Intracranial non-galenic pial arteriovenous fistula: A review of the literature

Abstract

An intracranial non-galenic pial arteriovenous fistula (NGPAVF) is a direct connection between the intracranial artery and vein without a nidus. NGPAVFs are clinically rare, and the current understanding of NGPAVFs is limited. This study searched PubMed for the currently available literature, and a review of the relevant publications revealed that NGPAVFs require aggressive treatment, spontaneous occlusion is uncommon, and the prognosis following conservative treatment is poor. NGPAVFs can be divided into congenital and traumatic (including iatrogenic) types. Clinically, NGPAVFs are characterized by congestive heart failure, epilepsy, hemorrhage, mass effects, and nerve function deficits. For the imaging examination of NGPAVFs, digital subtraction angiography (DSA) is still the gold standard for diagnosis, although magnetic resonance DSA (MRDSA) and 4D computed tomography angiography (CTA) can also provide hemodynamic data in a non-invasive manner. Current treatments for NGPAVFs include surgical resection and endovascular embolization, both of which can yield clinical improvements. However, potential postoperative complications should be addressed, such as fatal bleeding due to rupture and deep vein thrombosis. Some studies recommend postoperative anticoagulation to reduce postoperative thrombotic complications.

Introduction

Intracranial non-galenic pial arteriovenous fistula (NGPAVF) is a relatively rare clinical manifestation and has only recently been recognized as a distinct pathological entity. It was once considered to be a type of arteriovenous malformation (AVM) and was previously called fistulous AVM or intra-axial, intradural, cerebral, and pial arteriovenous fistula or shunt. The term PAVF is currently preferred.^1,2 NGPAVFs are located in the subpial space and consist of high-flow direct connections between pial arterial feeders and a large vein or venous varix with the absence of a nidus. Feeding arteries can have one or more arterial pedicles, and the drainage vein is a single draining vein that may be expanded.³ By definition, NGAVFs are Borden class III AVFs because the feeding arteries are directly connected to cortical veins without drainage through the dural sinus or meningeal veins.⁴

NGPAVFs can occur in any location in the brain tissue, but they are most commonly found in the supratentorial regions. They may occur at rare sites, such as the Rosenthal PAVF of the anterior choroidal artery and the basal vein at the base of the skull.⁵ Most NGAVFs are considered to be congenital in nature and usually present in childhood or early adulthood; some even remain undetected until later in life. However, NGAVFs can also be acquired. Congenital and acquired NGAVFs differ in some aspects but are similar in their anatomic and hemodynamic characteristics. Therefore, they are discussed together in this study.

This study excluded intracranial galenic PAVF, a type of high-flow direct intracranial fistula involving the persistent embryonic median prosencephalic vein with aneurysmal dilatation of the galenic vein. Intracranial galenic PAVFs located in the subarachnoid space are more commonly seen in children.⁶ Therefore, this study did not explore this type of disease. Because NGPAVFs are rare, it is difficult to study their etiology, clinical manifestations, and imaging features. Strategies for their treatment are often complex due to this lack of understanding. Therefore, this study reviewed the currently available literature on intracranial pial arteriovenous fistula or shunt to summarize the current knowledge base on NGPAVF pathology and treatment.

Pathogenesis

The causes of NGPAVFs are not fully clear at present, but NGPAVFs can generally be divided into congenital and acquired. The causes of NGPAVFs in infants, children, and young patients are more often congenital, whereas NGPAVs in adults are usually acquired traumatically or iatrogenically.

Congenital causes

In the earliest stages of embryonic vascular development, shunts between arteries and veins are common in the transient stages during vascular genesis, but they regress with the development of a capillary network and maturation of the vessel walls. If there are fistulous connections between pial arteries and veins, PAVFs occur; in addition, abnormal angiogenesis and associated vascular growth factors and cytokines may play a role.⁷ Congenital NGAVFs mainly occur in childhood. For instance, Paramasivam et al. in 2013 reported 16 children under 5 years of age with pial AVF; these NGPAVFs were considered congenital. However, some congenital NGAVFs remain undetected until adulthood.⁸

NGPAVFs may accompany other congenital diseases, the most common of which is Rendu–Osler–Weber syndrome; approximately one-quarter of NGPAVF cases in children co-present with this syndrome.^9–14 In addition, associations with the rare Klippel–Trenaunay–Weber syndrome have been reported.^15,16 A study found that there is a high incidence of RASA1 mutations in children with NGPAVFs.¹⁷ One report described an association with encephalocraniocutaneous lipomatosis syndrome.¹⁸ These findings support the hypothesis that NGPAVF is congenital.

Traumatic and iatrogenic PAVF

Trauma can cause PAVFs, especially when the blood vessels of the cerebral cortex are damaged and communications form between the vessels. For instance, Nomura et al. in 2015 reported a case of a 61-year-old man with a brain contusion and laceration as well as traumatic subarachnoid hemorrhage. The patient’s symptoms were aggravated after 7 days, and digital subtraction angiography (DSA) revealed an NGPAVF in the injured brain region with peripheral edema.¹⁹

Surgical trauma can also cause NGPAVFs; these NGPAVFs are most commonly located on the brain surface. For instance, Schuette et al. reported one case of hydrocephalus caused by a ruptured aneurysm in 2012. After placing a ventriculostomy catheter for hydrocephalus, DSA revealed a PAVF at the site of the bur hole; the PAVF was surgically removed.²⁰ Even routine craniotomy can lead to the occurrence of PAVFs; for instance, Nishiyama et al. also reported one case of a surgically induced PAVF caused by dural tenting. In that case, a needle penetrated the blood vessels in the brain and caused a PAVF, which was detected during the review and clipped to avoid rupture and hemorrhage. This type of iatrogenic PAVF often has a single smaller fistula orifice, which makes it easier to treat and yields good curative outcomes.²¹

Iatrogenic PAVF can also occur after revascularization; for instance, Feroze et al. in 2015 reported one patient with moyamoya disease in whom a PAVF occurred after bypass. The PAVF at the anastomotic orifice was found after 6 months, and there was a close association with cortical veins near the bypass graft, suggesting the potential for fistula formation within the operative bed. The development of leptomeningeal collaterals may have created venous connections leading to fistulization in a pressurized state.²² In addition, radiotherapy can also lead to PAVF. In 2008, Saito et al. reported a case of multiple pial AVFs in an adult in whom lesions developed after radiosurgical treatment of dural AVFs.²³

Cerebral vein thrombosis

Intracranial venous sinus thrombosis may cause dural arteriovenous fistulas (DAVF) as a result of the reconstruction of blood flow after venous sinus occlusion.^24,25 Venous sinus thrombosis can simultaneously lead to DAVFs and PAVFs, suggesting that they have the same pathogenesis.^26–28 In some cases, DAVFs and PAVFs appear at the same time, but the causes remain unclear.⁹ Simple cortical vein thrombosis can also induce PAVFs. In 1999, Phatouros et al. reported one case in which cerebral cortical vein thrombosis led to an acquired PAVF.²⁹

Unknown reasons

The causes of some PAVFs are still unclear. In 2015, Lo Presti et al. reported a 15-year-old boy with sickle cell disease-related moyamoya syndrome. The boy exhibited a PAVF in the sylvian fissure 8 months after STA-MCA bypass, accompanied by a varix. The cause of the NGPAVF in this case remained unclear; it may have been related to sickle cell disease because sickle cell disease can induce intracranial artery injury.³⁰

Natural history

At present, the natural history and risk of bleeding associated with NGPAVFs have not been thoroughly documented. However, the natural history of NGPAVFs is unfavorable, especially in children and patients with multiple feeding arteries; if untreated, PAVFs with high blood flow can lead to serious consequences, and researchers believe that the mortality rate after conservative treatment can reach as high as 63%.³¹ NGPAVFs can quickly damage the brain tissue surrounding the fistula orifice, resulting in subependymal or cortical atrophy, white matter calcification, and delayed myelinization. Therefore, early intervention is essential for optimal neurological and cognitive development.³²

Moreover, adult PAVF can cause high-flow occlusive venopathy in a major sinus within a relatively short time period, resulting in the onset of symptoms.³³ Aggressive treatment is recommended for these types of PAVFs. Some NGPAVFs achieve good results after conservative treatment, while some result in occlusion. In 1992, Iizuka et al. reported two cases in which spontaneous thrombosis occurred in multiple AVFs after conservative treatment.⁹ If AVFs are small and the blood flow is low, spontaneous occlusion is possible; even without thrombosis, aggressive treatment is still needed.³⁴

Angioarchitecture

NGPAVF has a complex configuration and consists of a feeding artery, a fistula, and a draining vein. The supply artery has one or more pedicles, the fistula may be a single hole or multiple arterial connections, and the blood flow may be high or low. However, drainage occurs through a single vein and is often accompanied by expansion.

Feeding arteries

Due to the long-term high velocity of blood flow, arteries that feed NGPAVF often exhibit compensatory expansion and even aneurysm with hemodynamic properties in a mechanism similar to that of AVM with aneurysm of the feeding arteries.³⁵ For instance, in 2014, Cai et al. described PAVFs with multiple aneurysms in the feeding arteries due to hemodynamic stress.³⁶

Drainage veins

NGPAVFs are most commonly located in the subpial space. Drainage veins must travel a very long distance before reaching the intracranial venous sinus. Under long-term increased pressure and high turbulence, drainage veins often exhibit varicosis, the formation of a venous varix, and space-occupying effects.^37,38 For instance, Yang et al. reviewed the literature in 2011 and found that varices were present in 77.1% of patients, most commonly in pediatric patients, and that the absence of a varix was significantly correlated with hemorrhage.³⁹ Even drainage veins have multiple varices.⁴⁰ In addition to the increase in circuitry and expansion of the drainage veins, adult NGPAVFs can cause high-flow occlusive venopathy in a major sinus within a relatively short time period, and stenosis or obstruction of venous drainage systems can cause venous hypertension.³³

Fistula characteristics

The fistula orifice of an NGPAVF can appear as a single hole or as multiple holes, and its distribution exhibits certain characteristics. For instance, in 2015, Lin et al. found that the average age of patients with single-hole fistulas was lower than the average age of patients with multi-hole fistulas; it was speculated that multi-hole NGAVFs in adults begin with a dominant single arterial supply and recruit collateral feeders to the fistula over time, whereas multi-hole NGAVFs in children originate with multiple dominant arterial feeders and therefore are common in neonates and infants.⁴¹ The nature of the fistula is associated with clinical manifestations. Multi-hole NGAVFs are more likely to present in neonates with congestive heart failure; single-hole NGAVFs predominate in older children presenting with seizures, hemorrhage, or focal neurologic deficits.⁴²

NGPAVF classification

There is currently no specific classification of intracranial NGPAVF. According to the anatomic and hemodynamic characteristics of PAVFs, the classification of three types of spinal intradural AVFs proposed by Bao and Ling in 1997 could be referenced and applied to intracranial classification: type I represents a low-flow fistula without arterial or venous dilatation; type II represents a high-flow fistula with dilatation of the feeding artery and draining vein; and type III represents a high-flow lesion with multiple feeding arteries and draining veins.⁴³ However, this classification system has not been widely accepted or applied, so a better classification method is still needed.

Other studies have produced similar results. The literature not listed in this section is presented in Table 1.^{8,13,37,44,45}

Table 1.

Reviewed literature not listed in the paper.

Year	Author	Section	Research content
1987	Viñuela44	Angioarchitecture	The authors reported eight cases of intracranial high-flow AVFs accompanied by giant varices and resulting in intracranial mass effects.
1996	Coubes11	Treatment	The authors reported one case of a large NGPAVF in the posterior fossa and adopted double micro-catheters to inject NBCA; total occlusion was obtained without distal migration.
2004	Wang65	Clinical manifestations	One case of NGPAVF in the cerebellopontine angle characterized by hydrocephalus was reported.
2005	Gupta66	Clinical manifestations	The authors reported one case with NGPAVF before the brainstem characterized by hydrocephalus.
2005	Weon13	Angioarchitecture	The authors found venous ectasia in 87.8% of patients and pial venous stenosis in 41.5%. Drainage veins exhibited not only expansion but also stenosis.
		Clinical manifestations	Among 41 children with 63 supratentorial PAVFs, the most common clinical symptom was cardiac insufficiency (31.7%), followed by epilepsy (24.4%) and macrocrania (14.6%).
2006	Passacantilli45	Angioarchitecture	The authors reported a PAVF fed by the posterior inferior cerebellar artery (PICA) with a blood flow-related aneurysm, which was clipped.
2008	Kakino56	Treatment	Temporal epilepsy was induced by the mass effects of the varix of drainage veins and edema of the surrounding area. Considering that the varix was actively growing, the PAVF orifice and varix were removed together.
2009	Lv51	Treatment	The authors used Onyx 34 to treat embolism in three cases of PAVFs and achieved good results.
2011	Yang39	Clinical manifestations	The authors performed a statistical analysis of 83 cases of AVFs from 1977 to 2009 in patients ranging in age from 12 weeks to 65 years (mean age 20.2 years) with equal gender representation.
		Treatment	The study revealed an obliteration rate of 86.5% for endovascular treatment, but surgical treatment yielded a higher obliteration rate of 96.8%.
2011	Hoh63	Clinical manifestations	The authors reported nine cases of NGPAVFs that were characterized by epilepsy, including seven adults with intracranial hemorrhage and one 10-year-old girl.
2011	Guimaraens91	Treatment	One NGPAVF in the posterior fossa was treated. Coils were released in the feeding arteries to reduce flow and facilitate migration of the glue from the venous side; NBCA was safely injected to achieve complete occlusion of the fistula.
2012	Sugiyama14	Treatment	The authors reported one case of hereditary hemorrhagic telangiectasia with NGPAVF accompanied by a large calcified varix. Direct disconnection of surgical flow was performed followed by removal of the varices.
2013	Paramasivam8	Angioarchitecture	The authors found that of 16 children with congenital pial AVF, 14 had a single fistula, and two had multiple fistulas.
2013	Madsen7	Treatment	The authors reported five cases of pediatric NGPAVFs, of which three cases were treated with coils combined with NBCA due to the higher flow rate.
2015	da Silva37	Angioarchitecture	The authors reported one case of NGAVF with multiple aneurysms in the feeding arteries; the blood flow of the feeding arteries decreased when the aneurysms disappeared after treatment of the NGPAVF.
2015	Requejo64	Clinical manifestations	The authors reported 10 cases of NGPAVFs in children, including two PAVF cases with intracerebral hemorrhage, three NGPAVF cases characterized by epilepsy, and one case that exhibited hydrocephalus in the frontal PAVF.
		Treatment	Of 10 cases of PAVFs, two cases were treated by both coils and NBCA.

Clinical manifestations

NGPAVFs can present at all ages. Cases in children are most often congenital, whereas adult cases are more often traumatic and iatrogenic. However, NGPAVFs are very rare in the elderly.⁴⁶ Clinical manifestations of NGPAVF mainly originate from the steal phenomenon due to high-velocity arteriovenous shunt, the rupture of a fistula orifice, venous hypertension, and the mass effects of the expanded varix.^39,47 However, the clinical manifestations are not the same in children and adults.⁴⁴ In neonates and infants, high-velocity blood flow increases the risk of heart failure, hemorrhage, seizure, bruit, skull erosion, and macrocephaly. However, exceptions to this rule exist; some infants show hemorrhage.⁴⁸ Adults are more likely to exhibit hemorrhage and mass effect or cerebral ischemia due to the steal phenomenon.³⁹

Cardiac decompensation

The excessive physiological stress produced by high blood flow in the PAVF can result in cardiac failure at a young age, especially in neonates and infants.^44,49 The incidence of cardiac symptoms varies among different age groups; the incidence of systemic cardiac manifestations is 54% in neonates, whereas the incidence of cardiac manifestations is reduced by 16% in infants.⁵⁰

Intracerebral hemorrhage

The fistula orifice of an NGPAVF is relatively weak, and long-term high-velocity blood flow increases the risk of rupture and hemorrhage. However, unlike AVM, only a relatively small proportion of PAVFs show bleeding symptoms.^11,41 Bleeding is more often seen in adults and older children. For instance, in 2009, Lv et al. studied 16 cases of PAVFs and found six cases of intracranial hemorrhage.⁵¹ Hemorrhage is more often seen in large-scale NGPAVF, but smaller PAVFs can also result in rupture and hemorrhage.³¹ Intracerebral hemorrhage can also be characterized by extensive subarachnoid hemorrhage,⁵² subdural hematoma,¹ and ventricular hemorrhage.⁴⁸ Hemorrhage may even induce severe cerebrovascular spasm.⁵³

Epileptic seizure

Epilepsy is not rare in patients with NGPAVFs. For instance, in 2013, Madsen et al. described five children with NGPAVFs, including three cases with epileptic seizures.⁷ Epilepsy was even reported as the primary symptom in a 7-month-old baby.⁵⁰ NGPAVFs elicit seizures via a mechanism similar to that of AVM; the mechanism may be associated with the steal caused by the high-velocity blood flow of PAVFs. This blood flow may cause neurons in the cerebral cortex to remain in an excited state due to ischemia, increasing the risk of seizures. In addition, the space-occupying effects of NGPAVFs can cause epilepsy.^54,55 Brain edema in the area surrounding the varix may also cause seizures.⁵⁶

Focal neurologic deficits

The focal neurological deficits of NGPAVFs can have many causes and result in corresponding clinical symptoms.³⁷ The steal phenomenon due to high-velocity PAVFs causes arterial ischemia in the adjacent brain area, with symptoms similar to transient ischemic attack.⁵⁷ In addition, single-channel AVFs limit venous drainage, which presumably causes venous hypertension, thus leading to brain edema and neurological symptoms.^46,58 The occurrence of cerebral edema is similar to that of the venous congestive myelopathy of spinal AVF.^46,59,60 In 2013, Gupta et al. reported a case of NGPAVF characterized by bilateral thalamic congestion. It was speculated that the stagnation and increase of pressure in the deep venous system led to congestion in the thalami.⁶¹ Furthermore, the mass effects of NGPAVF can also oppress the surrounding brain tissue and produce focal neurological deficits. Mass effects will be discussed in the next section.

Mass effect

The mass effects of NGPAVFs mainly originate from the varix. Large varices can lead to increased intracranial pressure.³⁷ The mass effects of NGPAVFs will undoubtedly increase the difficulty of treatment, especially when calcification is present. In 2008, Tabatabai et al. reported one case with giant parietal NGPAVF, which was successfully removed, although the surgery was very difficult.⁶² In addition, in 2015, da Silva et al. reported one case of NGPAVF in which variceal dilatation caused a significant mass effect due to its very stiff and thick walls. The variceal dilatation was resected due to this mass effect.³⁷

Hydrocephalus and ventriculomegaly

Hydrocephalus associated with NGPAVFs is mainly correlated with varices; it compresses adjacent structures and impairs the cerebrospinal fluid pathway. Other factors may contribute to hydrocephalus in NGPAVFs. For example, increased venous pressure resulting from the AVF is exerted at the dural sinus level and compromises the ability to absorb cerebrospinal fluid. For instance, in 1987, Vinuela et al. reported eight cases of giant intracranial varices secondary to high-flow AVF, including three cases accompanied by hydrocephalus.⁴⁴ In addition, children with serious blood steal may develop ventriculomegaly, which is similar to hydrocephalus, after parenchymal, subcortical, and subependymal atrophy.¹¹

Other studies have produced similar results. The literature not listed in this section is presented in Table 1.^{13,39,63–66}

Imaging characteristics

NGPAVFs have definitive imaging characteristics on DSA, which is the gold standard for diagnosis. On DSA, NGPAVFs show the connection of feeding arteries and drainage veins without a nidus, and hemodynamics can be assessed. Similar changes are also visible by computed tomography angiography (CTA), and high-resolution magnetic resonance angiography (MRA). CT and magnetic resonance imaging (MRI) are preliminarily carried out for the inspection of NGPAVF. They may reveal many abnormal images of small feeding arteries, but it is difficult to determine the origin. Specific characteristics are occasionally difficult to identify on AVM.

DSA

DSA is the gold standard for the diagnosis of NGPAVFs. The diagnostic criteria on DSA for AVFs include: (a) rapid circulation time due to the high-velocity flow; (b) an enlarged feeding artery; and (c) direct filling of a large varix.⁶⁷ Anatomic and dynamic changes of AVFs such as the presence/absence of expansion of the feeding artery or aneurysm, single-hole, multi-hole, or plexiform AVFs, and the presence/absence of varicose veins or stenosis of the drainage veins can be dynamically observed.

CT and MRI

It is very difficult to diagnose NGPAVFs simply by CT, but they are characterized by expansion of the drainage vein and homogeneous contrast enhancement, which can be seen when directly imaging NGPAVFs. In addition, CT can be used to detect indirect signs of NGPAVFs, including cerebral hemorrhage, hydrocephalus, encephalatrophy, and hydrocephalus.⁵⁸ MRI can be used in further auxiliary examination after NGPAVFs are detected by CT. The anatomic location, feeders, venous varix and regional, hemispheric, or diffuse cerebral malacia can be found on MRI, but no flow-empty actions are formed by a nidus.⁶⁵

MRA and CTA

These two types of examinations can clearly display feeding arteries and veins of NGPAVF, but they still cannot be compared with DSA, mainly because MRA and CTA both generate static images and are unable to record the hemodynamic characteristics of NGPAVFs. However, time-resolved contrast-enhanced magnetic resonance digital subtraction angiography (MRDSA) can effectively overcome these obstacles in evaluating NGPAVFs. Characteristics of DSA can be simulated by observing the hemodynamic characteristics at different time phases to observe the feeding arteries and drainage veins of PAVFs.⁶⁸ Multiple studies have reported that MRDSA is valuable in the evaluation of intracranial AVMs and dural AVFs, and it is a relatively mature technology. After NGPAVFs are identified, this strategy may facilitate the diagnosis of PAVFs.^69,70 Similar to MRDSA, 4D-CTA can also be used to dynamically observe AVFs. In 2011, Willems et al. evaluated intracranial DAVFs with 4D-CTA.⁷¹ Yamaguchi et al. evaluated spinal AVF with 4D-CTA in 2013.⁷² Therefore, 4D-CTA should have a broad application for studying NGPAVFs in the future.

Ultrasonography

This technique is suitable for prenatal diagnosis. In 2005, Garel et al. reported three cases of AVFs with prenatal ultrasonography, including two cases of NGAVFs.⁷³

Treatments

A thorough interruption of blood flow is the key to NGPAVF treatment, and sometimes it is not necessary to remove the entire lesion.³ The blood flow of the feeding artery must be reduced in treatment because partial occlusion of the venous varix without the reduction of arterial flow could lead to intraprocedural rupture.^8,37 Treatments for NGPAVF include surgery and endovascular treatment. In areas of easy surgical access, surgeries provide greater benefit. For some lesions, the two procedures need to be combined.⁵²

Endovascular interventional treatment

Coils or liquid embolic agents can be adopted. The currently available mainstream liquid embolic materials include NBCA (n-butyl cyanoacrylate) and Onyx. Due to the high perfusion pressure of NGPAVF, embolization may be very difficult, and the distal migration of embolic materials is more likely to occur.⁶⁵ Therefore, satisfactory control of the arterial flow is needed during embolism.⁸

Coils

Coils can provide better control of positioning, and they are not easily carried away by high-velocity blood flow.^74–77 When the fistula orifice is smaller, coil embolization is more successful.⁷⁸ In 2006, Luo et al. utilized transarterial Guglielmi detachable coils to treat intracranial high-flow AVFs in single-session embolization and achieved satisfactory treatment.⁷⁹ In some cases, many coils are needed.⁸⁰ The key process in achieving total occlusion of PAVFs is closure of the venous portion of the arteriovenous shunt, and the simple supplication of a coil can sometimes completely block the fistula orifice.⁶⁴ Due to a high level of control, coils present some advantages in treating complicated PAVFs.⁴⁰

NBCA

NBCA has good dispersivity. When the tortuosity or size of the arteries feeding the NGPAVF prohibits safe distal catheterization, NBCA alone is preferred in small arteries.^43,81 For instance, in 2002, Campos et al. reported one case of NGPAVF in the frontoparietal region. In this case, good recovery was obtained after injection of NBCA; to avoid NBCA migration during embolism, hypotension and the valsalva maneuver were adopted during glue injection to reduce the flow into the fistula.¹² In addition, NBCA is suitable for embolizing complex PAVFs that have many connections or multiple arterial feeders with a single vein outlet. The application of NBCA is preferred due to its capability to completely fill all the AV connections.⁶⁵

Onyx

Onyx embolization is another option for high-flow fistulas because it offers the ability to redirect flow during delivery and thus allows for precise application. For instance, in 2015, Lo Presti et al. reported one case of PAVF in the deep sylvian fissure, accompanied by a varix; the fistula was fed by the enlarged lenticulostriate artery, and a micro-catheter was introduced to the feeding arteries. Onyx-18 was slowly injected into the fistula. The material propagated through the fistula into the draining vein and varix. A small amount of reflux was seen in the lenticulostriate artery but not in the M1 trunk. The catheter was removed, and the effects of the treatment were satisfactory.³⁰

Combined embolization

High-velocity NGPAVF can be treated with a combination of coils and NBCA. The coil framework is first constructed at the fistula, and a low concentration of NBCA is injected. The mesh of coils creates a barrier that impedes the undue migration of the NBCA. For instance, in 2010, Youn et al. treated 11 patients who harbored 12 NGPAVFs with a combination of NBCA and coils and achieved good curative effects, suggesting that coil-based endovascular treatment can achieve safe and stable occlusion.⁸² In addition, in 2015, Paramasivam et al. reported 16 children with congenital pial AVF in 2013. The combination of NBCA and coils was used in 10 cases (63%) to reduce flow before NBCA embolization. Coils were placed in the venous pouch located close to the fistula and only drained the fistula to control flow. Systemic hypotension was induced during NBCA injection, and variable concentrations of NBCA were used to modify the polymerization time. Alternatively, oversized coils can be placed in the feeding artery to reduce flow.⁸

Balloon-assisted embolism

To prevent the dislodgement of embolism materials by high-velocity blood, transarterial balloon occlusion can be performed in the feeding arteries. For instance, Andreou et al. treated two cases of NGPAVFs with the assistance of a hyperform balloon in 2008; a mixture of 70–100% GLUBRAN 2 glue and Lipiodol was injected to induce embolism.⁸³ In addition, Newman et al. reported two cases of pediatric NGPAVFs in 2011; due to the high flow rate, a hyperform balloon was placed in the feeding arteries to reduce blood flow, and Onyx 34 was then injected to achieve satisfactory embolism of NGPAVFs. Coiling was performed in one of these cases in which the coil migrated out of the fistulous point and into the venous pouch. A balloon was then used for auxiliary treatment.⁸⁴

Venous approach

Transarterial approaches are often used for embolization therapy of NGAVFs, but similar to DAVFs, transvenous approaches can also be used. In multi-hole pial AVF, which has many feeding arteries but does not have a major feeding artery, embolism can be induced through transvenous approaches. For instance, Cooke et al. reported one baby with multi-hole pial AVF in 2012; first, coiling via a transarterial approach was adopted, but after 3 months, ventricular hemorrhage and hydrocephalus appeared, so another surgery was performed. At this time, coils and Onyx were used to embolize the PAVF via transarterial and transvenous approaches, and satisfactory results were achieved.⁸⁵

Surgical resection

Microsurgical approaches are reserved for NGPAVF cases in which embolization is deemed dangerous because the arterial feeder is a short branch of a cortical artery and cannot be occluded. Surgery can not only occlude the fistula orifice but also remove the mass effect caused by variceal dilatation. Therefore, it is an effective method for the treatment of NGPAVFs. Intraoperative fluorescence angiography can be utilized if necessary.²¹ For instance, Jouibari et al. reported two cases of supratentorial NGPAVFs accompanied by varices, both of which had very large, surgically accessible varices that supported resection of the lesion. The lesions could be dissected from the surrounding tissues, and the obliteration of the feeding arteries and draining veins did not cause new neurological deficits.⁸⁶

NGPAVFs with a superficial location and lower flow rate are easy to treat. However, the surgical treatment of NGPAVFs accompanied by venous hypertension and multiple fistulous channels is challenging because preexisting venous hypertension may precipitate severe bleeding. In microsurgical resection, various measures can be adopted to reduce the risks of the operation, such as intraoperative induction of hypotension, temporary clipping of the feeding arteries, and pharmacological neuroprotection. More radical measures are adopted in difficult surgeries to reduce the risks of surgical treatment. For instance, in 1997, Meyer et al. reported one case of a temporooccipital parenchymal PAVF; deep hypothermic circulatory bypass was used intraoperatively to facilitate the incision of the NGPAVF.⁸⁷

The fistula orifice is prone to rupture and hemorrhage and requires careful treatment. Similar to intracranial AVM, calcification may occur in PAVF, which makes surgical treatment difficult.⁸⁸ For instance, in 2008, Tabatabai et al. reported one patient with calcification in the NGPAVF who underwent surgical resection. The mechanism of calcification of the pial AVFs involved a dystrophic process due to hypoperfusion caused by the steal phenomenon or venous congestion over a long time period.⁶²

Sometimes indocyanine green (ICG) fluorescence can also be adopted during the surgical treatment of NGPVFs. For instance, in 2013, Holling et al. reported three NGPAVF cases treated with surgical resection with the help of ICG fluorescence. ICG fluorescence provides additional information about the flow characteristics of the draining vein and tissue perfusion, thereby facilitating the surgical treatment of arteriovenous fistulae and enabling the easy removal of PAVFs.⁸⁹ When these fistulae are located in superficial regions and are easily accessible via craniotomy, direct disconnection via intraoperative ICG fluorescence, which allows the shunting point to be accurately confirmed, is recommended.⁹⁰

Endovascular intervention with combined surgical treatment

Although simple endovascular therapy or surgery can be used to treat NGPAVFs, combinations of these techniques can sometimes be more effective. These combination techniques include the incision of NGPAVFs assisted by intraoperative DSA in a hybrid operating room or incision after the partial embolism of NGPAVFs. For instance, in 2013, Walcott et al. described seven cases of NGPAVFs in pediatric patients, including five patients who had partial embolism of PAVFs who received a combination of endovascular and surgical treatment.¹⁷ In another instance, in 2015, Kanai et al. described a 73-year-old man with PAVF in the posterior fossa who was treated with embolism of the feeding artery to reduce blood flow and then surgical resection. The risk of treatment was thereby reduced.⁴⁶

Outcome and complications

Both surgical incision and endovascular treatment can be used to obtain satisfactory results. In Weon et al.’s study, the postoperative mortality rate was 5.6%, and the permanent neurological morbidity rate was 3%.¹³ Postoperative complications were more common in patients under 2 years of age (85%) than in those over 2 years of age (33%), and children 2 years of age or younger required more treatment procedures than did older children.⁴² Single-hole NGPAVFs are easy to treat, with favorable effects.^63,65 However, the difficulty of treatment increases when the AVF is located in an area of function and exhibits a high flow rate, multiple feeding arteries, or the expansion of venous drainage. In 1987, Vinuela et al. treated eight cases of high-flow AVF with large intracranial varices and found that occlusion of these AVFs may result in the development of cerebral edema or hemorrhage or systemic cardiovascular decompensation. These complications may be decreased by staging the endovascular and/or surgical procedures or by controlling intra- and postoperative hypotension.⁴⁴

Even if PAVFs are successfully cured, there may be fatal complications. For instance, in 2002, Campos et al. reported one case of NGPAVF treated by embolism in which the patient exhibited fatal bleeding 26 hours after the treatment. This death was attributed to an ischemic phenomenon of venous origin created by total occlusion of the fistula with a thrombosis of the giant venous pouch, which led to venular dysfunction of the tissue surrounding the fistula secondary to hyperpressure, also called the normal perfusion pressure breakthrough phenomenon.¹² In addition, postoperative venous thrombosis and parenchymal bleeding or swelling of brain tissue may occur.^57,82

Do all NGPAVFs require complete treatment?

A study found that satisfactory effects could be achieved after disconnection of the main feeding artery without isolation of the entire venous pouch and ligation of all feeders because a markedly reduced flow into the venous varix could induce thrombosis and occlusion of the fistula.⁶⁷ This method may be more applicable for low-flow NGAVFs in adults. In their 2001 study of surgical and endovascular flow disconnection of intracranial single-channel PAVFs, Hoh et al. showed that for single-channel PAVFs, the pathological aspects of pial AV fistulae originated from their high-flow dynamics; therefore, the disconnection of the AV shunt was sufficient to obliterate the lesion, and resection of the lesion was unnecessary.⁶³

However, the treatment of single-hole NGPAVFs should be approached with caution because pial single-channel AVFs are not always cured by interruption of the feeding arteries identified in cerebral angiography; successful treatment might require removal of the varix. In a case of NGPAVF with temporal epilepsy reported by Kakino et al. in 2008, the varix still exhibited blood flow even when all feeding arteries visible in the imaging were blocked. Many small feeding arteries were identified, and the varix was dissected and removed so that the NGPAVF could be treated as thoroughly as possible.⁵⁶

Other studies have produced similar results. The literature not listed in this section is presented in Table 1.^{7,11,14,39,51,56,91}

The necessity of anticoagulation therapy

The drainage veins of AVF, which adjust to the high velocity of arterial blood flow, are prone to the formation of thromboses due to the slower blood flow in the AVF after treatment. This outcome has been shown in the treatment of spinal dura AVF.^92,93 Intracranial NGPAVF may also exhibit venous thrombosis after treatment. For some NGPAVFs, sudden surgical incision of the PAVF may lead to the thrombosis of drainage veins. For instance, Gonzalez et al. reported one case of high-flow PAVFs with large venous pouches. The patient underwent surgical clipping, but visual impairment appeared within 24 h after the operation. MRI and CT suggested the presence of a thrombosis in the varix.⁹⁴

For the above reasons, postoperative anticoagulation should be administered. For example, in 1996, Coubes et al. suggested that the main danger of NGPAVF after treatment was the post-embolization thrombosis of feeding arteries and/or draining veins, which must be controlled by strict hemodynamic monitoring. Therefore, they recommend the intravenous administration of heparin (100 mg/d) for 5 days to prevent secondary thrombosis of the venous system.¹¹ In another instance, in 2011, Guimaraens et al. reported one case of NGPAVF in the posterior fossa; this lesion underwent complete embolization prior to the administration of steroids and low-molecular-weight heparin for 1 week to avoid thrombosis in the drainage veins.⁹¹ In addition, in 2013, Yang et al. reported one case of NGPAVFs in the temporo-occipital area with varices. Three days later, a thrombosis formed in the varix and drainage veins; to slow thrombus formation in the varix, the patient was given anti-platelet and/or anticoagulation therapy, and the symptoms were gradually alleviated over the next 3 days.⁹⁵

Except in cases of complete disconnection of PAVF, even partial embolization can lead to the formation of thromboses in the drainage veins. For instance, in 2016, Ji et al. reported an NGPAVF fed by the middle cerebral and posterior cerebral arteries and accompanied by giant venous pouches; the PAVF was partially embolized. Because the AVF was not completely occluded, anticoagulation therapy was not given, but the patient exhibited postoperative venous thrombosis that secondarily developed into an intracranial hematoma.⁹⁶ Therefore, anticoagulation was recommended.

Conclusions

NGPAVFs are rare intracranial vascular shunts that involve the direct communication of arteries and veins. They require aggressive treatment, and the prognosis of conservative treatment is poor. NGPAVFs can be congenital or related to trauma and iatrogenic injury. The clinical manifestations are mainly related to the age of onset. NGPAVFs in children are mainly characterized by congestive heart failure and epilepsy, whereas adult cases are mainly characterized by bleeding and neural function deficits. Currently, DSA is the gold standard in the diagnosis of NGPAVFs, but the development of MRDSA and 4T-CTA in recent years has allowed assessment of the hemodynamics of NGPAVFs. NGPAVFs can be treated with surgical excision or endovascular embolization, and both methods show satisfactory effects. However, potential postoperative complications include fatal rupture, bleeding, and postoperative drainage vein thrombosis. Some studies recommend postoperative anticoagulation therapy to reduce the risk of postoperative thrombotic complications.

Declaration of conflicting interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.