Introduction Pial arteriovenous fistulas (AVF) are vascular disorder of the brain consisting of a direct connection between arteries and veins without a nidus located in the subpial space, and are frequently associated with venous varix.
Materials and Results This study reviewed a series of 16 children with congenital pial AVF, treated between January 2005 and August 2011. All cases presented before 5 years of age and the mode of presentation varied with age. Fourteen had a single fistula while two had multiple fistulas, one among them had cutaneous features suggestive of RASA1 mutation. MRI is the preferred initial imaging, to demonstrate anatomical location, feeders, venous varix and regional, hemispheric or diffuse cerebralmalacia. Digital subtraction angiography performed during the first therapeutic attempt showed venous varix along with arterial enlargement as the most common angio-architecture. All cases were embolized with N-butyl-cyanoacrylate (NBCA) with or without coiling of the venous sac to attain flow control. Hypotension and a higher concentration of glue were used to aid controlled glue injections. Dural AVF and reactive angiogenesis are not uncommon sequlae found on follow-up angiogram. Outcomes were excellent in 75% and good in 19%.
Conclusion Congenital pial AVF are caused by a missed step in vascular development during the early embryonic stage. Transarterial endovascular embolizaiton using NBCA with or without using coils to attain flow control is the treatment of choice, with low morbidity. The efficacy of treatment is high as demonstrated by the high cure rate. Follow-up angiogram is mandatory to look for recanalization, reactive angiogenesis and denovo dural AVF development.
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Pial arteriovenous fistulas (AVF) are a rare vascular disorder of the brain. Once thought to be a type of arteriovenous malformation (AVM), they are now recognized as a distinct vascular anomaly1 consisting of a direct connection between arteries and veins without a nidus in the subpial space.2 AVF can occur anywhere in the brain, with preference for a supratentorial location,3 and are frequently associated with venous varix. Most are congenital, but may be traumatic or iatrogenic and are treated by endovascular embolization, surgery or a combination of embolization and surgery.
We reviewed our series of children with congenital pial AVF, focusing on embryological aspects, their clinical features, angio-architecture, treatment indications, management options, with emphasis on the role of endovascular management and their outcome.
Materials and methods
We retrospectively analyzed cases of congenital pial AVF treated at our center between January 2005 and August 2011. Only cases with true pial AVF were included. All fistulas that formed part of AVM, choroidal fistulas of vein of Galen malformations and post-traumatic or post-surgical AVF were excluded. In all, we reviewed 16 cases and gathered information from the clinical case records, imaging by CT scan and MRI on presentation and during follow-up, angiographic images and records during each of the procedures and during follow-up. We recorded the patient demographics, their clinical presentation, the timing of the procedure, MRI characteristics, angio-architecture, management details, follow-up angiographic changes, their management and outcome. The results were compared with data previously published in the literature and have discussed in detail the embryology behind development and various other aspects including management options associated with congenital pial AVF.
In total, we had 16 cases between 2005 and 2011, detected from as early as the antenatal period to 5 years of age. Eight out of 16 cases (50%) presented before the first birthday. The management was timed based on the urgency of clinical presentation. It commenced between the neonatal period to 5 years of age. The mean time interval between diagnosis and treatment ranged from immediate management to 12 months, with a mean of 2.9 months. The presentation varied with the age. Eighty per cent (four of five) neonates presented with congestive heart failure. Most infants presented with ventriculomegaly or macrocephaly with or without developmental delay possibly secondary to increased intracranial venous congestion. As they grew out of infancy they commonly presented with seizures and rarely with a focal neurological deficit (table 1). Hemorrhagic presentation was seen in two cases.
Of the 16 cases, there were seven male and nine female children. In 75% of cases fistulas were located in the supratentorial location, with seven on the lateral surface and five on the medial surface of the cerebral hemisphere. The location did have an influence on the venous drainage of the fistulas, with all medial fistulas draining exclusively into the deep venous system except one fistula that had associated cortical venous drainage. The lateral fistulas drained through cortical veins in all cases, with associated drainage into the deep venous system in three cases. Cortical vein reflux from sinus due to high flow was detected in seven cases (44%) and developed subsequently in one case due to secondary sinus occlusion. Fifteen of our cases (94%) had venous varix with size ranging from 14 mm to 70 mm. Stenosis of the veins was detected in only four cases (25%). Thrombosis was detected in venous varix in pre-procedure MRI in one case. The associated non-communication between transverse sinus and jugular vein possibly due to jugular bulb dysmaturation was detected in four cases (25%) and was bilateral in one. Three cases developed transverse sigmoid sinus occlusion during the course of the treatment. None of our cases had arterial stenosis, while two cases had aneurysm of the feeding artery (12%).
Most cases (80%) had a single location of the fistula. At each fistulous location, the fistula was organized to have multiple feeding arteries with multiple holes in 12 cases (75%) while four cases had single vessel–single hole fistula. In all we embolized 83 feeders in 16 cases. On excluding the single hole fistulas and the cases with multiple fistulas, the average number of feeders in each fistulous location was 4.3. One of our patients had a family history of AVM and cutaneous features suggestive of capillary malformation–AVM due to RASA1 mutation but had no systemic AVF. No patient had features suggestive of hereditary hemorrhagic telengiectasia.
We managed all our cases with N-butyl-cyanoacrylate (NBCA) embolization and used coils in 10 cases (63%) to reduce flow before NBCA embolization. In no instances were coils alone used to close the feeders. In 72% of fistulas we used NBCA with a concentration of 50–90%, while in 28% we used more dilute NBCA. We used flow-guided coils (Berenstein liquid coils; Boston Scientific, Freemont, California, USA) in five cases and other detachable coils in six cases.
Following treatment, four cases developed denovo dural arteriovenous fistula (25%) and will be reported in a separate report; while reactive angiogenesis in the vicinity of the treated fistula was seen in six cases (37%). One case developed ventricular dilatation and needed cerebrospinal fluid diversion. Two of our cases had transverse sigmoid sinus occlusion, in one it was bilateral. One neonate presenting with severe congestive heart failure, following embolization developed subarachnoid hemorrhage and subsequently died. We followed 87% of our patients with MRI and digital subtraction angiography with periods ranging from 1 day to 18 months post-treatment. We defined the outcome as excellent (12/16 or 75%) when there was no residual shunt and no additional neurological deficit, good (3/16 or 19%) when there was minimal residual shunting with no additional neurological deficit and all others were considered poor outcome (1/16 or 6%).
Pial AVF are rare vascular disorders of the brain. The reported incidence in literature varies: 3% (13 of 500 AVM) in one4 to 4.8% (12 of 251 AVM) in another series,5 and 7.3% (11 of 151 AVM) in a series from our institution.6 From 1977 to 2009, only 112 cases have been reported in 43 reports with different management options, such as endovascular embolization, surgical disconnection, surgical excision of AVF with or without varix, a combination of embolization with surgical disconnection and radiosurgery of a few selected cases.7 None of the reports has discussed the embryology of the development of such fistula.
The development of the vasculature of the brain is complex. The extraordinary work of Padget8 has advanced our understanding. The venous system of the brain is the earliest vascular system to develop, with large venous channels developing first, with smaller primitive venous channels developing in the 11–14 mm stage, and definitive arteries branching from the circle of Wills become recognizable later. During the 20 mm stage the pial arteries and veins are mere endothelial tubes crossing each other at various angles. The more acute the angle, the surface area of crossing between the endothelial tubes is maximized and the chance of the development of arteriovenous shunt is high.8 Embryologically, a fistula is a likely explanation of abnormally dilated capillary nets that shunt blood from developing arteries to veins. Such fistulas are common in transient stages during development, they regress with the development of the proper capillary network and with vessel wall maturity. In congenital pial fistulas, we hypothesize that the fistulous connection of the dilated capillary nets that develop at this early stage of vascular development randomly persisted with the failure of the structured and more mature capillary network to develop. This is supported by evidence that in a rare genetic disorder, hereditary hemorrhagic telengiectasia, endoglin an auxiliary receptor for transforming growth factor β normally required for proper vascular development and maintenance is defective,9 resulting in normal in-situ differentiation of endothelial cells with subsequent failure to remodel into a more mature vascular network,10 ,11 and in this disorder multiple pial AVF are a characteristic feature. The antenatal diagnosis in some cases and the persistence of falcine sinus in fistulas draining through the vein of Galen support the theory that they are formed early during development.
Single fistulas may be single hole with one arterial feeder or have multiple feeders feeding through adjacent holes drained by a single venous channel. Multiple fistulas are anatomically distant and harbor a distinctly separate vein draining each fistula.2 Two of our patients had multiple fistulas. Congenital pial AVF are most often diagnosed during the first 5 years of life,12 approximately 50% of our cases presented before the first birthday and the oldest was diagnosed at 5 years of age. The presentation includes hydrocephalus, developmental delay, enlarged head circumference, cranial bruit, cardiac failure, hemorrhage, seizures, while headaches and neurological deficits are the clinical manifestations in older children.3–5 ,12 ,13 Four of our five neonates presented with cardiac failure. Two among them warranted immediate endovascular management, while the rest were medically managed giving time for infants to mature before elective treatment. During infancy our patients presented with ventriculomegaly, macrocephaly with or without developmental delay secondary to venous hypertension, while older children commonly presented with seizures and focal neurological deficit. We had two hemorrhagic presentations (table 1).
One patient had a family history of AVM and pinkish red multiple cutaneous capillary malformation of varying sizes involving the trunk suggestive of RASA1 mutation causing capillary malformation–AVM. It is an autosomal dominant disorder with high penetrance having macrofistulous AVM in the brain, face and limbs presenting at birth or during infancy.14 The other congenital disorders associated with pial AVF are hereditary hemorrhagic telangiectasia and phosphatase and tensin homolog hamartomatous tumor syndrome, these also have associated systemic involvement of the high flow vascular malformations.14
Non-invasive imaging by ultrasound or MRI may establish the diagnosis. MRI is the preferred initial imaging, to demonstrate the anatomical location, possible feeders, presence of venous varix with or without clots and to show evidence of regional, hemispheric, or diffuse cerebralmalacia. The natural history with diffuse cerebralmalacia is extremely poor as they are irreversible, despite curative treatment, and so are considered a contraindication to active treatment.2 Fatima et al 15 have shown, in a case of pial AVF, a new technique called time-resolved contrast-enhanced magnetic resonance digital subtraction angiography to be of greater clinical significance in diagnosis and treatment planning.
Digital subtraction angiography is performed as a part of the first embolization session.2 Venous ectasia along with arterial enlargement was the most commonly noted angio-architectural change of AVF. Most of the arteries feeding the pial AVF open into a single ectatic draining vein frequently associated with large to giant venous varix, and their presence is determined by the high flow across the shunt against venous outflow obstruction. Weon et al 12 have observed large or giant venous pouches in up to 88% of cases and associated stenosis in 42%. In our series, 94% had venous varix ranging from 14 mm to 70 mm, with associated venous stenosis in 25%. From a review of the literature, Yang et al 7 ascertained that patients presenting at younger ages (<15 years old) had varix in angiographic study compared with the adult group, and the absence of varix did have significant correlation with hemorrhage. We had just four cases with possible jugular bulb dysmaturation (25%) similar to the observation of Weon et al 12 who postulated that dominant drainage of these supratentorial AVF into the superior sagittal sinus or transverse sinus sparing the straight sinus may not oppose the regression of the medial occipital sinus and maturation of the jugular bulbs.
The goal of treatment in cortical AVF in young children, even when asymptomatic, is rapid control of the shunt, because of high mortality and worse neurocognitive prognosis when managed conservatively.2 ,4 Successful obliteration can be achieved by endovascular embolization or by surgery. Over the past two decades, improvements in microcatheters, guidewires, increased endovascular experience leading to evolution of techniques and the less invasive nature of the procedure have made endovascular treatment the preferred treatment modality, with surgery reserved for a few selected cases. Review of the literature from 1977 to 2009 has revealed an obliteration rate of 86.5% (32 patients) for endovascular treatment, but comparatively surgical treatment offered a higher obliteration rate (total obliteration rate 96.8% in 30 patients).7 We should take into consideration that surgical treatment was offered only to selected superficial fistulas while the rest were treated by endovascular means.
Endovascular treatment by the transarterial approach is performed by percutaneous femoral puncture under general anesthesia. Embolic agents such as NBCA, coils, Onyx 34 have been used for the successful occlusion of the fistula.16 Endovascular management is challenged by the large size of the afferent and efferent vessels, associated with very high flow through the fistula. Techniques have evolved to counter these such as the use of tandom balloon,17 balloon-assisted NBCA embolization.18 ,19 We treated all our cases with NBCA (100%) (figure 1) and used coils to assist glue embolization by reducing the flow through the high flow fistulas in 63% (figure 2 and 4). Our strategy is to place coils in the venous pouch that are located close to the fistula and draining only the fistula to attain flow control, along with systemic hypotension during NBCA injection and using variable concentrations of NBCA to modify the polymerization time. Alternatively, oversized coils can be placed in the feeding artery to reduce flow. In one of our cases, flow-guided coils (Berenstein liquid coils; Boston Scientific) were used in a feeding artery dysplastic aneurysm just proximal to the fistula to reorient vascular supply safely and effectively as distal cortical vessels were arising from the dysplastic pouch (figure 3).
Unfavorable angiographic features include drainage of the normal vein into the venous varix, multiple enpassage feeders draining into the fistula and normal cortical vessels arising close to the fistula.3 These features do not necessarily mean a contraindication for embolizaiton. They necessitate modification of the technique to embolize the fistulous location precisely and if necessary to consider surgical disconnection. Proper analysis of the angio-architecture and decision on the choice and sequence of the embolic materials will determine the outcome.
We had one death due to subarachnoid hemorrhage, following the procedure in a neonate with severe congenital heart failure, which represents the only bad outcome of the series, while another case needed cerebrospinal fluid diversion due to ventricular enlargement. Interesting sequelae include the development of transverse sigmoid sinus occlusion post-embolization in two cases presenting acutely with signs of venous hypertension that subsequently resolved. Dural AVF developed de novo in four of 16 (25%) cases post-embolization, detected during follow-up, who were treated by embolization (table 2). Reactive angiogenesis developed in six of 16 (37%) in the vicinity of the thrombosed venous sac. We treated two with NBCA embolization (figure 4), and left four untreated due to a high risk of occlusion of the cortical supply. Two among them resolved spontaneously and two persisted without clinical manifestation. Overall we had excellent outcomes in 75%, good outcomes in 19% and poor outcomes in 6% (table 2).
Hemodynamic derangements after occlusion of high flow lesions, resulting in a clinical phenomenon called the normal perfusion pressure barrier breakthrough (NPPB), is controversial. Although there have been no reported instances with the use of cerebral blood flow techniques to document this phenomenon after treatment of intracranial fistulas, several series have reported clinical evidence that NPPB can occur.20 ,21 Giller et al 22 used single photon emission CT and transcranial Doppler studies during balloon test occlusion, and after single stage occlusion, the lack of development of significant hyperemia allowed consideration of treatment plans involving acute fistula occlusion without the difficulty imposed by gradual occlusion. We have not seen any case of NPPB, and believe that the clinical phenomenon most likely occurs due to abrupt venous or sinus thrombosis. We advocate the use of staged embolization (10/16) followed by post-procedure heparinization to prevent excess thrombosis on the venous side to avoid this complication.
The microsurgical disconnection of the fistulous malformation was popular in the pre-endovascular era. Surgery may now be considered in very few cases with unfavorable morphology for endovascular embolization. Surgical management is more invasive, and it is difficult to localize the fistula as there are no nidus and the veins are arterialized. Deep-seated fistulas and fistulas over the eloquent cortex are unfavorable for surgical treatment.
The role of radiotherapy is even more limited. Weon and coworkers12 in 2004 have reported a pial AVF with post-embolization thrombosis of the pouch, which promoted in-situ angiogenesis for which adjuvant radiotherapy was performed with good outcome.
We followed 87% of our patients with both MRI and cerebral angiogram. The follow-up period varied from 1 day to 18 months, but in most cases it was between 6 and 12 months. In the absence of new findings, MRI was used as a benchmark for future follow-up. At follow-up we were able to find either recanalization, reactive angiogenesis with reopening of the shunt and de-novo dural AVF in 38% of followed cases that required renewed treatment.
Congenital pial AVF is a rare disease caused by a missed step in vascular development during the early embryonic stage. We hypothesize it to be the persistence of the primitive capillary nets that are common during vasculogenesis. Earlier, if possible preventive treatment is warranted in view of the early onset of symptoms and signs and the vulnerability of the brain at that age. In our experience, transarterial endovascular embolization using NBCA with or without using coils on the venous side to attain flow control is the treatment of choice with low morbidity. The efficacy of the treatment is high as demonstrated by the high cure rate. Follow-up is mandatory to look for recanalization, reactive angiogenesis with shunt and de-novo dural AVF development, as they can be effectively treated in most instances.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
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