commonly, the lateral mesencephalic vein to open into the superior petrosal sinuses, which gives the characteristic angiographic epsilon shape or epsilon vein on the lateral angiogram. The straight sinus is usually absent, with a falcine sinus draining the malformation to the superior sagittal sinus.

In some instances it may be difficult to distinguish between a VGAM and a thalamic or tectal AVM draining into a dilated vein of Galen, and a medially located pial AVF draining into the vein of Galen. In general, 2 types of angioarchitecture are described in VGAMs: choroidal and mural. The former corresponds with a primitive condition involving all of the choroidal arteries and an interposed network before opening into the large venous pouch. The latter type corresponds with direct AVF within the wall of the median vein of the prosencephalon. The fistulas may be single but are often multiple, converging into a single venous chamber or into multiple venous chambers located along the anterior aspect of a venous pouch or along 1 dilated choroidal vein before reaching the venous pouch.

VGAM is rare, but is the most common intracranial AV shunt presenting in the neonatal period. Our institution receives around 1 to 2 new VGAM referrals per month, but it is difficult to be certain what catchment population this comes from, or what proportion reaches us. Disproportionate attention is given to VGAM, because the logic for treatment of all other high-flow AVSs of the neonatal period is based largely on our experience with VGAMs.

Paget first explicitly dealt with the embryology of this condition, referring to the possibility of an early embryonic AV shunt developing in the tela choroidea of the third ventricle, and postulating as to its consequences. Raybaud and colleagues in 1989 stated that the ectatic vein in VGAM was the embryonic precursor, the median vein of the prosencephalon, and not the vein of Galen itself.

Presentation

Antenatal diagnosis of VGAM is increasingly made using ultrasound and MR imaging. It is puzzling that it has never been shown on a 20-week gestational age antenatal scan, because the embryology suggests that it must be present at this stage. Antenatal diagnosis of VGAM raises some difficult considerations; some develop in utero parenchymal brain damage, and have a poor prognosis. Most have normal brain in utero, and present with either antenatal or perinatal heart failure.

Gold in 1964 described the following clinical stages in patients with VGAMs: (1) neonates with cardiac insufficiency, (2) infants and young children with hydrocephalus and seizures, and (3) older children or adults with headaches and subarachnoid hemorrhage. Amacher later added a further clinical group that included neonates and infants with macrocephaly and minimal cardiac symptoms. The most common mode of presentation in a neonate is heart failure caused by extremely low-resistance flow through the AV shunt. These children are often gravely ill, and may progress to multiorgan failure and ischemic brain damage within hours to days, despite optimal support in an intensive care unit. Infants and children may also present with hydrocephalus or macrocephaly, often associated with the development of jugular bulb stenosis and venous hypertension.

Ventricular drainage in VGAM should be avoided if possible. Johnston and colleagues, in a literature review, noted that of 11 shunted infants 7 died and only 1 had no deficit. In an additional group of 6 shunted children, only 2 had no deficit. In the series by Zerah and colleagues, only 1 of 17 infants had an uneventful shunting procedure. Wherever possible in this group, we advocate embolization, aiming to cure the AV shunt, and deferral of ventricular drainage wherever possible. Third ventriculostomy has been used successfully in this setting, although preferably after embolization to reduce the rate of the AV shunt.

Older children or adults sometimes present with previously undiagnosed (or untreated or partially treated) VGAM. Most present with hemorrhage, or signs of increased intracranial pressure caused by venous hypertension. Treatment is technically difficult, and has a higher complication rate than in children.

Natural history

The natural history data are not robust; the diagnosis is often never made, and the literature confuses VGAMs with other disorders. Most neonates in heart failure die untreated. Infants and children presenting with hydrocephalus have a more indolent course, but often evolve toward chronic venous ischemia resulting in developmental delay, seizures, and parenchymal hemorrhage. Adults typically present with hemorrhage or signs of increased intracranial pressure. Spontaneous thrombosis of VGAM is probably rare; in the series by Lasjaunias and colleagues, 5 out of 120 patients (4%) developed spontaneous thrombosis, with 2 neurologically normal.

Diagnosis

Antenatal diagnosis is usually by identification of an anechoic structure in the region of the cistern of the vein of Galen with demonstrable flow within it on Doppler ultrasound, although ultrasound is poor at assessing the brain parenchyma. Fetal MR imaging is useful, both to characterize the VGAM and to assess the brain parenchyma. Many neonates are not diagnosed promptly; any neonate with unexplained high-output cardiac failure should have imaging of the head to exclude a VGAM. MR imaging is optimal in this regard, because it allows both diagnosis and assessment of brain parenchyma, although CT and CT angiography (CTA) are more often used in the clinical setting. Older children and adults are best imaged by MR imaging.

However, the angioarchitecture of the lesion is best shown and appreciated by catheter angiography. Catheter angiography should only be performed as a prelude to treatment; iliac artery occlusion is common in angiography in neonates, and becomes an issue in subsequent treatment. The dominant arterial supply usually comes from the posterior choroidal arteries, although their morphology is distorted from the usual adult pattern. The pericallosal and anterior choroidal arteries also often contribute. In older children, subependymal vessels passing through the thalamus and midbrain also often contribute to the AV shunt.

Although the distinction in angioarchitecture is well described as choroidal and mural types according to Lasjaunias and colleagues, in our experience there is a spectrum ranging from a single AV shunt to innumerable arterial feeders from multiple sources. In VGAM, the dilated median vein of the prosencephalon is thought not to communicate with the deep venous system of the brain, although there are reports of thalamic hemorrhage after embolization; in this regard we have observed at least 2 cases in which we performed retrograde catheterization of the thalamic veins off the sac.

Neonates

Whether presenting antenatally, or more commonly perinatally, it is not clear when these children are best treated (see Fig. 7 ); Lasjaunias traditionally decided by a scoring system, aiming to avoid treatment of neonates wherever possible, to allow treatment when the child is larger and it is technically easier and safer. At Great Ormond Street Hospital (GOSH) for Children, our approach has changed over time, influenced by both the death of neonates and infants from heart failure while awaiting treatment, and excellent outcomes in children who were regarded as too systemically unwell to treat by other operators. Our current approach is to perform embolization on any VGAM with cardiac failure as soon as possible after delivery, provided there is no imaging evidence of severe parenchymal damage to the brain.

The initial aim of treatment is to relieve heart failure, rather than cure the malformation. Subsequent staged embolization aims for cure by 6 months. It is self-evident that the very sick children with low scores tend to have worse outcomes, but at GOSH for Children we offer treatment to even very sick children provided there is not evidence of diffuse parenchymal damage. We have seen cured patients growing up as normal children.

The first step is catheter angiography (see Fig. 2 ). We generally use a femoral approach, using a 4-Fr sheath, and a short Berenstein diagnostic catheter. Bilateral internal carotid and left vertebral high-frame-rate angiography is performed, which consumes most of the available contrast dose in a neonate, and most of the subsequent intervention is performed under fluoroscopy, with occasional microcatheter angiography.

In our practice at GOSH for Children, all neonates are treated by transarterial embolization using concentrated Histoacryl rendered radiopaque with tantalum. This technique is quick, and reliably relieves heart failure in these gravely ill children. All neonates return to the intensive care unit after embolization, and almost all need a combination of positive inotropes and vasodilators, aiming for management of pulmonary arterial hypertension, and careful control of systemic pressure. They are generally kept heavily sedated and intubated in the intensive care unit for 48 hours after embolization.

Although no clear statement can be made, the optimal target is probably around 50% reduction in cardiac output in the first stage of embolization. The fraction of cardiac output passing through the AV shunt in a VGAM has exceeded 90% in all neonates in whom we have measured, a state that is clearly incompatible with life, and for which no animal model exists. Sudden closure of a shunt of this magnitude often precipitates severe left ventricular failure, and occasionally intracranial hemorrhage. Such an abrupt physiologic alteration needs to be carefully managed; before, during and after the procedure, and requires the input of pediatric cardiology, intensive care unit specialists, anesthesia, and experienced pediatric interventional neuroradiologists.

Infants and children

Those children who are not treated in the neonatal period usually present, sometimes repeatedly, with hydrocephalus, macrocephaly, seizures, or developmental delay, probably mediated by increased intracranial venous pressure ( Fig. 3 ). The logical approach would be an attempt at reduction of intracranial venous pressure. In contrast, the optimal solution is cure of the AV shunt, although this should probably be staged, and is not always possible because by this age there are often innumerable transthalamic and transtectal arterial feeders. Cerebrospinal fluid diversion should be avoided wherever possible.

Every conceivable approach has been used for VGAM; transarterial occlusion with coils, glue, or Onyx, retrograde transvenous embolization with coils, and, in our center, retrograde embolization using glue and stent placement of stenosis of the jugular bulb. Stereotactic radiosurgery and conventional neurosurgery have also been attempted. It is not clear which of these approaches is best in any set of circumstances and hence a multidisciplinary approach is essential.

Outcomes

The poorer the state of the child at the outset of the disease process, the lower the probability of a good outcome. Our reluctance to use the rigid Lasjaunias clinical criteria for treatment stems from our personal experience. At our institution, we have seen children deemed too sick to treat by these criteria who end up normal, and children deemed too well to treat end up dead. Our approach in VGAM has evolved to mirror that in any other pediatric neurovascular disorder: a multidisciplinary decision involving pediatric neurology, neurosurgery, interventional neuroradiology, and pediatric intensive care specialists is made, taking into account the radiological state of the brain, the clinical state of the child, and the wishes of the parents. The only absolute exclusion to treatment is evidence of severe parenchymal damage to the brain (see Fig. 7 ). Severe physiologic derangement (high shunt volume, renal failure, hepatic failure, heart failure on maximal inotropes, requirement of high-frequency ventilation and so forth) makes periprocedural management more difficult, but tends to polarize outcomes into death or good outcome, provided the brain is intact at the time of embolization. Overall, neonates presenting to GOSH for Children now have around a 60% chance of being neurologically intact, 15% chance of mild disability, 10% chance of severe disability, and 15% chance of death. This probability includes many patients who would be refused treatment by conventional criteria.

Definition and cause

Pial AVFs of the brain (see Fig. 4 ) are sometimes termed single-hole AVFs and account for approximately 3.3% to 4.7% of all intracranial AVMs. They are characterized by direct connections between arteries and veins with arterial supply derived from cortical or pial arteries, and are frequently associated with large to giant venous pouches, which can occur as a solitary fistulae, but frequently are multiple, which is a characteristic finding of this entity. Most of these are situated in the supratentorial neuroparenchyma and are more common in the frontal and temporal lobes.

Natural history

The exact incidence of a pial AVF in children is not known because of its rarity. Most published papers have included this type of angioarchitecture within the overall population of the cerebral AVMs or even the VGAMs. As within most vascular anomalies in this age group, there is a male predominance and strong genetic association in pediatric cases in which there are multiple intracranial AVFs. Conditions such as HHT and encephalocraniocutaneous lipomatosis are well-recognized associations in the literature.

Presentation

Presentation is usually within the first 5 years of life with the mean age in one series at 23 months. Symptoms attributable to pial AVFs are usually the consequence of high-flow AV shunting, leading to cardiac failure, hemorrhage, macrocrania, seizures, focal neurologic deficits, edema, or mass effect from the venous varices. When presenting with hemorrhage, AVF can also be associated with false arterial or venous aneurysms; these should be vigilantly identified, because this is an indication and a focal target for treatment. Venous outflow obstruction in the form of pial venous outflow stenosis, dural sinus stenosis and thrombosis seems to be associated with hemorrhagic presentations, similar to the experience with AVMs.

Diagnosis and treatment

The diagnosis follows the imaging algorithm of pial AVM as detailed earlier using CT, CTA, MR imaging, MR angiography, and catheter angiography methods.

The goal of treatment in pial AVFs in young children, even when asymptomatic, is the rapid control of the lesion (AV shunt), because of the worse neurocognitive prognosis and mortality when managed conservatively. Surgery has been reported to be successful in a small number of cases of neonates and infants presenting with a symptomatic nongalenic AVF. However, our experience is that endovascular embolization is a safe and often curative treatment ; the technique used is identically to that described with concentrated glue and coils to occlude the fistula.

Definition and cause

These disorders are collectively rare (see Figs. 5 and 6 ) and the true incidence and prevalence are difficult to quantify accurately. We receive around 1 per year; around 10% of the neonatal VGAM caseload. DSMs are thought to be a consequence of uncontrolled development of the posterior sinuses, including transverse sinus, sigmoid sinus, and/or confluence of sinuses, rather than of embryologic nondevelopment.

Presentation

DSMs generally present in the neonatal and infancy periods, although they usually become symptomatic on the average at 5 month of age. The most frequent clinical presentation is macrocrania followed by seizures, psychomotor delay, and intracranial hemorrhage. The other clinical presentations include congestive cardiac failure, cranial bruit, facial vein dilatation, and intracranial hypertension (intracranial hypertension being associated with macrocrania).

Natural history

Anatomically there are 2 types of DSM :

• 1.
  

  DSM involving the adjacent posterior sinuses, with giant pouches and slow-flow mural AV shunting. Partial thrombosis of the sinus may occur and can also be observed in utero. The dural sinus pouch at birth communicates with the other sinuses and drains normal cerebral veins.

  
  
• 2.
  

  DSM of the jugular bulb malformation with otherwise normal sinuses that appears as a sigmoid sinus-jugular bulb diaphragm and is associated with a petromastoid-sigmoid sinus high-flow AVF, which is usually a single-hole type. DSMs usually have a benign course, remain asymptomatic for a long time, and are incidentally discovered. Their treatment by embolization is technically easy, and the outcome of most patients is complete exclusion of the shunt and favorable neurologic outcome.

Associated multiple slow-flow AV shunts are consistently shown within the dural wall of the DSM contributing to the hydrovenous restriction by venous congestion of the brain. The brain at birth has to drain solely through the diseased sinus before cavernous capture. Early and rapid spontaneous thrombosis of a DSM lake and secondary dysmaturation of the jugular outlets further compromise cerebral venous drainage and can lead to venous infarction and lethal intraparenchymal hemorrhage. Unilateral DSMs, which have lateralized from the torcular, have a more favorable outcome as 1 normal draining venous sinus is maintained. It is important to have the ipsilateral cerebral hemisphere drain via an alternate normal venous pathway, either by cavernous capture or by a persistent medial occipital sinus bypassing the thrombosed sinus into the ipsilateral jugular vein or into the contralateral sinus via the superior sagittal sinus.

Diagnosis and treatment

Diagnosis on antenatal ultrasonography or MR imaging is possible but requires recognition of the disease condition by an experienced sonographer or neuroradiologist. Following antenatal diagnosis, MR imaging of the brain should be performed to determine the location of the DSM and quantify the extent of brain damage. If the DSM is located on the midline and large, early angiography is recommended to assess the anatomy of the cerebral veins. The physiologic issues and decision making are similar to other AVSs but the techniques used are more variable.

The therapeutic options thus depend on the angioarchitecture of each individual case and the state of maturation or dysmaturation of the venous sinuses. When partial or no cavernous capture and no pial reflux are seen, there is an option of treating with heparin and embolization of the shunts with glue, in anticipation of cavernous capture to take place with minimal or no consequences for the hydrovenous equilibrium of the maturing brain. If there is a significant shunt causing pial reflux, embolization is necessary to prevent venous hypertension and cerebral ischemic damage. The goal is to reduce pial reflux by occluding the shunts while maintaining patency of the sinuses. If there is complete occlusion of a mural AVS, this will likely lead to complete sinus thrombosis, resulting in an absence of a venous outlet for the brain and leading to poor outcome.

The prognosis, and specifically the mortality, associated with dural AVSs reported in the literature are extremely high, on the order of 38% in all ages and 67% in the neonatal subgroup. However, the perception of a DSM at the torcular being lethal has not been verified by our experience. Although these lesions are difficult to manage, we have achieved outcomes broadly similar to those of VGAM. Pial AVF and infantile dural AVF have a better prognosis.

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  Cranial AV shunts key facts:

  
  
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  Divided into AVM and AVF

  
  
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  Presentation is different in adults (eg, heart failure in neonates)

  
  
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  Commonest cause of hemorrhagic stroke in children

  
  
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  Digital subtraction angiography is the gold standard method of investigation

  
  
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  High lifetime risk for significant mortality and morbidity warrants more aggressive treatment strategy